FitSugar

Another Reason to Eat Carbs: Boost Your Mood

FitSugar — Wed, 11 Nov 2009 03:00:56 -0800

The majority of Fit readers call themselves carb queens, and Winter can make those carbohydrate cravings even more intense. But have no fear: scientists are finding even more reasons not to avoid this essential food group.

A recent study of more than 100 obese and overweight adults in Australia found that dieting put people in a better mood; a drop in pounds led to increased satisfaction. But for people on low-carb diets, the mood boost didn't last.

The study group was split, with half the subjects on a lowfat diet and the other half low-carbing it. Interestingly, folks in both groups lost the same amount of weight on average, about 30 pounds. But after a year, the low-carb dieters also lost the positive mood effects, while the low-fat dieters did not. Here's more from the study.

Runner's High Is as Addictive as Opiates

FitSugar — Fri, 28 Aug 2009 03:00:17 -0700

If you're a runner, you're probably familiar with runner's high. You know - that energetic, overwhelmingly awesome feeling you experience after a workout that makes you feel like the happiest person alive. The feel-good sensations come when endorphins are released from your brain, and new research shows that a runner's high mimics the same sense of euphoria as drug use. So scientists at Tufts University set out to test whether the feeling a runner gets could be considered an addiction.

Instead of testing actual runners, the scientists tested rats. The 84 rodents were divided into two types of cages, ones with wheels and ones without. Over a week, the rats that had access to the wheel naturally increased how much they ran. On day nine, about half the group was only given access to food for one hour per day, while the others continued to have food all the time. The food-restricted rats began exercising even more, and also started to lose weight. All the rats were then given the drug Naloxone, a chemical compound that is often used to help drug abusers recover from addiction and immediately causes withdrawal symptoms. The biggest "gym rats" showed the greatest degree of withdrawal symptoms, while rats that couldn't exercise displayed fewer withdrawal symptoms.

The scientists concluded that the release of chemicals during exercise mimics the sensations morphine and heroin users feel. If a runner's high is similar to a high brought on by drugs, the researchers propose that exercise could be used as a replacement "drug" to help drug addicts recover. What do you think?

Fibromyalgia

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Causes

People with fibromyalgia have decreased activity in opioid receptors in parts of the brain that affect mood and the emotional aspect of pain, researchers have found. This might explain why fibromyalgia patients are likely to experience depression, and are not very responsive to opioid painkillers.
Researchers have identified a conflict between sensory perception and nervous system processing in people with fibromyalgia. One study suggests that people with the condition might have greater awareness of, or less tolerance for, movement problems (such as tremor) that don't match with their expected sensory feedback. This mismatch in sensory signals might enhance the perception of pain.

Treatment

New research adds to the evidence that exercise relieves some of the symptoms of fibromyalgia. Women with fibromyalgia who took part in a program that combined aerobic, strength training, and flexibility exercises had better physical and emotional function, as well as reduced symptoms. Another study found that an at-home exercise program improved upper body pain and function, especially in women who were having functional difficulties at the beginning of the study.
An anti-convulsant medication, gabapentin (Neurontin), significantly improved pain in fibromyalgia patients compared to placebo. Patients who took gabapentin also reported that they slept better and felt less tired.
The selective serotonin-reuptake inhibitor paroxetine (Paxil) significantly lowered patient scores on a fibromyalgia symptom questionnaire, and was well-tolerated, although the drug do much for their pain.

Introduction

Fibromyalgia is a syndrome of unknown causes that results in lasting, sometimes debilitating, muscle pain and fatigue. Fibromyalgia is also known as fibrositis or fibromyositis.

Pain. The primary symptom of fibromyalgia is pain. The pain can be in one place or all over. The exact locations of the pain are called tender points. The pain of fibromyalgia is often is described as follows:

Tender point pain occurs in local sites, usually in the neck and shoulders. The pain then spreads out from these areas. The actual pain starts at the muscles. The joints are not affected. There are no lumps or nodes associated with these points of pain, and no signs of inflammation (swelling). People diagnosed with fibromyalgia feel pain in at least 11 of 18 specific tender points.
Widespread pain described as stiffness, burning, and aching. The pain also "radiates," or spreads, to nearby areas. Most patients report feeling some pain all the time. Many describe it as "exhausting." The pain can vary depending on the time of day, weather changes, physical activity, and the presence of stressful situations. The pain is often more intense after disturbed sleep.

Fatigue and Sleep Disturbances. Another major complaint is fatigue. Some patients report that fatigue is more unbearable than their pain. Sleep disturbances, particularly restless legs syndrome, are also very common. Fatigue and sleep disturbances are almost universal in patients with fibromyalgia. Some experts believe that if these symptoms are not present, doctors should seek a diagnosis other than fibromyalgia.

Depression and Mood. Up to a third of patients have depression. Disturbances in mood and concentration are also very common. These conditions often go undiagnosed in patients with fibromyalgia.

Other Symptoms. The following symptoms may also be present:

Digestive problems, including irritable bowel syndrome with gas, and alternating diarrhea and constipation
Dizziness
Painful menstrual periods
Tension or migraine headaches
Tingling or numbness in the hands and feet
Urinary frequency caused by bladder spasms

Symptoms in Children. In general, children with fibromyalgia most often have sleep disorders and widespread pain.

Causes

The most common type is primary fibromyalgia, in which the causes are not known. Many experts believe that fibromyalgia is not a disease, but rather a chronic pain condition brought on by several abnormal body responses to stress. Physical injuries, emotional trauma, or viral infections such as Epstein-Barr may be triggers of the disorder, but none have proven to be a cause of primary fibromyalgia.

Research published in the December 2006 issue of Current Pain and Headache Reports found that the areas in the brain that are responsible for the sensation of pain are different in fibromyalgia patients from the same areas in healthy people.

People with fibromyalgia have been found to have decreased activity in opioid receptors in parts of the brain that affect mood and the emotional aspect of pain. This reduced response might explain why fibromyalgia patients are likely to havedepression, and are less responsive to opioid painkillers, researchers say.

Sleep disturbances are common in fibromyalgia. Both adult and young patients with fibromyalgia have a higher-than-average rate of a sleep disorder called periodic limb movement disorder (PLMD). PLMD used to be called nocturnal myoclonus. Patients with PLMD involuntarily contract their leg muscles every 20 - 40 seconds during sleep. This may occasionally wake up the patient.

Some researchers believe that fibromyalgia does not lead to poor sleeping patterns, but that sleep disturbances come first. Researchers continue to investigate the link between fibromyalgia and sleep.

In one study, healthy volunteers reported fibromyalgia-like pain after they had been subjected to disrupted deep sleep. Disturbed sleep appears to trigger factors in the immune system that cause inflammation, pain, fatigue, and lower tolerance to pain. A 2004 study found that patients with fibromyalgia have increased rates of cyclic alternating sleep pattern (CAP). Increased CAP produced serious sleep problems, which were strongly linked to symptom severity. Previous studies have also suggested that CAP may be related to PLMD.
A 2004 report found that sleep disorders that cause breathing problems are common in women with fibromyalgia.
Other biological measures of troubled sleep, however, such as levels of the hormone melatonin, which helps regulate circadian rhythms and the sleep-wake cycle, appear to be normal in most people with fibromyalgia.

Many abnormalities of hormonal, metabolic, and brain chemical activity have been described in studies of fibromyalgia patients. Changes appear to occur in several brain chemicals, although no regular pattern has emerged that fits most patients. Since there has been no clear cause-and-effect relationship established, this may be a result of the effects of pain and stress on the central nervous system, and not a cause of fibromyalgia.

Serotonin. Of particular interest to researchers is serotonin, an important nervous system chemical messenger found in the brain, gut, and other areas of the body. Serotonin plays important roles in feelings of well-being, adjusting pain levels, and promoting deep sleep. Serotonin abnormalities have been linked to many disorders, including depression, migraines, and irritable bowel syndrome. Lower serotonin levels have also been noted in some patients with fibromyalgia.

Stress Hormones. Researchers have also found abnormalities in the hormone system known as the hypothalamus-pituitary-adrenal gland (HAP) axis. The HAP axis controls important functions, including sleep, response to stress, and depression. Changes in the HAP axis appear to produce lower levels of the stress hormones norepinephrine and cortisol. (By contrast, levels of stress hormones in depression are higher than normal.) Deficiencies in the levels of stress hormones produce impaired and weaker responses to psychological or physical stresses. (Examples of physical stress include infection or exercise.)

The hypothalamus is a highly complex structure in the brain that regulates many important brain chemicals.

Click the icon to see an image of the adrenal glands.

Low Growth Hormone Levels. Some studies have reported low levels of insulin-like growth factor-1 (IGF-1) in about a third of fibromyalgia patients. IGF-1 is a hormone that is controlled by the adult growth hormone, and promotes bone and muscle growth. Low levels of growth hormone are related to impaired thinking, lack of energy, muscle weakness, and intolerance to cold. Studies suggest that changes in growth hormone likely stem from the hypothalamus in the brain. While researchers did not find a link between IGF-1 levels and fibromyalgia, a 2005 study indicated that serum growth hormone levels may be a marker of the disorder.

Abnormal Pain Perception and Substance P. Some studies have suggested that fibromyalgia may involve too much activity in the parts of the central nervous system that process pain (the nociceptive system). Brain scans of fibromyalgia patients have suggested abnormalities in pain processing centers. For example, researchers have detected up to three times the normal level of substance P in the cerebrospinal fluid of fibromyalgia patients. Substance P, a chemical messenger of the nervous system, is associated with increased pain perception.

Some fibromyalgia patients may also be oversensitive to external stimulation, and overly anxious about the sensation of pain. This increase in awareness is called generalized hypervigilance. One study compared patients with fibromyalgia or rheumatoid arthritis to those without chronic pain. Researchers then measured the different groups' responses to pain and noise. Of the three groups, the fibromyalgia patients were least tolerant, and most aware, of such stimuli. However, one analysis of studies on fibromyalgia found no strong support for the hypervigilance theory.

A conflict between sensory perception and nervous system processing might occur in people with fibromyalgia. Fibromyalgia patients have been found to have greater awareness of, or less tolerance for, movement problems (such as tremor) that don't match with their expected sensory feedback. This mismatch in sensory signals might enhance the perception of pain.

Fibromyalgia has symptoms that resemble those of some rheumatic illnesses, including rheumatoid arthritis and lupus (systemic lupus erythematosus). These are autoimmune diseases in which a defective immune system mistakenly attacks the body's own healthy tissue, producing inflammation and damage. The pain in fibromyalgia, however, does not appear to be due to autoimmune factors, and there is little evidence to support a role for an inflammatory response in fibromyalgia.

Although not primary causes, psychological and social factors may contribute to fibromyalgia in three ways:

They could make individuals susceptible to fibromyalgia.
They may play some role in triggering the onset of the condition.
They may perpetuate, or be responsible for, the condition.

Studies have reported a greater number of severe experiences of emotional and physical abuse in patients with fibromyalgia, compared with the general population. Most often, the abuse came from family members or partners. This suggests that post-traumatic stress disorder (PTSD) or chronic stress may play a strong role in the development of fibromyalgia in some patients. PTSD, an anxiety disorder, is a reaction to a specific traumatic event. Symptoms of this condition, which can last for years after the traumatic event, include emotional withdrawal, hopelessness, irritability, mood swings, sleep problems, inability to concentrate, and an excessive startle response to noise. Some evidence indicates that PTSD actually results in changes in the brain, possibly from long-term over-exposure to stress hormones.

Some research found muscle abnormalities in fibromyalgia patients. These problems can be classified as the following:

Biochemical abnormalities: For example, one study reported that fibromyalgia patients had lower levels of the muscle-cell chemicals phosphocreatine and adenosine triphosphate (ATP). Such chemicals regulate the level of calcium in muscle cells. Calcium is an important component in the muscles' ability to contract and relax. If ATP levels are low, calcium is not "pushed back" into the cells, and the muscle remains contracted.
Functional abnormalities: The pain and stress of the disease itself may harm muscle function.
Structural and blood flow abnormalities: Some researchers saw overly thickened capillaries (tiny blood vessels) in the muscles of fibromyalgia patients. The abnormal capillaries could produce lower levels of compounds essential for muscle function, as well as reduce the flow of oxygen-rich blood to the muscles.

To date, none of these abnormalities have a clearly defined relationship with fibromyalgia.

Risk Factors

About 3.7 million Americans have fibromyalgia. The condition affects 2% of Americans, including 3.4% of women and 0.5% of men.

Some evidence suggests that several factors may make people more susceptible to fibromyalgia. These risk factors include:

Being female
Coming from a very stressful culture or environment
Having a psychological vulnerability to stress
Having had difficult experiences in childhood

Nine out of 10 fibromyalgia patients are women. Women may be more prone to develop fibromyalgia during menopause.

The disorder usually occurs in people ages 20 - 60 years, though it can occur at any time. Some studies have noted peaks around age 35. Others note that fibromyalgia is most common in middle-aged women. In one study, cases of fibromyalgia increased with age, and reached a frequency of more than 7% among people in their 60s and 70s.

Juvenile Primary Fibromyalgia. This type of fibromyalgia appears in adolescents, typically after age 13, with a peak incidence at age 14. It is uncommon, but studies indicate that its incidence may be increasing. One study found that 1.2% of school children, all girls, met the criteria for fibromyalgia. Other studies have found an even higher frequency of fibromyalgia in children. Symptoms are similar to adult fibromyalgia, but outcomes may be better in young people.

Studies report a higher incidence of fibromyalgia among family members. It is not clear if genetic or psychological factors, or both, are involved.

One study reported that 28% of the children of mothers with fibromyalgia also develop the disorder. Offspring who developed fibromyalgia were no more likely to have psychological disorders than those who did not.
Another study noted that 66% of parents of children with fibromyalgia reported some sort of chronic pain. About 10% of them had fibromyalgia.

Diagnosis

There is no obvious, objective method for diagnosing fibromyalgia. The criteria used for studying fibromyalgia are very helpful, particularly if the patient does not have any accompanying disorder, such as depression or arthritis, which could complicate the diagnosis. Failure to meet the criteria, however, does not rule out fibromyalgia. Fibromyalgia should be suspected in any person with muscle and joint pain with no identifiable cause.

In 1990, the American College of Rheumatology (ACR) set the following criteria for the classification of fibromyalgia:

A. Widespread pain must be present for at least 3 months. This pain must appear in all of the following locations:

Both sides of the body
Above and below the waist
Along the length of the spine

B. Pain in at least 11 of 18 specific areas called tender points on the body. The pain experienced when pressing on a tender point is very localized and intensely painful (not just tender). Tender points are located in the following areas:

The left or right side of the back of the neck, directly below the hairline
The left or right side of the front of the neck, above the collar bone (clavicle)
The left or right side of the chest, right below the collar bone
The left or right side of the upper back, near where the neck and shoulder join
The left or right side of the spine in the upper back between the shoulder blades (scapula)
The inside of either arm, where it bends at the elbow
The left or right side of the lower back, right below the waist
Either side of the buttocks below the hip bones
Either kneecap

Other Factors. The ACR classification provides a guideline, but doctors will also use a patient's medical history and other symptoms to reach a diagnosis. Fibromyalgia is often diagnosed when other diseases have been excluded. Long-term symptoms that may indicate fibromyalgia include:

Fatigue
Headache
Morning stiffness
Numbness or tingling in the hands and feet
Sleep disturbance

The 18 fibromyalgia tender points are located throughout the body. According to the American College of Rheumatology, a diagnosis of fibromyalgia requires widespread body pain plus localized pain in 11 of these 18 specific points.

A doctor should always take a careful personal and family medical history, which would include a psychological profile and a history of any factors that might indicate disorders other than fibromyalgia. Such factors might include:

Infectious diseases
Muscle weakness
Physical injuries
Rashes
Recent weight change
Sexual, physical, or substance or alcohol abuse

Patients should report any drugs they take, including vitamins and over-the-counter or herbal medications.

Pressure on Tender Spots. Any physical examination for fibromyalgia requires that the doctor press firmly on all potential tender spots. They must be painful when pressed, not simply tender. In addition, for a doctor to reach a diagnosis of fibromyalgia, these tender sites should normally not show signs of inflammation (redness, swelling, or heat in the joints and soft tissue). The tender points may also change in location and sensitivity over time. A doctor, then, may recheck tender points that do not respond the first time, in patients who have other significant symptoms.

Detection of Other Causes of Symptoms. A health care provider will also examine nails, skin, mucous membranes, joints, spine, muscles, and bones to help rule out arthritis, thyroid disease, and other disorders.

No blood, urine, or other laboratory tests can provide a definitive diagnosis of fibromyalgia. If such tests show abnormal results, the doctor should look for other disorders. Tests for specific diseases depend on family histories and other symptoms. They may include:

Blood count
Sedimentation rate
Tests of certain antibodies
Thyroid and liver function tests

The doctor may suggest follow-up psychological profile testing, if laboratory results do not indicate a specific disease.

Conditions with Similar Symptoms

Between 10 - 30% of all doctor office visits are due to symptoms that resemble those of fibromyalgia, including fatigue, malaise, and widespread muscle pain. Since no laboratory test can confirm a diagnosis of fibromyalgia, doctors will usually first test for similar conditions. It should be noted that a diagnosis of many of the disorders below may not always rule out fibromyalgia, since it can accompany other common and similar conditions.

Several conditions overlap or often coexist with fibromyalgia, and have similar symptoms. It is not clear if these conditions cause fibromyalgia, are risk factors for the disorder, have causes in common with fibromyalgia, or have no relationship at all with it.

Chronic Fatigue Syndrome. There is a significant overlap between fibromyalgia and chronic fatigue syndrome (CFS). In a 2003 study, for example, 43% of CFS patients also had a diagnosis of fibromyalgia. As with fibromyalgia, the cause of CFS is unknown. A doctor can diagnose either disorder based only on symptoms reported by the patient. The two disorders share most of the same symptoms. They are also treated almost identically. The differences are primarily the following:

Pain with tender points is the primary symptom in fibromyalgia. Some patients with CFS exhibit similar tender pressure points. However, muscle pain is less prominent in patients with CFS.
Fatigue is the dominant symptom in CFS. It is severe and not relieved by rest or sleep, and it is not the result of excessive work or exercise.

Some doctors believe that fibromyalgia is simply an extreme type of chronic fatigue syndrome. There Some physical evidence, however, indicates that the two disorders are distinct, with treatments that are specific to each.

Myofascial Pain Syndrome. Myofascial pain syndrome can be confused with fibromyalgia and may also accompany it. Unlike fibromyalgia, myofascial pain tends to occur in trigger points, as opposed to tender points, and typically there is no widespread, generalized pain. Trigger-point pain occurs in tight muscles, and when the doctor presses on these points, the patient may experience a muscle twitch. Unlike tender points, trigger points are often small lumps, about the size of a pencil eraser.

Major Depression. The link between psychological disorders and fibromyalgia is very strong and problematic. Certain studies report that 50 - 70% of fibromyalgia patients have a lifetime history of depression. Only 18 - 36% of fibromyalgia patients, however, also have major depression, a severe form of depression.

Some studies found that people who have both psychological disorders and fibromyalgia are more likely to seek medical help, compared with patients who simply have symptoms of fibromyalgia. If this is the case, study results may be biased, favoring a higher-than-actual association between depression and fibromyalgia.

Depression most likely does not cause fibromyalgia, but it may increase susceptibility. Depressed feelings in people with fibromyalgia can certainly be normal responses to the pain and fatigue caused by this syndrome. Such emotions, however, are temporary and related to the situation a person is in. They are not considered to be a depression disorder. Unlike ordinary periods of sadness, an episode of major depression disorder can last many months.

Symptoms of major depression include the following:

Depressed mood every day
Feeling worthless or inappropriately guilty
Inability to concentrate or make decisions
Insomnia or excessive sleeping
Low energy every day
Restlessness or a sense of being slowed down
Significant weight gain or loss (of 10% or more of an individual's typical body weight)
Suicidal thoughts

If several of the above symptoms are present, and none of the physical symptoms (particularly the tender points) of fibromyalgia exist, the condition is most likely major depression.

Chronic Headache. Chronic primary headaches such as migraines are common in fibromyalgia patients. Some experts believe that migraine headaches and fibromyalgia may even share common defects in the systems that regulate certain chemical messengers in the brain, including serotonin and epinephrine (adrenaline). Low levels of magnesium have also been noted in patients with both fibromyalgia and migraines. In fact, chronic migraine sufferers who fail to benefit from usual therapies may also have fibromyalgia.

Symptoms of a migraine attack may include heightened sensitivity to light and sound, nausea, vision problems (auras), speech difficulty, and intense pain predominating on one side of the head.

Multiple Chemical Sensitivity. Multiple chemical sensitivity (MCS) is a term that describes conditions in which certain chemicals can cause symptoms similar to CFS or fibromyalgia in some people. Still, as with CFS and fibromyalgia, some experts are uncertain whether MCS is a medical condition or if it is psychologically based.

In one study, for example, CFS patients who believed their problem was chemically triggered were exposed to either an active chemical or a placebo (an inactive substance). Both groups reported symptoms, including those only exposed to a placebo. Because everyone is exposed to many chemicals on a daily basis, it is very difficult to determine whether chemicals are responsible for specific symptoms.

Experts have come up with criteria to help recognize MCS:

Symptoms can be produced by exposure to the chemical at levels lower than previously or usually tolerated.
Symptoms can be triggered by multiple substances that are chemically unrelated.
Symptoms involve multiple organ systems.
The condition is chronic.
The symptoms always happen with repeated exposure to a chemical. (These are often common chemicals found in popular products, such as perfumes, fabric softeners, and air fresheners.)
The symptoms improve when the chemical is removed.

Restless Legs Syndrome. About 15% of people with fibromyalgia have restless legs syndrome. Restless legs syndrome is an unsettling and poorly understood movement disorder that is sometimes described as a sense of unease and weariness in the lower leg that is aggravated by rest and relieved by movement.

Disorders Affected by the Sympathetic (also called Autonomic) Nervous System. Other conditions that commonly accompany fibromyalgia include:

Chest pain and heart palpitations
Mitral valve prolapse
Sudden drop in blood pressure

Certain stress-related disorders commonly occur with fibromyalgia, and have overlapping symptoms. In fact, some experts believe these disorders so often interact that they may all be part of one general condition.

Chemicals and environmental toxins -- exposure to various chemicals and environmental toxins such as solvents, pesticides, or heavy metals (cadmium, mercury, or lead) can cause fatigue, chronic pain, and other symptoms of fibromyalgia.
Irritable bowel syndrome
Osteoarthritis -- a common form of arthritis than can coexist with fibromyalgia. The two conditions may be confused, particularly in elderly people. Osteoarthritis, however, causes joint pain, not widespread or generalized pain.

Osteoarthritis is a chronic disease of the joint cartilage and bone. It is often thought to result from "wear and tear" on a joint, although there are other causes, such as congenital defects, trauma, and metabolic disorders. Joints appear larger, are stiff and painful, and usually feel worse the more they are used throughout the day.

Temporomandibular joint disorders

Some tests may be positive for one or more of these diseases. However, if the results are uncertain or weak, or if these conditions have been treated successfully, fibromyalgia should not be ruled out if the patient still meets the criteria for it.

Multiple sclerosis. This condition may have symptoms similar to those of fibromyalgia. Magnetic resonance imaging (MRI) scans often detect patches of tissue in the brain that confirm the presence of multiple sclerosis (MS). MRI findings combined with other tests and clinical findings usually make this diagnosis fairly certain. However, some patients may have symptoms that suggest MS, but diagnostic tests cannot confirm the diagnosis. Some of these patients may have symptoms similar to those of fibromyalgia.

Click the icon to see an image of multiple sclerosis.

Sjogren syndrome. This condition, characterized by dry eyes and mouth, is sometimes mistaken for fibromyalgia.

Autoimmune diseases. Rheumatoid arthritis, systemic lupus erythrometosis, and Sjogren syndrome are usually easy to diagnose but may develop slowly and be difficult to diagnose at first. Even if a doctor determines that a patient is most likely to have fibromyalgia, the doctor should keep track of any changes in symptoms over time in case one of these other illnesses is actually present.

Lyme Disease. Lyme disease is a bacterial disease transmitted by ticks. Health care providers can usually diagnose early Lyme disease correctly, but a delayed response or recurrence of this disorder may be mistaken for fibromyalgia. Some experts believe that 15 - 50% of patients referred to clinics for Lyme disease actually have fibromyalgia. Late Lyme disease can usually (but not always) be ruled out using blood tests that identify the organism that causes this disease. If fibromyalgia patients are incorrectly diagnosed and treated for Lyme disease with prolonged courses of antibiotics, the drugs may have serious side effects.

Drugs and Alcohol. Fatigue is a side effect of many prescription and over-the-counter medications, such as antihistamines. In addition, symptoms of dependency on, or abuse of, alcohol or drugs appear as constant fatigue. Health care providers should consider medications as a possible cause of fatigue if an individual has recently started, stopped, or changed medications. Withdrawal from caffeine can produce depression, fatigue, and headache.

Polymyalgia Rheumatica. Polymyalgia rheumatica is a condition that causes pain and stiffness, and generally occurs in older women. Tender points are also present with this disorder, although they almost always occur in the hip and shoulder area. Morning stiffness is common, and patients may also experience fever, weight loss, and fatigue. A higher-than-normal erythrocyte sedimentation rate (ESR) can suggest polymyalgia rheumatica. Elevated ESR, however, also occurs with other conditions. Polymyalgia rheumatica often gets better in about a year, but there is a risk of persistent disease. Worse, it is sometimes associated with a rare condition called temporal arteritis, which may cause blindness if not treated, so an accurate diagnosis of polymyalgia rheumatica is important.

Prognosis

Fibromyalgia can be mild or disabling, and the emotional toll can be substantial. About half of all patients have difficulty with routine daily activities, or are unable to perform them. An estimated 30 - 40% of patients have had to quit work or change jobs. In a 2003 study, patients with either CFS or fibromyalgia were more likely to suffer losses of jobs, possessions, and support from friends and family than were people suffering from other conditions that caused fatigue.

The pain, emotional consequences, or sleep disturbances that come with fibromyalgia may lead to self-medication and overuse of sleeping pills, alcohol, drugs, or caffeine.

Outlook in Adults. Some studies show that fibromyalgia symptoms remain stable over the long term, while others report a better outlook, with 25 - 35% of patients reporting improvement in pain symptoms over time. Studies suggest that regular exercise specifically improves the outlook. Those with a significant life crisis, or who were on disability, had a poorer outcome than others. Outcome was determined by improvements in the patients' ability to work, their own feelings about their condition, pain sensation, and levels of disturbed sleep, fatigue, and depression. Although the disease is life-long, it does not get worse and is not fatal.

Outlook in Children. Children with fibromyalgia tend to have a better outlook than adults with the disorder. Several studies reported that more than half of children with fibromyalgia recover in 2 - 3 years.

Treatment

Many patients with fibromyalgia are treated first with medication; however, the American Pain Society Fibromyalgia Panel recommends a combined approach using cognitive-behavioral therapy, education, medication, and exercise.

Fibromyalgia is a mysterious condition. Its causes are still largely unknown, as is how it inflicts damage. No strong evidence indicates that any single treatment (or combination of treatments) has any significant effect for most patients. However, in 2007 the U.S. Food and Drug Administration approved pregabalin (Lyrica) as the first drug treatment for fibromyalgia after a study showed the medicine reduced fibromyalgia pain by at least 50% in 63% of patients.

Treatment usually involves not only relieving symptoms but also changing a pateint's attitude about their disease. Treatment should also teach patients behaviors that help them cope.

Treatments usually involve trial and error:

Patients may start with physical therapy, exercise, stress reduction techniques, and cognitive-behavioral therapy.
If these methods fail to improve symptoms, an antidepressant or muscle relaxant may be added to the treatment. Doctors usually prescribe these drugs because they can may improve pain tolerance.
Patient education and programs that encourage coping skills are an important part of any treatment plan.

According to a 2005 study published in the Clinical Journal of Pain, a combination of non-drug therapies works just as well as drug therapy in improving pain, depression, and disability. This combination includes exercise, stress management, massage, and diet.

Patients must have realistic expectations about the long-term outlook of their condition, and their own individual abilities. It is important to understand that fibromyalgia can be managed, and patients can live a full life. The following tips may be helpful when starting a treatment program for fibromyalgia:

The goal of therapy is to relieve symptoms, not cure them.
Treatment must be tailored to each patient, and a combination approach is often needed.
Patients must begin all treatments with the attitude that these treatments are trial-and-error. There is no clear treatment solution. Patients and doctors need to work together to make the best choices for individual symptoms and concerns.
Treatments are long-lasting, in some cases life-long, and patients should not be discouraged by the return of symptoms (relapses).
Enlisting family members, partners, and close friends, particularly to help with exercise and stretching programs, can be helpful.
Becoming involved with support groups of fellow patients also benefits many patients. Support groups may also benefit family members, particularly parents of children with fibromyalgia. One study noted that the severity of the disorder increased in children whose parents were less able to cope with their child's pain.

The definition of improvement is personal. For example, some patients are pleased with only a 10% reduction in pain and other symptoms.

Lifestyle Changes

Many studies have shown that exercise is the most effective component in managing fibromyalgia, and patients must expect to take part in a long-term exercise program. Physical activity prevents muscle wasting, increases well-being, and, over time, reduces fatigue and pain. Many studies have also demonstrated the exercise can improve physical and emotional function, as well as reduce symptoms, including pain.

Programs often combine aerobic, strength-training, and flexibility exercises with self-management education. Some studies have shown improvements lasting for up to 9 months after the exercise program.

Graded Exercise. The basic approach used for fibromyalgia is called graded exercise. Graded exercise means you slowly increase the amount of your physical activity.

In general, graded exercise involves:

A very gradual program of activity, beginning with mild exercise and building in intensity over time.
Stretching exercises before exercising. A daily stretching routine can help relax tense muscles and prevent muscle soreness.
Walking, swimming, and using equipment such as treadmills or stationary bikes. Swimming and water therapy are good because they don't require putting weight on the joints.

Patients who try hard exercises too early actually experience an increase in pain, and are likely to become discouraged and quit.

Every patient must be prepared for relapses and setbacks, but should not get discouraged. Patients who do not respond to one type of exercise might consider experimenting with another form.

Physical therapy can be very helpful. Studies suggest that physical therapy may reduce muscle overload, lessen fatigue from poor posture and positioning, and help condition weak muscles.

Sleep is essential, particularly since sleep disruptions worsen pain. Many patients with fibromyalgia have trouble getting a restful and healing night's sleep. Those who are unable to sleep consistently have low improvement. Swing shift work, for example, is extremely hard on fibromyalgia patients. Poor sleep habits can add to sleep problems. Tips for good sleep habits include:

Avoid caffeine or alcohol 4 - 6 hours before bedtime.
Avoid drinking fluids right before bedtime so that needing to uriniate does not disturb your sleep.
Avoid exercising 6 hours before bedtime.
Avoid large meals before bedtime. A light snack, however, may help you sleep.
Avoid naps, especially in the evening or late afternoon.
Establish a regular time for going to bed and getting up in the morning. Maintain this schedule even on weekends and during vacation.
If you are unable to fall asleep after 15 or 20 minutes, go into another room and start a quiet activity. Return to bed when you feel sleepy.
Minimize light and maintain a comfortable, moderate temperature in the bedroom. Keep the bedroom well ventilated.
Use the bed only for sleep and sexual relations.

[For more information see In-Depth Report #27: Insomnia.]

Fibromyalgia patients should maintain a healthy diet low in animal fat and high in fiber, with plenty of whole grains, fresh fruits, and vegetables. Although everyone should be careful about calories from fats, some are healthy.

Omega-3 Fatty Acids. Oils containing omega-3 fatty acids are of particular interest for arthritic pain. Such oils are found in cold-water fish. You can also purchase these oils as supplements called EPA-DHA or omega 3.

Omega-3 fatty acids are a form of polyunsaturated fat that the body gets from food. Omega-3s are known as essential fatty acids (EFAs) because they are important for good health. These healthy fatty acids can be found in certain fish, dark green leafy vegetables, and some oils. Omega-3 fatty acids have anti-inflammatory properties, which help prevent blood clots, lower cholesterol and triglyceride levels, and reduce blood pressure. Omega-3s may also reduce the risks and symptoms of diabetes, stroke, rheumatoid arthritis, asthma, inflammatory bowel disease, ulcerative colitis, some cancers, and mental decline.

Vegetarian Diet. A vegan diet has no meat, dairy, or eggs and includes uncooked fruits, vegetables, nuts, and germinated seeds. The actual benefit of various vegetarian diets remains unproven.

Relaxation and stress-reduction techniques are proving to be helpful in managing chronic pain. Evidence shows that people with fibromyalgia have a more stressful response to daily conflicts and encounters than those without the disorder. Several relaxation and stress-reduction techniques may be helpful in managing chronic pain:

Biofeedback
Deep breathing exercises
Hypnosis
Massage therapy
Meditation
Muscle relaxation techniques

Biofeedback. Evidence from controlled trials does not suggest that biofeedback techniques may be very helpful for fibromyalgia patients. During a biofeedback session, electric leads are taped to a subject's head. The person is encouraged to relax using any method that works. Brain waves are measured and an audio signal sounds when alpha waves are detected. Alpha waves are brain waves that occur with a state of deep relaxation. By repeating the process, people using biofeedback connect the sound with the relaxed state, and learn to achieve relaxation on their own.

Meditation. Meditation, used for many years in Eastern cultures, is now widely accepted in this country as an effective relaxation technique. A number of studies are reporting its benefits for fibromyalgia patients who practice on a continued and regular basis. The practiced meditator can achieve the following physical benefits:

Reduced heart rate, blood pressure, adrenaline levels, and skin temperature while meditating.
Improved well-being.
Better sleep -- some research has reported an increase in melatonin levels in experienced meditators. Melatonin is important in regulating the sleep-wake cycle.
Less pain, possibly from reductions in levels of cortisol, a stress hormone.

An important goal for both religious and therapeutic meditation practices is to quiet the mind, essentially to relax thought. This redirection of brain activity from thoughts and worries to the senses disrupts the stress response and prompts relaxation and renewed energy. Several meditation techniques are available. Some may be more useful for fibromyalgia than others.

Breath meditation. Other meditative forms involve focusing on the present moment and observing (but not examining or judging) one's thoughts. During breath meditation, one sits upright with the spine straight and the eyes closed. The subject begins to breathe regularly and continues to observe the outward exhalation of the breath. As the mind wanders, one simply notes the thoughts as a fact and returns to the breath. A variant of this technique called mindfulness meditation has been helpful for fibromyalgia patients. It involves focusing on the present moment and letting thoughts pass without the accompanying breathing exercises.
Fixed point meditation involves focusing on a stationary object, mental image (such as a candle flame), or internal sound (such as a mantra). When the mind begins to wander, the meditator gently brings concentration back to the central image or sound. This exercise promotes focus, but it is often experienced as a thinking exercise. A popular variety of this type of meditation is known as transcendental meditation, or TM.
Mini-meditation. This method involves heightening awareness of the immediate surrounding environment. One should first choose a simple routine activity when alone. For example, while washing dishes concentrate on the feel of the water and dishes. Allow the mind to wander to any immediate sensory experience, such as sounds outside the window, smells from the stove, or colors in the room. If the mind begins to think about the past or future, abstractions, or worries, redirect it gently back.

People who try meditation for the first time should understand that it can be difficult to quiet the mind, and should not be discouraged by lack of immediate results. Some recommend meditating for no longer than 20 minutes in the morning after awakening and then again in the early evening before dinner. Even once a day is helpful. A person should probably not meditate before going to bed, because it causes some people to wake up in the middle of the night, alert and unable to return to sleep.

Hypnosis. In one small, short-term controlled study, hypnosis was more effective than physical therapy in improving function and reducing pain.

Massage Therapy. Massage therapy is thought to stimulate the parasympathetic nervous system, which slows down the heart and relaxes the body. In one study, patients who were given 30-minute massage sessions twice a week experienced lower stress and anxiety and less pain after 5 weeks compared to a group receiving an alternative therapy called transcutaneous electrical stimulation (TENS).

Because of the difficulties in treating fibromyalgia, many patients seek alternative therapies. Everyone should be wary of those who promise a quick cure or urge the purchase of expensive but potentially dangerous treatments.

Although some studies have reported benefit from these treatments, there is not enough evidence to recommend them. In one analysis, evidence was weakest on the advantages of so-called manipulative ("hands-on") approaches, such as chiropractic treatments.

Acupuncture. Studies continue to report conflicting results on acupuncture's ability to relieve pain. Several small studies suggest that it offers some benefit, especially to those who cannot take medicines because of their side effects. A larger controlled study found that inserting needles at fibromyalgia-related pressure points was no better at relieving pain for fibromyalgia than randomly inserting needles ("sham acupuncture"). A 2006 review of five randomized, controlled trials did not find enough evidence to support the use of acupuncture for fibromyalgia.

Click the icon to see an image of acupuncture.

Chiropractic or Osteopathic Manipulation. Chiropractic or osteopathic manipulation may also help some patients. While some studies have reported pain relief and improved sleep with osteopathic manipulation, larger controlled studies are needed to clearly identify whether manipulation is an effective treatment. Osteopathic techniques may include manipulation of the spine or muscle tissue release. Note that there is always some very small risk for adverse effects from any of these techniques. For example, in rare cases manipulation of the neck has caused stroke or damage to the large blood vessels in the neck.

Hydrotherapy and Similar Treatments. Hydrotherapy, also called balneotherapy, involves soaking in water, such as hot tubs, pools, or baths, to help relieve pain.

Herbal or Natural Remedies. Some alternative agents are being investigated for fibromyalgia:

Melatonin, a natural hormone associated with the sleep-wake cycle, may have benefits for some patients with fibromyalgia.
S-adenosylmethionine (SAMe) is a natural substance that has antidepressant, anti-inflammatory, and analgesic properties. It has shown some benefit in controlled studies.

It is extremely important for patients to realize that any herbal remedy or natural medicine that has positive effects most likely has negative side effects and toxic reactions, just as any conventional drug does. You should consult a doctor before using any untested products or dietary supplements. You should also discuss with your doctor any potential interactions between the supplements and any medications you take.

Generally, manufacturers of herbal remedies and dietary supplements do not need approval from the U.S. Food and Drug Administration to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even deadly side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Behavioral Therapy

Studies continue to show that fibromyalgia patients feel better when they deal with the specific conditions of their disorder and their lives. Cognitive-behavioral therapy (CBT) enhances a patient's belief in their own abilities and helps them develop methods for dealing with stressful situations. CBT, also called cognitive therapy, is a known, effective method for dealing with chronic pain from arthritic conditions. Some evidence also suggests that cognitive-behavioral therapy can help some patients with fibromyalgia.

Although the effects of CBT and other non-medication treatments for fibromyalgia do not always last over the long-term, they may help certain groups of people, particularly those with a high level of psychological stress.

CBT may be particularly useful for addressing insomnia, one of the hallmark symptoms of fibromyalgia. Patients who received CBT for insomnia woke up 50% less at night, and had fewer symptoms of insomnia and improved mood.

The Goals of CBT. The primary goals of CBT are to change any unclear or mistaken ideas and self-defeating behaviors. Using specific tasks and self-observation, patients learn to think of pain as something other than a negative factor that controls their life. Over time, the idea that they are helpless against the pain goes away and, instead, they learn that they can manage the pain.

Cognitive therapy is particularly helpful in defining and setting limits -- a behavior that is extremely important for these patients. Many fibromyalgia patients live their lives in extremes. They first become heroes or martyrs, pushing themselves too far until they collapse. This collapse reverses the way they view themselves, and they then think of themselves as complete failures, unable to cope with the simplest task. One important aim of cognitive therapy is to help such patients discover a middle route. Patients learn to prioritize their responsibilities and drop some of the less important tasks or delegate them to others. Learning these coping skills can eventually lead to a more manageable life. Patients learn to view themselves and others with a more flexible attitude.

The Procedure. Cognitive therapy usually does not last long, typically 6 - 20 one hour sessions. Patients also receive homework, which usually includes keeping a diary and trying tasks they have avoided because of negative attitudes.

A typical cognitive therapy program may involve the following measures:

Keep a Diary. Patients are usually asked to keep a diary, a key part of cognitive therapy. The diary serves as a general guide for setting limits and planning activities. Patients use the diary to track any stress factors, such as a job or a relationship that may be making the pain worse or better.
Confront Negative or Discouraging Thoughts. Patients are taught to challenge and reverse negative beliefs. For example, "I'm not good enough to control this disease, so I'm a total failure" becomes the coping statement, "Where is the evidence that I can control this disease?"
Set Limits. Limits are designed to keep both mental and physical stress within manageable levels, so that patients do not become discouraged by getting "in over their heads." For example, tasks are broken down into incremental steps, and patients focus on one at a time.
Seek out Pleasurable Activities. Patients list a number of enjoyable low-energy activities that they can conveniently schedule.
Prioritize. Patients learn to drop some of the less critical tasks or delegate them to others.

Patients should learn to accept that relapses occur, and that over-coping and accomplishing too much too soon can often cause a relapse of symptoms. Patients should respect these relapses and back off. They should not consider them a sign of failure.

Research also shows that patient education can be effective in treating fibromyalgia, especially when combined with CBT, exercise, and other therapies. Educational programs can take the form of group discussions, lectures, or printed materials, although there isn't any clear evidence on which type of education works best.

Cognitive therapy may be expensive and not covered by insurance. Alternative and effective approaches that are free or less costly include strong, intelligently managed support groups or group psychotherapy. In one center, educational discussion groups were as effective, or even more so, than a cognitive therapy program. Such results are not typical in all centers, of course. Therapeutic success varies widely depending on the skill of the therapist.

Medications

Typically the first choice in drug treatment of fibromyalgia has consisted of an antidepressant or a muscle relaxant. The goal has been to improve sleep and pain tolerance. Medications from other drug classes (such as sleeping aids and pain relievers) may also be prescribed. Patients receive drug treatments in combination with exercise, patient education, and behavioral therapies. In 2007 the Food and Drug Administration approved Pregabalin (Lyrica) as the first drug for the treatment of fibromyalgia.

Pregabalin is an anti-epileptic. Also called anti-seizure drugs and anti-convulsants, these medicines affect the chemical messenger gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing.

Pregabalin was previously approved in 2004 to treat nerve pain and diabetic peripheral neuropathy. A 2005 study of 529 patients with fibromyalgia reported that 450 mg per day of pregabalin reduced pain and improved sleep quality and fatigue symptoms. Study results presented in November 2006 showed pregabalin cut fibromyalgia pain by at least 50% in 63% of patients, and the effect was long-lasting. The study, lasting 6 months, was one of the longest controlled studies of pregabalin in fibromyalgia to date. The most common side effects include mild-to-moderate dizziness and sleepiness. Pregabalin can impair motor function and cause problems with concentration and attention. Patients should talk to their doctor about whether pregabalin may impair their ability to drive.

Studies have shown that another anti-convulsant, gabapentin (Neurontin), which is approved for treatment of postherpetic neuralgia, affects pain transmission pathways and may relieve pain associated with fibromyalgia when compared with placebo. Patients who took gabapentin also reported that they slept better and were less tired.

The main classes of antidepressants used for treating fibromyalgia are tricyclics, selective serotonin-reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). Although these drugs are antidepressants, doctors prescribe them to improve sleep and relieve pain in non-depressed patients with fibromyalgia. The dosages used for managing fibromyalgia are generally lower than dosages prescribed for treating depression. If a patient has depression in addition to fibromyalgia, higher doses may be required.

Tricyclics. Tricyclic antidepressants cause drowsiness and can be helpful for improving sleep. The tricyclic drug most commonly used for fibromyalgia is amitriptyline (Elavil, Endep), which produces modest benefits with pain, but which can lose effectiveness over time. Other tricyclics include desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), amoxapine (Asendin), and nortriptyline (Pamelor, Aventyl).

Generally, only small doses of tricyclic antidepressants are needed to relieve fibromyalgia. Therefore, although tricyclics have several side effects, these side effects may be less frequent in fibromyalgia patients than in those taking tricyclics for depression. Side effects most often reported include:

Blurred vision
Difficulty urinating
Dizziness
Drowsiness
Dry mouth
Heart rhythm disturbances
Sexual dysfunction
Weight gain

As with all medications, tricyclics must be taken as directed. An overdose can be life-threatening.

Unfortunately, not all patients respond to tricyclics, and their effects wear off in some patients, sometimes after only a month.

Selective Serotonin-Reuptake Inhibitors. Selective serotonin-reuptake inhibitors (SSRIs) increase serotonin levels in the brain, which may have specific benefits for fibromyalgia patients. Commonly prescribed SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), and fluvoxamine (Luvox). Studies suggest they may improve sleep, fatigue, and well-being in many patients. Studies are mixed on whether they improve pain. SSRIs should be taken in the morning, since they may cause insomnia. Common side effects are agitation, nausea, and sexual dysfunction, including delay or loss of orgasm and low sex drive.

Serotonin-Norepinephrine Reuptake Inhibitors. Serotonin-norepinephrine reuptake inhibitors (SNRIs) are also known as dual inhibitors because they act directly on two chemical messengers in the brain -- norepinephrine and serotonin. These drugs include:

Duloxetine (Cymbalta) is gaining attention as a treatment for fibromyalgia. In a 2004 study, 207 patients with fibromyalgia were randomized to receive either 60 mg of duloxetine twice a day or placebo for 12 weeks. Duloxetine significantly improved pain and tenderness and was effective for both depressed and non-depressed patients. Duloxetine was most effective for women, but very few men were enrolled in this trial.
Venlafaxine (Effexor) is similar to fluoxetine (Prozac) in effectiveness and tolerability for most patients. As with SSRIs, and unlike other newer antidepressants, venlafaxine impairs sexual function. Although clinical trials have shown that the drug is safe and effective in most people, there have been reports of changes in blood pressure. There have also been reports of problems with the electrical system of the heart when taking this drug. These side effects may cause serious problems in elderly patients. Some patients report severe withdrawal symptoms, including dizziness and nausea.
Milnacipran (Ixel) is under investigation and is not yet approved in the United States. It is specifically being researched for helping people with fibromyalgia and similar pain syndromes. In a 2004 study of 125 patients, milnacipran improved fibromyalgia pain and other symptoms, including fatigue, sleep, and depression.

Cyclobenzaprine (Flexeril) relaxes muscle spasms in specific locations without affecting overall muscle function. Cyclobenzaprine is related to the tricyclic antidepressants and has similar side effects, including drowsiness, dry mouth, and dizziness. A 2004 review of five randomized controlled trials found that patients who received cyclobenzaprine were three times more likely to report improvement in fibromyalgia symptoms than patients who received placebo.

Zolpidem (Ambien) or other newer sleep medications such as zaleplon (Sonata) and eszopiclone (Lunesta) may improve sleep for patients who suffer from insomnia.

Pain relief is of major concern for patients with fibromyalgia. Pain relievers for fibromyalgia include:

Tramadol (Ultram), used alone or in combination with acetaminophen (Tylenol), is commonly prescribed for relief of fibromyalgia pain. Its most common side effects are drowsiness, dizziness, constipation, and nausea. Tramadol should not be used in combination with tricyclic antidepressants.
For relief of mild pain, acetaminophen is most often recommended. Anti-inflammatory drugs, which are commonly used for arthritic conditions, are less useful for the pain of fibromyalgia, since the pain is not caused by muscle or joint inflammation. Anti-inflammatory drugs include corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen (Advil).
Capsaicin (Zostrix) is an ointment prepared from the active ingredient in hot chili peppers. Capsaicin is helpful in relieving painful areas in other disorders. It may have some value for fibromyalgia patients.
Opioids, or narcotics, may be used occasionally by certain patients with moderate-to-severe pain, or those with significant problems performing everyday tasks. Such patients should use narcotics only if they cannot find relief with other, less potent treatments. Some patients may get combinations of narcotic pain relievers and acetaminophen for periodic pain. Some physicians prescribe opioids, such as oxycodone (Roxicodone) or morphine sulfate (Duramorph), for patients who need ongoing relief. However, the benefit of opioids in fibromyalgia treatment is highly controversial. Physicians should take a careful medical and psychological profile of the patient before prescribing opioids. The patients should be evaluated periodically for continuing pain relief, side effects, and indications of dependence.
Pramipexole, a drug used to treat Parkinson’s disease and restless legs syndrome, may help relieve pain and fatigue in people with fibromyalgia, according to one study. Pramipexole stimulates production of dopamine, a chemical messenger in the brain. Researchers compared pramipexole with a dummy pill (placebo). After 3.5 months, 36% of those who took pramipexole said they felt much better, compared to 9% of those who received a dummy pill. Overall, patients had a 50% or greater decrease in pain.
One small 2005 study conducted in Spain suggests that the atypical antipsychotic olanzapine (Zyprexa) may be a beneficial add-on therapy for patients with fibromyalgia. Although proven effective for some chronic pain conditions, olanzapine and other antipsychotics cause unpleasant and potentially serious side effects.

Tropisetron. Tropisetron (Navoban) is a drug used to reduce vomiting during chemotherapy. European studies suggest that it may also help patients with fibromyalgia by reducing pain, dizziness, and depression, and by improving sleep. Fatigue and dizziness are the most common side effects.

Much of the pain patients experience occurs where muscles join tendons or bones, particularly when the muscles are stretched. Stretching or flexibility exercises are part of the warm-up and cool-down routines of any regular exercise program. Stretching techniques may also use injections or cooling agents to inactivate the pressure points so that muscles can be more effectively stretched. These techniques must be performed by a person other than the patient, usually a family member or close friend. With either injections or the spray, the benefits may last from a few days to weeks. Neither the spray nor the injection is useful without muscle stretching.

Spray and Stretch. One technique is known as "spray and stretch." This method uses the following approach:

The patient must be in a comfortable position.
The partner presses on suspected tender points and the patient reports any pain.
The points, when targeted, are sprayed with either ethyl chloride (Chloroethane) or Fluori-Methane. These chemicals are not numbing medicines. They cool the blood vessels in the skin to inactivate the tender points. Numbing skin creams do not appear to be effective for this treatment.
The spray bottle is held upside-down about 12 - 18 inches from the targeted area. The patient's face should be covered if the spray is being used near the head.
The patient's partner then slowly stretches the affected muscle.

After the procedure, the muscle should feel looser, and the patient should have a greater range of motion with that muscle.

Trigger-Point Injections. In some cases, "trigger-point injections" of a numbing drug, such as lidocaine, may be used for particularly painful tender points as an aid to stretching.

The injection causes intense, but brief, pain in the trigger point. After the medication has taken effect, however, the muscle's ability to stretch is much greater.
There is some soreness afterward, which can be severe. After an injection, spraying the whole muscle with cooling agents may inactivate less severe tender points.
In some cases, injections may be needed several times over 6 - 8 weeks.

Resources

www.rheumatology.org -- American College of Rheumatology
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.arthritis.org -- Arthritis Foundation
www.fmaware.org -- National Fibromyalgia Foundation
www.fmpartnership.org -- National Fibromyalgia Partnership
www.fmnetnews.com -- Fibromyalgia Network
www.aapainmanage.org -- American Academy of Pain Management
www.ampainsoc.org -- American Pain Society
www.medicalacupuncture.org -- American Association of Medical Acupuncture
www.asch.net -- American Society of Clinical Hypnosis
www.aabt.org -- Association for Advancement of Behavior Therapy
www.clinicaltrials.gov -- Find a clinical trial

References

Arnold LM, Goldenberg DL, Stanford SB, Lalonde JK, Sandhu HS, Keck PE, et al. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled multicenter trial. Arthritis & Rheumatism. 2007;56:1336-1344.

Assefi NP, Sherman KJ, Jacobsen C, Goldberg J, Smith WR, Buchwald D. A randomized clinical trial of acupuncture compared with sham acupuncture in fibromyalgia. Ann Intern Med. 2005; 143(1): 10-9.

Da Costa D, Abrahamowicz M, Lowensteyn I, Bernatsky S, Dritsa M, Fitzcharles MA, Dobkin PL. A randomized clinical trial of an individualized home-based exercise programme for women with fibromyalgia. Rheumatology. 2005;44:1422-1427.

Harris RE, Clauw DJ. How Do We Know That the Pain in Fibromyalgia Is "Real"? Current Pain and Headache Reports. 2006;10:403-7.

Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. Decreased central u-opioid receptor availability in fibromyalgia. J Neurosci. 2007;27:10000-10006.

Holman AJ, Myers RR. A Randomized, Double-Blind, Placebo-Controlled Trial of Pramipexole, a Dopamine Agonist, in Patients With Fibromyalgia Receiving Concomitant Medications. Arthr Rheum. 2005; 52(: 2495-2505.

Mannerkorpi K, Henriksson C. Non-pharmacological treatment of chronic widespread musculoskeletal pain. Best Pract Res Clin Rheumatol. 2007;21:513-534.

McCabe CS, Cohen H, Blake DR. Somaesthetic disturbances in fibromyalgia are exaggerated by sensory-motor conflict: implications for chronicity of the disease? Rheumatology. 2007;46:1587-1592.

Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol Suppl. 2005;32(10):2063.

Rico-Villademoros F, Hidalgo J, Dominguez I, García-Leiva JM, Calandre EP. Atypical antipsychotics in the treatment of fibromyalgia: a case series with olanzapine. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(1): 161-4.

Rooks DS, Gautam S, Romeling M, Cross ML, Stratigakis D, Evans B, et al. Group exercise, education, and combination self-management in women with fibromyalgia. Arch Intern Med. 2007;167;2192-2200.

Van Koulil S, Effting M, Kraaimaat FW, van Lankveld W, van Helmond T, Cats H, et al. Cognitive-behavioural therapies and exercise programmes for patients with fibromyalgia; state of the art and future directions. Ann Rheum Dis. 2007;66:571-581.

Zheng L, Faber K. Review of the Chinese medical approach to the management of fibromyalgia. Curr Pain Headache Rep. 2005;9(5): 307-12.

Review Date:
12/17/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Chronic fatigue syndrome

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Risk Factors
Causes
Diagnosis
Prognosis
Treatment
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Causes

Four out of five people with chronic fatigue syndrome (CFS) are infected with an enterovirus -- one of the viruses that cause respiratory and gastrointestinal infections -- compared with only one out of five healthy people. The virus might be a trigger for CFS, although research has not yet confirmed a cause-and-effect relationship.

Diagnosis

According to new guidelines, symptoms that suggest a diagnosis of CFS include disabling fatigue that starts suddenly, lasts a long time, keeps coming back, and can't be explained by another condition. Other symptoms may include difficulty concentrating or sleeping, dizziness, headaches, muscle or joint pain, sore throat, and palpitations. Doctors should consider a diagnosis of CFS if symptoms have lasted for 4 months in adults or 3 months in children.
Researchers have found that people with CFS have altered amounts of slow wave sleep, which could indicate a problem with sleep regulation.

Treatment

According to one study, people with CFS who used cognitive behavioral therapy (CBT) had higher mental health scores, and were able to walk faster and with less fatigue than those who didn't use the therapy.
A 2007 study found that taking two 10 milligram doses of methylphenidate (Ritalin) each day works much better than placebo at relieving fatigue and concentration problems in people with CFS.

Introduction

Chronic fatigue syndrome (CFS), sometimes called immune dysfunction syndrome or myalgic encephalomyelitis (in Europe), is not a new disorder. In the 19th century the term neurasthenia, or nervous exhaustion, was applied to symptoms resembling CFS. In the 1930s through the 1950s, outbreaks of disease marked by prolonged fatigue were reported in the United States and many other countries. Beginning in the early- to mid-1980s, interest in chronic fatigue syndrome was revived by reports in America and other countries of various outbreaks of long-term debilitating fatigue.

Unexplained chronic fatigue describes fatigue that lasts for more than 6 months, impairs normal activities, and has no identifiable medical or psychological problems to account for it. In addition to fatigue, people may complain of other problems, such as difficulty with memory or concentration, headaches, or sore muscles or joints.

The symptoms of CFS may be categorized as follows:

Chronic fatigue syndrome (CFS). A number of criteria must be met in order for a patient's symptoms to be described as CFS. Six million patient visits are made each year because of fatigue, although only a very small percentage of these visits can be attributed to actual chronic fatigue syndrome.
Idiopathic chronic fatigue. If the symptoms do not meet the criteria for CFS, the condition is referred to as idiopathic chronic fatigue, meaning the cause is unknown.

Although the exact causes of CFS are not known, researchers think infection, genetics, hormonal imbalances, and chemical toxins play roles in different patients.

Risk Factors

In studies of large patient groups, 15 - 27% of people complain of long-term fatigue, but the majority of this fatigue can be explained by other medical or psychological problems. According to surveys, chronic fatigue syndrome (CFS) itself affects more than four out of every 1,000 Americans.

CFS occurs in both sexes, at all ages, and in all racial and ethnic groups. The Centers for Disease Control and Prevention estimates 1 million people in the U.S. have the disease, but only 20% of people with CFS may be properly diagnosed. Nevertheless, the true prevalence of CFS is very difficult to determine, since an accurate diagnosis is hard to obtain.

People ages 40 - 50 most often experience chronic fatigue. Studies have found that four out of five people with CFS are women, although a woman's symptoms do not appear to be more severe symptoms than those of men with the disorder.

Children and adolescents are not immune to CFS. Most studies indicate that girls are more likely than boys to develop CFS, although one study found the incidence of the syndrome to be equal in children among the genders.

The link between psychological disorders and chronic fatigue syndrome is problematic because so many of the symptoms overlap. The rates of depression are very high in CFS patients, possibly higher than in patients with other conditions (notably fibromyalgia and multiple chemical sensitivity).

Studies report that most children and adolescents with CFS have psychiatric disorders. Psychological factors during childhood may increase susceptibility for later CFS, although these factors are not consistent. Studies have not found any consistent association between emotional or personality disorders and CFS to explain any causal role. Some psychological factors may, however, serve as a risk factor for CFS.

Depression, in any case, is very common in the general population. It affects up to one-fifth of all Americans at some point in their lives, and most depressed people feel fatigued.

There is some evidence that stress may be a trigger for CFS in people genetically at risk for the disease.

A number of conditions overlap or coexist with chronic fatigue syndrome and have similar symptoms. Patients with CFS may also have a diagnosis of fibromyalgia, multiple chemical sensitivity, or both. It is not clear whether these conditions or others are risk factors for CFS, are direct causes, have common causes, or have no relationship at all with CFS.

Fibromyalgia. Fibromyalgia causes prolonged fatigue and widespread muscle aches. It is the disease most often confused with CFS. The two conditions also commonly appear together. In fact, many experts believe fibromyalgia is simply another variant of chronic fatigue syndrome or different manifestations of the same disease. CFS patients experience severe fatigue, whereas fibromyalgia patients experience more pain. One hypothesis proposes that the connection between the two conditions may be found in central sensitization, which is thought to cause fibromyalgia and may also cause CFS.

A characteristic feature of fibromyalgia is the existence of at least 11 distinct sites of deep muscle tenderness that hurt when touched firmly. The sites often include the following:

The side of the neck
The top of the shoulder blade
The outside of the upper buttock and hip joint
The inside of the knee

Some patients with CFS exhibit similar tender pressure points. Recurrent sore throat, headache, low fever, and depression are also common symptoms of fibromyalgia. Like CFS, fibromyalgia is chronic and not curable.

Multiple Chemical Sensitivity. Multiple chemical sensitivity (MCS) is a term now used to describe a condition in which certain chemicals are believed to cause symptoms similar to CFS in some people. It has also been observed in people with CFS. The following proposed criteria can help recognize people with MCS:

The symptoms are reproducible with repeated exposure to a chemical. (These are often common chemicals found in popular products, such as perfumes, fabric softeners, and air fresheners.)
The condition is chronic.
Symptoms can be produced by exposure to the chemical at levels lower than previously or commonly tolerated.
The symptoms improve when the chemical is removed.
Symptoms can be triggered by multiple substances that are chemically unrelated.
Symptoms involve multiple organ systems.

Still, as with CFS and fibromyalgia, there is uncertainty as to whether MCS is an actual medical condition or is psychologically based. In one study, for example, CFS patients who believed their problem was chemically triggered were exposed to either an active chemical or a placebo (an inactive substance). Both groups reported symptoms, including those exposed only to the placebo. It should be noted that everyone is exposed to many chemicals on a daily basis, and it is very difficult to determine whether chemicals are responsible for specific symptoms.

Post-ADD. Young adults who had attention deficit disorder as children can flip from hyperactivity to fatigue. Such patients have severe hypersomnolence (sleeping too much, sleeping at any time or anywhere). These patients respond well to psychostimulant medications.

Eating Disorders. Eating disorders, notably bulimia and anorexia, have been observed in patients with CFS. The conditions often have overlapping risk factors, although it is unclear whether there is a causal relationship.

Other Conditions that Commonly Coexist With CFS. A number of other conditions also often coexist with CFS and, in fact, occur at higher-than-average rates among CFS patients:

Chronic headaches
Cognitive problems such as difficulty concentrating, impaired memory, and symptoms of attention deficit disorder
Interstitial cystitis
Irritable bowel syndrome
Sleep problems
Temporomandibular disorder (TMD)

Causes

Theories abound about the causes of chronic fatigue syndrome. Indeed, no primary cause has been found that explains all cases of CFS, and no blood tests or brain scans can definitively diagnose the condition.

Convergence of Factors. A number of experts believe that CFS develops from a convergence of conditions that may include the following:

Genetic factors
Brain abnormalities
A hyper-reactive immune system
Viral or other infectious agents
Psychiatric or emotional conditions

For example, the majority of patients report some preceding moderate-to-serious physical illness (such as a chronic viral infection) or emotional event (like an episode of depression). Some experts theorize that such events, alone or in combination, may interact with certain neurologic and genetic abnormalities to trigger the event.

Still, it is not clear what sequence of events actually leads to the fatigue and other prominent symptoms of this disorder. Nor is there any specific brain or nervous system problem that experts can point to with assurance. Research indicates that CFS is more common among identical twins (who share the same genes) than fraternal twins (who share only some genes). Inheritance, then, may play a role in roughly 30 - 50% of cases, similar to the influence thought to occur in depression or alcoholism, although specific genes have not yet been identified.

New evidence suggests genes involved in the body's response to stress may play key roles in CFS. A series of 14 articles published in 2006 linked CFS with genes involved in the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. The researchers were able to locate a common variation of DNA sequences that predicted CFS with 76% accuracy. The genes control response to trauma, injury, and other stressful events. Nevertheless, the researchers were unable to find genetic markers of CFS or to determine how the genetic variations influenced symptoms.

In 2005, English researchers found that people with CFS are more likely than people without CFS to have human leukocyte antigen (HLA) class II alleles, variations that produce antibodies to certain immune factors. Another British study of people with CFS found alterations in 16 specific genes involved with immune function, communication between cells, and transfer of energy to cells.

Abnormal levels of certain chemicals regulated in the brain system known as the hypothalamus-pituitary-adrenal (HPA) axis have been proposed as a cause of CFS. This system controls important functions, including sleep, response to stress, and depression. Of particular interest to researchers are the following chemicals and other factors controlled by the HPA axis:

Changes in Important Neurotransmitters. Research has reported that some patients with CFS have abnormally high levels of serotonin, a neurotransmitter (chemical messenger in the brain). Such elevated levels in the brain are associated with fatigue. Studies also suggest that deficiencies of dopamine, an important neurotransmitter associated with feelings of reward, may play a role in CFS. Imbalances between norepinephrine and dopamine have been identified in certain CFS patients in several studies. Unfortunately, routine clinical testing for such chemical imbalances is cost-prohibitive.
Stress Hormone Deficiencies. A number of studies on CFS patients have observed lower levels of cortisol, a stress hormone produced in the adrenal glands. Cortisol is a precursor of dehydroepiandrosterone (DHEA), a weak male hormone that may also be important in CFS. Deficiencies may be the reason why CFS patients have an impaired and weaker response to psychological or physical stresses, such as infection or exercise. (Administering replacement cortisol improves symptoms only in some patients, indicating other factors are involved.)
Disturbed Circadian Rhythms. Evidence suggests that, in certain patients, CFS is a disorder of the sleep-wake cycle, which is regulated by the so-called circadian clock, a nerve cluster in the hypothalamus-pituitary-adrenal (HPA) axis. Some mentally or physically stressful event, such as a viral infection, may disrupt natural circadian rhythms, and an inability to reset these rhythms results in a perpetual cycle of sleep disturbances. Medications that improve sleep can be very helpful for certain patients with CFS.

However, it is still not clear whether any of these changes are causes of chronic fatigue syndrome, or merely findings in some patients.

Because most of the features of CFS resemble those of a lingering viral illness, many researchers have focused on the possibility that a virus or some other infectious agent causes the syndrome in some cases.

Still, not all CFS patients show signs of infection. Although experts have long been divided on whether infections play any role in this disorder, subtypes of viral-related and non-viral CFS may both exist.

Viruses. The theory that CFS has a viral cause is not based on hard evidence, but on various observations that suggest an association, such as the following:

CFS patients typically have elevated levels of antibodies to many organisms that cause fatigue and other CFS symptoms. Such organisms include those that cause Lyme disease, candida ("yeast infection"), herpesvirus type 6 (HHV-6), human T cell lymphotropic virus (HTLV), Epstein-Barr, measles, coxsackie B, cytomegalovirus, or parvovirus. Many of these infectious agents are very common, however, and none has emerged as a significant cause of CFS.
In up to 80% of cases, chronic fatigue syndrome starts suddenly with a flu-like condition.
In the U.S., there have been reports of cluster outbreaks of CFS occurring within the same household, workplace, and community (but most have not been confirmed by the Centers for Disease Control and Prevention).
One study found that four out of five people with CFS are infected with an enterovirus -- one of the viruses that causes respiratory and gastrointestinal infections -- compared to only one out of five healthy people. The virus could be a trigger for CFS, although research has not confirmed a cause-and-effect relationship.

Some researchers are suggesting that changes in normally harmless bacteria found in the intestine may play a role in the development of CFS.

Evidence suggesting that some CFS cases may not be due to a virus includes the following:

Most cases of CFS occur sporadically. They occur in individuals and do not appear to be contagious.
There is no evidence that CFS is spread through casual contact, such as shaking hands or coughing, or by intimate sexual contact.
No single virus has been implicated in chronic fatigue syndrome. Well-designed studies of patients who met strict criteria for chronic fatigue syndrome and of patients with chronic fatigue without any known cause have not found an increased incidence of any specific infections.

CFS has sometimes been referred to as the "chronic fatigue immune dysfunction syndrome." A number of studies have found many irregularities of the immune system. Some components appear to be over-reactive, while others appear to be under-reactive, but no consistent picture has emerged to explain CFS as a disease of the immune system.

Allergies. Some studies have reported that a majority of CFS patients have allergies to foods, pollen, metals (such as nickel or mercury), or other substances. One theory is that allergens, like viral infections, may trigger a cascade of immune abnormalities leading to CFS. (Most allergic people do not have CFS.)

Autoimmune Abnormalities. The risk profile for chronic fatigue syndrome is similar to the risk profiles for a number of autoimmune diseases. Studies are inconsistent, however, in reporting the presence of autoantibodies (antibodies that attack the body's own tissues) in CFS, and the disease is unlikely to be due to autoimmunity.

Studies have observed that some patients who fit the strict criteria for chronic fatigue syndrome also have symptoms of a condition known as neurally mediated hypotension (NMH). NMH causes a dramatic drop in blood pressure when a person stands up, even for as short a time as 10 minutes. Its immediate effects can be lightheadedness, nausea, and fainting.

However, not all CFS patients experience NMH, and studies have reported no higher incidence of NMH in chronic fatigue patients.

Psychological, personality, and social factors are strongly associated with chronic fatigue in most patients. The complex relationship between physical and emotional factors has yet to be fully understood, however. Studies have not found any consistent association between emotional or personality disorders and CFS to explain a causal role. Psychological factors, then, are unlikely to be a primary cause of CFS. They may play a role in increasing susceptibility to the disorder. Certainly, in many cases, CFS promotes psychological and social dysfunction.

Overall, doctors are increasingly adopting the view that CFS is probably a disease category that includes a range of subtypes, in the same way that cancer is a broad term within which numerous specific forms occur. Mounting evidence suggests that different subtypes of CFS have different causes and manifestations, and that these various types require different treatment approaches.

Research on subgroups of CFS is underway, but it is still in the very early stages. To date, however, clinical experience and limited data suggest that subgroups of CFS may include the following:

Post-ADD CFS: Young adults who had attention deficit disorder as children, who have flipped from hyperactivity to fatigue. Such patients have severe hypersomnolence (sleeping too much, sleeping any time or anywhere). Such patients respond well to psychostimulant medications.
Neurological CFS: These patients have more severe cognitive symptoms than do patients in the other groups. They may have trouble thinking, remembering, and paying attention. Although cognitive difficulties affect the vast majority of patients with CFS, this group experiences significantly more severe symptoms. Visual-spatial problems are common, as are sensitivities to light and noise. Other symptoms in this group include seizure-like episodes and other abnormalities that suggest temporal lobe seizures. Patients in this group tend to have severe sleep problems in which they never achieve stages 3 or 4 of the sleep cycle, awaken unrefreshed, and respond well to sleep-improving drugs.
Post-viral CFS versus gradual-onset CFS: According to some experts, an estimated 70% of patients are healthy until a particular illness strikes. In gradual-onset patients, however, symptoms develop gradually, and patients are unable to recall any specific viral or infectious illness that initiated the process.
Patients with immune abnormalities versus those without such abnormalities: Immune dysfunction (such as CD4, CD8, RNase, and TH1-TH2 imbalances) can leave some CFS patients unable to fight viruses effectively and cause their bodies to launch wrongful attacks against healthy tissues. Other CFS patients, however, do not have these immune abnormalities, or have only borderline shifts in immune factors.
CFS with Orthostatic Intolerance or Neurally Mediated Hypotension (NMH). These conditions cause dizziness (or unconsciousness) when a person stands up, due to a drop in blood pressure.
CFS with neuroendocrine abnormalities: Such problems may include dysregulation of cortisol or ACTH levels.
Activity level: There may be a difference between low-active versus high-active patients.
Patients with CFS alone: This subgroup may be different than CFS in patients with other conditions, such as fibromyalgia or multiple chemical sensitivity.

Observations that different treatments work for select patients appear to support the idea that subtypes of CFS require distinct approaches. The existence of subgroups may also explain why CFS researchers are frequently unable to replicate their results in subsequent studies; patient selection in studies to date has not reflected such careful discrimination. Researchers are now, however, working to define the subgroups of CFS and identify which treatments are most effective for each.

It should be noted that while the subgroup theory is interesting, in some cases the differences among patient populations may also reflect stages of disease. For instance, in the initial stages of the disease, many patients are symptomatic and have particular psychological symptoms, including alarm, denial, and anger. In contrast, patients in later phases of the disease typically have learned to cope better with their symptoms and have a degree of acceptance. Patients' mental and emotional status may have biological consequences that bear on their physical symptoms. Such a relationship is not yet documented in CFS patients, however, and remains subject to research.

Sudden- and Gradual-Onset CFS. One interesting theory is that CFS can be categorized as either sudden- or gradual onset, with each subgroup having different causes. In over half of patients, the onset is sudden, while the remaining patients have a slow onset. Some experts believe that sudden-onset CFS may be triggered by a virus or neurologic abnormality, while gradual-onset CFS might have a psychological or other cause. Supporting this theory was a study that looked at MRI scans of the brains of CFS patients who didn't have an accompanying psychiatric problem, and showed small injuries suggesting either a viral infection or neurologic problem. Still other experts believe that in some cases, gradual-onset CFS may be traced to cognitive disorders that were present during childhood, but went unrecognized until symptoms advanced into adulthood.

Diagnosis

It is very difficult to diagnose chronic fatigue syndrome. Even experts do not have a clear definition of what chronic fatigue actually is or what mechanisms in the brain or nervous system are responsible for it. The best diagnostic approach is to determine if the patient matches the criteria for CFS and to rule out other possible causes of symptoms.

In May 2006, the Centers for Disease Control and Prevention (CDC) released a revised definition for Chronic Fatigue Syndrome based on a consensus of many of the leading CFS researchers and doctors (including input from patient group representatives). In the revised definition, chronic fatigue syndrome is considered a subset of chronic fatigue, a broader category defined as unexplained fatigue that lasts for 6 months or longer. Chronic fatigue is considered a subset of prolonged fatigue, which is defined as fatigue that lasts for 1 month or more.

Unexplained chronic fatigue can be classified as CFS if the patient meets the following criteria:

Unexplained persistent or relapsing chronic fatigue that is either new or that started at a definite period of time; is not the result of ongoing exertion; is not substantially relieved by rest; and significantly reduces activities such as work, education, and social life.
Also, four or more of the following symptoms, which must have continued or recurred during 6 or more consecutive months of illness and must not have started before the fatigue:
- Significant impairment in short-term memory or concentration
- Sore throat
- Tender lymph nodes
- Muscle pain
- Joint pain without swelling or redness
- Headaches of a new type, pattern, or severity
- Unrefreshing sleep
- Malaise that lasts more than 24 hours after exertion

Any active medical condition that may explain the presence of chronic fatigue, such as:
- Untreated hypothyroidism
- Sleep apnea and narcolepsy
- Side effects of medication
An illness (such as cancer or hepatitis B or C virus infection) that relapsed or did not completely get better during treatment, that could explain the presence of chronic fatigue.
A past or current major depressive disorder, such as:
- Bipolar affective disorder
- Schizophrenia
- Delusional disorder
- Dementia
- Anorexia nervosa or bulimia nervosa
Alcohol or other substance abuse that occurs within 2 years of the onset of chronic fatigue and any time afterward.
Severe obesity as defined by a body mass index (BMI) equal to or greater than 45. (Note: Body mass index values vary considerably among different age groups and populations. No "normal" or "average" range of values can be suggested. The range of 45 BMI or higher was selected because it falls within the range of severe obesity.)

Any other abnormality found during an exam or other tests that could explain CFS symptoms must be resolved before further attempting to classify the condition.

In 2007, the National Institute for Health and Clinical Excellence (NICE) released new guidelines for the diagnosis and management of CFS in adults and children. According to these guidelines, CFS may be diagnosed if the person has disabling fatigue that starts suddenly, lasts a long time, keeps coming back, and can't be explained by another condition.

People with CFS also can have the following symptoms:

Difficulty thinking, concentrating, remembering, finding the right words, planning, and organizing
Difficulty sleeping
Dizziness or nausea
General malaise or flu-like symptoms
Headaches
Muscle or joint pain in many areas of the body without inflammation
Painful lymph nodes without disease
Fast heartbeat (palpitations) without heart problems
Sore throat
Worsening of symptoms with physical exertion

After ruling out other possible causes, the doctor should consider a diagnosis of CFS if symptoms have lasted for 4 months in adults or 3 months in children. Children should be diagnosed by a pediatrician.

A doctor should first take a careful personal and family medical history, which may include a psychological profile, as well as perform a thorough physical examination. Patients should be prepared to answer questions such as:

When did the fatigue first begin?
Does anything make it worse or better?
Is it better at certain times of the day?
Does physical activity make it worse?
Are there any other symptoms?
Has anyone else in the family ever complained of fatigue?
Is your personal and professional life stressful?

The doctor may also ask about any changes in weight or request a patient to monitor morning and afternoon body temperatures. Patients should report any drugs they are taking, including vitamins and over-the-counter or herbal medications.

Standard tests are typically recommended to rule out specific conditions that can cause persistent fatigue. These tests include:

Blood count
Blood tests for gluten sensitivity
C-reactive protein
Creatine kinase
Erythrocyte sedimentation rate or plasma viscosity
Liver function
Random blood sugar (glucose)
Serum calcium
Serum creatinine
Serum ferritin levels (only in children)
Thyroid function
Urea and electrolytes
Urine test for protein, blood, and glucose

No blood, urine, or other laboratory test can specifically diagnose CFS. If any test is abnormal, it is not useful for diagnosing CFS specifically, and the doctor should look for other causes of these abnormalities.

That being said, research published in 2005 found that certain components in urine were unique in people with CFS, and may someday be considered biomarkers of the disease. Additionally, antibodies to Epstein-Barr virus and increased levels of isoprostanes -- markers of oxidative stress -- have been found in the blood of people with CFS.

Among the many other common conditions that can lead to feelings of temporary exhaustion are the following:

Depression
Infections
Pregnancy
Extreme exercise
Excessive stress

In most of these cases, fatigue can be relieved with adequate rest. It is important to note that longstanding fatigue can be the harbinger of a serious medical or psychological problem. A number of more serious conditions may cause persistent fatigue and other symptoms of CFS and should be ruled out. Patients and doctors should not overlook these diseases, even if the conditions have been previously treated, because they may not have completely resolved or they may cause residual fatigue. Doctors can usually distinguish these diseases from CFS after a clinical evaluation and laboratory testing.

Infectious Mononucleosis and Epstein-Barr Virus. Infectious mononucleosis is marked by fatigue and swollen glands. It primarily affects adolescents and young adults. Some patients may have lingering fatigue that lasts for many months and blood tests that indicate a persistence of the Epstein-Barr virus (EBV), which causes mononucleosis.

Autoimmune Diseases. Some diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis, are caused by autoimmunity, a condition in which the person's immune system attacks the body's own tissues. The early symptoms of these conditions may mimic some of those that appear in CFS, such as muscle and joint pain and fatigue. These diseases, like CFS, also occur more often in women than in men. Most of these conditions can be confirmed with laboratory or x-ray/radiologic findings. However, some autoimmune diseases may evolve slowly, and even if a diagnosis of chronic fatigue syndrome is considered, doctors should keep track of any changes in symptoms over time in order to rule out these serious illnesses.

Post-Lyme Disease Syndrome. Rarely, patients treated for a diagnosis of Lyme disease continue to have nonspecific symptoms, which can last for years after antibiotic treatment and that resemble symptoms of chronic fatigue syndrome.

Psychosis and Severe Mental Disorders. The Centers for Disease Control (CDC), which set up the definitions in the U.S. for research in chronic fatigue syndrome, recognizes depression as one of the symptoms of CFS. However, according to the CDC, anyone with a history of major depression or other severe psychiatric disorders, including bipolar disorder and schizophrenia, does not meet the criteria for chronic fatigue syndrome.

Symptoms of major depression include the following:

A depressed mood every day
Significant weight gain or loss (10% or more of an individual's typical body weight)
Insomnia or excessive sleeping
Restlessness or a sense of being slowed down
Low energy every day
Worthless or inappropriately guilty feelings
An inability to concentrate or to make decisions
Suicidal thoughts

Major depression is likely to be responsible if a person has several of these symptoms and no physical symptoms (such as sore throat, aches and pains, or fever). The longer fatigue has continued without such physical symptoms, the more likely that the diagnosis is depression.

Of note, a persistent form of minor depression called dysthymia may be more difficult to differentiate from CFS and may actually account for a subset of CFS cases. Dysthymia is characterized by many of the same symptoms that occur in major depression, but they are less intense and last much longer, at least two years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities.

Patients with depression and those with CFS generally perceive their illnesses differently:

Patients with depression have significantly lower self-esteem, more thought distortions (for instance, focusing on the negative or personalizing their situations), and believe their conditions stemmed from psychological factors.
CFS patients, even those with concurrent depression or dysthymia, tend to identify medical causes as the source of their problems and to focus on physical symptoms.

Many previously healthy patients with CFS become depressed and anxious because they feel so exhausted all the time. CFS may also lead to highly stressful socioeconomic situations, such as social isolation and poverty, that can contribute to and even cause emotional disorders in susceptible individuals, which in turn can worsen CFS.

Sleep Disturbances. Certain sleep disorders may cause persistent fatigue and can be confused with CFS:

Sleep apnea is a common disorder that can cause daytime fatigue without the patient being aware of the problem. Apnea is actually a breathing disorder often marked by loud snoring and thrashing in bed. A person may not realize the problem exists unless it is brought to his or her attention by a sleeping partner or observer.
Narcolepsy is a peculiar and rare disorder in which a person suddenly falls asleep without any previous signs of fatigue.
Other sleep disorders that cause daytime fatigue include insomnia and restless legs syndrome.

Researchers have found that people with CFS have altered amounts of slow wave sleep, which could indicate a problem with sleep regulation. Non-restorative sleep and nighttime restlessness are the most common complaints of people with CFS.

Conditions that Cause Joint Pain, Muscle Aches, or Both. A number of illnesses cause one or more of CFS symptoms, including arthritic symptoms, fever, and fatigue.

Severe Obesity. People who are severely obese often have symptoms of chronic fatigue because of the stress imposed by the weight. People who are obese are also at particular risk for sleep apnea, which can confuse the diagnosis.

Other Medical Conditions that Usually Rule Out CFS. Many diseases, both benign and serious, can fully explain prolonged or chronic fatigue, including:

Hepatitis
Anemia
Hemochromatosis (a hereditary disease caused by iron overload) infections
Various forms of cancer
Neuromuscular diseases (such as myasthenia gravis)
Hypothyroidism
Diabetes

Drugs and Alcohol. Fatigue is a side effect of many prescription and over-the-counter medications, such as antihistamines. In addition, dependency on or abuse of alcohol or illicit drugs may manifest as chronic fatigue. Medications should be considered as a possible cause of fatigue if an individual has recently started, stopped, or changed medicines. Withdrawal from caffeine can produce depression, fatigue, and headache.

Prognosis

The physical severity of chronic fatigue syndrome varies. Most commonly, patients with CFS report that they have trouble fulfilling both home and work responsibilities.

CFS sufferers typically work part-time. In extreme cases, patients are severely disabled and even bedridden. Such patients can do virtually nothing, including even light housework.

Patients with CFS are more likely to lose their jobs, possessions, and support from friends and family than are people who have other conditions that cause fatigue.

Most patients say that while fatigue is the most incapacitating symptom, mental impairment, such as an inability to concentrate or remember, is the most distressing symptom. The effects of CFS on mental functioning are complex, however. Some experts believe that the impaired mental functioning is due to depression, which is common in CFS patients.

Some studies indicate that, although general intelligence is not impaired, CFS patients test lower in certain mental functions, particularly speed and efficiency in processing complex information, and that 40 - 60% have memory impairments. In such studies, this impaired mental function occurs regardless of the presence or absence of depression or other psychiatric disorders.

Because the illness remains elusive and poorly defined, and there are few objective measures for recovery, experts have found it difficult to determine the long-term course of the disease. Many patients are not covered by insurance or have difficulty finding good care, so available statistics may be incorrect. Bearing these factors in mind, some studies have reported that more than half of patients who complain of chronic fatigue are still fatigued at 2 years. Although a variety of studies have attempted to identify factors that predict a more chronic or severe course, no clear conclusions can be made. Even if patients get progressively worse, however, the disorder is not fatal.

Although children with symptoms of chronic fatigue have not been as rigorously studied as adults, limited evidence suggests that CFS can be significantly disabling in young people. Studies report that adolescents who meet the criteria for CFS also have greater anxiety, depression, and school absenteeism than their peers. Still, some studies indicate that children have a better prognosis than adults and that most will recover after 1 - 4 years. Several studies have indicated that cognitive-behavioral therapy is an effective treatment for adolescents with CFS.

Treatment

There is no proven or reliable cure for CFS, and no drug has been developed specifically for this disorder. Because CFS remains poorly understood, many patients have problems finding good care. Overall, the recommended strategy for treatment includes a combination of the following:

A healthy diet
Antidepressant drugs in some cases, usually low-dose tricyclics
Cognitive-behavioral therapy (CBT) and graded exercise for certain patients
Medication
Sleep management techniques

Patients with the best chance for improvement are those who remain as active as possible and who seek to have some control over the course of the disorder. Patients should choose physicians who are willing to consider the problem as a medical condition with psychiatric components. They should be very wary, however, if the physician recommends excessive and expensive treatments that may have serious adverse effects and that have no proven benefits. For patients with severe CFS that cannot be managed with lifestyle changes and standard medications, asking the physician about enrolling in any available clinical trials may be helpful.

Cognitive-Behavioral Therapy

CBT is designed to help CFS patients regain a sense of control, and is proving to have substantial benefits for some patients. Some experts believe that patients who are diagnosed with CFS should be referred to therapists trained in cognitive-behavioral therapy. (Psychoanalysis and other interpersonal psychological therapies, which are concerned with subconscious thoughts and early childhood memories, are not generally helpful for the CFS patient.)

The Goals of Cognitive-Behavioral Therapy. The primary goals of cognitive-behavioral therapy (referred to below as just cognitive therapy) are to change any distorted perceptions that individuals have of the world and of themselves, and to change their behavior accordingly. For CFS patients, this means learning to think differently about their fatigue and to improve their ability to deal with stressful situations and manage their disorder. It can also help manage their sleep problems and find the appropriate activity levels for them. Cognitive therapy is particularly helpful in defining and setting limits, behaviors that are extremely important for these patients.

The Procedure. CBT is usually performed over 6 - 20 sessions, each lasting about an hour. Patients are also given homework, which usually includes keeping a diary and attempting tasks that they have avoided because of negative attitudes.

A typical cognitive therapy program may involve the following measures:

Keep a Diary. The patient is almost always asked to keep an energy diary, which can be a key component of CFS cognitive therapy. The diary serves as a general guide for setting limits and planning activities. The patient uses the diary to track any factors, such as a job or a relationship that may be making the fatigue worse or better. It is also used to track the times of day when energy levels are at their highest and lowest peaks.
Adjust Schedule. The patient adjusts schedules to conform to energy peaks and valleys recorded in the diary. For instance, the patient may plan to take a nap during low-energy times and plan important activities during high-energy times. Developing fairly rigid daily routines around probable energy spurts or drops may help establish a more predictable pattern.
Confront Negative or Discouraging Thoughts. Patients are taught to challenge and reverse negative beliefs (such as "I'm not good enough to control this disease, so I'm a total failure."), and to use coping statements ("Where is the evidence that I can control this disease?")
Be Flexible. Energy levels will most likely never be entirely predictable. Patients must be prepared to adapt to energy variations. Instead of taking a long nap, for instance, patients may need 5- to 10-minute rest periods every hour or more, possibly involving relaxation or meditation.
Set Limits. Limits are designed to keep both mental and physical stress within a manageable framework so that patients do not get discouraged by forcing themselves into situations in which they are likely to fail. For example, tasks are broken down into incremental steps and patients focus on one step at a time.
Prioritize. Patients learn to drop some of the less critical tasks or delegate them to others.
Manage Impaired Concentration. Patients seek out activities that are appealing, focus attention, and help increase alertness. They learn to request instructions given as concise, simple statements. External distractions, such as music or talking, are kept to a minimum.
Accept Relapses. Over-coping and accomplishing too much too soon can often cause a relapse of symptoms. Patients should respect these relapses and back off. They should not consider them a sign of treatment- or self-failure.

Using both self-observation and specific tasks, patients gradually shift their fixed ideas that they are helpless against the fatigue that dominates their lives. They move to the perception that fatigue is only one negative and, to a degree, a manageable experience among many positive ones.

Success Rates. One review of CFS trials reported that, of all therapies available to CFS patients, only cognitive behavioral therapy (CBT) and graded exercise showed conclusive benefits. Although CBT doesn't appear to bring patients completely back to normal, research has found that people who used the therapy had higher mental health scores, and were able to walk faster and with less fatigue than those who didn't use CBT. A 2005 study found that cognitive therapy is an effective treatment for adolescents with CFS. Patients who received CBT reported improvements in fatigue, functional status, and school attendance.

Not all studies support the benefits of cognitive therapy for CFS. It is important to note that different therapists may have different fundamental assumptions about CBT and may use different techniques. For instance, some therapists believe that CFS is purely a psychological problem and that patients must reject the notion of physical causes, abandon all reliance on assistive devices, and participate in challenging exercise programs. In contrast, other therapists do not attempt to change patients' underlying beliefs at all, but instead focus on helping patients conserve energy and better cope with the limitations of their illness. When considering CBT, patients and their families must be aware of such important differences.

Regardless of whether specific organic causes of CFS are identified, the power of the mind to improve or oppose health problems is significant, and treatments that promote a positive outlook are beneficial for any disease.

A number of studies have suggested that a graded exercise program, in which patients perform increasingly more intense levels of exercise tailored to their individual abilities, has benefits for many patients with CFS. Exercise is best performed in combination with cognitive behavioral therapy.

Reports have found that 75% of CFS patients who were able to engage in exercise, particularly aerobic exercise, reported less fatigue and better daily functioning and fitness after a year. A 2004 review of clinical trials found that exercise therapy is beneficial for CFS, particularly when combined with patient education.

Some patient groups and experts contend that such studies use only patients with less severe conditions and do not apply to many CFS patients. Many patients have severe conditions, and some are very incapacitated (such as being wheelchair bound). These patients are unlikely to undergo even graded exercise. All CFS patients, in fact, have a lower exercise capacity than healthy individuals, and over-exercising can intensify symptoms. Some patients experience profound fatigue following even modest exercise. It is the primary factor in perpetuating the low-activity levels observed in these patients.

The following tips may be helpful for CFS patients when embarking on an exercise program:

Work with your health care provider to determine a good starting level of activity for you. Start slowly and incrementally, beginning with as few as 3 - 5 minutes of moderate exercise a day. The goal is to increase activity by about 20% every 2 - 3 weeks, until you can handle about 30 minutes a day. Once you reach 30 minutes a day, start to increase the aerobic intensity of your workouts. (Capacity varies greatly among CFS sufferers, however, and some may not be able to achieve this.)
Establish limits and keep within them in order to avoid overexertion and relapse.
Experiment with different forms of physical activity that suit your available energy levels. Some patients report great benefits from yoga or Tai Chi, which combine exercise with meditation.
Setbacks will occur, but do not become discouraged.

Work with your health care provider to find a level of activity you can handle. Then gradually increase your activity level. Activity management should involve:

Balancing your time between activity, rest, and sleep
Spreading out more challenging tasks throughout the week
Breaking big tasks into smaller, more manageable ones
Avoiding doing too much on days when you feel tired

Although there is no evidence to support any specific dietary factors in CFS, patients should be sure to maintain a healthy diet that includes:

Plenty of fresh dark-colored fruits and vegetables, which are rich in antioxidants
Fiber-rich foods
Limited saturated fats (found in animal products)
Omega-3 essential fatty acids, found in certain fish and oils
Increased salt (only for those with demonstrated low blood pressure)
Starchy foods, particularly for nausea

Stress Reduction Techniques. One panel of experts concluded that relaxation and stress-reduction techniques were helpful in managing chronic pain. These techniques also can help relieve the stress associated with the disease. They are not useful, however, as the primary treatment for CFS. A number of relaxation techniques are available:

Biofeedback
Deep breathing exercises
Hypnosis
Massage therapy
Meditation
Muscle relaxation techniques
Yoga

Light Therapy. Patients with seasonal affective disorder (SAD) experience more depression during the winter, when the hours of sunlight decrease. With light therapy (phototherapy), the patient sits for about 30 minutes each day a few feet away from a box-like device that emits very bright fluorescent light (4,000 lux). Light therapy is best performed immediately after awakening in the morning.

Some CFS patients don't have much improvement from light therapy. However, the treatment may still help some patients with CFS whose symptoms are similar to those of patients with seasonal affective disorder (SAD).

Supportive Family and Groups. Having strong, supportive relationships with family and friends can help CFS patients get better. However, CFS patients should try not to impose unreasonable expectations on loved ones that cannot be met. Ongoing support groups with fellow patients may be very helpful. In one study, sharing experiences in a group therapy setting proved to be the most valuable component in treatment, and one that improved patients' coping abilities.

Medications

No medications are specifically approved for the treatment of CFS. However, some may be useful for pain or other specific symptoms, or in cases where CFS may have a specific cause. Doctors generally use combinations of drugs to accomplish specific goals, such as medication at night to improve sleep and medication in the morning to improve cognition and energy. Treatment is very individualized.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Patients with CFS may find relief using NSAIDs -- common pain relievers that reduce pain and swelling. Types of NSAIDs include aspirin, ibuprofen (Motrin, Advil, Nuprin), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox).

Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding. Due to its proven cardiovascular benefits, aspirin was excluded from these labeling revisions.

NSAIDs can also increase blood pressure, particularly among people already being treated for hypertension. (About 12 - 15% of elderly people take both an NSAID and an antihypertensive drug.) Piroxicam, naproxen, and indomethacin appear to pose the greatest risk of high blood pressure. Sulindac has the smallest effect.

Other side effects of NSAIDs include:

Dizziness
Ringing in the ears
Headaches
Skin rashes
Possibly depression

NSAIDs can cause kidney damage. (The damage gets better once the patient stops using the drug.) People with high blood pressure, severe circulation disorders, or kidney or liver problems, as well as people taking diuretics or oral hypoglycemics, must be closely monitored if they need to use NSAIDs on a long-term basis. Because NSAIDs reduce blood clotting, NSAID users scheduled for surgery should stop taking those drugs a week before the operation.

COX-2 Inhibitors (Coxibs). Coxibs block an inflammation-promoting enzyme called COX-2. This class of drugs was initially believed to work as well as traditional NSAIDs, but with fewer stomach problems. However, numerous reports of cardiovascular events, skin rashes, and other adverse effects prompted the FDA to re-evaluate the risks and benefits of the COX-2 drugs. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the U.S. market following reports of heart attacks in patients taking the drugs. Celecoxib (Celebrex) was still available at the time of this report, but labeled with strong warnings and a recommendation that it be prescribed at the lowest possible dose for the shortest duration possible. Patients should ask their doctor whether the drug is appropriate and safe for them.

Because of the association between depression and CFS, antidepressants are often tried, with varying degrees of success. Common side effects of many antidepressants include:

Dry mouth
Restlessness
Reduced sexual drive
Slightly increased heart rate
Constipation

Virtually all antidepressants have complicated interactions with other drugs, and some are very serious.

Tricyclic Antidepressants. Antidepressants known as tricyclics may be particularly helpful for CFS patients. For example, the tricyclic amitriptyline (Elavil) is known to relieve many of the symptoms of CFS, including sleeplessness and low energy levels. These drugs may provide benefits by promoting deep sleep and inhibiting pain pathways in the nervous system. Improvement in symptoms can take 3 - 4 weeks. Other tricyclics include doxepin (Sinequan), desipramine (Norpramin), nortriptyline (Pamelor), clomipramine (Anafranil), and imipramine (Tofranil, Janimine). Patients with CFS normally respond to much lower doses than those used to treat people with depression. In fact, many CFS patients cannot tolerate the higher doses commonly used to treat the psychiatric disorder. Like all medications, tricyclics must be taken as directed. Overdose can be life-threatening. Tricyclics should not be taken together with SSRIs, because of the possibility of dangerous side effects.

Other Antidepressants. Newer, so-called designer SSRIs, including bupropion (Wellbutrin), nefazodone (Serzone), or mirtazapine (Remeron), affect combinations of different neurotransmitters, and some may have moderate benefits for CFS patients. For example, in one study, nefazodone improved mood, fatigue, and sleep disturbances.

SSRIs. The popular antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) may be helpful for the subgroup of CFS patients who experience significant depression. They include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). Cymbalta (duloxetine) is a new antidepressant that is classified as a selective serotonin and norepinephrine reuptake inhibitor (SSNRI).

In a 2006 UK study of 275 CFS patients, those treated with antidepressants recovered faster than those who did not receive the medication. SSRIs were found to be more effective than tricyclic antidepressants, producing improvements, including a reduction in fatigue, that were maintained at the 3-year follow-up.

Psychostimulants. Psychostimulants may be helpful for a subgroup of patients with CFS who have cognitive problems, such as difficulty concentrating, memory problems, and other attention deficit disorder (ADD)-like characteristics. Psychostimulants include Dexamphetamine, Adderal, methylphenidate (Ritalin) and Ritalin-like drugs such as Focalin, Concerta, Ritalin LA, and Metadate, as well as Strattera and Provigil. The NICE guidelines for CFS do not advise taking Dexamphetamine or Ritalin. However, a 2007 study found that taking two 10 mg doses of Ritalin each day works much better than placebo at relieving fatigue and concentration problems. More research is needed to study the long-term effects of Ritalin on CFS patients.

Because of the difficulties in treating chronic fatigue syndrome, many patients seek alternative therapies. Some, such as acupuncture, yoga, and relaxation techniques, may be helpful and are not dangerous. No scientific evidence exists that vitamin and mineral supplements will relieve CFS, but some people do report that they find supplements helpful.

Herbal and Supplements. Popular herbal and dietary supplement remedies for CFS include coenzyme Q10, vitamin B12, vitamin C, magnesium, multivitamins, DHEA, ginseng, and acetylcarnitine. None have been rigorously tested. Some herbs, such as St. John’s wort, ginkgo, and comfrey, may cause serious side effects and drug interactions.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products.

Some so-called natural remedies have been found to contain standard prescription medication. Of specific concern are studies suggesting that up to 30% of herbal patent remedies imported from China have been laced with potent pharmaceuticals, such as phenacetin and steroids. Most reported problems occur in herbal remedies imported from Asia. One study reported that a significant percentage of such remedies contain toxic metals.

CFS patients should be wary of any company that promises a cure or urges the purchase of expensive but useless and sometimes potentially dangerous treatments, such as the following:

St. John's wort. This herbal remedy is being investigated for mild depression. In one study, St. John's wort lessened fatigue in CFS patients, even in those who did not consider themselves to be depressed. However, the substance may have some serious side effects; for example, it can interact with blood thinning medication. In a brand comparison, only three St. John's wort products out of eight contained within 10% of the active ingredient amounts claimed on the labels.
Melatonin. Some patients use melatonin, based on the association between CFS and possible sleep abnormalities. However, the small amount of research available has not shown melatonin to be helpful.
Gingko. Although the risks for gingko appear to be low, there is an increased risk of bleeding at high doses. In addition, gingko can interact with high doses of vitamin E and anti-clotting medications. Commercial gingko preparations have also been reported to contain colchicine, an agent that can be harmful in pregnant women and people with kidney or liver problems. Some brands of gingko have no effect at all.
Comfrey. Comfrey is an herbal remedy used for a number of inflammatory problems. Recently, evidence has emerged that comfrey can be toxic to the liver, and animal studies have reported a possible cancer risk. Comfrey is banned in Canada and other countries, but is widely available in the U.S.

Of particular note for CFS patients are products containing the ingredient Ma Huang, which contains the stimulants ephedrine and kola nut, a caffeine source. Serious adverse reactions, including seizures, psychosis, and several deaths, have been reported in people taking this supplement for increased energy or weight loss. Products that have only one of these ingredients do not appear to have the same effect, but people should take so-called energy boosting supplements only with the knowledge and recommendation of their doctor.

Other alternative remedies with no proven benefit and possible toxic and dangerous side effects include the following:

Hydrogen peroxide injection (can cause blood clots or strokes)
Megadoses of vitamins (can be toxic and have shown no benefits)
High colonic enemas
Bee pollen (can cause an allergic reaction)
Injections of liver extract
Superoxide dismutase (SOD)

Resources

www3.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov/cfs - Centers for Disease Control and Prevention, Chronic Fatigue Syndrome information
www.cfids.org -- The Chronic Fatigue and Immune Dysfunction Syndrome Association of America
www.ncfsfa.org -- National Chronic Fatigue Syndrome and Fibromyalgia Association
www.aacfs.org -- American Association for Chronic Fatigue Syndrome
www.theacpa.org -- American Chronic Pain Association
www.ampainsoc.org -- American Pain Society
www.iasp-pain.org -- International Association for the Study of Pain
www.medicalacupuncture.org -- American Association of Medical Acupuncture
www.aabt.org -- Association for Advancement of Behavior Therapy

References

Armitage R, Landis C, Hoffmann R, Lentz M, Watson NF, Goldberg J, Buchwald D. The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome. Sleep. 2007;30:657-662.

Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006;119:e23-30.

Chia J, Chia AY. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol. 2008;61:43-48.

Goldman L, Ausiello D. Cecil Textbook of Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier, 2007.

Hampton T. Researchers find genetic clues to chronic fatigue syndrome. JAMA. 2006;295(21):2466-2467.

Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes preciptated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006;333(7568):575. Epub Sept 1.

Jones JF. Orthostatic instability in a population-based study of chronic fatigue syndrome. Am J Med. 2005;118:1415.

Kato K, Sullvan PF, Evengard B, Pedersen NL. Premorbid predictors of chronic fatigue. Arch Gen Psychiatry. 2006;63(11):1267-1272.

Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. 2006. Nov 18 (Epub ahead of print).

National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children. August 2007.

O'Dowd H, Gladwell P, Rogers CA, Hollinghurst S, Gregory A. Cognitive behavioural therapy in chronic fatigue syndrome: a randomized controlled trial of an outpatient group programme. Health Technol Assess. 2006;10:iii-iv, ix-x, 1-121.

Thomas MA, Smith AP. An investigation of the long-term benefits of antidepressant medication in the recovery of patients with chronic fatigue syndrome. Hum Psychopharmacol. 2006;21(:503-509.

Vermeulen RC, Scholte HR. Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of clinical data. J Transl Med. 2006;4:34.

Review Date:
1/4/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Skin wrinkles and blemishes

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Blemishes
Risk Factors
Prevention
Treatment
Resurfacing Treatments
Implant Procedures
Plastic Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Smoking and Skin Damage

The skin of smokers ages more rapidly than the skin of non-smokers, even in areas of the body not exposed to sunlight, according to a 2007 study. Women in the study who smoked also had much lower levels of vitamin E secretions in their skin. Vitamin E may protect the skin from sun damage.
There may be an association between smoking and higher frequency of a type of acne (noninflammatory acne) in adult women, according to a European study.

Antioxidants and Your Skin

A study in the Journal of Nutrition found that a combination of antioxidants and trace elements supplementation raises the risk of skin cancer in women, but not in men.

Ultraviolet Radiation

Overall, exposure to ultraviolet radiation from sunlight (radiation referred to as UVA or UVB) accounts for about 90% of the symptoms of premature skin aging.
UVB primarily affects the outer skin layers. It is most intense when sunlight is brightest. People receive slightly over 70% of their yearly UVB dose during the summer.
UVA penetrates more deeply and efficiently. The intensity of UVA rays is less dependent on the time of day and season of the year than that of UVB rays.

Vitamin D

A report analyzing studies of vitamin D supplementation found that people who take vitamin D supplements live longer than those who do not. People who avoid sunlight are at risk for vitamin D deficiency.

Introduction

As you age, your skin undergoes progressive changes:

The cells divide more slowly, and the inner layer of skin (the dermis) starts to thin. Fat cells beneath the dermis begin to shrink. In addition, the ability of the skin to repair itself decreases with age, so wounds heal more slowly. The thinning skin becomes vulnerable to injuries and damage.
The deeper layer of the skin, which provides scaffolding for the surface skin layers, loosens and unravels. Skin then loses its elasticity (ability to stretch). When pressed, it no longer springs back to its initial position. Instead, older skin sags and forms furrows.
The sweat- and oil-secreting glands atrophy (waste away), leaving the skin without a protective layer of water and fat. The skin's ability to stay moisturized then decreases, and it becomes dry and scaly.
Frown lines (those between the eyebrows) and crow's feet (lines that spread from the corners of the eyes) appear to develop because of permanent small muscle contractions. Habitual facial expressions also form characteristic lines.
Gravity makes the situation worse, contributing to the formation of jowls and drooping eyelids. Eyebrows, surprisingly, move up as a person ages, possibly pulled up by forehead wrinkles.

Wrinkles can have a profound impact on self-esteem. The stigma attached to looking old is evidenced by the more than $12 billion Americans spend each year on cosmetics to hide the signs of aging. Our society places a premium on youthfulness, and age discrimination in the workplace, although illegal, has stalled many people's careers. Indeed, the emotional consequences of aging explain in large part why the cosmetics industry and plastic surgeons thrive.

The sun is the most important cause of prematurely aging skin (a process called photoaging) and skin cancers. Overall, exposure to ultraviolet radiation from sunlight (radiation referred to as UVA or UVB) accounts for about 90% of the symptoms of premature skin aging. Most of these effects occur by age 20:

Even small amounts of UV radiation trigger the processes leading to skin wrinkles.
Long-term repetitive exposure to sunlight adds up, and likely is responsible for the vast majority of unwanted consequences of aging skin, including basal cell and squamous cell cancers.
Intense exposure to sunlight in early life is an important cause of melanoma, a particularly aggressive type of skin cancer.

Initial Damaging Effects of Sunlight. Ultraviolet radiation penetrates the layers of the skin. Both UVA and UVB rays cause damage leading to wrinkles, lower immunity against infection, aging skin disorders, and cancer. They appear to damage cells in different ways, however.

UVB is the main cause of sunburns, and primarily affects the outer skin layers. UVB is most intense at midday when sunlight is brightest. People receive slightly over 70% of their yearly UVB dose during the summer. We receive only 28% during the remainder of the year. Window glass filters out UVB.
UVA penetrates more deeply and efficiently. The intensity of UVA rays is less dependent on the time of day and season of the year than that of UVB rays. For example, you receive only about half of your yearly UVA dose during the summer months, with the balance spread over the rest of the year. Window glass does NOT filter out UVA.

Both UVA and UVB rays cause damage to the body, including genetic injury, wrinkles, aging skin disorders, and skin cancers. Exactly how they cause this damage is not yet fully understood.

Processes Leading to Wrinkles. Even small amounts of UV radiation trigger the processes that can cause wrinkles:

Sunlight damages collagen fibers (the major protein that gives structure to the skin). Sunlight also causes damage to elastin, a protein in the skin that normally maintains springiness and strength of tissue beneath the skin.
In response to this sun-induced elastin accumulation, the body produces large amounts of enzymes called metalloproteinases. One study indicated that when people with light to moderate skin color are exposed to sunlight for just 5 - 15 minutes, the metalloproteinase levels in their body remain high for about a week.
The normal function of these metalloproteinases is generally positive -- to remodel the sun-injured tissue by producing and repairing collagen. This is an imperfect process, however, and some of metalloproteinases produced by sunlight actually degrade (break down) collagen. The result is an uneven formation (matrix) of disorganized collagen fibers called solar scars. Repetition of this imperfect skin rebuilding causes wrinkles.
An important event in this process is the over-production of oxidants, also called free radicals. These are unstable molecules that are normally produced by chemical processes in the body, a process called oxidation. Environmental damage, however, causes an overproduction of oxidants. Excessive amounts of oxidants damage the body's cells and even alter their genetic material. Oxidation may contribute to wrinkling by activating the specific metalloproteinases that degrade connective tissue.

In addition to sunlight, other factors may hasten the formation of wrinkles:

Cigarette Smoke. Smoking produces oxygen-free radicals, which accelerate wrinkles and aging skin disorders, and increase the risk for non-melanoma skin cancers. Studies also suggest that smoking and subsequent oxidation produce higher levels of metalloproteinases, the enzymes associated with wrinkles.

Air Pollution. Ozone, a common air pollutant, may be a particular problem for the skin. One study reported that it might deplete the amount of vitamin E in the skin. This vitamin is an important antioxidant.

Rapid Weight Loss. If weight loss occurs too rapidly, the volume of fat cells that cushion the face are also decreased before chemicals in the skin can react. This not only makes a person look gaunt, but can cause the skin to sag.

Blemishes

This report covers three types of blemishes: Liver spots, purpura, and seborrheic keratoses (or warts).

Liver spots (known as lentigos, or sun-induced or pigmented lesions) are flat brown spots on the skin. They are almost universal signs of aging. Occurring most noticeably on the hands and face, these blemishes tend to enlarge and darken over time. The extent and severity of the spots are determined by a combination of skin type, sun exposure, and age. These spots are harmless, but should be distinguished from lentigo maligna, which is an early sign of melanoma.

Liver spots or age spots are a type of skin change that are associated with aging. The increased pigmentation may be brought on by exposure to sun, or other forms of ultraviolet light, or other unknown causes.

Treating Liver Spots. Liver spots do not require treatment, although some people are distressed by their appearance. Treatments may include the following:

Trichloroacetic acid (a chemical peel).
Tretinoin (Retin A) alone or in a combination with Mequinol (Solagé). Tretinoin is related to vitamin A, and is also effective in treating wrinkles.
Gentle freezing with liquid nitrogen (cryotherapy).
Laser treatment. Specific lasers, such as the Nd:YAG, are effective in eliminating 80% of liver spots in one treatment. It may be more effective than cryotherapy and have fewer side effects.
Bleaching creams -- these are commonly available but are not as satisfactory as peels, and high concentrations can sometimes cause permanent loss of skin color.

Purpura occurs when tiny capillaries (blood vessels) break and leak blood into the skin. In older people, the condition (called senile or actinic purpura) is usually caused by fragile blood vessels. The capillaries appear as flat purplish patches. These patches are called petechiae when they are smaller than 3 mm (about a tenth of an inch). When they are greater than 3 mm, they are referred to as ecchymoses. Patients typically complain of a rash, which may appear reddish at first but gradually change color, turning brown or purple.

Treatment. Although there is no specific treatment for purpura, patients are advised to avoid trauma, including vigorous rubbing of the skin, which may be sufficient to damage the capillaries. Emollients that soften the skin may be helpful. Some doctors also recommend vitamin C, but its effectiveness is unproven.

Seborrheic keratoses, (also called seborrheic warts), are among the most common skin disorders in older adults. Their cause or causes are unknown. They usually appear on the head, neck, or trunk and can range in size from 0.2 - 3 cm (a little over an inch). They are well defined and appear to be pasted onto the skin, but their appearance can vary widely:

They can be smooth with tiny, round, pearl-like formations embedded in them.
They can be rough and warty.
They can be brown or black.

Seborrheic keratoses sometimes look like melanoma, since they can have an irregular border, but they are always benign. A dermatologist can tell the difference between them, although experts warn that melanomas may "hide" among these benign lesions and go unnoticed without close inspection. In general, seborrheic keratoses have a uniform appearance while melanomas often have a smooth surface that varies in height, color density, and shading. In some cases, keratoses may cause itching or irritation. They can be easily removed with surgery or freezing. Vitamin D3 ointment is also showing promise in clinical trials.

Risk Factors

Exposure to Sun in Childhood. It is estimated that 50 - 80% of skin damage occurs in childhood and adolescence from intermittent, intense sun exposure that causes severe sunburns. In spite of this now well-known effect, many people still believe that a tan in children signifies health. And even though many parents are concerned about sun exposure, they still rely too much on sunscreen and not enough on protective clothing.

The Elderly. Most people over 70 have at least one skin disorder. Many have three or four. Everyone experiences skin changes as they age, but a long life is not the sole determinant of aging skin. Family history, genetics, and behavioral choices all have a profound impact on the onset of aging-skin symptoms.

Of all the risk factors for aging skin, exposure to UV radiation from sunlight is by far the most serious. Indeed, the vast majority of undesirable consequences of aging skin occur in individuals who are repetitively exposed to the sun, including the following:

Outdoor workers, such as farmers, fishermen, construction workers, and lifeguards
Outdoor enthusiasts
Sunbathers
People who regularly attend tanning salons or use tanning beds (One study indicated that regular use significantly increases the risk for non-melanoma skin cancers. Fair-skinned women under age 50 may be at particular risk.)

Experts have devised a classification system for skin phototypes (SPTs) based on the sensitivity to sunlight. It ranges from SPT I (lightest skin plus other factors) to IV (darkest skin). People with skin types I and II are at highest risk for photoaging skin diseases, including cancer. It should be noted, however, that premature aging from sunlight can affect people of all skin shades.


Skin Type	Tanning and Burning History
I	Always burns, never tans, sensitive to sun exposure
II	Burns easily, tans minimally
III	Burns moderately, tans gradually to light brown
IV	Burns minimally, always tans well to moderately brown
V	Rarely burns, tans profusely to dark
VI	Never burns, deeply pigmented, least sensitive

The common belief is that women are at greater risk for wrinkles than men. Some evidence suggests, however, that given the same risk factors, men and women in the same age groups have comparable risks for skin photoaging. In a French study, the evidence of moderate-to-severe photoaging was observed in the following:

Twenty two percent of women and 17% of men ages 45 - 49
Thirty six percent of women and 38% of men by age 54
Nearly half of both men and women by age 60

Some studies report that men are more likely to develop non-melanoma skin cancers.

Heavy smokers are almost five times more likely to have wrinkled facial skin than nonsmokers, according to one study. The skin of smokers in areas of their bodies not exposed to sunlight also seems to age more rapidly, compared to non-smokers in the same age group, according to a 2007 study. In fact, heavy smokers in their 40s often have facial wrinkles more like those of nonsmokers in their 60s.

Studies of identical twins have found smokers to have thinner skin (in some cases by as much as 40%), more severe wrinkles, and more gray hair than their non-smoking twins. Even worse, cigarette smokers are more prone to skin cancers, including squamous cell carcinoma and giant basal cell carcinomas. A European study found an association between smoking and higher frequency of a particular type of acne in adult women. The study also found that women who smoked had much lower levels of vitamin E secretions in their skin. Vitamin E is an antioxidant that may help protect the skin from sun damage. [See In-Depth Report #41: Smoking.]

Prevention

The best long-term prevention for overly wrinkled skin is a healthy lifestyle.

Eat Healthy. A diet with plenty of whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil) may protect against oxidative stress in the skin. One study reported that people over age 70 years had fewer wrinkles if they ate such foods. Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries. Benefits from these foods may be due to high levels of anti-oxidants found in them.

Exercise. Daily exercise keeps blood flowing, which brings oxygen to the skin. Oxygen is an important ingredient for healthy skin.

Reduce Stress. Reducing stress and tension may have benefits on the skin.

Quit Smoking. Smoking not only increases wrinkles, but smokers have a risk for squamous cell cancers that is 50% higher than nonsmokers' risk. Smokers should quit smoking to prevent many health problems, not just unhealthy skin.

The following are some daily measures for skin protection:

Don't wash your face too often with tap water. (Once a day is enough.) It strips the skin of oil and moisture. In addition, chlorinated water, particularly at high temperatures, poses special risks for wrinkles.
Wash your face with a mild soap that contains moisturizers. Avoid alkaline soaps, especially with deodorant.
Pat the skin dry and immediately apply a water-based moisturizer.
Always apply sunscreen, even if going outdoors for short periods.
Avoid drinking alcohol within 3 hours of bedtime. Alcohol increases the risk for leaks in the capillaries, which allows more water in and causes sagging and puffiness. Capillary leakage increases when one is lying down.
Lie on the back when sleeping. This helps offset the effects of gravity.

One of the most important ways to prevent skin damage is to avoid episodes of excessive sun exposure. The following are some specific guidelines:

Use sunscreens that block out both UVA and UVB radiation. However, do not rely only on sunscreen for sun protection. Wear protective clothing and sunglasses in addition.
Avoid exposure particularly from 10 a.m. to 4 p.m., when sunlight pours down 80% of its daily UV dose.
Avoid reflective surfaces, such as water, sand, concrete, and white-painted areas. Clouds and haze are not protective and in some cases may intensify UVB rays.
Ultraviolet intensity depends on the angle of the sun, not heat or brightness. So the dangers are greater the closer to the summer-start date. For example, in the Northern Hemisphere, UV intensity in April (2 months before summer starts) is equal to that in August (2 months after summer begins).
The higher the altitude the quicker one sunburns. One study suggested, for example, that an average complexion burns in 6 minutes at an altitude of 11,000 feet at noon, compared with 25 minutes at sea level in a temperate climate.
Avoid sun lamps and tanning beds or salons. They provide mostly high-output UVA rays. Some experts believe that 15 - 30 minutes at a tanning salon is as dangerous as a day spent in the sun. People should not be misled by advertising claims of "safe" tanning or promotions offering unlimited tanning.

Sunscreens. The use of sunscreens is complex, and everyone should understand how and when to use them. The bottom line is not that people should avoid sunscreens or sunblocks, but that they should always use them in combination with other sun-protective measures.

Protective Clothing. Wearing sun-protective clothing is extremely important and protects even better than sunscreens. Special clothing is now available for blocking UV rays and is rated using SPF ratings or a system called the UPF (ultraviolet protection factor) index, with 50 UPF being the highest. (According to one study, this is a very reliable indicator of protection.) The clothing is expensive, however. The following are some tips for everyone:

Adults and children should wear hats with wide brims. Even wearing a hat, however, may not be fully protective against skin cancers on the head and neck.
People should look for loosely fitted, unbleached, tightly woven fabrics. The tighter the weave, the more protective the garment.
Washing clothes over and over improves UPF by drawing fabrics together during shrinkage. An easy way to assess protection is simply to hold the garment up to a window or lamp and see how much light comes through. The less the better.
Everyone over age 1 should wear sunglasses that block all UVA and UVB rays.

Chemical Tanners. Some research suggests that melanin and dihydroxyacetone (DHA), the active ingredients in many self-tanning lotions, may help filter out UVA and UVB radiation and are therefore protective against sun damage More research is underway. A preliminary study funded by the National Cancer Institute found that people who received numerous daily injections of melanotan-1 (MT-1) before going in the sun or a tanning bed tanned more quickly and showed fewer signs of sun-related damage. MT-1 is a synthetic version of the hormone melanin, which helps produce the skin's natural pigment (color).

In choosing a sunscreen, look at the ingredients. Preparations that help block UV radiation are sometimes classified as sunscreens or sunblocks, according to the substances they contain. In general, sunscreens contain organic formulas and sunblocks inorganic formulas. However, the term sunblock is used less and less as sunscreens increasingly contain both kinds of ingredients:

Organic formulas contain UV-filtering chemicals such as octocrylene, octyl salicylate, homosalate, and octyl methoxycinnamate (block UVB), avobenzone-Parsol 1789 (blocks UVA), cinoxate, ethylhexyl p-methoxycinnamate (blocks UVB and small amounts of UVA), oxybenzone, benzophenone-3 (blocks UVA/UVB). People should look for a wide-spectrum sunscreen that contains combinations of these ingredients and filter both UVA and UVB. Of note: para-amino benzoic acid (PABA), once a popular ingredient, is now used infrequently. PABA may actually break down in the presence of UV exposure and release harmful oxidants. In addition, many people have an allergic reaction to it. Some products contain PABA derivatives, such as padimate O or octyl dimethyl PABA. It is not known if they have the same effects.
The Food and Drug Administration approved Anthelios SX in July 2006. This new sunscreen prevents sunburn and protects against ultraviolet A and B rays. The product contains ecamsule, an ingredient not previously marketed in the United States.
Inorganic formulas contain the UV-blocking pigments zinc oxide or titanium dioxide. Zinc and titanium oxides lie on top of the skin and are not absorbed. They prevent nearly all UVA and UVB rays from reaching the skin. Older sunblocks are white, pasty, and unattractive, but current products use so-called microfine oxides, either zinc (Z-Cote) or titanium. They are transparent and nearly as protective as the older types. Microfine zinc oxide may be more protective and less pasty-colored than microfine titanium oxide.

Inexpensive products work as well as expensive ones with the same ingredients. Unfortunately, there are still no standards for sunscreens, and even those claiming UVA protection may offer very little. In one study, the average UVA protection from a wide range of brands was only 23%. In fact, the average protection of brands not making the claim was 37%!

Organic formulas and inorganic microfine oxides do not protect against visible light, which is a problem for people who have light-sensitive skin conditions, including actinic prurigo, porphyria, and chronic actinic dermatitis. Inorganic sunscreens that protect against visible light and are still cosmetically acceptable are now available in Europe, but not yet in the US.

Calculating the SPF. The sun protection factor (SPF) on all sunscreen labels is a ratio based on the amount of UVB (not UVA) radiation required to turn sunscreen- or sunblock-treated skin red compared to non-treated skin. For instance, people who sunburn in 5 minutes and who want to stay in the sun for 150 minutes might use an SPF 30. The formula would be: 30 (the SPF number) times 5 (minutes to burn) = 150 minutes in the sun.

Protection offered by sunscreens may be classified as follows:

Minimal: SPF 2 to 11.
Moderate: SPF 12 through 29.
High: 30+. (Although some sunscreens claim SPFs higher than 30, the added protection at such higher levels is insignificant.)

SPF Levels by Age Group. Certain groups should have higher or lower SPFs depending on age and other factors:

Although sunscreens are safe in most toddlers and children, they should not be the first and only lines of defense. In fact, experts are worrying that by relying too much on sunscreen and not providing other protective measures, parents may actually be increasing their children's risk for melanoma. All young children should be well covered with clothing, sunglasses, and hats as the first line of defense against sunburn. Children should be kept out of the sun during peak sunlight periods. Sunscreens should not be used on babies younger than 6 months without consulting a doctor.
Older children and adults (even those with darker skin) benefit from using SPFs of 15 and over. Some experts recommend that most people should use SPF 30 on the face and 15 on the body.
Adults who burn easily instead of tanning and anyone with risk factors for skin cancer should use at least SPF 30.

Timing and Amount of Application. You should apply sunscreen or sunblock liberally as follows:

Adults should include sunscreen with a daily skin regimen, even if going outdoors for only a short time.
Apply a large amount to all exposed areas, including ears and feet. To achieve protection as indicated by the sunscreen's SPF, experts recommend half a teaspoon each for the head, neck, and each arm and a teaspoon each for the chest area, the back, and each leg.
Apply initially 30 minutes before venturing outdoors for best results. (This allows time for the sunscreen to be absorbed. Then reapply every 15 - 30 minutes while being in the sunlight.
Also reapply each time after exercise or swimming. (Choose a waterproof or water-resistant formula even if activities don't include swimming. Waterproof formulas last for about 40 minutes in the water, whereas water-resistant formulas last half as long.)
Insect repellents reduce sunscreen SPFs by up to one-third. Use higher SPFs and very liberal application when applying both.

Sunscreen Use May Not Protect Against Basal Cell and Melanoma Cancers and May Even Increase the Risk. Although sunscreens help prevent squamous cell carcinomas and other skin disorders, sunscreens do not appear to provide protection against melanoma and some basal cell cancers. In fact, some studies have reported a higher association with sunscreen use and these skin malignancies, though not all studies report such negative results.

The reasons for this possible increased risk are unclear, though some theories include the following:

Until recently, many sunscreens blocked only or mostly UVB rays and not UVA, the more deeply penetrating rays now known to be especially dangerous. Past studies may not have reflected the effects of the broad-spectrum sunscreens now available, which block both UVA and UVB.
People who apply sunscreens may feel safe and stay out longer during high sun-exposure hours than is safe. Even if a person doesn't sunburn, UVA rays can still penetrate the skin and do harm.
People may not put on enough sunscreen. According to a 2002 study, people generally apply only 20 - 60% of the recommended amount, which can provide significantly less protection than the given SPF. (Of note, a 2003 study reported that when applied at the recommended amount, a broad-screen sunscreen prevents DNA damage from UV exposure. However, omitting it even once resulted in significant cell injury.)

Sunscreen Use May Increase the Risk for Health Problems Related to Sunlight Deficiencies. There is some major concern that underexposure to sunlight, due to the use of sunscreens or sun-avoidance measures, may produce other health problems, such as the following:

Vitamin D Deficiency. Vitamin D is found in only a few foods, such as fortified dairy products and fish, but it is produced in the skin in response to UVB sunlight. A medical literature review published in the journal Nutrition and Cancer reported that UVB rays may outshine dietary supplements for building the body's vitamin D reserves. Without an appropriate mix of diet and supplements, vigorous sun protection measures may increase a person's risk for developing vitamin D deficiency. Vitamin D is important for prevention of rickets, osteoporosis, and some cancers, including melanoma. People who need to avoid sunlight and whose diet is low in foods that contain vitamin D should check with their doctor about taking supplements. People with darker skin are at higher risk for deficiencies from sun protection than those with whiter skin. Note: vitamin D is toxic in high doses. Most doctors recommend 200 IU a day (for young adults) to 600 IU a day (above age 70). Doses up to 2,000 IU a day are considered safe. A report analyzing studies of vitamin D supplementation found that people who take vitamin D supplements live longer than those who do not. The researchers looked at 18 studies. They found that participants who received vitamin D supplements were, on average, 7% less likely to die during the study they were in, compared with those receiving "sugar pills."
Other Cancers. Although sunlight is implicated in skin cancers, it is also associated with lower risks for breast, prostate, ovarian, and colon cancers. Some protection against these cancers may be related to vitamin D production by sunlight.
Depression. Many people suffer from SAD (seasonal affective disorder), a form of depression that generally occurs in winter and is associated with exposure to less sunlight.

The bottom line is that some sunlight is important and even necessary for a healthful and high-quality life. Adults may benefit from daily moderate tanning (20 - 30 maximum minutes of exposure during lower-risk hours) over several days to slowly build up pigment in the skin.

Treatment

An increasing number of dermatology patients are looking for a way to improve the appearance of their skin. As a result, more and more products have become available to treat skin wrinkles and blemishes. From vitamins and supplements to exfoliants and chemical peels -- the options can be overwhelming. In some cases, more than one approach may be needed.

Antioxidants are substances that hunt oxygen-free radicals, the unstable particles that can damage cells. Free radicals may also cause sun damage and even skin cancers. Exposure to sunlight depletes antioxidants in the skin, and therefore they must be replaced.

Antioxidant ointments, creams, and lotions ("topical products") may help reduce the risk of wrinkles and protect against sun damage. Unlike sunscreens, they build up in the skin and are not washed away, so the protection may last. Selenium, coenzyme Q10 (CoQ10), and alpha-lipoic acid are types of antioxidants that come in topical form. Many are proving to be very beneficial for the skin.

Vitamin A. Vitamin A is important for skin health. UV radiation produces vitamin A deficiencies in the skin. Topical products containing natural forms of vitamin A (retinol, retinaldehyde) or vitamin A-related products called retinoids (tretinoin, tazarotene) may help repair skin damage due to sunburn and natural aging.

Tretinoin (Retin-A). Tretinoin (known commercially as Retin-A) is the only topical agent approved for treating photoaging and is available in prescription form (Avita, Renova, Differin). The June 2004 issue of Dermatology Surgery reported that tretinoin (0.25% concentration) was an effective and well-tolerated treatment for photodamaged facial skin. This drug produces a rosy glow and reduces fine and large wrinkles, liver spots, and surface roughness. It also may help prevent more serious effects of ultraviolet radiation. Patients may apply tretinoin to the face, neck, chest, hands, and forearms, and should do so at least twice a week. Noticeable improvement takes 2 - 6 months. Because Retin-A increases a person's sensitivity to the sun, patients should apply just a tiny amount at bedtime, and wear sunblock during the day. Patients should also avoid overexposure to the sun. Almost all patients experience redness, scaling, burning, and itching after 2 or 3 days that can last up to 3 months. In women who experience irritation, a daytime moisturizer or low-dose corticosteroid cream, such as 1% hydrocortisone, may help. There is some concern that overuse of high-dose tretinoin may cause excessive skin thinness over time. Studies now suggest that low concentrations (as low as .02%) of tretinoin can produce significant improvements in wrinkles and skin color, with less irritation than the higher doses.
Retinol. Retinol, a natural form of vitamin A, could not, until recently, be used in skin products because it was unstable and easily broken down by UV radiation. Stable preparations are now sold over the counter. In the right concentrations, retinol may be as effective as tretinoin, and studies indicate that it has fewer side effects. An animal study suggests that adding antioxidant creams (such as those containing vitamins C or E) may offer added protection against degradation of retinol, but not tretinoin. The Food and Drug Administration warns that over-the-counter retinol skin products are unregulated. The amount of active ingredients is unknown, and some preparations, in fact, may contain almost no retinol.
Tazarotene. Tazarotene (Tazorac, Zorac, Avage) is a retinoid used for acne and psoriasis. It has now been approved for treating wrinkles, skin discoloration, and blemishes due to photoaging. One short-term study suggested that it may be as effective as tretinoin and even slightly better at high doses. At such high doses, however, it can cause very severe irritation. Redness and peeling may be reduced by administering tretinoin first to get the skin acclimated. A randomized study of 562 patients with facial photodamage found that a daily application of tazarotene 0.1% cream resulted in a minimum 1 grade improvement in fine and coarse wrinkling, uneven skin color, pore size, skin roughness, and overall photodamage. More research is needed to determine if it produces any long-lasting significant benefits.

Warning: Pregnant women and those who may become pregnant should avoid any vitamin A derivative (a product related to vitamin A). For example, oral tretinoin causes birth defects, and women should avoid even topical Retin-A when pregnant or trying to conceive.

Vitamin C. Vitamin C, or ascorbic acid, is a very potent antioxidant. Most studies on the effects of antioxidants on the skin have used this vitamin. In laboratory studies, large amounts of vitamin C reduced skin swelling and protected immune factors from sunlight. It may even promote collagen production. Vitamin C by itself is unstable, but products that solve the delivery problem are now available (such as Cellex-C, Avon's Anew Formula C Treatment Capsules, Physician Elite, and others). More research is needed.

Antioxidants Under Investigation for Skin Care. Other antioxidants are also being investigated for their value in skin protection. Most available brands, however, contain very low concentrations of these antioxidants. In addition, they are also not well absorbed and have a short-term effect. New delivery techniques, however, may prove to offset some of these problems.

Vitamin E. Studies suggest that topical vitamin E, particularly alpha tocopherol cream (a form of vitamin E), decreased skin roughness, length of facial lines, and wrinkle depth. Studies on mice have also reported reductions in UV-induced skin cancer with its use.
Both green and black tea may provide some protection against skin cancers and photoaging. There is also some evidence that pomegranate and soy extracts may help rejuvenate aging skin.
Aloe, ginger, grape seed extract, and coral extracts contain antioxidants and are promoted as being healthy for the skin, although evidence of their effects on wrinkles is weak.

A small study found that taking vitamin C and E supplements by mouth -- at the same time -- may help reduce sunburn, although it doesn't work as well as sunscreen. Taking the vitamins separately did not have any effect. Vitamin C and E are also antioxidants.

One of the basic methods for improving skin and eliminating small wrinkles is exfoliation (also called resurfacing), which is the removal of the top layer of skin to allow regrowth of new skin. Methods for doing this run from simple scrubs to special creams to intensive peeling treatments, including laser resurfacing. People with darker skin are at particularly higher risk for scarring or discoloration with the more powerful exfoliation methods.

Abrasive Scrubs. Scrub gently with a mildly abrasive material and a soap that contains salicylic acid to remove old skin so that new skin can grow. The motion should be perpendicular to the wrinkles. Use textured material or cleansing grains with microbeads. Organic materials, such as loofahs or sea sponges, may harbor bacteria. Avoid cleansing grains that contain pulverized walnut shells and apricot seeds, which can scratch skin on a microscopic level. Cleansing grains with microbeads don't have sharp edges and remove skin without cutting it. Exfoliation using scrubs, however, can worsen certain conditions, such as acne, sensitive skin, or broken blood vessels.

Topical Alpha Hydroxy Acid and Similar Substances. Alpha hydroxy acids (AHA) ease the shedding of dead skin cells and may even stimulate the production of collagen and elastin. Their natural forms are:

Lactic acid (milk)
Glycolic acid (sugar cane)
Malic acid (found in apples and pears)
Citric acid (oranges and lemons)
Tartaric acids (grapes)

Most alpha hydroxy acid products contain glycolic acid. Skin care products are also made from polyhydroxy acids (PHAs) and beta hydroxy acids (BHAs). Research suggests that PHA products may cause less skin irritation than AHA or BHA products.

Acid concentrations in over-the-counter AHA preparations are 2 - 10%. One clinical study suggested that 8% concentrations showed modest skin improvement Some examples include Avon's Anew Intensive Treatment (8% glycolic), Pond's Age Defying Complex (8%), Elizabeth Arden's Alpha-Ceramid Intensive Skin Treatment (3 - 7.5%), and BioMedic's home product (10%). Prescription strength creams contain at least 12% glycolic acid, and glycolic acid peels of 30 - 70% concentration may be administered in a doctor's office at weekly or monthly intervals.

Response to AHA varies, and the treatment is not without risk, particularly in high-concentration products. Side effects from over-the-counter creams, prescription products, and professional AHA peels can include burns, itching, pain, and possibly scarring. Studies also suggest that AHA may increase susceptibility to sun damage, even at concentrations as low as 4%. Such effects can persist up to a week after a person stops using the product. Experts advise that people purchase products with AHA concentrations of 10% or less. Chemical peels of up to 60% are available without prescription on the Internet. Such concentrations are not recommended, except under a doctor's supervision. If any adverse effects occur, stop using the product immediately. Always avoid sunlight or use proper sun protection when using these products.

Copper Peptides. Certain copper-containing compounds may protect skin and help repair it. Note: copper is a toxic metal. When using products containing copper, buy only those that contain peptides (small protein fragments) that bind to copper. Most studies have been conducted on the copper peptide glycyl-l-histidyl-l-lysine:copper (II) or GHK-Cu. It is currently used in a number of products (such as CP Serum, Neutrogena's Visibly Firm, ProCyte's Neova).

Furfuryladenine. Furfuryladenine (Kinetin, Kinerase) is a naturally occurring growth hormone found in plant and animal DNA. It has antioxidant and anti-aging properties. Some small laboratory studies suggest that furfuryladenine may delay the onset and decrease the effects of aging on skin. However, there are no well-conducted human studies to support this suggestion.

Vitamin K. Microsponge-based vitamin K is said to clear bruises spider veins, and other small blood vessel damage. Vitamin K is important for blood clotting.

Moisturizers help prevent dryness, bruising, and tearing. They have no effect on wrinkles by themselves. Moisturizers should be applied while the skin is still damp. These products retain skin moisture in various ways:

Occlusives, such as petroleum jelly, prevent water from evaporating.
Humectants, including glycerin, act by pulling water up to the surface of the skin from deep tissues. People with oily skin generally should use the humectant type.
More powerful compounds, such as monolaurin (Glylorin), contain mixtures of fatty molecules (lipids), which may help restore the skin's natural barriers against moisture loss and damage.

Most moisturizers contain combinations of these compounds. They usually have other ingredients as well, such as alpha hydroxy acids, sunscreens, collagen, and keratin. Collagen and keratin leave a protein film and temporarily stretch the skin. They range widely in price, and a major consumer organization found little difference in general between the more and less expensive products.

The skin under the eyes is very thin and does not produce as much of the protective oils that keep skin soft and supple. Manufacturers market their under-eye gels as being able to reduce puffiness and dark circles. The creams typically work in one of two ways:

By temporarily constricting blood vessels to prevent the build-up of fluids
By firming the skin with an invisible film

Never rub the creams under the eyes, as this may cause more wrinkles to form. Instead, apply these products with a light tapping motion to stimulate the skin.

Cosmetics, if properly applied, can be surprisingly effective in camouflaging the signs of aging skin, including wrinkles and age spots. Moreover, they offer additional benefits by retarding water loss and providing a physical barrier to UV radiation. However, as women age, less is more.

Here are some suggestions for older women:

Moisturizers. Apply moisturizers before foundation. If reddish discoloration is extensive or the skin is sallow, tinted moisturizers may be helpful and can be worn alone or under foundation.

Foundations. Caking on make-up will cause cracks at the wrinkle lines and only increase the appearance of aging. Try to cover large areas of the face with a moderate-coverage foundation that has a matte or semi-matte finish. Facial powder reflects light and thus minimizes wrinkles, but people with dry skin should avoid it.

Correcting Color. When blemishes are especially prominent, applying color correctors under the foundation can be very effective:

Green neutralizers mask red lesions.
Yellow will camouflage dark circles and bruises.
Mauve (a purplish-pink color) helps neutralize sallow skin or yellowish blemishes.
A white, pearled base helps to minimize wrinkles.

Blushes. Blushes and color washes can help conceal the spidery network of dilated capillaries on the nose and cheeks. Powder blushes are preferred because they blend easily on top of foundation.

Eyes. Powder eye shadows applied on top of a moisturizer are better than cream-based shadows. Light-colored shadow, applied along the upper eyelid crease and above the iris (the colored part of the eye) is best for offsetting the appearance of deep-set eyes. You should then apply a slightly deeper shade of the same color to the lower part of the eyelid, and draw it out to the corner.

Lips. A lip-setting cream or facial foundation should be applied before lipstick to help prevent it from bleeding into surrounding wrinkles. Try using a stiff bristle brush instead of a lip pencil. The brush will help keep the lipstick on and prevent bleeding. (Some women use the pencil itself for the full lip, which gives color but appears natural.) Some make-up artists recommend cream lipsticks instead of matte.

The Food and Drug Administration (FDA) does not regulate herbal remedies and dietary supplements. In other words, the manufacturers and distributors of such products do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been numerous reported cases of serious and even deadly side effects from herbal products.

Overexposure to sunlight can damage skin. The following natural remedies may cause extra sensitivity to light (photosensitivity):

St. John's wort (Hypericum perforatum) is a popular herbal remedy for depression. People who are sensitive to light should not use it. A case report suggests that St. John's wort may cause skin reactions in patients who have laser treatment.
Kava (Piper methysticum) is an herb used to calm nerves and reduce stress. In addition to photosensitivity, it can cause liver damage.
Yohimbe (Pausinystalia yohimbe) is used to treat erectile dysfunction. Both the herb and the pharmaceutical drug (yohimbine) can cause sensitivity to light.
Essential oils in many botanical aromatherapy products can trigger photosensitivity. Avoid citrus oils (grapefruit, lemon, lime, and orange) as well as bergamot, cumin, ginger, and angelica root oils.

Resurfacing Treatments

There are many choices for skin resurfacing (also called exfoliation), and the patient must consider several different factors that affect the choice. Resurfacing can achieve the following:

Removal of abnormal tissue and rough skin
Stimulation of new skin growth
Stimulation of collagen and elastin production

In addition to determining the skill of the surgeon and the safety of the procedure, the patient must discuss the desired depth of the resurfacing and the capability of each procedure to reach this depth safely. All resurfacing procedures require a healing period afterward, during which the skin is red and sensitive. The deeper the procedure, the higher the risk for complications, including delayed healing, infection, loss of pigment (skin color), and scarring.

If you make the decision to pursue intensive treatments, consider the following factors, among others, and discuss them with your dermatologist or plastic surgeon:

The ability of the procedure to safely reduce wrinkles
The ease and safety record of the procedure
The skill of the doctor
The length of recovery
Possible complications
How long the benefits will last

A person's age also helps determine the procedure:

For people in their 30s, a simple chemical peel is sufficient.
After age 40, people may benefit from collagen or fat implants.
At age 50 and over, plastic surgeons recommend laser resurfacing and customized treatments for individual needs.

In older individuals, combination procedures may be beneficial. Some examples include the following:

Laser surgery may be used for deep lines (such as those around the mouth) and chemical peels used over the rest of the face.
For enhancing the eye by correcting droopy eyelids, bags, and a "sinking" brow, combinations of eyelift (blepharoplasty), Botox, and laser resurfacing may be used.

Chemical peels, also known as chemosurgery, help restore wrinkled, lightly scarred, or blemished facial skin. Much like chemical paint strippers, chemical peels strip off the top layers of skin, and new, younger-looking skin grows back. The procedure is very effective for the upper lip but cannot be performed around the eyes. Partial peels are often done in conjunction with a face-lift. Combinations of the topical antioxidants, such as tretinoin and vitamin C, along with a chemical peel, may be particularly effective.

The Procedure.

A dermatologist applies chemicals to the skin. They include trichloroacetic acid, high concentrations of alpha hydroxy or beta hydroxy acids, or combinations of all three.
In some cases, tretinoin or alpha hydroxy is applied 4 - 6 weeks before, and starting one day after, the peel. Such treatments can enhance the effects of a peel and reduce the risk of discoloration in people at risk for this complication. Tretinoin is being tested as a chemical peel.
A crust or scab generally forms within 24 hours after surgery. You can remove this scab by gently cleansing with soap and water.
The skin takes 6 - 7 days to heal.
After the scab disappears, the visible skin is deep red but gradually lightens as it regenerates.

Complications. Complications include white heads, cold sores, infection, scarring, numbness, and permanent discoloration, particularly in people with darker skin. Refinement of chemical peel techniques are now permitting doctors to reach deeper skin, improvements which make it easier to apply peels to non-facial skin and to individuals with darker skin.

Dermabrasion affects deeper layers of skin than chemical peels, and may be useful for removing disfiguring marks, such as deep acne scars or deep wrinkles. As with chemical peels, it is effective for wrinkles on the upper lip and chin, and cannot be used around the eyes. Some doctors prefer dermabrasion to lasers for skin surfacing of people with darker skin colors.

Standard Dermabrasion. Standard dermabrasion uses a rotating brush that removes the top layers of a person's skin. As with chemical peels, dermabrasion selectively strips away the upper layers of skin, leaving the underlying skin layers exposed. Similar to chemical peels, after the procedure, the treated skin oozes and forms a scab, a reaction that looks and feels uncomfortable, but only temporary. Postoperative care is similar for both procedures.

Microdermabrasion. A gentler variation called microdermabrasion uses very tiny crystals to polish the skin and a vacuum technique to remove them. It has largely replaced the older dermabrasion, and, in fact, was the fourth most common non-surgical cosmetic procedure performed in 2005, with over a million done. Results are similar to light chemical peels. Patients can have this procedure done on their lunch hour and return to work. Only mild redness occurs after treatment, although for best results five or six repetitive treatments are needed every 1 - 2 weeks. To date, overall patient satisfaction has been very high.

Lasers are currently the most effective exfoliation tools for eliminating wrinkles. Their unique advantages over other resurfacing methods are their ability to tighten the skin. A successful procedure can make patients look 10 - 20 years younger, and the results can last up to 10 years.

The procedure is most beneficial for the following areas:

It is best around the mouth and eyes. Recent evidence suggests CO₂ lasers may be even better than dermabrasion for the upper lip.
It is slightly less beneficial for the area around the nose.

Used alone, current laser therapy does not eliminate crow's feet, broken blood vessels, or dark circles under the eye. The evidence of the effects of lasers on acne scars is incomplete.

Standard laser dermabrasion is too harsh for thinner skin layers, such as on the neck. Newer and gentler laser techniques, however, stimulate collagen without removing skin layers, and may prove to be useful for necklines.

The Laser Resurfacing Procedure. In general the procedure works in the following way:

Laser pulses penetrate the skin quickly, vaporizing water and surface skin without damaging the deeper layers, allowing new top skin to grow.
In addition, the laser delivers enough heat to shorten collagen fibers, restoring some elasticity to the skin.

Choice of Lasers. The lasers used depend on skin type and severity of the condition. Some of the more common laser types are:

The carbon dioxide (CO₂) laser. This is the most powerful laser treatment and is used for deep wrinkles and skin imperfections. People who have had silicone injections should not have CO₂ procedures, which can burn and scar the skin over the implanted area.
The erbium: YAG (Er:YAG). This laser is gentler than the CO₂ laser, and is effective for mild wrinkles and for providing a smooth skin texture. It has a shorter recovery time. Some experts have even found the YAG laser as effective in removing deep wrinkles as CO₂ when used to sufficient depth. A variable pulse YAG laser can shift between pulses that destroy skin tissue to those that heat the skin. This process effectively resurfaces the skin with fewer side effects than CO₂ laser therapy.
Pulsed dye laser. Pulsed dye laser uses yellow light, which is easily absorbed by hemoglobin, the molecule that gives blood its red color. Pulsed dye laser treatments are used to treat skin blemishes that are due to blood vessel abnormalities, such as port-wine stains.

A gentle laser procedure called non-ablative laser resurfacing (NLite), also called photorejuvenation, is now approved for the treatment of all facial wrinkles. The procedure uses light energy to gently stimulate new collagen, and possibly elastin production, without removing the skin tissue itself. Its effects are less pronounced than those of other laser procedures. However, because it does not injure the external layers of skin, it can be used on delicate skin areas, such as the neck and around the eyes. It also causes very little irritation afterward.

Some surgeons are using combination techniques that employ more than one laser technology in one session, to achieve different effects. For example, one combination technique uses CO₂, YAG, pulsed-dye laser, and one other laser technology to both improve wrinkles and clear under-eye dark circles and acne scarring. Pretreatment with botulinum (Botox) injections before laser resurfacing significantly improved the treatment of crow's feet in one study.

Post-Procedure Recovery. The procedure itself is relatively painless, but the redness and irritation that occur during the healing process can be severe. Non-ablative laser resurfacing does not have the same severe after-effects as other laser treatments. For 8 - 9 days, the face looks skinned and swollen, and requires continuous moisturizing. Some doctors suggest that people with very sensitive skin, who cannot tolerate the necessary medications and lubricants, should avoid laser resurfacing. Redness and sensitivity can persist for 1 - 4 months. The patient must stay out of the sun as much as possible during this time, and should always avoid sunbathing and damaging their skin again. Early research suggests that silicone dressings may reduce post-procedure pain and crusting.

Complications. Scarring and infections can occur in about 1% of procedures. The risk of complications depends on the experience of the surgeon. People with a history of herpes simplex may experience flare-ups of fever, facial pain, and flu-like symptoms for 5 or 6 days after the procedure. In addition, people with darker skin may wish to avoid the procedure, because it can cause unpredictable and dramatic lightening of the skin.

A new skin rejuvenation technology, called Plasma Skin Resurfacing, or Portrait Plasma, was introduced in February 2005. The technology uses plasma energy (heat and light energy) to rejuvenate the skin from the deeper layers outwards. While new skin regenerates, the outer layers of the skin act as a natural bandage. When the outer layers peel off in the week after treatment, the new skin emerges. The process prevents or minimizes the raw appearance that follows laser treatments. This system uses radio waves to "excite" nitrogen gas, resulting in the release of energy. According to the manufacturer, skin regeneration using the Portrait Plasma system is rapid, and satisfaction with the procedure appears high. Long-term follow-up studies are not available yet for this new method. In 2006, the Food and Drug Administration approved this method for the treatment of wrinkles on other areas of the body, besides the face.

Cold Ablation. Cold ablation, called coblation for short, delivers saline (salt water) to the skin, through which a cool electric current is passed. A subsequent reaction heats and vaporizes the top shallow layer of skin. The procedure is very specific and appears to minimize any damage to other areas of the skin.

Radiofrequency Resurfacing. A promising technique uses low radiowave energy to resurface the skin. Preliminary research indicates that this procedure may eventually be as effective as laser surgery in reducing severe wrinkles around the eyes and mouth, with minimal pain and a shorter recovery time. In one study, one radiofrequency treatment with only a skin anesthetic resulted in tighter facial skin for 14 out of 15 patients within 12 weeks. All but one patient returned to normal activity immediately afterward. A small clinical trial published in Dermatology Surgery found that a noninvasive radiofrequency technique called NARF safely and effectively improved drooping lower eyelids.

Intense Pulsed Light. Intense pulsed light (IPL) uses filters to deliver different wavelengths of light. Doctors use it to treat a number of photoaging skin problems, and it appears to have long-term effects. Typically, four to six treatments are performed over a four-month period. Each treatment takes 15 - 20 minutes. Unlike laser light, which uses one color wavelength (such as green or red), intense pulsed light starts with a full spectrum of light. It then allows the doctor to selectively block off specific wavelengths, depending on how shallow or deep the procedure should go. IPL machines are less expensive and safer than lasers.

Implant Procedures

Implants, also called injectable fillers, are becoming a common means of erasing wrinkles and folds. Several materials are being used for deep wrinkles, depression under the eyes, lip enhancements, and acne scars.

After being banned from the market in 1992, silicone is making a comeback in research settings as a potential permanent wrinkle eraser. Scientists are looking into a new microdroplet technique (the use of very small drops) combined with purified silicone as a way to eliminate any danger. The past problems with silicone occurred when it was mixed with a foreign substance, like mineral oil, or when it was injected in large doses.

Most implants to date, however, are not completely satisfactory. Collagen implants and biologic fillers from animal, bacterial, or human sources do not provide long-lasting benefits. Synthetic fillers are permanent but may cause an allergic reaction, which can lead to chronic problems. Such reactions are rare, but they can be painful and unattractive.

The U.S. Food and Drug Administration (FDA) approved the Juvéderm product line in June 2006. Juvéderm is an injectable treatment of moderate-to-severe facial wrinkles and folds. Juvéderm products are gels made from hyaluronic acid. They are injected into the face. Doctors report good results after a single treatment with Juvéderm, and the results last for at least 6 months.


Name and Material Used	Procedure	Specific Areas Affected	Benefits	Drawbacks
Collagen implants. Collagen is the protein that forms the structures in the body (such as skin, bones, cartilage). The implant procedure has typically used bovine (cow) collagen. A form of human collagen (CosmoDerm, CosmoPlast) has now been approved.	Injected into target wrinkles with needle and syringe. Several weeks after injection, cow collagen breaks down and is replaced by newly created human collagen.	Wrinkles around the eyes and mouth. It is used to give lips greater fullness.	Very simple with faster recovery than many other implant techniques.	Wrinkles form again, and require repeat treatments 3 - 12 months later. Rarely, severe allergic reactions occur. Should not be used by children, pregnant women, and people with a history of autoimmune disease.
Microlipoinjection. Fat tissue from the patient's own thigh or abdomen.	Injected into target wrinkles with needle and syringe.	Deep wrinkles around the nose and mouth, folds in the forehead, and wrinkles on the hands.	No allergic or immune reaction because substance is patient's own fat.	Body eventually absorbs the fat, resulting in a need for multiple injections. Some studies suggest that 70% of the fat may still be in place after at least a year.
Gore-Tex. Highly porous (full of tiny holes) and inert (not chemically active) synthetic material.	Requires some surgery. Tiny patches are inserted under the skin to fill out wrinkles. Skin cells and blood vessels pass through the porous material easily, reducing the risk of severe irritation.	Deep wrinkles.	Material does not break down.	Possible scarring from surgical procedure. Allergic reactions are rare but can occur even with chemically inactive materials.
Artecoll. Contains PMMA, or polymethylmethacrylate, an inert substance, enclosed in tiny droplets of natural collagen.	Material is injected. Body absorbs collagen. PMMA remains and stimulates new collagen growth.	Deep wrinkles.	Although part of the implant is a natural collagen implant, it does not degrade as quickly as a full collagen implant.	Repeat treatments may still be needed. Possible allergic reaction.
Hyaluronic acid. Natural (non-animal) substance acts like a molecular sponge to absorb water. The FDA approved Restylane in 2003, Captiva, Hylaform-Plus, and Hylaform in 2004, and Juvéderm in 2006.	Gel is injected under the skin.	Moderate-to-severe wrinkles.	Low risk for allergic reaction. May last longer than cow collagen.	Repeat treatments needed.
Poly-L-lactic acid. Synthetic polymer. Approved in US as Sculpta. Approved in other countries as New-Fill.	Material is injected under the skin.	Approved in U.S. only for patients with facial fat loss due to HIV. Approved in other countries for wrinkles.	Low risk of allergies. Treatment effects can last 18 - 24 months.	Doctors require special training.

The popularity of Botox injections has skyrocketed in the United States. Between 2004 and 2005, the number of procedures performed jumped 16 percent. Botox injection was the number one non-surgical cosmetic procedure in 2005, with more than 3.2 million injections. Botulinum, the deadly toxin found in uncooked foods, is also a powerful muscle-relaxant. Tiny amounts of a purified form (Botox) are injected into wrinkles to relax the surrounding muscles. It may benefit forehead and frown lines, crow's feet, lower eyelids, lines on the side of the nose, and the area between the upper lip and the nose. It is also useful for treating involuntary muscle movements that can occur after a face-lift.

The injections need to be repeated every few months, since the effects wear off. The treatment decreases the ability to frown or squint and may cause the corners of the mouth to turn down. When used for areas around eyes, it produces a rounder appearance afterward, which patients should be aware of before they undertake the procedure.

The drug does not cross the blood-brain barrier, and, to date, the only side effects are temporary muscle weakness near the injection site. Although there have been some reports that Botox can reduce migraine and tension headaches, Botox also causes headaches in about 1% of cases. In some cases, the headaches can be very severe and long lasting (from 8 days to a month). Some researchers suggest that either a contaminated batch of Botox or a specific injection technique may be the cause, but additional investigation is needed.

Plastic Surgery

In 2005, there were over 2.1 million cosmetic surgeries, up 1% from the year before. Most of these surgeries were liposuction and breast surgeries. However, over 200,000 each of eyelid and nose surgeries were performed. Facial plastic surgeries range from being fairly minimal, such as a brow lift, to a full face-lift.

Several face-lift procedures (called rhytidectomies) are available. Face-lifts can provide individuals with a more youthful look. The degree of improvement, however, depends on many factors, including age, bone structure, skin type, and personal habits, such as smoking and sunbathing.

The Procedure. When a face-lift is a relatively simple procedure, it can take about 2 hours under local anesthetic in a doctor's office. Complicated face-lifts are done under general anesthesia in a hospital and can take 3 - 6 hours. The face-lift procedure may be one of the following:

Superficial musculoaponeurotic system (SMAS) is the most common face-lift procedure. The surgeon makes an incision at the hairline and separates the skin from the underlying tissue and muscles. The muscles are tightened and excess fat and tissue, such as fat under the chin and neck, are removed.
The endoscopic subperiosteal or subgaleal face-lift is a less invasive surgical technique. The surgeon raises facial structures rather than cutting away flaps of skin. Only a few half-inch incisions are made, and scarring is minimal. Not all individuals are candidates for this procedure, however.

Neither SMAS nor the endoscopic version is effective for the middle part of the face, particularly the deep lines (naso-labial folds) that run down from the nose beside the mouth. Some time after the SMAS face-lift, the upper face begins to age again while the lower area keeps its shape, causing the face to look imbalanced. Researchers are looking at other approaches, such as one called composite face-lift, that lift most muscles in the face.

Recovery Process. Recovery normally lasts from several weeks to several months. Swelling and discoloration are common. Some patients report tingling or numbing sensations after surgery. These sensations generally decrease as damaged nerves regenerate.

Complications. A face-lift is not without risks. A postsurgical hematoma is a collection of blood that can occur after a face-lift. In one study, major hematomas occurred in 2.2% of patients and minor hematomas in 6.65% of patients. They generally develop within 2 weeks of the surgery and require draining. Even minor hematomas need fast treatment to prevent greater complications. Such complications can include infection, changes in skin color, fluid buildup, and prolonged recovery time.

Other less common complications may include the following:

Infection
Excessive bleeding
Imbalanced facial muscles
Delayed healing
Scarring
Permanent injury to the nerves that control facial movements

These complications are rare, particularly with a skilled surgeon, but the more complex the face-lifts, the greater the risk.

Blepharoplasty. Blepharoplasty is the primary surgical procedure for eye lifts. Results usually last 5 -10 years. Although simple, it has potential complications, including permanent difficulty in closing the eyes or making a stern expression. Newer techniques, however, are preventing this complication. Assuming the surgeon is experienced, laser surgery is now preferred to the standard surgical scalpel approach. Laser surgery reduces bleeding and bruising, and both the operation and recovery are faster. Temporary blurred or double vision is common. More serious complications include infection, bleeding, dry eyes, difficulty in closing the eyes, and pulling down of the lower lids. Rare cases of blindness have been reported.

Transconjunctival Upper Blepharoplasty. An innovative procedure called transconjunctival upper blepharoplasty removes fat from the membrane that lines the eyelids (the conjunctiva) and is an effective technique for treating both the upper and lower eyelids. Unlike traditional blepharoplasty, this procedure does not cause scarring in the nasal area. In patients who have scars from previous surgeries, transconjunctival removal of fat can also make existing scars less obvious. Long-term side effects and effectiveness of this procedure have not been studied.

Laser Liposculpture and Platysma Resurfacing. A procedure called laser neck and jowl liposculpture and platysma resurfacing may prove to be an alternative to face-lifts. The procedure requires only a one-inch incision under the chin and removing excess fat. After the fat is removed, the surgeon tightens the platysma, the thin muscular sheet under the skin of the neck, which improves the shape of the neck. Only local anesthetic is needed, and the patient can return to normal activities in 2 days. The patient's skin should be elastic enough to be able to reform without sagging.

Resources

www.aad.org -- American Academy of Dermatology
www.asds.net -- American Society for Dermatologic Surgery
www.plasticsurgery.org -- American Society of Plastic and Reconstructive Surgeons
www.surgery.org -- American Society for Aesthetic Plastic Surgery
www.skincarephysicians.com/agingskinnet -- Aging Skin Net

References

Autier P, Gandini S. Vitamin D Supplementation and Total Mortality : A Meta-analysis of Randomized Controlled Trials. Arch Intern Med. 2007;167:1730-1737.

Cho HS, Lee MH, Lee JW, et al. Anti-wrinkling effects of the mixture of vitamin C, vitamin E, pycnogenol and evening primrose oil, and molecular mechanisms on hairless mouse skin caused by chronic ultraviolet B irradiation. Photodermatol Photoimmunol Photomed. 2007;23(5):155-62.

Edison BL, Green BA, Wildnauer RH, Sigler ML. A polyhydroxy acid skin care regimen provides antiaging effects comparable to an alpha-hydroxyacid regimen. Cutis. 2004;73(2 Suppl):14-17.

Gordon, ML. A conservative approach to the nonsurgical rejuvenation of the face. Dermatol Clin. 2005 Apr;23(2):365-71.

Helfrich YR, Yu L, Ofori A, et al. Effect of smoking on aging of photoprotected skin: evidence gathered using a new photonumeric scale. Arch Dermatol. 2007;143(3):397-402.

Hercberg S, Ezzedine K, Guinot C, et al. Antioxidant supplementation increases the risk of skin cancers in women but not in men. J Nutr. 2007;137(9):2098-105

Kang S. A multicenter, randomized, double-blind trial of tazarotene 0.1% cream in the treatment of photodamage. J Am Acad Dermatol. 2005; 52(2): 268-274.

Mitsuhashi Y, Kawaguchi M, Hozumi Y, Kondo S. Topical vitamin D3 is effective in treating senile warts possibly by inducing apoptosis. Dermatol. 2005;32(6):420-423.

Rubino C, Farace F, Dessy LA, Sanna MP, Mazzarello V. A prospective study of anti-aging topical therapies using a quantitative method of assessment. Plast Reconstr Surg. 2005;115(4):1156-1162.

Samuel M, Brooke RC, Hollis S, Griffiths CE. Interventions for photodamaged skin. Cochrane Database Syst Rev. 2005;(1):CD001782.

Sudel KM, Venzke K, Mielke H, et al. Novel aspects of intrinsic and extrinsic aging of human skin: beneficial effects of soy extract. Photochem Photobiol. 2005;81(3):581-587.

Thornfeldt C. Cosmeceuticals containing herbs: fact, fiction, and future. Dermatol Surg. 2005;31(7 Pt 2):873-880.

Vochelle D. The use of poly-L-lactic acid in the management of soft-tissue augmentation: a five-year experience. Semin Cutan Med Surg. 2004;23(4):223-226.

Yarosh D, Klein J, O'Connor A, Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group. Lancet. 2001;357(9260):926-9.

Review Date:
10/23/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Infertility in men

FitSugar — Wed, 08 Oct 2008 17:35:50 -0700

In This Report

Highlights
Introduction
Male Reproductive System...
Sperm Abnormalities
Causes
Diagnosis
Treatment
Assisted Reproductive Techn...
Complications of Assisted R...
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New At-Home Fertility Test Kit

Fertell, the first at-home fertility test kit, became commercially available in June 2007. The Fertell kit contains tests to screen for both male and female infertility. Men can test their semen for concentrations of motile sperm, while women can test their urine for levels of follicle-stimulating hormone (a marker for egg quality). Results are available in fewer than 90 minutes and, according to the test kit's manufacturer, are 95% accurate. However, Fertell does not screen for all types of infertility problems and should not be used as a replacement for a complete evaluation by a doctor.

Intracytoplasmic Sperm Injection May Be Overused

Use of intracytoplasmic sperm injection (ICSI), in combination with in vitro fertilization (IVF), has increased 5-fold over the past decade, even though the proportion of men treated for male infertility has remained the same. This increase suggests that doctors are now using ICSI to treat problems other than male infertility, according to a 2007 study in the New England Journal of Medicine. Some doctors recommend ICSI for women who have failed IVF cycles or who have few or poor-quality eggs. According to the Society for Assisted Reproductive Technology, there is little evidence that ICSI can help couples conceive when male infertility is not a factor.

Infertility and Birth Defects

Although there has been concern that assisted reproductive technologies (ART) may increase the risk for birth defects, infertility itself may be a risk factor, regardless of whether ART is used. Even children born to infertile couples who do not use ART have a slightly increased risk for birth defects, indicates a 2006 study in the British Medical Journal.

Varicocele Embolization

Varicocele embolization, a minimally invasive surgical approach to varicocele repair, can help improve sperm count and motility, according to research presented at the 2006 annual meeting of the Radiological Society of North America. Varicoceles (varicose veins in the testicles) are often linked to male infertility.

Introduction

Infertility is the failure of a couple to become pregnant after one year of regular, unprotected intercourse. In both men and women the fertility process is complex. Even under ideal circumstances, the probability that a woman will get pregnant during a single menstrual cycle is only about 30%. And, when conception does occur, only 50 - 60% of pregnancies advance beyond week 20. In many cases, infertility is caused by a combination of problems in both partners that conspire to prevent conception from occurring.

About 8 - 10% of couples of reproductive age experience infertility, and in around 40% of these cases male infertility is the major factor. Another 40% of infertility problems are caused by abnormalities of the woman's reproductive system, and the remaining 20% involve couples who both suffer reproductive difficulties.

Infertility affects one in 25 American men. More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. Whether sperm counts are declining overall in industrialized countries is a controversial issue. However, over the last few years the number of assisted reproductive procedures that target male infertility have increased, while female procedures have declined.

The male reproductive system creates sperm that is manufactured in the seminiferous tubules within each testicle. The head of the sperm contains the DNA, which when combined with the egg's DNA, will create a new individual. The tip of the sperm head is the portion called the acrosome, which enables the sperm to penetrate the egg. The midpiece contains the mitochondria which supplies the energy the tail needs to move. The tail moves with whip-like movements back and forth to propel the sperm towards the egg. The sperm have to reach the uterus and the fallopian tube in order to fertilize a woman's egg.

Male Reproductive System

Male fertility depends on the proper function of a complex system of organs and hormones:

The process begins in the area of the brain called the hypothalamus-pituitary axis, a system of glands, hormones, and chemical messengers called neurotransmitters, all of which are critical for reproduction.
The first step in fertility is the production of gonadotropin-releasing hormone (GnRH) in the hypothalamus, which prompts the pituitary gland to manufacture follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
FSH maintains sperm production, and LH stimulates the production of the male hormone testosterone.
Both sperm and testosterone production occurs in the two testicles, or testes, which are contained in the scrotal sac (the scrotum). (This sac develops on the outside of the body because normal body temperature is too high to allow sperm production.)

The male reproductive structures include the penis, the scrotum, the seminal vesicles, and the prostate.

Sperm are manufactured in several hundred microscopic tubes, known as seminiferous tubules, which make-up most of the testicles.

Surrounding these tubules are clumps of tissue containing so-called Leydig cells. Here, testosterone is manufactured.

Sperm Development. The life cycle of sperm consists of a remarkable journey that depends on hormonal signals combined with a mechanical process. It takes about 74 days:

Sperm begin partially embedded in nurturing amoebae-like cells known as Sertoli cells, which are located in the lower parts of the seminiferous tubules.
As they mature and move along, they are stored in the upper part of the tubules. Young sperm cells are known as spermatids.
When the sperm has completed the development of its head and tail, it is released from the cell into the epididymis. This remarkable C-shaped tube is 1/300 of an inch in diameter and about 20 feet long. It loops back and forth on itself within a space that is only about one and a half inches long. The sperm's journey through the epididymis takes about 3 weeks.
The fluid in which the sperm is transported contains sugar in the form of fructose, which provides energy as the sperm matures. In the early stages of its passage, the sperm cannot swim in a forward direction and can only vibrate its tail weakly. By the time the sperm reaches the end of the epididymis, however, it is mature and looks like a microscopic squirming tadpole.
At maturity, each healthy sperm consists of a head that contains the man's genetic material, his DNA, and a tail that lashes back and forth at great speed to propel the head forward at about four times its own length every second. The ability of a sperm to move forward rapidly and straight is probably the most significant determinant of male fertility.

Ejaculation. When a man experiences sexual excitement, nerves stimulate the muscles in the epididymis to contract, which forces the sperm out through the penis:

In the penis, the sperm first pass into one of two rigid and wire-like muscular channels, called the vasa deferentia. (A single channel is called a vas deferens.)
Muscle contractions in the vas deferens from sexual activity propel the sperm along past the seminal vesicles. These are clusters of tissue that contribute fluid, called seminal fluid, to the sperm. The vas deferens also collects fluid from the nearby prostate gland. This mixture of various fluids and sperm is the semen.
Each vas deferens then joins together to form the ejaculatory duct. This duct, which now contains the sperm-containing semen, passes down through the urethra. (The urethra is the same channel in the penis through which a man urinates, but during orgasm, the prostate closes off the bladder so urine cannot enter the urethra.)
The semen is forced through the urethra during ejaculation, the final stage of orgasm when the sperm is literally shot out of the penis.

Click the icon to see an image of the vas deferens.

Semen. In addition to providing the fluid that transports the sperm, semen also has other benefits:

It provides a very short-lived alkaline environment to protect sperm from the harsh acidity of the female vagina. (If the sperm do not reach the woman's cervix within several hours, the semen itself becomes toxic to sperm and they die.)
It contains a gelatin-like substance that prevents it from draining from the vagina too quickly.
It contains sugar in the form of fructose to provide instant energy for sperm locomotion.

The Path to the Egg. The sperm's passage to the egg is a perilous journey.

Usually about 100 - 300 million sperm are delivered into the ejaculate at any given time. Even under normal conditions, however only about 15% of these millions of sperm are sound enough to fertilize an egg.
To compound the problem, after the stress of ejaculation, only about 400 sperm survive the orgasm to complete the journey.
Out of this number, a mere 40 or so sperm survive the toxicity of the semen and the hostile environment of the vagina to reach the vicinity of the egg. Normally, the cervical mucus forms an impenetrable barrier to sperm. However, when a woman ovulates (releases her egg, the oocyte), the mucous lining thins to allow sperm penetration.
Sperm that manage to reach the mucous lining in the woman's cervix (the lower part of her uterus) must survive about four more days to reach the woman's fallopian tubes. (Here, the egg is positioned for fertilization for only 12 hours each month.)
The few remaining sperm that penetrate the cervical mucus and are able to reach the fallopian tubes become capacitated.
Capacitation is a one-time explosion of energy that completes the sperm's journey. It boosts the motion of the sperm and triggers the actions of the acrosome, a membrane that covers the head of the sperm and resembles a warhead. The acrosome is dissolved, and enzymes contained within it are released to allow the sperm to drill a hole through the tough outer coating of the egg.
In the end, only one sperm gets through to fertilize the egg.

Click the icon to see an image of the uterus.

Sperm Abnormalities

More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. In 30 - 40% of cases of sperm abnormalities, the cause is unknown. It may be the end result of one or more factors that include chronic illness, malnutrition, genetic defects, structural abnormalities, and environmental factors. Partial obstruction anywhere in the long passages through which sperm pass can reduce sperm counts. In one study, obstruction was believed to be a contributing factor in over 60% of low sperm count cases. Obstruction itself can be caused by many factors.

Sperm abnormalities are categorized by whether they affect sperm count, sperm quality, or sperm shape.

In the past, a sperm count of less than 40 million/mL in the ejaculate was believed to cause infertility. Now, however, if the woman is fertile and young, a count as low as 10 million can often accomplish conception over time, even without treatment. In fertilization clinics, men with low sperm counts report fertilization rates of about 30%, while those with average sperm counts have rates between 60 - 80%. Sperm count varies widely over time, and temporary low counts are common. Therefore, a single test that reports a low count may not be a representative result.

Sperm motility is the sperm's ability to move. If movement is slow, not in a straight line, or both, the sperm have difficulty invading the cervical mucous or penetrating the hard outer shell of the egg. If 60% or more of sperm have normal motility, the sperm is at least average in quality. If less than 40% of sperm are able to move in a straight line, the condition is considered abnormal. Sperm that move sluggishly may also have genetic or other defects that render them incapable of fertilizing the egg. An important 2001 study identified a protein in the tail of the sperm called CatSper, which might play a central role in the ability of the sperm to swim and penetrate the egg.

Morphology refers to the shape and structure of an object. Morphology may be even more important than count or motility in determining potential fertility. Abnormally shaped sperm cannot fertilize an egg. About 60% of the sperm should be normal in size and shape for adequate fertility.

The perfect structure is an oval head and long tail. Abnormally shaped sperm may include a number of variations:

A very large round head. (In one study, if 14% or more of sperm had round enlarged heads, the chances for pregnancy fell to about 20%. Such an abnormality indicates early unraveling of genetic material.)
An extremely small pinpoint head
A tapered head
A crooked head
Two heads
A tail with kinks and curls

Sperm carry half the genetic material necessary to make a complete human being. (The egg holds the other half.) Genes are contained in the rod-like structures called chromosomes. The genes themselves are made up of chains of molecules called DNA, which carry the information that defines a human. Genetically fragile sperm are important factors in male infertility. Such sperm have fragmented DNA chains, which make them less capable of fertilization and may also contribute to low quality.

Causes

In one study, the causes of infertility in men seeking to conceive included:

Vasectomy. In the study, 56% of men were seeking a reversal of this procedure. Thirty years ago, this was a factor in only 5% of men seeking help for fertility.
Varicocele (14%). A network of veins carries blood away from the testicles and back up into the body. If these veins become enlarged, twisted, and swollen (similar to varicose veins in the leg), this condition is termed a varicocele. Varicoceles can impair testicular function and fertility.
Unknown infertility (8%).
Absence of sperm (6%). There are many biologic and environmental factors that can lead to low sperm count. For instance, abnormalities in production or obstruction of the tubes that carry sperm can reduce sperm levels. A condition called Sertoli cell-only syndrome is one in which the cells that produce sperm (the Sertoli cells) are absent. This can be a congenital problem that a man is born with or caused by infection, injury, medication, radiation, or genetics. In addition, other conditions may cause infertility in men.

The effect of aging on male fertility is not totally clear. However, growing evidence suggests that it may be a factor (although not to the extent that it is in women). This evidence indicates that age-related sperm changes in men are not abrupt, but are a gradual process. Aging can adversely affect sperm counts and sperm motility (the sperm's ability to swim quickly and move in a straight line). A 2006 study also suggested that the genetic quality of sperm declines as a man ages. The researchers found that poor sperm motility was associated with DNA fragmentation. This led to some older men having an increased risk of passing on gene mutations that cause dwarfism and possibly other genetic diseases.

Nearly any major physical or mental stress can temporarily reduce sperm count. Some common conditions that lower sperm count, temporarily in nearly all cases, include:

Emotional Stress. Stress may interfere with the hormone GnRH and reduce sperm counts.

Sexual Issues. In fewer than 1% of cases, impotence, premature ejaculation, or psychological or relationship problems contribute to male infertility, although these conditions are usually very treatable. Lubricants used with condoms, including spermicides, oils, and Vaseline, can affect fertility. Astroglide, Replens, or mineral oil may not be as harmful to sperm. However, oil-based lubricants can damage latex condoms and should be avoided.

Testicular Overheating. Overheating, such as from high fevers, saunas, and hot tubs, may temporarily lower sperm count. Persistent exposure to high temperatures during work may impair fertility. Several studies have found no negative effects on fertility from wearing tight trousers, briefs, or athletic supports, even every day.

Substance Abuse. Cocaine or heavy marijuana use appears to temporarily reduce the number and quality of sperm by as much as 50%. Sperm actually have receptors for certain compounds in marijuana that may impair the sperm's ability to swim and also inhibit their ability to penetrate the egg. Alcohol does not appear to affect fertility, unless it is so abused that it causes liver damage.

Smoking. Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that affect the offspring. One study found that men or women who smoke have lower success rates with assisted reproductive technologies. Another study reported that men who smoke also have lower sex drives and less frequent sex.

Malnutrition and Nutrient Deficiencies. Deficiencies in certain nutrients, such as vitamin E, vitamin C, selenium, zinc, and folate, may be particular risk factors for infertility

Obesity. Obesity may be a risk factor for male infertility. A 2006 epidemiological study found that a 20-pound increase in a man's weight increased the chance for infertility by about 10%.

Bicycling. Bicycling has been linked to impotence in men and also may affect fertility. Pressure from the bike seat may damage blood vessels and nerves that are responsible for erections. Mountain biking, which involves riding on off-road terrain, exposes the perineum (the region between the scrotum and the anus) to more extreme shocks and vibrations and increases the risk for injuries to the scrotum. One study found that men who mountain bike are far more likely to have scrotal abnormalities, including calcium deposits, cysts, and twisted veins. Men who cycle can reduce such risks by:

Taking frequent rests while biking
Wearing padded bike shorts
Using a padded or specially contoured bike seat that is raised high enough and sits at the proper angle

Problems in the genes that regulate male fertility and in the genetic material of sperm itself are important contributors to infertility problems in men. In fact, even in men with no known fertility problems, 19% of the sperm are genetically defective. Certain inherited medical conditions also contribute to male infertility. Defective genes themselves can be inherited, produced by environmental assaults (such radiation exposure), or both. Of some concern is the possibility that these mutations will be passed to offspring in men who undergo fertilization techniques that retrieve sperm and directly fertilize the egg. (Under natural conditions, genetically abnormal sperm would be very unlikely to reach and fertilize the egg.)

Defective Genetic Material. Sperm carry half the genetic material necessary to make a human being. Infertile men have been reported to have a relatively high percentage of sperm with broken or damaged DNA (the molecular chain that makes up a gene).

Genetic Factors Specifically Affecting Sperm Production or Quality. Abnormalities in genes that specifically regulate sperm production and quality are major factors in male infertility. Some research suggests that about 10% of cases of male infertility may be due to problems, most likely genetic, in the acrosome. The acrosome is the enzyme-filled membrane cap on the sperm -- its warhead -- that is critical for piercing the egg. In one study, pregnancy was impaired if 7% or more of sperm had abnormalities in the acrosome.

Inherited Disorders that Affect Fertility. Certain inherited disorders can impair fertility. Examples include:

Cystic fibrosis patients often have missing or obstructed vas deferens (the tubes that carry sperm). In fact, men whose infertility is caused by an inborn missing vas deferens have a 60% chance that they carry the gene for cystic fibrosis (even if they don't have the disease itself).
Klinefelter syndrome patients carry two X and one Y chromosomes (the norm is one X and one Y), which leads to the destruction of the lining of the seminiferous tubules in the testicles during puberty, although most other male physical attributes are unimpaired.
Kartagener syndrome, a rare disorder that is associated with a reversed position of the major organs, also includes immotile cilia (hair-like cells in lungs and sinuses that have a structure similar to the tails of sperm). Sperm motility may also be impaired by this condition.
Polycystic kidney disease, a relatively common genetic disorder that causes large cysts to form on the kidneys and other organs during adulthood, may cause infertility as the first symptom if cysts develop in the reproductive tract.

Exposure to toxins, chemicals, or infections may reduce sperm count by either affecting testicular function or altering hormone systems. The extent of the impact and specific environmental assaults involved, however, are often controversial. Some researchers believe environmental toxins are contributing to a general worldwide decline in male fertility. Data indicate that testosterone levels in American men may have declined over the last several decades. The reasons for this decline have not yet been determined. However, even if testosterone levels are declining, the proportion of men treated for fertility problems has not changed much over the past decade.

Free Radicals (Oxidants). The primary suspects in the link between environmental assaults and infertility are free radicals, also called oxidants. These are unstable molecules, usually containing oxygen, that are released as a by-product of many natural chemical processes in the body. Infections, chemicals, and other environmental assaults can produce high levels of these particles. High levels may even affect the genetic material in cells. Sperm are particularly vulnerable to the damaging effects of this oxidation process. There have been reports that significant levels of oxidants occur in the semen of about 25% of infertile men.

Exposure to Estrogen-Like and Hormone-Disrupting Chemicals. European studies have increasingly reported a worsening in male reproductive health and an increase in testicular and prostate cancers. Many investigators strongly suspect environmental causes, particularly excessive chemicals that disrupt hormones, as a major cause for both these events. Estrogen-like chemicals found in pesticides and other chemicals are of particular concern. Overexposure to estrogen in male animals reduces the number of Sertoli cells (the cells necessary for the initial development of sperm). Some hormone-disrupting chemicals under investigation include:

Treatment of prostate cancer varies depending on the stage of the cancer and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

Bisphenol A is a widely used chemical found in plastic food containers and bottles that has provoked concern. It has potent estrogen-like effects in low dose. Use of the chemical in female rats has produced prostate abnormalities in their male offspring.
Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Specific phylates of special concern include dibutyl phthalate (DBP), which is found in many products, including cosmetics and clay products sold to children (Fimo, Sculpey). Animals exposed to phylates have significantly impaired sperm count and abnormalities in their reproductive structures, such as the testes. In addition, there is some concern that exposure in pregnant women may affect the offspring,
Organochlorines are compounds that combine chlorine and organic substances -- usually petrochemicals. Many have estrogen-like effects, including those previously used to make plastics (PCBs) and pesticides (DDT and p,p-DDE). Some, such as dioxins and furans, are byproducts of many chemical processes. Fortunately, most of these chemicals have been banned, but they were heavily used in manufacturing before 1970 and are still widespread in the environment. Studies report that when men had a history of moderate or high on-the-job exposure to pesticides containing organochlorines, their fertility rates were lower than men without such exposures. Studies have found a strong correlation between high levels of polychlorinated biphenyls (PCBs) or p,p-DDE with reduced sperm quality and quantity. In one of the studies, even men with healthy sperm with high organochlorine levels had a lower sperm count than those with lower levels of these compounds.

Most evidence on the hormone of chemical estrogens has occurred in animals and birds. Tests of single chemicals containing estrogen have reported little danger for people. Some studies suggest, however, that exposure to more than one of these chemicals may be very harmful. At this time, there is no strong evidence supporting a serious harmful effect in people who have normal exposure to these chemicals. Major efforts are underway to determine the extent of any possible harm from these chemicals.

Exposure to Heavy Metals. Chronic exposure to heavy metals such as lead, cadmium, or arsenic may affect sperm quality. Trace amounts of these metals in semen seem to inhibit the function of enzymes contained in the acrosome, the membrane that covers the head of the sperm.

Radiation Treatments. X-rays and other forms of radiation affect any rapidly dividing cell, so cells that produce sperm are quite sensitive to radiation damage. Cells exposed to significant levels of radiation may take up to 2 years to resume normal sperm production and, in severe circumstances, may never recover.

Men with fertility problems because of low semen levels when they ejaculate may have a structural abnormality in the tubes transporting the sperm. (A normal amount of semen is 2.5 - 5 mL, or about 1/2 - 1 teaspoon.)

A varicocele is an abnormally enlarged and twisted (varicose) vein in the spermatic cord that connects to the testicle. Varicoceles are found in 15 - 20% of all men and in 25 - 40% of infertile men, although it is not clear how or even if they affect fertility. They tend to occur more commonly (85%) on the left side. Some theories supporting their possible effect on infertility include:

Click the icon to see an image of a varicocele.

Varicoceles may partially obstruct the passages through which sperm pass.
Varicoceles may elevate temperature in the testes.
Varicoceles may produce higher levels of nitric oxide, a substance that has beneficial effects on blood flow and other functions but which might, in excess, injure sperm.
Varicoceles may block oxygen supply to the sperm.
Varicoceles have been associated with abnormalities in cellular material in the sperm. One study suggested that some men with fertility problems may have genetic defects that cause both varicoceles and impaired sperm.

Some reports indicate that only varicoceles that are large enough to be felt (or palpable) may impact fertility. On the other hand, however, an 8-year study of men with and without varicoceles found no differences in sperm quality or in the ability to conceive. Furthermore, the few well-conducted studies on repair of varicoceles suggest that the procedure does not improve pregnancy rates. Their effect on fertility remains unclear.

Hypogonadism is the general name for a severe deficiency in gonadotropin-releasing hormone (GnRH), the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones. Low levels of testosterone from any cause may result in defective sperm production.

Hypogonadism is uncommon and is most often present at the time of birth, usually the result of rare genetic diseases affecting the pituitary gland that may include selective deficiencies of the hormones FSH and LH, Kallman syndrome, or panhypopituitarism, in which the pituitary gland fails to make almost all hormones. It can also develop later in life from brain or pituitary gland tumors or as a result of radiation treatments. Defects in the gene on the X chromosome that regulates receptors that bind to androgens (male hormone) may also prove to be very important causes of male infertility.

Click the icon to see an image of the pituitary gland.

Autoimmunity is a condition in which antibodies of the immune system attack specific cells in the body, mistaking them for foreign microinvaders. In the case of male infertility, these so-called autoantibodies ("self" antibodies) target the sperm. Antibodies bind to specific parts of the sperm, such as the head or tail and, depending on the site of attachment, cause various problems:

Sperm may stick together (agglutinate)
They may fail to interact with cervical mucous
They may be unable to penetrate the egg

Some experts believe that in most cases the presence of these antibodies will not prevent conception unless a large percentage of sperm are affected.

Vasectomy and Anti-Sperm Antibodies. Vasectomy, the primary sterility procedure in men, is the most common cause of sperm autoantibodies (also called anti-sperm antibodies). Their typical development may be as follows:

Vasectomy works by severing the vas deferens, the tube that carries sperm from the testicles to the urethra (which leads out of the penis).
After vasectomy, sperm continue to be produced but, instead of being confined to the reproductive passages, they leak out into the body.
Here, the immune system may perceive them as foreign invaders and develop antibodies to attack them.

Such antibodies often persist, even if a man restores sperm flow by a successful reversal procedure (vasovasostomy). The persistence of anti-sperm antibodies may result in infertility.

Click the icon to see an illustrated series detailing vasectomy.

Other Causes of Autoantibodies. Antibodies to sperm can also appear in men without previous vasectomies and have been reported to be present in 10% of all men with fertility problems. They may be linked to genital infections or injury, although the cause is usually not known.

Retrograde ejaculation occurs when the muscles of the urethra do not pump properly during orgasm and sperm are forced backward into the bladder instead of forward out of the urethra. Sperm quality is often impaired.

Retrograde ejaculation can be the consequence of several conditions:

Surgery to the lower part of the bladder or prostate (the most common cause of retrograde ejaculation)
Diabetes
Multiple sclerosis
Back surgery
Spinal cord injury

Medications such as tranquilizers, certain antipsychotics, or hypertension medications also may cause temporary retrograde ejaculation.

Any structural abnormalities that affect the testes, tubes, or other reproductive structures can have a profound effect on fertility.

Testicular Dysgenesis Syndrome. Testicular dysgenesis syndrome is a recently observed occurrence of three conditions -- impaired sperm production and quality, testicular cancer, and genital tract abnormalities. Environmental factors that increase damage from oxidants are believed to be responsible.

The genital abnormalities identified with this syndrome are undescended testes and hypospadias, each of which is associated with infertility:

Undescended Testes (Cryptorchidism). In some cases, there is a failure of the testes to descend from the abdomen into the scrotum during fetal life. Cryptorchidism is associated with mild to severe impairment of sperm production. In one survey, 38% of men who as youngsters had two undescended testicles and 10% of men with one undescended testicle were infertile, compared with 5% of men who had normal testes. Even one undescended testicle may impair fertility. In cryptorchidism, the testes are exposed to the higher internal body heat, but this may not totally explain the damage in sperm production that can occur. (Men who suffer from this condition should be aware that even if the testicle is surgically moved to the scrotum, their risk of testicular cancer is significantly increased, warranting careful self-exams and regular follow-up with a doctor.)
Hypospadias. This is a birth defect in which the urinary opening is on the underside of the penis, can prevent sperm from reaching the cervix if not surgically corrected.

Click the icon to see an image of an undescended testicle.

Click the icon to see an image of hypospadias.

Blockage in the Tubes that Transport Sperm. Some men are born with a blockage in the epididymis or ejaculatory ducts or other problems that later affect fertility. One center reported that 2% of men seeking treatment had no vas deferens.

Anorchia. In the very rare condition known as anorchia, a man is born without any testes.

Syringomyelia. This is a disease of the spinal cord that results in no ejaculate at all (aspermia).

Birth rates among cancer survivors are only 40 - 85% of normal rates. Certain cancers, particularly testicular cancer, impair sperm production, often severely. Cancer treatments such as chemotherapy and radiation can damage sperm quality and quantity, causing infertility. The closer radiation treatments are to reproductive organs, the higher the risk for infertility. Fortunately, while men may fail to produce sperm for as long as 5 years after radiation therapy, many men eventually recover their sperm production ability. Chemotherapy with drugs that harm reproductive function tends to affect fertility more severely in men than in women. New drug regimens are helping to improve fertility rates.

Adolescents and adult men undergoing cancer treatments who may want to father children should consider banking and freezing their sperm for later use in assisted reproductive therapies. This technique is called sperm cryopreservation. Sperm cryopreservation is recommended by the American Society of Clinical Oncology as the method with the highest likelihood of success for male cancer survivors. However, these banking methods are not appropriate for pre-adolescent boys being treated for childhood cancers such as leukemia. Researchers are investigating ways that stem cell transplantation may someday help these children regain their fertility while avoiding leukemia relapse.

There is some controversy over the effect of infections on infertility. Simply detecting the presence of an infection in infertile men does not necessarily mean that it has any relationship to the infertility itself. The immune response to some infections may release inflammatory factors and oxidants, chemically unstable particles that can damage sperm. The exact impact of this process on sperm is unclear, however. Infections may alter the liquidity of semen and sperm motility, although these are likely to be temporary effects. Among the infections most implicated in infertility are:

Sexually Transmitted Diseases. Repeated Chlamydia trachomatis or gonorrhea infections are most often associated with male infertility. Such infections can cause scarring and block sperm passage. Human papilloma viruses, the cause of genital warts, may also impair sperm function.

Mycoplasma. Mycoplasma is an infectious organism that appears to fasten itself to sperm cells and render them less motile.

Mumps. When mumps develops after puberty, it damages the testicles in 25% of men afflicted with the disease. (Interferon, an anti-viral drug, may help prevent infertility in adult males with active mumps, but the drug is highly toxic and caution is essential.)

Glandular Infections in the Urinary Tract or Genitals. Glandular infections that may affect fertility include prostatitis (in the prostate gland), orchitis (in the testicle), semino-vesculitis (in the glands that produce semen), or urethritis (in the urethra), perhaps by altering sperm motility. Even after successful antibiotic treatment, infections in the testes may leave scar tissue that blocks the epididymis.

Medical Conditions. Other medical conditions that can affect male fertility include any severe injury or major surgery, diabetes, HIV, thyroid disease, Cushing syndrome, heart attack, liver or kidney failure, and chronic anemia.

The effects of medications on sperm quality and count have not been rigorously studied, and many medicines are commonly prescribed without knowing whether they impair fertility. Anabolic steroids (which are often abused by weight lifters and other athletes) deserve special notice because they are known to severely impair sperm production. Among the other drugs that can affect male fertility are cimetidine (Tagamet), sulfasalazine (Azulfidine), salazopyrine, colchicine, methadone, methotrexate (Folex), phenytoin (Dilantin), corticosteroids, spironolactone (Aldactone), thioridazine (Mellaril), and calcium channel blockers.

Diagnosis

In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. It should be done earlier if a woman is over age 35 or if either partner has known risk factors for infertility. A work-up can not only uncover the causes of infertility but also detect other potentially serious medical problems as well, including genetic mutations, cancer, or diabetes.

The patients will provide the doctor with a detailed history of any medical or sexual factors that might affect fertility:

Frequency and timing of sexual intercourse
Duration of infertility and any previous fertility events
Childhood illnesses and any problems in development
Any serious illness (diabetes, respiratory infections, cancer, previous surgeries)
Sexual history, including any sexually transmitted diseases
Any exposure to toxins, such as chemicals or radiation
History of any medications and allergies
Any family history of reproductive problems

A fertility specialist, usually a urologist, will perform a physical examination. A physical examination of the scrotum, including the testes, is essential for any male fertility work-up. It is useful for detecting large varicoceles, undescended testes, absence of vas deferens, cysts, or other physical abnormalities.

Varicoceles large enough to possibly interfere with fertility can be felt during examination of the scrotum. In such cases, they are described as feeling like "a bag of worms." They disappear or are greatly reduced when the patient lies down, so the patient should be examined for varicocele while standing.
Checking the size of the testicles is helpful. Smaller-sized and softer testicles along with tests that show low sperm count are strongly associated with problems in sperm formation. Normal testicles accompanied by a low sperm count, however, suggest possible obstruction. The doctor may also take the temperature of the scrotum with a test called scrotal thermography.
The doctor will also check the prostate gland for abnormalities.
The penis is checked for warts, discharge from the urinary tract, and hypospadias (incorrect location of the urethra opening).

A urine sample to detect sperm after ejaculation may rule out or indicate retrograde ejaculation. It also may be used to test for infections.

The basic test to evaluate a man's fertility is a semen analysis. The sperm collection test for men who can produce semen involves the following steps:

A man should abstain from ejaculation for several days before the test because each ejaculation can reduce the number of sperm by as much as a third. To ensure an accurate sample, most doctors recommend abstaining from ejaculation for at least 2 days, but not more than 5 days, prior to semen collection.
A man collects a sample of his semen in a collection jar during masturbation either at home or at the doctor's office. Proper collection procedure is important, since the highest concentration of sperm is contained in the initial portion of the ejaculate. Specially designed condoms are also available that enable collection of a sample during sexual intercourse. (Regular condoms are not useful, since they often contain substances that kill sperm.)
The sample should be kept at body temperature and delivered promptly. If the sperm are not analyzed within 2 hours or kept reasonably warm, a large proportion may die or lose motility.
A semen analysis should be repeated at least three times over several months.

The sperm count test is performed if a man's fertility is in question. It is helpful in determining if there is a problem in sperm production or quality of the sperm as a cause of infertility. The test may also be used after a vasectomy to make sure there are no sperm in the semen.

The man and woman should both be present when the doctor discusses the results of this analysis so that both partners understand the implications. The analysis report should contain results of any abnormalities in sperm count, motility, and morphology as well as any problem in the semen. However, semen analysis alone is not necessarily a definitive indicator of either infertility or fertility.

In June 2007, the first at-home fertility test kit became commercially available. Fertell includes both male and female tests that allow couples to test sperm motility (for men) and follicle-stimulating hormone (for women). Results are available in less than 90 minutes, and are 95% accurate. The test is available on-line and at some pharmacies. It does not require a prescription. However, Fertell does not screen for all types of fertility problems and should not be used as a substitute for a professional evaluation by a doctor.

Sperm Count. A low sperm count should not be viewed as a definitive diagnosis of infertility but rather as one indicator of a fertility problem. Although in a large analysis sperm counts below 13.5 million were considered a strong indication of infertility, pregnancy was possible so long as any motile sperm were present. If there are no sperm cells at all in the semen, the doctor checks for obstruction in the tubes or for Sertoli cell-only syndrome, in which there are no sperm-producing cells in the testes. An at-home test (FertilMARQ) is now available to help gauge sperm quantity.

Sperm Motility. Motility (the speed and quality of movement) is graded on a 1 - 4 ranking system. For fertility, motility should be greater than 2.

Grade 1 sperm wriggle sluggishly and make little forward progress. (Sperm that, in fact, clump together may indicate that antibodies to the sperm are present.)
Grade 2 sperm move forward, but they are either very slow or do not move in a straight line.
Grade 3 sperm move in a straight line at a reasonable speed and can home in on an egg accurately.
Grade 4 sperm are as accurate as Grade 3 sperm, but move at terrific speed.

More than 63% of sperm should be motile for normal fertility, but even men whose motile sperm constitutes only about a third of the total sperm count should not rule out conception. Testing for sperm motility is particularly valuable for predicting the success of artificial insemination and which men might be candidates for the intracytoplasmic sperm injection (ICSI) fertilization technique, in which the sperm is inserted directly into the egg and motility plays almost no role.

Sperm Morphology. Morphology is the shape and structure of the sperm and, of the three main sperm values, may be the best predictor of fertility. Older reports indicated that about 60% of the sperm should be normal in size and shape for adequate fertility. However, one major analysis used a much broader range of criteria for sperm morphology and concluded that values over 12% were good predictors of fertility. Determining the morphology of the sperm is particularly important for the success of the fertility treatments in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Seminal Fluid. The seminal fluid (semen) itself is analyzed for abnormalities. The color is checked and should be whitish-gray.

The amount of semen is important. Most men ejaculate 2.5 - 5 milliliters (mL) or cubic centimeters (cc) (1/2 - 1 teaspoon) of semen. Either significantly higher or lower amounts can be a sign of trouble:

Amounts greater than 1 cc but lower than 2.5 cc may indicate prostate problems or frequent intercourse.
A semen sample that is less than 1 cc could indicate a blockage of the ejaculatory ducts or other tubular abnormalities.
No ejaculate at all may signal retrograde ejaculation.
High amounts of ejaculate may, in some cases, also contribute to infertility.

The semen will be tested for how liquid it is. (Normal semen is liquefied within 20 minutes after adding certain enzymes.) Abnormal results suggest the following:

Overly sticky fluid suggests problems in the prostate gland (which adds fluid to sperm)
Overly watery fluid suggests lack of sperm

The amount of sugar (fructose) in sperm will be measured:

Since fructose is added to the semen in the epididymis, an absence of fructose indicates that an obstruction has occurred either in the vas deferens or the epididymis.
Conversely, if there is fructose in the semen but no sperm, then the channel from the epididymis is open but there is a defect in sperm production.

Other factors may also be measured:

White blood cell counts are taken to detect infection.
Low levels of a substance called inhibin B, which appears to be produced only in the testes, may indicate blockage or other defects in the seminiferous tubules.
Low levels of another compound, alpha-glucosidase, may also indicate blockage in the epididymis.

Blood tests are used for measuring several factors that might affect fertility:

Hormonal Levels. Tests for certain hormone levels are indicated if semen analysis is abnormal (especially if sperm concentration is less than 10 million per milliliter) or there are other indications of hormonal disorders.

Blood tests for testosterone and follicle-stimulating hormone (FSH) levels are usually taken first.
If testosterone levels are low, then luteinizing hormone (LH) are measured.

Low levels of FSH, LH, and testosterone indicate a diagnosis of hypogonadotropic hypogonadism. Very high FSH levels with normal levels of other hormones indicate abnormalities in initial sperm production. Usually this occurs only if the testicles are severely defective, causing Sertoli cell-only syndrome, in which sperm-manufacturing cells are absent. Other hormones, such as prolactin, estrogen, or stress hormones may be measured if there are symptoms of other problems, such as low sexual drive or the presence of breasts.

Infections. Blood tests can also determine the presence of any infections that might affect fertility, including HIV, hepatitis, and Chlamydia.

The postcoital test, also known as the cervical mucus penetration test, is designed to evaluate the effect of a woman's cervical mucus on a man's sperm. Typically, a woman is asked to come into the doctor's office within 2 - 24 hours after intercourse at mid-cycle (when ovulation should occur). A small sample of her cervical mucus is examined under a microscope. If the doctor observes no surviving sperm or no sperm at all, the cervical mucus should then be cultured for the presence of infection. The test cannot evaluate sperm movement from the cervix into the fallopian tubes or the sperm's ability to fertilize an egg.

If a man has had a vasectomy reversed and still cannot conceive or if semen analysis shows sperm clumping together, blood tests for anti-sperm antibodies will be conducted. Anti-sperm antibodies may also develop after genital infection or injury to the testes. The primary negative effect of these antibodies is to bind the sperm to the woman's cervical mucus, preventing the sperm from swimming further up.

Occasionally, a testicle biopsy may be performed, particularly for the following:

If Sertoli cell-only syndrome is suspected, in which sperm-producing cells in the testes are absent. It should be noted that specific cellular patterns can determine whether this condition is congenital (inborn) or caused by some later injury. This distinction is important in predicting the potential success of later sperm retrieval procedures.
For detecting obstruction in the transport system when sperm production looks normal but the count is low.

The standard biopsy procedure requires incisions (called an open approach) under anesthesia. It can be painful afterward. More than one biopsy may be needed in the case of suspected Sertoli cell-only syndrome, since one area may not have cell-producing cells, but other regions may contain normal sperm. Biopsies of both testes are more accurate than one. (Doctors must be careful to avoid the epididymis during a biopsy, since it is a continuous tiny tube and would be destroyed.) Patients may consider freezing any sperm retrieved during biopsy for later use.

Ultrasound imaging may be used to accurately determine the size of the testes or to detect cysts, tumors, abnormal blood flow, or varicoceles that are too small for physical detection (although such small veins may have little or no effect on fertility). It also can detect testicular cancer, which some experts believe make it worthwhile as a routine procedure for any male infertility work-up.

Click the icon to see an image of testicular ultrasound.

Genetic testing may be warranted in men who are severely deficient in sperm and who show no evidence of obstruction, particularly in men undergoing the intracytoplasmic sperm injection (ICSI) procedure. One study of men attending a fertility clinic showed that a third had genetic defects. If genetic abnormalities are suspected in either partner, counseling is recommended. Researchers are testing techniques such as preimplantation genetic diagnosis (PGD) that can examine all the chromosomes in a human embryo and detect defective genes, such as those for cystic fibrosis, at the very earliest stages. If it proves useful, it may help identify numerous abnormalities that increase the risk for infertility, treatment failures, or genetic defects in the offspring. In fact, a 2003 study suggested that performing an initial genetic analysis to determine DNA fragmentation in sperm may be a better way of predicting whether conception will succeed than analyzing semen.

In men who wish to undergo fertility treatments, certain tests will help determine the right strategies.

The Hamster Test. The hamster test, or micro-penetration assay test, uses the sperm sample to fertilize hamster eggs that have had their covering removed to allow penetration. If fewer than 5 - 20% of the eggs are fertilized, infertility is diagnosed. It may be useful for determining the best assisted reproductive treatment options for men with infertility.

The Human Zona Penetration Test. The human zona penetration test uses sperm to fertilize dead human eggs, which are usually obtained from an ovary that was removed for medical purposes. (Like the hamster test, the procedure cannot result in a living embryo.) Results may provide the same information as the hamster test and also indicate whether the sperm can penetrate the outer coating of an egg.

Acrosome Reaction Test. Tests that induce the ability of the sperm's enzyme-rich covering (acrosome) to dissolve can be very useful.

Other Tests. Additional advanced laboratory tests to measure sperm function, such as computer-aided sperm motility analysis, may also be performed. Some of these tests assess such factors as level of cell-damaging oxidants.

Treatment

Many men diagnosed with infertility in the past would be considered treatable now, even some men with spinal cord injuries. Unless a man produces no sperm at all, recent developments in treatment have made fertility possible for many men willing to undergo treatment and bear the expense. Before undergoing more advanced procedures, most couples trying to conceive should attempt some simple lifestyle changes.

Both male and female hormone levels fluctuate according to the time of day, and they also vary from day to day and month to month. Some timing tips might be helpful.

Male Hormone Levels and Sexual Activity. Male hormone levels are highest in the morning. In one study of men, their sexual activity was highest in October, when conception rates were also high.

Fertility and Seasonal Changes. Different studies have reported higher sperm counts in the winter than in the summer. For women, fertility rates as measured by treatment success are highest in months when days are longest.

Monitoring Basal Body Temperature. To determine the most likely time of ovulation and therefore the time of fertility, a woman is instructed to take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations.

By studying the temperature patterns after a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly. Couples must try to avoid becoming fixated on the chart, however, in scheduling their sexual activity. Spontaneity can be lost, and the stress on the relationship can be quite severe.

Hormone Monitoring Systems for Women. A device called a saliva fertility monitor (Fertility Tracker) uses a microscope to view slides containing saliva and monitors estrogen levels. Home test kits that monitor reproductive hormone levels in the urine are also available. They are less costly than the saliva test but are messier. Monitoring hormone levels helps to determine when a woman is ovulating.

Frequency of Intercourse. The question of how often a couple should have intercourse is in debate. Some experts say that having sex more than 2 days a week adds no benefits. And, in fact, frequent sexual activity lowers sperm count per ejaculation. Some studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg.

Everyone should eat a healthy diet rich in fresh fruits, vegetables, and whole grains. Replace animal fats with monounsaturated oils, such as olive oil. Fish is also a good choice, and fish oils may have benefits for men with infertility. Certain specific nutrients, vitamins and minerals may also improve fertility.

Higher antioxidant intakes of vitamin C, vitamin E, and beta-carotene may help improve sperm numbers and motility, according to a 2005 study. The study included both food and supplement sources.
Vitamins C and E may also help repair DNA damage to sperm. According to a 2005 study, men who took 1 gram per day of these vitamins significantly reduced their percentage of DNA sperm fragmentation within 2 months.
The dietary supplements L-carnitine and L-acetylcarnitine may help improve sperm motility, according to several recent clinical trials.

A man who wants to increase his sperm count should also pursue a healthy lifestyle.

Avoid cigarettes and any drugs that may affect sperm count or reduce sexual function.
Overweight men should try to reduce their weight.
Get sufficient rest, and exercise moderately but regularly. (Those who exercise excessively might cut back, but not stop altogether.)
Stress may contribute to reduced sperm quality. It is not known if stress reduction techniques can improve fertility, but they may help couples endure the difficult processes involved in fertility treatments.
Although studies now indicate that tight underwear and pants pose no threat to male fertility, there is no harm in wearing looser clothing.
To prevent overheating of the testes, men should avoid hot baths, showers, and steam rooms.

The fertility process is a roller coaster of emotions that are present throughout both failure and success. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other seemingly fertile couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful.

Planning for Emotional Turmoil.

Decide in advance how many and what kind of procedures will be emotionally and financially acceptable and attempt to determine a final limit. Fertility treatments are expensive.
Determine alternatives (adoption, donor sperm or egg, or having no children) as early as possible in the fertility process. This can reduce anxiety during treatments and feelings of hopelessness in case conception does not occur.

Managing Emotional Stress During the Process. Managing negative emotions in both men and women can be viewed as important as medical treatment. The process of fertility evaluation can be very difficult for many men. In a 2003 study, over 10% of men who required a second semen sample were unable to collect a semen sample using masturbation. Such men had had no problems with a first collection, but after being asked for additional samples they suffered severe anxiety during both masturbation in the fertility clinic and during regular sexual activity at home. Numerous studies reported a significant association between psychologic factors, particularly anxiety, and fertility treatment failure in women.

Managing the Emotional Effects of the Outcome. After enduring the process of fertility evaluation, the couple must face the outcome, and even a positive outcome has emotional repercussions.

Effects of Failure. Needless to say, the emotional stress of failure can be devastating even on the most loving and affectionate relationships and even in those who have prepared for the possibility of failure. Neither the male nor female partner should hesitate to seek professional help if the emotional burdens are too heavy.
Effects of Genetic Testing. As advanced technologies allow testing and greater genetic information at the earliest stage, potential parents will have to learn to deal with the uncertainties of possible chromosomal abnormalities, which may or may not be significant.
Effects of Multiple Births. A successful pregnancy that results in a multiple birth introduces new complexities and emotional problems. One study reported a very high rate of depression in women with triplets, particularly if they had little help from others, and especially if their husbands weren't involved.
Effects on Parenting. Once the fertility treatment-assisted child arrives, parents (both men and women) are more likely to be anxious and to have less confidence than those who conceive naturally.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:

A couple's own eggs or sperm
Donor eggs, sperm, or embryos

Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART increased by 128% from 1996 - 2002. More than 45,000 babies are now born in the U.S. each year using assisted reproductive technologies.

ART includes fertility drug treatments, artificial insemination (AI), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other procedures.

Choosing a good fertility clinic is important. The government does not always regulate centers offering assisted reproductive techniques, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.

The clinic should always provide the following information:

The live-birth rate (not just pregnancy success rate) for other couples with similar infertility problems. (Multiple births, such as twins or triplets, are counted as one live birth.)
Such statistics should include high-risk women, such as those who are older or fail to produce eggs. (Some disreputable clinics give success percentages that exclude high-risk women from their total, thereby making the percentage of success much higher.)

Advanced fertility procedures and medications are extremely expensive and often not covered by insurance. Couples should be cautious about offers of rebates in the event of failure. The clinics offering them are often significantly more expensive than those that don't.

Artificial insemination it is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. Artificial insemination either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard artificial insemination procedure.

It is useful under the following circumstances:

When the woman's cervical mucus is unreceptive.
When donor sperm are required.
If the man's sperm count is very low (although it is preferable if at least 5 million per milliliter are motile).
When unexplained infertility exists in both partners.

Those in whom artificial insemination fails, couples with specific fertility defects, or older women may be candidates for more advanced reproductive technologies.

Pregnancy Rates. A review of 45 studies reported that in unexplained infertility cases, the per-cycle pregnancy rates were 4% for intrauterine insemination (IUI) alone and 8 - 17% per cycle for IUI combined with superovulation, a procedure that uses fertility drugs to bolster egg recovery.

Researchers in one study suggested IUI as a reasonable first option for many women under age 43. It is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. Although in vitro fertilization procedures are more effective per cycle, couples tend to be able to afford more IUI cycles, so the pregnancy rates over time are very similar.

The Artificial Insemination Procedure. The artificial insemination procedure is as follows:

A woman usually (but not always) takes fertility drugs in advance.
The man must produce sperm at the time the woman is ovulating.
The sperm are subjected to certain so-called "washing" procedures. They are then inserted into the uterine cavity through a long, thin catheter.

The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with time of ovulation. One study suggested that women who lay quietly for 10 minutes after sperm were implanted had a significantly higher rate of pregnancy than those who got up immediately.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main factor. It involves injecting a single sperm into an egg obtained from in vitro fertilization (IVF). The procedure is very simple:

A tiny glass tube (called a holding pipet) stabilizes the egg.
A second glass tube (called the injection pipet) is used to penetrate the egg's membrane and deposit a single sperm into the egg.
The egg is released into a drop of cultured medium.
If fertilized, the egg is allowed to develop for 1 - 2 days and then is either frozen or implanted.

The greatest concern with this procedure has been whether it increases the risk for birth defects. However, several studies have reported no higher risks of birth defects in children born using ICSI procedures. While other studies have shown a higher number of birth defects in children conceived with ICSI, the results may have more to do with the genetic background of the parents than ICSI itself. A 2006 study of 8-year-old children conceived with ICSI, meanwhile, found no important differences between these children and children who were conceived naturally.

A 2007 study in the New England Journal of Medicine indicated that ICSI use has increased 5-fold over the past decade, even though the proportion of men receiving treatment for male infertility has remained the same. In 1995, 11% of IVF cycles used ICSI. By 2004, 57.5% of IVF cycles used ICSI.

While ICSI is an important assisted reproductive technology for male infertility, it may be overused. Some doctors recommend ICSI for women who have failed prior IVF attempts or who have few or poor-quality eggs, even if their male partners have normal semen measurements. There is little evidence that ICSI helps improve pregnancy success for couples who do not have a problem with male factor infertility, according to the Society for Assisted Reproductive Technology.

About 71% of ART procedures now use in vitro fertilization (IVF) with the woman's own eggs. An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births.

The best candidates for IVF are women with damaged fallopian tubes, and some experts believe it is a better option than attempting surgical repair. IVF is also used when infertility is unexplained or when the male partner has the infertility problem. A typical IVF procedure is as follows:

The doctor first induces superovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. Higher doses of fertility drugs for subsequent cycles do not appear to add any advantage in women who have a poor response the first time.
To harvest eggs, the doctor generally inserts a probe into the vagina and is guided by ultrasound. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved.
The eggs and sperm are combined in a Petri dish. Between 48 - 72 hours later the eggs are fertilized.
The resulting embryos (the first stage toward the development of the fetus) are reimplanted into the woman's uterus.
It takes about 2 weeks to determine if the process is successful.

IVF success rates for the first three cycles of treatment are about equal. They then decline modestly for the fourth cycle and drop significantly after the fifth cycle.

Gamete/Zygote Intrafallopian Transfer. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are adaptations of IVF. GIFT and ZIFT are used in unexplained female infertility and in mild male infertility. The success rates are similar to those of IVF, but a woman must have at least one functioning fallopian tube.

GIFT: The procedure is as follows:

The eggs are harvested as in IVF.
They are mixed with the sperm but not actively fertilized.
They are immediately injected back into the woman. Laparoscopy, a technique that employs a miniature viewing device, is used with this procedure to guide the placement of the embryos or egg through a long, thin catheter into the fallopian tubes.
The sperm and egg are placed exactly where they would be in natural fertilization.

ZIFT: The procedure is as follows.

The eggs are harvested as in IVF.
They are then mixed with the sperm and, in this case, are fertilized in the laboratory.
They are then implanted in the fallopian tubes as in GIFT. (The advantage of this procedure over GIFT is that the doctor and couple are assured that fertilization has taken place and the eggs can be examined for defects before implantation.)

Success rates have increased in all age groups (although they are still considerably lower in older than in younger women). Chances for assisted reproductive technology success are also greater among women who do not have uterine abnormalities and have had previous successful pregnancies.

Success rates are also higher or lower depending on whether the woman uses her own eggs or whether they are donated and also whether the eggs are fresh or frozen. The highest live birth rates are with donated fresh eggs (an average of 50% per transfer) and the lowest rates are when a woman uses her own frozen eggs (an average of 29% per transfer). However, using frozen eggs is less expensive than fresh eggs, so a couple may be able to afford more cycles with frozen eggs.

Use of Donor Eggs. Older women are more likely to use donor eggs. In one study, success rates were the same for women who used donors with an age range of 20 - 40. There were also no differences in delivery rates for recipients up to age 45. Women over age 45, however, increasingly had problems with implantation, pregnancy, and delivery.

Use of Frozen Eggs. Frozen eggs tend to have lower success rates because of toxins released by cells damaged in the freezing and thawing tissues.

In Vitro Maturation. A new technique called in vitro maturation allows fertilization without the use of fertility drugs. In this process, follicles are harvested a few days before ovulation. In such cases, up to 50 have already begun to mature. About 15 of these maturing follicles can be removed, out of which 2 or 3 can produce healthy embryos.

Blastocyst Transfer. Blastocyst transfer is very promising. Instead of implanting the standard 2- or 3-day-old embryos in the uterus, the procedure implants blastocysts, which are more complex, 5-day-old embryos. Fewer blastocysts than embryos need to be implanted, reducing the risk for multiple births. (There is, however, a higher risk for identical twins compared to other procedures.) Offspring may be more likely to be males than females. Pregnancy rates are about 36% with a first attempt but then drop significantly. The procedure is more likely to be successful in younger than older women.

Ooplasmic Transfer. Ooplasmic transfer is a controversial experimental procedure that uses the woman's own egg and a female donor's egg and the male sperm for fertilization. Genetic material from the donor's egg plus the sperm are added to the woman's own egg. This has been successful in a few cases, but studies are very early and long-term effects are unknown. Research on this and similar procedures are currently conducted outside the United States.

Before fertilization using intrauterine insemination (IUI) or advanced assisted reproductive technologies (ART) can take place, the sperm must be collected and prepared for optimal chances for success.

Retrieval Procedures

When a man has no available sperm in the ejaculate (usually from blockage, vasectomy, or lack of vas deferens), the sperm must be retrieved from the testes or the epididymis. Various microsurgical techniques are now available for retrieval. The procedure may be done under local or general anesthesia, using a spring-loaded biopsy device, a thin needle, incisions, or microsurgical techniques.

Surgical Biopsy. In men without obstruction, sperm can be retrieved using a surgical testicular biopsy.

Testicular Fine Needle Aspiration. With testicular fine needle aspiration (TFNA), the surgeon uses a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have to be experienced in microsurgeries.

Microsurgical Epididymal Sperm Aspiration. Microsurgical epididymal sperm aspiration (MESA) uses microsurgical techniques to collect sperm that are close to blocked portions of the epididymis. It involves an open incision and may be done under general or spinal anesthesia in a hospital setting, although the patient can often go home the same day. The doctor accesses the epididymis and retrieves sperm with an extremely fine needle-like device. It has the advantage that it can retrieve the largest number of sperm compared to other procedures. However, as with any invasive procedure, it carries some risks of complications, such as bleeding or infection.

Percutaneous Epididymal Sperm Aspiration. Percutaneious epididymal sperm aspiration (PESA) uses a needle to obtain mature sperm from areas in the upper parts of the epididymis (the coiled tube where sperm are stored before ejaculation). It is done under local anesthesia, sometimes in the doctor's office, is less expensive than other techniques, and recovery is fairly painless. However, it has less of a chance of achieving sufficient sperm than MESA, and there is also a chance of hitting a blood vessel, causing bleeding.

Testicular Sperm Extraction. Testicular sperm extraction (TESE) is a microsurgery that removes a small amount of tissue from one or more areas of the testes using incisions and microsurgery techniques. The tissue is placed in a culture and chopped into tiny pieces. Sperm are liberated from the tiny tubes and extracted. It is a complex process, however. This is the second best method for men with vasectomies, according to some experts. It is more painful than PESA, however. In addition, if the procedure is repeated too often, it can cause permanent alterations in testicular function that may even reduce male hormone levels.

Testicular Sperm Aspiration. Testicular sperm aspiration (TESA) uses a needle-like biopsy device to draw a small sample of testicular tissue. Multiple attempts are sometimes required to retrieve sperm, and it is not as effective or as safe as TESE, although imaging techniques using ultrasound may improve results.

Sperm Washing

A sperm's energy output is 20 times greater once it is removed from the seminal fluid. Methods for washing sperm can have a dramatic effect on the ability of sperm to move towards the egg. The simplest method involves:

The sperm is mixed with a nutrient-rich fluid (or culture media) in a test tube.
They are then centrifuged (spun very rapidly) for about 5 minutes.
The sperm, which are heavy, settle on the bottom, forming a dense button of millions of pure sperm. The fluid left on top is siphoned off.
This procedure may be repeated.

This simple method of sperm washing, however, does not eliminate heavy debris, such as dead sperm, white blood cells, or bacteria, which may impair fertility. Scientists are developing new techniques, such as adding a substance called platelet-activating factor during the sperm washing process, which may enhance pregnancy rates.

Swim-Up Technique

The swim-up technique is not only a useful diagnostic procedure for testing the ability of sperm to escape from the semen into the cervical mucus, but it also achieves the goal of removing sperm from semen.

A specially prepared semen sample is placed in a tube.
A culture media (a nutrient-rich substance in which cells thrive) is placed on top of the sample.
The medium is a hospitable environment for sperm, and those that are healthy will swim up to it.
After an hour or more, the culture is examined, and the number of sperm that have reached the medium is compared to the number still remaining in the semen.

The result gives a fair estimation of the number of sperm potentially capable of fertilization. It is superior to sperm washing because the live sperm will swim up to the culture media, leaving behind most of the debris, although some may float up into the medium. There is also some evidence that such sperm may have fewer genetic abnormalities than those retrieved through sperm washing. The strongest sperm, which are those at the top of the medium, can be collected for in vitro fertilization or artificial insemination. A good swim test yields about half a million very active sperm.

Freezing Sperm

Sperm can be fresh or frozen in advance. Studies are reporting that frozen sperm provide excellent results and can be used confidently for fertilization procedures. Fresh sperm, however, are preferred by some centers for cases when low sperm count is not caused by obstruction.

Complications of Assisted Reproductive Technology

Since assisted reproductive technology (ART) procedures have become more widespread since 1980, multiple births have significantly increased. About 35% of all ART births are multiple ones, with 4.3% being triplets or more. Multiple births increase the risk of complications, for both the mother and the child.

Assisted reproductive technology (ART), and multiple births, increase the risks for pregnancy complications. According to a 2005 study, the type of complications may depend on the infertility treatment:

Fertility drugs. Increase risks of the placenta becoming detached from the uterus (placental abruption), third trimester miscarriage, and gestational diabetes.
IVF. Increase risks of placental abruption, the placenta developing in the lower section of the uterus (placenta previa), dangerously high blood pressure during pregnancy (pre-eclampsia), and Caesarean sections.

Multiple births can also increase the risk of pregnancy death. A 2006 study indicated that women who carry multiple fetuses have a 3.6 times greater risk of dying from pregnancy complications than women with singleton pregnancies. The leading causes of death were blood clot (embolism), high blood pressure complications, excessive bleeding (hemorrhage), and infections.

The main risks for children conceived with assisted reproductive technology (ART) are complications associated with pregnancy problems and multiple births. Children conceived with ART are more likely to be born premature and to have extremely low birth weight. These conditions increase the risk for heart and lung problems, as well as learning and developmental disabilities. Premature delivery is also associated with cerebral palsy, a brain injury condition that affects muscle coordination. A 2006 study indicated that children born after in vitro fertilization have an increased risk for cerebral palsy.

However, unlike earlier research, recent studies suggest that ART does not increase the risk for chromosomal damage or other major birth defects. Couples undergoing ART may have other factors, such as older age or genetic predispositions, which make complications more likely. Infertility itself, even without ART, can pose a risk factor for birth defects. Children conceived naturally by couples with fertility problems tended to have more disorders of the nervous system, digestive system, and musculoskeletal system than children born to fertile couples, according to a 2006 study in the British Medical Journal. Children born to couples treated for infertility with ART may also have a slightly increased risk for these problems, as well as genital organ malformations, but the overall risk for birth defects appears to be very small.

Preimplantation genetic diagnosis (PGD) is now available in a few fertility centers. It can help identify genetic defects in the offspring and may help parents determine future problems. Such testing, however, also raises significant emotional issues that should be addressed beforehand.

Given the hazards of multiple births, parents must make some hard decisions if the treatment produces multiple embryos. The choices are limited:

Carry all of them to term, which increases health risks for both the mother and the developing fetuses
Complete abortion
Embryo reduction, in which the doctor removes one or more embryos (possibly endangering the remaining embryos)

At this time, the best approach is to limit the number of implanted embryos in the first place. Experts are attempting to develop methods to reduce the risk for multiple births:

Most centers now implant two to three embryos at a time, and the remainder can be frozen for future use. (Frozen eggs do not appear to pose a risk for developmental problems in children conceived using them.) This limits the chance for success, but implanting more than three embryos only increases success rates very slightly, whereas the risk for multiple births increases significantly.
Reducing the dosage of fertility drugs also reduces the risk for multiple births, but not significantly and it too reduces the chance for successful outcome.
Blastocyst transfer may help reduce the chances for multiple births.

Other Treatments

Hormone therapy has been effective for women with infertility problems, but has been disappointing in men except in a few specific cases:

Gonadotropin-releasing hormone (GnRH) is often very helpful in restoring fertility in men with gonadotropin deficiency and hypogonadism.
GnRH may be useful for restoring sperm production after chemotherapy treatments.
Sperm production occasionally responds to low doses of estrogen and testosterone or testosterone alone, menotropins (Pergonal, Repronal), clomiphene citrate (Clomid), human chorionic gonadotropin (hCG), or human follicle-stimulating hormone (r-hFSH, Gonal-F).
Prolonged treatment with follicle-stimulating hormone (FSH) prior to intracytoplasmic sperm injection (ICSI) may improve implantation rates.
Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These drugs include anastrozole (Arimidex) and letrozole. (Femara). They may be helpful for specific men whose infertility is associated with abnormal testosterone-to-estrogen ratios.

Bromocriptine. Bromocriptine (Parlodel) is used in men whose infertility is related to excess prolactin manufactured by the pituitary.

Antibiotics. Infections interfering with fertility may be successfully treated with antibiotics.

Mast Cell Blocking Antihistamines. Studies report that certain antihistamines that block mast cells may be beneficial for some men with low sperm counts. Mast cells are inflammatory immune factors that may play a role in lower sperm quality. Studies have reported that two such drugs used overseas, ebastine and tranilast, improved pregnancy rates. Similar antihistamines in the U.S. are fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec).

Repair of a varicocele (varicocelectomy) in men with infertility problems is a common surgical practice. Nevertheless, although many urologists favor varicocele repair, the few well-conducted studies on this procedure suggest that it does not improve the chances for a successful pregnancy. Some experts argue that such studies were not using the most advanced techniques, which may be more effective. Some studies report that repair may improve the success rate of assisted reproductive technologies, such as intrauterine insemination (IUI). Still, the overall benefits remain uncertain, and additional rigorous trials are needed. In any case, the procedure does not appear to be beneficial for improving fertility in men whose varicoceles are very small.

Varicocele repair for fertility is sometimes considered when the following conditions are met:

When the varicocele can be felt during a physical examination.
Surgical treatment of varicoceles may be important in boys and adolescents to prevent later testicular damage.
When the male partner with varicoceles has abnormal semen quality or abnormal sperm function test results.
When the couple has known infertility, and the man has varicoceles but the woman is either fertile or can be treated for her infertility.

Varicocelectomy. Varicocelectomy, the standard repair procedure, involves tying off the swollen and twisted veins. Recovery takes 6 days, and most men cannot resume full activity for about 3 weeks. This technique eliminates 90% of varicoceles.

Recent surgical techniques use laparoscopy, which only requires tiny incisions (less than an inch). This approach allows for quicker recovery, although the procedure itself takes longer. It also has a higher rate of complications than the standard approach.

Varicocele Embolization. A nonsurgical technique called varicocele embolization may eventually prove to be an effective and less painful treatment for varicoceles, including those in young boys. It involves inserting a narrow tube (catheter) through a small incision in the neck or leg. Tiny steel plugs are passed through the catheter to block off the affected veins. The procedure takes 15 - 45 minutes to perform and uses local anesthetic. Some studies suggest that recurrence occurs in more than 10% of men, often requiring conventional surgery. This procedure is not yet widely available, and it may not be appropriate for some men.

Men with retrograde ejaculation and failure of emission caused by surgery, severe disease, or spinal cord injury are treated with various methods.

Drugs known as alpha-adrenergic agonists, including pseudoephedrine (Sudafed, Actifed), stimulate muscle contraction and help ejaculation. The tricyclic antidepressant imipramine (Tofranil) has similar effects, and in one analysis of 35 studies was more effective than pseudoephedrine. Promising investigational drugs include amezinium, which increases blood pressure.
If drugs are not effective, a technique called electrovibration (or electrical stimulation) is often beneficial. (Drugs in any case are not helpful for men with complete failure of emission.)

With any of these methods, the sperm can be collected for intrauterine insemination or assisted reproductive techniques. Spontaneous conception is possible, but not common, even with these treatments.

To prepare sperm for in vitro fertilization (IVF), men with retrograde ejaculation typically use sodium bicarbonate four times a day to reduce the acidity of the urine. After ejaculation, the man urinates or has a catheter (a tube) inserted to withdraw urine, which is then submitted for washing techniques to separate out the sperm.

Procedures that assist ejaculation are helping men with spinal cord injury conceive children. Vibratory or electronic stimulation is proving to be very beneficial for many of these men. The sperm retrieved using these methods are inserted into the women using self-insemination, intrauterine insemination, in vitro fertilizaiton, or intracytoplasmic sperm injection. Nearly a third of couples achieve pregnancy, a success rate that approaches natural conception.

Vasovasostomy. For men who wish to conceive after vasectomy, reversal surgery (vasovasostomy) may restore fertility. In vasovasostomy the severed ends of the vas deferens (which were cut during vasectomy) are reconnected to reestablish the flow of sperm. The reversal procedure is difficult. It involves sewing together the two ends of both tubes, each with pinhead sized openings. [See In-Depth Report #37: Vasectomy and vasovasostomy.]

Pregnancy Rates After Vasovasostomy. An Australian study reported that pregnancy rates in the late 1990s after reversal surgery were nearly four times higher than they were in the early 1980s. Pregnancy rates of over 50% are now being reported after a vasovasostomy. One study indicated that when successful conception occurs, it does at an average of 1 year after the surgery.

A successful reversal is more likely if the following conditions are present:

The section removed during vasectomy was not long
The original procedure was performed on straight sections of the vas deferens
The pieces joined during the vasovasostomy are of equal size

The closer in time the vasovasostomy is to the original vasectomy, the better. In one large study, the pregnancy rates were 76% for those who had vasectomy less than 3 years before reversal surgery, but decreased to 30% for those men who had a vasectomy more than 15 years earlier. The decrease in rates as time goes by is probably due to an increase in the chance for obstruction of the epididymis and the development of anti-sperm antibodies. Success rates, according to some studies, are slightly better if the male partner does not change female partners after the procedure. Other studies suggest that it makes no difference if the man has a new female partner. The age of the woman is an important factor, and the chances of achieving pregnancy are best for women younger than age 35. Some research suggests that men who have a vasectomy reversal may have a greater rate of sperm chromosomal abnormalities than normal fertile men.

Reversal Versus Assisted Reproductive Technologies. Even though newer techniques such as ICSI are improving pregnancy rates after vasectomy, vasovasostomy is still a better choice than assisted reproductive technologies (ART) for most men who want children.

Success rates with reversal surgeries are improving, and the costs are lower than with ART. In addition, a vasovasostomy does not pose a risk for multiple births. In one study, the pregnancy rate for vasovasostomy was 52%, whereas success after intracytoplasmic sperm injection (ICSI) was 25 - 30% (ICSI is the ART treatment of choice for men who have had vasectomy). Even for men who have failed vasovasostomy, a repeat procedure appears to be less expensive than embarking on fertility treatments at that time.

ART may, however, be a better approach than reversal for men with evidence of anti-sperm autoantibodies due to vasectomy. ICSI may also be more effective than reversal surgeries in men whose vasectomy was conducted at least 15 years or more beforehand.

Surgical Treatment of Obstructions. Obstructions in the area of the ejaculatory ducts have been successfully treated by excising or scraping the area where the prostate gland surrounds the urethra and by reconstructing the ducts.

Correcting Undescended Testicles. Undescended testicles of young boys may be repositioned surgically to prevent later infertility. It is important to perform the operation before 15 - 18 months of age to prevent the destruction of most of the sperm-producing cells, which occurs if the testicles remain in the abdomen.

Stem Cells. Researchers are investigating using sperm stem cells to treat male infertility. The research is still in its earliest stages. In 2004, researchers announced that they had successfully grown sperm progenitor cells in the laboratory. These types of cells could potentially develop into sperm cells capable of fertilizing an egg. This discovery was an important first step for developing stem cell infertility treatments.

Resources

www.resolve.org -- National Infertility Association
www.asrm.org -- American Society for Reproductive Medicine
www.urologyhealth.org -- American Urological Association
www.afafamilymatters.com -- American Fertility Association
www.ssmr.org -- Society for the Study of Male Reproduction
www.sart.org -- Society for Assisted Reproductive Technology
www.cdc.gov/ART/index.htm -- Centers for Disease Control: Assisted Reproductive Technology Report

References

Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in the United States. N Engl J Med. 2007 Jul 19;357(3):251-7.

Travison TG, Araujo AB, O'Donnell AB, Kupelian V, McKinlay JB. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab. 2007 Jan;92(1):196-202. Epub 2006 Oct 24.

Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006 Sep 30;333(7570):679. Epub 2006 Aug 7.

Review Date:
10/17/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Weight control and diet

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Biological and Medical Caus...
Cultural and Emotional Caus...
Risk Factors
Complications
Weight Loss and Maintenance...
Weight Management
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer and Weight Control:

Cancer prevention guidelines from the American Cancer Society stress the importance of maintaining a healthy weight throughout life. A healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Drug Warning:

The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

New Over-the-Counter Medication:

In February 2007, the FDA approved the first over-the-counter (OTC) weight-loss drug. Orlistat, previously available only by prescription as Xenical, will be available OTC at half its prescription strength. It will be sold under the name alli. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Research News:

A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets with varying amounts of fat and carbohydrates.
A study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9.

Effects of Obesity on the Body:

Obesity is associated with certain problems related to infertility, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.
People who are obese are at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands.
The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Introduction

A stable weight depends on a good balance between the energy you get from food and the energy you use. You use energy during the day in three ways:

As energy expended during rest (basal metabolism)
As energy used to break down food (thermogenesis)
As energy used during physical activity

Basal metabolism accounts for about two-thirds of spent energy. Your body generally uses this energy to keep your body temperature steady and keep the muscles of your heart and intestine working. Thermogenesis accounts for about 10% of spent energy.

When a person consumes more calories than the energy they use, the body stores the extra calories in fat cells. Fat cells function as energy reservoirs. They enlarge or shrink depending on how people use energy. If people do not balance energy input and output by eating right and exercising, fat can build up. This can lead to weight gain.

When energy input is equal to energy output, there is no expansion of fat cells (lipocytes) to accommodate excess. It is only when more calories are taken in than used that the extra fat is stored in the lipocytes and the person begins to accumulate fat.

Obesity is determined by measuring body fat, not just body weight. People might be over the weight limit for normal standards, but if they are very muscular with low body fat, they are not obese. Others might be normal or underweight, but still have excessive body fat. The following measurements and factors are used to determine whether or not a person is overweight to a degree that threatens their health:

Body mass index (BMI) (a measure of body fat)
Waist circumference (size around the waist)
Waist-hip ratio
Skin fold measurement (anthropometry)
The presence or absence of other disease risk factors (e.g., smoking, high blood pressure, unhealthy cholesterol levels, diabetes, relatives with heart disease)

A person's disease risk factors plus BMI may be the most important components in determining health risks with weight.

The Body Mass Index (BMI). The current standard measurement for obesity is the body mass index (BMI). In general, a BMI of 25 - 29.9 means you are overweight. Obesity is a BMI of 30 and above. Obesity is then classified into three categories:

Class 1: BMI of 30 - 34.9
Class II: BMI 35 - 39.9
Class III: BMI of 40 and greater

These guidelines are very important for people at risk for diabetes, heart disease, or certain cancers. It is also used to determine treatment approaches such as when surgery may be appropriate. The higher the BMI, the greater the risk for significant health problems.

Calculating Body Mass Index (BMI). One's body mass index (BMI) is calculated by multiplying a person's weight in pounds by 703, dividing by the height in inches, and then dividing that number by the height in inches. The steps are as follows:

Multiply one's weight in pounds by 703
Divide that answer by height in inches
Divide that answer again by height in inches

For example, a woman who weighs 150 pounds and is five feet eight inches (or 68 inches) tall has a BMI of 22.8.

Waist Circumference and Waist-Hip Ratio. The extent of abdominal fat can also be used in assessing risk of disease. Some studies suggest that:

Women whose waistlines are over 31.5 inches and men whose waists measure over 37 inches should watch their weight.
A waist size greater than 35 inches in women and 40 inches in men is associated with a higher risk for heart disease, diabetes, and impaired functioning.

Evidence strongly suggests that more body fat around the abdomen and hips (the apple-shape) is a more consistent predictor of heart problems and health risks than BMI.

The distribution of fat can be evaluated by dividing waist size by hip size. For example, a woman with a 30-inch waist and 40-inch hip circumference would have a ratio of 0.75; one with a 41-inch waist and 39-inch hips would have a ratio of 1.05. The lower the ratio the better. The risk of heart disease rises sharply for women with ratios above 0.8 and for men with ratios above 1.0.

Click the icon to see a depiction of the waist-to-hip ratio.

Anthropometry. Anthropometry is the measurement of skin fold thickness in different areas, particularly around the triceps, shoulder blades, and hips. This measurement is useful in determining how much weight is due to muscle or fat.

Biological and Medical Causes

Obesity results when a person consumes more calories than they need for the energy they use. Several different factors may influence weight gain.

About 90% of people who lose weight through dieting gain every pound back regardless of their weight-loss method.

Some evidence suggests that every person has an inherited weight. This range varies by only about 10% either up or down from some set point. For instance, a man whose "genetically-determined" weight is 200 pounds would tend to swing from 180 - 220 pounds. He would be unlikely to lose or gain more than this.

Genetic factors may play some part in 70 - 80% of obesity cases.

Appetite is determined by processes that occur both in the brain and gastrointestinal tract. Eating patterns are controlled by areas in the hypothalamus and pituitary glands (in the brain). The body produces a number of molecules that increases or decreases appetite. In some cases, the following factors may produce imbalances in this process:

Insulin. Insulin is a hormone that helps change blood sugar (glucose) into energy. During digestion, carbohydrates from our diet break down into different types of sugar molecules (including glucose). Proteins from our diet break down into smaller molecules called amino acids. Immediately after eating, blood glucose levels rise. This triggers the release of insulin, which pours into the bloodstream. Insulin pushes the glucose and amino acids into cells and muscles. Insulin and other hormones determine which nutrients will be burned for energy or stored for future use. The inability to use insulin efficiently (insulin resistance) has been associated with both obesity and diabetes.
Leptin. Leptin is a hormone that is released by fat cells. A number of scientists think this hormone may also be released by cells in the stomach. Leptin appears to play an important role in insulin resistance and fat storage in the body, but its role in obesity is unclear. The most likely scenario is that leptin levels rise as the cells store more fat. This increase in leptin levels decreases appetite. Falling levels of leptin make you feel hungry. In people who have genetically lower levels of leptin, however, the brain may be tricked into thinking that it is always starving because there is no leptin to decrease appetite. This can lead to weight gain.
Resistin. Resistin is a hormone produced by fat cells. It makes the body resistant to insulin activity. Some experts believe it may help explain the role of obesity in diabetes type 2.
Intestinal Chemicals. Ghrelin is a chemical produced in the stomach. It appears to be important in triggering the desire to eat. Peptide YY3–36 (PYY) is a substance secreted in the intestines after a meal. The level of PYY is proportionate to the number of calories a person eats. PYY tells the brain that you feel full. Deficiencies in ghrelin and PYY may contribute to some cases of obesity. Researchers are hoping that blocking ghrelin or infusing PYY may be possible treatments for obesity.
Other Chemicals. Many brain chemicals are being studied for their role in appetite stimulation and weight gain. Among them are neuropeptide Y, melanocortins, agouti-related protein, and melanocyte stimulating hormone. Pain-relieving chemicals called endorphins may be critical in reducing appetite and regulating energy use. Cholecystokinin, a hormone released in the upper intestine that stimulates digestive juices, may work to control meal size.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Genetics may directly contribute to severe obesity in people with family histories of the problem. Genetic factors such as slow metabolisms may also make people more likely to be overweight. At least seven genetic mutations have been associated with specific and uncommon cases of severe obesity. Some are outlined below.

HOB1 (human obesity 1) is a gene that is linked to a high BMI in women.
Leptin gene variants have been linked to leptin deficiencies and obesity.
Melanocortin-4 receptor is a gene that helps turn off the urge to eat. It may not work properly in those with a family history of obesity.
Researchers have also identified a mutation in a gene for a protein called proopiomelanocortin, which results in a syndrome of obesity, red hair, and deficiencies in stress hormones.
A protein called agouti-related protein increases hunger. About 5% of severely obese people have mutations that over-respond to agouti-related protein.

Genetics also determine the number of fat cells a person has. Some people are simply born with more. It should be noted that even when genetic factors are present, a person can still control their diet.

The Thrifty Gene. Some experts think the existence of a so-called "thrifty" gene regulates changes in hormone levels, to accommodate seasonal changes. Theoretically, it works in the following manner:

In certain populations, hormones are released during seasons when food supplies have traditionally been low. This leads to insulin resistance and increased fat storage.
The process is reversed in seasons when food is readily available.
Because modern industrialization has made high carbohydrate and fatty foods available all year long, the gene no longer serves a useful function. Fat, originally stored for famine situations, is not used.

This theory could explain why the previously nomadic Native American tribes who now have Western dietary habits have such high rates of Type 2 diabetes and obesity. In the past, the traditional low-fat, high-fiber foods tribe members ate may have protected them from obesity and type 2 diabetes. Today, these tribes' diet consists of more Western foods, which are higher in fat. Furthermore, these foods are readily available year-round, and many members of the tribe are sedentary. The result is a very high incidence of Type 2 diabetes and obesity. Although genetic abnormalities may make it harder or easier to lose weight, the occurrence of obesity has dramatically increased over the past two decades, and genes cannot have changed within that short amount of time. Our ability to use the food that we eat evolved so that our body could conserve energy and store fat during times of famine. Most cases of obesity now occur in people with normal body function who live in industrialized nations, where there is more than enough food.

A number of medical conditions may contribute to being overweight, but rarely are they a primary cause of obesity.

Hypothyroidism is sometimes associated with weight gain. But, patients with an underactive thyroid generally show only a moderate weight increase of five to 10 pounds.
Very rare genetic disorders, including Froehlich's syndrome in boys, Laurence-Moon-Biedl, and the Prader-Willi syndromes, cause obesity.
Abnormalities or injury to the hypothalamus gland can cause hypothalamic obesity.
Cushing's disease is a rare condition caused by high levels of steroid hormones. It results in obesity, a moon-shaped face, and muscle wasting.
Obesity is also linked to polycystic ovarian syndrome, a hormonal disorder in women.

Click the icon to see an image of polycystic ovaries.

Some prescription medications contribute to weight gain, usually by increasing appetite. Such drugs include the following:

Corticosteroids
Female hormone treatments, including some oral birth control pills (effect is usually temporary), and certain progestins (such as Megestrol) used to treat cancer
Antidepressants and anti-psychotic drugs, including lithium and valproate
Insulin and insulin-stimulating drugs used to treat diabetes often lead to weight gain, a particularly unfortunate conflict of interest for obese individuals with type 2 diabetes

You should not stop taking any medications without your doctor's knowledge.

Cultural and Emotional Causes

Enough food is produced in the US to supply 3,800 calories every day to each man, woman, and child in the country, far more than the average person needs to sustain life. In a 2002 study, participants carefully recorded everything they ate and drank, and all activities and psychological factors surrounding the eating events. The people who gained weight ate more and their portions were larger than those who did not. This may be an obvious conclusion, but the public press often plays up biologic factors involved with obesity and overlooks the simple notion that Americans eat too much and exercise too little.

Obesity is dramatically increasing not only in American children and adults, but also in every country that has adopted similar cultural habits. The World Health Organization now considers obesity to be a global epidemic and a public health problem as more nations become "Westernized." In spite of the proven health risks of obesity, the government, insurance companies, and the medical profession do not spend nearly enough money to balance the commercial and cultural pressures that are producing millions of overweight people.

In 2007, the Robert Wood Johnson Foundation sounded a positive note with the announcement of a $500 million initiative, aimed at “reversing the childhood obesity epidemic by 2015.” The money will be used for research, education, and activities that promote healthy eating among America’s children.

Perhaps the primary reason for the dramatic rise in obesity is the sedentary (inactive) lives led by most Americans, including children and young people. In a 2003 study comparing modern life to the past, researchers found that labor saving devices had reduced a person's energy use by 111 calories a day -- adding up to an extra 11 pounds a year. Half the difference in energy use was due to less walking. At the same time, according to the U.S. Centers for Disease Control and Prevention, between 1970 and 2000 the typical American man increased his caloric intake by 168 calories a day (good for 17 pounds a year) while the average woman added 335 calories a day.

Regular television watching has been singled as the most hazardous pastime. According to a major 2003 study, for every 2 hours a person spends in front of the TV each day, the risk for obesity increases by 23% and for type 2 diabetes by 14%. In the study, TV watching produced the lowest metabolic rates compared to sewing, playing board games, reading, writing, and driving a car. Just the act of watching TV encourages unhealthy snacks and eating patterns. In addition, the advertising on the television complicates the problem by promoting fast foods, cereal, and snack products that are high in salt, fats, and carbohydrates. Even worse, much of these advertisements are directed at children -- the most vulnerable group.

People are not only eating more food than they did 20 years ago, they are also replacing home cooking with packaged foods, fast food, and dining out. This behavior, according to studies, places people at higher risk for obesity. Fast foods may be more harmful than restaurant cooking. These foods tend to be served in larger portions. They generally contain more calories and unhealthy fats, and less nutritious ingredients, than homemade or restaurant meals. Snack foods and sweet beverages, including juice and soft drinks, are specific problems that add to the increasing rates of obesity. Frequent small, healthy meals (instead of two or three large daily meals) have been associated with lower weights.

People react differently to stress. Some overeat and gain weight and others stop eating and lose weight. People who gain weight in response to stress often overeat foods high in sugar, fats, and salt. A 2003 study on rats suggested that stress hormones increase the pleasure of eating such so-called "comfort foods." Furthermore, the study supported previous research showing that stress-related eating was connected to the unhealthy accumulation of abdominal fat.

Risk Factors

Where you live plays a role in your risk for obesity. Simply living in the United States makes a person more susceptible to obesity. The prevalence of obesity in America has risen dramatically over the past few years and continues to increase.

According to the latest figures available, 32.2% of American adults (aged 20 and older) are obese (BMI over 30) -- up from about 23% in the early 1990s.
The number of Americans aged 20 - 74 who were overweight also increased -- from about 44.8% in 1960 to 65.2% in 2002.
The rate of extreme obesity (BMI > 40) increased from 0.8% in 1960 to 4.9% in 2002.
Obesity has increased in every state, in both men and women, across all age groups, and in every ethnic group, although some groups may face slightly higher risks than others.

Fat tends to settle in certain regions, depending on gender. Women gain fat predominantly in the stomach, hips and thighs, while men tend to gain fat in the belly and waist.

Risk by Age. People of any age are at risk for obesity. More children and adolescents are overweight in America than ever before. Gaining some weight is inevitable with age and adding about 10 pounds to a normal base weight over time is not harmful. The current weight gain in American adults over 50, however, is significant. By age 55, the average American has added nearly 40 pounds of fat during the course of adulthood. This condition is made worse by the fact that muscle and bone mass decrease with age.

Risk by Gender. In men, BMI tends to increase until age 50 and then it levels off. In women, weight tends to increase until age 70 before it plateaus. A 2000 study found that there are three high-risk periods for weight gain in women.

The first is at the onset of menstruation, particularly if it is early. In fact, a study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9. This, in turn, increases the risk for more weight gain as girls enter puberty.
The second is after pregnancy, with higher risk for women who are already overweight.
Finally, many women gain weight after menopause.

These findings are significant because they may allow women to target high-risk times, and consequently prevent unnecessary weight gain.

Risk by Economic Group. Obesity is more prevalent in lower economic groups. One 2002 study reported that women who reported that they did not have enough food were more likely to be overweight than those who said they had sufficient food. Researchers discovered that the low-income women tended to have fewer fruits and vegetables but were actually taking in more calories a day than higher-income women. However, obesity is increasing in young adults with college education as well as in other groups.

Ethnic Groups. Among ethnic groups in general, African-American women are more overweight than Caucasian women but African-American men are less obese than Caucasian men. (Currently, 80% of African-American women are overweight.) Hispanic men and women tend to weigh more than Caucasians.

US Regions. Regionally, the prevalence of obesity is lowest in the Western states and highest in the South.

A number of dietary habits put people at risk for becoming overweight:

Night-Eating Syndrome. Night-eating syndrome is defined as having no appetite in the morning, insomnia, and consuming more than half of daily food intake after 6:00 PM. It is associated with obesity and is difficult to treat. Stress reduction and relaxation techniques may be helpful.
Binge Eating and Eating Disorders. About 30% of people who are obese are binge eaters who typically consume 5,000 - 15,000 calories in one sitting. To be diagnosed as a binge eater, a person has to binge at least twice a week for 6 months. Many experts believe that binge-eating carbohydrates causes an increase in a natural opiate leading to dependence on carbohydrates. Therefore, this condition should be treated as an addiction. Other eating disorders are bulimia and anorexia. Bulimia is binge eating followed by purging in order to lose weight. Anorexia nervosa is a mental illness in which the person refuses to maintain weight at the normal level. The patient with anorexia has a terrible fear of getting fat, and an abnormal perception of what his or her body looks like. Both conditions pose risks for serious medical problems, and anorexia nervosa can be life-threatening. A combined approach using behavioral therapy and antidepressants may help these individuals. [See In-Depth Report #49: Eating disorders.]
Restrained Eating. Some people, mostly middle-aged women who have normal weight, have a pattern referred to as restrained eating. This pattern requires a high level of conscious control and usually maintains a lower weight. However, such restraint places these individuals at higher risk for loss of control and subsequent overeating.
Infrequent Eating. There is some evidence to suggest that eating small frequent meals uses more calories than infrequent large meals. It should be strongly noted, however, that packaged snack foods add calories and some do not produce a feeling of being full, so that people simply eat more than they should.

Anyone with Sedentary Lifestyles. Office workers, drivers, and anyone whose lifestyle involves sitting for long periods are at higher risk for obesity.

Ex-Smokers. The trend toward weight increase has followed the trend for quitting smoking. Nicotine increases the metabolic rate, and quitting, even without eating more, can cause weight gain, which may be considerable. It is important to note that weight control is not a valid reason to smoke. People in previous centuries did not smoke cigarettes, nor were they usually obese.

Shift-Workers. A recent study found that individuals who work late shifts (between 4 p.m. and 8 a.m.) tend to eat more and take longer naps than day workers and are more likely to gain excess weight.

People with Disabilities. Obesity rates are higher than average in people with physical or mental disabilities. Those with disabilities in the lower part of the body, such as the legs, are at highest risk.

Overweight in children and adolescents is rising at an alarming rate. In 2004, 19% of young children aged 6 - 11 were overweight, an increase of 8% from 1994. Among children aged 25, 13.9% were overweight in 2004, up from 7.2% 10 years earlier.

Definition of Overweight in Children

Children and adolescents are considered to be overweight if their BMI is above 95% of the children in their age and sex categories. Ethnic variations, timing of growth spurts, and higher normal fat levels around puberty can affect these measurements.

Causes and Risk Factors for Overweight in Children

Lifestyle Factors. Without educational or parental guidance, children are extremely vulnerable to the intense cultural pressures that are largely responsible for the obesity epidemic. The following are some specific problems created by the culture:

Excessive television watching plays a critical role in obesity in children. Not only is it a sedentary activity, but television also offers innumerable temptations with its advertisements for fast foods, sugar cereals, and unhealthy snacks. In one study obesity rates were lowest in children who watched television 1 hour or less a day and highest in those who watched 4 or more hours.
Sugar, particularly from soda, other sweetened beverages, and fruit juice, may be the major contributor to childhood obesity. One study reported that drinking soda regularly increases a child's risk for obesity by 60%. The average American adolescent consumes 15 - 20 extra teaspoons of sugar a day just from soda and sugary drinks. (Juice, while better than soda, is still filled with sugar.)
Less physical exercise and greater sedentary activities play another significant role in obesity in children. A high level of physical activity -- not just using up energy -- is important for weight control in young people. Unfortunately, according to one study, the annual distance walked by children has fallen by nearly 30% since 1972, partially because more parents are driving their children to school out of fear of abduction, molestation, and traffic accidents. Schools are also offering fewer opportunities for daily physical activities than in the past.

Neither the media nor the educational system has strong well-financed programs that encourage healthy alternatives, including exercise and healthy foods.

Family History. Parental obesity more than doubles the risk that a young child, whether thin or overweight, will become obese as an adult. In older children and teenagers, obesity in parents starts to count less as a predictor for body weight than their own weight. The risk for obesity may be due to environmental or genetic factors, or both.

Ethnic and Socioeconomic Factors. As in adult populations, children from lower socioeconomic groups and minority populations are at higher risk for obesity. For example, among young Mexican Americans and African-Americans, there has been an increase in overweight prevalence of about 13% to over 23%.

Factors Surrounding Birth. The following factors surrounding birth are associated with a child's weight:

Low birth weight is a risk factor for later obesity and diabetes. One theory is that humans have a "thrifty gene" that produces metabolic changes in infants with low birth weight. Such changes affect insulin and fat accumulation, in order to produce a "catch-up" weight in these young children as quickly as possible. This rapid weight gain in infancy increases the risk for obesity in children and young adults.
In a study of African-American children, having an overweight pregnant mother increased the risk for later weight gain, but low birth weight did not.

Although some small studies have reported protection against obesity from breastfeeding, evidence is weak. In a 2003 study, for example, children who were breast fed for 3 - 5 months had a lower risk for obesity, but prolonged breastfeeding had no effect. Nevertheless, given the healthful effects of breast feeding and the possibility that it may have even a slight impact on childhood obesity, it is highly recommended.

Biological Effect of Childhood Overweight on Adult Weight

Achieving a healthy weight becomes more difficult as children get older. The odds of obesity persisting into adulthood ranges from 20% in 4 year olds to 80% in teenagers. One reason for the persistence is biological. The fat cells change in number or mass depending on a person's age:

Fat cells themselves multiply during two growth periods: early childhood and adolescence. Overeating during those times increases the number of fat cells. Some people are also just born with more fat cells.
After adolescence, fat cells tend to increase in mass rather than quantity, so that adults who overeat and gain weight tend to have larger fat cells, not more of them. This growth in mass may be responsible for the greater risk of persistent obesity among teenagers compared to small children who are overweight. Losing weight after adolescence reduces the size of the fat cells but not their number, so weight loss becomes much more difficult.

Health Consequences of Childhood Overweight

Children and adolescents who are overweight have poorer health than other children. Studies are reporting unhealthy cholesterol levels and high blood pressure in overweight children and adolescents. Of great concern is the dramatic increase in type 2 diabetes in young people, which is largely due to the increase in overweight children. Overweight in children is also linked to asthma, gallbladder problems, sleep apnea, and liver abnormalities. Overweight girls are more likely to enter puberty early, according to a new study, and subsequently be at higher risk for breast cancer.

It is not clear yet how many of these childhood problems persist in people who achieve normal weight as adults. Staying overweight into adulthood certainly carries health risks.

Managing Overweight Children

Childhood obesity is best treated by a non-drug, multidisciplinary approach including diet, behavior modification, and exercise. Evidence suggests that reducing calories by only 200 - 260 per day would prevent weight gain in most overweight children. Here some tips for children who are overweight:

Limit (or avoid, if possible) take out, fast foods, high-sugar snacks, commercial packaged snacks, soda, and sugar-sweetened beverages (including too much juice).
Let children snack but make sure the snacks are healthy. Eating small frequent healthy meals (instead of two or three large ones) has been associated with being thinner and having a better cholesterol profile.
Let children choose their own food portions. One study indicated that children naturally ate 25% less when they chose their own portion size. When they were given larger portions their bite sizes were larger and they ate more.
Do not criticize a child for being overweight. It does not help and such attitudes could put children at risk for eating disorders, which are equal or even greater dangers to their health.
Limit television, video games, and computer use to a few hours a week. This can contribute significantly to weight control, regardless of diet and physical activity.
For young children, try the traffic-light diet. Food is designated with stoplight colors depending on their high caloric content: Green for go (low calories); yellow for "eat with caution" (medium calories); red for "stop" (high calories).
Try a low glycemic index diet. This may be as beneficial, and possibly more, than a standard reduced-fat diet in overweight children. Such a diet focuses on certain carbohydrates (for example, dried beans and soy), which raise blood sugar more slowly than other types of carbohydrates. This diet is sometimes used in diabetes, and as a dietary approach in overweight adults. [See In-Depth Report #42: Diabetes diet.]

Click the icon to see an image about TV watching.

Click the icon to see an image of childhood overweight.

Complications

General Adverse Effects of Obesity. Obesity, defined as a BMI of 30 or over, accounts for nearly 300,000 deaths in the U.S. each year. It is associated with more chronic health problems than smoking, heavy drinking, or poverty. Furthermore, given the current increase in obesity, it will surpass smoking as the most important preventable cause of death in America.

Some studies indicate the following health risks by body mass:

The lowest risks for heart disease, diabetes, and some cancers are in people with BMI values of 21 - 25.
The risks increase slightly when BMI values are between 25 - 27.
The risks are significant in BMIs between 27 - 30.
The same risks are dramatic at BMIs over 30.

Anyone with chronic health problems such as heart or lung disease, stroke, or arthritis, should be concerned about extra weight. This same concern also applies to people with known risk factors for such conditions.

Metabolic Changes. As fat stores increase, the fat cells themselves enlarge and produce chemicals that increase the risk for several diseases. Such diseases may include diabetes, high blood pressure, gallbladder disease, and some cancers.
Increased Mass. The increased body weight itself causes problems that result in injury and diseases, including osteoarthritis and sleep apnea.
Harmful Fat Cell Types. Weight concentrated around the abdomen and in the upper part of the body (the apple shape) poses a higher health risk than fat that settles around the hips and flank (the pear shape). Fat cells in the upper part of the body appear to have different qualities from those found in the lower parts. In fact, studies suggest a higher risk for diabetes in people with the "apple shape" and lower risk in those who are "pear shaped."

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

General Adverse Effects of Being Overweight (Not Obese). It is still not clear if being overweight (a BMI of 25 - 29.9) hurts healthy people with no risk factors for serious illnesses.

According to one 2001 study, just being overweight increased the risk for developing diabetes, gallstones, hypertension, heart disease, stroke, and colon cancer. The risk rose according to how much the individuals were overweight. In any case, adults who are overweight in middle age face a poor quality of life as they age, with the quality declining the greater the weight. One study suggested, however, that being over 65 and overweight (but not obese) is not associated with higher mortality rates.

Some experts argue, in fact, that in anyone who is not severely obese, it is the unhealthy diet and sedentary lifestyle that causes harm -- not weight per se. In support of this argument, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Being somewhat overweight may also have some benefits under specific circumstances:

In older women, some excess fat may produce extra estrogen that helps slow down bone loss, and insulates bones from fall-related injuries. It should be strongly noted, however, that when older overweight women lose weight they report less pain, improved vitality, and improved physical function. The same positive effect of overweight does not appear to hold in older men.
Conditioned athletes may have high BMIs because of very dense muscle tissue. Being fit in general may protect many overweight people.
Some evidence suggests that Caucasians have the lowest mortality with BMIs of 24.3 - 24.7 while African-Americans are better off in the range of 26.8 - 27.1.
Children may have higher normal fat levels during growth spurts and around puberty.

Individuals with a BMI of at least 30 have a 10 - 50% increased rate of death from all causes, compared with individuals with a BMI of 20 - 25. Mortality rates from many causes are higher in obese people, but heart disease is the primary cause of death. People who are obese have almost three times the risk for heart disease as people with normal weights. Being physically unfit adds to the risk.

Weight concentrated around the abdomen and in the upper part of the body (apple shape) is particularly associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Fat that settles in a pear shape around the hips and lower body appears to have a lower association with these conditions.

Obesity poses many dangers to the heart and circulatory system.

Damage in the Blood Vessels. As people age, changes in body fat (particularly increasing abdominal fat) seem to cause stiffness in the aorta, the major blood vessel leading from the heart. Studies are finding higher levels of a factor called C-reactive protein (CRP) in people with obesity and abdominal fat. CRP is now considered to be a marker for inflammation and damage in the arteries. (Losing weight reduces CRP levels.)

High Blood Pressure. High blood pressure is the health problem most commonly associated with obesity, and the greater the weight, the greater the risk. High blood pressure carries serious risks of stroke, heart attack, and heart failure. The link between obesity and high blood pressure is complex, and may be a combination of genetic, population, and biological factors. Many studies have reported that modest weight loss is beneficial for reducing existing high blood pressure. [See In-Depth Report #14: High blood pressure.]

Heart Failure. An important 2002 study reported that obesity might account for 11% of heart failure cases in men and 14% in women. This link existed independently of other risk factors, such as high blood pressure, sleep apnea, and diabetes, which are also associated with obesity. The biologic mechanisms involved in obesity that lead specifically to heart failure are not clear. [See In-Depth Report #13: Heart failure.]

Unhealthy Cholesterol Levels and Lipid Levels. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels (the major form of fat storage in the body) are usually high, while HDL levels (the "good" cholesterol) tend to be low. Both conditions are risk factors for heart disease. [See In-Depth Report #23: Cholesterol.]

Click the icon to see an image of coronary artery disease.

Stroke. Obesity is also associated with a higher risk for stroke. [See In-Depth Report #45: Stroke.]

Type 2 Diabetes and Insulin Resistance. Most people with type 2 diabetes are obese and, in fact, studies strongly suggest that weight loss may be the key in controlling the current epidemic of type 2 diabetes. The common factor appears to be insulin resistance. Insulin is a critical hormone in the use of sugar. In type 2 diabetes, different factors cause the body to become insulin resistant -- that is, the body can no longer respond properly to insulin. This has the effect of increasing sugar levels in the blood, the hallmark of diabetes. Both obesity and insulin resistance, at different phases, are marked by high levels of certain chemicals. It is not known yet if the higher levels are simply a product of obesity, or play some role in causing diabetes.

Insulin resistance is also associated with high blood pressure and abnormalities in blood clotting. Some research indicates that obesity, in fact, is the one common element linking insulin resistance, diabetes type 2, and high blood pressure. [See In-Depth Report #60: Diabetes - type 2.]

Metabolic Syndrome. Metabolic syndrome (also called syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome. A combination of weight loss and exercise is an effective treatment for this syndrome.

The American Cancer Society released new cancer prevention guidelines in September 2006. The guidelines stress the importance of keeping a healthy weight throughout life. The Society indicates that healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Obesity has been associated with a higher risk for cancer in general and specific cancers in particular. Studies have also suggested that restricting calories reduces the risk for cancer. Some experts believe that effective weight control for children and adults could reduce cancer rates by 30 - 40%. One way obesity may increase the risk for cancer is its association with high levels of hormones called growth factors, which can trigger rapid cell production leading to cancer.

Uterine Cancers. The risk of uterine cancer in obese women appears to be two or three times higher than in thinner women.

Prostate Cancer. New studies from 2005 and 2006 report that obesity is associated with an increase in prostate cancer mortality, although not with the risk for less aggressive forms of prostate cancer.

Click the icon to see an image of prostate cancer.

Breast Cancer. Studies are mixed on the association between obesity and breast cancer. A number of studies have linked obesity to breast cancer in postmenopausal women, particularly in women who begin to gain weight after age 18.

Click the icon to see an illustrated series detailing a breast cancer surgery (mastectomy).

Gallbladder Cancer. Obese women are at higher risk for gallbladder cancer.

Gastrointestinal Cancers. A number of cancers in the gastrointestinal tract have been associated with obesity:

Cancer of the esophagus may be due to a higher incidence of gastroesophageal reflux disorder (heartburn) in people who are overweight.
Colon cancer has been linked to increased body mass in both men and women.
Pancreatic cancer and obesity have been weakly linked, with one study reporting a lower risk in overweight people who are physically active.

Click the icon to see an illustrated series detailing a colon cancer surgery.

Muscles and Bones

Obesity places stress on bones and muscles. Studies report that the incidence of osteoarthritis is significantly increased in people who are overweight. People who are obese are also at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands. It should be noted that some weight may be protective against osteoporosis (loss of bone thickness).

Obesity increases the risk for the following mouth and eye disorders:

Gum disease
Cataracts
Maculopathy, an eye disease related to aging

Infertility. Abnormal amounts of body fat, either 10 - 15% too high or too low, can contribute to infertility in women. Obesity is specially related to certain infertility problems, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.

Effect on Pregnancy. Obesity has many dangerous effects on pregnancy. These include high blood pressure, gestational diabetes (diabetes, usually temporary, that occurs during pregnancy), urinary tract infections, blood clots, prolonged labor, and higher fetal death rate in late stages of pregnancy. Obesity is also associated with increased rates of cesarean delivery. Infants of women who are obese are also at higher risk for neural tube birth defects, which affect the brain or spine. Folic acid supplements, ordinarily effective in preventing these conditions, may not be as protective in overweight women.

Obesity is thought to be a risk factor for symptoms of adult-onset asthma. Though there is evidence that obesity causes wheezing and shortness of breath, it does not appear to be strongly associated with the disease mechanisms in the lungs that cause true asthma.

Obesity also puts people at risk for hypoxia, a condition in which there is not enough oxygen to meet the body's needs. Obese people need to work harder to breathe. They tend to have breathing muscles and lungs that do not work as well as those in thinner people.

The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Nonalcoholic Fatty Liver Disease. People with obesity, particularly if they also have type 2 diabetes, are at higher risk for a condition called nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH). This condition causes liver damage that is similar to liver injury seen in alcoholism. In some cases, it can be very serious and require liver transplantation. It occurs in about half of people with diabetes, and 20 - 50% of obese people, depending on how severe their obesity is. NASH can also occur in overweight children.

Gallstones. The incidence of gallstones is significantly higher in obese women and men. The risk for stone formation is also high if a person loses weight too quickly. In people on ultra-low calorie diets, gallstones may be prevented by taking ursodeoxycholic acid (Actigall).

Click the icon to see an image of gallstones.

People who are obese and nap tend to fall asleep faster and sleep longer during the day. At night, however, it takes them longer to fall asleep, and they sleep less than people with normal weights. In an apparent vicious circle, studies have suggested that obesity not only interferes with sleep but that sleep problems may actually contribute to obesity.

Sleep Apnea. Obesity, particularly the apple shape, is strongly associated with sleep apnea, which occurs when the upper throat relaxes and collapses from time to time during sleep. This collapse temporarily blocks the passage of air. Sleep apnea is increasingly being viewed as a potentially serious health problem, which may lead to complications such as heart disease and stroke. Some studies suggest that among overweight people, those who have sleep apnea have a greater risk of heart disease than those without it. In one study, the more obese a person with sleep apnea was, the higher the pressure on the airway, and therefore the greater the obstruction of the airway. Obstructive sleep apnea may also add to obesity, however, as sleepy people tend to be sedentary. Some studies indicate that treating sleep apnea may help people lose abdominal fat.

Narcolepsy. A small European study found a link between narcolepsy (a sleep disorder characterized by excessive daytime sleepiness with frequent daily sleep attacks) and high BMI.

Depression. A number of studies have reported an association between depression and obesity, particularly in obese women. There may be a number of factors to explain the link. In some cases of atypical depression, people overeat and may gain weight. Overweight people may also become depressed because of social problems and a poor self-image. In these cases, depression usually disappears when people lose weight.

There is evidence, however, that obesity itself may impair levels of tryptophan -- a chemical needed to make serotonin, a brain chemical associated with mental well-being. In one study, even after people lost weight, tryptophan levels were lower than normal.

There does not appear to be any association between depression and obesity in men.

Social Problems. One long-term study reported that overweight young women completed fewer years of school, were 20% less likely to be married, and had 10% higher rates of household poverty than their thinner peer. Obese young men were also less likely to be married, and their incomes were lower than their thinner peers. Nevertheless, studies consistently show that overweight males (both boys and men) are not as severely emotionally affected as females of any age. Women and girls tend to blame themselves for being heavy, while males tend to blame being overweight on outside factors.

Weight Loss and Maintenance

Even modest weight loss can reduce the risk factors for heart disease and diabetes. The simplest (but still difficult) approach to weight loss is reducing calories and exercising at least 150 minutes a week. Behavioral and mental changes in eating habits, physical activity, and attitudes about food and weight are also essential to weight management. For people who are very overweight and cannot lose weight through lifestyle changes, a number of effective weight-loss medications are available. For those with severe obesity, surgical procedures are proving to be very beneficial.

Some Tips for Losing Weight. The following are some general suggestions for dieters:

Start with realistic goals. Diet failure is extremely common, and the odds of significant weight loss are low, particularly in people with the highest weights. People who are able to restrict calories, engage in an exercise program, and get help in making behavioral changes can expect to lose between 5 - 10% of their current body weight. That is generally all that is needed to achieve meaningful health changes. Certainly, the distorted image of a super-thin female shape should not be anyone's goal.
Maintain a regular exercise program, assuming you have no health problems that will stop you. Choose a program that you enjoy. Check with your doctor about any health considerations. [See In-Depth Report #29: Exercise.]
Do not use hunger pangs as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat and start by recording all calories in writing. Studies suggest that when many people report their own calories intake they significantly underestimate their consumption of high-calorie and over-estimate the low-calorie foods. People who do not carefully note everything they eat tend to take in too many calories when they believe they are dieting.
Observe weekend eating. People tend to eat more on the weekends. If it is difficult to monitor all meals during the week, it be may be useful to at least track eating habits during the weekends.
Once the pounds are lost, do your best to keep the healthier weight. Make daily, even hourly, conscious decisions about eating and exercising activities. Such thinking, in many cases, can become automatic and not painful.
Don't give up, even after repeated weight loss failures. Most studies indicate that yo-yo dieting or weight cycling have no bad psychological or physical effects. Repeated dieting also does not harm the body's ability to burn calories efficiently.
Weight loss, in any case, should not be the only or even the primary goal for people concerned about their health. The success of weight loss efforts should be evaluated according to improvements in disease risk factors or symptoms, and by the adoption of healthy lifestyle habits, not just by the number of pounds lost.


Lifestyle	Reduce rate of eating. Keep food records. Eliminate environmental triggers to eating. Identify high-risk situations for overeating. Separate eating from other activities.
Exercise	Face up to emotional barriers to exercise. Understand the link between exercise and weight control. Establish reasonable exercise goals. Develop a plan for regular activity. Add increased activity into daily lifestyle.
Attitudes	Develop reasonable weight-loss goals. Avoid "all or none" thinking. Focus attention away from the scale and toward behavior. Uncouple weight from self-esteem. If you "fall off the wagon," take steps to ensure the situation does not repeat (recover from lapses with constructive action).
Relationships	Understand the key role of social support to health. Identify supportive others. Match personal style to support-seeking activities. Be specific in making support requests. Be assertive but reinforcing in drawing help from others.
Nutrition	Resist the temptation of popular fad diets. Eat with your health in mind; do not concentrate on what should be "off-limits." Eat with moderation in mind. Maximize fiber. Develop a tailored plan.
From Brownell KD. The LEARN Program for Weight Control. 7th ed. Dallas, Tex: American Health Publishing Company; 1998.

Weight Management

There are many approaches to dieting and many claims for great success with various fad diets. To date, although many diets achieve effective immediate weight loss, none has emerged as an effective tool for maintaining healthy weight. The only definite recommendation that can be made about any diet plan is to be sure it includes an exercise program, assuming there are no health problems to forbid it.

The original food pyramid, with four food groups, has been replaced with an updated food guide called "My Pyramid." This illustrates the relative proportions of different foods that make up a nutritious, well-balanced diet and includes exercise.

Calorie restriction has been the cornerstone of obesity treatment. The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories. A person could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine your daily calories requirements, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Extreme diets of less than 1,100 calories carry health risks. They are also often followed by bingeing or overeating, and a return to the obese state. Such diets often do not have enough vitamins and minerals, which must then be taken as supplements. Most of the initial weight loss is in fluids. Later, fat is lost, but so is muscle, which can account for more than 30% of the weight loss. No one should be on severe diets for longer than 16 weeks, or fast for more than 2 or 3 days. Severe dieting has unpleasant side effects including fatigue, intolerance to cold, hair loss, gallstone formation, and menstrual irregularities. There have been rare reports of death from heart arrhythmias when liquid formulas did not have sufficient nutrients. Pregnant women who excessively diet during the first trimester put their unborn children at risk for birth defects. Of note, those whose diets include a high intake of fluids and much reduced protein and sodium are at risk for hyponatremia, which can cause fatigue, confusion, dizziness, and in extreme cases, coma and death.

This dietary approach requires counting only grams of fat with the goal of achieving 30% or fewer calories from fat. One gram of fat contains nine calories, while one gram of carbohydrates or protein has only four calories. Fat in your diet converts more readily to fat in the body, compared with carbohydrates or proteins. Simply switching to low-fat or skimmed dairy products may be enough for some people.

There are possible drawbacks to this approach:

Some people who reduce their fat intake may not get enough basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low-fat diets should eat a wide variety of foods and take a multivitamin supplement, if appropriate. Calcium deficiencies may be particularly harmful in women at risk for osteoporosis.
Many people start eating foods with too many carbohydrates, believing that they are not adding calories. No one should use a low-fat diet as an excuse for eating too many carbohydrates, particularly starchy foods and sugar. A high-calorie diet from any source will add pounds.
A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets that had varying amounts of fat and carbohydrates in each. The diets contained the same amount of calories, but differed in the percentage and type of fat. People on the low-fat, high-carbohydrate diet reported more anger and depression compared with the other two diets.
Replacing fatty foods, such as cakes, cookies, and chips, with their commercial "low-fat" counterparts does not constitute a low-fat diet. These foods generally contain more sugar and hence calories, not to mention other ingredients, which have virtually no nutritional value. In fact, a 2002 study suggested that increasing sugar may, over time, reduce levels of HDL ("good") cholesterol.
Very low-fat diets may increase the risk for stroke from hemorrhage in the brain.

Some fat in a diet is essential. It should come from plant oils and fish, however, and not from animal products or hardened oils, such as margarine. Trans-fatty acids, found in hardened oils, are actually more of a risk factor for obesity than saturated fats from animal products, although both should be avoided.

Fiber and Complex Carbohydrates. In all cases, complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Fiber is an important component of many complex carbohydrates. Fiber is almost always found only in plants, particularly vegetables, fruits, whole grains, nuts, and legumes (beans and peas). One exception is chitosan, a dietary fiber made from shellfish skeletons. Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, and fruit and vegetable peels) has been associated with weight loss. Studies also suggest that diets rich in fiber from whole grains reduce the risk for type 2 diabetes.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly benefiting blood pressure as well. Simply adding breakfast cereal to a diet appears to reduce cholesterol levels. People who increase their levels of soluble fiber should also increase water and fluid intake.

High-protein, low carbohydrate diets, such as the Atkins and South Beach diets, have been touted as effective ways to produce short-term weight loss. Because of their emphasis on fats and proteins, many experts are concerned about long-term health problems. A report in the March 2006 Lancet linked the Atkins diet to life-threatening complications that caused the death of one woman. The 40-year-old woman had a deadly buildup of acids called ketones in her blood, a condition called ketoacidosis. Ketoacidosis can cause coma and death. Ketones are a known by-product of high protein, low carbohydrate diets. At low levels they can cause nausea, lightheadedness, and bad breath.

The long-term effects of these diets are still unknown. For example, the Atkins diet restricts some vegetables and most fruits, which are known to protect against serious diseases such as heart problems and cancer. The diet may also cause too much calcium to build up in the urine. This can increase the risk for kidney stones and osteoporosis. In addition, high-protein intake, particularly from meat, can be harmful in people with kidney problems. Individuals at risk for kidney stones, or those who have other kidney problems, should not go on high-protein diets without talking to their doctor first. Unfortunately, many people with diabetes are at risk of kidney problems, which could reverse any possible benefits a high-protein diet may bring them. Eating a lot of meat has also been associated with certain common cancers, notably prostate and colon cancers. A 2002 study suggested that such diets during pregnancy may increase the risk for high blood pressure in the child.

Still, significant studies say that such diets improve cholesterol and blood sugar levels. Studies in 2002 and 2003 have indicated that these diets lower blood glucose levels, which can be important in people who are diabetic. The diets also reduce triglyceride levels (unhealthy fat molecules) and increases HDL (" good") cholesterol levels. High triglyceride and low HDL levels are important risk factors for heart disease, and are common in people with type 2 diabetes. Studies are mixed on whether this type of diet reduces overall cholesterol or LDL ("bad") cholesterol levels.

Experts that promote the low carbohydrate approach argue that heart problems from obesity are due to insulin disturbances from sugar imbalances. Therefore, they believe that restricting carbohydrates is the best approach for obesity -- especially for overweight people with diabetes. More research is needed, however, to determine the long-term impact of such diets on health.

High-protein, low-carbohydrate diets include Atkins, Protein Power, Sugar Busters, and Dr. Stillman. The Atkins diet is one of the most popular and has a four-phase program:

Induction. For the first 2 weeks, individuals consume no more than 20 grams of carbohydrates a day. The diet consists of pure protein and fats. There is no fruit, bread, grains, starchy vegetables, or dairy products other than cheese, cream, or butter. This phase is not suitable for children, pregnant women, or anyone with kidney disease.
On-going Weight Loss. After the first phase, individuals continue to lose weight while they increase carbohydrate levels by five grams each day.
Premaintenance. When individuals get close to their weight goal, they add another 10 grams of carbohydrates per day as long as they do not begin to gain weight. Weight loss is very slow at this time, but the individual is now getting used to maintenance.
Maintenance. Lifetime maintenance is usually between 40 and 100 grams of carbohydrates a day, depending on steady weight level.

Anyone who chooses this diet should prefer fish or soy products to meat as protein sources. Fish may reduce leptin, a hormone associated with fat storage and heart diseases, and would be the best protein source. People on this diet should also choose monounsaturated fats (as in olive oil) over saturated fats or trans-fatty acids fat. Patients often need supplements, at least a multivitamin and possibly calcium, chromium, omega-3 fatty acids (found in fish oil), and other supplements.

The South Beach and Zone diets encourage healthy fats. They also allow certain carbohydrates. For example the Zone uses healthy carbohydrates (vegetables and dried beans) and unsaturated fats. The South Beach diet uses carbohydrates that have a lower impact on blood sugar levels. This is called a low-glycemic index. Low-glycemic foods include barley, dried bean and peas, milk, strawberries, and apples. High-glycemic foods include refined grains, white bread, white potatoes, and bananas and other tropical fruits. The glycemic index was developed for use in diabetes -- not for weight loss. Nevertheless, there is some evidence that foods with low glycemic indexes may produce a feeling of fullness and so discourage further eating. As with any high-protein diets, people at risk for kidney stones, or those who have other kidney problems, should avoid these plans.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In fact, in one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat substitute (derived from oats) as part of a low-calorie diet. At the end of the 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from a diet can be harmful to general health.

Fat substitutes include the following:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand, as part of a low-fat, diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that the use of stanols can allow lower doses of statins (cholesterol lowering medications). Stanols do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Note that simply adding snacks containing olestra does not appear to have any effect on cholesterol or weight loss.) Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The side health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (e.g., Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-substitutes are also available. Although studies to date are not showing any significant side effects, these products' effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners and reduced their sugar intake weighed less over time than those who took in similar types and amounts of drinks and food containing sugar. It should be noted that using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain, as long as the total amount of calories in the diet is under control. There is some public concern about chemicals used to produce many of these sweeteners, and the side effects seen in studies using rats. Natural low-calories sweeteners are available that may be more acceptable to many people.

Saccharin (Sugar Twin, Sweet n' Low, Sucaryl, and Featherweight). Saccharin has been used for years. Some studies found that large amounts of saccharin cause bladder cancer in rats. However, the rats were fed huge amounts that do not apply to human diets. Currently there is no evidence that saccharin causes cancer in humans.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of nervous system disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing part of the sugar with chlorine. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period, with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the U.S. since 1988 with no reported side effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame, but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced-calorie sweetener is made from lactose, which is the sugar found in dairy products and other foods. It may be especially beneficial for people with type 2 diabetes. It may also have additional benefits that help the intestinal tract.
Alitame (Aclame) is formed from amino acids, the building blocks of proteins. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been carefully tested.

Other sugar substitutes being investigated include glycyrrhizin (derived from licorice) and dihycrochalcone (derived from citrus fruits).

Some studies have reported good success with meal replacement beverages (Slim-Fast, Sweet Success). They contain major nutrients needed for daily requirements. Each serving typically contains between 200 - 250 calories and replaces one meal. (Note: Using them for all meals reduces calories to a severe extent and can be harmful.)

One study reported that most subjects who had undergone a 12-week weight loss program and then used Ultra Slim Fast supplements as directed for maintenance kept off more than half their weight loss after more than 3 years. A quarter of the subjects were still losing weight.

Medical evidence suggests that a diet rich in magnesium could reduce a person's risk of metabolic syndrome, a cluster of problems including obesity, high blood pressure, and high cholesterol. Metabolic syndrome can lead to diabetes and heart disease. A long-term study of thousands of Americans found that the risk for metabolic syndrome decreased in those who consumed the most magnesium from meals. The findings were published in the journal Circulation.

Commercial and Non-Profit Support Programs for Weight Loss. There are many different types of weight-loss program. (This report cannot address all of the many commercial and nonprofit weight-loss programs currently available, nor can it assess their claims.)

Taking off Pounds Sensibly (TOPS), a nonprofit support organization with many local chapters, is one of the least expensive programs, costing $20 a year.

Most of the commercial programs such as Weight Watchers, Jenny Craig, and NutriSystem offer individual or group support, lifestyle changes and packaged meals. These programs tend to be expensive. There are few well-conducted studies on these programs. One 2003 study reported modest weight loss over 2 years with Weight Watchers compared to a self-help program. There were no differences in heart risk factors.

Cognitive Behavioral Approaches. Most support programs use some form of cognitive-behavioral methods to change the daily patterns associated with eating. They are very useful for preventing relapse after initial weight loss. The following is a typical approach:

The patient first records in a diary all activity related to eating patterns, including the times of day, length of meal, emotional states, companions, and, of course, the kind and amounts of food eaten. Most people -- even professional dieticians, according to one study -- tend to underreport their daily calorie intake. However, writing it down is still a good method for increasing a person's awareness of eating patterns. (One patient said that recording circumstances surrounding relapses was a particularly valuable guide for understanding the stresses leading to her own eating behaviors.)
The patient reviews the diary with a therapist or group to set realistic goals and identify patterns that the patient can change. For instance, if food is normally eaten while watching television, then the patient may be advised to eat in another room instead.
Good eating habits are reinforced by rewards. These rewards are other pleasures that substitute the high calorie consumption and sedentary activities.

Behavioral modification has been shown to be helpful particularly for people who have an overly strong response to the taste, smell, and appearance of food. It also may be useful for binge eaters.

Stress-Reduction Techniques. Stress reduction and relaxation techniques may be helpful for some people with obesity, such as those whose weight is related to night-eating syndrome. [See In-Depth Report #31: Stress.]

Changing Sedentary Habits. Making even small changes in physical activity can expend energy. For example, simply getting up to turn the TV on and off instead of using the remote, and standing (instead of sitting) while talking on the phone may help a person lose up to five pounds a year. Other suggestions include cooking one's own food (instead of eating take-out or fast food), walking to as many places as possible, using stairs instead of escalators or elevators, and gardening. Even fidgeting may be helpful in keeping pounds off, and, in one study, chewing gum increased energy expenditure.

No one should rely on such mild activities, however, for serious weight loss. Only high levels of physical activity -- not just using up energy -- help prevent obesity.

Approach to Exercise. Exercise, which replaces fat with muscle, is the critical companion for any weight control program. In a one-year study, women who regularly averaged 3.5 days (176 minutes) of exercise each week lost significantly more weight than women who did not exercise regularly. Women who exercised more than 195 minutes a week lost nearly 7% of their abdominal fat.

People who exercise are more apt to stay on a diet plan. Exercise improves psychological well-being and replaces sedentary habits that usually lead to snacking. Exercise may even act as a mild appetite suppressant. Moreover, exercise improves overall health even with modest weight loss. In support of this, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Be aware, however, that the pounds won't melt off magically. Losing significant weight requires both intensive exercise and calorie restriction. In addition, if a person exercises but doesn't diet, any actual pounds lost may be minimal, because denser and heavier muscle mass replaces fat. Nonetheless, regardless of weight loss, a fit body will look more toned and be healthier. In addition, exercise benefits the heart even with modest weight loss.

The following are some suggestions and observations on exercise and weight loss:

The more strenuous the exercise, the better the chances for short-term and long-term success. With intense exercise, the metabolism continues to burn calories before returning to its resting level. This state of elevated metabolism can last for as little as a few minutes after light exercise to as long as several hours after prolonged or heavy exercise.
Of the standard aerobic machines, the treadmill burns the most calories. It may be particularly effective when used in short multiple bouts during the day. In fact, frequent exercise sessions as short as 10 minutes in duration (about four times a day) may be the most successful exercise program for obese people.
Resistance, or strength, training is excellent for replacing fat with muscles. It should be performed two or three times a week.
As people slim down, their initial level of physical activity becomes easier and they burn fewer calories per mile of walking or jogging. The rate of weight loss slows down, sometimes discouragingly so, after an initial dramatic head start using diet and exercise combinations. People should be aware of this phenomenon and keep adding to their daily exercise program.
As people age, they also need to exercise more to keep off the same amount of weight.
Changes in fat and muscle distribution may differ between men and women as they exercise. Men tend to lose abdominal fat (which lowers their risk for heart disease faster than reducing general body fat). Exercise, however, does not appear to have the same effect on weight distribution in women. In one interesting study, women in aerobic and strength training programs lost fat in their arms and trunk, but did not gain muscle tissue in these regions.

Warning Note. Because obesity is one of the risk factors for heart disease and diabetes, anyone who is overweight must discuss their exercise program with a doctor before starting. Sudden demanding exercise, in such cases, can be very dangerous. [See In-Depth Report #29: Exercise.]

Medications

There are several different drugs used for weight loss. Unless specifically instructed by a doctor, people should use non-drug methods for losing weight. Except under rare circumstances, pregnant or nursing women should never take diet medications of any sort, including herbal and over-the-counter remedies.

A 2001 study reported that 7% of American adults use nonprescription weight-loss products. People must be cautious when using any weight-loss medications, including over-the counter diet pills and herbal or so-called natural remedies. Buying unverified products over the Internet can be particularly dangerous.

Green tea. Perhaps the best alternative advice for people who are overweight is to drink tea. Studies have indicated that regular tea drinking is associated with lower weight, particularly in people who drink it for years. Green tea specifically has been associated with increased energy expenditure. One study reported that people who took a green tea extract (Exolise) lost weight and reduced their waist size. Better evidence is needed to confirm the results on this supplement.

Thermogenic Approach to Weight Loss. An approach to weight loss called thermogenic (also hepatothermic) therapy is based on the idea that certain natural compounds have properties that enable the liver to increase energy in the cells and stimulate the metabolism. Theoretically, the result would be fat loss. Among the natural substances used in such products are EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aloe vera, aspartate, chromium, coenzyme Q10, green tea polyphenols, aloe vera, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs.

Nearly all the current over-the-counter dietary aids contain some combination of these ingredients. There is no evidence that any of these ingredients can produce weight loss, and some may even have harmful effects.

Chromium is a common ingredient in many diet supplements (e.g., Xenadrine, Dexatrim, Acutrim Natural, Twinlab Diet Fuel). It is claimed to specifically promote fat loss, rather than lean muscle loss. Some evidence suggests that niacin-bound chromium may improve insulin sensitivity. On the negative side, animal studies have suggested that chromium may have damaging effects on genetic materials in cells. This could cause sterility.

Ephedra, Ephedrine, and Ma Huang. The FDA does not allow the sale of drugs that contain ephedrine. In May 2004, the FDA banned the sale of dietary supplements that contain ephedra (also called Ma Huang). Ephedra has been linked to serious side effects, including strokes and heart attacks.

Brazilian Diet Pill. The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

Conjugated Linoleic Acid (CLA). Conjugated linoleic acid is found in many dietary products (e.g., Biosculpt Liquid, Body Success, GNC Optibolic Body Answers Dietary Formula). There is no evidence that it produces weight loss. Furthermore, there is some concern that CLA might increase insulin resistance and a dangerous inflammatory response in people with obesity.

Tiratricol. Over-the-counter products containing tiratricol, a thyroid hormone, have been sold for weight loss. Such products may increase the risk for thyroid disorders, heart attack, and stroke.

Laxative Actions in Natural Substances. Many dietary herbal teas contain laxatives, which can cause gastrointestinal distress, and, if overused, may lead to chronic pain, constipation, and dependency. In rare cases, dehydration and death have occurred. Some laxative substances found in teas include senna, aloe, buckthorn, rhubarb root, cascara, and castor oil.

Guar Gum. Some fiber supplements containing guar gum have also caused obstruction of the gastrointestinal tract.

Chitosan. Chitosan, a dietary fiber from shellfish, prevents a small amount of fat from being absorbed in the intestine. Well-conducted studies, however, have not found it to be effective. Products containing it include Cheat & Lean Fat Blocker, Natrol, Chroma Slim, and Enforma. People who are allergic to shellfish should not take these supplements.

Plantain. Dietary remedies that list the ingredient plantain may contain digitalis, a powerful chemical that affects the heart. NOTE: This substance should not be confused with the harmless banana-like plant also called plantain.

Orlistat (Xenical) can help about one-third of obese patients with modest weight loss, and can assist in long-term maintenance of weight loss. It works by slowing the absorption of fat (by about 30%) in the intestine. Studies indicate that between 50 - 80% of patients can achieve weight loss of 5% or greater, depending on other lifestyle changes. However, many people regain a significant portion of this weight back within 2 years. It does not work for all patients, however. In one survey of patients who took it, 10% gained weight or did not lose any, and 43% lost less than 5%. Nevertheless, orlistat may delay or even prevent the onset or progression of diabetes and improve cholesterol levels, regardless of weight loss.

The drug can cause gastrointestinal problems and may interfere with absorption of the fat-soluble vitamins A, D, and E and other important nutrients. The most unpleasant side effect is oily leakage of feces from the anus. Restricting fats can reduce this effect. People with bowel disease should probably avoid it. In spite of these side effects, most patients are able to tolerate this agent.

In February 2007, the FDA approved an over-the-counter (OTC) version of orlistat. It will be sold under the name alli, and will be available at half the prescription strength of Xenical. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Sibutramine (Meridia) helps balance the brain chemicals serotonin and norepinephrine. This helps increase metabolism, causes a feeling of fullness, and increases energy levels. It may be particularly useful for binge-eaters. Studies indicate that sibutramine is effective in achieving weight loss, although the weight loss slows considerably after the first 3 months. The drug also appears to improve cholesterol and lipid (fat) levels, and may have other effects that benefit the heart.

Side effects of sibutramine are common. They include dry mouth, constipation, and insomnia. In one study, almost half the patients dropped out as a result of these side effects. There have been reports of increases in heart rate and blood pressure while taking this medication, although a 2001 study indicates that blood pressure stabilizes over time.

At this time, people who have a history of high blood pressure, stroke, heart disease, or arrhythmias should not take this drug. People taking decongestants, bronchodilators (such as for asthma), monoamine oxidase inhibitors, or serotonin reuptake inhibitors should also avoid sibutramine.

Phentermine and Other Sympathomimetics. Sympathomimetics are drugs that act like the stress hormone (and chemical messenger) norepinephrine. These medications act as stimulants in the brain. Some are approved for treating obesity, but only for short-term use. They include:

Phentermine (Ionamin, Adipex-P, Fastin)
Benzphetamine (Didrex)
Phendimetrazine (Adipost, Bontril, Melfiat, Plegine, Prelu-2, Statobex)

Phentermine is the most commonly prescribed appetite suppressant, and is less expensive than orlistat or sibutramine. Its effects are not long lasting, however. It can also raise blood pressure. In addition, phentermine is associated with depression, which is already a problem in many cases of obesity. A combination (Phen-Pro) containing phentermine and the antidepressant fluoxetine (Prozac) is being investigated to help reduce this problem. Note: Neither phentermine nor such combinations are associated with the heart problems linked to the previous phentermine combination known as Fen-Phen (phentermine and fenfluramine).

Amphetamines. The amphetamines dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), and phenmetrazine (Pleudin) are powerful stimulants. They were used most often in the past but are no longer prescribed for weight loss. These drugs improve mood and produce some modest weight loss over the short term, but carry serious risks of addiction, agitation, and insomnia.

Rimonabant. Rimonabant (Accompli) belongs to a new class of drugs called selective CB1 blockers. The drug is designed to block receptors in the brain associated with the regulation of eating. Rimonabant also targets receptors in fat tissue. The Rimonabant in Obesity-Lipids (RIO-Lipids) study looked at how rimonabant affected metabolic risk factors in high-risk overweight or obese patients with blood fat disorders. The study involved more than 1,000 participants. The findings, published in the November 2005 New England Journal of Medicine, said that people who took the drug significantly reduced their body weight and size of their waist.

Earlier studies involving the drug reported that obese patients treated with 20 mg of rimonabant lost significantly more weight and inches from their waist than patients who received placebo. The drug also appeared to have beneficial effects on raising HDL ("good") cholesterol levels.

Note: Fake rimonabant has been found for sale on several web sites. Patients should be aware that this drug is still experimental, and rimonabant is not available for sale. Buying and taking counterfeit drugs can have serious health consequences. In addition, an FDA advisory panel in April 2007 rejected the drug, citing fears it may cause psychiatric problems and seizures in some patients.

Axokine. Axokine is a type of drug called a ciliary neurotrophic factor. It signals the brain to suppress one's appetite. It is proving to be effective in achieving weight loss, and also improves cholesterol, lipid, and glucose levels regardless of food intake. It could be particularly helpful for people with type 2 diabetes. Early study results found that severely obese patient who took the drug lost more weight than those who took a dummy pill (placebo). Nearly half (46%) of patients who took the drug lost at least 10 pounds, compared to 5% of those who received the placebo. Study participants tolerated the drug well. There were no reports of serious side effects.

Zonisamide. Zonisamide (Zonegran) is an anti-seizure medication that is also being investigated for weight loss. In one study, patients who took it lost more weight than those on placebo. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Other side effects include dizziness, forgetfulness, headache, and nausea.

Topiramate. Topiramate (Topamax) is another anti-seizure medication being investigated for weight reduction. Three clinical trials have reported that patients given topiramate lost more weight than those receiving placebo. Weight loss was sustained for up to 1 year. The drug is also being studied for binge-eating disorders associated with obesity.

Other Treatments

Surgical procedures for obesity may be appropriate for some dangerously obese people, and may reduce heart problems and many of the risks associated with obesity. These risks include high blood pressure, sleep apnea, and diabetes. In fact, some evidence suggests that surgery may provide much greater control of weight and diabetes than nonsurgical weight-loss methods. Studies are reporting significant reductions in diabetes, and the need for diabetic medications, after surgery. Other medical conditions that often improve after surgery include heartburn, arthritis, and other joint and circulation problems.

Bariatric surgeries produce weight loss through one of two approaches:

Restrictive Banding Procedures. These procedures restrict the amount of food by closing off parts of the stomach with bands.
Malabsorptive Bypass Procedures. This approach restricts the amount of food and also reduces absorption by using a bypass of parts of the intestine.

The malabsorptive procedures are more successful in achieving weight loss than the banding approach, but they carry a greater risk for nutritional deficiencies.

Most people who have bariatric surgery lose about two-thirds of excess weight within 2 years. In addition, diseases associated with obesity (such as diabetes, high blood pressure, sleep apnea, joint pain, and incontinence) often improve.

Researchers at the Mayo Clinic looked at records from patients who had the surgery between 1990 and 2003. They found that those who had bariatric surgery reduced their risk of cardiovascular events such as a heart attack much more than those who lost weight without surgery. The findings were published in the September 2005 Mayo Clinic Proceedings.

Other studies have shown that even though most patients maintain significant weight loss, the majority regain about to 10% of their weight. Patients must still develop a healthy life style and be calorie conscious after the operation. Follow-up must be life-long.

Any surgical candidate must have failed consistently in losing weight through less invasive methods. Experts recommend bariatric surgery only for the following:

Those whose BMI is above 40 (about 100 pounds overweight)
Those with BMIs of over 35 who have type 2 diabetes or serious obesity-related medical problems
Those with severe obesity that interfered with employment, normal physical activity (e.g., walking), and important relationship

About a third of people who undergo these procedures achieve normal weight, and 80% experience some weigh loss. They are less successful than the bypass procedures, but carry a lower risk of nutritional deficiencies.

Vertical Banded Gastroplasty. Vertical banded gastroplasty (VBG) was the most common restrictive procedure. It involves creating a hole through both stomach walls and sealing the edges with a staple. This narrows the stomach, similar to a funnel, and allows only small amounts of food to pass through.

Laparoscopic Gastric Banding. Laparoscopic gastric banding (the Lap-Band) usually does not require a major incision and avoids some of the major complications of gastric bypass:

It employs an adjustable silicone band that is placed around the upper part of the stomach.
A small balloon-like reservoir attached to the band under the abdominal skin contains saline, which can be added or removed to tighten or loosen the band.
The procedure restricts the amount of food a person can eat and gives the feeling of fullness.

The band is removable, if necessary. Studies to date indicate that the intestinal tract returns to normal afterward. Studies, including those done in the elderly, have reported significant weight loss and improved quality of life with the procedure.

Malabsorptive procedures produce greater weight loss than restrictive procedures. Patients generally achieve about two-thirds of their weight loss within 2 years. Furthermore, in a 2003 study, after standard bypass surgery, 83% of patients with type 2 diabetes experienced normal blood glucose levels and the rest had significant reductions.

Roux-en-Y Gastric Bypass Procedure. This is the most common and successful malabsorptive surgery in the United States. It involves creating a small stomach pouch that serves as a reservoir and restricts food intake. The pouch eventually holds up to 3 ounces of food and has a small outlet that delays emptying and causes a feeling of fullness. Then the surgeon creates a Y-shaped section in the small intestine that attaches to the pouch. This section allows food to bypass the lower stomach and upper part of the intestine. One 2003 study reported that this procedure was associated with significant weight loss, and 80% of patients with type 2 diabetes were able to reduce their medications. A more recent study, published in the March 14, 2006, issue of Archives of Surgery, found that gastric bypass surgery also helps lower the blood pressure of very obese patients.

The procedure produces greater and more sustained weight loss than banding procedures, but it is also more complicated, and carries a higher risk of nutritional deficiencies. Laparoscopy techniques, which are less invasive, are now preferred over open surgery. They achieve equally good results with fewer complications.

Biliopancreatic Diversion. This procedure is more complicated and removes portions of the stomach. The pouch that is created attaches directly to the lower part of the small intestine. It poses a higher risk for nutritional deficiencies than other procedures and is not used as often.

Click the icon to see an image of gastric bypass surgery.

General Side Effects and Complications. Side effects and complications of bariatric procedures are common, and up to 25% of patients require corrective or repeat procedures. After any of these procedures people must chew all their food carefully, and they cannot eat large amounts of food at one time. If patients do not follow these guidelines, they will experience nausea, abdominal distress, or both.

Complications from any bariatric procedure includes the following:

Vomiting: This is the most common complication, and it is most common with banding procedures.
Nutritional deficiencies: There is a strong risk of nutritional deficiencies, particularly with malabsorptive operations. This complication can lead to anemia and increase the risk of bone loss and osteoporosis. Taking enough mineral and vitamin supplements is important after bariatric surgery.
Deep-vein thrombosis: There is a significant risk for deep-vein thrombosis (blood clots in the veins).
Abdominal hernia: This is another common complication. Newer, laparoscopic techniques do not carry this risk, but not all individuals are candidates for this less-invasive approach.
Rapid weight loss after surgery: This complication puts people at high risk for gallstones.
Women who wish to be pregnant should wait until their weight has stabilized. Rapid weight loss and nutritional deficiencies can harm the fetus.

People at highest risk for complications are those with heart or lung problems, severe obesity, and a history of abdominal surgeries. The mortality rate from bariatric surgeries is 0.2%, which is lower than the morality rates from severe obesity itself. Other surgical variations and less invasive techniques using laparoscopy have been developed.

Specific Complications of Restrictive Banding Procedures. Nausea, vomiting, or both occurs in half the patients, and severe heartburn occurs in a third. Device-related complications include band slippage, pouch dilation (widening), or both in nearly a quarter of patients, and obstruction in 12% of patients. Very serious complications are rare, but include blood clots, bleeding, infection, pneumonia, and perforation (tearing) of the stomach.

Specific Complications of Malabsorptive Bypass Procedures. Vomiting often occurs. Nutritional deficiencies occur more often in these procedures. The so-called dumping syndrome is a common unpleasant side effect, which occurs when food waste moves too quickly through the intestine. Symptoms include nausea, weakness, sweating, and faintness (particularly after eating sweets).

Spot Exercising. Anyone seeking to lose weight must expect that the results may not be as cosmetically satisfying as one would wish. Spot exercising (training particular areas of the body) is ineffective in reducing fat in specific locations because exercise draws on fat stores throughout the body. Gimmicky devices such as bust developers, vacuum pants, and exercise belts do absolutely nothing to reduce fat or add bulk in specific locations. Electrical pads wrapped around the waist, arms, or thighs were reported to cause burns and fires.

Cellulite-Removal Creams. Many women try to reduce fat in their thighs (cellulite) with creams that contain aminophylline (Skinny Dip, Thermojetics Body Toning Cream, Smooth Contours). Studies provide no evidence that these creams are effective. Their apparent effect on fat may simply be from narrowing blood vessels and forcing water from the skin, which could be dangerous for people with blood flow problems.

Endermologie. Endermologie uses motorized rollers and regulated suction to smooth out cellulite. In one study, about 28.6% of patients reported improved appearance after using it.

Liposuction. Liposuction eliminates fat in specific areas, such as the abdomen, thighs, buttocks, or knees. Special instruments are inserted through the skin into the pockets and suction is used to move the fat, break it up, and remove it. Small tubes may be used to drain blood and fluid during the first few days. The pain after the operation can be severe and often the skin does not contract, resulting in a flabby look. Complications can include burns from the vibrators, bruising, blood clots, and bleeding. Weight gain generally tends to develop in other locations after the operation. Some doctors are using this procedure in overweight people with diabetes to remove abdominal fat. Although there is no proof that it has an effect on diabetes, some experts believe the procedure deserves attention.

Liposuction is not recommended for major weight loss.

Resources

www.healthierus.gov/dietaryguidelines -- Dietary Guidelines for Americans 2005
www.naaso.org -- North American Association for the Study of Obesity
www.eatright.org -- American Dietetic Association
www.nutrition.gov. -- Nutrition.gov
www.asbs.org -- American Society for Bariatric Surgery
www.cnpp.usda.gov -- Center for Nutrition Policy and Promotion
http://fnic.nal.usda.gov -- Food and Nutrition Information Center
www.americanheart.org -- American Heart Association
www.nationaleatingdisorders.org -- National Eating Disorders Organization
www.aabt.org -- Association for Advancement of Behavior Therapy
www.fda.gov -- Food and Drug Administration
http://win.niddk.nih.gov -- Weight-Control Information Network

References

US Food and Drug Administration FDA Approves Orlistat for Over-the-Counter Use. Rockville, MD: National Press Office; February 7, 2007.

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. Journal of the American Medical Association. 2006; 295:1549-1555.

National Center for Health Statistics. Chartbook on Trends in the Health of Americans. Health, United States, 2005. Hyattsville, MD: Public Health Service. 2005

National Institute of Diabetes and Digestive and Kidney Diseases - Weight-control Information Network. Statistics Related to Overweight and Obesity. Available online.

National Center for Health Statistics. Prevalence of Overweight Among Children and Adolescents: United States, 2003-2004.

Morino M, Toppino M, Bonnet G, Rosa R, et al. Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of efficacy. Surg Endosc. 2002 Nov;16(11):1566-72.

Brethauer SA, Schauer PR, Chand B. Risks and benefits of bariatric surgery: Current evidence. Cleveland Clinic Journal Of Medicine. 2006 Nov; 73(11): 993-1007.

Rosenthal RJ, Szomstein S, Kennedy CI, et al. Laparoscopic surgery for morbid obesity: 1,001 consecutive bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Obes Surg. 2006 Feb;16(2):119-24.

He K, Liu K, Daviglus ML, et al. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation. 2006: Published online before print. March 27, 2006.

Chen TY, Smith W, Rosenstock JL, Lessnau KD. A life-threatening complication of Atkins diet. Lancet. 2006 Mar 18;367(9514):958.

Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc. 2005 Sep;80(9):1157-62.

Sidhaye A, Cheskin LJ. Pharmacologic treatment of obesity. Adv Psychosom Med. 2006;27:42-52.

Fernstrom JD, Courcoulas AP, Houck PR, Fernstrom MH. Long-term changes in blood pressure in extremely obese patients who have undergone bariatric surgery. Arch Surg. 2006 Mar;141(3):276-83.

Despres JP, Golay A, Sjostrom L; Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005 Nov 17;353(20):2121-34.

Lanningham-Foster L, Nysse LJ, Levine JA. Labor saved, calories lost: the energetic impact of domestic labor-saving devices. Obes Res. 2003 Oct;11(10):1178-81.

Review Date:
6/14/2007
Reviewed By:
A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (4/30/2007).

A.D.A.M. Copyright

adam.com

Diabetes diet

FitSugar — Wed, 08 Oct 2008 17:35:01 -0700

In This Report

Highlights
Introduction
General Dietary Guidelines...
Major Food Components
Weight Control for Type 2 D...
Heart-Healthy Diets
Diabetic Exchange Lists
Exercise
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Lifestyle Changes Essential for People at Risk for Diabetes

Lifestyle interventions that include weight loss, dietary changes, and increased physical activity can definitely help prevent or delay the progression to diabetes among at-risk people, suggest several recent studies. Weight loss through diet and exercise is especially important for overweight people with pre-diabetes.

Grain Fiber Important for Diabetes Prevention

Eating whole-grain, fiber-rich, cereal foods may help reduce the risk of developing type 2 diabetes, indicates a 2007 study in the Archives of Internal Medicine. In the study, people who consumed the most fiber from grains and cereals had a 33% lower risk of developing diabetes than people with the lowest fiber intakes. The study also found an association between high magnesium intake and reduced diabetes risk. Although fruits and vegetables also contain fiber, they did not appear to affect diabetes risk.

Low-Fat Dairy Products

Incorporating low-fat dairy products (such as yogurt and milk) into a healthy diet may help reduce diabetes risk for women, suggests a study in Diabetes Care.

Beware of Internet Dietary Supplement Scams

In 2006, the FDA alerted consumers not to be misled by dietary supplements advertised on the Internet as treatments or cures for diabetes. These products have not been scientifically studied or approved.

Low-Glycemic Index Diets

Food low on the glycemic index -- such as whole grains, fruits, lentils, and soybeans -- can help promote weight loss and heart health. Illustrating the complexity of this area, a 2006 study in the New England Journal of Medicine indicated that a low-carb, low-glycemic index diet was beneficial while another study in the Archives of Internal Medicine suggested advantages for a high-carb, low-glycemic index diet.

Low-Fat Vegan Diets

A low-fat diet that excludes meat and dairy products may help improve glycemic control and increase insulin sensitivity, suggests a Diabetes Care study. Researchers think that the high fiber content of these diets, in addition to their reduced fat, may be a factor.

Introduction

The two major forms of diabetes are type 1, previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, and type 2, previously called non-insulin-dependent diabetes mellitus (NIDDM) or maturity-onset diabetes. [See In-Depth Report #9: Diabetes - type 1 and In-Depth Report #60: Diabetes - type 2.]

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to absolute or relative insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It normally works in the following way:

During and immediately after a meal the process of digestion breaks carbohydrates down into sugar molecules (of which glucose is one) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply. (Glucose levels after a meal are called postprandial levels.)
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 10 minutes after a meal insulin rises to its peak level.
Insulin then enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (The brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

Click the icon to see an image of the liver.

In type 1 diabetes, the disease process is more severe than with type 2, and onset usually begins in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."

Click the icon to see an image of the pancreas.

Patients with type 1 diabetes need to take insulin. Dietary control in type 1 diabetes is very important and focuses on balancing food intake with insulin intake and energy expenditure from physical exertion. [See In-Depth Report #9: Diabetes - type 1.]

Type 2 diabetes is the most common form of diabetes, accounting for up to 95% of all diabetes cases. About 20 million Americans have type 2 diabetes, and half are unaware they have it. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that the disease may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin, and in the beginning this amount is usually sufficient to overcome such resistance. Patients whose blood glucose levels are higher than normal, but not yet high enough to be classified as diabetes, are considered to have “pre-diabetes.” It is very important that people with pre-diabetes control their weight to stop or delay the progression to diabetes.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

Obesity is common in patients with type 2 diabetes and this condition appears to be related to insulin resistance. The primary dietary goal for overweight type 2 patients is weight loss and maintenance. Studies indicate that when people with type 2 diabetes maintain intensive exercise and diet modification programs, many can minimize or even avoid medications. Weight loss medications or bariatric surgery may be appropriate for some patients. [See In-Depth Report #60: Diabetes - type 2 and In-Depth Report #53: Weight control and diet.]

General Dietary Guidelines

For people who have pre-diabetes, or who are at high risk of developing type 2 diabetes, lifestyle changes of diet and exercise are extremely important. Several studies have shown that lifestyle interventions are very effective in preventing or postponing the progression to diabetes. These interventions are especially important for overweight people -- even moderate weight loss can help reduce diabetes risk.

The American Diabetes Association recommends that people at high risk for type 2 diabetes eat high-fiber (14g fiber for every 1,000 calories) and whole-grain foods. A 2007 study in the Archives of Internal Medicine also suggested that high intake of fiber and magnesium, especially from whole grain cereals and breads, can help reduce type 2 diabetes risk.

For people who have diabetes, the treatment goals for a diabetes diet are:

Achieve near normal blood glucose levels. People with type 1 diabetes and people with type 2 diabetes who are taking insulin or oral medication must coordinate calorie intake with medication or insulin administration, exercise, and other variables to control blood glucose levels. New forms of insulin are now allowing more flexibility in timing meals.
Protect the heart and aim for healthy lipid (cholesterol and triglyceride) levels and control of blood pressure.
Achieve reasonable weight. Overweight patients with type 2 diabetes who are not taking medication should aim for a diet that controls both weight and glucose. A reasonable weight is usually defined as what is achievable and sustainable, rather than one that is culturally defined as desirable or ideal. Children, pregnant women, and people recovering from illness should be sure to maintain adequate calories for health.
Manage or prevent complications of diabetes. People with diabetes, whether type 1 or 2, are at risk for a number of medical complications, including heart and kidney disease. Dietary requirements for diabetes must take these disorders into consideration.
Promote overall health.

Overall Guidelines. Overall Guidelines. There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

For example, a patient with type 2 diabetes who is overweight and insulin-resistant may need to have a different carbohydrate-protein balance than a thin patient with type 1 diabetes in danger of kidney disease. Because regulating diabetes is an individual situation, everyone with this condition should get help from a dietary professional in selecting the best method.

Healthy eating habits along with good control of blood glucose are the basic goals in managing this complex disease, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 - 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists.
Fats should provide 25 - 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 - 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat.
Lose weight if body mass index (BMI) is 25 - 29 (overweight) or higher (obese).

Several different dietary methods are available for controlling blood sugar in type 1 and insulin-dependent type 2 diabetes:

Diabetic Exchange Lists (for maintaining a proper balance of carbohydrates, fats, and proteins throughout the day)
Carbohydrate Counting (for tracking the number of grams of carbohydrates consumed each day)
Glycemic index (for tracking which carbohydrate foods increase blood sugar)

Tests for Glucose Levels. Both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia) are of concern for patients who take insulin. It is important, therefore, to monitor blood glucose levels carefully. Patients should aim for the following measurements:

Pre-meal glucose levels of 90 - 130 mg/dL
Bedtime levels of 110 - 150 mg/dL

In general, patients who are tightly controlling glucose levels need to take readings four or more times a day. Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so experts usually recommend that these patients measure blood levels only once or twice a day. Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Tests for Glycosylated Hemoglobin. Another test examines blood levels glycosylated hemoglobin, also known as hemoglobin A1c (HbA1c). Measuring glycosylated hemoglobin is useful for determining the severity of diabetes. The test is not affected by food intake so it can be taken at any time. A home test has been developed that may make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Other Tests. Other tests are needed periodically to determine potential complications of diabetes, such as high blood pressure, unhealthy cholesterol levels, and kidney problems. Such tests may also indicate whether current diet plans are helping the patient and whether changes should be made. Annual urine tests showing even microscopic traces of a protein known as albumin can indicate a future risk for serious kidney disease.

For prevention of long-term complications of diabetes, experts now recommend that all patients with diabetes aim at keeping blood levels as close to normal as possible. Such intensive insulin treatment can increase the risk of hypoglycemia, which occurs when blood sugar is extremely low (below 60 mg/dL). The following tips may help avoid hypoglycemia or prepare for attacks.

Patients are at highest risk for hypoglycemia at night. Bedtime snacks may be helpful.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is also particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients on therapies that put them at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes designed for individuals with diabetes.

Food Labels. Every year thousands of new foods are introduced, many of them advertised as nutritionally beneficial. It is important for everyone, most especially people with diabetes, to be able to differentiate advertised claims from truth. The current food labels show the number of calories from fat, the amount of nutrients that are potentially dangerous (fat, cholesterol, sodium, sugars) as well as useful nutrients (fiber, carbohydrates, protein, vitamins).

Labels also show "daily values," the percentage of a daily diet that each of the important nutrients offers in a single serving. Unfortunately, the daily value is based on 2,000 calories, generally much higher than most patients with diabetes should have, and the serving sizes may not be equivalent to those on the Exchange Lists. Most people will need to recalculate the grams and calories listed on food labels to fit their own serving sizes and calorie needs.

Weighing and Measuring. Weighing and measuring food is extremely important in order to get the correct number of daily calories.

Along with measuring cups and spoons, choose a food scale that measures grams. (A gram is very small, about 1/28th of an ounce.)
Food should be weighed and measured after cooking.
After measuring all foods for a week or so, most people can make fairly accurate estimates by eye or by holding food without having to measure everything every time they eat.

Timing. Meals should not be skipped, particularly for those who are on insulin. Skipping meals can upset the balance between food intake and insulin and also can lead to weight gain if the patient eats extra food too often to offset low blood sugar levels.

The timing of meals is particularly important for people taking insulin:

Patients should coordinate insulin administration with calorie intake. In general, they should eat three meals each day at regular intervals. Snacks are often required.
They should try to take an insulin injection 30 minutes before they eat, although this timing could vary, depending on the form. Some experts recommend a fast acting insulin (insulin lispro) at each meal and a longer (basal) insulin at night.

Diabetes can lead to kidney disease and failure. People with early-stage kidney failure need to follow a special diet that slows the build-up of wastes in the bloodstream. The diet restricts protein, potassium, phosphorus, and salt intake. Fat and carbohydrate intake may need to be increased to help maintain weight and muscle tissue.

People who have late-stage kidney disease usually need dialysis. Once patients are on dialysis, they must have more protein in their diet. Patients must still be very careful about restricting salt, potassium, phosphorus, and fluids. Patients on peritoneal dialysis may have fewer restrictions on salt, potassium, and phosphorus than those on hemodialysis.

Major Food Components

Compared to fats and protein, carbohydrates have the greatest impact on blood sugar. Both the amount and type of carbohydrate affect blood glucose. Carbohydrate types are either complex (as in starches) or simple (as in fruits and sugars). One gram of carbohydrates equals four calories. The current general recommendation is that carbohydrates should provide between 40 - 65% of the daily caloric intake. Carbohydrate intake should not fall below 130 grams/day. Most experts do not recommend low-carb diets for diabetes management or weight control.

Vegetables, fruits, whole grains, and beans are good sources of carbohydrates. Whole grain foods provide more nutritional value than pasta, white bread, and white potatoes. Brown rice is a better choice than white rice. Patients should try to consume a minimum of 20 - 35 grams of fiber daily (ideally 50 grams/day), from vegetables, fruits, whole grain cereals, breads, nuts and seeds.

Complex Carbohydrates. Complex carbohydrates found in whole grains and vegetables are preferred over carbohydrates found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Most of these are high in fiber, which is important for health. Whole-grains specifically are extremely important for people with diabetes or at risk for it. [For specific benefits, see Box Whole Grains, Nuts, and Fiber-Rich Foods and Table Some Examples of Healthy Foods.]

Simple Carbohydrates (Sugar). Sugars are generally one of two types:

Sucrose (table sugar). Sucrose has been associated with higher triglycerides and harmful cholesterol levels. A 2002 study suggested that a high level of sugar consumption may also reduce levels of HDL cholesterol, the so-called good cholesterol.
Fructose (sugar found in fruits). Fructose may produce a slower increase in blood sugar than sucrose, which may have some advantages for people with diabetes. Dark-colored fruits are rich in important vitamins and other nutrients, and studies continue to report their benefits for the heart and health in general. Other fruits, such as apples and grapes also have important beneficial food chemicals.

Sugar itself, either as sucrose or fructose, adds calories, increases blood glucose levels quickly, and provides no other nutrients. High levels of sugar consumption -- both fructose and sucrose -- have been associated with higher triglycerides and lower levels of HDL cholesterol, the so-called good cholesterol. The high consumption of sugar is most likely one of the factor in the current obesity epidemic. Soda, other sweetened beverages, and fruit juice in fact may be singled out as major contributors to childhood obesity.

People with diabetes should avoid products listing more than 5 grams of sugar per serving, and some doctors recommend limiting fruit intake. If specific amounts are not listed, patients should avoid products with either sucrose or fructose listed as one of the first four ingredients on the label. [See Box Fat Substitutes and Artificial Sweeteners.]

Of increasing interest to researchers is possible harm from sugar from advanced glycation end-products (called AGEs). These are end-products of the chemical reaction between sugar and protein. This reaction occurs most intensively when cooking at high temperatures -- particularly animal fats. (Steaming or cooking food in water does not produce these chemicals. Low, slow cooking also produces fewer AGEs.) AGEs can also be formed by chemical reactions in the body itself. They may promote factors in the inflammatory response that cause a number of diseases or their complications, including diabetes and other serious conditions (Alzheimer's, atherosclerosis, cataracts, and osteoporosis).

The Carbohydrate Counting System. Some people plan their carbohydrate intake using a system called carbohydrate counting. It is based on two premises:

All carbohydrates (either from sugar or starch) will raise blood sugar to a similar degree. In general, 1 gram of carbohydrates raises blood sugar by 3 points in people who weigh 200 pounds, 4 points for people who weigh 150 pounds, and 5 points for 100 pounds.
Carbohydrates have the greatest impact on blood sugar; fats and protein play only minor roles.

In other words, the amount of carbohydrates eaten (rather than fats or proteins) will determine how high blood sugar levels will rise. There are two options for counting carbohydrates: advanced and simple. Both rely on collaboration with a doctor, dietitian, or both. Once the patient learns how to count carbohydrates and adjust insulin doses to their meals, many find it more flexible, more accurate in predicting blood sugar increases, and easier to plan meals than other systems.

The basic goal is to balance insulin with the amount of carbohydrates eaten in order to control blood glucose levels after a meal. The steps to the plan are as follows:

The patient must first carefully record a number of factors that are used to determine the specific requirements for a meal plan based on carbohydrate grams:

Multiple blood glucose readings (taken several times a day)
The time of meals
Amount in grams of all the carbohydrates eaten
Time, type, and duration of exercise
The time, type, and dose of insulin or oral medications
Other relevant factors, such as menstruation, illness, and stress

The patient works with the dietitian for two or three 45 - 90 minute sessions to plan how many grams of carbohydrates are needed. There are three carbohydrate groups:

Bread/starch
Fruit
Milk

One serving from each group should contain 12 - 15 carbohydrate grams. (Patients can find the amount of carbohydrates in foods from labels on commercial foods and from a number of books and web sites.)

The dietitian creates a meal plan that accommodates the patient's weight and needs, as determined by the patient's record, and makes a special calculation called the carbohydrate to insulin ratio. This ratio determines the number of carbohydrate grams that a patient needs to cover the daily pre-meal insulin needs.

Eventually, patients can learn to precisely adjust their insulin doses to their meals.

Patients who choose this approach must still be aware of protein and fat content in foods. These food groups may add excessive calories and saturated fats. Patients must still follow basic healthy dietary principles.

The Glycemic Index. The glycemic index helps determine which carbohydrate-containing foods raise blood glucose levels more or less quickly after a meal. The index uses a scale of numbers for specific foods that reflect greatest to least delay in producing an increase in blood sugar after a meal. The lower the index number, the better the impact on glucose levels. Some evidence suggests that the benefit of foods with a low glycemic index is due to their ability to increase insulin levels quickly and so remove blood sugar rather than their ability to slow the release of blood sugar itself.

There are currently two indices in use. One uses a scale of 1 - 100 with 100 representing a glucose tablet, which has the most rapid effect on blood sugar [See Table The Glycemic Index of Some Foods]. The other common index uses a scale with 100 representing white bread (so some foods will be above 100).

A major 2003 analysis suggested that choosing foods with a low glycemic index scores may have a small but significant effect on controlling the surge in blood sugar after meals. Many of these foods are also high in fiber and so have heart benefits as well. Substituting low- for high-glycemic index foods may also help prevent weight gain.

One easy way to improve glycemic index is to simply replace starches and sugars with whole grains and legumes (dried peas, beans, and lentils). However, there are many factors that affect the glycemic index of foods, and maintaining a diet with low glycemic load is not straightforward. The following are some considerations:

The numbers attributed to each carbohydrate-rich food cannot be added to equal a certain number. In other words, adding All Bran cereal (index of 49) to a banana (index of 61) does not equal 110.
Adding certain fats to a food (for example butter to potato) can slow down the food's impact on blood sugar. One study reported that when patients ate fatty foods first, their blood glucose levels were significantly lower an hour after the meal than when carbohydrates were eaten first.
Adding foods with organic acids (pickles, yogurt) to meals may reduce the impact of foods with high glycemic scores on blood sugar. (It should be noted that yogurt alone, however, has the same high glycemic index as regular milk.)

No one should use the glycemic index as a complete dietary guide, since it does not provide nutritional guidelines for all foods. It is simply an indication of how the metabolism will respond to certain carbohydrates. Some experts believe it is too complicated to be practical and that simply tracking carbohydrates, eating healthily, and maintaining a healthy weight is sufficient. Nevertheless, a study on children with type 1 diabetes suggested that the glycemic index offered as many choices as the exchange diet, and they did not report feeling any greater limitations. [For additional information on low-glycemic index diets, see "Heart-Healthy Diets" section of this report.]

Fiber is an important component of many complex carbohydrates. It is almost always found only in plants, (particularly vegetables), fruits, whole grains, nuts, and legumes (dried beans, peanuts, and peas). (One exception is chitosan, a dietary fiber made from shellfish skeletons.) Fiber cannot be digested but passes through the intestines, drawing water with it and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, legumes, and fruit and vegetable peels) may help achieve weight loss. Consuming whole grains on a regular basis appears to provide many important benefits, especially for people with type 2 diabetes. Whole grains may even lower the risk for type 2 diabetes in the first place. Of special note, nuts, such as almonds, macadamia, and walnuts may be highly heart protective, independent of their fiber content. However, nuts are high in calories.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly reducing blood pressure as well. Evidence on the heart benefits of beans continues to grow. For example, a 2001 study indicated that eating beans four or more times a week reduced the risk for heart disease by 22%.
Soluble fiber supplements, such as those that contain psyllium or glucomannan, may be beneficial. Psyllium is taken from the husk of a seed grown in India. It is found in laxatives (Metamucil), breakfast cereals (Bran Buds), and other products. In a 2002 study, patients with type 2 diabetes who consumed psyllium (Plantaben) for breakfast for 11 weeks experienced lower total and LDL cholesterol levels. There was no difference in glucose or HbA1c levels. Psyllium can increase sodium so people who increase their levels of soluble fiber should also increase water and fluid intake.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat replacer (derived from oats) as part of a low-calorie diet. At the end of 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking, deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from your diet can be harmful to general health. Some fat substitutes include:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand as part of a low-fat diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that their use can allow lower doses of statins (cholesterol -lowering drugs). These products do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does. They can be hydrogenated, however, and can contain some trans-fatty acids.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Simply adding snacks containing olestra do not appear to have any effect on cholesterol or weight loss.) However, it can cause cramping and diarrhea. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The adverse health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-replacers are also available. Although studies to date do not show any significant adverse health effects, their effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners in beverages and foods and reduced their sugar intake weighed less over time than those who ate similar types and amounts of drinks and food containing sugar. However, using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain as long as the total caloric intake is under control. There is some public concern about chemicals used to produce many of these sweeteners and adverse effects in studies using rats. Natural low-calorie sweeteners that may be more acceptable to many people are also available. Low-calorie sweeteners include:

Saccharin (Sugar Twin, Sweet n’Low, Sucaryl, and Featherweight). Saccharin has been used for years but is not used as commonly now. Some studies found that large amounts of saccharin caused bladder cancer in rats. Although the rats were fed huge amounts that do not apply to human diets, some evidence suggests that people who have six or more servings of saccharin per day may have an increased risk.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of neurologic disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a rare genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing hydroxyl atoms with chlorine atoms. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the US since 1988 with no reported adverse effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced calorie sweetener is a novel low-calorie sweetener derived from lactose, which is found in dairy products and other foods. It may be specifically beneficial for people with type 2 diabetes and have additional benefits that aid the intestinal tract.
Alitame (Aclame) is formed from amino acids. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been rigorously tested.

Other artificial sweeteners being investigated include, glycyrrhizin (derived from licorice), and dihycrochalcones (derived from citrus fruits).


Based on 100 = a Glucose Tablet
BREADS
pumpernickel	49
sour dough	54
rye	64
white	69
whole wheat	72
GRAINS
barley	22
sweet corn	58
brown rice	66
white rice	72
BEANS
soy	14
red lentils	27
kidney (dried and boiled, not canned)	29
chickpeas	36
baked	43
DAIRY PRODUCTS
milk	30
ice cream	60
CEREALS
oatmeal	53
All Bran	54
Swiss Muesli	60
Shredded Wheat	70
Corn Flakes	83
Puffed Rice	90
PASTA
spaghetti-protein enriched	28
spaghetti (boiled 5 minutes)	33
spaghetti (boiled 15 minutes)	44
FRUIT
strawberries	32
apple	38
orange	43
orange juice	49
banana	61
POTATOES
sweet	50
yams	54
new	58
mashed	72
instant mashed	86
white	87
SNACKS
potato chips	56
oatmeal cookies	57
corn chips	72
SUGARS
fructose	22
refined sugar	64
honey	91
Note. These numbers are general values, but may vary widely depending on other factors, including if and how they are cooked and foods they are combined with.

Protein intake in diabetes is complicated. Protein recommendations vary among experts and depend on various factors. These factors include whether a patient has type 1, type 2, or pre-diabetes. There are additional guidelines for patients who show signs of kidney damage (nephropathy).

In general, diabetes dietary guidelines recommend that proteins should provide 12 - 20% of total daily calories. This daily amount poses no risk to the kidney in people who do not have kidney disease. Protein is important for strong muscles and bone. Some experts recommend a higher proportion of protein (20 - 30%) for patients with pre- or type 2 diabetes. They think that eating more protein helps people feel more full and thus reduces overall calories. In addition, protein consumption helps the body maintain lean body mass during weight loss.

Because protein causes the kidneys to work harder, patients with diabetic nephropathy need to limit their intake of protein. A typical protein-restricted diet limits protein intake to no more than 10% of total daily calories. Patients with kidney damage also need to limit their intake of phosphorus, a mineral found in dairy products, beans, and nuts. (However, patients on dialysis need to have more protein in their diets.) Potassium and phosphorus restriction is often necessary as well.

One gram of protein contains 4 calories. Protein is commonly recommended as part of a bedtime snack to maintain normal blood sugar levels during the night, although studies are mixed over whether it adds any protective benefits against nighttime hypoglycemia. If it does, only small amounts (14 grams) may be needed to stabilize blood glucose levels.

Good sources of protein include fish, skinless chicken or turkey, nonfat or low-fat dairy products, soy (tofu), and legumes (kidney beans, black beans, chick peas, lentils).

Fish. Fish is probably the best source of protein. Evidence suggests that eating moderate amounts of fish (twice a week) may improve triglycerides and help lower the risks for death from heart disease, dangerous heart rhythms, blood pressure, a tendency for blood clots, and the risk for stroke.

The most healthy fish are oily fish such as salmon, mackerel, or sardines, which are high in omega-3 fatty acids. Three capsules of fish oil (preferably as supplements of DHA-EPA) is about equivalent to eating one serving of fish.

Some studies have reported a higher incidence of heart attack in men who ate fish daily. Such findings may be due to mercury toxicity, which has harmful effects on the heart. High mercury content has been observed in swordfish and shark and, to some extent, in tuna, trout, pike, tilapia, and bass.

Fish oil supplements may also have some adverse effects on LDL levels and glucose control in type 2 diabetes. More research is needed to further define the risk and benefits of fish, but at this time most guidelines recommend eating fish two or three times a week.

Soy. Soy is an excellent food. It is rich in both soluble and insoluble fiber, omega-3 fatty acids, and provides all essential proteins. Soy proteins have more vitamins and minerals than meat or dairy proteins. They also contain polyunsaturated fats, which are better than the saturated fat found in meat. The best sources of soy protein are soy products (tofu, soy milk, soybeans). Soy sauce is not a good source. It contains only a trace amount of soy and is very high in sodium.

For many years, soy was promoted as a food that could help lower cholesterol and improve heart disease risk factors. But an important 2006 American Heart Association (AHA) review of studies found that soy protein and isoflavone supplement pills do not really have any effects on cholesterol or heart disease prevention. The AHA still encourages patients to include soy foods as part of an overall heart healthy diet, but does not recommend using isoflavone supplements.

Meat and Poultry. Lean cuts of meat are the best choice for heart health and diabetes control. Saturated fat in meat is the primary danger to the heart. The fat content of meat varies depending on the type and cut. For patients with diabetes, experts recommend choosing skinless chicken or turkey over red meat. (Fish is an even better choice.) A large, long-term 2006 study found that high heme iron intake from red meat increases the risk of developing type 2 diabetes in women. Another 2006 study suggested that replacing red meat with chicken improves kidney function and lipid levels in patients with diabetic nephropathy.

Dairy Products. A 2002 study reported that a high intake of dairy products can lower risk factors related to type 2 diabetes and heart disease (insulin resistance, high blood pressure, obesity, and unhealthy cholesterol). Some researchers suggest the calcium in dairy products may be partially responsible for these benefits. However, because many dairy products are high in saturated fats and calories, doctors recommend that patients choose low-fat and nonfat dairy items. Other studies have indicated that increasing the amount of low-fat diary products in a daily diet may help reduce type 2 diabetes risk, particularly for women.

Some fat is essential for normal body function. Fats can have good or bad effects on health, depending on their chemistry. New research suggests that the type of fat is more important than the total amount of fat when it comes to reducing heart disease.

Current dietary guidelines for diabetes and heart health recommend that total fat be 25 - 35% of total daily calories. Monounsaturated fats (olive oil, canola oil, peanut oil, nuts, avocados) and omega-3 polyunsaturated fats (fish, flaxseed, walnuts) should be the first choice for fats. Omega-6 polyunsaturated fats (corn oil, safflower, oil, sunflower oil, soybean oil) are the second choice. Limit saturated fat to less than 7% of total daily calories. Limit trans-fats (margarine, commercial baked goods, snack and fried foods) to less than 1% of total calories.

All fats, good or bad, are high in calories compared to proteins and carbohydrates. In order to calculate daily fat intake, multiply the number of fat grams eaten by nine (1 fat gram is equal to 9 calories, whether it's oil or fat) and divide by the number of total daily calories desired. One teaspoon of oil, butter, or other fats equals about 5 grams of fat. All fats, no matter what the source, add the same calories. The American Heart Association recommends that fats and oils have less than 2 grams of saturated fat per tablespoon.

Try to replace saturated fats and trans fatty acids with unsaturated fats from plant and fish oils. Omega-3 fatty acids, which are found in fish and plant sources, are a good source of unsaturated fats. Generally, two servings of fish per week provide a healthful amount of omega-3 fatty acids.

The Chemistry of Fats and Cholesterol.

Fatty Acids. All fats and oils found in foods are made up of chains of molecules called fatty acids. There are three major chains: saturated fatty acid (found mostly in animal products) and two unsaturated fatty acids -- monounsaturated and polyunsaturated fatty acids (found in plant products). The oils and fats that people and animals eat are nearly always mixtures of these three chains, but one type of fatty acid usually predominates in specific oils or fats.
Essential Fatty Acids. In addition, there are three chemical subgroups of polyunsaturated fatty acids called essential fatty acids: omega-3 and omega-6 polyunsaturated fatty acids, and omega-9 monounsaturated fatty acids.
Trans Fatty Acids. To complicate matters, there are also trans-fatty acids, which are not natural but are manufactured by adding hydrogen atoms to polyunsaturated fatty acids (called hydrogenation).

Harmful Fats. Reducing consumption of saturated fats and trans-fatty acids is the first essential step in managing cholesterol levels through diet.

Saturated Fats. Saturated fats are found predominantly in animal products, including meat and dairy products. They are strongly associated with higher cholesterol levels, and they may be even more dangerous in women than in men. High-fat meals are associated with sudden surges in triglyceride levels and other lipids along with impaired blood flow in the arteries to the heart. (Tropical oils such as palm, coconut, and cocoa butter are also high in saturated fats.)
Trans Fatty Acids. Trans fatty acids are manufactured fats created during a process called hydrogenation, which is aimed at stabilizing polyunsaturated oils to prevent them from becoming rancid and to keep them solid at room temperature. They are particularly dangerous for the heart and may pose a risk for certain cancers. These partially hydrogenated fats are even worse than saturated fats. Studies report that high consumption of these fats reduces HDL and raises LDL cholesterol levels, has harmful effects on the linings of the arteries, and may increase the risk for type 2 diabetes. Hydrogenated fats are used in stick margarine and in many fast foods and baked goods, including most commercially produced white breads. (Liquid margarine is not hydrogenated and is recommended.) The FDA ordered that food labels list the amount of trans fatty acids in food products beginning in January 2006.

Beneficial Fats and Oils. Some fat is essential for health, and fat is essential for healthy development in children. Public attention has mainly focused on the possible benefits or hazards of monounsaturated (MUFA) and polyunsaturated (PUFA) fats.

Polyunsaturated fats are found in safflower, sunflower, corn, and cottonseed oils and fish.
Monounsaturated fats are mostly present in olive, canola, and peanut oils and in most nuts. (Canola is the least saturated of all the fats.) Studies report that replacing carbohydrates with monounsaturated fats improves glucose control after meals and reduces triglycerides in people with type 2 diabetes. Oils are more calorie-dense, however, and such patients should be wary of weight gain.

Researchers are most interested in the smaller fatty-acid building blocks contained in both oils, which may have more specific effects on lipids. Three important fatty acids are the essential fatty acids omega-3, omega-6, and omega-9.

Omega-3 fatty acids are found in fish oil (docosahexaenoic and eicosapentaneoic acids) and plants (alpha-linolenic acid).

Docosahexaenoic (DHA) and Eicosapentaneoic (EPA) Acids. DHA and EPA are found in fish oils, and evidence suggests that they have significant benefits for the heart, including reducing sudden death from heart disease, inflammation, blood clotting factors, blood pressure, and improving triglyceride and HDL levels. Results from a study presented at the 2005 meeting of the American Heart Association suggested that daily EPA supplements plus statin therapy can protect against heart attack, angina, and coronary artery disease. However, although fish and fish oil are good for the heart, patients who have an implantable defibrillator should not take fish oil supplements.

Alpha-linolenic Acid. Alpha-linolenic acid is a plant precursor of DHA, which means the body can convert it to DHA. Sources include canola oil, soybeans, flaxseed, and certain nuts and seeds (walnut, flax, chia and sometimes pumpkin seed). Some, but not all, studies suggest that oils or foods containing these oils may also be heart-protective. Supplements or foods containing these oils may also protest the heart. For example studies have reported heart protection from flaxseed supplements and also from nuts, such as almonds, macadamia, and walnuts. Nuts are high in calories, however.

Omega-6 polyunsaturated fatty acids are found in corn, safflower, soybean, and sunflower oil. PUFA oils containing omega-6 fatty acids constitute most of the oils consumed in the US. Some omega-6 fatty acids are important for health. However, high intake of these fats may be associated with weight gain in the abdomen (the so-called apple shape), a risk factor for heart disease. High consumption is also associated with a higher risk for certain cancer and some chronic diseases.

Omega-9 monounsaturated fatty acids are contained in canola and olive oil, which help protect the heart.

Research suggests that a healthy balance of all these fats may be important and that our current Western diet contains an unhealthy ratio of omega-6 to omega-3 fatty acids (10 to 1). Omega-9 fatty acids may also contain chemicals that block harmful factors found in omega-6 fatty acids. Researchers suggest that the most benefits may be found in mixture of all three fatty acids found in both poly- and monounsaturated oils, but in modest amounts that do not add too many calories.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking, deliver some of the desirable qualities of fat, but do not add as many calories. [See Box Fat Substitutes and Artificial Sweeteners.]

The story on cholesterol found in the diet is not entirely straightforward. The body produces cholesterol naturally or obtains it through meals. Animal-based food products contain cholesterol. High amounts occur in meat, dairy products, egg yolks, and shellfish. (Plant foods, such as fruits, nuts, grains, do not contain cholesterol.) The American Heart Association recommends no more than 300 mg of dietary cholesterol per day for the general population and no more than 200 mg daily for those with high cholesterol.

Antioxidant Vitamins. Vitamins C and E are most studied for their health effects because they serve as antioxidants. Antioxidants are chemicals that act as scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). High intake of foods rich in these vitamins (as well as other food chemicals) have been associated with many health benefits, including prevention of heart problems.

Research on the effects of vitamin supplements on heart disease and diabetes, however, has been mixed. Although some research initially observed favorable effects from vitamin E in preventing blood clots and build-up of plaque on blood vessel walls, most studies found no heart protection from either vitamin E or C supplements. A 2005 Journal of the American Medical Association study found that vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases. In addition, vitamin E had no effect on preventing cancer or heart disease.

Because of the lack of scientific evidence for benefit, the American Diabetes Association does not recommend regular use of vitamin supplements, except for people who have vitamin deficiencies. Researchers, however, are still studying the treatment possibilities of antioxidants. A 2006 study suggested that alpha-lipoic acid, another type of antioxidant, may have promise as a treatment for diabetic peripheral neuropathy, the nerve damage condition that is a common complication of diabetes.

B Vitamins and Folic Acid. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure.

Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks. Several major 2006 studies indicated that while B vitamin supplements help lower homocysteine levels, they have no effect on heart disease. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or who suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took folic acid, B6, and B12 vitamins and those who received placebo. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A doctor should prescribe niacin in order to ensure its safety and effectiveness.

Patients with type 2 diabetes who take metformin (Glucophage) should be aware that this drug can interfere with vitamin B12 absorption. Calcium supplements may help counteract metformin-associated vitamin B12 deficiency.

Most experts recommend salt restriction in people who have high blood pressure. Some people, however, are much more sensitive to harmful effects from salt than others:

People at Risk for Salt-Sensitivity. About half of people with hypertension have blood pressure that reacts significantly to salt. Such people are known as salt-sensitive. Among those at highest risk for salt sensitivity are African Americans, people with diabetes, and elderly people.
Overweight People. Overweight individuals may absorb and retain sodium differently from people with normal weights. One study reported that high sodium intake was associated with an increased risk of heart disease and all-cause mortality in overweight, but not in normal weight, people. Reducing sodium can also help reduce the risk of stroke in people who are overweight.

Simply eliminating table and cooking salt can be beneficial. Salt substitutes, such as Cardia, (containing mixtures of potassium, sodium, and magnesium) are available, but they are expensive. About 75% of the salt in the typical American diet comes from processed or commercial foods, not from food cooked at home, so the benefits of table-salt substitutes are likely to be very modest. Some sodium is essential to protect the heart, but most experts agree that the amount is significantly less than that found in the average American diet. If people cannot significantly reduce the amount of salt in their diets, adding potassium-rich foods might help to restore a healthy balance.

Calcium. Calcium supplements may be important in older patients with diabetes to help reduce the risk for osteoporosis, particularly if their diets are low in dairy products.

Potassium. Evidence strongly indicates that a potassium-rich diet can help achieve healthy blood pressure levels, and that potassium supplements can lower systolic blood pressure by 1.8 m Hg and diastolic blood pressure by 1 mm Hg. In fact, there is some evidence that a potassium-rich diet can reduce the risk of stroke by 22 - 40%. Current guidelines support the use of potassium supplements or enough dietary potassium to achieve 3,500 mg per day for people with normal or high blood pressure (who have no risk factors for excess potassium levels). This goal is particularly important in people who have high sodium intake. The best source of potassium is from the fruits and vegetables that contain them. Potassium-rich foods include bananas, oranges, pears, prunes, cantaloupes, tomatoes, dried peas and beans, nuts, potatoes, and avocados.

However, patients with diabetic nephropathy (kidney disease) and kidney failure need to restrict dietary potassium, as well as phosphorus. Kidney problems can cause potassium overload and medications commonly used in diabetes, (such as ACE inhibitors or potassium-sparing diuretics), also limit the kidney's ability to excrete potassium. No one should take potassium supplements without consulting a doctor. The best source of potassium is from the fruits and vegetables that contain them.

Magnesium. Magnesium deficiency may have some role in insulin resistance and high blood pressure. Research indicates that magnesium-rich diets may help lower type 2 diabetes risk. Whole grain breads and cereals, nuts (almonds, cashews, soybeans), and certain fruits and vegetables (spinach, avocados, beans) are excellent dietary sources of magnesium. Dietary supplements do not provide any benefit. Persons who live in soft water areas, who use diuretics, or who have other risk factors for magnesium deficiency may require more dietary magnesium than others.

Chromium. Some studies have reported an association between deficiencies in the mineral chromium and a higher risk for type 2 diabetes. Studies on fat rats that were given chromium reported improvement in insulin sensitivity and glucose metabolism. Most studies on type 2 patients, however, reported little or no effect on glucose metabolism and some even reported adverse side effects.

Selenium. Selenium, a trace mineral, does not reduce diabetes risk. In fact, it may increase it. In a 2007 study, researchers found that people who took selenium supplements had more than 1.5 times the risk of developing type 2 diabetes as those who did not take the supplements. The higher the blood level of selenium, the greater the risk. An average healthy diet supplies adequate amounts of selenium and there is no need to take dietary supplements.

Zinc. Many patients with type 2 diabetes are also deficient in zinc; more studies are needed to establish the benefits or risks of taking supplements. Zinc has some toxic side effects, and some studies have associated high zinc intake with prostate cancer.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Traditional herbal remedies for diabetes include bitter melon, fenugreek, and Gymnema sylvestre. These herbs may have properties that help lower blood sugar. However, there have been few well-designed studies and there is not enough evidence to recommend them for prevention or treatment of diabetes.

Several recent preliminary studies suggest that cinnamon may help improve blood sugar and lipid levels. One small study found beneficial effects for people with type 2 diabetes who took between 1 - 6 grams (equivalent to 0.25 - 1.25 teaspoons) of cinnamon each day.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. In 2006, the FDA and Federal Trade Commission (FTC) launched a crackdown on these scams. The FDA and FTC warn patients with diabetes not to be duped by bogus and unproven remedies.

Water. Many heart risk factors, especially those associated with blood clotting, are elevated with dehydration. In one study, drinking five or more glasses of water a day was significantly associated with a lower risk for fatal heart events than drinking two or fewer glasses a day.

Alcohol. A number of studies have found that light to moderate intake of alcohol may provide protection from heart disease and type 2 diabetes. Some research suggests that alcohol has anti-inflammatory properties that protect arteries from injury. Red wine in particular may have specific benefits for people with type 2 diabetes. It has strong antioxidant effects that benefit the heart. Some evidence also suggests that red wine may improve insulin sensitivity and reduce blood glucose levels and may even protect against type 2 diabetes. The American Diabetes Association recommends limiting alcoholic beverages to 1 drink per day for non-pregnant adult women and 2 drinks per day for adult men.

Tea. Although it contains caffeine, tea, both black and green, is often cited for its health benefits. Green tea is especially is rich in chemicals that offer protection against damaging forms of LDL. In one study, for example, higher intake, particularly by women, was associated with a lower risk for severe coronary artery disease. Black tea has also been associated with heart health. In one study oolong tea, a partially fermented tea, was specifically associated with lower blood sugar levels in patients with type 2 diabetes.

Coffee. Many studies have noted an association between coffee consumption and reduced risk for developing type 2 diabetes. A 2006 study of 29,000 postmenopausal women confirmed this reduced risk. Compared to non-coffee drinkers, women who drank at least 6 cups a day of coffee (either regular or decaf) were 22% less likely to develop type 2 diabetes. Decaffeinated coffee was even more beneficial -- women who drank at least 6 cups a day of decaf were 33% less likely to develop diabetes than women who did not drink coffee. Researchers are still not certain how coffee protects against diabetes. Neither the caffeine in coffee nor the mineral magnesium have a preventive effect. It may be that coffee contains antioxidant properties that protect the pancreas’ insulin-producing cells.

Weight Control for Type 2 Diabetes

The American Diabetes Association recommends that patients aim for a small but consistent weight loss of ½ - 1 pound per week. Most patients should follow a diet that supplies at least 1,000 - 1,200 kcal/day for women and 1,200 - 1,600 kcal/day for men.

Even modest weight loss can reduce the risk factors for heart disease and diabetes. There are many approaches to dieting and many claims for great success with various fad diets. They include calorie restriction, low-fat/high-fiber, or high protein and fat/low carbohydrates. Some evidence suggests that people may respond differently to specific diets depending on whether their weight is overly distributed around the abdomen.

Lifelong changes in eating habits, physical activity, and attitudes about food and weight are essential to weight management. Unfortunately, although many people can lose weight initially, it is very difficult to maintain weight loss. People with type 2 diabetes may have a particularly difficult time. Here are some general suggestions that may be helpful:

Start with realistic goals. When overweight people achieve even modest weight loss they reduce risk factors in the heart. Ideally, overweight patients should strive for 7% weight loss or better, particularly people with type 2 diabetes.
A regular exercise program is essential for maintaining weight loss. If there are no health prohibitions, choose one that is enjoyable. Check with a doctor about any health consideration. [See In-Depth Report #29: Exercise.]
Hunger pangs should not be taken as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat, and track calories carefully. Studies on weight control that depend on self-reporting of food intake frequently reveal that subjects badly misjudge how much they eat (typically underestimating high-calorie foods and overestimating low-calorie foods). In one study, even dietitians underreported their calorie intake by 10%. People who do not carefully note everything they eat tend to take in excessive calories when they believe they are dieting.
For patients who cannot lose weight with diet alone, effective weight-loss medications are now available, including orlistat (Xenical) and sibutramine (Meridia). Orlistat may have particular benefits for patients with type 2 diabetes. This drug may delay or even prevent the onset or progression of diabetes. It may also improve cholesterol levels, regardless of weight loss. A non-prescription form of orlistat, Alli, is now available. Sibutramine is also helpful in weight loss but should not be used by patients with high blood pressure or kidney or liver problems.
Once a person has lost weight, maintenance is required. To maintain a healthy weight, make careful decisions about how many calories you consume in food and how many calories you expend through physical activity. Such thinking will eventually become automatic.
A procedure known as bariatric surgery has been very helpful in producing rapid weight loss and improving insulin and glucose levels in people with diabetes.

Even repeated weight loss failure is no reason to give up. [See In-Depth Report #53: Weight control and diet.]

Calorie restriction has been the cornerstone of obesity treatment. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels.

The standard dietary recommendations for losing weight are:

As a rough rule of thumb, 1 pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine the daily calorie requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance a 50-year-old moderately active woman who wants to maintain a weight of 135 pounds and is mildly active might need only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might need 25 calories per pound (2,025 calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Avoid saturated fats (found in animal products).

Heart-Healthy Diets

In 2006, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balance calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 - 90 minutes, of daily exercise.)
Consume a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choose whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Consume fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish -- such as salmon, mackerel, and sardines -- are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to reduced risk of sudden death and death from coronary artery disease.
Limit daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Use little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Limit beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey).
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 2 drinks per day for men and 1 drink per day for women.

[See In-Depth Report #43: Heart-healthy diet.]

Dietary guidelines from the National Cholesterol Education Program recommend:

Choose five or more servings of fresh fruits and vegetables and six or more servings of whole grains and legumes. Soluble fiber is preferred (from cereal grains, beans, peas, legumes, and many fruits and vegetables).
Fats can be up to 35% of daily calories, but no more than 7% should be from saturated fat. (People with high triglycerides or low HDL or both may need a higher fat intake.) Choose fats containing unsaturated fatty acids (from vegetables, fish, legumes, and nuts). Choose margarines containing sterols or stanols (such as Benecol or Take Control). Avoid trans fatty acids found in commercial products.
Protein choices should be fat-free and low-fat milk products, fish, legumes, skinless poultry, and lean meats.
Limit cholesterol intake to less than 200 mg per day.
Maintain healthy body weight and a healthy level of physical fitness.

The Mediterranean diet is rich in heart-healthy fiber and nutrients, including omega-3 fatty acids and antioxidants. The diet consists of fruits, vegetables, and unsaturated "good" fats, particularly olive oil. Olive oil has been associated with lower blood pressure, a lower risk for heart disease, and other benefits for people with type 2 diabetes.

There are several variations to the Mediterranean diet, but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet's main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season foods with garlic, onions, and herbs.
Use virgin olive oil.

Low-carb diets, such as South Beach, The Zone, and Sugar Busters, rely on a concept called the "glycemic index (GI)," which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include white bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans.

A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women. However, another 2006 study suggested that low-glycemic index diets that are high in carbohydrates can also promote weight loss and reduce body fat.

A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride levels and raise HDL (“good”) cholesterol levels, they also raised overall and LDL (“bad”) cholesterol levels. A 2007 Journal of the American Medical Association study that compared four different diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet helped raise HDL levels, and reduce triglyciderides, but had no effect on LDL levels nor insulin or glucose measurements. Women who followed the Atkins diet also had improved blood pressure compared to patients on the other diets. The Atkins diet resulted in slightly better weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors. Some experts think that the main finding from this study is that even a moderate weight loss can help improve heart health.

Although low-carbohydrate diets may produce good short-term weight loss, they do not appear to help patients maintain weight loss in the long term. The American Diabetes Association does not recommend low-carb diets (less than 130 g of carbohydrates per day) for treatment of overweight and obesity.

Dietary guidelines recommend keeping total fat intake to 25 - 35% of total daily calories, with saturated fat less than 7% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories.

In 2006, the largest study to date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 - 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated and omega-3 polyunsaturated) and bad fats (saturated and trans fats).

Another 2006 study indicated that low-fat, vegan diets may help improve glycemic control and increase insulin sensitivity. The higher fiber content of these diets, plus lower intake of total and saturated fat, may account for some of these benefits. A vegan diet eliminates all meat and dairy products.

The DASH diet (Dietary Approaches to Stop Hypertension) is proven to help lower blood pressure. Results are sometimes seen within a few weeks. Restricting sodium improves results. The diet appears to have antioxidant effects and may help lower LDL cholesterol levels, although beneficial HDL levels also decline. This diet is not only rich in important nutrients and fiber but also includes foods that contain far more electrolytes, potassium (4,700 mg/day), calcium (1,250 mg/day), and magnesium (500 mg/day) than are found in the average American diet.

The DASH diet recommends:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal).
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include dairy products that are non- or low-fat. Low-fat dairy products appear to be especially beneficial for lowering systolic blood pressure.)
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. In one study people who increased their intake of fruits and vegetables experienced a drop in blood pressure after 6 months. Many of these foods are rich in potassium, fiber, or both, which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with more protein or monounsaturated fats may help reduce heart disease risk factors. [See In-Depth Report #14: High blood pressure.]

Diabetic Exchange Lists

The objective of using diabetic exchange lists is to maintain the proper balance of carbohydrates, proteins, and fats throughout the day. Patients should meet with a dietician or diabetes nutrition expert for help in learning this approach.

In developing a menu, patients must first establish their individual dietary requirements, particularly the optimal number of daily calories and the proportion of carbohydrates, fats, and protein. The exchange lists should then be used to set up menus for each day that fulfill these requirements.

The following are some general rules:

The diabetic exchanges are six different lists of foods grouped according to similar calorie, carbohydrate, protein, and fat content; these are starch/bread, meat, vegetables, fruit, milk, and fat. A person is allowed a certain number of exchange choices from each food list per day.
The amount and type of these exchanges are based on a number of factors, including the daily exercise program, timing of insulin injections, and whether or not an individual needs to lose weight or reduce cholesterol or blood pressure levels.
Foods can be substituted for each other within an exchange list but not between lists even if they have the same calorie count.
In all lists (except in the fruit list) choices can be doubled or tripled to supply a serving of certain foods. (For example 3 starch choices equal 1.5 cups of hot cereal or 3 meat choices equal a 3-ounce hamburger.)
On the exchange lists, some foods are "free." These contain less than 20 calories per serving and can be eaten in any amount spread throughout the day unless a serving size is specified.

The following are the categories on exchange lists:

Starches and Bread. Each exchange under starches and bread contains about 15 grams of carbohydrates, 3 grams of protein, and a trace of fat for a total of 80 calories. A general rule is that a half-cup of cooked cereal, grain, or pasta equals one exchange. One ounce of a bread product is 1 serving.

Meat and Cheese. The exchange groups for meat and cheese are categorized by lean meat and low-fat substitutes, medium-fat meat and substitutes, and high-fat meat and substitutes. Use high-fat exchanges a maximum of 3 times a week. Fat should be removed before cooking. Exchange sizes on the meat list are generally 1 ounce and based on cooked meats (3 ounces of cooked meat equals 4 ounces of raw meat).

Vegetables. Exchanges for vegetables are 1/2 cup cooked, 1 cup raw, and 1/2 cup juice. Each group contains 5 grams of carbohydrates, 2 grams of protein, and 2 - 3 grams of fiber. Vegetables can be fresh or frozen; canned vegetables are less desirable because they are often high in sodium. They should be steamed or cooked in a microwave without added fat.

Fruits and Sugar. Sugars are included within the total carbohydrate count in the exchange lists. Sugars should not be more than 10% of daily carbohydrates. Each exchange contains about 15 grams of carbohydrates for a total of 60 calories.

Milk and Substitutes. The milk and substitutes list is categorized by fat content similar to the meat list. A milk exchange is usually 1 cup or 8 ounces. Those who are on weight-loss or low-cholesterol diets shoudl follow the skim and very low-fat milk lists -- while avoiding the whole milk group. Others should use the whole milk list very sparingly. All people with diabetes should avoid artificially sweetened milks.

Fats. A fat exchange is usually 1 teaspoon, but it may vary. People, of course, should avoid saturated and trans fatty acids and choose polyunsaturated or monounsaturated fats instead.


Calories	1,200	1,500	1,800	2,000	2,200
Starch/Bread	5	8	10	11	13
Meat	4	5	7	8	8
Vegetable	2	3	3	4	4
Fruit	3	3	3	3	3
Milk	2	2	2	2	2
Fat	3	3	3	4	5

Exercise

Sedentary habits, especially watching TV, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise, even of moderate intensity (such as brisk walking), improves insulin sensitivity and may play a significant role in preventing type 2 diabetes -- regardless of weight loss. An important study reported a 58% lower risk for type 2 diabetes in adults who performed moderate exercise for as little as 2.5 hours a week.

Aerobic Exercises. Aerobic exercise has significant and particular benefits for people with diabetes. Regular aerobic exercise, even of moderate intensity, improves insulin sensitivity. People with diabetes are at particular risk for heart disease, so the heart-protective effects of aerobic exercise are especially important. Moderate exercise protects the heart in people with type 2 diabetes, even if they have no risk factors for heart disease other than diabetes itself. (In general, patients with diabetes should aim for a heart rate target of 55 - 85% of their maximum heart rate when exercising.)

Strength Training. Strength training, which increases muscle and reduces fat, may also be helpful for people with diabetes.

Some Precautions for People with Diabetes Who Exercise. The following are precautions for all people with diabetes, both type 1 and type 2:

Because people with diabetes are at higher than average risk for heart disease, they should always check with their doctors before undertaking vigorous exercise. For fastest results, frequent high-intensity (not high-impact) exercises are best for people who are cleared by their doctors. For people who have been sedentary or have other medical problems, lower-intensity exercises are recommended.
Strenuous strength training or high-impact exercise is not recommended for people with uncontrolled diabetes. Such exercises can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet.

Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before embarking on a workout program:

Monitor glucose levels before, during, and after workouts (glucose levels swing dramatically during exercise).
Avoid exercise if glucose levels are above 300 mg/dl or under 100 mg/dl.
Inject insulin in sites away from the muscles used during exercise; this can help avoid hypoglycemia.
Drink plenty of fluids before and during exercise; avoid alcohol, which increases the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates prior to exercise, but may need to take an extra dose of insulin after exercise (stress hormones released during exercise may increase blood glucose levels).
Wear good, protective footwear to help avoid injuries and wounds to the feet.

Some blood pressure drugs can interfere with exercise capacity. Patients who use blood pressure medication should consult their doctors on how to balance medications and exercise. Patients with high blood pressure should also aim to breathe as normally as possible during exercise. Holding the breath can increase blood pressure. [See In-Depth Report #29: Exercise.]

Chronic stress has been associated with the development of insulin resistance, a primary factor in diabetes. Stress can also worsen existing diabetes by impairing the patient's ability to manage the disease effectively. Stress-relieving techniques include meditation, biofeedback, relaxation response, and yoga. One study reported that yoga helped patients with type 2 diabetes reduce their need for oral medications. Studies have also indicated that yoga and Tai Chi (an ancient Chinese exercise involving slow relaxing movements) may lower blood pressure almost as well as moderate-intensity aerobic exercises. [See In-Depth Report #31: Stress.]

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.jdrf.org -- Juvenile Diabetes Research Foundation
www.kidney.org -- National Kidney Foundation
www.joslin.org -- Joslin Diabetes Center
www.eatright.org -- American Dietetic Association
www.nal.usda.gov/fnic -- Food and Nutrition Information Center
www.gourmetconnection.com/diabetic -- Diabetic Gourmet Magazine

References

American Diabetes Association. Nutrition recommendations and interventions for diabetes: A position statement of the American Diabetes Association. Diabetes Care. 2007 Jan;30 Suppl 1:S48-65.

American Heart Association Nutrition Committee; Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006 Jul 4;114(1):82-96. Epub 2006 Jun 19.

Barnard ND, Cohen J, Jenkins DJ, Turner-McGrievy G, Gloede L, Jaster B, et al. A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes. Diabetes Care. 2006 Aug;29(:1777-83.

Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77.

Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007 Feb 10;334(7588):299. Epub 2007 Jan 19.

Halton TL, Willett WC, Liu S, Manson JE, Albert CM, Rexrode K, et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med. 2006 Nov 9;355(19):1991-2002.

Lindstrom J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson JG, Hemio K, et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet. 2006 Nov 11;368(9548):1673-9.

Liu S, Choi HK, Ford E, Song Y, Klevak A, Buring JE, et al. A prospective study of dairy intake and the risk of type 2 diabetes in women. Diabetes Care. 2006 Jul;29(7):1579-84.

McMillan-Price J, Petocz P, Atkinson F, O'Neill K, Samman S, Steinbeck K, et al. Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Arch Intern Med. 2006 Jul 24;166(14):1466-75.

Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H. Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med. 2007 May 14;167(9):956-65.

Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 2007 Jul 9; [Epub ahead of print]

Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM. Risk factors of vitamin B(12) deficiency in patients receiving metformin. Arch Intern Med. 2006 Oct 9;166(18):1975-9.

Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006 Nov;29(11):2365-70.

Review Date:
7/20/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Melanoma and other skin cancers

FitSugar — Wed, 08 Oct 2008 17:35:01 -0700

In This Report

Highlights
Introduction
Melanoma
Nonmelanoma Skin Cancer
Precancerous Skin Condition...
Causes
Risk Factors
Prevention
Screening
Diagnosis
Staging
Treatment for Melanoma
Treatment for Nonmelanoma S...
Prognosis
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Risk factors

According to a report in the Archives of Dermatology, marathon runners are more likely than the general population to develop skin changes that increase the risk for melanoma.

Prevention

A study published in The Lancet indicates that the best ways to avoid sun damage are to reduce the time you spend in the sun and to wear a hat and clothing to protect as much of your skin as possible. Fabrics that are thick and tightly woven offer the best protection.

The U.S. Food and Drug Administration has approved a new type of sunscreen that may more effectively block UVA than products currently available in the United States. UVA light penetrates the skin deeper than other forms of sunlight. Exposure to UVA is believed to contribute to skin cancers. The new sunscreen, called Anthelios SX, is available over the counter.

Screening

A study published in CANCER has shown that older men are more likely to undergo a whole body skin exam if they understand their personal risk factors for melanoma and know where to go to have such an exam. The study emphasizes the importance of skin cancer awareness and education.

One-time melanoma screening for adults over age 50 seems to be as cost-effective as other nationally recommended cancer screening programs, according to a report in the Archives of Dermatology. The study authors also found that screening brothers and sisters of someone with melanoma every 2 years may also be cost-effective.

Diagnosis

Dermatologists detect melanoma earlier than other health care providers, according to an article in the Archives of Dermatology. The earlier melanoma is diagnosed and treated, the greater your chances of survival.

Introduction

Skin cancer is cancer that starts in the skin. Skin cancers are divided into two major groups:

Nonmelanoma, which includes basal cell cancer and squamous cell cancer
Melanoma, the deadliest form of skin cancer

Different skin cancers start in different layers or cells of the skin. To understand how skin cancer develops, it is useful to know something about the skin.

The Skin. The skin is the largest organ in the body and consists of layers.

The outermost layer of the skin is called the epidermis. It is only about 20 cells deep, roughly as thick as a sheet of paper.
The dermis ranges in thickness from 1 - 4 millimeters (about 1/32 - 1/8 inch). The dermis contains tiny blood and lymph vessels, which increase in number deeper in the skin.

The skin is the largest organ of the body. The skin and its derivatives (hair, nails, sweat, and oil glands) make up the integumentary system. One of the main functions of the skin is protection. It protects the body from external factors, such as bacteria, chemicals, and temperature. The skin contains secretions that can kill bacteria, and the pigment melanin provides a chemical pigment defense against ultraviolet light that can damage skin cells. The skin also helps control body temperature.

Melanocytes. A layer of cells between the epidermis and the dermis, called melanocytes, produces a brown-black skin pigment ( melanin) that determines skin and hair color. Melanin also helps protect against the damaging rays of the sun.

As a person ages, melanocytes often proliferate, forming concentrated clusters that appear on the surface as small, dark, flat, or dome-shaped spots, which are usually harmless moles or liver spots.

When cell proliferation occurs in a controlled and contained manner, the resulting lesion is benign and is commonly referred to as a mole or nevus.
Sometimes, however, pigment cells grow out of control and become a cancerous and life-threatening melanoma.

Click the icon to see an image of melanin.

Melanoma

At first, melanoma cells are found in the epidermis and top layers of the dermis. However, once they grow downward into the dermis, the cancer can come into contact with lymph and blood vessels. The thicker the melanoma, the greater the likelihood that it could spread to distant sites.

Removal of the lesion before it reaches the deeper layers of the skin is important for achieving a cure.

Superficial Spreading Melanoma. Superficial spreading melanoma is the most common and most curable. It is flat, asymmetrical, unevenly colored, and usually grows outward across the surface of the skin.

Nodular Melanoma. Nodular melanoma appears as a fast-growing brown or black lump, and its characteristics do not always fit the definitions described above. It is important to check for this type of melanoma because it is associated with an outbreak of other tumors.

Lentigo Maligna. Lentigo maligna (sometimes called Hutchinson's freckle) usually occurs in elderly people and is marked by flat, mottled, tan-to-brown freckle-like spots with irregular borders. These lesions often appear on the face or other sun-exposed areas and typically enlarge slowly for 5 - 15 years before cancer appears.

Acral Lentiginous Melanoma. Although rare, acral lentiginous melanoma is the most common melanoma among African and Asian populations. It commonly appears as a dark patch on the palms, soles, fingers, toes, under fingernails or toenails, or in mucous membranes.

Melanoma cells usually spread first through the lymph vessels or glands. Melanoma cells can also spread by way of blood vessels to various organs, spreading cancer to the liver, lungs, brain, or other sites.

Melanomas tend to grow in stages:

Most melanomas tend to be flat initially and spread laterally across the skin surface as they grow. At this early stage, which can last 1 - 5 years or longer, removal of the growth has an excellent chance of curing the melanoma. Still, there is a chance that some of these melanomas are invasive, and they should be treated aggressively.
Lesions that become raised or dome-shaped over at least part of their surface indicate that downward growth has occurred. In some cases, this growth is very rapid, occurring over a period of weeks to months.

Any suspicious lesion should be checked immediately, particularly if it has grown quickly or is partially flat and partially raised.

Common sites of melanoma in men include:

Head
Middle of the body (trunk)
Neck

Common sites of melanoma in women include:

Arms
Legs

However, any area of the skin may be affected. You may not notice melanomas if they appear on areas that are difficult to examine, such as the scalp or the back.

Less common sites for melanoma include:

Fingers
Palms
Soles of the feet
Genitals
Lips
Under the fingernails or toenails

The presence of a dark lesion under the nail that runs into the adjoining skin and doesn't heal may signal melanoma.

Rarely, melanomas appear in the mouth, in the iris of the eye, or in the retina at the back of the eye, where they may be detected during dental or eye examinations.

Click the icon to see an image of melanoma.

Nonmelanoma Skin Cancer

The two other types of skin cancers are called basal cell cancer and squamous cell cancer. These are nonmelanoma skin cancers.

Basal cell cancer starts in the lowest part of the epidermis in round cells called basal cells. Basal cell is the most common form of skin cancer. It occurs in about 800,000 - 900,000 people every year.

Basal cell cancer usually develops later in life in areas that have received the most sun exposure, such as the head, neck, back, and especially the nose. However, some basal cell cancers appear in areas not exposed to the sun.

Basal cell cancers have many different appearances:

They usually appear as a round area of thickened skin that does not change color or cause pain or itching.
Very slowly, the lesion spreads out and develops a slightly raised edge, which may be translucent and smooth. Infrequently, basal cell cancers resemble malignant melanomas in color.
Eventually, the center becomes hollowed and covered with a thin skin, which can become sore and open.
A form known as aggressive-growth basal cell cancer resembles a scar with a hard base. This type is more likely to spread and must be treated very aggressively.

Basal cell cancer is a cancerous (malignant) skin tumor involving basal skin cells. Basal cell skin cancers usually occur on areas of skin that are regularly exposed to sunlight or other ultraviolet radiation. Once a suspicious lesion is found, a biopsy is needed to prove the diagnosis of basal cell cancer. Treatment varies depending on the size, depth, and location of the cancer.

Basal cell cancers are sometimes hard to tell from benign skin conditions. For instance, occasionally they arise in unexposed skin, where they may mimic an ordinary mole, cyst, or pimple. They may be particularly difficult to distinguish from benign cysts when they occur near the eyes.

Usually, basal cells grow slowly. They are rarely deadly. Most basal cell cancers need not be treated as an emergency, although late treatment can cause disfigurement, so they should be removed as early as possible.

Basal cell cancers that are most likely to spread include those that are larger than 1 centimeter, scar-like, and those located on the cheek, nose, neck, earlobe, eyelid, or temple.

Some studies have shown that people with basal cell cancer may be at higher risk for second cancers, including melanoma, cancer of the lip, salivary glands, larynx, lung, breast, and kidney, and non-Hodgkin's lymphoma. Those at higher risk for such cancers appear to be men and anyone diagnosed before 60 with basal cell cancer.

Squamous cell cancer develops from flat, scale-like skin cells called keratinocytes, which lie under the top layer of the epidermis. Most squamous cell cancers occur on sun-exposed areas, especially the forehead, temple, ears, neck, and back of the hands. People who have spent considerable time sunbathing may develop them on their lower legs.

Types of squamous cell cancer:

Squamous cell carcinoma in situ (also called Bowen's disease) is the earliest form of this type of cancer. The cancer has not spread. Cancer areas appear as large reddish patches (often over 1 inch) that are scaly and crusted.
Invasive squamous cell carcinoma is highly likely to spread (metastasize). The skin cancer lesions can grown rapidly (over months) or slowly (over years). Eventually they become ulcerated.

Click the icon to see an image of squamous cell cancer.

Prompt treatment is desirable because squamous cell cancers are more likely to spread to local lymph nodes than basal cell cancer. Squamous cell cancers most likely to spread include:

Deep lesions, those larger than 2 cm in diameter, or patches with poorly defined margins
Recurrent lesions
Squamous cell cancer on neck, earlobe, eyelid, lips, or temple
Squamous cell cancer that develops in ulcers
Squamous cell cancer that develops on skin areas that have been previously treated with radiation or exposed to cancer-killing chemicals

People with squamous cell cancers seem to be at higher risk for other cancers, including melanoma, lung cancer, non-Hodgkin's lymphoma, bladder cancer, leukemia, testicular and prostate cancer in men, and breast cancer in women.

Precancerous Skin Conditions

Actinic (Solar) Keratosis. Actinic keratosis (also called solar keratosis) is a precancerous skin lesion caused by too much sun exposure. Such lesions can turn into cancer, but not always.

Actinic keratoses occur after years of sun exposure. They appear predominantly on sun-exposed skin, such as the face, neck, back of the hands and forearms, upper chest, and upper back. Men may develop keratoses along the rim of the ear.

Actinic keratoses have the following characteristics:

Lesions typically occur on the surface of the skin and have a sandpaper-like feel. In fact, they are sometimes more easily felt than seen.
Most lesions are pink and even flesh-colored. Some are red or brown, scaly, and tender. At times, they can resemble melanomas; even dermatologists may have trouble telling the two apart.
They can range in size from microscopic to several inches in diameter.

Keratoacanthomas. Keratoacanthomas closely resemble squamous cell cancers, but they are not malignant. The majority occur in sun-exposed skin, usually on the hands or face. They are typically skin colored or slightly red when they first develop, but their appearance typically changes:

In the early stages, keratoacanthomas are smooth, red, and dome shaped.
Within a few weeks, they can grow rapidly, usually to 1 or 2 centimeters. Some reach the size of a quarter in less than a month and can be rather disfiguring.
They eventually stop growing and become crater-like with a surrounding outer rim of tissue and sometimes have a crusty interior.

Most will spontaneously get better within 1 year, but they almost always scar after healing. Also about 25% develop into squamous cell cancers, most frequently in older people and in sun-exposed areas. Removal by surgery (sometimes by radiation) is recommended. They may also be treated with 5-fluorouracil, either as a cream or injections.

Causes

You cannot overestimate the role of the sun as the most important cause of prematurely aging skin (called photoaging ) and skin cancers.

Long-term repetitive and cumulative exposure to sunlight appears to be responsible for the vast majority of undesirable consequences of aging skin, including basal cell and squamous cell cancers.

Melanoma is more likely to be caused by intense exposure to sunlight in early life.

UVA and UVB Radiation. When sunlight penetrates the top layers of the skin, ultraviolet (UVA or UVB) radiation strikes the DNA inside the skin cells and damages it.

UVB is the main type of radiation responsible for sunburns. It primarily affects the outer skin layers. This type of ultraviolet light is most intense at midday when sunlight is brightest.
UVA penetrates more deeply and efficiently. Unlike UVB, window glass does not filter out UVA rays.

Damaging Effects of UV Radiation. Both UVA and UVB rays cause damage, including genetic injury, wrinkles, lower immunity against infection, aging skin disorders, and cancer, although the mechanisms are not yet fully clear. The following are some ways in which cancer may develop and some defensive actions that the skin uses to defend itself against DNA damage.

Oxidation and Antioxidants. The effects of UV radiation are implicated in the production of oxidants, also called free radicals. Free radicals are unstable molecules produced by normal chemical processes in the body that, in excess, can damage the body's cells and even alter the DNA. This contributes to the aging process and sometimes to cancer.
Defective DNA Repair and Protective Enzymes. Some skin cancers are caused by a breakdown in the body's mechanisms that help repair DNA damage. For example, xeroderma pigmentosum (XP) is a rare genetic disease in which the body cannot repair damage caused by ultraviolet light. Normally, a number of enzymes in the skin help protect against this damage.
Breakdown of Immune Protection. Specific immune factors protect the skin, including white blood cells called T lymphocytes and specialized skin cells called Langerhans cells. These immune system cells attack developing cancer cells at the very earliest stages. However, certain substances in the skin, particularly a chemical called urocanic acid, can suppress such immune factors when exposed to sunlight.

Defective Cell Death (Apoptosis). Apoptosis is the last defense of the immune system. It is a natural process of cell-suicide, which occurs when cells are very severely damaged. Apoptosis in the skin kills off cells harmed by UVA so that they do not turn cancerous. The peeling after sunburn is the result of these dead skin cells. However, some gene defects or other factors interfere with apoptosis. If this occurs, damaged cells can continue to spread, resulting in skin cancer.

A number of genetic factors are being investigated for their role in melanomas, including inherited genes and genetic defects that are acquired from environmental assaults (particularly sunlight).

Mutations in Genes that Regulate Cell Growth. Noninherited mutations in a number of genes that block tumor growth or other cell-protecting properties may account for cancerous changes in moles and for aggressive melanomas. The following are some examples.

Important studies have now identified a mutation in the BRAF gene that appears to be the most common event in the process that leads to melanoma. Some researchers have observed mutations in 66% of malignant melanomas. Researchers hope that agents that block this gene may be a viable treatment path.
P16 is a tumor suppressive gene that may be abnormal in some melanoma cases.
Genetic mutations that regulate Ku70 and Ku80 proteins may disrupt processes that repair strands of DNA.
Researchers are also studying mutations in a gene that encodes for a substance called epidermal growth factor (EGF). EGF plays a role in skin cell growth and wound healing, and may account for many sporadic (non-inherited) cases of melanoma.
Of further interest are mutations in genes that regulate Fas proteins, which are involved in apoptosis, a natural process of cell self-destruction. When apoptosis goes awry in melanoma cells, proliferation can become rampant.

CDKN2A Mutations. Mutations in a gene regulator called CDKN2A are the most common causes of inherited melanoma, which is still very uncommon. Mutations in this gene also appear in non-inherited cases of melanoma. Genetic tests are being developed for CDKN2A, although it is not clear if knowing the results of the test would benefit people carrying the gene.

Variations in the Melanocortin-1 Receptor Gene. One study found that the greater the number of variations from normal in a gene called the melanocortin-1 receptor gene, the greater the risk for melanoma. The gene plays an important role in determining if a person has red hair, fair skin, and sensitivity to UV radiation. Interestingly, people who had olive and darker skin and who carried one or more variations of the gene had a higher than average risk for melanoma.

Aging may weaken the body's ability to fend off impending cancers, including melanomas. As a person ages, they lose Langerhans cells that help fight off early skin cancers. The number of these immune cells decreases with age, possibly setting the stage for skin cancers in later life.

Risk Factors

In the United States, the rate of melanoma is rising more rapidly than any other cancer. According to the American Cancer Society, about 59,940 persons will be diagnosed with melanoma in 2007. More than 8,000 people will die from the cancer.

Survival rates have been improving, however, and the increase in melanomas has occurred principally with thin, less aggressive forms of the disease. Some experts believe this is due to the increased awareness from effective public programs and earlier diagnosis.

A risk factor is anything that increases your chance of getting a disease. The following factors increase your risk for skin cancer:

Age over 40
Being male
Fair skin
Too much exposure to sunlight and ultraviolet radiation
Personal history of skin cancer
Family history of skin cancer
Smoking
Certain chronic or severe skin problems
Certain medical conditions or treatments that affect your immune system
Exposure to chemicals or radiation

Melanoma in Adults. Melanoma is most common in people over 40, and the incidence increases significantly as people get older. Before age 40, melanomas are slightly more common in women than men, but after age 40 men are more often affected. Men are also more likely to have invasive and fatal melanoma than are women, although some research suggests that the higher rates are only because men fail to seek a diagnosis of suspicious skin changes before they become dangerous. The rate in women levels off somewhat between age 45 and 60; researchers speculate that menopause could have some sort of protective effect during those years.

Melanoma in Children. Melanoma is rare in children under age 10. Among children ages 10 - 14 the incidence is only 0.3 per 100,000. Between ages 14 - 19, it is still very rare, 1.3 per 100,000. Parents, then, should not be unduly alarmed by every minor skin imperfection in their children. Nevertheless, melanoma is as serious in children as in adults, and early detection is still critical.

Skin cancer is associated with both duration and intensity of sun exposure. Risk of melanoma increases with excessive sun exposure during the first 10 - 18 years of life. Sunburns are also dangerous, with five or more sunburns doubling the risk of developing cancer. Cancer typically arises many years later.

Marathon runners are more likely than the general population to develop skin changes that increase your risk for melanoma. That's because marathon runners spend a lot of time outdoors. The study findings are published in the Archives of Dermatology.

Tanning Devices. Tanning beds and sunlamps increase the risk for developing melanoma, according to a 2005 review of epidemiologic studies. Previous findings have suggested that women who use tanning devices more than once a month significantly increase their melanoma risk. Women in their 20s, as well as blondes and redheads, are especially at risk.

Ethnic Groups and Complexion. People with light skin, blue, gray, or green eyes, red or blond hair, and lots of freckles are at highest risk for developing melanoma. The risk increases for those who are easily sunburned and rarely tan, particularly if they live close to the equator where sunlight is most intense. Darker ethnic groups or those with swarthy complexions are not immune, however.

Experts have devised a classification system for skin phototypes (SPTs) based on the sensitivity to sunlight. It ranges from SPT I (lightest skin plus other factors) to IV (darkest skin). Tanning and Sunburn Risk People with skin types I and II are at highest risk for photoaging skin diseases, including cancer. It should be noted, however, that premature aging from sunlight can affect people of all skin shades.


Skin Type	Tanning and Burning Risk
I	Always burns, never tans, sensitive to sun exposure.
II	Burns easily, tans minimally.
III	Burns moderately, tans gradually to light brown.
IV	Burns minimally, always tans well to moderately brown.
V	Rarely burns, tans profusely to dark.
VI	Never burns, deeply pigmented, least sensitive.

Australia has the highest melanoma rate in the world. In the United States the rate is highest in California, Florida, and Texas. The disease is by no means limited to such sunny states and countries, however. In general, the risks are highest in regions where the population tends to be blonde and fair-skinned. Norway, for example, has had the highest rate of melanoma in Europe, and rates are soaring in the UK, particularly among men, perhaps because Britons are increasingly vacationing in sunny climates.

Melanoma. Individuals who have been diagnosed with melanoma are at increased risk for a second primary melanoma. According to one 2003 study, the risk over time for developing a second melanoma is 1% in the first year after diagnosis, 2.1% at 5 years, 3.2% at 10 years, and 5.3% at 20 years. The risk is especially higher in older men and in those with first melanomas on the upper body and face.

People with family members who have or had melanoma should also be considered at high risk and examined on a regular basis.

Nonmelanoma Skin Cancers. Nonmelanoma skin cancers, including basal and squamous cell carcinomas, increase the risk of dying from other cancers, including melanoma itself, lung cancer, non-Hodgkin's lymphoma, bladder cancer, and leukemia as well as testicular and prostate cancers (in men) and breast cancer (in women).

Psoriasis. Psoriasis increases the risk for squamous cell carcinoma, but studies conflict on whether it has any effect on melanoma. One study, in fact, reported a lower risk. Nevertheless, there is some evidence that long-term treatment for psoriasis using UVA radiation (PUVA) may increase the risk for melanoma. In one study, there was a significantly higher risk even with relatively few treatments. In one study, invasive melanoma had occurred in 2.8% of patients 15 or more years after the initial treatment.

Moles (Nevi) and Other Dark Blemishes. Certain moles and dark blemishes increase the risk for skin cancer. Any mole ( nevus) or other blemish that seems new, changing, or unusual in any way should be evaluated by a health care professional.

Some specific moles or dark blemishes that are risk factors for melanoma include:

Freckles. Freckles typically appear in children on sun-exposed areas and are usually evenly brown or tan. The more freckles a person develops as a child, the greater the risk for melanoma in adulthood.
Dysplastic (or Atypical) Nevi. About 30% of the population has moles called dysplastic nevi, or atypical moles. They are larger than ordinary moles (most are 5 mm across, about the size of a pencil eraser, or larger), have irregular borders, and are various shades or colors. Individuals who have dysplastic nevi plus a family history of melanoma (a syndrome known as FAMM) are at a high risk for developing melanoma at an early age (younger than 40). The risk for those with atypical moles and no family history of melanoma is less clear.
Large birthmarks (giant congenital nevi). Very large birthmarks more than 8 inches across are major risk factors for melanoma. In such cases, cancer usually appears by age 10. Medium-sized congenital nevi do not appear to increase the risk for melanoma. Whenever possible, very large birthmarks should be removed during infancy. Experts disagree, however, about whether small birthmarks need to be removed. Parents should watch any birthmark for changes.

The more moles one has the higher the risk that one of them will become cancerous, although the danger is still very small. A 2003 study estimated that the risk for a single mole to develop into melanoma by age 80 is 1 in 3,164 in men and 1 in 10,800 for women.

The risk is higher, however, with atypical moles. One study of people with melanoma indicated that the presence of even one atypical mole doubled the normal risk.

Some skin blemishes can look like -- but are not -- melanoma. Noncancerous moles typically have the following characteristics:

They generally remain small with clearly defined, regular borders, and uniform coloration. Some have a regular stippled or net-like pattern of pigmentation, however, and may even resemble early melanoma.
They typically first appear during childhood, puberty, or young adulthood. They may naturally grow, darken, or increase in number at certain times of life, such as adolescence or pregnancy.

Examples of moles or blemishes that may resemble skin cancer include:

Blue nevus. A benign mole that may easily be mistaken for melanoma. It is a blue-black, smooth, raised nodule and commonly occurs on the buttocks, hands, or feet.

Liver Spots. Liver spots are usually evenly brown or tan sun-induced lesions that are universal signs of aging. Occurring most noticeably on the hands and face, these harmless blemishes tend to enlarge and darken over time.

Spindle Cell (Spitz) Nevus. Children may develop a benign lesion called a spindle cell (or Spitz) nevus. The mole is firm, raised, and pink or reddish-brown. It may be smooth or scaly and usually appears on the face, particularly the cheeks. It is not harmful, but it may be difficult to differentiate from a melanoma, even for experts.

Non-Hodgkin's Lymphoma. Survivors of either non-Hodgkin's lymphoma or melanoma face a higher risk for the other malignancy. These may have common causes, such as exposure to UV radiation or shared genetic factors.

Human papillomavirus (HPV). Genital warts (human papillomavirus, or HPV) may also increase the risk of squamous cell cancer in the genital and anal areas and around fingernails.

Immunosuppression. Skin cancer risk is increased in persons whose immune systems are suppressed because of certain medications, organ transplantation, or medical conditions such as AIDS. Melanoma has also developed in patients who received heart transplants from donors who had the disease. Immune-suppressing drugs used to treat autoimmune disorders may also increase the risk of skin cancer. Potential skin cancer risks have been associated with the eczema drugs pimecrolimus (Elidel) and tacrolimus (Protopic).

Rheumatoid arthritis. Despite previous concerns, the rheumatoid arthritis drug etanercept (Enbrel) does not raise the risk for developing squamous cell skin cancer. The findings are reported in the Archives of Dermatology. Etanercept works by blocking tumor necrosis factor (TNF), an immune system chemical messenger that is involved in inflammatory processes and diseases.

Occupational exposure to radiation, such as in health care or industrial settings, may increase the risk for melanoma. Airline pilots, too, are at increased risk for melanoma. It is uncertain, however, whether this higher risk is from excessive exposure to ionizing radiation at high altitudes or because they have more opportunity to spend time in sunny regions. Experts disagree over whether frequent flyers are also at increased jeopardy.

Prevention

The best way to lower the risk your risk of skin cancer is to protect your skin from the sun and UV light.

Wear sunscreen. The use of sunscreens is complex, and everyone should understand how and when to use them. Follow instructions closely and reapply as directed after swimming or sweating. The bottom line is not that people should avoid sunscreens or sunblocks, but that they should always use them in combination with other sun-protective measures.

Many parents are now taking effective steps to protect their children, although experts worry that they are relying too much on sunscreen and less on other protective measures. Adolescents are at special risk for sun-related cancers because, according to a 2002 study, most of them do not take protective measures when out in the sun. According to the study, boys are less likely to use sunscreen than girls, but girls are more likely to get sunburn and use tanning salons more often.

The best way to prevent skin damage in any case is to avoid episodes of excessive sun exposure. The following are some specific guidelines:

Use sunscreens that block out both UVA and UVB radiation. Do not rely on sunscreen alone for sun protection. Also wear protective clothing and sunglasses.
Avoid exposure particularly during the hours of 10 a.m. to 4 p.m., when UV rays are the strongest.
Clouds and haze do not protect you from the sun and in some cases may intensify UVB rays.
Avoid reflective surfaces such as water, sand, concrete, and white-painted areas.
UV intensity depends on the angle of the sun, not heat or brightness. The dangers are greater the closer to the start of summer.
Skin burns faster at higher altitudes. One study suggested that an average complexioned person burns in 6 minutes at 11,000 feet at noon compared to 25 minutes at sea level.
Avoid sun lamps, tanning beds, and tanning salons. The machines use mostly high-output UVA rays. Some experts believe that 15 - 30 minutes at a tanning salon are as dangerous as a day spent in the sun. People should not be misled by advertising claims of "safe" tanning.

Wear protective clothing, sunglasses, and a hat to shield your face from the sun's rays. Special clothing can block out UV rays and is rated using sun protection factor (SPF) ratings or a system called the UPF (ultraviolet protection factor) index, with 50 UPF being the highest. (According to one study, this is a very reliable indicator of protection.) The clothing is expensive, however.

Everyone, including children, should wear hats with wide brims. (Even wearing a hat, however, may not be fully protective against skin cancers on the head and neck.)
People should look for loosely fitted, unbleached, tightly woven fabrics. The tighter the weave the more protective the garment.
Washing clothes over and over improves UPF by drawing fabrics together during shrinkage. An easy way to assess protection is simply to hold the garment up to a window or lamp and see how much light comes through. The less the better.
Everyone over age 1 should wear sunglasses that block all UVA and UVB rays when in the sun.

Click the icon to see a depiction of sun protection.

When choosing a sunscreen, look at the ingredients. Preparations that help block UV radiation are sometimes classified as sunscreens or sunblocks, according to the substances they contain. In general, sunscreens contain organic formulas and sunblocks inorganic formulas. However, the term sunblock is used less and less as sunscreens increasingly contain both kinds of ingredients:

Organic formulas contain UV-filtering chemicals such as octocrylene, octyl salicylate, homosalate, and octyl methoxycinnamate (block UVB), avobenzone-Parsol 1789 (blocks UVA), cinoxate, ethylhexyl p-methoxycinnamate (blocks UVB and small amounts of UVA), oxybenzone, and benzophenone-3 (blocks UVA/UVB). People should look for a wide-spectrum sunscreen that contains combinations of these ingredients and filter both UVA and UVB. Of note: para-amino benzoic acid (PABA), once a popular ingredient, is now used infrequently. PABA may actually break down in the presence of UV exposure and release harmful oxidants. And many people have an allergic reaction to it. Some products contain PABA derivatives, such as padimate O or octyl dimethyl PABA.
Inorganic formulas contain the UV-blocking pigments zinc oxide or titanium dioxide. Zinc and titanium oxides lie on top of the skin and are not absorbed. They prevent nearly all UVA and UVB rays from reaching the skin. Older sunblocks are white, pasty, and unattractive, but current products use so-called microfine oxides, either zinc (Z-Cote) or titanium. They are transparent and nearly as protective as the older types. Microfine zinc oxide may be more protective and less pasty-colored than microfine titanium oxide.

Calculating the SPF. SPF is a ratio based on the amount of UVB radiation needed to turn sunscreen- or sunblock-treated skin red compared to non-treated skin. For instance, people who sunburn in 5 minutes and who want to stay in the sun for 150 minutes might use an SPF 30. The formula would be: 30 (the SPF number) times 5 (minutes to burn) = 150 minutes in the sun.

Protection offered by sunscreens may be classified as follows:

Minimal: SPF 2 to 11
Moderate: SPF 12 through 29
High: 30+

Although some sunscreens claim SPFs higher than 30, the added protection at such higher levels is insignificant.

SPF Levels by Age Group. Although sunscreens are safe in most toddlers and children, they should not be the first and only lines of defense. All young children should be well-covered with clothing, sunglasses, and hats. Children should be kept out of the sun during peak sunlight periods. Do not use sunscreens on babies younger than 6 months without consulting a doctor.

Older children and adults (even those with darker skin) benefit from using SPFs of 15 and over. Some experts recommend that most people should use SPF 30 on the face and 15 on the body.

Adults who burn easily instead of tanning and anyone with risk factors for skin cancer should use at least SPF 30.

Timing and Amount of Application. Apply sunscreen or sunblock liberally as follows:

Adults should include sunscreen every day, even if going outdoors for only a short time.
Apply a large amount to all exposed areas, including ears and feet. To achieve protection as indicated by the sunscreen's SPF, experts recommend half a teaspoon each for the head, neck, and each arm and a teaspoon each for the chest area, the back, and each leg.
Apply initially 30 minutes before venturing outdoors for best results. This allows time for the sunscreen to be absorbed. Then reapply every 15 - 30 minutes while being in the sunlight.
Also reapply each time after exercise or swimming. Choose a waterproof or water-resistant formula even if activities don't include swimming. Waterproof formulas last for about 40 minutes in the water, whereas water-resistant formulas last half as long.
Insect repellents reduce sunscreen SPFs by up to one-third. Use higher SPFs and very liberal application when applying both.

Possible Hazards of Sunscreens, Sun Avoidance, or Both. When used generously and appropriately, sunscreen products and sun avoidance help reduce the severity of many aging skin disorders, including squamous cell cancers. There are certain concerns, however. Sunscreens do not appear to provide protection against melanoma and some basal cell cancers. In fact, some studies have reported a higher association with sunscreen use and these skin malignancies, though not all studies report such negative results.

The reasons for this possible increased risk are unclear, though some theories include:

Until recently, many sunscreens blocked only or predominantly blocked UVB rays and not UVA, the more deeply penetrating rays now known to be especially dangerous. Studies then may not have reflected the effects of the broad-spectrum sunscreens now available, which block both UVA and UVB.
People who apply sunscreens may stay out too long during peak sunlight hours. Even if a person doesn't sunburn, UVA rays can still penetrate the skin and do harm.
People may not put on enough sunscreen. A 2002 study found that people generally apply only 20 - 60% of the recommended amount, which can provide significantly less protection than the given SPF. A later study reported that when applied at the recommended amount, a broad-screen sunscreen prevents DNA damage from UV exposure.

Underexposure to sunlight. There is some major concern that underexposure to sunlight, due to the use of sunscreens or sun-avoidance measures, may produce other health problems such as:

Vitamin D deficiency. The body makes vitamin D through a chemical reaction to UVB sunlight. Too many sun-protection measures may increase the risk for developing vitamin D deficiency. Vitamin D helps prevent rickets, osteoporosis, and some cancers, including melanoma. People who need to avoid sunlight and whose diet is low in foods that contain vitamin D should check with their doctor about taking supplements. (Warning: Vitamin D is poisonous when taken in high doses.) People with darker skin are at higher risk for deficiencies from sun protection than those with whiter skin.
Other Cancers. Although sunlight is implicated in skin cancers, it is also associated with lower risks for breast, prostate, ovarian, and colon cancers. Some protection against these cancers may be related to vitamin D production by sunlight.
Depression. Many people suffer from seasonal affective disorder (SAD), a form of depression that generally occurs in winter and is associated with exposure to less sunlight.

The bottom line is that some sunlight is important and even necessary.

A study published in 1994 in the New England Journal of Medicine found that persons with a history of nonmelanoma skin cancer who ate a low-fat diet were much less likely to develop actinic keratosis, a precancerous skin condition.

However, the low-fat diet did not appear to have any effect on the development of basal cell cancer.

Chemoprevention is the use of a substance to prevent or reduce your risk of cancer. Certain drugs have been used to help block the development of skin cancers, including melanoma. For example, a medicine called imiquimod is approved to prevent skin cancer in certain individuals. This medicine prompts the immune system to fight off foreign substances, including cancer cells. Chemopreventive agents under investigation and showing promise for skin cancer include:

Nonsteroidal anti-inflammatory drugs
Difluoromethylornithine (DFMO)
Catechins (phytochemicals found in certain foods)
Anti-aging drugs called retinoids (vitamin A derivatives)

Retinoids have been shown to prevent nonmelanoma skin cancer in patients with basal cell nevus syndrome, xeroderma pigmentosum, and transplanted organs. Oral retinoids include isotretinoin and acitretin. They may also prevent the development of squamous cell carcinoma in patients who are taking such medicines to treat psoriasis.

Early animal studies had suggested that cholesterol-lowering statins or fibrates may reduce the risk of skin cancer, but human studies have produced inconsistent results. A review of several studies has concluded that such drugs do not decrease your risk of melanoma. The findings are published in the Journal of the National Cancer Institute.

Researchers are also studying chemopreventative compounds that target genetic mechanisms in the skin. They may prove to be beneficial ingredients in creams or lotions used to prevent skin cancers on a molecular level. They include cytokine interleukin-12 and T4 endonuclease 5 (T4N5).

Studies have shown that mice with round-the-clock access to an exercise wheel developed skin cancer more slowly when exposed to UVB. Their tumors were also fewer in number and smaller. Analysis of the data suggested that exercise might trigger the death of the developing cancer cells faster than they can grow. Exercise also made the mice lose weight, and the number of tumors decreased as fat disappeared.

Antioxidants are chemicals or drugs that help prevent cell damage from unstable molecules called free radicals. Antioxidants promote to protect the skin include vitamins C and E, and coenzyme Q10 (CoQ10).

Studies suggest that vitamin E creams, particularly those made from a type of Vitamin E called alpha tocopherol, decreased skin roughness, length of facial lines, and wrinkle depth. Studies on mice have also shown that such creams reduce UV-related skin cancer.

Vitamin C is a very potent antioxidant. It is also called ascorbic acid. Most studies on the effects of antioxidants on the skin have used this vitamin. In laboratory studies, large amounts reduced skin swelling and protected immune factors from sunlight.

Selenium in the form of L-selenomethionine has protected against sun damage and even delayed skin cancer in animal studies. It is not known if such benefits apply to people.

Click the icon to read about the antioxidant selenium.

Antioxidant Skin Creams. There are wide claims about the benefits of antioxidants for wrinkles when used in skin creams. However, to date, only vitamin E, C, and selenium-based skin products have been shown to help reduce sun damage to the skin. However, most available brands contain very low concentrations of these antioxidants. In addition, the antioxidants are also not well absorbed by the skin, so the effect may be short-term.

Antioxidant Pills. One small study found that taking a combination of vitamins C and E supplements by mouth may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins alone does not appear to have the same effect.

Other Natural Substances. The following natural substances have antioxidant properties and are being tried for sun-protection:

Both green and black tea appear to have properties that may provide some protection against skin cancers and photoaging. A 2001 study using extracts of topical green tea suggested that it might protect against ultraviolet damage. Green tea skin care products are now available, but their quality is unregulated.
Ginger also appears to have some sun protective qualities.
Silymarin, a substance found in the milk thistle family (which includes artichokes), may prevent UVB-promoted cancers in animals.
Garlic has been shown to protect animals against UVB damage. Whether these results may be applied to humans, and what quantities of garlic might be beneficial, is still unknown.

Warning Note: A wide range of herbal products may contribute to dermatological problems. Some Chinese herbal creams have been found to contain corticosteroids. Mercury or arsenic contaminants have been found in some Ayurvedic therapies. In addition, several oral herbal remedies used for medical or emotional conditions may produce irritation in reaction to sunlight (photosensitivity). They include, but are not limited to, St. John's wort, kava, and yohimbe.

Screening

Education and prevention programs have led to improved screening for skin cancer, which in turn has improved diagnosis and survival rates for melanoma. For example, a study published in CANCER has shown that older men are more likely to undergo a whole body skin exam if they were aware of personal risk factors and where they could go to have an exam performed.

Skin cancers may have many different appearances. They can be small, shiny, or waxy, scaly and rough, firm and red, crusty or bleeding, or have other features. Itching, tenderness, scaling, bleeding, crusting, or sores can signal potentially cancerous changes in any mole.

A mnemonic device, ABCDE, is used to describe several features that help to distinguish skin cancer from noncancerous growths.

Asymmetry (A). Skin cancers usually grow in an irregular, asymmetric fashion. That means one half of the abnormal skin area is different than the other half.
Border Irregularity (B). Noncancerous lesions generally have clearly defined borders. Melanoma lesions often have notched or indistinct borders that may signal ongoing growth and spread of the cancer.
Color Variation (C). One of the earliest signs of melanoma may be the appearance of various colors within the lesion. Because melanomas arise within pigment-forming cells, they are often varicolored lesions of tan, dark brown, or black, reflecting the production of melanin pigment at different depths within the skin. Occasionally, lesions are flesh colored or surrounded by redness or lighter areas of depigmentation.
- Pink or red areas may result from inflammation of blood vessels within the skin.
- Blue areas reflect pigment in the deeper layers of the skin.
- White areas can arise from dead cancerous tissue.
Diameter (D). A diameter of 6 millimeters or larger (about the size of a pencil eraser) is worrisome. Melanomas start out small; by the time a lesion has grown this large, other abnormalities will most likely be present. A doctor should examine any suspicious lesion, no matter what size it is.
Evolution (E). A lesion that is growing or changing deserves evaluation.

The ABCDE plan is a general guide. It will not help detect the early stages of nodular melanoma and may also miss amelanotic melanoma, which is not pigmented.

You should keep in mind that the most important warning sign of melanoma is a new or changing skin lesion, regardless of size or color. Changes that occur over a short period of time (particularly over a few weeks) are most worrisome.

Anyone with risk factors for skin cancer should check the entire body about once a month. People who regularly check moles on their skin may have a lower risk of developing advanced melanoma.

Experts suggest drawing a map of the body, indicating locations of moles, areas of discoloration, lumps, or other blemishes. Whenever a person conducts a self-examination, they should compare their body to the map to check for new lesions, lumps, or moles and for changes in shape, color, and size.

Some experts have defined three specific body areas to look for skin cancers, including melanomas:

Areas visible to anyone, such as the arms or face -- about 60% of melanomas are found on such areas.
Areas usually covered with clothing and visible only to the patients or their partners -- about 34% of melanomas are detected in these areas.
Hidden areas such as the scalp, buttock folds, and mouth -- about 6% of melanomas, usually more advanced, are found here.

Ask a partner to help you check these areas. Turn on a hair dryer to separate hair and examine the scalp.

Some experts recommend that everyone, especially those with a high risk of developing melanoma, have a dermatologist perform a whole body skin exam. Dermatologists detect melanoma earlier than other health care providers, according to an article in the Archives of Dermatology.

High-risk people include those with a personal or family history of melanoma and individuals with atypical nevi (irregular moles that are also larger than normal).

Such people should protect themselves from overexposure to sunlight and have a medical examination of the entire skin surface every 3 - 12 months, with the frequency depending on risk factors. Doctors may take photographs of any moles at each visit and compare them with previous photos for any changes.

Examinations for Patients Previously Treated for Melanoma. People who have had melanoma and have been treated successfully are at risk for recurrence or a second primary melanoma. Based on recurrence rates by cancer stage, a team of researchers suggested the following guidelines for being reexamined by the doctor after treatment:

Stage I patients: Yearly exam
Stage II patients: Every 6 months for years 1 and 2 and annually thereafter
Stage III patients: Every 3 months for the first year, every 4 months for year 2, and every 6 months for years 3 to 5

All patients should be checked annually after year 5. These are guidelines only and may be changed, depending on individual patient characteristics.

Some studies also suggest that regular screening of family members of people with melanoma could prevent a number of serious cases. A 2007 report in the Archives of Dermatology has called for expanded melanoma screening programs. The study found that one-time melanoma screening for adults over age 50 seems to be as cost-effective as other recommended cancer screenings. The study authors also found that screening brothers and sisters of someone with melanoma every 2 years may also be cost-effective.

Diagnosis

An experienced doctor should first rule out benign conditions that resemble melanoma, such as a noncancerous mole called a melanocytic nevi.

In rare instances, a melanoma will be difficult to detect. For example, an uncommon form, called a myxoid melanoma, may be mistaken for a benign skin disorder known as a myxoid fibrohistiocytic lesion. Other opinions from a second pathologist, computerized image processing or advanced staining techniques, may help to confirm the diagnosis.

A study published in the Archives of Internal Medicine has found that melanoma tends to be diagnosed at a later stage in persons who are not light-skinned. The study involved nearly 50,000 patients with melanoma, and included Caucasians, Hispanics, Asian/Pacific Islanders, African-Americans, and American Indians.

Some doctors now use dermoscopy (also called dermatoscopy or epiluminescence microscopy). This technique uses a handheld scope-like device that enhances the suspected lesion. It is still not clear if such devices are any better than the naked eye of a trained professional. Of interest, however, was a 2002 study suggesting that it was very useful in identifying possible melanomas in suspicious nail abnormalities and therefore avoiding many painful biopsies in this area. A 2004 study confirmed that adding dermoscopy to conventional naked-eye examination leads to fewer biopsies than using naked-eye examination alone.

A recently developed Australian device (the Solarscan) may improve detection. It is shaped like a hair dryer and takes an image of the suspicious lesion; it then reads the image and compares it with a databank of melanoma images to help determine if it is cancerous. It can also store the image of the lesion and compare it for changes with later images taken at subsequent check ups. The device is not yet used in the United States. It still requires FDA approval. Testing is under way to confirm its accuracy.

A skin biopsy is the removal of skin tissue for examination under a microscope. The exact type of biopsy depends on how deep the lesion has penetrated the skin.

Shave biopsy uses a thin surgical blade to shave off the top layers of skin. The doctor may use this type of biopsy to diagnose basal cell cancer.
Punch biopsy uses a round, cookie-cutter-like tool. It is used to take a deeper sample skin.
Incisional and excisional biopsies remove tumors that have grown deep into the skin. An incisional biopsy cuts out part of the tumor. An excisional biopsy removes the entire tumor. These biopsies are used to diagnose melanoma.

All of the above-mentioned biopsies can be done using local anesthesia.

A lymph node biopsy helps the doctor determine whether cancer has spread to one or more lymph nodes.

A procedure called sentinel lymph node (SLN) biopsy is now recommended for cancers that are thicker than 1 millimeter and generally unnecessary for those thinner than 0.75 millimeter, unless they are ulcerated. Although some evidence suggests this procedure may improve survival, no clinical trials have proven to date that this procedure improves the outlook in persons with melanoma.

Sentinel node biopsy is a technique that helps determine if a cancer has spread. When a cancer has been detected, often the next step is to find the lymph node closest to the tumor site and retrieve it for analysis. The concept of the "sentinel" node, or the first node to drain the area of the cancer, allows a more accurate staging of the cancer, and leaves unaffected nodes behind to continue the important job of draining fluids. The procedure involves the injection of a dye (sometimes mildly radioactive) to pinpoint the lymph node which is closest to the cancer site. Sentinel node biopsy is used to stage many kinds of cancer, including melanoma.

This procedure involves the following:

A tiny amount of a tracer, either a radioactively labeled substance (radioisotope) or a blue dye, is injected into the tumor site.
These substances then flow through the lymph system into the sentinel node, the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed and biopsied.

The results of the biopsy can help doctors decide whether or not to remove other lymph nodes:

If the sentinel node and others shows signs of cancer then the nearby lymph nodes are removed.
If they do not, then the remainder of the lymph nodes will likely be cancer-free, and further surgery is not needed.

If melanoma has been diagnosed, the doctor will perform other tests to see if the cancer has spread, such as a chest x-ray.

Blood tests that show high levels of lactate dehydrogenase suggest that the cancer has spread. Blood tests to assess liver function and other factors to help determine specific sites where the cancer may appear.

Advanced imaging techniques, such as computed tomography (CT) or positron emission tomography (PET), may also be used. PET is particularly accurate. One study reported that PET was able to diagnose melanoma that had spread even when other tests, including CT, did not. PET can also be very accurate for identifying recurrent melanomas.

Biomarkers are specific substances that are linked to cancer. Blood tests to detect biomarkers may be used to identify microscopic cancers if sentinel node biopsy results are uncertain. Researchers are continually investigating other biomarkers that may indicate whether the cancer had spread or how severe it is, which would help determine whether treatments should be more or less aggressive.

A number of proteins and other factors detected in blood tests are showing promise as markers for microscopic metastasis. Examples include antibodies to MART-1, Melan-A, tyrosinase, and microphthalmia transcription factor (Mitf). Combinations of some of these factors may improve detection rates.

Staging

Staging is the process used to determine the size of the tumor and where and how far it has spread. When a cancer spreads, it’s said to have metastasized. Staging helps the health care team plan for appropriate treatment.

Basal cell cancer is rarely staged, because it doesn't usually spread to other organs. However, it may be staged if it's very, very large.
Squamous cell cancer may be staged in persons who have a high risk of the cancer spreading.
Melanoma is always staged.

Health professionals have come up with various methods for staging the cancer. This report uses the TNM staging system recommended by American Joint Committee on Cancer.

T = tumor. T is followed by a number to indicate thickness.
N = node. N is followed by numbers to indicate the number of lymph nodes involved.
M = metastasis. Metastasis is the spread of cancer to far away sites.

In addition a stage will include whether the melanoma is ulcerated or not, an indication of severity. Ulceration is determined if skin layers over the tumor appear indistinct under the microscope.

In general, the thicker the lesion and the farther the cancer has spread, the higher the assigned stage. The higher the stage, the worse the long-term outlook.

The earliest melanomas, which do not penetrate beneath the surface of the skin and are known as melanoma in situ, are highly curable and are called stage 0 or not given a stage.
Melanomas less than 4 mm thick suggest Stage I or II cancers, and the next step is to attempt to determine if they have spread or are likely to spread to the lymph nodes.
Melanomas that are over 4 mm thick indicated later stages. In such cases, the lymph nodes are sometimes removed to attempt to prevent the cancer from spreading, although about 70% of these melanomas have already spread.

Specific stages are as follows:

Stage I. Cure rates are excellent with surgical removal, since they are least likely to have spread.

Stage 1A. Tumor has not spread to the nodes. It is less than 1 mm and is not ulcerated.
Stage IB. Tumor has not spread to the nodes. It is less than 1 mm, but is ulcerated, or the tumor is between 1.01 and 2 mm but is not ulcerated.

Stage II. Melanomas can be cured, but the success rate lags behind that of Stage I because a small number of cancer cells may have spread to distant sites. In addition to surgery, other forms of therapy may be recommended.

Stage IIA. Tumor has not spread to the nodes. It is between 1.01 and 2 mm and is ulcerated, or it is 2.01 to 4 mm without ulceration.
Stage IIB. Tumor has not spread to the nodes. It is between 2.01 and 4 mm and is ulcerated or greater than 4 mm without ulceration.

Stage III. Survival rate is lower than earlier stages.

Stage IIIA. Tumor has spread to 1 node and it is up to 4 mm without ulceration. Sentinel biopsy has detected microscopic evidence of tumor cells in the node (micrometastasis).
Stage IIIB. Tumor is up to 4 mm without ulceration and has spread to one node or there is evidence of micrometastasis in two nodes.
Stage IIIC. Tumor is any thickness and ulceration may or may not be present. It has spread to 2 or 3 nodes. Additional "satellite" melanomas on the skin more than 2 cm (about an inch) from the original lesion may be present; these are sometimes called "metastases in transit."

Treatment for Melanoma

Treatment for melanoma depends on various factors, including:

The site of the original lesion
The stage of the cancer
The patient's age and general health

Treatment options include:

Surgery to remove the melanoma cancer cells
Chemotherapy
Immunotherapy
Radiation therapy
Palliative therapy

Surgery is the primary treatment for all stages of melanoma. Some or all of the melanoma is often removed during the diagnosis biopsy. If cancerous tissue still remains after such a biopsy, a surgeon will cut away additional tissue from the surrounding area to remove any stray cancer cells.

Mohs micrographic surgery is a technique used to remove very thin layers of skin one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete.

The amount of tissue removed depends on the size, depth, and degree of invasion:

Stage I lesions that are less than 1 mm deep require the smallest surgical cuts, usually about 1 cm off each side and downward from the original lesion.
For melanomas that are 2 mm or thicker, a margin of 3 cm is important for reducing the risk of recurrence.
Thicker lesions require wider surgical cuts.

It used to be customary to remove a large area, regardless of the stage of cancer. This potentially disfiguring approach has been abandoned because studies have shown that excising wider margins does not improve survival. Nevertheless, sometimes skin grafts may need to be taken from other body sites to help cover the wound.

Lymph Node Removal. If there is evidence that melanoma has spread to nearby lymph nodes but has not spread beyond, removing them may reduce the chance of recurrence and help patients live longer.

Surgery for Metastatic Melanoma. In some cases, surgical removal of distant tumors may be possible and prolong survival, since often in melanoma the cancer spreads first only to a single site, such as the lung or the brain.

Cryosurgery. Cryosurgery freezes skin tissue and destroys it. This procedure is not useful for most melanomas, but it might have some value in specific situations. For example, it may be effective for smaller melanomas in the eye, a location that is difficult to treat with traditional surgery. It may be useful to eliminate residual cancer cells after standard surgery for lentigo maligna melanomas, an atypical form of melanoma that has a wide surface and is difficult to treat.

Recurrence rates are very high with lentigo maligna after conservative surgery. Although this is a very slowly progressive condition, lentigo maligna can develop into melanoma. Most of these lesions appear on the face and neck, so extensive surgery can be disfiguring. Patients should discuss with their doctor carefully staged surgery to remove all diseased tissue with as little cosmetic harm as possible.

Chemotherapy is often used to treat recurrent or metastatic melanomas. This type of therapy is not intended as a cure but can prolong life and improve its quality.

Drugs Used. The following are some of the chemotherapy drugs used to treat melanoma. They may be used alone or in combination under specific situations.

Methylating agents impair the ability of cancer cells to divide. Dacarbazine (DTIC) and temozolomide (Temodar) are the ones most often used.
Nitrosoureas, which include carmustine (BCNU) and lomustine (CCNU) are often used.
Taxanes, such as docetaxel (Taxotere) and paclitaxel (Taxol), are showing some low-level activity against melanoma.

Researchers continue to investigate other chemotherapy drugs and combinations of drugs to see which works best.

Side Effects. Side effects occur with all chemotherapy drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include the following:

Nausea and vomiting
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Anemia
Depression

Serious short- and long-term complications can also occur and may vary depending on the specific agents used. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia). Certain agents, such as taxanes, pose a higher risk for this than other chemotherapeutic drugs. White blood cell count may be improved with the addition of a drug called granulocyte colony-stimulating factor (either filgrastim or lenograstim).
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction.
Menstrual abnormalities and infertility in women. A natural hormone medication called a gonadotropin-releasing hormone analogue that puts women in a temporary pre-pubescent state during chemotherapy may preserve fertility in some women.
Rarely, secondary cancers such as leukemia.
Problems in concentration, motor function, and memory, which may be long-term.

Treating Side Effects

Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve nausea and vomiting in nearly all patients given moderate drugs and most patients who take more powerful drugs.

Erythropoietin stimulates red blood cell production and can help reduce or prevent anemia related to chemotherapy. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp persists longer in the blood than epoetin alfa and so requires fewer injections.

Benefits of Chemotherapy. About 20% of cancers shrink in response to one or more of these drugs, but the effects last only 3 - 6 months. If the tumors completely disappear, the cancer may stay in remission much longer, but in virtually all cases it returns.

Chemotherapeutic regional perfusion (also called isolated limb perfusion) is a technique used to give a person very high-dose chemotherapy. It is often used effectively for metastasized or recurrent melanoma that occurs on the arm or leg. It does not appear to be useful for preventing metastasis after a first occurrence of melanoma in one of these locations.

This technique involves the following:

The blood supply to the limb with melanoma is temporarily interrupted using a tourniquet and then rechanneled through a heart-lung machine.
Anticancer drugs are added to the blood in doses up to 10 times the standard doses.
The blood is then heated to enhance the drug's potency.
The chemo-infused blood is then sent directly to the melanoma site, minimizing the likelihood of drug toxicity.
Adverse effects occur in less than 1% of cases and include severe problems in the treated limb (rarely leading to amputation) and drug leakage into the bloodstream. This can severely reduce white blood cells and lead to serious infection.

In addition to arms and legs, perfusion techniques have been tested for the pelvis, head, neck, skin of the breast, and even the abdomen.

Immunotherapy uses drugs to boost the patient's own immune system. Immunotherapy after surgery may help prevent recurrence in certain persons with melanoma.

Cytokines. Cytokines are small proteins that play an important role in the body's immune response. Certain cytokines called interferons are used as a therapy for metastatic melanoma. These medicines are usually given along with chemotherapy or other immunotherapies, or both.

A number of cytokines and combinations are being investigated. They include:

Interferon alpha-2b (Intron) is the only FDA approved immunotherapy for late stage melanoma. The most common side effects are fatigue, depression, and flu-like symptoms, which can be severe. Starting an antidepressant, such as paroxetine (Paxil), several weeks before interferon therapy may help prevent depression.
Pegylated interferon and natural human interferon are long-acting forms are under investigation. One study showed that low-dose natural interferon after chemotherapy increased the 5-year relapse-free survival rate.
Interleukin-2 (Proleukin) is a hormone-like substance that stimulates the growth of cancer-fighting white blood cells. High-dose interleukin-2 has been shown to help patients with metastatic melanoma. The drug can cause significant side effects, including very low blood pressure, heart rhythm abnormalities, severe infections, and shortness of breath. The side effects are manageable and nearly always reversible.
Granulocyte-macrophage colony stimulating factor (GM-CSF, Leukine, Sargramostim) is an injectable cytokine under study. The drug boosts production of immune cells in the blood and bone marrow. An inhaled form of the drug is being tested for melanoma that has spread to the lungs.
T-cell therapy uses white blood cells, called tumor-infiltrating lymphocytes (TIL), that taken from the patient. The cells are modified so they better fight cancer and are then reinjected back into the patient. T-cell therapy is showing promising results, especially for patients with advanced melanoma who have failed to respond to other treatments.

A chemical called histamine is a powerful inhibitor of reactive oxygen species, ROS, which may inactivate immune cells that fight cancer. Researchers are investigating to see if it can be used along with interleukin-2 cytokine therapy. In one study, the added benefits of histamine were modest except in patients with liver metastatic; in these patients, survival improved by 129 days, which was significant.

Vaccine Immunotherapy. Vaccine immunotherapy is the use of a specific vaccine to treat an existing cancer. In this case, the vaccine targets one or more proteins that are uniquely expressed by melanoma cells.

Many therapeutic melanoma vaccines are in advanced stages of development, but none is approved for use in the United States.

There are two basic types of therapeutic vaccines:

Autologous vaccines
Allogenic vaccines

Sometimes a combination of the two are used. In this case, it's called a hybrid.

Autologous vaccines are made from the patient's own cancer cells. This produces a very specific immune response that can target the patient's cancer precisely. Oncophage (HSPPC-96) and M-Vax are autologous vaccines for melanoma that have shown promise in early clinical trials. One problem with the autologous approach is that there is no way to scientifically assess outcome or even guarantee repeated success since each vaccine is unique to the individual patient. This approach is also appropriate only for select patients.

Allogenic vaccines are made in a laboratory using cells from someone other than the patient. They may be made from proteins from tumor cells, genetic material, or even bacteria. One such vaccine is Canvaxin. Early studies showed this vaccine increased survival rates in some patients with Stage 3 melanoma. However, a later trial was halted because the vaccine did not appear to improve make such patients live any longer.

Vaccine immunotherapy requires the body to build up its own defenses. It can take months before beneficial effects occur, but when they do, tumor reduction is much more lasting than with chemotherapy. Vaccines also seem to have fewer side effects than interleukin and interferon.

Antisense Compounds. Antisense compounds can prevent defective cancer genes from being translated into proteins that cause abnormal cell proliferation.

Monoclonal Antibodies (MAb). Antibodies are natural substances produced by immune cells that home in and destroy cancer cells. Scientists are identifying specific antibodies that may attack melanoma cells and cloning them to create monoclonal antibodies. MAbs have shown promise for other cancers and are now being tested for melanoma, often in combination with vaccines and other forms of immunotherapy.

In general, radiation is used to help relieve pain and discomfort caused by cancer that has spread or recurred. Radiation is not used as often for treating melanoma as it is for other forms of cancer because melanoma cells tend to be more resistant to its effects. It may be useful in some cases, however.

In some patients with tumors less than 3 cm deep, however, radiation may help slow down metastasis when combined with a super-heating process using microwaves.
Brachytherapy, in which radioactive seeds are implanted close to the tumor, has also been used with success for melanoma of the eye.
Lentigo maligna may sometimes be treated successfully with specific radiation treatments called soft, or Grenz, x-rays.
Radiotherapy using a so-called gamma knife (very focused gamma radiation) is also effective for cancer that has metastasized to the brain, in some cases halting the growth and, in rare situations, even eliminating it.

The goal of palliative therapy is to improve the patient's quality of life and relieve symptoms. It is not a cure. Advanced melanoma that has spread to distant sites often cannot be cured, although surgical removal of metastatic tumors may provide some benefit by easing pain, increasing the general quality of life, and lengthening survival.

Patients should ask their doctor's about clinical trials, studies that examine new immunotherapies (vaccines, cytokines), gene therapies, chemotherapy combinations, or other treatments.

Tetracyclines. Chemically modified tetracyclines, a common antibiotic, have been shown to modify metalloproteinase, an enzyme in the skin that promotes skin cancers, including melanoma.

Anti-Angiogenesis Agents. An anti-angiogenesis drug is one that blocks the formation of new blood vessels. The growth of new blood vessels helps cancer cells grow and spread. The anti-angiogenesis drug thalidomide (Thalomid) is approved for treatment of melanoma but requires special prescribing precautions. This drug had gained notoriety in the 1960s because of devastating birth defects in the children of women who took it during pregnancy. Scientists are investigating drugs that are chemically similar to thalidomide but have fewer side effects.

Curcumin. The yellow spice found in turmeric and curry powders may contain cancer-fighting properties. In a preliminary laboratory study, curcumin stopped the growth of melanoma cells. It is far too early, however, to recommend curcumin for clinical use.

Treatment for Nonmelanoma Skin Cancer

A number of options are available for treating nonmelanoma skin cancer, including surgery, cryosurgery, phototherapy, radiation, and topical 5-fluorouracil.

For any skin cancer and for some keratoses that require removal, surgery is the first treatment. It is usually one of the following:

Excisional Surgery. This is the surgical removal of the cancerous lesion.

Curettage and Electrodesiccation. This procedure involves scraping away of the cancerous tissue followed by electric cauterization to stop the bleeding.

Mohs Micrographic Surgery. Mohs surgery is a meticulous procedure used for skin cancers at high risk for recurrence or becoming invasive. The technique removes very thin layers of skin one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete. A human skin substitute (Apligraf) is applied to the surgical area. It helps speed up wound healing to achieve a better cosmetic effect.

Good candidates for Mohs surgery include:

Persons with squamous cell cancer
Persons with basal cell cancer greater than 1 cm (about half an inch)
Persons with basal cell cancer on the face, ear, or neck
Young people with skin cancer

Mohs surgery saves more healthy tissue than other procedures and is highly effective. It results in a 99% cure rate for primary tumors and a 95% cure rate for recurrent ones. It can be safely performed in the doctor's office. Complications are uncommon but can include bleeding and infection.

Lasers. Laser surgery may be useful for certain basal cells and for keratoses that appear on the lips, although it is not clear whether lasers offer any advantages over other surgical treatments. Lasers do not appear to be very effective for thick or tough squamous cell cancers.

Cryosurgery removes skin cancer cells or actinic keratoses by freezing the affected tissue with liquid nitrogen. Studies have shown that cyrosurgery can be used to remove even wide areas of actinic keratoses and that it may be more successful over the long term than treatment with 5-fluorouracil, the standard drug. Cryosurgery also appears to reduce the risk for squamous cell cancer in these patients.

A head-to-head comparison of a freezing technique with Mohs micrographic surgery in patients with basal cell cancer reported similar recurrence rates with each approach. Over 85% of the patients with the freezing technique were satisfied with the appearance of the area afterwards. Five-year recurrence rates were only 2.1%.

Cryotherapy achieves good cosmetic results for many patients. However, it may cause blistering and ulceration, leading to pain and infection, as well as harmless, but undesirable, skin-color changes.

In unusual cases where the skin cancer may be in an inoperable position (such as the eyelid or the tip of the nose) or if cancer has recurred multiple times, radiation therapy may be indicated. Radiation is directed at the tumor. It may take 1 - 4 weeks with treatments performed several times a week. One technique being investigated for basal and squamous cell cancer uses radiation implants (brachytherapy) and custom-made molds to specifically target the radiation to the cancer site. Studies suggest that this treatment is very effective with few complications.

Topical phototherapy with the drug aminolevulinic acid (ALA) is a nonsurgical method that is proving to be a good choice for treating actinic keratoses and nonmelanoma skin cancers. The technique involves shining blue light onto the cancer area after that patient has taken ALA. ALA accumulates in the skin cells. When the cells are exposed to intense light, the chemical causes them to die. This approach allows precise targeting of one or more lesions, leaving healthy skin unaffected.

It does not penetrate deeper than the epidermis (the top layer of the skin), so it does not produce scarring or changes in skin color, as cryotherapy or other more invasive treatments do.

It can cause pain and irritation, including stinging, itching, and burning, but in one study only 3% of patients stopped using it for these reasons. In a 2002 study, the procedure was more painful for patients with actinic keratoses than for those with nonmelanoma skin cancers. It was also painful when large areas were affected, and men experienced more pain than women.

ALA Phototherapy for Actinic Keratoses. Phototherapy works best on flat lesions performed in two treatments, and is more effective for clearing lesions on the face than those on the scalp. Phototherapy can also treat multiple lesions at the same time instead of sequentially, as in cryotherapy. Studies suggest that it may work as well as cryotherapy and achieve better cosmetic results. (More patients report burning and itching with phototherapy, however.) Phototherapy is also equal to topical 5-fluorouracil in effectiveness and achieving a satisfactory appearance.

ALA Phototherapy for Nonmelanoma Skin Cancers. In patients with squamous cell cancer-in-situ and basal cell cancer, phototherapy has been equal to cryotherapy, with superior healing and appearance afterward. A 2003 study reported that it was more effective than topical 5-fluorouracil for patients with Bowen's disease, and there were fewer side effects.

Some studies have shown that about 10% of patients using phototherapy have a recurrence within 1 year. These recurrence rates are higher than with surgery and other standard treatments. Longer-term studies are required before ALA phototherapy can be recommended for most patients with nonmelanoma skin cancers.

Chemical peeling, or exfoliation, is useful for solar keratoses on the face, especially in people with fair, dry skin. Alpha-hydroxy acids, for example, are being investigated for keratoses. Dermabrasion, which "sands" the skin, may also be effective, although scarring is possible. A 2002 study found laser resurfacing to treat severe sun damage on the face; however, it may not prevent nonmelanoma skin cancers.

A number of medications are being used for keratoses and some may be helpful for skin cancers as well. Besides cryotherapy, 5-fluorouracil is the other most commonly used treatment for actinic keratoses. Other medications are also available.


Medication	Skin Conditions Affected	Oral or Topical		Comments
5-Fluorouracil	Actinic keratoses, Bowen's disease and small nonmelanoma skin cancers.		Topical cream (Efudex, Fluoroplex) or injected gel containing 5-FU and epinephrine (AccuSite).	5-Fluorouracil (5-FU) removes actinic keratoses and is useful for some patients with a large number of lesions. It requires twice daily application for 3 - 4 weeks. It can cause significant redness, irritation, swelling, and crusting, which takes 2 - 4 weeks to heal. Newer preparations are reducing these side effects. It is still unclear if this medication protects against recurrent keratoses or future skin cancer. Of concern is the possibility that (5-FU) will clear the top of a skin cancer and obscure the rest of the cancer that lies beneath the surface of the skin. A 10-year 2003 study of patients with Bowen's disease reported that 5-FU was safe and effective, with only 2 out of 26 cancers recurring.
Diclofenac and hyaluronan (Solaraze)	Actinic keratoses (approved). Investigated for basal cell.		Topical gel applied twice a day.	Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). When used to treat actinic keratoses, it is delivered to the skin with hyaluronan, a water-seeking molecule that helps maintain skin tension. It has modest effects and when healing occurs, it may not be evident for at least a month after treatment ends. However, it causes less irritation than 5-FU and may be useful for some people.
Imiquimod (Aldara)	FDA approved for the treatment of superficial basal cell cancer. Previously approved for treating actinic keratoses. Investigated for Bowen's disease and squamous cell cancer.		Imiquimod is a topical cream.	Imiquimod triggers the production of immune factors that help fight cell proliferation. Aldara should be used only when surgery for basal cell cancer is inappropriate. It is not approved for use on the face.
Alpha-Interferons	Basal cell cancer, squamous cell cancer.		Require injections administered three times a week.	Interferons are immune factors that are being used to treat a number of serious conditions. Alpha-interferon injections may be effective against skin cancers that are hard to treat using conventional surgical measures. Cosmetic results reported to be good or very good by 83% of patients.

Prognosis

Virtually all basal and squamous type skin cancers can be cured if treated early.

The outlook for melanoma depends on when it is diagnosed.

If melanoma is detected in its earliest form, the 5-year survival rate is 99%. Other localized forms of melanoma have very favorable outlooks.

If the cancer is found after the melanoma has spread, the 5-year survival rate drops.

If melanoma spreads to nearby areas (regional metastatic), the rate is 65%.
If melanoma has spread to distant areas of the body, the survival rate is 15%.

In general, after patients are treated for melanoma, the longer they remain free of cancer recurrence following treatment the better the chance of remaining disease-free. However, relapses are not uncommon in those whose initial melanoma was large.

Anyone who has recovered from melanoma should be especially strict about adhering to preventive guidelines and remain vigilant for suspicious lesions, since the risk for developing a new melanoma is increased even if the first one was successfully cured. Such relapses may occur years after the original diagnosis.

Resources

www.aad.org -- American Academy of Dermatology
www.cancer.org -- American Cancer Society
www.asds.net -- American Society for Dermatologic Surgery
www.mpip.org -- Melanoma Patients' Information Page
www.cancer.gov -- National Cancer Institute
www.nccn.org -- National Comprehensive Cancer Network
www.skincancer.org -- The Skin Cancer Foundation
www.epa.gov/sunwise/uvindex.html -- UV index information

References

Ambros-Rudolph CM, Hofmann-Wellenhof R, Richtig E, et al. Malignant melanoma in marathon runners. Arch Dermatol. 2006;142:1471-1474.

American Cancer Society. Cancer Facts and Figures 2007. Atlanta, GA: American Cancer Society; 2007.

Chemotherapy for Inoperable Liver Metastases from Ocular Melanoma. NCI Cancer Bulletin. November 30, 2004;1(46):7.

Dale KM, Coleman CI, Henyan NN et al. Statins and Cancer Risk: A Meta-Analysis. JAMA. 2006;295:74-80.

Delavalle RP. Melanoma chemoprevention. Program presented at: Annual meeting of the American Academy of Dermatology. March 3, 2006; San Diego, CA.

Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005;23(10):2346-2357.

Early Detection and Surgery for Melanoma in Lymph Nodes May Increase Survival. NCI Cancer Bulletin. May 17, 2005;2(20):2.

Freeman SR, Drake AL, Heilig LF, et al. Statins, Fibrates, and Melanoma Risk: a Systematic Review and Meta-analysis. J Natl Cancer Inst. 2006;98:1538-46.

Gallagher RP, Spinelli JJ, Lee TK. Tanning beds, sunlamps, and risk of cutaneous malignant melanoma. Cancer Epidemiol Biomarkers Prev. 2005;14(3):562-566.

Lautenschlager S, Wulf HC, Pittelkow MR. Photoprotection. The Lancet [early online publication]. May 3, 2007.

Lebwohl M. Cutaneous oncology. Program presented at: Annual meeting of the American Academy of Dermatology; March 7, 2006; San Diego, CA.

Michna L, Wagner GC, Lou YR, XE JG, Peng QY, Lin Y, Carlson K, Shih WJ, Conney AH, Lu XP. Inhibitory effects of voluntary running wheel exercise on UVB-induced skin carcinogenesis in SKH-1 mice. Carcinogenesis. May 2006.

Pennie M, Soon S, Risser J, et al. Melanoma outcomes for medicare patients. Arch Dermatol. 2007; 143:488-494.

Response to Immunotherapy for Melanoma Tied to Autoimmunity. NCI Cancer Bulletin. February 21, 2006;3(: 4.

Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer. 2005;104(4):879-890.

Treatment for Metastatic Ocular Melanoma. NCI Cancer Bulletin. March 7, 2006;3(10):8.

Veierod MB, Weiderpass E, Thorn M, et al. A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst. 2003;95(20):1530-1538.

Weinstock MA. Cutaneous melanoma: public health approach to early detection. Dermatologic Therapy. 2006;19(1):26-31.

Review Date:
6/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Impotence (Erectile dysfunction)

FitSugar — Wed, 08 Oct 2008 17:35:36 -0700

In This Report

Highlights
Introduction
Risk Factors
Lifestyle or Psychological ...
Physical Causes
Prognosis
Diagnosis
Treatment
Lifestyle Changes
Medications
Injections or Topical Treat...
Other Treatments
Natural Remedies
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

FDA Warns about Dietary Supplements

In 2006 and 2007, the FDA issued numerous warnings about “natural” dietary supplements promoted for erectile dysfunction and sexual enhancement. These products -- marketed under names such as “True Man,” “Energy Max,” “Rhino Max”-- contain illegal substances that can interact with prescription drugs and dangerously lower blood pressure. The interaction risks are greatest for men with diabetes, high blood pressure, high cholesterol, or heart disease who take prescription drugs that contain nitrates. The FDA has not approved any of these products and warns that consumers should not buy or use them.

Viagra and Similar Drugs Safe for Men with Diabetes

Phosphodiesterase inhibitors (PDE-5 inhibitors) are generally safe and often effective for men with diabetes, at least in the short term, according to a 2007 review published in the Cochrane Database. However, there is not enough evidence to determine if these drugs are safe for men with diabetes if used on a long-term basis. PDE-5 inhibitors include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). These drugs should be used with caution in men who have unstable heart disease, poorly controlled high blood pressure, or history of stroke. Discuss with your doctor whether a PDE-5 inhibitor drug is safe for you.

Testosterone Therapy Guidelines

In 2007, the Endocrine Society issued guidelines for testosterone treatment. The Endocrine Society advises that testosterone therapy works best for men who have been diagnosed with low testosterone levels and who demonstrate clear clinical symptoms such as erectile dysfunction. For patients with low libido or erectile dysfunction, but normal testosterone levels, it is unclear that testosterone therapy offers any benefits. Most experts recommend that patients with low testosterone levels and erectile dysfunction combine testosterone replacement therapy with a PDE-5 inhibitor drug.

Metabolic Syndrome Increases Risk for Erectile Dysfunction

Metabolic syndrome is a risk factor for erectile dysfunction, according to several recent studies. Metabolic syndrome is a cluster of conditions that include abdominal obesity, unhealthy cholesterol and triglyceride levels, high blood pressure, and insulin resistance.

Introduction

Erectile dysfunction (impotence) is the inability to achieve or maintain an erection sufficiently rigid for sexual intercourse, ejaculation, or both. Sexual drive and the ability to have an orgasm are not necessarily affected. Because all men experience erection problems from time to time, doctors consider impotence to be present if attempts at intercourse fail at least 25% of the time.

Erectile dysfunction is new in neither medicine nor human experience, but it is not easily or openly discussed. Cultural expectations of male sexuality inhibit many men from seeking help for a disorder that can, in most cases, benefit from medical treatment. The term "impotence" comes from Latin and means loss of power; a more accurate term is "erectile dysfunction."

The Structure of the Penis. The penis is composed of the following structures:

Two parallel columns of spongy tissue called the corpus cavernosa, or erectile bodies.
A central spongy chamber called the corpus spongiosum, which contains the urethra, the tube that carries urine from the bladder through the penis.

These structures are made up of erectile tissue. Erectile tissue is rich in tiny pools of blood vessels called cavernous sinuses. Each of these vessels are surrounded by smooth muscles and supported by elastic fibrous tissue composed of a protein called collagen.

Erectile Function and Nitric Oxide. The penis is either flaccid or erect depending on the state of arousal. In the flaccid, or unerect, penis, the following normally occurs:

Small arteries leading to the cavernous sinuses contract, reducing the inflow of blood.
The smooth muscles regulating the many tiny blood vessels also stay contracted, limiting the amount of blood that can collect in the penis.

During arousal the following occurs:

The man's central nervous system stimulates the release of a number of chemicals, including nitric oxide, which is now considered the main contributor for eliciting and maintaining erection.
Nitric oxide stimulates production of cyclic GMP, a chemical that relaxes the smooth muscles in the penis. This allows blood to flow into the tiny pool-like cavernous sinuses, flooding the penis.
This increased blood flow nearly doubles the diameter of the spongy chambers.
The veins surrounding the chambers are squeezed almost completely shut by this pressure.
The veins are unable to drain blood out of the penis and so the penis becomes rigid and erect.
After ejaculation or arousal, cyclic GMP is broken down by an enzyme called phosphodiesterase-5 (PDE5), and other compounds are released that cause the penis to become flaccid (unerect) again.

A proper balance of certain chemicals, gases, and other substances is critical for erectile health:

Collagen. The protein collagen is the major component in structural tissue in the body, including in the penis. Excessive amounts, however, form scar tissue, which can impair erectile function.

Oxygen. Oxygen-rich blood is one of the most important components for erectile health. Oxygen affects two substances that are important in achieving erection:

Oxygen suppresses transforming growth factor beta 1 (TGF-B1). TGF-B1 is a component of the immune system called a cytokine and is produced by smooth muscle cells. It appears to stimulate collagen production in the corpus cavernosum, which can lead to erectile dysfunction.
Oxygen enhances the activity of prostaglandin E1. Prostaglandin E1 is produced during erection by the muscle cells in the penis. It activates an enzyme that initiates calcium release by the smooth muscle cells, which relaxes them and allows blood flow. Prostaglandin E1 also suppresses production of collagen.

Oxygen levels vary widely from reduced levels in the flaccid state to very high in the erect state. During sleep, oxygen levels are high and a man can normally have three to five erections per night, each one lasting from 20 - 40 minutes.

Testosterone and Other Hormones. Normal levels of hormones, especially testosterone, are essential for erectile function, though their exact role is not clear.

Erectile dysfunction most commonly occurs when the penis is deprived of oxygen-rich blood. When oxygen levels to the penis are low, an imbalance occurs in two important substances, TGF-B1 and prostaglandin E1:

TGF-B1 levels increase, which trigger production of collagen, a tough protein that forms all types of connective tissue, including scar tissue.
In addition, there is a reduction in prostaglandin E1, a chemical that suppresses collagen production and relaxes the smooth muscles to allow blood flow resulting in an erection.

When TGF-B1 levels increase and prostaglandin E1 levels decrease, smooth muscles waste away and collagen is overproduced, causing scarring, loss of elasticity, and reduced blood flow to the penis. A number of conditions can deprive the penis of oxygen-rich blood.

Blockage of Blood Vessels (Ischemia). The primary cause of oxygen deprivation is ischemia-- the blockage of blood vessels. The same conditions that cause blockage in the blood vessels leading to heart problems may also contribute to erectile dysfunction. For example, when cholesterol and other factors are imbalanced, a fatty substance called plaque forms on artery walls. As the plaque builds up, the arterial walls gradually narrow, reducing blood flow. This process, known as atherosclerosis, is the major contributor to the development of coronary heart disease. It may also play a role in the development of erectile dysfunction.

Risk Factors

More than 18 million American men over age 20 have erectile dysfunction, and about 600,000 men age 40 - 70 experience erectile dysfunction to some degree each year.

For most men, erectile dysfunction is primarily associated with older age. While ED affects less than 10% of men in their 20s, and 20 – 46% of men age 40 – 69, about 80% of men age 75 or older have ED. Nevertheless, impotence is not inevitable with age. In a survey of men over 60 years old, 61% reported being sexually active, and nearly half derived as much if not more emotional benefit from their sex lives as they did in their 40s.

Severe erectile dysfunction in elderly men may have more to do with disease than age itself. In particular, older men are more likely to have heart disease, diabetes, and high blood pressure than younger men. Such conditions and some of their treatments are major risk factors for erectile dysfunction. Smoking and obesity are also prime risk factors for ED.

Many physical and psychological situations can cause erectile dysfunction, and brief periods of impotence are normal. Every man experiences erectile dysfunction from time to time. Nevertheless, if the problem is persistent, men should seek professional help, particularly since erectile dysfunction is usually treatable and may also be a symptom of a more widespread problem.

Lifestyle or Psychological Causes

Over the past decades, the medical perspective on the causes of erectile dysfunction has shifted. Common wisdom used to attribute almost all cases of impotence to psychological factors. Now investigators estimate that up to 85% of impotence cases are caused by medical or physical problems. Only 15% are psychologically based.

It is often difficult to determine if the cause of erectile dysfunction is a physical or psychological one, or even some combination. The following may be helpful:

Physical impotence can be caused by internal medical causes (diabetes, high blood pressure) or by external causes (surgery, injury, medications). Erectile dysfunction due to medical conditions usually develops gradually but continuously over a period of time. If impotence persists over a 3-month period and is not due to a stressful event, drug use, alcohol, or known medical conditions, then the patient needs medical attention by a urologist specializing in impotence.
Psychological impotence tends to develop rapidly and be related to a recent situation or event. The patient may be able to have an erection in some circumstances but not in others. Being able to experience or maintain an erection upon waking up in the morning suggests that the problem is psychological rather than physical.

In virtually every case of erectile dysfunction there are emotional issues that can seriously affect the man's self-esteem and relationships. Negative emotions may even perpetuate erectile dysfunction that has been caused by a medical condition that has been successfully treated. Many men tend to fault themselves for their impotence even if it is clearly caused by physical problems over which they have little or no control.

Anxiety. Anxiety has both emotional and physical consequences that can affect erectile function. It is among the most frequently cited contributors to psychological impotence. Excessive concern about sexual performance is often referred to as performance or "honeymoon" anxiety and may provoke an intense fear of failure and self-doubt. It can sometimes set off a cycle of chronic impotence. In response to anxiety, the brain releases chemicals known as neurotransmitters that constrict the smooth muscles of the penis and its arteries. This constriction reduces the blood flow into and increases the blood flow out of the penis. Even simple stress may promote the release of brain chemicals that disrupt potency in a similar way.

Depression. Depression is strongly associated with erectile dysfunction. In one study, 82% of men who reported moderate-to-severe erectile dysfunction also had symptoms of depression. Depression can certainly reduce sexual desire, but it is often not clear which condition came first.

Troubles in relationships often have a direct impact on sexual functioning. Partners of men with erectile dysfunction may feel rejected and resentful, particularly if the affected man does not confide his own anxieties or depression. Both partners commonly experience guilt for what they each perceive as a personal failure. Tension and anger frequently arise between people who are unable to discuss sexual or emotional issues with each other. It can be very difficult for the man to perform sexually when both partners harbor negative feelings.

Losing a job or having lower income or education increases the risk for impotence.

Smoking contributes to the development of impotence, mainly because it increases the effects of other disorders of the blood vessels, including high blood pressure and atherosclerosis. A 2006 study found that men who smoked at least a pack a day were 39% more likely to experience ED than non-smokers. Research presented at the 2006 meeting of the American Urological Association indicated that quitting smoking helps reverse ED.

Alcohol has also been implicated in causing impotence. A small amount releases inhibitions, but having more than one drink can depress the central nervous system and impair sexual function.

Some evidence suggests that exposure to estrogen-like chemicals, such as those found in DDT and other pesticides, may contribute to erectile dysfunction. (Such chemicals have been associated with low sperm counts and infertility in men.)

Infrequent erections deprive the penis of oxygen-rich blood. Without daily erections, collagen production increases and eventually may form a tough tissue that interferes with blood flow. The spontaneous erections men have while sleeping or awake may be a natural protection against this process.

Physical Causes

A number of conditions share a common problem with erectile dysfunction -- the impaired ability of blood vessels to open and allow normal blood flow. Such conditions include diabetes, hypertension, coronary artery disease, kidney failure, peripheral artery disease, and stroke. Increasingly, researchers are studying the role of nitric oxide, which plays a major role in keeping blood vessels open, in all of these disorders.

The following diseases are highly associated with erectile dysfunction:

Heart Disease. Erectile problems may be a warning sign of heart disease. Several important studies in 2005 and 2006 firmly established this link. The studies indicated that men with ED are more likely to have coronary artery disease (CAD) and high blood pressure, and more severe forms of heart disease, than men without erectile problems. In fact, the studies suggested that ED is a stronger predictor of CAD than smoking, family history, cholesterol levels, or high blood pressure. Men who experience ED are at greater risk for angina, heart attack, or stroke. Many experts now recommend that men with erectile dysfunction undergo a complete cardiovascular evaluation.
High Blood Pressure (Hypertension). Erectile dysfunction is a very common problem in men with high blood pressure. More than 40 percent of men with erectile dysfunction have hypertension. The disease process is the major contributor to impotence, but many of the drugs used to treat hypertension also cause it. Newer anti-hypertensive drugs, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are less likely to cause erectile dysfunction. In fact, ARBs may be particularly effective in restoring erectile function in men with high blood pressure who suffer from impotence.
Diabetes. Diabetes is a major risk factor for erectile dysfunction. It may increase the risk for ED by as much as 169% and contribute to as many as 40% of impotence cases. Between a third and a half of all men with diabetes report some form of sexual difficulty. Blocked arteries and nerve damage are both common complications of diabetes. When the blood vessels or nerves of the penis are involved, erectile dysfunction can result. Diabetes is also associated with heart disease, another risk factor for ED.
Obesity. Obesity increases the risk for diabetes, heart disease, and erectile dysfunction. According to a 2006 study, obese men are 60% more likely to develop ED than normal weight men.
Metabolic Syndrome. Metabolic syndrome -- a cluster of conditions that includes obesity and abdominal fat, unhealthy cholesterol and triglyceride levels, high blood pressure, and insulin resistance -- is also a risk factor for erectile dysfunction in men older than 50 years.

Parkinson's Disease. As a risk factor for impotence, Parkinson's disease (PD) is an under-appreciated problem. It is estimated that about a third of men with PD experience impotence. The physical cause of PD-related impotence is most likely an impaired nervous system. Depression and lowered self-esteem also contribute to erectile dysfunction in these patients.

Multiple Sclerosis. Multiple sclerosis (MS), which affects the central nervous system, also precipitates sexual dysfunction in as many as 78% of male patients. (Corticosteroids, which are common treatments for MS, may improve sexual function.)

Other Common Medical Conditions. Other medical conditions that have been associated with erectile dysfunction include allergies, thyroid problems, lung disease, and epilepsy.

Advanced prostate cancer can damage nerves needed for erectile function. Prostate surgery and surgical and radiation treatments for prostate cancer can also cause impotence. A number of treatments for sexual dysfunction are available that may help some men. [See In-Depth Report #33: Prostate cancer.]

Prostate Cancer Surgery (Radical Prostatectomy). The first nationally representative study to evaluate long-term outcomes after radical prostatectomy concluded that impotence occurs far more frequently than previously reported. Those who have so-called nerve-sparing surgeries have better results than those whose surgeries affect the nerves around the prostate. Some evidence also suggests that sexual function rates might improve if the nerve-sparing prostate surgeries also spare the ducts that carry semen.

Some studies suggest that impotence after prostate surgery may in part be due to injury to the smooth muscles in the blood vessels. Early treatments to maintain penile blood flow may help restore erectile function. Some men may benefit from PDE5 inhibitor drugs such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra). Other men may need alprostadil injections or suppositories. The vacuum pump is another option.

Radiation. Although it is generally believed that radiation poses a lower risk for impotence than does surgery, studies have reported similar rates after 3 years. Experts suggest radiation injures the blood vessels, leading to erectile dysfunction over time. Some studies report a lower risk for impotence from brachytherapy, a radiation technique that involves the implantation of radioactive "seeds" compared to external-beam radiation. Still, there have been very few studies that have lasted more than 2 years. One 5-year study reported a high long-term rate of impotence (53%) with brachytherapy, which is close to that of standard externally administered radiation. Early use of alprostadil injections and sildenafil (Viagra) may help these men as well as those who had surgery.

Drug Treatments. Prostate cancer medical treatments commonly employ androgen-suppressive treatments, which cause erectile dysfunction.

Surgery for Colon and Rectal Cancers. Surgical and radiation treatments for colorectal cancers can cause impotence in some patients. In general, colostomy does not usually affect sexual function. However, wide rectal surgery can cause short-term or long-term sexual dysfunction. Total mesorectal excision (TME) may pose fewer risks than standard surgery. Sildenafil (Viagra) may help many men who experience this after surgery.

Surgical Treatment of Inflammatory Bowel Disease. Rectal excision for inflammatory bowel disease (IBD) can cause impotence, but rates are low (2 - 4%). Sildenafil (Viagra) is very effective in restoring potency after IBD surgery.

Operations for Fistulas. Surgery to repair anal fistulas can affect the muscles that control the rectum (external anal sphincter muscles), sometimes causing impotence. (Repair of these muscles may restore erectile function.)

Surgery and drug treatments for benign prostatic hyperplasia (BPH) can also increase the risk for impotence, although to a much lesser degree than surgery for prostate cancer.

Between 4 - 10% of patients who have transurethral resection of the prostate (TURP) and open prostatectomy for BPH report impotence afterward. The risk is very low, however, in men who were functioning normally before surgery.
Finasteride (Proscar) has been associated with impotence in 6 - 19% of patients. Anti-androgen drugs used to treat BPH can also cause erectile dysfunction.

About a quarter of all cases of impotence can be attributed to medications. Many drugs pose a risk for erectile dysfunction. Some experts think that nearly every drug, prescription or nonprescription, can be a cause of temporary erectile dysfunction.

Drugs that commonly cause impotence may include:

Drugs used in chemotherapy.
Many drugs taken for high blood pressure, particularly diuretics and beta-blockers.
Most drugs used for psychological disorders, including anti-anxiety drugs, anti-psychotic drugs, and antidepressants, especially selective serotonin reuptake inhibitors (SSRIs). Newer antidepressants pose fewer problems.
Anti-androgens, including drugs known as gonadotropin-releasing hormone agonists. They are used in prostate cancer and also for treating BPH.

Drugs that sometimes cause impotence include:

Older anti-ulcer medications (cimetidine)
Anticholinergic drugs (including some antihistamines)
Antinausea drugs, particularly metoclopramide (Reglan)
Antifungal drugs (especially ketoconazole)
Nonsteroidal anti-inflammatory drugs (NSAIDs), when used on a daily basis

Injury to the Spine. Spinal cord injury and pelvic trauma, such as a pelvic fracture, can cause nerve damage that results in impotence. Other conditions that can injure the spine and effect impotence include spinal cord tumors, spina bifida, and a history of polio.

Orthopedic surgery. Erectile dysfunction can sometimes result from orthopedic surgery. A study of young men who underwent surgical repair (“intramedullary nailing”) for a broken thighbone reported that about 40% of these patients experienced erectile dysfunction after surgery. The researchers theorized that the surgery affected pelvic nerves that play a key role in erection. Patients who received a higher dose of muscle relaxant during surgery had better sexual function outcomes.

Bicycling. Studies have indicated that frequent bicycling may pose a risk for erectile dysfunction by reducing blood flow to the penis. The greatest risk is in cyclers who sit upright while cycling. In addition, a 2004 report in the Journal of Urology found that long distance cyclers may reduce their risk by riding a road bike instead of a mountain bike and by choosing saddles without a cutout.

Note: Vasectomy does not cause erectile dysfunction. When impotence occurs after this procedure, it is often in men whose female partners were unable to accept the operation.

Hypogonadism (Testicular Failure). Hypogonadism in men is a deficiency in male hormones, usually due to an abnormality in the testicles, which secrete these hormones. It affects 4 - 5 million men in the United States. In addition to impotence, hypogonadism causes reductions in energy, sex drive, lean body mass, and bone density. Hypogonadism can be caused by a number of different conditions. Among them are:

Disorders in the pituitary or hypothalamus glands
Malnutrition
Genetic factors
Myotonic dystrophy.
Orchitis (inflammation of the testicles)
Physical injury
Mumps
Radiation treatments
Exercise-induced hypogonadism. Only a few cases of exercise-induced hypogonadism have been identified in men. Some researchers believe, however, that certain athletes may be at risk, including those who began endurance training before full sexual maturity, have very low body weight, and have a history of stress fractures.

Low Testosterone Levels. Only about 5% of men who see a doctor about erectile dysfunction have low levels of testosterone, the primary male hormone. In general, lower testosterone levels appear to reduce sexual interest, not cause impotence.

Other Hormonal Abnormalities. Other hormonal abnormalities that can lead to erectile dysfunction include:

High levels of the female hormone estrogen (which may occur in men with liver disease).
Abnormalities of the pituitary gland that cause high levels of the hormone prolactin are particularly likely to cause impotence.
Other uncommon hormonal causes of impotence include an underactive or overactive thyroid or adrenal gland abnormalities.

A varicocele is an enlarged (varicose) vein in the cord that connects to the testicle. Varicoceles are found in 15 - 20% of all men and in 25 - 40% of infertile men. When varicoceles occur in both testicles, they may contribute to hormone imbalances that cause erectile dysfunction.

Premature Ejaculation. Premature ejaculation is the most common male sexual dysfunction and occurs in as many as 40% of men. It is defined as the inability to delay ejaculation to the point where both partners are satisfied. This can vary widely depending on the preferences of the partners. Younger men tend to have this problem more than older men. Anxiety is a major factor at any age. In general, the longer the duration between ejaculations, the faster they are. Various techniques are available to help delay orgasm.

The standard medications used for this condition are selective serotonin reuptake inhibitors (SSRIs), which include Prozac and Paxil. Some studies suggest that sildenafil (Viagra) in combination with an SSRI may be helpful. A new serotonin-related drug, dapoxetine, showed promise in several clinical trials but was ultimately rejected by the FDA in 2005. There is still no drug specifically approved for treating premature ejaculation.

Peyronie's Disease. Peyronie's disease is an accumulation of scar tissue within the penis shaft, which causes it to curve. The curvature can make erection and intercourse difficult and painful. This condition may be associated with an injury to the penis, but no clear information exists on its origin. Some men may not even be aware that they have it, and there is some evidence that it may be more common than currently believed. In one study, 6.7% of men with an average age of 62 had signs of curvature, but only 2.2% were aware of any difficulties. The disease often goes into a type of spontaneous remission, and some individuals who had previously experienced erectile dysfunction are able to resume sexual activity. Scarring may still cause erection problems, however, even in these cases.

Treatment for Peyronie's Disease. If Peyronie's disease is treated early, ultrasound, heat application, and anti-inflammatory drugs may help reduce scar formation. Some experts believe that the extracorporeal shock wave therapy (ESWT) is the safest and most effective first-line therapy. ESWT uses sound waves to break up scar tissue. It has been used with some success.

Studies also suggest that the calcium channel blocker verapamil may be very beneficial. It can be administered using injection, as a gel patch, or through a process called electromotive drug administration (EMDA), also referred to as iontophoresis. EMDA delivers the drug through an electrical transport of charged molecules. Some studies are reporting good success with EMDA delivery of verapamil along with the steroid dexamethasone.

In severe cases of scarring, the only treatment is surgery to straighten the penis and reduce the curve. Penile implants may also be beneficial.

Priapism. Priapism is a sustained, painful, and unwanted erection that persists despite a lack of sexual stimulation. Generally, priapism results when the smooth muscle tissue remains relaxed so that a constant flow of blood into the vessels of the penis occurs with no leakage back out. The development of priapism has been associated with urinary stones, certain medications, neurologic disorders, and, more recently, with self-injection therapy used for impotence.

Treatment of Priapism. If priapism occurs, applying ice for 10-minute periods to the inner thigh may help reduce blood flow. Erections that last 4 hours or longer require emergency care.

Prognosis

Temporary erectile dysfunction is very common and usually not a serious problem. Nevertheless, if the condition is persistent, psychological effects can be significant. Erectile dysfunction can have a devastating impact on a relationship and can cause extreme depression, which may become chronic if not treated. When a consistent pattern of sexual dysfunction extends over a prolonged period of time, a serious physical or emotional disorder may be present.

Persistent impotence may also be a symptom of a serious medical condition, such as heart disease, diabetes, hypertension, sleep disorders, or circulatory problems. For example, in a study of men who had suffered heart attacks, 75% of them had experienced erectile dysfunction on average 68 months before the heart attack.

Erectile dysfunction can also indicate the presence of injuries or the long-term effects of smoking, heavy drinking, or unhealthy diet.

Diagnosis

The doctor typically interviews the patient about many physical and psychological factors.

Medical and Personal History. The doctor should take a medical and personal history and may ask about the following:

Past and present medical problems
Medications or drugs being used
Any history of psychological problems, including stress, anxiety, or depression

Sexual History. In addition the doctor will ask about the patient's sexual history, which may include:

The nature of the onset of the dysfunction
The frequency, quality, and duration of any erections, and whether they occur at night or in the morning
The specific circumstances when erectile dysfunction occurred
Details of technique
The patient's motivation for and expectations of treatment
Whether problems exist in the current relationship

Interviewing the Sexual Partner. If appropriate, the doctor might also interview the sexual partner. In fact, including the partner in the counseling process is proving to be an important component in making the best treatment choices.

The doctor should perform a careful physical exam, including examination of the genital area and a digital rectal examination (the doctor inserts a gloved and lubricated finger into the patient's rectum) to check for prostate abnormalities.

A useful approach is to administer a treatment for erectile dysfunction and then observe the response. Doctors usually recommend a trial of sildenafil (Viagra) to test for an erection response 30 - 60 minutes after the drug is administered. This drug is replacing more invasive and expensive tests, such as an injection of papaverine or prostaglandin E1, medications that dilate blood vessels in the penis. They produce an erection in about 15 minutes.

After administering the treatment and waiting the appropriate amount of time, the doctor then observes the erectile response, curvature of the penis, and response after erection, sometimes using an ultrasound scanner to assess blood flow.

Blood Tests for Hormonal Abnormalities. Blood tests may be used to measure testosterone levels and, if necessary, prolactin levels to determine if there are hormone problems. The doctor may also screen for thyroid and adrenal gland dysfunction. In addition, various specific tests for erectile dysfunction can be performed.

Tests for Medical Conditions That May be Causing Erectile Dysfunction. Evidence of other medical conditions should be sought, particularly high blood pressure, diabetes, atherosclerosis, and nerve damage.

Tests that monitor nighttime erections may be used to determine if the causes of erectile dysfunction are more likely to be psychological than physical.

Snap-Gauge Test. The snap-gauge test monitors the man's ability to achieve an erection during sleep. It is a very simple test.

When the man goes to bed, he places bands around the shaft of his penis.
If one or more breaks during the course of the night, it provides evidence of an erection. In this case, a psychological basis for the erectile dysfunction is likely.

RigiScan Monitor. A more sophisticated and expensive device is the RigiScan monitor, which makes repetitive measurements of rigidity around the base and tip of the penis. This test is quite accurate but may fail to detect mild cases of erectile dysfunction.

The penile brachial index is a measurement that compares blood pressure in the penis with the blood pressure taken in the arm. Problems with the arterial flow to the penis can be detected using this method.

Imaging tests may be used in certain cases, but they are expensive and often limited to younger men. Anyone considering these tests should have them done in a specialized setting by professionals experienced in their use.

Dynamic Infusion Cavernosometry and Cavernosography. Dynamic infusion cavernosometry and cavernosography (DICC) is usually given only to young men in whom some blockage of the penis or physical injury of the pelvic area is suspected. After an erection is induced with drugs, the following four steps are taken:

The penile brachial index is taken.
The storage ability of the penis is gauged.
An ultrasound of the penile arteries is performed.
An x-ray of the erect penis is taken.

Unfortunately, this test and other similar imaging techniques used to determine blood flow in the penis are not very effective or accurate in diagnosing and determining treatment.

Duplex Doppler Ultrasound. An ultrasound technique called duplex Doppler ultrasound may be useful alone or with sildenafil (Viagra) in determining the severity of condition and also to determine impaired blood flow through the arteries.

Treatment

The cause of impotence dictates the mode of treatment. The first step is to define the cause, if possible, and then try the simplest and least-risky solution.

Before a certain treatment is prescribed, the following factors should be considered:

Any pre-existing illnesses and medications
The degree of comfort with the treatment method
Partner satisfaction and safety profiles need to be considered. Experts strongly recommend that the patient's partner be involved to help with any necessary sexual adjustment.

No matter what the treatment, embarking on a healthy lifestyle is the first and critical step for maintaining and restoring erectile function.

Medical and Surgical Treatments. Sildenafil (Viagra), the first effective oral drug for erectile dysfunction, has been on the market since 1998 and rapidly became the treatment of choice for most men with erectile dysfunction. In 2003, the FDA approved two other oral medications, vardenafil (Levitra) and tadalafil (Cialis), for the treatment of erectile dysfunction.

Men who cannot or choose not to take the drugs still have many other options, including:

Medications inserted or injected into the penis
Vacuum devices
Intracavernosal injection therapy
Invasive procedures, such as penile implants or surgery (limited to those for whom other treatments haven't worked and who have been carefully screened)

Ultimately, how successful the medical treatment is and how well it is accepted depends, in large part, on the man's expectations and how he and his partner both adapt to the procedure.

Psychotherapies. Some form of psychological, behavioral, or sexual therapy is often recommended for individuals suffering from severe impotence, regardless of cause.

Lifestyle Changes

Because many cases of erectile dysfunction are due to reduced blood flow from blocked arteries, it is important to maintain the same lifestyle habits as those who face an increased risk for heart disease.

Diet. Everyone should eat a diet rich in fresh fruits and vegetables, whole grains, and fiber and low in saturated fats and sodium. Because erectile dysfunction is often related to circulation problems, diets that benefit the heart are especially important.

Foods that some people claim to have qualities that enhance sexual drive include chilies, chocolate, scallops, oysters, olives, and anchovies. No hard evidence exists for these claims.

Exercise. A regular exercise program is extremely important. One study reported that older men who ran 40 miles a week boosted their testosterone levels by 25% compared to their inactive peers. Another study found that men who burned 200 calories or more a day in physical activity (which can be achieved by 2 miles of brisk walking) cut their risk of erectile dysfunction by half compared to men who did not exercise.

A study in the Journal of the American Medical Association found that adopting healthy lifestyle changes improved sexual function in obese men (BMI less than 30) with erectile dysfunction. After 2 years, a third of the study participants on the reduced calorie diet and an increased exercise regimen regained sexual function.

Limit Alcohol and Quit Smoking. Men who drink alcohol should do so in moderation. Quitting smoking is essential.

Staying sexually active can help prevent impotence. Frequent erections stimulate blood flow to the penis. It may be helpful to note that erections are firmest during deep sleep right before waking up. Autumn is the time of the year when male hormone levels are highest and sexual activity is most frequent.

The Kegel exercise is a simple exercise commonly used by people who have urinary incontinence and by pregnant women. It may also be helpful for men whose erectile dysfunction is caused by impaired blood circulation. The exercises consist of tightening and releasing the pelvic muscle that controls urination:

Since the muscle is internal and is sometimes difficult to isolate, practice first while urinating. (Once learned, however, Kegel exercises should not be regularly performed while urinating because doing them at that time may eventually weaken the muscles.)
Try to contract the muscle until the flow of urine is slowed or stopped. Attempt to hold each contraction for 10 seconds.
Then release the muscle.
Perform about 5 - 15 contractions three to five times daily.

It may be several months before the patient sees significant improvement.

If medications are causing impotence, the patient and doctor should discuss alternatives or reduced dosages.

Even if erectile dysfunction is caused by a physical problem, interpersonal, supportive, or behavioral therapy are often helpful for patients. Therapy may also ease the adjustment period after the initiation or completion of treatment. It is beneficial to have the partner involved in this process.

Medications

Three medicines taken by mouth are approved for the treatment of erectile dysfunction: Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). All three belong to a class of drugs called selective enzyme inhibitors. Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) block the enzyme phosphodiesterase-5 (PDE5). Blocking this enzyme helps maintain levels of cyclic guanosine monophosphate (GMP), a chemical produced in the penis during sexual arousal. Balanced levels of GMP cause the smooth muscles of the penis to relax and increase blood flow.

Good Candidates for PDE5 Inhibitors. PDE5 inhibitors are a good choice for men at any age and in any ethnic group who are in good health and who do not have conditions that preclude taking them (such as the use of nitrates or alpha-blockers; see Higher-risk candidates in this section.)

Effectiveness of PDE5 Inhibitors.

Tadalafil (Cialis). Tadalafil usually takes effect in 15 - 30 minutes. It is the only oral ED treatment shown to improve erectile dysfunction for up to 36 hours in most men. A randomized study of over 2,000 men found that nearly two-thirds reported successful intercourse attempts 24 - 36 hours after taking the drug.
Vardenafil (Levitra). Extensive clinical studies indicate that vardenafil improves erectile dysfunction in up to 85% of men with the condition. It also works well in patients with diabetes and in those who have had a radical prostatectomy.
Sildenafil (Viagra). Studies indicate that overall, sildenafil may help more than 70% of patients achieve sexual function.

Studies indicate that PDE5 inhibitors are safe and effective for many men whose erectile dysfunction is related to the following conditions:

Hormonal problems or psychologically induced impotence. These men achieve the highest success rates (80 - 100%).
Stable heart disease. However, PDE5 inhibitors should not be used by men who take nitrate drugs for chest pain or heart problems.
Mild-to-moderate heart failure. A study in the Archives of Internal Medicine found that men with moderate heart failure and ED can safely use sildenafil to improve their sexual function and overall quality of life, provided the men are not taking nitrates for their heart condition. Other research has also suggested that sildenafil is safe for this group of men.
Controlled high blood pressure.
Controlled diabetes (type 1 or 2). Diabetes has been associated with a lower than average response to sildenafil. Still, in a 2002 study over half of patients with type 2 diabetes achieved at least one successful sexual event.
Kidney conditions, including those that require chronic dialysis or kidney transplantation.
Parkinson's disease. Some evidence suggests that sildenafil may have properties that improve depression and help brain functions (attention, memory).
Depression. PDE5 inhibitors may help men who take antidepressant drugs that cause sexual dysfunction, notably selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac).

PDE5 inhibitors may also help restore erectile dysfunction in some men who have had the following conditions or treatments:

Treatments for prostate cancer. In men who have had radiation, advanced techniques, such as 3D conformal therapy, along with PDE5 inhibitors offer the best chances for success. In men who have had surgery, PDE5 inhibitors are most effective in younger men who were potent before surgery and who had bilateral nerve-sparing procedures. It is unlikely to be effective for men over age 55 who had unilateral or non-nerve-sparing procedures. Starting first with alprostadil injections right after treatment, followed by a PDE5 inhibitor, may be the best approach and considerably improve success rates.
Diabetes. PDE5 inhibitors appear to be safe and effective, at least in the short term, for most men with diabetes. There is not yet enough evidence to know whether these drugs are safe for long-term use.
Colon surgeries for cancer or inflammatory bowel disease.
Spina bifida, a congenital defect of the spinal cord.
Spinal cord injury. PDE5 inhibitors can be very effective in many of these men, especially those in which there is some erectile response and when the injuries are in the upper part of the spine.

Higher-Risk Candidates. PDE5 inhibitors are not suitable for everyone. Men who take nitrate drugs for angina, anticoagulants for heart conditions, or certain types of alpha-blockers for high blood pressure and benign prostatic hyperplasia (BPH), should not take PDE5 inhibitors. Men with the following conditions should not take PDE5 inhibitors without the recommendation of their doctors and even then should use them with caution:

Severe heart disease, such as unstable angina, a history of heart attack, or arrhythmias. Sildenafil increases nerve activity associated with cardiovascular function, especially during physical and mental stress. Men with heart disease may benefit from an exercise test to determine whether resuming sexual activity increases their risk of a heart attack.
Recent history of stroke
Hypotension (very low blood pressure)
Uncontrolled hypertension (high blood pressure)
Uncontrolled diabetes
Severe heart failure
Retinitis pigmentosa. (With this genetic disease, people do not produce phosphodiesterase-5 and do not respond to PDE5 inhibitors.)

Administration and Effect. PDE5 inhibitors work only when the man experiences some sexual arousal. They are generally effective within 30 - 120 minutes when taken on an empty stomach. Sildenafil should be taken on an empty stomach; vardenafil and tadalafil may be taken with or without food. The effects of these drugs may last for several hours. PDE5 inhibitors should not be used more than once a day.

Success rates increase with the number of attempts, so a man should not be discouraged if the drug does not work at first.

PDE5 inhibitors can also be used in combination with testosterone replacement therapy, but this combination may cause a number of side effects.

Side Effects and Other Limitations. Common side effects of PDE inhibitors include flushing, upset stomach, headache, nasal congestion, back pain, and dizziness.

Effects on the Heart. There have been reports of fatal heart attacks in a small percentage of men taking sildenafil (Viagra). Viagra can cause sudden and dangerous drops in blood pressure when the drug is taken with nitrate drugs, such as nitroglycerine, which are used for angina. No one taking nitrates, including the recreational drug amyl nitrate, should take sildenafil or any other PDE5 inhibitors.

Visual Effects. About 2.5% of men experience abnormal visual effects that include seeing a blue haze, temporary increased brightness, and even temporary vision loss in a few cases. Experts believe that visual disturbances are related to the inhibition of phosphodiesterase enzymes in the retina, but the effect appears to be temporary and insignificant, lasting a few minutes to several hours. Men at risk for eye problems who take PDE5 inhibitors regularly should have frequent eye examinations with an ophthalmologist. Men should also see an eye doctor if visual problems last more than a few hours.

In 2005, the FDA began investigating reports of partial vision loss in men who took sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). The vision loss was caused by non-arteric anterior ischemic optic neuropathy (NAION), a condition that occurs from poor blood flow to optic nerves. However, experts note that erectile dysfunction is itself linked to the same vascular problems that cause NAION. Patients who suffer from diabetes, high blood pressure, and heart disease are at higher risk for erectile dysfunction as well as other vascular problems such as NAION. Information concerning vision loss has been added to the labels of these drugs, but the risk of blindness appears small. Still, patients who use this medication and experience a sudden loss of vision should immediately stop taking the drug and contact their doctor.

Seizures. There have been a few reports of seizures in men taking sildenafil. These are rare occurrences and it is not clear if there is any causal association.

Risk of Priapism. PDE5 inhibitors pose a very low risk for priapism in most men. (Priapism is sustained, painful, and unwanted erection.) Exceptions are young men with normal erectile function.

Interactions with Other Drugs. In addition to serious interactions with nitrates, PDE5 inhibitors may also interact with certain antibiotics, such as erythromycin, and acid blockers, such as cimetidine (Tagamet). Patients should tell their doctor about any medications they are taking.

Decrease in Effectiveness. Over time, PDE5 inhibitors may lose effectiveness. A 2001 study found that after 2 years, 20% of patients had increased their dose of sildenafil to achieve the same effect, and 17% had discontinued the drug due to loss of efficacy. It is possible that these men were suffering from heart disease or other problems that made their impotence worse. An earlier study found that 96% of men who had been taking sildenafil for 2 - 3 years remained satisfied with the treatment. In addition, some research indicates that sildenafil treatment may be less effective in men with diabetes.

Other PDE5 Inhibitors. Avanafil and SLX-2101 are new PDE5 inhibitors that are showing promising results in clinical trials.

Melanocortin receptor agonists. Melanocortin receptor agonists work on the central nervous system instead of the vascular system. Bremelanotide (formerly PT-141) is the first of these drugs to be investigated in clinical trials. Researchers are testing the drug as a nasal spray given either alone or in combination with a PDE5 inhibitor.

Gene Therapy. Researchers are investigating gene transfer therapy as a possible cure for erectile dysfunction. Promising results from the first human trial were presented at the 2006 American Urological Association meeting. The gene-based therapy, called hMaxi-K, uses injections of a gene that helps the body manufacture proteins to improve smooth muscle relaxation. The treatment requires injections twice a year. It is still in the very early stages of research.

Injections or Topical Treatments

Penile injections have now largely been replaced by PDE5 inhibitors, such as sildenafil. Nevertheless, injection therapies use various drugs that have properties that help achieve erection, even in many men who do not succeed with PDE5 inhibitors. The standard drugs used in injections include:

Alprostadil
Phentolamine
Papaverine

Although any or all of these drugs are very effective, injections or other invasive methods of administration are awkward and uncomfortable.

Alprostadil is derived from a natural substance, prostaglandin E1, and acts by opening blood vessels. It is an effective treatment for some men. It can be administered by:

Injection into the erectile tissue of the penis (Caverject, Edex)
A device that administers the drug through the urethra (MUSE system)

Candidates. Regardless of how it is administered, alprostadil works in many men with a wide range of medical disorders related to erectile dysfunction, including men with:

Diabetes
Prostate cancer treatments (early use of alprostadil injections after prostate cancer treatment, particularly when followed by a PDE5 inhibitor, may be helpful)
Cholesterol problems treated with nitrates
Injury

Alprostadil is not an appropriate choice for men with:

Severe circulatory or nerve damage
Bleeding abnormalities or men who are taking medications that thin the blood, such as heparin or warfarin
Penile implants

Injected Alprostadil. Injected alprostadil (Caverject, Edex) uses a very small needle that the man injects into the erectile tissue of his penis. About 80% of men describe the pain of administering the injection as very mild. Edex is a newer and less expensive form of injected alprostadil. In one 12-month study of 894 patients, Edex injections achieved erections in 95% of attempts.

The drug should not be injected more than 3 times a week or more than once within a 24-hour period.

MUSE System. The MUSE system delivers alprostadil through the urethra. It works in the following way:

The device is a thin plastic tube with a button at the top.
The man inserts the tube into his urethral opening right after urination. (Urinating or urine leakage right after administration may reduce the amount of medication.)
He presses the button, which releases a pellet containing alprostadil.
The man rolls his penis between his hands for 10 - 30 seconds to evenly distribute the drug. To avoid discomfort, the man should keep the penis as straight as possible during administration.
The man should be upright, either sitting, standing or walking for about 10 minutes after administration. By that time, he should have achieved an erection that lasts between 30 - 60 minutes. (If a man lies on his back too soon after administration, blood flow to the penis may decrease and the erection may be lost.)
The erection may continue after orgasm.

The MUSE system should not be used more than twice a day and is not appropriate for men with abnormal penis anatomy.

Side Effects of Most Alprostadil Methods. Certain side effects are common to all methods of administration, although they may differ in severity depending on how the drug is given:

Pain and burning at the application site. In one study half of the men who injected alprostadil experienced some burning and pain at the injection site.
Scarring of the penis (Peyronie's disease), which is most likely to occur with injections.
Sudden, low blood pressure. Symptoms include dizziness, lightheadedness, and fainting. If these symptoms occur, the man should lie down immediately with his legs raised.
Priapism (prolonged erection). Possible with any method, but less chance with the MUSE system than with injections. If priapism occurs, applying ice for 10-minute periods to the inner thigh may help reduce blood flow. Erections that last 4 hours or longer require emergency care.
Women partners may experience vaginal burning or itching. The drug may have toxic effects if it reaches the fetus in pregnant women, so men should not use alprostadil for intercourse with pregnant women without the use of a condom or other barrier contraceptive device.
Other side effects. Other side effects include minor bleeding or spotting, redness in the penis, and aching in the testicles, legs, and area around the anus.

Until the introduction of alprostadil, the two drugs used for injection therapy had been papaverine (Pavabid, Cerespan) and phentolamine (Regitine). Adverse reactions are usually minor but include pain, ulcers, and prolonged erections (priapism).

According to 2006 guidelines from the Endocrine Society, testosterone replacement therapy works best for men with erectile dysfunction who have been diagnosed with hypogonadism (low testosterone levels). For these men, experts recommend combination of testosterone and other ED treatments, such as PDE-5 inhibitors. Men who have ED and normal testosterone levels are not likely to benefit from testosterone therapy.

Forms of testosterone therapy include:

Muscle injections using testosterone enanthate (Andryl, Delatestryl) or cypionate (Andro-Cyp, Depo-Testosterone, Virion). This has been the standard administration.
Skin patch (Testoderm, Testoderm TTS, Androderm). Depending on the brand, patches may be applied to the skin of the scrotum every 24 hours or to the abdomen, back, thighs, or upper arm. In the latter case, two patches are required every 24 hours. Testoderm and Testoderm TTS may cause less skin irritation than Androderm.
Skin gel (Androgel, Testim). At this time, the gel is applied only to the same parts of the body as the patch. A gel applied to the penile skin is being investigated for men with hypogonadism and erectile dysfunction. Pregnant women must avoid contact with the gel because theoretically the testosterone could harm the fetus.

Oral forms of testosterone are not recommended because of the risk for liver damage when taken for long periods of time.

Testosterone therapy may increase the risk for the following adverse effects, particularly in men with normal testosterone levels:

Lowering of HDL ("good" cholesterol)
Rapid growth of prostate tumors in men with existing prostate cancers. (Taking testosterone does not appear to increase the risk for prostate cancer, but experts remain concerned.)
Lower sperm count
Sleep apnea
Polycythemia, an abnormal increase in red blood cells
Benign prostatic hyperplasia

Other Treatments

Vacuum devices, or external management systems, are effective, safe, and simple to use for all forms of impotence except when severe scarring has occurred from Peyronie's disease.

Using the Device. Patients must receive thorough instructions in the proper use of such devices. They typically work as follows:

The man places the penis inside a plastic cylinder.
A vacuum is created, which causes blood to flow into the penis, thereby creating an erection.
A band is tightly secured around the base of the penis, which retains the erection, and the cylinder is removed.
It takes about 3 - 5 minutes to produce an erection.

Lack of spontaneity is this method's major drawback. The erection involves only part of the penis shaft, and the process will certainly seem peculiar in the beginning. When these psychological obstacles are overcome, many couples find the result highly satisfactory.

Success Rates. Studies have found that success with the vacuum device is about equal to other methods. Between 56 - 67% of men using it reported the device to be effective. In one study of men who had used the vacuum device for many years, almost 79% reported improvement in their relationships with their sexual partners, and 83.5% said they had intercourse whenever they chose. Nevertheless, dropout rates are high. In one study, for example, the overall drop out rate was 65%. Even in a high-success group, over half stopped using it.

Side Effects. Side effects include blocked ejaculation and some discomfort during pumping and from use of the band. Minor bruising may occur, although infrequently. It is very important to use a medically approved pump. There have been reports of injury from vacuum devices that do not have a pressure-release valve or other safety elements.

Vacuum-less devices that trap blood within the penis are also available. They are called venous flow controllers or simple constricting devices. These devices are typically rubber or silicone rings or tubes that are placed at the base of the erect penis to trap the erection. They can be used by men who can achieve erections but lose them easily. These devices should not be used for longer than 30 minutes or lack of oxygen can damage the penis, and they should not be used by patients who have bleeding problems or are taking anticoagulant medicines ("blood thinners").

Penile implants are available for men who cannot take medication or who fail less invasive treatments. A 2006 study reported that penile implants helped restore sexual function to 89% of men who had the procedure, and 81% of men were satisfied with the results.

Three types of surgical implants are used for the treatment of erectile dysfunction:

A hydraulic implant consists of two cylinders placed within the erection chambers of the penis and a pump. The pump releases a saline solution into the chambers to cause an erection, and removes the solution to deflate the erection.
A penile prosthesis is composed of two semi-rigid but bendable rods that are placed inside the erection chambers of the penis. The penis can then be manipulated to an erect or non-erect position.
A third implant uses interlocking soft plastic blocks that can be inflated or deflated using a cable that passes through them.

There appear to be no long-term immune problems related to the silicon or other materials in the devices.

Limitations. Erectile tissue is permanently damaged when these devices are implanted and procedures are irreversible. Although uncommon, mechanical breakdown can occur, or the device can slip or bulge, especially if the patient coughs or vomits vigorously after the operation. In addition, a less than optimal quality of erection may result. (Using the MUSE system may restore or improve the function of a penile prosthesis in patients with a failed device.)

Complications. Infection is the major concern with these devices. Redness and fever often accompany a full-blown infection. Any intermittent pain that continues to occur after an implant may be an indicator of a low-grade infection. If the infection can be caught early enough, implant failure can be prevented. Most infections are treated with antibiotics for at least 10 - 12 weeks. If antibiotics fail, a surgical exchange, in which the infected implant is simultaneously replaced with a new one, should be considered. This is a complex procedure, but some surgeons have reported a 90% success rate.

For men whose impotence is caused by damage to the arteries or blood vessels, vascular surgery might be an option. Two types of operations are available: revascularization (bypass) surgery, and venous ligation. The American Urologic Association stresses that vascular surgery is still investigational.

Revascularization. The revascularization procedure usually involves taking an artery from a leg and then surgically connecting it to the arteries at the back of the penis, bypassing the blockages and restoring blood flow. In a related procedure called deep dorsal vein arterialization, a penile vein is used for the bypass. Young men with local sites of arterial blockage or those with pelvic injuries generally achieve the best results. In studies of selected patients there was improvement in erectile dysfunction in 50 - 75% of men after 5 years.

Venous Ligation. Venous ligation is performed when the penis is unable to store a sufficient amount of blood to maintain an erection. This operation ties off or removes veins that are causing an excessive amount of blood to drain from the erection chambers. The success rate is estimated at between 40 - 50% initially, but drops to 15% over the long term. It is important to find a surgeon experienced in this surgery. In a variation of this technique called venous ablation, ethanol is injected into the deep dorsal vein, the main vein that drains blood from the penis. The ethanol causes scarring that closes off smaller veins and prevents blood leakage, thereby bolstering erectile function.

Natural Remedies

The following are special concerns for people taking alternative remedies for erectile dysfunction:

Yohimbe. Yohimbe, which is similar to yohimbine, is derived from the bark of a West African tree. Side effects include nausea, insomnia, nervousness, and dizziness. Large doses of yohimbe can increase blood pressure and heart rate and may cause kidney failure.

Gamma-Butyrolactone (GBL). GBL is found in products marketed for improving sexual function (Verve, Jolt). This substance can convert to a chemical that can cause toxic and life-threatening effects, including seizures and even coma.

Gingko. Although the risks for gingko appear to be low, there is an increased risk for bleeding at high doses and interaction with vitamin E, anti-clotting medications, and aspirin and other NSAIDs. Large doses can cause convulsions. Commercial gingko preparations have also been reported to contain colchicine, a substance that can be harmful in people with kidney or liver problems.

L-arginine (also called arginine). Arginine may cause gastrointestinal problems. It can also lower blood pressure and change levels of certain chemicals and electrolytes in the body. It may increase the risk for bleeding. Some people have an allergic reaction to it, which in some cases may be severe. It may worsen asthma.

DHEA. DHEA is a supplement related to certain male and female hormones. Studies show inconclusive results in its treatment for erectile dysfunction. DHEA may interact dangerously with other medications.

Aphrodisiacs. Aphrodisiacs are substances that are supposed to increase sexual drive, performance, or desire. Examples include:

Viramax is a well-marketed product that contains yohimbine and three herbal aphrodisiacs: catuaba, muira puama, and maca. It has not been proven to be either effective or safe, and interactions with medications are unknown.
Spanish fly, or cantharides, which is made from dried beetles, is the most widely-touted aphrodisiac but can be particularly harmful. It irritates the urinary and genital tract and can cause infection, scarring, and burning of the mouth and throat. In some cases, it can be life threatening. No one should try any aphrodisiac without consulting a doctor.

Other Alternative Products Marketed for Erectile Dysfunction. Vinarol is an over-the-counter supplement that was recalled by the FDA in 2003 after reports surfaced that it contained the same ingredients found in Viagra. Herbal supplements sold as Viagro and Vaegra have no association with Viagra. There are numerous other products marketed as “all-natural” dietary supplements and promoted as treatments for erectile dysfunction and sexual enhancement. The FDA has not approved any of these products and has issued many warnings concerning them. In 2006 and 2007, the FDA warned that “True Man,” “Energy Max,” “Rhino Max,” “VMax,” Libidus,” and similar dietary supplements contain illegal chemicals that can interact with prescription drugs and cause dangerously low blood pressure. These products are particularly dangerous for men with diabetes, high blood pressure, high cholesterol, or heart disease who take prescription drugs that contain nitrates.

Resources

www.niddk.nih.gov -- National Kidney and Urologic Diseases Information
www.auanet.org -- American Urologic Association
www.urologyhealth.org -- Urology Health

References

Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006 Jun;91(6):1995-2010. Epub 2006 May 23.

Heidler S, Temml C, Broessner C, Mock K, Rauchenwald M, Madersbacher S, et al. Is the metabolic syndrome an independent risk factor for erectile dysfunction? J Urol. 2007 Feb;177(2):651-4.

Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med. 2007 Feb;120(2):151-7.

Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24(1):CD002187.

Review Date:
6/27/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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