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Sex Is Healthy: Part II

FitSugar — Wed, 02 Jan 2008 03:00:00 -0800

If having more sex is one of your New Year's Resolutions for 2008 (don't laugh, it's on my husband's list every year) then you may be doing more for your health than you originally thought. Here are some reasons why:

Sleep enhancement. There’s no need to count sheep when sex, including masturbation, helps insomnia.
A better, younger looking you. Sex keeps you looking and feeling younger and, according to some research, may lead to shiny hair, a glowing complexion and bright eyes.
Mood lifter. Sex releases pleasure-inducing endorphins during arousal and climax that can relieve depression and anxiety, and increase vibrancy.
Longevity. There is a significant relationship between frequency of orgasm and risk of death, especially with men.
Decreased risk of breast cancer. One study of women who had never given birth found that an increased frequency of sexual intercourse was correlated with a decrease in the incidence of breast cancer.
Reproductive health benefits. According to at least one study, sex appears to decrease a man’s risk of prostate cancer, and the prevention of endometriosis in women.

Source

Sex Is Healthy: Part I

FitSugar — Thu, 20 Dec 2007 10:15:00 -0800

If have more sex is one of your New Year's resolutions for 2008 (don't laugh, it's on my husband's list every year) then you may be doing more for your health than you originally thought. Here are some reasons why:

Weight loss and control. Forget torturing yourself with the latest fad diet or hours on the elliptical machine when you can burn about 200 calories in 30 minutes of sex!
Pain management. Forgo popping a pain killer and opt for something a bit more au naturel.
Stress relief. Sex, even if only with ourselves, impacts the way we respond to stress, increasing levels of oxytocin and stimulating feelings of warmth and relaxation.
Immune booster. Stop spending late nights at the office. Sex wards off colds and the flu.
Better heart health. A little bit of heart and soul in the sack should be part of every doctor’s orders when it comes to cardiovascular care.
Increased self-esteem and intimacy. When sex is consistent and involves mutual pleasure, it can increase bonding since the surge in oxytocin at orgasm stimulates feelings of affection, intimacy, and closeness.

Source

Tina Fey Says No to Working Out

FitSugar — Thu, 08 Oct 2009 04:30:37 -0700

In the November issue of Harper's Bazaar, funny woman Tina Fey reveals that she doesn't work out - at all. Looking at 39-year-old Fey I would not have guessed that she stays away from the gym. She's slim and carries herself with style and sex appeal. It's also surprising to hear that any woman working in an industry driven in large part by image is able to escape having a personal trainer.

When asked why she stays away from the gym, it comes down to not enough time in her day. The woman is busy, very busy. She's got a hit show to write, is a wife and mother, and is an Emmy-award-winning actress.

To hear what Tina thinks about working out, read more.

"Work, come home, play, kid bounce, work again, go to bed." She has thought about yoga, even done it a couple times. "But," she notes, "even yoga classes go on 80 or 90 minutes." The ethos of Gwyneth Paltrow or Madonna, with their two hours plus of bendiness a day, is not for Tina. "You will still die," she observes. "I'll do grave yoga. Someone can come and stretch me in my grave."

Tina explains her relationship to the business of celebrity this way:

"I like to delude myself that I'm in the old-Hollywood mode. I just tailor my clothes well and try to keep my skin clear. While it would be great to work out an hour a day, there is something inherently sort of selfish about it. I can't do it."

Despite not working out, the actress does focus on maintaining a healthy diet. At the age of 29, Fey dropped an astounding 35 pounds after going on Weight Watchers. The actress describes it as a time in her life where she learned to eat properly, something she still continues to do.

What do you think? Does working in a workout seem selfish to you?

Which Foods Fuel Your Sex Drive?

FitSugar — Wed, 22 Jul 2009 04:30:00 -0700

Food can do more than fuel your workouts; it's also good for revving up your sex drive. Eating mood-boosting foods is a subtle way to lubricate your libido, so amp up your desire and reap the healthy benefits of having sex. Do you know which foods are known to help with your sex drive?

Take the quiz

How Jada Pinkett Smith Keeps Her Love Life Hot

FitSugar — Tue, 14 Jul 2009 04:30:59 -0700

Jada Pinkett Smith is no stranger to sharing details about her love life; with 12 years of a successful Hollywood marriage under her belt, she probably has some healthy secrets we could all use. She told Shape magazine that she is a firm believer in kegels. Pinkett Smith proclaims doing these simple pelvic floor exercises "keeps the sex hot."

Learn how to tone up down there when you read more.

If you practice yoga, you might refer to the pelvic floor (PF) as the mula bandha. The easiest way to find the correct area to activate is to stop the flow of urine when emptying your bladder. Then try to find that same sensation when not going to the restroom. A little more advanced variation is to create the sensation of the entire pelvic floor pulling up. The muscles of the pelvic floor fill in the space between your pubic bone (front of your pelvis), your coccyx (tail bone), and your sit bones (ischial tuberosities in anatomy lingo). The overall shape is similar to a kite and contains many different muscles. To activate the pelvic floor you want to imagine those aforementioned bones coming closer to one another as the muscles attached to them activate and pull up - like a sheet being held by four corners billowing up as the corners move toward the center. It helps to think of the PF as similar to your diaphragm, which moves up and down as you inhale and exhale.

Here is a subtle and simple exercise that you can do right now. It is so subtle that no one will know you are exercising your nether regions. On a four-count inhale, pull the PF up and in toward the center line of your body. Then release slowly on a four-count exhale. Allow your pelvic floor to completely relax in between repetitions. Repeat five to 10 times and throughout the day. Aside from beneficial side effects in the bedroom, a strong pelvic floor provides support while running and lifting weights too. After all, it is part of your core.

Weight control and diet

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

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., 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

Vitamins

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

In This Report

Highlights
Introduction
Carotenoids
Phytochemicals
Healthy Foods
Dietary Health Benefits
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer

Growing evidence suggests that vitamins and micronutrients, especially from foods, may play important roles in the prevention or treatment of certain cancers:

One study found that the risk of prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose.
A diet high in cruciferous vegetables has been found to reduce the risk of kidney cancer; low consumption of cruciferous vegetables increases the risk.

On the other hand, high amounts of folic acid (a B vitamin) may be associated with colorectal cancer, and beta-carotene supplements are associated with increased lung cancer risk in smokers and people exposed to asbestos.

Macular Degeneration

In 2007, the National Eye Institute recommended that people with intermediate or advanced macular degeneration in one eye take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc.

Osteoporosis

Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it also may be effective in treating rheumatoid arthritis.

Heart Disease

Although people with high levels of homocysteine are prone to developing blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with B vitamins and folic acid does not reduce the incidence of deep vein thrombosis (DVT). A 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with folic acid and other B vitamins had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke.

Introduction

Vitamins do not share a common chemistry, but they do share certain characteristics. They are all organic nutrients that are necessary in small amounts for normal metabolism and good health. Your diet or supplements provide most vitamins. The body can manufacture only three vitamins (D, K, and the B vitamin biotin) from nondietary sources. Unlike carbohydrates, fats, and proteins, vitamins are not sources of energy. Instead, vitamins are chemical partners for the enzymes involved in the body's metabolism, cell production, tissue repair, and other vital processes.

Vitamins are either fat soluble or water soluble. The fat-soluble vitamins, which include A, D, E, and K, are absorbed by the body using processes that closely parallel the absorption of fat. They are stored in the liver and used up by the body very slowly. The water-soluble vitamins include C and the B complex vitamins. The body uses these vitamins very quickly. Excess amounts are eliminated in urine.

The Recommended Daily Allowance (RDA) for vitamins, set by the Food and Nutrition Board of the National Academy of Sciences-National Research Council, has been used for years as a guide for determining the amount of vitamins needed for a healthy diet. The RDA refers to an estimate of the average daily requirement. It is not completely adequate, however, for informing people about the amounts of vitamins they may need.

The RDA is gradually being enhanced using a new standard called the Dietary Reference Intake (DRI). The DRI is based on the following ratings, which will eventually appear on labels:

The recommended daily allowance (RDA). This is the current rating on most vitamins.
The estimated average requirement (EAR). This is the amount adequate for 50% of all people, which will be put on labels when it can be calculated.
Adequate intake (AI). This is an amount that will be used if there is insufficient data to calculate the EAR.
Tolerable upper intake level (UL). This is the maximum dose likely to be safe in nearly all individuals. It will be included on labels if this amount is known.

Food and supplement labels now typically list the Daily Value (DV). This is the percentage of the amount of a nutrient that experts believe a person needs in their daily diet. On food labels it is usually based on one serving size for a person who takes in 2,000 calories a day.

Regulation of dietary supplements by the U.S. Food and Drug Administration (FDA) is a complex issue.

Labels on vitamins and other dietary supplements now include nutrient information and list all ingredients, including identifying parts of plants from which ingredients may be taken. Unlike the labels for drugs, however, labels for vitamins and supplements may not claim to prevent or treat any specific disease. Labels for vitamins and supplements include one of the following:

Health claim -- description of how the substance may reduce the risk of a health-related condition
Nutrient claim -- description of the amount of the nutrient in the product or
Structure or function claim -- description of how the product may affect organs or systems of the body, without claiming to prevent or treat specific disease

The quality of dietary supplements depends on the manufacturer and is not ensured by FDA. The U.S. government does not require that supplements be standardized, meaning that the amounts or quality of nutrients may vary depending on the batch. So, more expensive supplements are not necessarily better than the less expensive ones. Government regulations are in the process of catching up to the boom in the supplement industry. In the meantime, some companies voluntarily adhere to rigorous quality controls, while others do not.

The U.S. Pharmacopeia (USP), an independent organization that sets quality standards for drugs, has also implemented standards for vitamins. Consumers may look for the USP label on products of companies that adhere to these standards. USP verification means the following:

What is in the bottle matches what is listed on the label.
There are no harmful levels of contaminants.
The supplement will be absorbed properly into the body.
It has been produced according to good manufacturing standards.

Before selling any supplement introduced after 1994, manufacturers must submit information as to why the product is considered safe for people. The FDA may refuse to allow it on the market if it finds the evidence insufficient. The FDA does not require manufacturers to provide any scientific evidence that dietary supplements are safe and effective before a product is sold (unlike drugs, which must be proven both safe and effective through clinical trials). If a supplement causes side effects in people once it is for sale, the government may place restrictions on the supplement or withdraw it from the market. The FDA may also withdraw products from the market if their labels are misleading or false.

About 30% of Americans take at least one vitamin or mineral supplement daily. In a large study that examined the death rates of 11,000 people, however, there was no difference in mortality rate between those who took vitamin supplements and those who didn't. Most people who have a healthy diet do not need vitamins, but there are some exceptions.

Pregnant and Breast-Feeding Women. Women who are pregnant or who are breast-feeding generally need additional vitamins. Vitamins B6, B12, and folic acid are particularly important. Women who are vegetarians must be sure to avoid deficiencies, which can harm their offspring. Folic acid reduces the risk for neural tube defects and possibly facial abnormalities, such as cleft palate. Studies also show that low folate levels during pregnancy are associated with low birth weight, a risk factor for the development of cardiovascular disease in adulthood. Multivitamins that contain folic acid also appear to be somewhat protective. A woman's best approach is to take extra folic acid plus multivitamin supplements (which have additional benefits), starting them before becomming pregnant.

The human body stores several years' worth of vitamin B12, so nutritional deficiency of this vitamin is extremely rare. Although, people who follow a strict vegetarian diet and do not consume eggs or dairy products may require vitamin B12 supplements.

Pregnant women with healthy diets may have low folate levels and need to take supplements. Requirements are as follows:

The recommended daily allowance (RDA) for folic acid prior to conception and during pregnancy is 400 mcg.
During breast-feeding 260 - 280 mcg is recommended.

The following vitamins may have some value for pregnant women:

Choline, another vitamin B, is also essential for pregnant (450 mg) and nursing women (550 mg). Choline plays a key role in brain development. Not getting enough during pregnancy can lead to memory and cognitive defects in the baby. Choline supplements can also lessen the cognitive defects of prenatal alcohol exposure.
Vitamin B6 may help improve morning sickness.
Vitamin C may reduce the risk of urinary tract infections during pregnancy.
Vitamin D may help prevent preeclampsia.
One study also suggested that if pregnant women took vitamin K supplements, their infants might not need the required injection of this vitamin after birth, but supplements of vitamin K during pregnancy are not currently recommended.

Some women have low vitamin A reserves in their liver. It is important to note, however, that too much vitamin A significantly increases the risk for birth defects. Daily amounts of 10,000 IU (international units) of vitamin A in supplements and food (an amount not far above the RDA level) can pose a danger. Experts recommend that pregnant women take in no more than 8,000 IU per day and avoid eating liver.

Infants and Children. Infants who are breast-fed by healthy mothers receive enough vitamins except, in some cases, vitamins K and D. Human milk has low levels of K, and the newborn's immature intestinal tract may not produce enough of the baby's own supply. Most babies are given an injection of this vitamin at birth. Infants being breast-fed by malnourished women or those who lack sufficient exposure to sunlight may be deficient in vitamin D. In these cases, supplements of 200 - 300 IU are recommended. Formulas are required to contain sufficient vitamins and minerals. One study suggests that vitamin supplements for infants under 1 year of age may help protect them from developing type 1 diabetes later on. Beyond infancy, most American children receive all the vitamins they need from their diet unless they are living in severely deprived circumstances.

Smokers. Smoking interferes with absorption of several vitamins, importantly vitamins C and D. In one study nearly 25% of female smokers and 31% of male smokers were deficient in vitamin C. Smoking can interfere with the metabolims of vitamin D, resulting in poor muscle function. Taking high doses of antioxidant vitamins, however, may actually be harmful in smokers, especially beta carotene. Instead of taking supplements, most smokers should be sure their diets are rich in fresh fruits and vegetables and whole grains. Of course, smoking cessation is the most important intervention of all.

Click the icon to see an image of sources for vitamin C.

Alcoholics. Alcoholics often suffer from multiple vitamin deficiencies. The most dangerous deficiencies are from vitamins B1 (thiamin), folic acid, B6 (pyridoxine), B2 (riboflavin), and vitamin C. Low levels of B6 are associated with increased risk of colorectal cancer in men who drink large amounts of alcohol.

Overweight Adults. Overweight and obesity causes many problems that often result in metabolic syndrome or type 2 diabetes. Evidence suggests that isoflavones can help regulate cholesterol levels and reduce body weight and fat mass. Because some medications used to control blood sugar levels reduce folic acid and vitamin B12, some people may need vitamin supplements.

People Who Have Had Gastric Bypass Surgery. Vitamin deficiency is a recognized complication of gastric bypass surgery. Women, African-Americans of both sexes, and adults who have had laparoscopic Roux-en-Y bypass surgery are at highest risk. The deficiency is treated with water-soluble vitamin supplements.

Strict Vegetarians. Strict vegetarians need supplements of vitamin B12, unless they get enough of it from fortified cereals and other grain products.

Dieters and Vegetarians. People on weight-reduction diets with less than 1,000 calories a day should probably take a multivitamin and should also check regularly with a physician.

Vegetarians may need riboflavin, vitamin B12, and vitamin D supplements. Vegans, who do not eat dairy or eggs as well as meat, may be at further risk for vitamin A deficiencies if they do not also have plenty of dark colored fruits and vegetables. Those who eat eggs and dairy products need only watch their iron levels.

Deficiencies in vegetarian children may be particularly harmful. (One study, for example, reported that adolescents who had been on macrobiotic diets before age 6 and were deficient in vitamin B12 scored lower on psychological tests.) Pregnant and breast-feeding women who are vegetarians must be sure to have sufficient vitamins. Of special note, maternal deficiencies in vitamin B12 may cause delayed growth and neurologic problems in their newborns.

Click the icon to see an image of sources for vitamin D.

Older Adults. Deficiencies of vitamins and important minerals have been observed in almost a third of elderly people. Often their dietary habits slip and they fail to eat balanced meals regularly. Multiple drug regimens may prevent absorption of some vitamins. Elderly people, particularly if they are not exposed to sunlight, may be deficient in vitamin D. They also may have low levels of important B vitamins. (Older adults showing signs of dementia should be checked for B12 deficiencies as well as other disorders causing mental disturbances.) One study reported that the immune systems of elderly people may benefit from higher levels of vitamin E than the daily recommended dosage. It should be noted, however, that metabolism slows down as a person ages, and in elderly people it takes the liver longer to eliminate drugs and vitamins from the body. The effect of some vitamin supplements, therefore, may be intensified. Dosage levels of vitamin A, for instance, which might be harmless in a younger adult, could be toxic in an elderly patient. Nevertheless, experts are increasingly recommending extra vitamin and mineral supplements for older people.

People Who Need to Avoid Sunlight. People who need to avoid sunlight or are housebound, and whose diet is low in foods that contain vitamin D should take supplements. People with darker skin are at higher risk for deficiencies than those with whiter skin. (Note: vitamin D is toxic in high doses, and no one should exceed the recommended daily intake of vitamin D except under the direction of a physician.)


Benefits	Essential for growth, bone development, night vision, reproduction, and healthy skin.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	Vitamin A RDA and Upper Limit (when toxicity is risk) are the following: For children: 1,000 IU ages one to three (upper limit is 2,000 IU); 1,333 IU ages 4 - 8 (upper limit is 3,000 IU); and 2,000 IU for 9 - 13 (upper limit is 5,665 IU). For nonpregnant women: 2,330 IU ages 14 through adulthood. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For pregnant women: 2,500 IU for pregnant women under 18; 2,565 IU for pregnant women over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19. It should be noted that some experts recommend 8,000 IU as the upper limit during pregnancy.) Warning: Use of the topical acne medication tretinoin, a vitamin A derivative, during pregnancy can cause birth defects. For nursing women: 4,000 IU for nursing mothers under 18; 4,335 IU for nursing mothers over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For men: 3,000 IU ages 14 - 18; 3,000 IU for ages 19 and above. (Upper limit is 10,000 IU.) Note: In determining the daily vitamin A allowance, experts also take note of provitamins, such beta carotene, that convert to vitamin A. Some experts recommend 3 - 6 mg of beta-carotene. Vitamin A is also now being measured with a new unit called the Retinol Activity Equivalent (RAE or RE). One RE is equal to 1 mcg. Retinol is the most active form of vitamin A and it is also converted in the liver from carotenoids. One RE is equal to 12 mcg of beta-carotene or 24 mcg of alpha-carotene or beta-cryptoxanthin).
Foods containing the vitamin	Animal products, such as liver, dairy products, eggs, and fish liver oil. Provitamin A carotenoids are also found in dark red, green, and yellow vegetables and fruits. Requires some dietary fat to be absorbed.
Effects of deficiencies	Skin disorders, severe diarrhea, and eye damage. In less developed countries severe deficiencies cause blindness in 250,000 children each year. Diets low in vitamin A may also increase the risk of developing cancer. Low dietary intake of vitamin A has been associated with impaired lung function in children.
People at risk for deficiencies	Preschool children and any child with inadequate intake of protein, calories, and zinc. Iron deficiency may also impair metabolism of vitamin A. People with asthma. People with serious disorders in the intestine, liver or pancreas, such as cystic fibrosis, steatorrhea, biliary obstruction, inflammatory bowel disease, cirrhosis, and others. People who have undergone Roux-en-Y gastric bypass surgery. Vegans (vegetarians who do not eat eggs and dairy). Such individuals should be sure to have plenty of deep-colored fruits and vegetables. People who abuse alcohol. It should be noted, however, that people with alcoholism may be at risk for vitamin A deficiency, but a combination of high-dose vitamin A and alcohol may cause toxic effects in the liver. Healthy adults usually have a year's store of vitamin A in the liver, so temporary nutritional deficiencies or problems with fat absorption are unlikely to cause serious vitamin A deficiency problems.
Toxicities	Very toxic when taken in high-dose supplements for long periods of time. Symptoms of overdose include dizziness, nausea, vomiting, headache, skin damage, mental disturbances, and, in women, infrequent periods. Can affect almost every part of the body, including eyes, bones, blood, skin, central nervous system, liver, and genital and urinary tracts. Severe toxicity can cause blindness and may even be life threatening. In children, chronic overdose can cause fluid on the brain and as well as adult complications. High consumption of vitamin A may also increase the risk of gastric cancer and the risk of osteoporosis and fractures in both men and women. Pregnant women who take amounts not much higher than RDA levels increase the risk for birth defects in their children. Liver damage can occur in children who take RDA-approved adult levels over prolonged periods of time or in adults who take as little as five times the RDA-approved amount for 7 - 10 years.


	B Vitamins: General Information	Vitamin B1 (thiamin)
Benefits	The B vitamins have a wide and varied range of functions in the human body. Most B vitamins are involved in the process of converting blood sugar into energy.	Essential for converting blood sugar into energy and is involved in metabolic activities in nerves, heart, and muscles and in the production of red blood cells.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)		RDA is 1.2 mg per day for men and 1.1 mg for women.
Foods containing the vitamin		Best source is pork and good sources are dried fortified cereals, oatmeal, corn, nuts, cauliflower, and sunflower seeds. Supplements for people with normal diets and health are unnecessary.
Effects of deficiencies	Deficiencies are uncommon in the U.S., but when they occur, they usually involve several B vitamins, since many of them come from the same food groups.	Severe vitamin B1 deficiency is known as beriberi. It can cause visual disturbances, paralysis, staggering, loss of sensation in the legs and feet, psychosis, and congestive heart failure.
People at risk for deficiencies	Alcohol interferes with these vitamins, and some of the physical and mental problems that alcoholics experience may be attributed to a deficiency of B vitamins. Elderly people are also at risk for deficiencies because of inadequate diets and potential interference with B-vitamin absorption by medications. Deficiencies can occur in severely malnourished people or in those receiving long-term dialysis or intravenous feeding. Vegetarians may be at risk.	See general vitamin B description.
Toxicities	Because the B vitamins are water-soluble and eliminated in the urine, toxic reactions from oral administration of most of them are extremely rare. (Exceptions are niacin and B6.) It should be noted that substances known as B15 (pangamic acid) and B17 (laetrile) are neither vitamins nor nutrients; both chemicals are highly dangerous and have no proven nutritional or health value.	No toxic effects have been reported from thiamin.


	Vitamin B2 (riboflavin)	Vitamin B3 (niacin) also known as nicotinic acid	Vitamin B5 (Pantothenic Acid)
Benefits	Important in the production of energy.	Helps break down blood sugar for energy. Acts as a vasodilator, widening blood vessels and increasing blood flow. May be prescribed for improving cholesterol levels.	Important for metabolism of fats, carbohydrates, and proteins, as well as production of steroid hormones and other important chemicals.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 1.7 mg.	DRI is 20 mg.	Adequate intake (AI) is 4 - 7 mg.
Foods containing the vitamin	Liver, dried fortified cereals, dairy products, fish. Some dark green vegetables. Supplements for people with normal diets and health are unnecessary.	Mackerel, swordfish, chicken, veal, dried fortified cereals, pork, salmon, and beef liver. Supplements are unnecessary in people with normal health and diets.	Whole grains, beans, milk, eggs, and liver. Supplements are unnecessary in people with normal health and diets.
Effects of deficiencies	Deficiencies affect the skin and mucous membranes and can cause cracks on the lips or corners of the mouth, eczema of the face and genitals, a burning sensation on the tongue, eye irritation. May contribute to anemia when iron levels are low and contribute to elevated levels of homocysteine, a heart risk factor.	Deficiency causes pellagra; symptoms can include eczema, intestinal and stomach distress, depression, headache, thinning of the hair, and excess saliva production.	Deficiency is unlikely except in company with other B vitamin deficiencies. Symptoms include abdominal distress, burning sensation in the heels, and sleep problems.
People at risk for deficiencies	See general vitamin B description.	Alcoholics and any malnourished persons.	Alcoholics and any malnourished persons.
Toxicities	Until recently, no toxic effects had been reported even from large doses of riboflavin. However, one study indicated that high consumption of vitamin B2 might increase the risk of stomach cancer. More research is needed. (In the same study, vitamins B1, B3, and B6 were protective.)	Even mildly high doses of niacin can cause hot flushing of the face and shoulders, headache, itchiness, and stomach problems. Some report heart disturbances and temporarily lowered blood pressure. Large doses may produce ulcers, gout, diabetes, and liver damage, which are usually reversed when high doses are discontinued.	Although no toxicity has been reported in humans, high dosages have caused liver damage in rats.


	Vitamin B6 (pyridoxine)	Vitamin B12 (cobalamin)
Benefits	Has an effect on over 60 proteins in the body, importantly, those that play a role in the nervous system, in red and white blood cell production, and in heart disease.	Essential for the production of blood cells, manufacturing genetic material, and for healthy functioning of the nervous system. New evidence suggests that high levels of B12 may protect against colon and rectal cancer.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 1.3 mg in adults under 50 and 1.7 mg for older men and 1.5 for older women. (Some experts recommend 3 to 6 mg for people who need heart protection.) Upper limit is 100 mg for adults.	RDA is 2.4 mcg in men and nonpregnant women, 2.6 mcg in pregnant women, and 2.8 mcg in nursing mothers.
Foods containing the vitamin	Meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.	The only natural dietary sources are animal products, including meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). Like other B vitamins, however, B12 is added to commercial dried cereals.
Effects of deficiencies	Increased levels of homocysteine, associated with heart disease and possibly Alzheimer's disease. Skin problems and nervous system disorders, including impaired memory and concentration. Increased risk for kidney stones. One study found a correlation between vitamin B6 deficiency and inability to conceive or carry a child to term. In unborn children, some evidence shows that lack of vitamin B6, in addition to vitamin B12 and folic acid, may be responsible for defects such as cleft lip and palate and spina bifida. Supplementation with these vitamins is advised during pregnancy. Note: People who have been taking more than 50 mg for some time and stop suddenly are at risk for a so-called rebound deficiency. When people stop, they should taper off slowly.	Deficiencies elevate homocysteine, a possible risk factor for heart disease and Alzheimer's disease. Increased risk of bone fractures. Abnormal gaits in the elderly. May cause severe depression, memory loss, instability, disorientation, and decreased reflexes, and possibly hearing loss. Children who are deficient may experience growth failure. Deficiencies in pregnant and breast-feeding women may cause neurologic harm in their offspring. A genetic defect that causes vitamin B12 deficiencies is responsible for pernicious anemia, a serious disorder that causes rapid heart rate, shortness of breath, dizziness, weakness, and fatigue. It must be treated with injections of vitamin B12 or else neurologic damage may occur.
People at risk for deficiencies	Alcoholics and any malnourished person. In rare cases, infants are born unable to metabolize pyridoxine; in such cases, seizures or convulsions can occur and vitamin B6 must be administered.	Alcoholics and any malnourished persons. Evidence suggests deficiencies may be caused by Helicobacter pylori (H. pylori) bacteria (a cause of ulcers). Nearly 30% of patients with inflammatory bowel disease have vitamin B6 deficiency, as well as low levels of iron and vitamin D. People who take the antibiotic isoniazid, high blood pressure medication hydralazine, and the drug penicillimine are at risk for vitamin B6 deficiency. The elderly and people with Crohn’s disease and those who have undergone ileal and ileocolonic resection may have trouble absorbing natural vitamin B12 and require supplements. Some evidence shows that patients with Parkinson’s disease treated with levodopa plus dopa decarboxylase inhibitor (DDC-i) and catechol-O-methyltransferase inhibitor (COMT-i) have low levels of both vitamin B12 and folate. As a result, they need to take supplements of these vitamins. Other studies have found that patients with diabetes treated with metformin, but not roziglitazone, are at risk for low levels of vitamin B12. Vitamin B12 deficiency is also common in patients with polyneuropathy. In up to one-third of patients, vitamin B12 deficiency is the sole or major contributing cause of their neuropathy. Treatment with vitamin B12 has a high success rate in improving the symptoms. Vegetarians are at higher risk for deficiencies.
Toxicities	Very high doses can cause nerve damage with symptoms of instability and numbness in the feet and hands, which may be permanent in some cases. Of specific concern are possible adverse effects on nerve development in the offspring of pregnant women who take large doses, such as for morning sickness.	There is no evidence of toxicity with this vitamin.


	Biotin (a B vitamin)	Choline (a B vitamin)	Folate, or Folic Acid, its synthetic form (a B vitamin)
Benefits	Involved in the production of amino acid proteins and fatty acids.	Essential for fetal brain development and for learning and memory.	Important for many metabolic processes in the body. It is used in the manufacturing of neurotransmitters (chemical messengers in the brain), in protecting the heart, and for synthesizing genetic materials (DNA) in the cells. It may improve blood flow.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	There is no DRI for biotin; some experts suggest 30-100 mcg.	RDA 425 mg for nonpregnant women, 450 mg for pregnant women, and 550 mg for nursing women.	Supplements may be folate (natural) or folic acid (synthetic). Folic acid is nearly twice as potent as folate. DRI is 400 mcg (.4 mg) of folate for the general population, 600 mcg during pregnancy and 500 mcg while nursing. Women who are planning to be pregnant should certainly take 400 mcg of folic acid before conception, during pregnancy, and while nursing.
Foods containing the vitamin	Dietary sources are eggs, milk, liver, mushrooms, bananas, tomatoes, whole grains, nuts, and brewer's yeast. Also produced by bacteria in the intestines.	Peanuts, eggs, cauliflower, and meats, especially liver.	Avocado, bananas, orange juice, cold cereal, asparagus, green leafy vegetables, dried beans and peas, and yeast. Folic acid supplements are now added to commercial breads and cereals.
Effects of deficiencies	Deficiencies are almost unheard of.	Low levels during pregnancy increase risk of birth defects in newborns.	As with vitamins B6 and B12, deficiencies of folate elevate levels of homocysteine, an amino acid in the body that may increase the risk for heart disease, and possibly Alzheimer's disease. Folic acid supplements lower homocysteine levels, but with little or no impact on risk of atherosclerotic disease in the heart or in the peripheral arteries and veins. This suggests that homocysteine may be a marker of cardiovascular disease, rather than a cause. This being said, one 2007 study found that folic acid supplementation in patients with low folic acids levels substantially reduced the risk of a first stroke. Low levels during pregnancy increase risk of birth defects in newborns, and folic acid supplementation plays a key role in preventing birth defects. Folic acid deficiencies Deficiencies can also cause depression and megaloblastic anemia and impair concentration, memory, and hearing.
People at risk for deficiencies			Alcoholics, malnourished persons, people with conditions that disturb the small intestine, people taking certain drugs, particularly methotrexate. Other risk factors for deficiency: high-dose aspirin, smoking, treatment for seizures, taking oral contraceptives.
Toxicities		Excessive doses can cause intestinal problems, and there is also some concern that high doses can be carcinogenic.	Possible connection between high consumption of folate/folic acid and colorectal cancer now under exploration. Some link between high doses and central nervous system disorders, zinc deficiency, and seizures in epileptics. This risk appears to be low, but results indicate that megadoses should be avoided. High amounts in the elderly may mask symptoms of vitamin B12 deficiencies.


Benefits	Vitamin C is a water-soluble vitamin. Acts as an antioxidant (reduces harm from damaging chemical processes in the body). Essential for the production of collagen, the basic protein in bones, cartilage, tendons, and ligaments. A 2007 study found that vitamin C supplements can help prevent the development of complex regional pain syndrome following wrist fracture. Another study found that prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose. It may also protect against brochoconstriction during exercise in people with asthma. May help boost the immune system.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 75 mg (women) and 90 mg (men). (Smokers need an additional 35 mg.)
Foods containing the vitamin	Citrus fruits and juices, papayas, hot chili peppers, bell peppers, broccoli, potatoes, dark leafy greens, kale, red cabbage, cauliflower, cantaloupe, sweet potatoes, and Brussels sprouts. Orange juice is the most important source of vitamin C in the U.S., with frozen juice being the best source of the vitamin.
Effects of deficiencies	Scurvy is the primary deficiency disease. Affects most body tissues, particularly bones, teeth, and blood vessels. Early symptoms include tiredness, weakness, irritability, weight loss, and vague muscle aches. Later symptoms are bleeding gums, wounds that won't heal, rough skin, and wasting away of the muscles. Deficiencies may contribute to periodontal disease and gallstones. Low dietary intake of vitamin C has been associated with impaired lung function in children. Low intake may also increase lead levels in the blood.
People at risk for deficiencies	Deficiency has been uncommon in the U.S., usually occurring in the elderly, alcoholics, cancer patients, and some people on severely limited diets low in fresh fruits and vegetables. Surprisingly, however, studies now suggest that as many as 16% of middle-aged Americans, with the highest risk in smokers and middle aged men, are deficient in vitamin C. High doses of aspirin taken over a long period of time can interfere with vitamin C.
Toxicities	Tolerable upper limit is 2000 mg/day. High doses may cause headaches and diarrhea. Long-term high doses may increase risk for kidney stones. Ascorbic acid increases iron absorption so people with blood disorders, such as hemochromatosis, thalassemia, or sideroblastic anemia, should avoid high doses. Large doses may also thin blood and interfere with anticoagulant medications, blood tests used in diabetes, and stool tests. Rebound scurvy can occur after abrupt withdrawal from long-term large doses. This may affect infants or pregnant women who withdraw suddenly from high doses.


Benefits	Vitamin D is actually a single term for several hormones that are stored mainly in the liver and also in fat and muscle tissue. It is essential for the absorption of calcium into the bone and for normal bone growth.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 200 IU (5 mcg) per day for children and most adults to age 50, 400 IU (10 mcg) for people between ages 50 and 60, and 600 IU over age 70. and 1000 IU (15 mcg) for those over 70. People who are housebound, do not have sufficient exposure to sunlight, or are dark-skinned individuals, as well as breast-fed infants, should take need vitamin D supplements. The maximum tolerated dose after the age of 12 months is 2,000 IU/day
How the body gets the vitamin	There are two forms of vitamin D. Vitamin D3 is made in the body from a chemical reaction to the ultraviolet radiation in sunlight. Vitamin D2 is found in a few food sources, including vitamin D fortified milk, fatty fish, egg yolk, and liver.
Effects of deficiencies	Softening of the bones caused by low levels of calcium and phosphorous (called rickets in children and osteomalacia in adults). Also increases the risk for bone-related knee problems, and hip fractures in postmenopausal women. Associated with a higher risk for prostate cancer and breast cancer risk. Evidence suggests that vitamin D deficiency may be responsible for poor muscle strength after bone fracture. The deficiency is associated with high blood pressure and diabetes, but it is unknown whether supplementation with vitamin D impacts these diseases. Studies now suggest vitamin D plays a role in age-related macular degeneration (AMD), and that drinking milk with added vitamin D can help protect against AMD.
People at risk for deficiencies	Older people, particularly if they live in the North, who are underexposed to sunlight. Obesity may also increase risk. There is some concern, in fact, that vitamin D deficiency may be a growing problem in the US among younger adults as sunscreen use becomes widespread. Individuals at highest risk for vitamin D deficiency are those who assiduously avoid the midday sun, wear protective clothing, regularly use sunscreen, and have dark skin. Exposure to sunlight for about 15 - 20 minutes at mid-morning or mid-afternoon three times a week is recommended for most people who live in temperate climates.
Toxicities	Vitamin D is very toxic in high doses. In infants, daily amounts higher than 1,000 IU can cause mental and growth retardation, kidney failure, and death. In children and adults, daily amounts over 50,000 IU can cause weakness, anorexia, vomiting, diarrhea, and mental changes. Prolonged use of megadoses can cause calcification of soft tissue and life-threatening kidney failure. Low-calcium diets and withdrawal from the vitamin can usually reverse the side effects except for kidney failure.


	Vitamin E (Tocopherol or Tocotrienol)	Vitamin K
Benefits	A fat-soluble antioxidant vitamin that helps prevent cell membrane damage and may inhibit oxidation of LDL cholesterol (a process that increases its harmful effects on arteries). Researchers once thought that vitamin E might protect against cardiovascular disease. This theory has been debunked. However, a 2007 study found that vitamin E supplementation reduced the risk of deep vein thrombosis (DVT) in women at risk for, or with a history of, DVT. Vitamin E supplements have also been shown to produce a statistically significant decrease in menopausal hot flashes. There is also early evidence that vitamin E may protect against ovarian cancer.	The most important function of vitamin K is its role in blood clotting and prevention of bleeding. As a result, the vitamin may be able to help treat hepatoma, leukemia, and hepatocellular carcinoma, a form of liver cancer. The vitamin also contributes to maintaining healthy bones and healing fractures. Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it may be effective in treating rheumatoid arthritis.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 15 mg (22 IU) for all adults, including pregnancy women. Nursing mothers need 19 mg (28 IU). (Supplements should be taken along with some oil or fat to be absorbed.) Vitamin E is composed of 8 compounds (four tocopherols and four tocotrienols). Vitamin E is most often available as supplements of dl alpha tocopherol (a synthetic form). Other vitamin E compounds may prove to be more active than the standard synthetic supplement. They include natural vitamin E, called d-alpha- or RRR-alpha-tocopherol succinate (VES). Other vitamin E compounds of interest are tocotrienol and beta and gamma tocopherol. Supplements that contain a combination of some of these forms may be most beneficial.	RDA is 60 - 65 micrograms (women) and 70 - 80 micrograms (men).
Foods containing the vitamin	Vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Tocotrienol (a possibly beneficial form) is found in natural tropical oils. Palm oil sold in the US is refined and does not contain tocotrienol.	Best dietary sources are canola oil, cruciferous vegetables, and soybean oil. Good sources are beef liver, bran, and olive oil. Also produced by bacteria in the intestines.
Effects of deficiencies	Deficiencies have not been established.	Easy bruising, bleeding. May increase the risk of hip fractures in women.
People at risk for deficiencies	Low-birth weight infants. People who eat a low-fat diet. People with medical problems that impair fat absorption, such as Crohn's disease, cystic fibrosis, steatorrhea, liver diseases (such as cirrhosis). People with abetalipoproteinemia, a rare genetic disorder that impairs fat metabolism.	Deficiency may occur in patients who have problems absorbing fats, such as those with cirrhosis, people who are on long-term antibiotic therapy, or who are taking other medications, including cholestyramine, Dilantin, and phenobarbital. Some evidence suggests that more young people may be deficient than previously believed.
Toxicities	Upper level recommended is 1,500 IU of alpha tocopherol. Large doses may cause bleeding problems, particularly in people taking anti-clotting medications. Some research now indicates that vitamin E, like other antioxidants, may have pro-oxidant and damaging effects. Although vitamin E is one of the best studied vitamins, research has yielded conflicting results, and definitive conclusions about the benefits and toxicity of vitamin E have not yet been determined. In a major 2005 study, there was no significant difference in cancer rates between people who took 400 IU of vitamin E daily and those who did not, although those who took the supplement had a higher risk of heart failure. Additional studies also link high levels of vitamin E with a slightly increased risk of heart failure and death. On the other hand, studies show that vitamin E may reduce heart problems in high-risk patients such as certain people with diabetes.	Allergic-type responses, including rash and itching, to high doses have been reported. Those who are taking Coumadin, an anticoagulant, should not take vitamin K without consulting a physician. Vitamin K deficiency can cause anorexia, lethargy, growth retardation, bone loss, soft tissue calcification, and death.

Carotenoids

Carotenoids are a group of more than 700 fat soluble nutrients that produce the colors in foods such as carrots, pumpkins, sweet potatoes, tomatoes, and other deep green, yellow, orange, and red fruits and vegetables. Many are proving to be very important for health. Beta carotene is the most widely studied carotenoid, but others are proving to be of great interest. As with some, but not all, carotenoids, beta carotene is known as a provitamin A because it converts to the vitamin in the body.

They are categorized as either xanthophylls or carotenes according to their chemical composition.

Carotenes are hydrocarbons and most are found in yellow, orange, and red vegetables. They include beta and alpha carotene and lycopene.

Beta Carotene and other Provitamin A Carotenoids. Beta carotene, alpha-carotene, and beta-cryptoxanthin are carotenes that are converted into vitamin A or retinol (the active form of vitamin A) in the body. They are found in many yellow fruits and vegetables. Beta carotene is the most widely studied carotenoid. Evidence now strongly suggests that when taken as a separate supplement it can have harmful effects.
Lycopene. Lycopene is responsible for the red color in fruits and vegetables, including tomatoes, red grapes, watermelon, and pink grapefruit. It is also found in papayas and apricots. It does not convert to vitamin A but may have important cancer fighting properties and other health benefits.
The beneficial actions of most carotenes such as those tomatoes, corn, and carrots, appear to be enhanced by cooking them, especially in oil (preferably olive, canola, or another monounsaturated oil). (Note: Cooking can also destroy certain nutrients, such as vitamin C, in these vegetables.)

Xanthophylls contain oxygen and most are found in green vegetables, such as broccoli, cabbage, and kale. They are also in yellow fruits and vegetables. Xanthophylls include lutein and zeaxanthin, which are both stored in the retina of the eye. Neither converts to vitamin A. Both are powerful antioxidants and may be very important for healthy eyes. Unlike carotenes, cooking may reduce the antioxidant activity of some xanthophylls in foods, although probably not to any significant degree.

Phytochemicals

The word phytochemicals means plant chemicals. Hundreds of phytochemicals are being studied. Many are believed to have a major positive impact on human health. Some contribute to the bright and vivid colors found in fruits and vegetables. The results of studies on specific phytochemicals are not necessarily applicable to the vegetables or fruits that harbor small concentrations of these chemicals.

Nevertheless, it is obvious that vegetables and fruits are healthful, which is probably due to some balance of phytochemicals, carotenoids, vitamins, fibers, and minerals rather than any single substance.

The benefits of individual phytochemical supplements are largely unproven. Furthermore, they are not regulated and high concentrations of some may behave like drugs and can be toxic and possibly even contribute to cancer cell growth.

Polyphenols are important phytochemicals, and flavonoids (or catechins) are members of the polyphenol family that may have significant health benefits. Laboratory studies have shown that specific flavonoids suppress tumor growth, interfere with sexual hormones, prevent blood clots, and have anti-inflammatory properties. In general, flavonoids are found in celery, cranberries, onions, kale, dark chocolate, broccoli, apples, cherries, berries, tea, red wine or purple grape juice, parsley, soybeans, tomatoes, eggplant, and thyme. Most common berries contain flavonoids and are particularly rich in potent antioxidants.

Among the important flavonoids are resveratrol, quercetin, and catechin. Evidence suggests that resveratrol (found in red wine, grapes, olive oil) may be extremely potent. In laboratory studies, it increases cell survival and has been shown to increase the life span of worms and fruit flies. Catechins are the primary flavonoids in tea and may be responsible for its possible beneficial effects. Flavonoids in dark chocolate may also be health protective.

Isoflavones, commonly known as phytoestrogens, have actions that are similar to the female hormone estrogen. A high consumption of soy, which is primarily composed of isoflavones, may reduce symptoms resulting from estrogen depletion during menopause. In a recent study, supplementation with isoflavones decreased hot flashes by 57% and night sweats by 43%, but other research is less favorable.

Lignan is another phytoestrogen and is found in the fiber layers of whole-grains, berries, some seeds, some vegetables, and a few fruits.

Isothiocyanates and related substances, indoles, are also known as mustard oils and are responsible for the sharp taste in cruciferous (also called brassica) vegetables. Such vegetables include broccoli, cabbage, Brussels sprouts, cauliflower, collards, kale, kohlrabi, mustard greens, rutabaga, turnips, and bok choy. Isothiocyanates also stimulate enzymes that convert estrogen to a more benign form and may block steroid hormones that promote breast and prostate cancers. (Cruciferous vegetables are also high in fiber, vitamin C, and selenium.)

Monoterpenes have two important phytochemicals, perillyl alcohol and limonene. They block proteins that stimulate cell growth and reproduction and are being tested for actions against cancer. Limonene is found in the peels of citrus fruits.

Organosulfurs are part of the allium family of phytochemicals. Compounds, such as allicin, may have benefits on the immune system, assist the liver in rendering carcinogens harmless, and reduce production of cholesterol in the liver. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots.

Capsaicin seems to reduce levels of substance P, a compound that contributes to inflammation and the delivery of pain impulses from the central nervous system. Research suggests that it may inhibit cancer-generating substances. It is found in hot red peppers.

Sterols, which include sitosterol, stigmasterol, campesterol, and squalene, are found in vegetable oils. Sitosterol is the most studied and appears to have cholesterol-lowering effects.

Beta-sitosterols may help improve urine flow and urinary symptoms in men with enlarged prostate glands (benign prostatic hyperplasia, or BPH). A recent review study of five randomized trials (519 men) found that urinary flow and other urinary symptoms improved in men who took the herbal remedy from 4 - 26 weeks. The study’s authors cautioned that while beta-sitosterols show effectiveness in the short term, their long-term effectiveness, ability to prevent complications from BPH, and safety are not known. More research is necessary. Beta-sitosterols come from South African star grass, Hypoxis rooperi, or species of Pinus and Picea.

Healthy Foods

Evidence increasingly suggests that a varied diet, not individual food chemicals, is essential for basic health and a longer life. Such diets are rich in fresh fruits and vegetables and whole grains, and low in saturated fats.


Foods	Phytochemicals and Carotenoids	Vitamins and other valuable food components	Benefits
Apples	Flavonoids		May have activity against certain cancers (lung). Also may help maintain healthy cholesterol. May protect against asthma.
Beans	Flavonoids	Folate, iron, potassium, and zinc	Some experts believe beans are the perfect food.
Berries, all kinds of dark colored	Ellegic Acid	Vitamin C, minerals	The anthocyanins in berries such as bilberries, blueberries, cranberries, elderberries, and others, have numerous healthful properties including anti-cancer and antioxidant effects. Bilberry (Vaccinium myrtillis) is widely used to prevent macular degeneration. Blueberries may protect the aging brain. (In one study blueberries were most effective.)
Broccoli (also kale, Brussels sprouts, cauliflower)	Flavonoids, isothiocyanates, lutein, beta and alpha carotene. Note: Young sprouts of broccoli and cauliflower contain much higher levels of isothiocyanates than their mature forms.	Vitamin C, folate, fiber, and selenium	Anticancer properties. Protective against heart disease and stroke.
Carrots and other bright yellow vegetables	Lutein, beta carotene and other provitamin A carotenoids	Vitamin A (converted from carotenoids), vitamin C	Protects eyes, lungs. (Cooking carrots may increase the potency of food nutrients.)
Chocolate, dark. Note: Milk chocolate does not have benefits.	Flavonoids		Heart protective (may improve lipids and help prevent blood clotting. May have protective properties against lung cancer (not other cancers).
Eggs	Lutein	Many B vitamins, vitamin A, vitamin D	Although egg yolks are high in cholesterol, very little of it has a negative effect on people with normal levels. And the health benefits of eggs are now known to be very high. (People with diabetes or those with high cholesterol should restrict eggs, however.)
Fish, oily (mackerel, salmon, sardines)		Vitamin B3, B12. Essential fatty acids, selenium	Heart and brain protective.
Garlic	Allium (organosulfurs)		Possibly protective against certain cancers, heart diseases, and infection. Heating garlic can reduce benefits. Allowing crushed fresh garlic to stand 10 minutes before heating, however, may preserve beneficial chemicals while cooking.
Ginger	Zingiberaceae		Cancer fighting properties.
Grains (whole)	Lignans (phytoestrogens)	Vitamin B, Selenium (important antioxidant mineral), fiber, folate	May help reduce the ability of cancer cells to invade health tissue.
Grapes, including purple grape juice, and red wine	Flavonoids, (resveratrol, quercetin and catechin)		Fight heart disease and cancer. May help lower the risk for asthma.
Nuts		Vitamin E, vitamin B1, essential fatty acids, folate	Protects the heart and may help prevent stroke.
Onions	Flavonoids, allium (organosulfurs)		May have activity against certain cancers (lung).
Oranges	Monoterpenes	Vitamin C, folate, potassium.	Many health benefits. Increases HDL levels.
Potatoes (Sweet)		Vitamin C, vitamin E, vitamin A	Many health benefits.
Soy. The best products are tofu, soy milk, or whole soy protein.	Isoflavones (phytoestrogens), flavonoids, phytosterol, phytate, saponins.		May have effects similar to estrogen, including maintaining bone and benefiting the heart in women. May also be protective against prostate cancer and possibly other cancers. More studies are needed. Effects on breast cancer are uncertain. (Note: Soy may have different effects in men than in women. Of some concern is one study reporting more mental decline in men who consume greater amounts of tofu.)
Spinach and other dark green leafy vegetables	Zeaxanthin, Beta carotene	Vitamin C, folate, vitamin A (converted from carotenoids)	Protects lungs and brain.
Tea (Both black and green tea are beneficial. Best results associated with green tea.)	Flavonoids (primarily catechins)		Cancer fighting properties, particularly in green tea, which may be especially beneficial for smokers. Both black and green tea may protect against heart disease and stroke, although studies are mixed. Tea drinking also may help with weight control and help prevent osteoporosis.
Tomatoes	Lycopene, Flavonoids	Vitamin C, biotin, minerals	Studies link to reductions in prostate and other cancers. Infection fighters.
Note on Organic versus Inorganic Products. There is some evidence that organic produce has higher levels of antioxidants and that some agricultural chemicals may destroy flavonoids. Nevertheless, organic produce is expensive, and fruits and vegetables, no matter how they are grown, are still filled with healthful nutrients.

Dietary Health Benefits

The benefits of any dietary factors are very difficult to prove, and, to date, there is little evidence that most dietary supplements protect against major diseases in otherwise healthy people with normal eating habits. An exception is lutein, which is known to reduce the risk of macular degeneration. However, a diet naturally high in vitamins and minerals can be the best defense against many diseases. Fresh fruits and vegetables and whole grains are the primary sources of vitamins, carotenoids, and vitamins, as well as of fiber and important minerals.

Description of Oxygen-Free Radicals (Oxidants). Currently, the most important benefit claimed for vitamins A, C, E, and many of the carotenoids and phytochemicals is their role as antioxidants, which are scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). These chemically active particles are by-products of many of the body's normal chemical processes. Their numbers are increased by environmental assaults, such as smoking, chemicals, toxins, and stress. In higher levels, oxidants can be very harmful in the following way:

They can damage cell membranes and interact with genetic material, possibly contributing to the development of a number of disorders including cancer, heart disease, cataracts, and even the aging process itself.
Oxygen-free radicals can also enhance the dangerous properties of low-density lipoprotein (LDL) cholesterol, a major player in the development of atherosclerosis.

Description of Antioxidants and Warnings on High-Dose Supplements. Antioxidant vitamins (A, C, and E), carotenoids, and many phytochemicals can neutralize free radicals. Unfortunately, although it is clear that vitamins are required to prevent deficiency diseases, high doses of vitamin C, vitamin E, and beta carotene supplements may also have pro-oxidant effects, which can be harmful in patients with cancer. In these people, high doses of antioxidant vitamins may actually protect cancer cells just as they do healthy cells.

The strongest evidence on negative effects to date comes from studies reporting an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. One study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E.

Some evidence also indicates that high doses of vitamin C may speed up atherosclerosis, or hardening of the arteries. In one study, women with heart disease who took antioxidant vitamins had a higher risk for heart attack or death than those who didn't take one.

Another study also reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. Some researchers speculate that certain immune factors generate oxidants to fight bacteria. This antioxidant vitamin, then, may block that action. Research published in 2005 suggests that those who take large amounts of vitamin E (1,500 IU/day) may slightly increase their risk for heart failure and death, but this evidence is not considered conclusive. Further study is necessary.

Vitamins and Heart Protection.

Antioxidant Vitamins A, C, and E. Deficiencies in vitamins A, C, E, and beta carotene have been linked to heart disease. All of these nutrients have antioxidant effects and other properties that should benefit the heart. A study in patients with heart failure has shown that vitamin C can work with dobutamine, a powerful intravenous medication, to strengthen the heart’s ability to contract following a heart attack. In fact, a 2005 study has found that taking high doses of vitamin E is associated with an increased risk of heart failure. In 2007, the Women’s Antioxidant Cardiovascular Study failed to find that vitamins C, E, and beta carotene could reduce the risk of heart attack, stroke, need for revascularization, or cardiovascular death in women. According to the U.S. Preventive Service Task Force, evidence is insufficient to confirm or refute the benefits of supplements of any of these vitamins in protecting against heart disease.
Folate and B12 Vitamins. Deficiencies in the B vitamins folate (known also as folic acid) and B12 have been associated with elevated blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. One study, reported lower failure rates after heart surgery in patients who took folic acid and vitamins B12 and B6. And a major 2002 study suggested that lowering homocysteine levels with folic acid would reduce the risk for heart disease by 16% and stroke by 24%. However, a 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with B vitamins and folic acid had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke. More evidence is needed to determine whether homocysteine plays a causal role in cardiovascular disease and whether the B vitamins are protective. Folate improves blood flow through the arteries, which may be important for the heart, regardless of its effect on homocysteine. Although people with high levels of homocysteine are prone to damaging blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with folic acid and other B vitamins does not reduce the incidence of blood clots in the peripheral veins (deep venous thrombosis).
Niacin. 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 physician should prescribe niacin in order to ensure its safety and effectiveness. [See In-Depth Report #23, Cholesterol.]

Carotenoids and Heart Protection. Studies have reported that a diet high in fruits and vegetables containing beta carotene, lycopene, and other carotenoids may reduce the risk of heart attack. A small Finish study found that a diet high in tomatoes reduced total cholesterol and LDL ("bad") cholesterol. Diets low in lycopene (particularly from tomatoes) were associated with a significantly higher risk of heart disease and stroke.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Phytochemicals and Heart Protection. Several phytochemicals are associated with heart protection.

Flavonoids. Certain flavonoids, found in both black and green tea, dark chocolate, onions, red wine or red grape juice, and apples, appear to be strongly heart protective. In one study, people who consumed the most flavonoids in foods had a 20% lower risk for heart disease than those with low consumption. Flavonoids may protect against damage done by cholesterol and help prevent blood clots. A number of studies have now reported heart protection from the flavonoid catechin, which is found in both black and green tea. The flavonoid resveratrol, which is found in grape skin, appears to be responsible for the well-known heart protective effects in red wine and purple grape juice.
Organosulfurs. Organosulfurs found in onions and garlic have been under investigation for possible beneficial effects on cholesterol levels. One study reported an association between taking garlic capsules and significantly lower cholesterol-build up in the arteries of older women but not in older men. In the study, daily garlic supplements dramatically reduced the build-up of newly formed plaque in the arteries, while having much less effect on older, harder plaque deposits. Garlic supplements for cardiovascular disease may be most beneficial when used during earlier years among men and later years among women.
Isoflavones. Soy protein is the most studied source of isoflavones (known as phytoestrogens, or plant estrogens). Not all studies are consistent, but the majority has shown an improvement in at least one of the cholesterol components in people who consumed at least 25 grams of soy protein. A 2007 meta-analysis of all soy protein studies performed from 1990 - 2006 found that soy protein significantly decreased total cholesterol and LDL cholesterol, but had no effect on HDL or triglycerides. The effect was particularly evident in people with hypercholesterolemia. A 2007 study found that 12 weeks of soy supplement lowered total cholesterol and LDL levels in both Caucasian and African-American postmenopausal women. Soy may also reduce other heart risk factors, at least in certain populations. For example, in one 2002 study, soy was beneficial for controlling blood sugar and lowering LDL in postmenopausal women with type 2 diabetes. In a 2007 study of overweight men and postmenopausal women, soy protein reduced blood pressure and arterial stiffness. In another study, soy protein was associated with lower systolic blood pressure in men. The best sources are soy products (tofu, soy milk) or whole soy protein. Powdered soy protein that contains at least 60 mg of isoflavones may provide similar benefits.
Sterols. The plant sterols, including sitosterol, are also proving to be potent cholesterol fighters by blocking the absorption of cholesterol in the intestine. Sitostanol, a derivative of sitosterol, is being used in new margarine products to lower cholesterol levels. Sterols and stanols are now found in breads, cereals, yogurt, and fruit juices.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for a first stroke, perhaps by helping to protect against high blood pressure -- a major risk factor for stroke.

Vitamins and Stroke Protection. The effects of antioxidant vitamins and carotenoids on stroke, dementia, or both are being studied. Studies are conflicting, however. A 2007 study of 8,171 women with cardiovascular disease reported that vitamins C, E, and beta carotene offered no protection against heart attack and stroke.

The B vitamin folate (usually in the form of folic acid) may protect against stroke. However, exactly which people benefit from this therapy has yet to be determined. Studies have suggested that people who have higher blood levels of folate have a lower than average risk for stroke. Its primary benefit in this case appears to be to reduce levels of homocysteine, an amino acid that has been strongly linked to an increased risk of coronary artery disease, stroke, and Alzheimer's disease. A 2007 meta-analysis of 8 trials found that folate supplements decreased homocysteine 20% and lowered stroke risk 18%. Interestingly, lowering homocysteine with folic acid and B vitamins had no effect on heart attack, strokes, amputations, need for dialysis, or death in patients with chronic or end-stage kidney disease.

Carotenoids and Stroke Protection. Some, but not all, studies have reported a lower risk of stroke from carotenoids, including beta carotene and lycopene.

Many fresh fruits and vegetables contain chemicals that may fight many cancers, including lung, breast, colon, and prostate cancers. Examples of important cancer fighting foods include the following:

Cruciferous vegetables (such as cabbage, Brussels sprouts, and broccoli)
Tomatoes (which contain lycopene)
Carrots (which contain alpha carotene)

Some evidence suggests that antioxidants may enhance the anticancer effects of chemotherapy. In multiple studies, patients who maintained their antioxidant levels were better able to withstand the high stress caused by chemotherapy or radiation therapy compared to those with low antioxidant levels. Antioxidant nutrients that may help reduce the side effects of chemotherapy include vitamins E and C, beta carotene, genistein and daidzein (isoflavones found in soy), and quercetin (found in red wine an purple grape juice).

Any protective effects of vitamins or specific phytochemical against cancer, however, appear to depend on the cooperative effort among them. Individual supplements of any vitamin or food chemical have not as yet shown any benefits.

Additionally, certain supplements may actually encourage tumor growth, particularly when taken in large amounts. Two 2007 studies found a connection between folate supplements and colorectal cancer. In one study, which was designed to evaluate the benefits of folic acid in patients who had previous colorectal adenomas (precancerous polyps), the researchers instead found that folic acid was associated with a higher risk of having 3 or more adenomas and noncolorectal cancers. In another study, it was noted that the downward trend in colorectal cancer diagnoses abruptly started to rise in 1996 when mandatory folate enrichment of grains within the U.S. and Canada began. Rates continue to exceed pre-1996 levels. Additionally, a large 2007 National Cancer Institute/AARP study found an increased risk of advanced and fatal prostate cancer in men who took more than 7 multivitamins a week, but no association between multivitamin use and localized prostate cancer.

High consumption of cruciferous vegetables (at least once per week) was associated with lower risk of kidney cancer, and low consumption (less than once per month) of cruciferous vegetables was associated with higher risk of kidney cancer in a multinational 2007 European study. Cruciferous vegetables also appear to offer protection against head and neck cancer resulting from chemical toxins found in cigarettes and alcohol, for example.

Vitamins and Cancer Protection. Because many cancers are thought to be initiated by the effects of oxygen-free radicals on DNA, the antioxidants A, C, and E and beta carotene have been intensively studied. A major study found that men who took selenium for 6 or 7 years reduced their risk of prostate cancer by 52%. Nevertheless, most individual supplements have not been proven to protect against cancer, and high doses may be dangerous.

A 2007 review of the diets of men exposed to asbestos found a decreased risk of prostate cancer associated with increasing intakes of vitamin C-rich vegetables, but not fruits and vegetables high in vitamin A. The chemopreventive role of silymarin (Silybum marianum), found in milk thistle extract, has been extensively studied and has shown anticancer efficacy against various cancers, especially prostate and skin, by inhibiting UVB radiation.

A review of 13 cancer registries found 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer. Rates from cancer registries in sunny countries (such as Australia and Spain) and less sunny countries (such as Canada and Iceland) were compared. The researchers concluded that vitamin D production in the skin decreases the risk of several solid cancers, especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder, and kidney cancers. The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma.

Consumption of aflatoxins, a common fungus-related toxin infecting cereal grains, oil seeds, spices, tree nuts, and the milk of animals fed contaminated feed, is known to cause hepatocellular carcinoma, a deadly form of liver cancer. Rodent studies have shown that phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids may act as chemopreventive agents, dispersing aflatoxins and protecting against hepatocellular carcinoma. Human trials are planned. A similar study found that several isothiocyanates, diallyl sulfide, and polyphenolic compounds can prevent esophageal dysplasia from progressing to squamous cell carcinoma.

A review of all articles on vitamins and cancer published through February 2007 found that multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. With few exceptions, neither beta-carotene nor vitamin E had benefits for preventing cancer. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos.

A 2007 study of nearly 82,000 men and women in Sweden found that high intake of methionine was associated with reduced risk of pancreatic cancer. The same relationship was not seen with vitamin B6 or folate.

Vitamin A, C, and E. Although some studies have reported an association between low blood levels of these antioxidant vitamins and a higher risk for cancer, supplements of vitamins A, C, and E appear to have few advantages in most cases. And there are some studies finding higher cancer risks with high intakes of antioxidants. For example, a 2003 study reported a higher risk in melanoma in people with vitamin-C rich diets. Another study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. (Vitamin E may be protective against bladder cancer and ovarian cancer.)
Vitamin D. Some studies have suggested that certain vitamin D compounds may inhibit certain cancer cells, specifically prostate cancer, from proliferating. More research is needed. In 2007, the National Cancer Institute confirmed that ultraviolet (UV) radiation exposure may reduce the risk of developing non-Hodgkin lymphoma (NHL), but only in patients with certain variations in the D vitamin receptor gene. A second 2007 study found that variations in this gene increase the risk of diffuse large B-cell lymphoma. A 2007 prospective analysis of 31,500 women in the Women’s Health Study evaluated calcium and vitamin D intake. The researchers found a moderately lower risk of premenopausal, but not postmenopausal, breast cancer with higher intakes of total calcium and vitamin D. A 2007 review of breast cancer cases reported in Ontario, Canada, found reduced breast cancer risks were associated with increasing sun exposure in women ages 10 - 19, less evidence for associations in women ages 20 - 29, and no evidence for ages 45 - 54. Researchers concluded that sun exposure earlier in life, particularly during breast development, may be key in the connection between vitamin D exposure and breast cancer risk.
Folic acid and B12. These B vitamins convert the amino acid homocysteine to methionine, a substance that helps prevent cells from becoming malignant. Folic acid may provide some protection against cervical and colon cancer. One small study showed a reduction of lung cancer cells in smokers taking folic acid and vitamin B12, but the study was very small, of short duration, and other factors might have biased the results. Still another study reported that folic acid may reduce the risk for breast cancer among women who regularly drink alcohol. (In the study, folic acid had no other effect on breast cancer.)

In 2006, a study for the National Institutes of Health reviewed randomized trials evaluating the effectiveness and safety of multivitamin and mineral supplements in preventing cancer and chronic disease. The studies had mixed results, and some supplements reduced cancer rates in certain populations. However, the reviewers concluded that current evidence is not sufficient to determine whether multivitamin and mineral supplements may prevent cancer and chronic disease.

Carotenoids and Cancer Protection. A number of studies have reported that fruits and vegetables rich in carotenoids are associated with protection against many cancers. Lycopene, found in tomatoes, may have particular value in protection against prostate, colon, lung, and bladder cancer. A 2005 study found that in one out of four men with genetic variations that cause them to be more sensitive to oxidative stress, supplementation with selenium, vitamin E, and lycopene significantly reduces the risk of prostate cancer. Individual supplements, however, do not offer any advantage. In fact, evidence now strongly suggests that beta carotene supplements increase the risk for lung cancer in smokers and people exposed to asbestos

Phytochemicals and Cancer Protection. The following phytochemicals appear to have cancer-protecting properties.

Isothiocyanates. Isothiocyanates and sulforaphane, found in cruciferous vegetables, may block the effects of carcinogens and suppress tumor growth. In one study, for example, women with the highest consumption of cruciferous vegetables had a 24% lower risk of breast cancer than women with the lowest consumption.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Researchers are very interested, then, in their effects on hormone-related cancers, including breast and prostate cancers. Much research has focused on soy. In general, a number of Asian studies have reported an association between a higher intake of soy and a lower incidence of reproductive and breast cancers. The effects of phytoestrogens, however, in all women are far from settled. Some evidence suggests the genistein in soy may have properties that are protective against lung cancer. Nonfermented soy products (tofu, soy milk) also may protect against stomach cancer, while fermented soy products (miso, soy paste) appears to increase the risk.
Organosulfurs. The organosulfur compounds found in the onion and garlic family may have very potent properties in suppressing or blocking carcinogenic substances. A 2007 study found that synthetic organosulfur compounds act as selective inhibitors of growth in breast cancer cells. Studies indicate that people who regularly consume fresh or cooked garlic have about half the risk of developing stomach cancer and two thirds the risk of colorectal cancer as people who eat little or no garlic. One possible explanation for garlic's anti-cancer effect in the stomach is its antibacterial action against H. pylori, which can promote stomach cancer. Taking garlic supplements, however, did not offer these benefits.

It should be noted that studies on the health benefits of vitamins and minerals have some important limitations. Some are held to rigorous standards, while others are not. In most cases, the results of existing research are complex, as they can easily be complicated by factors such as diet, exercise, the presence of healthy or unhealthy lifestyle behaviors, environmental factors, and more.


Disease or Condition	Vitamins	Carotenoids, Phytochemicals, and Healthy Foods
Alzheimer's Disease	Vitamin E. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. (One study suggested that the vitamin protected only those who carried the apoE4 gene. No strong evidence to date has found any protection from antioxidant supplements.) Some studies performed since 2002 challenge this finding, while others agree with it. B Vitamins. Some studies suggest that deficiencies of the B vitamins B6, B12, and folate may be a risk factor for Alzheimer' diseases, possibly because deficiencies elevate homocysteine levels, which some research now associated with a higher risk for Alzheimer's disease. Of these, folates may offer the best protection. In 2007, researchers at Tufts-New England Medical Center reviewed all human studies on folate, vitamin B-6, vitamin B-12, and cognitive function in the elderly conducted between 1966 and November 2006. Six of 10 folate studies reported a significant association between low baseline blood folate concentrations and poor cognitive test performance; 4 of 9 folate studies found associations between low blood folate concentrations and increased prevalence of Alzheimer's disease. No association between vitamin B-6 and vitamin B-12 blood concentrations and cognitive-test performance or Alzheimer's disease was seen, and B-vitamin dietary intake was not associated with cognitive function. Although the majority of studies indicated that low blood folate concentrations predicted poorer cognitive function, data are not solid, due to variations in the way the studies were conducted and lack of agreement on what constitutes a low B-vitamin status.	According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. The estrogen-like properties in isoflavones are of interest in the study of Alzheimer's disease. Animal studies suggest that soy might be protective against AD, particularly in postmenopausal women. Of some concern, however, were one population and a few animal studies suggesting that soy intake may pose a risk for greater mental decline among older men. More research is needed to confirm the effects of soy on the aging brain and to determine if there are gender differences.
Infectious Disease	Studies are mixed whether vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place, even after exposure to a cold virus. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems. A review of all studies on vitamin C and pneumonia prevention found only 1 placebo-controlled, randomized trial conducted in an English boarding school during World War II. The trial found a statistically significant (80% or greater) reduction in pneumonia incidence among boys consuming vitamin C. Two less-well-constructed trials arrived at the same conclusion. Therapeutic trials were even scarcer. Only one randomized, double-blind, placebo-controlled study of vitamin C for treatment of pneumonia was found. In this trial, elderly patients given vitamin C had lower mortality and respiratory symptom scores. However, the benefits were restricted to the sickest patients. One other trial of adults in the former Soviet Union found a dose-dependent reduction in the time to recover with two vitamin C doses. One 2007 study on vitamin D found that a single dose by mouth of this vitamin might prevent healthy individuals from activating the bacterium that causes tuberculosis in patients who harbor the infection. Studies on vitamin E specifically have been mixed. A 2002 study, in fact, reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. However, a 2004 clinical trial conducted among elderly nursing home residents found that daily supplementation with 200 IU of vitamin E did provide protection from upper respiratory infections, especially the common cold. At present, there is not enough evidence to recommend vitamin E for infection prevention. Diarrhea is a worldwide problem, particularly in developing countries and those with poor sanitation. Taking supplements with B-complex vitamins, vitamin C, vitamin E, and selenium may reduce the risk of diarrhea, depending upon the organism that causes the disease. Meanwhile, iron supplements appear to increase the risk of infection from organisms that cause diarrhea. Vitamin A has not been shown to prevent diarrhea. Urinary tract infections (UTIs) may affect as many as 25% of pregnant women. A 2007 study found that women who took vitamin C (100 mg) for 3 months had significantly fewer UTIs than women who did not take vitamin C supplements. Rotavirus is a common cause of acute gastric pain in children under age 5. A 2007 study showed that the high amount of isoflavones found in soy-based infant formula can help prevent rotavirus infection.	Lycopene, found in tomatoes, appears to have properties that protect infection-fighting white blood cells. Saponins extracted from ginseng and allicin (found in garlic) have properties that boost the immune system. Both ginseng and garlic have long been traditionally used for their health benefits.
Asthma	Vitamin C from diet has been associated with lower risk for asthma. In one study, some people with exercise-induced asthma benefited from taking vitamin C one hour before strenuous physical activity. In a 2007 study, taking 1,500 mg supplements of vitamin C for 2 weeks helped prevent exercise-induced airway narrowing in patients with asthma.	Flavonoids found in apples and red wine may help lower the risk for asthma. Some evidence indicates that a low dietary intake of antioxidant nutrients could increase the risk for lung damage. Such nutrients should be obtained from fresh, deep green and yellow-orange fruits and vegetables. A 2007 study found low blood lycopene levels in people with asthma. Increasing lycopene- and vitamin A-rich foods may help raise lycopene levels.
Eye Disorder	Cataracts and Macular Degeneration. Oxygen-free radicals play a role in cataract formation and age related macular degeneration, the most common cause of irreversible blindness in the elderly. Bilberry (Vaccinium myrtillis), which contains powerful anthocyanins, is widely used to prevent macular degeneration. Low levels of vitamin C in the lens of the eye have been particularly strong predictors of cataracts. People with cataracts are frequently deficient in vitamin A, the carotenes, lutein, and zeaxanthin. Studies on protection against cataracts using antioxidant supplements have been mixed, including two identically conducted studies that reported opposite results. Vitamin C currently has the strongest evidence for protection, but even with this antioxidant studies are not consistent. A combination of zinc and antioxidants, including vitamin C and E, may slow the progression of macular degeneration. (Vitamin E alone does not appear to be protective.) Glaucoma. Although no evidence exists that antioxidants will prevent glaucoma, some studies reported an association between vitamin E and improved visual fields in patients with glaucoma.	Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein, lycopene, and zeaxanthin, are especially eye-protective and may help prevent cataracts and macular degeneration. The National Eye Institute in 2007 suggested that people with intermediate- or advanced macular degeneration in one eye may want to take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc. They also suggest that a diet high in lutein and zeaxanthin may help reduce the risk of advanced age-related macular degeneration. Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein lycopene, and zeaxanthin are especially eye-protective and may help prevent cataracts and macular degeneration.
Skin Disorders and Wrinkles	Topical vitamin A (retinol) has been shown to improve fine wrinkles due to aging, by increasing glycosaminoglycan, which retains water, and increasing collagen production. One small study found that taking a combination of vitamins oral C and E supplements may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins singly did not have any effect. In fact, a 2002 study reported that oral vitamin C had no effect on sunburn reaction. Of concern, in the same study some natural antioxidants in the body were reduced in people who took the vitamin. Also of concern are studies reporting no benefits and possibly harm from topical vitamin C in the form of ascorbyl palmitate, which is soluble in fat. One study reported that older adults had fewer wrinkles if they ate whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil). Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries.	The following foods and phytochemicals may be especially skin protective: Both green tea and ginger appear to have properties that may provide some protection against skin cancer. Green tea skin care products are now available. The substance silymarin, found in the milk thistle family (which includes artichokes), may inhibit UVB-promoted cancers in animals. In one interesting study, eating garlic protected animals very effectively against UVB damage by interfering with urocanic acid in the skin. Whether these results may apply to humans (and what quantities of garlic might be beneficial) is still unknown.
Osteoporosis	Vitamin D. Vitamin D is the essential companion to calcium in maintaining strong bones. Supplements may be needed for people who have poor exposure to sunlight. It should be noted that diet supplies most people's need and high amounts of vitamin D can be toxic. Of interest: Taking vitamin D supplements does not prevent bone loss in post-menopausal African American women, according to research published in 2005. Further study will be needed to determine whether vitamin D prevents bone loss in women from other ethnic groups. Vitamin K. Studies suggest that vitamin K has properties that protect bone and prevent fracture. Vitamin K2 (menatetrenone), a form of vitamin K, is proving to prevent fractures in people with osteoporosis. Vitamin K affects blood clotting, and supplements are not recommended without specific physician instruction. Vitamin B12. One study reported that in people with osteoporosis and pernicious anemia, taking vitamin B12 (which is used to treat the anemia) also increased bone density. Vitamin C and E. There has been some indication of a positive association between vitamin C and E intake and bone density, although evidence proving actual benefits is weak. Note on Vitamin A. High amounts of dietary vitamin A reduces bone density and may even increase the risk for fracture in both postmenopausal women and men. (A form of vitamin A, retinoic acid, has been found to stimulate bone break down.) Beta carotene does not appear to increase risk. Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones.	Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones. Studies are suggesting that isoflavones-rich soy products may actually improve bone density in postmenopausal women. A 2007 study of postmenopausal women in Italy found that 24 months of treatment with genistein plus calcium and vitamin D increased bone density, while women who took calcium and D alone lost bone density. Flavonoids and other compounds in tea may protect the bones.
Menstrual Disorders	Vitamin B6. Limited clinical evidence suggests that vitamin B6 may be beneficial in reducing premenstrual symptoms, including depression. Typically, women take 100 mg per day, although one study suggested that a lower dose (50 mg) may have the same effect. Other preliminary research indicates that women who receive the equivalent of 1,200 mg of calcium and 400 IU of vitamin D per day (through food or supplements) have a significantly lower incidence of premenstrual symptoms than women who did not. Vitamin B1. One study reported relief from menstrual pain using vitamin B1 (thiamin). Vitamin E. Several randomized controlled trials have shown that vitamin E significantly improves both physical and emotional premenstrual symptoms. One study reported that high doses of vitamin E helped reduce menstrual cramps. The doses were much higher than those recommended and could possibly increase the risk for bleeding. Although anecdotal evidence reports that vitamin E helps reduce the frequency of hot flashes for menopausal women, there is no clinical evidence to support this claim.

Resources

http://fnic.nal.usda.gov -- The Food and Nutrition Information Center
http://dietary-supplements.info.nih.gov -- Office of Dietary Supplements, National Institutes of Health
www.ars.usda.gov/ba/bhnrc/ndl -- Nutrient Data Laboratory
www.fda.gov -- Food and Drug Administration
www.eatright.org -- The American Dietetic Association
www.acsh.org -- American Council on Science and Health
www.aicr.org -- American Institute for Cancer Research
www.nutritiondata.com -- Information on vitamins and nutrients in foods
www.consumerlab.com -- Independent testing of nutritional supplements' contents and quality
www.usp.org -- US Pharmacopeia
www.herbs.org -- Herb Research Foundation

References

Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch Ophthalmol. 2007;125(9):1225-1232.

Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B. Fruit, vegetable, vitamin A intakes, and prostate cancer risk. Prostate Cancer Prostatic Dis. 2007 May 22; [Epub ahead of print]

Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Six months of isoflavone supplement increases fat-free mass in obese-sarcopenic postmenopausal women: a randomized double-blind controlled trial. Eur J Clin Nutr. 2007 Feb 21; [Epub ahead of print]

Bermudez Y, Ahmadi S, Lowell NE, Kruk PA. Vitamin E suppresses telomerase activity in ovarian cancer cells. Cancer Detect Prev. 2007;31(2):119-28. Epub 2007 Feb 28.

Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin d deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007 ;92(9):3517-22. Epub 2007 May 29.

Clements RH, Katasani VG, Palepu R, Leeth RR, Leath TD, Roy BP, Vickers SM. Incidence of vitamin deficiency after laparoscopic Roux-en-Y gastric bypass in a university hospital setting. Am Surg. 2006;72(12):1196-202.

Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Colorectal Dis. 2007;9(6):562-566.

Dietary Guidelines for Americans 2005. Dept of Health and Human Services, US Dept of Agriculture. Accessed 10/3/2007.

Fischer Walker CL, Black RE. Micronutrients and diarrheal disease. Clin Infect Dis. 2007;45 Suppl 1:S73-S77.

Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE. Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study. Circulation. 2007;116(13):1497-503.

Headstrom PD, Rulyak SJ, Lee SD. Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn's disease. Inflamm Bowel Dis. 2007 Sep 20; [Epub ahead of print]

Inderjeeth CA, Glennon D, Petta A, Soderstrom J, Boyatzis I, Tapper J.Vitamin D and muscle strength in patients with previous fractures. N Z Med J. 2007;120(1262):U2730.

Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S, Tsugane S; Japan Public Health Center-based Prospective Study Group. Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. J Nutr. 2007;137(7):1808-1814.

J.G. Ray, C. Kearon, Q. Yi, P. Sheridan, and E. Lonn, for the Heart Outcomes Prevention Evaluation 2 (HOPE-2) Investigators. Randomized Trial of Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism. Ann Intern Med. 2007;146(11):761-767.

Kitchin B, Morgan SL. Not just calcium and vitamin D: other nutritional considerations in osteoporosis. Curr Rheumatol Rep. 2007;9(1):85-92.

Kune G, Watson L. Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutr Cancer. 2006;56(1):11-21.

Lim MR, Huang RC, Wu A, Girardi FP, Cammisa FP Jr. Evaluation of the elderly patient with an abnormal gait. J Am Acad Orthop Surg. 2007;15(2):107-117.

Martin H, Lindblad B, Norman M. Endothelial function in newborn infants is related to folate levels and birth weight. Pediatrics. 2007;119(6):1152-1158.

Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1325-1329.

Nardin RA, Amick AN, Raynor EM. Vitamin B(12) and methylmalonic acid levels in patients presenting with polyneuropathy. Muscle Nerve. 2007;36(4):532-535.

Ochoa-Brust GJ, Fernández AR, Villanueva-Ruiz GJ, Velasco R, Trujillo-Hernández B, Vásquez. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obstet Gynecol Scand. 2007;86(7):783-787.

Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol. 2007;125(5):661-669.

Pham DQ, Plakogiannis R. Vitamin E supplementation in Alzheimer’s disease, Parkinson’s disease, tardive dyskinsia, and cataract: Part 2. Ann Pharmacother. 2005;39(12): 2065-2072.

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Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Systemic lupus erythematosus

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

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Treatment for Cutaneous and...
Treatment for Severe SLE...
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Systematic Lupus Erythematosus (SLE)

SLE is an autoimmune disease that causes a chronic inflammatory condition. The inflammation triggered by SLE affects many organs in the body, including skin, joints, kidneys, lung, and nervous system. Women, especially African-American and Asian women, are at highest risk for developing SLE.

Symptoms and Diagnosis

Not all patients with SLE experience the same symptoms. The most common symptoms are joint pain, skin rash, and fever. Symptoms can develop slowly or appear suddenly. Many patients with SLE have “flares,” in which symptoms suddenly worsen and then disappear for long periods of time. Diagnosing SLE is complicated because symptoms vary widely and can resemble other conditions. A doctor will base an SLE diagnosis on certain specific criteria including symptom history and the results of blood tests for antinuclear antibodies.

Treatment

No drug can cure SLE, but many different drugs can help control symptoms and relieve discomfort. The choice of drugs depends on the severity of the condition as well as other factors. Patients with mild SLE may be helped by nonsteroidal anti-inflammatory drugs (NSAIDs) while patients with more severe SLE may require corticosteroids or immunosuppressants. Researchers are working to develop new drugs and treatments for SLE.

Living with SLE

Patients can make lifestyle changes to help cope with SLE. These include:

Avoid excessive sunlight exposure, and wear sunscreen (ultraviolet light is the one of the main triggers of flares).
Get plenty of rest (fatigue is another common SLE symptom).
Engage in regular light-to-moderate exercise to help fight fatigue and heart disease, and to keep joints flexible.

Introduction

Systemic lupus erythematosus (SLE) is a chronic, often life-long, autoimmune disease. It can be mild to severe, and affects mostly women. SLE may affect various parts of the body, but it most often manifests in the skin, joints, blood, and kidneys. SLE was first described in 1828. Its very name helps define the disease:

Systemic is used because the disease can affect organs and tissue throughout the body.
Lupus is Latin for wolf. It refers to the rash that extends across the bridge of the nose and upper cheekbones and was thought to resemble a wolf bite.
Erythematosus is from the Greek word for red and refers to the color of the rash.

Lupus has many different symptoms. Common ones include:

Fatigue
Joint pain or swelling
Skin rashes

Causes

Systemic lupus erythematosus is a complex disorder that occurs as a consequence of a number of independent processes and factors.

Environmental factors, such as viruses, exposure to chemicals, or sunlight trigger inflammatory or immune activity. This immune activation may begin as an appropriate response to an unwanted "invader." But, because of a combination of genetic factors, an individual with lupus develops an ongoing immune response that does not shut itself off appropriately. This leads to waxing and waning flares of inflammation that can involve various organs of the body, depending on specific features of this self-perpetuating immune response in individual patients.

The exact combination of genes that predispose individuals to SLE may differ somewhat from patient to patient, but probably share certain common features which tend to impair the ability of the body to get rid of immune-triggering particles and which tend to prolong or increase the degree of immune responsiveness to these triggers.

A major characteristic of lupus is that it is an autoimmune response in which immune factors, called autoantibodies, attack the person's own cells. Some autoantibodies are normal in a well-balanced immune system, and serve various roles to help the body dispose of wastes, protect from infectious invaders, and to keep blood vessels clear. In healthy people, autoantibodies tend to be well-regulated and well "masked," or covered up, until needed. Therefore, it is probably the high activity and high detectability of autoantibodies that makes lupus unique, not the fact that they exist.

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body's immune system, which fights infection and heals wounds and injuries:

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign proteins, such as a virus.
The masses of blood cells that gather at the injured or infected site produce factors to fight any infections.
In the process, the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting any bleeding blood vessels and initiating fiber-like patches to the tissue.
Under normal conditions, the immune system has special factors that control and limit this inflammatory process.

The Infection Fighters. B cells and T cells are two important components of the immune system that play a role in the inflammation associated with lupus. Both B cells and T cells belong to a family of immune cells called lymphocytes. Lymphocytes help fight infection.

B cells and T cells are involved in the immune system's response to infection. Antigens are foreign bodies (such as bacteria and viruses) that stimulate the immune system to produce autoantibodies. When a T cell recognizes an antigen it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion.

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

For reasons that are still not completely understood, both the T cells and B cells become overactive in lupus patients. In lupus, a complex interaction between activated immune cells and an impaired antigen-elimination process leads to a greater than normal range of what the antibodies recognize. Eventually, antibodies are made that recognize more of the body's own tissues in a stronger or more persistent manner than is healthy, and inflammatory responses are mounted in these tissues.

Autoantibodies. In the majority of patients with SLE, antinuclear antibodies (ANA) are detectable. Such autoantibodies may be present in individuals up to 7 years prior to their developing symptoms of lupus. Some subtypes of ANA are found in lupus patients and only rarely in people without lupus. These include:

Anti-ds DNA. An autoantibody called anti-double stranded DNA (anti-ds DNA) may play an important role in some lupus patients.
Anti-Sm antibodies. This antibody is found most often in lupus patients of African descent and is almost never detected in people without lupus.
Anti-Ro (SSA) and Anti-La (SSB)
Antiphospholipid antibodies

Cytokines. Most immune cells secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for maintaining the balance of the body during immune responses, including:

Infections
Injuries
Tissue repair
Blood clotting
Clearing of debris from inflamed blood vessels
Other aspects of healing.

If overproduced, however, they can cause serious damage, including dangerous levels of inflammation and cellular injury. Specific cytokines called interferons and interleukins play a critical role in SLE by regulating the secretion of autoantibodies by B cells.

Complement. Another immune factor of high interest in SLE is the complement system. This is comprised of more than 30 proteins and is important for defending and regulating the immune response. Inherited deficiencies in certain complement components (C1q, C1r, C1s, C4, and C2) have long been associated with SLE.

Researchers estimated that 20 - 100 different genetic factors may be involved in the alterations of the immune system set point that could make a person susceptible to SLE.

Research published in 2003 identified a particular set of genes, now commonly called the "interferon signature," that is activated by interferon in patients with severe lupus. This discovery may help doctors identify patients at particular risk for severe disease before they develop symptoms.
A genetic risk factor for lupus in African-American women has been identified.
Other research has identified defects in genes that regulate apoptosis, the natural process by which cells self-destruct.
An abnormal gene identified in some patients with SLE promotes the build-up of immune complexes that can cause kidney damage. HLA (human leukocyte antigen) is a protein that presents antigens to T cells by holding them up from the surface of macrophages or other antigen-presenting cells. Among the types of HLA associated with lupus are HLA-DR2, -DR3, -A1, -B8, and DMA-0104.

In genetically susceptible people, there are various external factors that can provoke an immune response. Possible SLE triggers include colds, fatigue, stress, chemicals, sunlight, and certain drugs.

Viruses. Blood tests reveal that patients with SLE are more likely to have been exposed to certain viruses than the general population. These viruses include the Epstein-Barr virus (the cause of mononucleosis), cytomegalovirus, and parvovirus-B1.

Results from a 2005 study, conducted by researchers at the National Institute of Environmental Health Sciences, suggested a strong association between Epstein-Barr virus (EBV) and increased risk of lupus, particularly for African-Americans. The association was not as strong for whites, but increased with age (patients over 50 years of age had four times higher risk).

The researchers also observed that a genetic variation in CTLA-4, a protein that helps regulate T cell immune system response, appeared to modify the risk of lupus associated with EBV-IgA antibodies. Therefore, an individual’s CTLA-4 genotype could determine the immune system’s responsiveness in fighting repeat episodes of EBV infection.

Click the icon to see an image of mononucleosis.

Some research suggests that different viruses may imprint specific types of SLE. For instance cytomegalovirus may affect blood vessels and cause problems such as Raynaud's phenomenon or blood abnormalities, but may not affect the kidney as much. These are speculations, however, and not a proven association.

Sunlight. Ultraviolet (UV) rays found in sunlight are important SLE triggers. When they bombard the skin, they can alter the structure of DNA in cells below the surface. The immune system may perceive these altered skin cells as foreign and trigger an autoimmune response against them. UV light is categorized as UVB or UVA depending on the length of the wave.

UVB are short waves (280 - 320 nm). The shorter the wavelengths, the more damage they do.
UVA are longer waves (320 - 400 nm). Some research suggests that UVA wavelengths in the longest range, known as UVA1 (340 - 400 nm), may actually repair DNA and normalize immune responses.

Chemicals. Clusters of SLE cases have occurred in populations with high exposure to certain chemicals. Chlorinated pesticides and crystalline silica are two suspects. A number of other chemicals are under investigation. However, it is very difficult to determine a causal role for any specific chemicals. (Silicone breast implants have been under intense scrutiny as a possible trigger of autoimmune diseases, including SLE. The weight of evidence to date, however, finds no support for this concern.) Some drugs have been associated with a temporary lupus syndrome (drug-induced lupus), which resolves when these drugs are stopped.

Hormones. Cytokines, major immune factors that are active in SLE, are directly affected by sex hormones. In general, estrogen enhances antibody production, and testosterone reduces antibody production, although their exact role in SLE may be more complicated than that since there are various ways in which each hormone might influence various immune cells. Women with SLE may have lower levels of several active male hormones (androgens), and some men who are affected by SLE may also have abnormal androgen levels.

Premature menopause, and its accompanying symptoms (such as hot flashes), is common in women with SLE. Hormone replacement therapy (HRT), which is used to relieve these symptoms, increases the risk for blood clots and heart problems. It is not clear whether HRT triggers SLE flares. Women should discuss with their doctors whether HRT is an appropriate and safe choice. Guidelines recommend that women who take HRT use the lowest possible dose for the shortest possible time. Women with SLE who have active disease, antiphospholipid antibodies, or a history of blood clots or heart disease should not use HRT.

Oral Contraceptives. Female patients with lupus used to be cautioned against taking oral contraceptives (OCs) due to the possibility that estrogen could trigger lupus flare-ups. However, recent evidence indicates that OCs are safe, at least for women with inactive or stable lupus. Women who have been newly diagnosed with lupus should avoid OCs. Lupus can cause complications in its early stages. For this reason, women should wait until the disease reaches a stable state before taking OCs. In addition, women who have a history of, or who are at high risk for, blood clots (particularly women with antiphospholipid syndrome) should not use OCs. The estrogen in OCs increases the risk for blood clots.

Risk Factors

The number of people diagnosed with lupus has more than tripled over the past four decades. Some experts believe this may simply indicate a greater degree of doctor training in recognizing the syndrome.

About 90% of lupus patients are women, most diagnosed when they are in their childbearing ages. Hormones may be an explanation. After menopause, women are only 2.5 times as likely as men to contract SLE. Flares also become somewhat less common after menopause in women who have chronic SLE.

African-Americans are three to four times more likely to develop the disease than Caucasians and to have severe complications. Hispanics and Asians are also more susceptible to the disease.

A family history plays a strong role in SLE. A brother or sister of a patient with the disorder has 20 times the risk as someone without an immediate family member with SLE.

The disease is rare in childhood. When it does occur, it is often associated with thrombotic thrombocytopenia purpura, a condition resulting from abnormally low levels of blood platelets. SLE in children may also be caused by certain medications, including minocycline and zafirlukast.

Rheumatoid Arthritis. Studies have investigated the relationship among hormones, SLE, and rheumatoid arthritis, another autoimmune disease. Higher levels of estrogen are associated with SLE, while lower levels are associated with rheumatoid arthritis. Some research suggests that some patients, in fact, progress from one disease to the other, and that such transitions occur during major hormonal shifts, such as the onset of menopause or pregnancy.

Rheumatoid arthritis is a systemic autoimmune disease that initially attacks the lining, or synovium, of the joints.

Many prescription drugs can cause lupus-like skin symptoms. In one study, the most common drugs causing these symptoms were high blood pressure (hypertension) medications, including hydrochlorothiazide, angiotensin-converting-enzyme inhibitors, and calcium-channel blockers. About 40 different drugs have been linked to lupus onset. Anyone diagnosed with cutaneous lupus erythematosus should be sure to tell their doctors all the medications (including herbs and supplements) that they are taking.

Smoking. Smoking may be a risk factor for triggering SLE and can increase the risk for skin and kidney problems in women who have the disease.

Symptoms

SLE symptoms may develop slowly over months or years, or they may appear suddenly. Symptoms tend to be worse during winter months, perhaps because prolonged exposure to sunlight in the summer causes a gradual build-up of factors that trigger symptoms months later.

The most common symptom is joint pain, which occurs in about 90% of patients with SLE. Characteristics of this symptom vary widely:

It is often accompanied by swelling and redness.
It can last from hours to months.
It may be mild or severe.
It can occur in one joint, move from one to another, or flare erratically.
Pain often occurs in the morning and improves during the day, only to return later when the patient tires.
The joints most affected are fingers, wrists, elbows, knees, and ankles. (Joints in the spine and neck are not affected.)

Children may experience these symptoms as growing pains, and, in all patients, they may be the only symptoms for many years.

Fever occurs in 90% of patients with SLE and is usually caused by the inflammatory process of the disease, not by infection. It is low-grade except during an acute lupus crisis.

Three-quarters of patients with SLE have skin inflammation and skin lesions (ulcers, rashes, or other injured areas). About half of these lesions are photosensitive; that is, they are aggravated by ultraviolet (UV) radiation from sunlight, even from light coming through a window. (UV radiation may even trigger systemic flares in patients with SLE.)

A number of different skin conditions have been described in patients with SLE.

Discoid Lupus Erythematosus. About 20% of patients have discoid lesions. In such cases, the condition is often known as discoid lupus erythematosus (DLE). Patients with this condition may have the following skin abnormalities:

Discoid means coin-shaped, so these lesions are round and raised. They are also scaly. Untreated, the margins gradually extend outward as the center dries out and shrivels, causing severe scarring. If discoid lesions appear on the scalp, they can plug hair follicles and cause irreversible hair loss. Discoid lesions can also appear on the upper body.

Lupus, discoid -- view of lesions on the chest: This close-up picture of the neck clearly shows the typical rounded appearance of discoid lupus. The whitish appearance is caused by scaling. The two dark spots are biopsy sites and are not part of the disease.

A butterfly-shaped rash across the face may accompany this condition. This rash causes little scarring, although spidery, branching lines of swollen capillaries (the tiniest blood vessels) may appear.

Click the icon to see an image of systemic lupus erythematosus.

Most patients with this condition have only a limited skin disorder. In only about 10% of cases does discoid lupus develop into full-blown SLE.

Subacute Cutaneous Lupus Erythematosus. Subacute cutaneous lupus erythematosus (SCLE) can cause skin lesions on parts of the body that are exposed to sunlight. These lesions do not cause scarring.

Vasculitis. Patients with SLE sometimes develop inflammation in the blood vessels (vasculitis) that may have the following effects on the skin:

Red welts may form across large areas of the body.
Sometimes deep red bumps may appear, particularly on the leg, where they may ulcerate.
In some people, reddish-purple lesions appear on the pads of fingers and toes or near the nails of fingers and toes.
Lesions caused by vasculitis may ulcerate or blister if they erupt on mucous membranes in the mouth, nose, or vagina and can be painful if they occur on the throat.
Vasulitis can attack blood vessels in almost any other organ, including the brain, the heart, and the gastrointestinal tract.

Click the icon to see an image of vasculitis.

Other symptoms include:

Fatigue
Loss of appetite, nausea, and weight loss
Chest pain
Bruising
Menstrual irregularities
Thought and concentration disturbances
Personality changes
Sleep disorders, such as restless legs syndrome and sleep apnea
Dryness of the eyes and mouth
Brittle hair or hair loss

Hair loss or breakage may also occur in about half of patients with SLE during severe flares or after pregnancy or severe illness. In such cases, hair grows back.

Raynaud's phenomenon is a condition in which cold or stress can cause spasms in impaired blood vessels, resulting in pain in fingers and toes. It occurs as part of the inflammatory response in blood vessels, which can narrow them and reduce circulation. In extreme cases, gangrene can result.

Click the icon to see an image of Raynaud's phenomenon.

A number of conditions may resemble SLE:

Scleroderma: Hardening of the skin caused by overproduction of collagen
Multiple sclerosis: Fatigue, heaviness or clumsiness in the arms and legs
Rheumatoid arthritis: Inflammation of the lining of the joints
Sjögren syndrome: Characterized by dry eyes and dry mouth
Mixed connective tissue disorder: Similar to SLE, but milder
Myositis: Inflammation and degeneration of muscle tissues
Rosacea: Flushed face with pus-filled blisters
Seborrheic dermatitis: Sores on lips and nose
Lichen planus: Swollen rash that itches, typically on scalp, arms, legs, or in the mouth
Dermatomyositis: Bluish-red skin eruptions on face and upper body
Lyme disease: Bulls-eye rash, joint inflammation, and flu-like symptoms

Complications

Systemic lupus erythematosus (SLE) is one of the most serious rheumatic diseases. According to a 2002 government study, the annual number of deaths has risen from 879 - 1,406 since 1979. About a third of these deaths occur in people aged 15 - 44 years, mostly women. Such numbers may be underestimates, since SLE can affect so many organs that a cause of death in some people with SLE may not be directly attributed to the condition. A primary cause of death among patients with lupus is atherosclerosis, a disease of the coronary blood vessels resulting from accelerated buildup of plaque.

SLE is unpredictable and varies greatly form one individual to the next. Severity also appears to differ among ethnic groups and countries. In European and North American patients with SLE for example, overall 5-year survival rates are 93 - 95%, while in Asia or Africa they are considerable lower (60 - 70%). Other research indicates that African-American and Hispanic American patients suffer greater organ damage than Caucasian patients. Genetic factors appear to have some influence on specific effects of SLE on organ damage among ethnic groups. However, the poorer outlook among minority groups and in underdeveloped nations is probably due to less access to good health care.

Mild SLE. About 20 - 30% of cases are mild. For many of these patients, the only symptoms may be the skin rashes of discoid lupus erythematosus (DLE) or subacute cutaneous lupus erythematosus (SCLE) with or without joint aches. The number and intensity of symptoms in mild cases often decrease over time, as does the likelihood of major organ involvement. These skin conditions, however, are not absolute insurance against more severe disease, and patients with mild SLE should be tested for organ involvement.

Widespread SLE. Most commonly, SLE is a chronic, life-long disease, alternating between periods of symptom relapse, (called flares), and remission. The disease may begin in any of the various systems of the body and progress unpredictably to others. The following are typical patterns:

Symptom relapses, or flares, occur on the average of two or three times a year.
Between flares, most patients with SLE function at about 90% of normal capacity.

The degree of severity depends on different factors:

Severity of the inflammatory response
Frequency of episodes
The degree of organ or system involvement

Vital organs or systems, such as lungs, kidneys, nervous system, joints skin, and others are affected in 50 - 75% of patients with SLE. Infections followed by kidney failure are the chief causes of death in patients with SLE.

Because of more effective and aggressive treatment, the prognosis for SLE has improved markedly over the past two decades. Long-term progress of the disease is affected greatly by treatment in the initial acute phase of the disease, so a speedy and accurate diagnosis is all-important. The 10-year survival rate with treatment is now 85 - 95%, and many people have a normal life span. SLE that develops later in life is generally less serious than SLE that strikes in childhood.

Almost 85% of patients with SLE experience problems associated with abnormalities in the blood.

Anemia. About half of patients with SLE are anemic. Causes include:

Iron deficiencies resulting from excessive menstruation
Iron deficiencies from gastro-intestinal bleeding caused by some of the treatments
A specific anemia called hemolytic anemia, which destroys red blood cells
Anemia of chronic disease

Hemolytic anemia can occur with very high levels of the anticardiolipin antibody. It can be chronic or develop suddenly and be severely (acute).

Antiphospholipid Syndrome. Between 34 - 42% of patients with SLE have antiphospholipid syndrome (APS). This is a specific set of conditions related to the presence of autoantibodies called lupus anticoagulant and anticardiolipin. These autoantibodies react against fat molecules called phospholipids, and so are called antiphospholipids. Their actions have complex effects that include causing narrowing and abnormalities of blood vessels.

Patients who have APS have a very incidence of blood clots, which most often occur in the deep veins in the legs (32%). Blood clotting, in turn, puts patients at higher risk for stroke (13%) and pulmonary embolism (clots in the lungs) (9%).

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (iliofemoral veins). Such a clot prevents normal return of blood from the leg to the heart.

About 22% of patients have thrombocytopenia -- a reduction in blood platelets that can cause bleeding.
The effects on blood vessels have also been associated with confusion, headaches, and seizures. Leg ulcers can also develop.
Patients with APS who become pregnant have a high incidence of pregnancy loss, especially in the late term.

Not all patients with APS carry both of the autoantibodies, and they can also wax and wane and so have varying effects. APS also occurs without lupus in about half of patients with the syndrome.

Thrombocytopenia. In thrombocytopenia, antibodies attack blood platelets. In such cases, blood clotting is impaired, which causes bruising and bleeding from the skin, nose, gums, or intestines. (This condition can also occur in APS, but it is not considered to be one of the standard features of the syndrome.)

Neutropenia. Neutropenia is a drop in the number of white blood cells. Patients with SLE often neutropenia, but the condition is usually harmless unless the reductions are so severe that they leave the patient vulnerable to infections.

Acute Lupus Hemophagocyte Syndrome. A rare blood complication of SLE that occurs primarily in Asians is called acute lupus hemophagocytic syndrome. It is generally of short duration and characterized by fever and a sudden drop in blood cells and platelets.

Lymphomas. Patients with SLE and other autoimmune disorders have a greater risk for developing lymph system cancers such as Hodgkin’s disease and non-Hodgkin’s lymphoma (NHL). A 2005 study reported that patients with SLE were over seven times more likely to develop NHL than healthy patients.

Heart disease is a primary cause of death in lupus patients. The immune response in SLE can cause inflammation and other damaging effects that can cause significant injury to the arteries and tissues associated with the circulation and the heart. In addition, SLE treatments (particularly corticosteroids) affect cholesterol, weight, and other factors that can also affect the heart. For decades, experts questioned the extent to which the drugs used to treat SLE contributed to the high rate of atherosclerosis in such patients. Numerous studies now suggest that something about the disease process itself, possibly the chronic inflammation of the blood vessels, probably lies at the root of this dangerous problem. In any event, patients with SLE, have a higher chance for the following conditions, which put them at risk for heart attack or stroke:

Atherosclerosis, or plaque buildup in the arteries
Increased stiffness in the arteries
Unhealthy cholesterol and lipid (fatty molecules) levels
High blood pressure, most likely because of kidney injury and corticosteroid treatments
Congestive heart failure
Pericarditis, an inflammation of the tissue surrounding the heart (occurs in about 30% of patients)
Myocarditis, an inflammation of the heart muscle itself (rare)

Click the icon to see an image of pericarditis.

Abnormalities in the valves of the heart (rare)
Blood clots

The risk for cardiovascular disease, heart attack, and stroke is much higher than average in younger women with SLE. The risks decline as such women age.

SLE affects the lungs in about 60% of patients:

Recurrent inflammation of the membrane lining the lung (pleurisy) is the most common problem.
In some cases, fluid accumulates, a condition called pleural effusion, and can cause stabbing localized pain that worsens when coughing, sneezing, laughing, or taking a deep breath.
Inflammation of the lung itself in SLE is called lupus pneumonitis. It can be caused by infections or by the SLE inflammatory process. Symptoms are the same in both cases: fever, chest pain, labored breathing, and coughing. Rarely, lupus pneumonitis becomes chronic and causes scarring in the lungs, which reduces their ability to deliver oxygen to the blood.
A very serious and also rare condition called pulmonary hypertension occurs when high pressure develops in the vessels supplying blood to the lungs.

Click the icon to see an image of primary pulmonary hypertension.

The kidneys are a crucial battleground in SLE because it is here that the debris left over from the immune attacks is most likely to be deposited. About 50% of patients with SLE exhibit inflammation of the kidneys (called lupus nephritis).This condition occurs in different forms and can vary widely in severity.

Click the icon to see an image of the kidney.

Proliferative nephritis is a serious variant of lupus nephritis. It occurs when the inflammatory process causes widespread damage and scarring in the blood vessels of the kidneys, which filters waste products, water, and salts out of the blood. The condition is associated with high blood pressure and kidney deterioration.
Membranous lupus nephritis is another variant that is often associated with a good outlook. In some cases, however, if the kidney is persistently exposed to high protein levels, the disorder can progress to fatal end-stage kidney (renal) disease.

Serious complications occur eventually in about 30% of patients. If kidney injury develops, it almost always occurs within 10 years of the onset of SLE, rarely after that.

Nearly all patients with SLE report some symptoms relating to problems that occur in the central nervous system (CNS), which includes the spinal cord and the brain. Most of these symptoms are minor and some, such as headache, may be related to depression rather than the disease itself. CNS involvement is more likely to occur in the first year, usually during flare-ups in other organs. Symptoms vary widely and may be indistinguishable from psychiatric or neurologic disorders or from the side effects of some medications used for SLE. Central nervous system symptoms are usually mild, but there is little effective treatment available for them. CNS symptoms get worse as the disease progresses.

The most serious CNS disorder is inflammation of the blood vessels in the brain, which occurs in 10% of patients with SLE. Fever, seizures, psychosis, and even coma can occur. Other CNS side effects include:

Irritability
Emotional disorders (anxiety, depression)
Mild impairment of concentration and memory
Migraine and tension headaches
Problems with the reflex systems, sensation, vision, hearing, and motor control

Infections are a common complication and a major cause of death in all stages of SLE. The immune system is indeed overactive in SLE, but it is also abnormal and reduces the ability to fight infections. Patients are not only prone to the ordinary streptococcal and staphylococcal infections, but they are also susceptible to fungal and parasitic infections (called opportunistic infections), which are common in people with weakened immune systems. They also face an increased risk for herpes, salmonella, and yeast infections. Corticosteroid and immunosuppressants, treatments used for SLE, also increase the risk for infections, thereby compounding the problem.

About 45% of patients with SLE suffer gastrointestinal problems, including nausea, weight loss, mild abdominal pain, and diarrhea. Severe inflammation of the intestinal tract occurs in less than 5% of patients and causes acute cramping, vomiting, diarrhea, and, rarely, intestinal perforation, which can be life-threatening. Fluid retention and swelling can cause intestinal obstruction, which is much less serious but causes the same type of severe pain. Inflammation of the pancreas can be caused by the disease and by corticosteroid therapy.

Arthritis caused by SLE almost never leads to destruction or deformity of joints. The inflammatory process can, however, damage muscles and cause weakness. Patients with SLE also commonly experience reductions in bone mass density (osteoporosis) and have a higher risk for fractures, whether or not they are taking corticosteroids (which can increase the risk for osteoporosis). Women who have SLE should have regular bone mineral density scans to monitor bone health.

Click the icon to see an image of osteoporosis.

Inflamed blood vessels in the eye can reduce blood supply to the retina, resulting in degeneration of nerve cells and a risk of hemorrhage in the retina. The most common symptoms are cotton-wool-like spots on the retina. In about 5% of patients sudden temporary blindness may occur.

In one study, 40% of patients with SLE quit work within 4 years of diagnosis, and many had to modify their work conditions. Significant factors that predicted job loss included high physical demands from the work itself, a more severe condition at the time of diagnosis, and lower educational levels. People with lower income jobs were at particular risk for leaving them.

Women with lupus who conceive face high-risk pregnancies. It is important for women to understand the potential complications and plan accordingly. The most important advice is to avoid becoming pregnant when lupus is active.

Research suggests that the following factors predict a successful pregnancy:

Disease state at time of conception. Experts strongly recommend that women wait to conceive until their disease state has been inactive for at least 6 months.
Kidney (renal) function. Women should make sure that their kidney function is evaluated prior to conception. Poor kidney function can worsen high blood pressure and cause excess protein in the urine. These complications increase the risk for preeclampsia and miscarriage.
Lupus-related antibodies. Antiphospholipid and anticardiolipin antibodies can increase the risks for preeclampsia, miscarriage, and stillbirths. Anti-SSA and anti-SSB antibodies can increase the risk for neonatal lupus erythematosus, a condition that can cause skin rash and liver and heart damage to the newborn baby. Levels of these antibodies should be tested at the start of pregnancy. Certain medications (aspirin, heparin) and tests (fetal heart monitoring) may be needed to ensure a safe pregnancy.
Medication use during pregnancy. Women with active disease may need to take low-dose corticosteroids, but women with inactive disease should avoid these drugs. Steroids appear to pose a low risk for birth defects, but can increase a pregnant woman’s risks for gestational diabetes, high blood pressure, infection, and osteoporosis. For patients who need immunosuppressive therapy, azathioprine (Imuran) is an option. Methotrexate (Rheumatrex) and cyclophosphamide (Cytoxan) should not be taken during pregnancy.

Pregnancy Risks

Women with lupus are 20 times more likely to die during pregnancy than women without the disease. The risk for maternal death is due to the following serious conditions that can develop during pregnancy:

Miscarriages. About 25% of lupus pregnancies result in miscarriage. The risk is highest for patients with antiphospholipid antibodies, active kidney disease, or high blood pressure.
Blood clots. Women with lupus have a 6 times greater risk for developing deep vein thrombosis (blood clots) than women without the disease.
Clotting complications. Low blood platelet count and anemia are also risks. Women with lupus are 3 times more likely to need a transfusion during pregnancy than women without lupus.
Infections. Blood infections (sepsis), pneumonia, and urinary tract infections are more common in pregnant women with lupus.
Preeclampsia. Women with lupus are three times more likely than healthy women to develop preeclampsia (pregnancy-related high blood pressure), which can be potentially life threatening.

Birth Complications

Pre-term birth. Women with lupus are 2.5 times more likely to have pre-term labor than women without lupus. Pre-term labor increases the risk for giving birth to low-weight babies.
Stillbirths. A 2005 study reported that the risk of still births was 10 times greater for women who had not yet been diagnosed with lupus, and 4 times greater for women with diagnosed lupus, compared with healthy women. This suggests that lupus may have a pre-disease state.
Caesarean section. Thirty-seven percent of women with lupus require a C-section compared with 22% of women without the disease.

Despite these obstacles, many women with lupus have healthy pregnancies and deliver healthy babies. To increase the odds of a successful pregnancy, it is important for women to plan carefully before becoming pregnant. Be sure to find knowledgeable doctors with whom you can communicate and trust. Experts recommend that pregnant women with lupus assemble an interdisciplinary health care team that includes a rheumatologist, high-risk obstetrician, and (for patients with kidney disease) a nephrologist.

Diagnosis

No single test can confirm or rule out SLE. A number of tests are required before SLE can be diagnosed definitively. The first symptoms of SLE can resemble one of many syndromes or disorders, including rheumatoid arthritis, Still's disease, rheumatic fever, Lyme disease, multiple sclerosis, thrombotic thrombocytopenia purpura, cryoglobulinemia, Weber-Christian disease, viral infections, vasculitis, psychosis, and other conditions. Other autoimmune disorders, such as Sjögren syndrome or scleroderma, may even be present at the same time as SLE.

1. Characteristic rash across the cheek

2. Discoid lesion rash

3. Photosensitivity

4. Oral ulcers

5. Arthritis

6. Inflammation of membranes in the lungs, the heart, or the abdomen

7. Evidence of kidney disease

8. Evidence of severe neurologic disease

9. Blood disorders, including low red and white blood cell and platelet counts

10. Immunologic abnormalities

11. Positive antinuclear antibody (ANA)

Note: A patient must experienced four of the criteria before a doctor can classify the condition as SLE. These criteria, proposed by the American College of Rheumatology, are not to be relied upon solely for diagnosis, however.

Methods for measuring the antibodies involved with SLE vary, and the range of results can be bewildering. Repeat tests may be needed.

Antinuclear Antibodies (ANAs). A primary test for SLE checks for antinuclear antibodies (ANA), which attack the cell nucleus.

High levels of ANA are found in more than 98% of patients with SLE. A number of other conditions, however, also cause high levels of ANA, so a positive test is not a definite diagnosis for SLE:

Antinuclear antibodies may be strongly present in other autoimmune diseases (such as scleroderma, Sjögren syndrome, or rheumatoid arthritis).
They also may be weakly present in about 20 - 40% of healthy women.
Some drugs can also produce positive antibody tests, including hydralazine, procainamide, isoniazid, and chlorpromazine.

A negative ANA test makes a diagnosis of SLE unlikely but not impossible. High or low concentrations of ANA also do not necessarily indicate the severity of the disease, since antibodies tend to come and go in patients with SLE.

In general, the ANA test is considered a screening test:

If SLE symptoms are present and the ANA test is positive, other tests for SLE will be administered.
If SLE symptoms are not present and the test is positive, the doctor will look for other causes, or the results will be ignored if the patient is feeling healthy.

ANA Subtypes. In some cases, doctors may test for specific ANA subtypes.

Anti-double stranded DNA (Anti-ds DNA) is usually found only in patients with SLE. It may play an important role in injury to blood vessels found in SLE, and high levels often indicate kidney involvement. Anti-ds DNA levels tend to fluctuate over time and may even disappear.
Anti-Sm antibodies are also usually found only with SLE. They are more constant and are more likely to be detected in African-American patients. Although the antibody is not usually seen in lupus patients, its confirmed presence almost always indicates SLE.
When the ANA is negative but the diagnosis is still strongly suspected, a test for anti-Ro (also called anti-SSA) and anti-La (also called anti-SSB) antibodies may identify patients with a rare condition called ANA negative, Ro lupus. These autoantibodies may be involved in the sun-sensitive rashes experienced by patients with SLE and are also found in association with neonatal lupus syndrome, in which a pregnant mother's antibodies cross the placenta and cause inflammation in the developing child's skin or heart.

Antibodies to SR Proteins. An advance in diagnosing SLE has been the detection of antibodies to molecules called SR proteins, which are carried by most patients. The test accurately detects lupus in 50 - 70% of patients who test positive for these antibodies.

Antiphospholipid Antibodies. In patients with SLE in whom blood abnormalities are suspected, tests may be able to detect the presence of the two major antiphospholipid antibodies:

A quarter to a half of patients with SLE may have these antibodies. They attack blood-clotting regulator proteins that stick to phospholipids, fatty compounds found in cell membranes throughout the body. Antiphospholipid antibodies increase the risks for blood clots and may be responsible for narrowing of (and irregularities in) blood vessels. Antiphospholipid antibodies are linked with miscarriages and other pregnancy complications, strokes, heart attacks and blood clots in almost any part of the body, including kidneys, legs, lungs, and eyes.
The test for the lupus anticoagulant antibody measures the time it takes blood to clot. A longer than normal blood clotting time indicates a higher chance for clotting in the body and, therefore, the presence of lupus anticoagulant.
An ELISA test (enzyme-linked immunosorbent assay) is performed to detect the anticardiolipin antibody.

As with the ANA, these antibodies also have a tendency to appear and disappear in a single patient. Patients who have these autoantibodies as well as blood clotting problems or frequent miscarriage are diagnosed with antiphospholipid syndrome (APS), which often occurs in SLE but can also develop independently.

Complement. Blood tests of patients with SLE often show low levels of serum complement, a protein in the blood that aids the body's infection fighters. Individual proteins are termed by the letter "C" followed by a number. Common complement tests measure C3, C4, C1q, and CH50. There is some evidence that complete deficiencies of C1q may be a key factor in the inability of the immune system to contain the autoimmunity process. Complement levels are especially low if there is kidney involvement or other disease activity.

LE Cell Tests. The first blood test ever used for SLE called LE (lupus erythematosus) cell test is positive in only about half of patients with SLE and is no longer used that often.

Blood Count. White and red blood cell and platelet counts are usually lower than normal and, depending on severity, are used to determine complications, such as anemia or infection.

Click the icon to see an image of the formed elements of blood.

If a skin rash is present, the doctor may take a biopsy (a tissue sample) from the margin of a skin lesion. A test known as a lupus band detects antibodies known as immunoglobulin G (IgG), which are located just below the outer layer of the tissue sample. They are present in about 80% of patients with active SLE and in 30 - 40% of those with inactive disease. The biopsy will not differentiate between systemic and discoid lupus, but it can rule out other diseases. Tests for other antibodies will rule out or confirm discoid lupus and subacute cutaneous lupus.

Kidney Damage and Lupus Nephritis. Kidney damage in patients already diagnosed with SLE may be detected from the following tests:

Blood tests that measure creatinine, a protein metabolized in muscles and excreted in the urine. High levels suggest kidney damage, although it can also be present with normal creative levels.
Tests for detecting anti-ds DNA antibodies and complement. High levels of anti-ds DNA and low levels of complement C3 suggest kidney damage. (It should be noted, however, that some patients with severe kidney damage show low levels of anti-ds DNA.) Testing for anti-C1q antibodies now appears to be an even more reliable indicator of lupus nephritis.
Urine analysis. Urine analyses should be performed at 4- to 6-month intervals to check for signs of kidney involvement.
A kidney biopsy. This may be performed to determine if lupus nephritis is present when less invasive tests indicate kidney involvement. It is not absolutely accurate but it helps determine treatment. Electron microscopy (very high-powered electronic microscopes) may be especially important in obtaining critical information on the degree of kidney damage.

Lung and Heart Involvement. A chest x-ray may be performed to check lung and heart function. An electrocardiogram and an echocardiogram are administered if heart disease is suspected.

Click the icon to see an image of an electrocardiogram.

Central Nervous System Complications. SLE occurring in the central nervous system (CNS) can be difficult to diagnose because its symptoms are easily confused with other psychiatric and neurologic conditions.

Tests of the cerebrospinal fluid (CSF) for elevated levels of autoantibodies are the most reliable ways to detect CNS complications caused by a faulty immune system.
Additional tests, including electroencephalograms (EEGs), magnetic resonance imaging (MRI), computed tomography (CT), or x-rays may be useful when blood vessel blockage in the brain is suspected.
If the doctor suspects that CNS symptoms are caused by infection, especially for patients who are receiving immunosuppressant therapy, a lumbar puncture should be performed.

Osteoporosis. To detect early osteoporosis in patients with SLE whose disease has lasted more than 3.5 years, experts recommend an imaging test called dual energy x-ray absorptiometry (DEXA) to measure bone mineral density.

Treatment

No treatment cures systemic lupus erythematosus, but many therapies can suppress symptoms and relieve discomfort. Treatment of SLE varies depending on the extent and severity of the disease.

Only three drugs are FDA-approved for the treatment of lupus:

Prednisone
Aspirin
Hydroxychloroquine

However, none of these drugs are the current standard of care. In everyday practice, numerous other drugs are commonly used. Researchers are conducting numerous clinical studies and drug investigations. Genetic research in lupus is progressing very rapidly, and hopefully new drugs will be approved in the future. There are also different drugs available to treat some of the conditions associated with lupus.

Less intensive treatments may be effective for symptoms of mild lupus. They include:

Creams and sunblocks for rashes
Nonsteroidal anti-inflammatory drugs for fever, arthritis, and headache
Antimalarial drugs for pleurisy, mild kidney involvement, and inflammation of the tissue surrounding the heart

More aggressive treatment is needed if there is serious disease progression, as evidenced by:

Hemolytic anemia
Low platelet count with an accompanying rash (thrombocytopenia purpura)
Major involvement in the lungs or heart
Significant kidney damage
Acute inflammation of the small blood vessels in the extremities or gastrointestinal tract
Severe central nervous system symptoms

The primary approach to treating severe SLE is to suppress the immune factors, most often first with corticosteroids and other immunosuppressant drugs. Investigational drugs and procedures are also showing promise.

The major complications of the disease must be treated as separate problems, keeping in mind the specific aspects of SLE. They are discussed elsewhere in this report.

Treatment for Cutaneous and Mild SLE

Creams. Steroid creams are often used for skin lesions. However, many patients with discoid lupus do not respond to steroids, particularly if they have eruptions that are caused by sun sensitivity. A cream derived from vitamin A (Tegison) may help some lesions that do not clear up with steroid creams.

Sun Protection. Sun protection is essential. Patients should always use sunblock creams (not just sunscreens) and always wear hats and clothing made of tightly woven fabrics.

Common NSAIDs. NSAIDs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs.

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin, Advil), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil).

For people with lupus, NSAIDs may help relieve:

Joint pain and swelling
Muscle pain

Side Effects. Regular, long-term use of NSAIDs can cause ulcers and gastrointestinal bleeding, which can lead to anemia. To avoid these problems, it’s best to take NSAIDs with food or immediately after a meal. Long-term use of NSAIDs (with the exception of aspirin) can also increase the risk for heart attack and stroke.

Other NSAID side effects may include:

Upset stomach
Dyspepsia (burning, bloated feeling in pit of stomach)
Drowsiness
Skin bruising
High blood pressure
Fluid retention
Headache
Rash
Reduced kidney function

Patients who have kidney problems associated with lupus (lupus nephritis) should be especially cautious about using NSAIDs. Experts recommend that patients with lupus who take NSAIDs on a regular basis should have their liver and kidney function tested every 3 - 4 months.

An ulcer is a crater-like lesion on the skin or mucous membrane caused by an inflammatory, infectious, or malignant condition. Patients can take certain medicines to suppress the acid in the stomach causing the erosion of the stomach lining. Endoscopic therapy can be used to stop bleeding from the ulcer.

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers. Ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are more likely to bleed than those caused by the bacteria Helicobacter pylori.

Those at high risk for bleeding include people over age 60, anyone with a history of ulcers or gastrointestinal bleeding, patients with serious heart conditions, people who abuse alcohol, and those who take medications such as anticoagulants (blood thinners) and corticosteroids.

Proton-pump inhibitor (PPI) drugs may help prevent and heal ulcers caused by NSAIDs. PPIs include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid).

A doctor may prescribe antimalarial drugs for discoid lupus (skin sores) or mild lupus when skin problems and joint pains are the predominant symptoms:

Hydroxychloroquine (Plaquenil) is the most common antimalarial drug used for lupus. This drug is effective as maintenance therapy to reduce flares in patients with mild or inactive disease. Hydroxychloroquine may help protect against blood clots in people with antiphospholipid syndrome, high cholesterol levels, and bone loss.
Other antimalarial drugs include chloroquine (Aralen) or quinacrine (Atabrine).

Treatment may start initially with high doses in order to accumulate high levels of the drug in the bloodstream. It is not known exactly why antimalarials work. Some researchers believe they inhibit the immune response, and others think they interfere specifically with inflammation.

A 2006 study suggested that anti-malarial drugs work best in patients who have genetic predispositions to certain types of immune-fighting proteins. The study found that patients who had genetic variations causing abnormally high levels of tumor necrosis alpha (TNF-alpha) and abnormally low levels of interleukin-10 (IL-10) responded best to these drugs.

Side Effects. Side effects of antimalarials may include:

Skin rash
Change in skin color (yellow in the case of quinacrine)
Gastrointestinal problems
Headache
Hair loss
Muscle aches
Eye damage

The most serious is damage to the retina, although this is very uncommon at low doses. Eye damage after taking hydroxychloroquine is reversible when caught in time and treated, but it is not reversible if the damage develops after taking chloroquine. An eye exam is advisable about every 6 months.

Antimalarials may also be used in combination with other anti-SLE drugs, including immunosuppressants and corticosteroids. It should be noted that smoking significantly reduces the effectiveness of antimalarial drugs.

Treatment for Severe SLE

Severe SLE is treated with corticosteroids, also called steroids, which suppress the inflammatory process. Steroids can help relieve many of the complications and symptoms, including anemia and kidney involvement.

Oral prednisone (Deltasone, Orasone) is usually prescribed. Other drugs include methylprednisolone (Medrol, Solumedrol), hydrocortisone, and dexamethasone (Decadron).

Some people need to take oral prednisone for only a short time; others may require it for a long duration. An intravenous administration of methylprednisolone using "pulse" therapy for 3 days is proving useful for flare-ups in the joints. Combinations with other drugs, particularly immunosuppressants, may be beneficial.

Regimens vary widely, depending on the severity and location of the disease. Most patients with SLE can eventually function without prednisone, although some may have to choose between the long-term toxicity of corticosteroids and the complications of active disease.

Side Effects of Long-Term Oral Corticosteroids. Unfortunately, serious and even life-threatening complications have been associated with long-term steroid use. The bone-thinning condition osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, alendronate etidronate, risedronate, or hormone replacement therapy in post-menopausal women. Vitamin C and E may help reduce the risk of cataracts.

Other side effects associated with prolonged use of oral steroids include:

Cataracts
Glaucoma
Diabetes
Fluid retention
Susceptibility to infections
Weight gain
High blood pressure
Acne
Excess hair growth
Wasting of the muscles
Menstrual irregularities
Irritability
Insomnia
Psychosis

Withdrawal from Long-Term Use of Oral Corticosteroids. Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. A few cases of severe adrenal insufficiency have occurred when patients switched from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a doctor first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctors measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

Drugs known as immunosuppressants are often used, either alone or with corticosteroids for very active SLE, particularly when kidney or neurologic involvement or acute blood vessel inflammation is present. These drugs suppress the immune system by damaging cells that grow rapidly, including those that produce antibodies. About a third of patients take immunosuppressants at some point in the course of the disease.

Specific Immunosuppressants. The most common immunosuppressants are:

Cyclophosphamide (Cytoxan) used to be considered the gold standard of treatment for lupus kidney disease (lupus nephritis). Cyclophosphamide is given intravenously and is sometimes used in combination with corticosteroids or other drugs. It has been used for lupus since the 1970s. Side effects are very severe and include nausea, vomiting, hair loss, infertility, and infections.
Mycophenolate mofetil (CellCept) is now becoming the new standard. Many recent studies have shown that CellCept works better than cyclophosphamide and causes far fewer severe side effects (diarrhea is the main side effect). Unlike cyclophosphamide, it is taken by mouth. Most doctors now recommend CellCept as a first-line treatment for newly diagnosed patients with mild or moderate lupus kidney disease. It may not be appropriate for patients with kidney failure or rapidly progressing kidney disease.
Azathioprine (Imuran) has the lowest toxicity, but is less effective than other immunosuppressants.
Cyclosporine (Sandimmune) has been used for years, mostly for SLE associated with kidney involvement. High blood pressure is common, however, with this drug.

The most frequent side effects of immunosuppressants include:

Stomach and intestinal problems
Skin rash
Mouth sores
Hair loss

Serious side effects of immunosuppressants include:

Low blood cell counts
Anemia
Menstrual irregularity
Early menopause
Ovarian failure
Infertility
Herpes zoster (shingles)
Liver and bladder toxicity
Increased risk of cancer

In general, immunosuppressants should not be used alone unless corticosteroids are ineffective or inappropriate. Grapefruit juice has an enzyme that may enhance the effects of some immunosuppressants.

Monoclonal Antibodies (MAbs). A MAb is a laboratory-made protein that targets specific immune cells, such as B cells. B cell over-activation has been identified as a key component of the lupus disease process. Promising MAbs in development for SLE treatment include:

Epratuzumab is being investigated for treatment of moderate-to-severe lupus. It is currently in Phase III trials.
Belimumab (Lymphostat-B) is also in Phase III trials.
Rituximab (Rituxan), a lymphoma cancer and rheumatoid arthritis drug, has shown good results in early trials in improving lupus symptoms. Researchers think it may affect how T cells and B cells interact. However, in December 2006 the FDA warned of several cases of progressive multifocal leukoencephalopathy (PML) in patients with lupus who took this drug. PML is a life-threatening brain infection. Some patients developed PML as late as 12 months after their last dose of rituximab. Two patients with lupus died from PML.

Intravenous Immunoglobulins. Intravenous immunoglobulins (IVIG) are sometimes used for patients who have not responded to other SLE treatments. Immunoglobulins are antibodies produced by immune system B-lymphocyte cells. IVIG is a blood product that contains these antibodies.

Dehydroepiandrosterone (DHEA). Dehydroepiandrosterone (DHEA) is a natural steroid hormone that is produced by the adrenal glands and converted into estrogen and androgen. The synthetic equivalent of DHEA, prasterone (Prestara), is being investigated as a potential treatment for SLE. Several clinical trials have indicated promising, although mixed, results for prasterone’s effect on preventing bone mineral density loss in women who take prednisone. Prasterone is still in the drug development stage and it is not clear when, or if, it will be commercially available.

Autologous Stem Cell Transplantation. Some patients with severe lupus have achieved at least short-term remission after undergoing autologous transplantation of stem cells and high-dose drug therapy to suppress the damaging immune factors. Stem cells are the early forms for all blood cells in the body. An autologous transplant is one in which marrow or blood cells used are the patient's own. (The advantage to an autologous transplant is that the patient's own cells are not at risk for rejection by the immune system.)

The procedure first removes the cells from the patient, who then receives high-dose immunotherapy. The stem cells are then reintroduced. Early results of small studies are encouraging, especially for treatment of antiphospholipid syndrome. Evidence suggests that these re-introduced stem cells do not repeat the original autoimmune errors. A 2006 study in the Journal of the American Medical Association indicated that autologous stem cell transplantation can help boost the immune system and lead to remission. Patients in the study had severe lupus that was resistant to standard treatments. Results were long-lasting. Researchers calculated that patients had a 50% chance of remaining disease-free after 5 years.

UVA-1 Phototherapy. A promising treatment uses ultraviolet A-1 (UVA-1) radiation, long UVA wave lengths that do not promote sunburn and may actually block inflammatory immune factors. Small studies have suggested that UVA-1 phototherapy may have some benefits for lowering disease activity in SLE.

Plasmapheresis. Plasmapheresis is a process in which the fluid part of the blood, called plasma, is removed from blood cells. The procedure involves first taking blood from the patient. The plasma, which contains the inflammatory antibodies and other immunologically active substances, is discarded and replaced with other fluids. The blood is then returned. Plasmapheresis is not useful for routine management of patients but may have some benefits for patients who do not respond to standard treatments or in specific cases, such as lupus patients with hemolytic anemia.


Infections, Inflammation, or Hypertension in the Lungs	Preventive Measures. Immunizations with inactive viruses and preventive antibiotics should be considered for patients with SLE who are at high risk for infection. Treating Infections. Lung infections need to be treated aggressively with antibiotics. However, antibiotic drugs such as penicillin or the sulfa drugs may cause sensitivity rashes that can be confused with SLE rash. Treating Lung Inflammation. While inflammation of the lung (pneumonitis) resembles pneumonia, it is not an infection but is a result of the autoimmune process. This condition needs to be treated with corticosteroids or immunosuppressants, but only if the doctor is sure infection is not present. Treating Pulmonary Hypertension. Pulmonary hypertension is very serious. Drugs known as prostacylins -- which include epoprostenol, iloprost, and treprostinil -- are standard drugs. Bosentan (Tracleer) is the first oral drug approved for pulmonary hypertension. An inhaled iloprost formulation (Ventavis) was approved in 2004. Sildenafil (Viagra, Revatio) may also be used for this condition. Lung transplantation may be required.
Bleeding and Clotting Disorders	Antiphospholipid Syndrome and Clotting Disorders. Hydroxychloroquine or aspirin may help prevent blood clots in women with antiphospholipid syndrome (APS). (Aspirin does not appear to be protective in men who carry the autoantibodies responsible for APS.) In patients who have experienced blood clots, treatment with the anticoagulant warfarin (Coumadin) is advisable. This blood-thinning drug may be needed lifelong. Scientists are investigating other treatment options, including autologous stem cell transplantation. The procedure has shown promise in studies for treating lupus-associated APS, but it is still experimental. Excess Bleeding from Thrombocytopenia (Drop in Blood Platelets). Treatments that may be effective for thrombocytopenia include combinations of a corticosteroid and either danazol (a male hormone) or the antimalarial hydroxychloroquine. Immunosuppressants or intravenous immunoglobulin IgG may be helpful in some patients. Surgical removal of the spleen may be advisable if bleeding disorders are a serious problem, but this option should be considered carefully, because the spleen provides one line of defense against infection. (Abnormal spleen function, in any case, appears to be fairly common in SLE.)
Kidney Disease	Drugs. Mycophenolate mofetil (CellCept), a newer drug, can help treat kidney disease associated with SLE and has fewer side effects than other immunosuppressants. It is taken by mouth. Recent studies suggest that it works better than cyclophosphamide. CellCept may be best for patients with mild-to-moderate lupus kidney disease and may not be appropriate for patients with advanced kidney disease. Intravenous cyclophosphamide is the most effective drug at this time for proliferative lupus nephritis, and, in combination with a steroid, has been shown to control advanced kidney disease in 60 - 90% of patients. It has severe side effects, including nausea, vomiting, hair loss, and infertility. Steroids are also useful for treating active kidney disease and for managing milder forms of nephritis. Procedures. Kidney transplant or dialysis should be considered for patients with SLE with severe kidney damage. For unknown reasons, SLE does not generally recur in the transplanted kidneys. Studies are conflicting, however, over whether SLE transplant patients have higher organ-rejection rates than other kidney-transplant recipients. Both transplantation and dialysis have potentially serious complications. Plasmapheresis. It is not clear if plasmapheresis is beneficial for SLE kidney disease.
Osteoporosis	Treatments for osteoporosis include calcium, vitamin D, bisphosphonates, parathyroid hormone, and selective estrogen-receptor modulators (SERMs). [For more information, see In-Depth Report #18: Osteoporosis.]
Heart Disease	The need for aggressive treatment of high blood pressure often accompanies kidney disease. SLE is also accompanied by high cholesterol levels, which requires diet changes and drug therapies. [For more information, see In-Depth Reports #3: Coronary artery disease; #14: High blood pressure; #23: Cholesterol; and #43: Heart healthy diet.]

The spleen is an organ that helps produce and maintain red blood cells. It also aids the body's immune system by producing white blood cells that destroy harmful substances in the body. Removal of the spleen makes a person more susceptible to infection.

Click the icon to see an illustrated series detailing kidney transplant.

Lifestyle Changes

People with SLE should try to maintain a healthy and active lifestyle. Light-to-moderate exercise, interspersed with rest periods, is good for the heart, helps fight depression and fatigue, and can help keep joints flexible.

Patients should minimize their exposure to crowds or people with contagious illnesses. Careful hygiene, including dental hygiene, is also important.

It is very important that patients with SLE avoid excessive exposure to sunlight. Simple preventive measures include avoiding overexposure to ultraviolet rays and wearing protective clothing and sunblocks. There is some concern that allergy shots may cause flare ups in certain cases. Patients who may benefit from them should discuss risks and benefits with an SLE specialist. In general, patients with SLE should use only hypoallergenic cosmetics or hair products.

Chronic stress has profound physical effects and influences the progression of SLE. Getting adequate rest of at least 8 hours and possibly napping during the day may be helpful. Maintaining social relationships and healthy activities may also help prevent the depression and anxiety associated with the disease.

Resources

www.lupus.org -- Lupus Foundation of America
www.lupusny.org -- SLE Foundation of America
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.lupusresearchinstitute.org -- Lupus Research Institute

References

Bernatsky S, Ramsey-Goldman R, Isenberg D, Rahman A, Dooley MA, Sibley J, et al. Hodgkin's lymphoma in systemic lupus erythematosus. Rheumatology (Oxford). 2007 May;46(5):830-2. Epub 2007 Jan 25.

Crosbie D, Black C, McIntyre L, Royle PL, Thomas S. Dehydroepiandrosterone for systemic lupus erythematosus. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005114.

D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet. 2007 Feb 17;369(9561):587-96.

Dörner T, Kaufmann J, Wegener WA, Teoh N, Goldenberg DM, Burmester GR. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res Ther. 2006;8(3):R74. Epub 2006 Apr 21.

Gompel A, Piette JC. Systemic lupus erythematosus and hormone replacement therapy. Menopause Int. 2007 Jun;13(2):65-70.

Harel-Meir M, Sherer Y, Shoenfeld Y. Tobacco smoking and autoimmune rheumatic diseases. Nat Clin Pract Rheumatol. 2007 Dec;3(12):707-15.

Khamashta MA. Systemic lupus erythematosus and pregnancy. Best Pract Res Clin Rheumatol. 2006 Aug;20(4):685-94.

Klareskog L, Padyukov L, Alfredsson L. Smoking as a trigger for inflammatory rheumatic diseases. Curr Opin Rheumatol. 2007 Jan;19(1):49-54.

Kocis P. Prasterone. Am J Health Syst Pharm. 2006 Nov 15;63(22):2201-10. Lane NE. Therapy Insight: osteoporosis and osteonecrosis in systemic lupus erythematosus. Nat Clin Pract Rheumatol. 2006 Oct;2(10):562-9.

Mackillop LH, Germain SJ, Nelson-Piercy C. Systemic lupus erythematosus. BMJ. 2007 Nov 3;335(7626):933-6.

Mease PJ, Ginzler EM, Gluck OS, Schiff M, Goldman A, Greenwald M, et al. Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy. J Rheumatol. 2005 Apr;32(4):616-21.

Sabahi R, Anolik JH. B-cell-targeted therapy for systemic lupus erythematosus. Drugs. 2006;66(15):1933-48.

Sánchez-Guerrero J, González-Pérez M, Durand-Carbajal M, Lara-Reyes P, Jiménez-Santana L, Romero-Díaz J, et al. Menopause hormonal therapy in women with systemic lupus erythematosus. Arthritis Rheum. 2007 Sep;56(9):3070-9.

Vigna-Perez M, Hernández-Castro B, Paredes-Saharopulos O, Portales-Pérez D, Baranda L, Abud-Mendoza C, et al. Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res Ther. 2006;8(3):R83. Epub 2006 May 5.

Walsh M, James M, Jayne D, Tonelli M, Manns BJ, Hemmelgarn BR. Mycophenolate mofetil for induction therapy of lupus nephritis: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2007 Sep;2(5):968-75. Epub 2007 Aug 8.

Walsh M, Jayne D. Rituximab in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis and systemic lupus erythematosus: past, present and future. Kidney Int. 2007 Sep;72(6):676-82. Epub 2007 Jul 4.

Review Date:
1/21/2008
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

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AIDS

admin — Wed, 03 Sep 2008 17:50:46 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

AIDS (acquired immune deficiency syndrome) is the final and most serious stage of HIV disease, which causes severe damage to the immune system.

Alternative Names

Acquired immune deficiency syndrome

Causes, incidence, and risk factors

AIDS is the fifth leading cause of death among people aged 25-44 in the United States, down from number one in 1995. About 25 million people worldwide have died from this infection since the start of the epidemic, and 40.3 million people around the world are currently living with HIV/AIDS.

Human immunodeficiency virus (HIV) causes AIDS. The virus attacks the immune system and leaves the body vulnerable to a variety of life-threatening infections and cancers.

Common bacteria, yeast, parasites, and viruses that ordinarily do not cause serious disease in people with healthy immune systems can cause fatal illnesses in people with AIDS.

HIV has been found in saliva, tears, nervous system tissue and spinal fluid, blood, semen (including pre-seminal fluid, which is the liquid that comes out prior to ejaculation), vaginal fluid, and breast milk. However, only blood, semen, vaginal secretions, and breast milk generally transmit infection to others.

The virus can be transmitted:

Through sexual contact -- including oral, vaginal, and anal sex
Through blood -- via blood transfusions (now extremely rare in the US) or needle sharing
From mother to child -- a pregnant woman can transmit the virus to her fetus through their shared blood circulation, or a nursing mother can transmit it to her baby in her milk

Other transmission methods are rare and include accidental needle injury, artificial insemination with infected donated semen, and organ transplantation with infected organs.

HIV infection is not spread by casual contact such as hugging, by touching items previously touched by a person infected with the virus, during participation in sports, or by mosquitoes.

It is NOT transmitted to a person who DONATES blood or organs. Those who donate organs are never in direct contact with those who receive them. Likewise, a person who donates blood is not in contact with the person receiving it. In all these procedures, sterile needles and instruments are used.

However, HIV can be transmitted to a person RECEIVING blood or organs from an infected donor. To reduce this risk, blood banks and organ donor programs screen donors, blood, and tissues thoroughly.

People at highest risk for getting HIV include:

Intravenous drug users who share needles
Infants born to mothers with HIV who don't receive HIV therapy during pregnancy
People engaging in unprotected sex
People who received blood transfusions or clotting products between 1977 and 1985 (prior to when standard screening for the virus began)
Sexual partners of those who participate in high-risk activities (such as anal sex)

AIDS begins with HIV infection. People infected with HIV may have no symptoms for 10 years or longer, but they can still transmit the infection to others during this symptom-free period. Meanwhile, if the infection is not detected and treated, the immune system gradually weakens, and AIDS develops.

Acute HIV infection progresses over time (usually a few weeks to months) to asymptomatic HIV infection (no symptoms) and then to early symptomatic (some symptoms) HIV infection. Later, it progresses to AIDS (very advanced HIV infection with T-cell count below 200).

Almost all people infected with HIV, if not treated, will develop AIDS. There is a small group of patients who develop AIDS very slowly, or never at all. These patients are called nonprogressors, and many seem to have a genetic difference that prevents the virus from damaging their immune system.

Symptoms

The symptoms of AIDS are primarily the result of infections that do not normally develop in individuals with healthy immune systems. These are called opportunistic infections.

People with AIDS have had their immune system depleted by HIV and are very susceptible to these opportunistic infections. Common symptoms are fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss.

See the signs and tests section below for a list of common opportunistic infections and major symptoms associated with them.

Note: Initial infection with HIV can produce no symptoms. Some people, however, do experience flu-like symptoms with fever, rash, sore throat, and swollen lymph nodes, usually 2 weeks after contracting the virus. Some people with HIV infection remain without symptoms for years between the time the are exposed to the virus and when they develop AIDS.

Signs and tests

The following is a list of AIDS-related infections and cancers that people with AIDS may get as their CD4 count decreases. In the past, having AIDS was defined as having HIV infection and getting one of these additional diseases. Today, according to the Centers for Disease Control and Prevention, a person is diagnosed as having AIDS if they have a CD4 cell count below 200, even if they don't have an opportunistic infection.

AIDS may also be diagnosed if a person develops one of the numerous infections and cancers that occur with HIV infection. These infections are unusual in people with a healthy immune system.

CD4 cells are a type of immune cell. They are also called "T cells" or "helper cells."

Many other illnesses and corresponding symptoms may develop in addition to those listed here.

Common with CD4 count below 350 cells/mL:

Herpes simplex virus -- causes ulcers/small blisters in the mouth or genitals, happens more frequently and usually much more severely in an HIV-infected person than before HIV infection
Tuberculosis -- infection by the tuberculosis bacteria that mostly affects the lungs, but can affect other organs such as the bowel, lining of the heart or lungs, brain, or lining of the central nervous system (brain and spinal cord)
Oral or vaginal thrush -- yeast infection of the mouth or vagina
Herpes zoster (shingles) -- ulcers/small blisters over a patch of skin. it is caused by the varicella zoster virus
Non-Hodgkin's lymphoma -- cancer of the lymph glands
Kaposi's sarcoma -- cancer of the skin, lungs, and bowel, associated with a herpes virus (HHV-8). Can happen at any CD4 count, but is more likely to happen at lower CD4 counts, and is more common in men than in women

Common with CD4 count below 200 cells/mL:

Pneumocystis carinii pneumonia, "PCP pneumonia," now called Pneumocystic jiroveci pneumonia
Candida esophagitis -- painful yeast infection of the esophagus
Bacillary angiomatosis -- skin lesions caused by a bacteria called Bartonella, which is usually acquired from cat scratches

Common with CD4 count below 100 cells/mL:

Cryptococcal meningitis -- infection of the lining of the brain
AIDS dementia -- worsening and slowing of mental function, caused by HIV itself
Toxoplasmosis encephalitis -- infection of the brain by a parasite, called Toxoplasma, which is frequently found in cat feces; causes lesions (sores) in the brain
Progressive multifocal leukoencephalopathy -- a viral disease of the brain caused by a virus (called the JC virus) that results in a severe decline in mental and physical functions
Wasting syndrome -- extreme weight loss and loss of appetite, caused by HIV itself
Cryptosporidium diarrhea -- Extreme diarrhea caused by one of several related parasites

Common with CD4 count below 50/mL:

Mycobacterium avium -- a blood infection by a bacterium related to tuberculosis
Cytomegalovirus infection -- a viral infection that can affect almost any organ system, especially the large bowel and the eyes

In addition to the CD4 count, a test called HIV RNA load may be used to monitor patients. Basic screening lab tests and regular cervical Pap smears are important to monitor in HIV infection, due to the increased risk of cervical cancer in immunocompromised women. Anal Pap smears to detect potential cancers may also be important in both HIV infected men and women.

Treatment

There is no cure for AIDS at this time. However, a variety of treatments are available that can help keep symptoms at bay and improve the quality of life of those who have already developed symptoms.

Antiretroviral therapy suppresses the replication of the HIV virus in the body. A combination of several antiretroviral agents, termed highly active antiretroviral therapy (HAART), has been highly effective in reducing the number of HIV particles in the blood stream, as measured by a blood test called the viral load. Preventing the virus from replicating can help the immune system recover from the HIV infection and improve T-cell counts.

HAART is not a cure for HIV, and people on HAART with suppressed levels of HIV can still transmit the virus to others through sex or sharing of needles. But HAART has been enormously effective for the past 10 years. There is good evidence that if the levels of HIV remain suppressed and the CD4 count remains high (above 200 cells/mL), life can be significantly prolonged and improved.

However, HIV may become resistant to HAART in patients who do not take their medications on schedule every day. Genetic tests are now available to determine whether a particular HIV strain is resistant to a particular drug. This information may be useful in determining the best drug combination for each individual, and adjusting the drug regimen if it starts to fail. These tests should be performed any time a treatment strategy begins to fail, and prior to starting therapy.

When HIV becomes resistant to HAART, other drug combinations must be used to try to suppress the resistant strain of HIV. There are a variety of new drugs coming out on the market for the treatment of drug-resistant HIV.

Treatment with HAART has complications. HAART is a collection of different medications, each with its own side effects. Some common side effects are nausea, headache, weakness, malaise (a general sick feeling), and fat accumulation on the back ("buffalo hump") and abdomen. When used for a long time, these medications increase the risk of heart attack by increasing the levels of fat and glucose in the blood.

Any doctor prescribing HAART should carefully watch the patient for possible side effects associated with the combination of medications the patient takes. In addition, routine blood tests measuring CD4 counts and HIV viral load (a blood test that measures how much virus is in the blood) should be taken every 3-4 months. The goal is to get the CD4 count as close to normal as possible, and to suppress the HIV amount of virus in the blood to an undetectable level.

Other antiviral medications are being investigated. In addition, growth factors that stimulate cell growth, such as Epogen (erthythropoetin) and G-CSF are sometimes used to treat anemia and low white blood cell counts associated with AIDS.

Medications are also used to prevent opportunistic infections (such as Pneumocystis uiroveci pneumonia) if the CD4 count is low enough. This keeps AIDS patients healthier for longer periods of time. Opportunistic infections are treated when they happen.

Support Groups

Joining support groups where members share common experiences and problems can often help the emotional stress of devastating illnesses. See AIDS - support group.

Expectations (prognosis)

Right now, there is no cure for AIDS. It is always fatal if no treatment is provided. In the US, most patients survive many years after diagnosis because of the availability of HAART. HAART has dramatically increased the amount of time people with HIV remain alive.

Research continues in the areas of drug treatments and vaccine development. Unfortunately, HIV medications are not always available in the developing world, where the bulk of the epidemic is raging.

Complications

When a person is infected with HIV, the virus slowly begins to destroy that person's immune system. How fast this occurs differs in each individual. Treatment with HAART can help slow and even halt the destruction of the immune system.

Once the immune system is severely damaged, that person has AIDS, and is now susceptible to infections and cancers that most healthy adults would not get. However, antiretroviral treatment can still be very effective, even at that stage of illness.

Calling your health care provider

Call for an appointment with your health care provider if you have any of the risk factors for HIV infection, or if you develop symptoms of AIDS. By law, AIDS testing must be kept confidential. Your health care provider will review results of your testing with you.

Prevention

See the article on safe sex to learn how to reduce the chance of acquiring or spreading HIV, and other sexually transmitted diseases.
Try not to use injected drugs. If IV drugs are used, do not share needles or syringes. Many communities now have needle exchange programs, where you can get rid of used syringes and get new, sterile ones for free. These programs can also provide referrals to addiction treatment.
Avoid contact with another person's blood. Protective clothing, masks, and goggles may be appropriate when caring for people who are injured.
Anyone who tests positive for HIV can pass the disease to others and should not donate blood, plasma, body organs, or sperm. An infected person should tell any prospective sexual partner about their HIV-positive status. They should not exchange body fluids during sexual activity, and should use whatever preventive measures (such as condoms) will give the partner the most protection.
HIV-positive women who wish to become pregnant should seek counseling about the risk to unborn children, and medical advances that may help prevent the fetus from becoming infected. Use of certain medications can dramatically reduce the chances that the baby will become infected during pregnancy.
Mothers who are HIV-positive should not breast feed their babies.
Safe-sex practices, such as latex condoms, are highly effective in preventing HIV transmission. HOWEVER, there remains a risk of acquiring the infection even with the use of condoms. Abstinence is the only sure way to prevent sexual transmission of HIV.

The riskiest sexual behavior is unprotected receptive anal intercourse -- the least risky sexual behavior is receiving oral sex. Performing oral sex on a man is associated with some risk of HIV transmission, but this is less risky than unprotected vaginal intercourse. Female-to-male transmission of the virus is much less likely than male-to-female transmission. Performing oral sex on a woman who does not have her period carries low risk of transmission.

HIV-positive patients who are taking anti-retroviral medications are less likely to transmit the virus. For example, pregnant women who are on effective treatment at the time of delivery, and who have undetectable viral loads, give HIV to the infant less than 1% of the time, compared with about 20% of the time if medications are not used.

The US blood supply is among the safest in the world. Nearly all people infected with HIV through blood transfusions received those transfusions before 1985, the year HIV testing began for all donated blood. Currently, the risk of infection with HIV through a blood transfusion or blood products is almost zero in the United States, even in geographic areas with a lot of HIV infections.

If you believe you have been exposed to HIV, seek medical attention IMMEDIATELY. There is some evidence that an immediate course of antiviral drugs can reduce the chances that you will be infected. This is called post-exposure prophylaxis (PEP), and has been used to treat health care workers injured by needlesticks, to prevent transmission.

There is less information available about how effective PEP is for people exposed to HIV through sexual activity or IV drug use. However, if you believe you have been exposed, you should discuss the possibility with a knowledgeable specialist (check local AIDS organizations for the latest information) as soon as possible. Anyone who has been raped should be offered PEP and should consider its potential risks and benefits.

References

Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007: sect XXIV.

Review Date: 5/19/2008

Reviewed By: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine; Jatin M. Vyas, MD, PhD, Instructor in Medicine, Harvard Medical School, Assistant in Medicine, Division of Infectious Disease, Massachusetts General Hospital. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Source Doc: 1_000594

Infertility in women

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

In This Report

Highlights
Introduction
The Reproductive System
Risk Factors
Causes
Diagnosis
Treatment
Lifestyle Changes
Medications
Assisted Reproductive Techn...
Complications of Assisted R...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New At-Home Fertility Test for Couples

Fertell is a new at-home fertility test kit for couples. It screens for sperm motility concentrations and follicle-stimulating hormone (FSH) levels. Fertell may be helpful as an initial test for infertility, but for a definitive diagnosis it is important to consult a doctor. Infertility can be due to many different factors.

Intracytoplasmic Sperm Injection Overused for Female Infertility

The assisted reproductive technology intracytoplasmic sperm injection (ICSI) is being increasingly used in combination with in vitro fertilization (IVF), even for couples who do not have problems with male infertility, suggests a 2007 study in the New England Journal of Medicine. Researchers found that use of ICSI has increased 5-fold in the past decade. Some doctors are now recommending ICSI for women who have failed prior IVF cycles or who have few or poor-quality eggs. Doctors caution that ICSI should be used only to improve pregnancy chances for couples with male-factor infertility.

Clomiphene Best for PCOS-Associated Infertility

The infertility drug clomiphene (Clomid) works better than the diabetes drug metformin (Glucophage) for treating infertility resulting from polycystic ovarian syndrome (PCOS), indicates a 2007 study in the New England Journal of Medicine.

Fertility Drugs and Breast Cancer

Fertility drugs such as clomiphene and gonadotropins do not increase the risk for breast cancer, indicate several studies. In fact, according to a 2006 study in the Archives of Internal Medicine, clomiphene may decrease breast cancer risk.

Iron Deficiency and Female Infertility

Iron deficiency may increase the risk for ovulatory infertility, suggests a 2006 study in Obstetrics and Gynecology. Researchers found that women who took daily iron supplements were 40% less likely to be infertile than women who did not take supplements. Some experts recommend screening for iron deficiency as part of the clinical evaluation for 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.

About 10% of couples who wish to have a baby are still unable to after a year of unprotected sex. About half of these couples can achieve pregnancy within 2 years after appropriate treatment of the woman, the man, or both. 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 the 20th week. (The inability of a woman to produce a live birth because of abnormalities that cause miscarriages is called infecundity and is not discussed in detail in this report.)

Males and females each account for 40% of infertility. In the remaining 20%, either both partners are responsible or the cause is unclear. Although this report specifically addresses infertility in women, it is equally important for the male partner to be tested at the same time. [See In-Depth Report #67: Infertility in men.]

The Reproductive System

The Primary Organs and Structures in the Reproductive System. The primary structures in the reproductive system are:

The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix.
When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy the walls of the uterus are pushed apart as the fetus grows.
The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina.
Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary.
Ovaries are egg-producing organs that hold 200,000 - 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.
The inner lining of the uterus is called the endometrium. During pregnancy, it thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed as part of the menstrual flow. Menstrual flow also consists of blood and mucus from the cervix and vagina.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Reproductive Hormones. The hypothalamus (an area in the brain) and the pituitary gland regulate the reproductive hormones.

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

The pituitary gland is often referred to as the master gland because of its important role in many vital functions, many of which require hormones. In women, six key hormones serve as chemical messengers that regulate the reproductive system:

The hypothalamus first releases the gonadotropin-releasing hormone (GnRH).
This chemical, in turn, stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

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

Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH and complete the hormonal group necessary for reproductive health.

Ovulation. The process leading to fertility is very intricate. It depends on the healthy interaction of two sets of organs and hormone systems in both the male and female. In addition, reproduction is limited by the phases of female fertility. Nevertheless, this astonishing process results in conception within a year for about 80% of couples. Only 15% conceive within a month of their first attempts, however, and about 60% succeed after 6 months.

A woman's ability to produce children occurs after she enters puberty and begins to menstruate. The process of conception is complex:

With the start of each menstrual cycle, follicle-stimulating hormone (FSH) stimulates several follicles to mature over a 2-week period until their eggs nearly triple in size. Only one follicle becomes dominant, however, during a cycle.
FSH signals this dominant follicle to produce estrogen, which enters the bloodstream and reaches the uterus. There, estrogen stimulates the cells in the uterine lining to reproduce, therefore thickening the walls.
Estrogen levels reach their peak around the 14th day of the cycle (counting days beginning with the first day of a period). At that time, they trigger a surge of luteinizing hormone (LH).

LH serves two important roles:

First, the LH surge around the 14th cycle day stimulates ovulation. It does this by causing the dominant follicle to burst and release its egg into one of the two fallopian tubes. Once in the fallopian tube, the egg is in place for fertilization.
Next, LH causes the ruptured follicle to develop into the corpus luteum. The corpus luteum provides a source of estrogen and progesterone during pregnancy.

Click the icon to see an image of the corpus luteum.

Fertilization. The so-called "fertile window" is 6 days long and starts 5 days before ovulation and ends the day of ovulation. Fertilization occurs as follows:

The sperm can survive for up to 3 days once it enters the fallopian tube. The egg survives 12 - 24 hours unless it is fertilized by a sperm.
If the egg is fertilized, about 2 - 4 days later it moves from the fallopian tube into the uterus where it is implanted in the uterine lining and begins its 9-month incubation.
The placenta forms at the site of the implantation. The placenta is a thick blanket of blood vessels that nourishes the fertilized egg as it develops.

Click the icon to see an image of the placenta.

The corpus luteum (the yellow tissue formed from the ruptured follicle) continues to produce estrogen and progesterone during pregnancy.

If the egg is not fertilized, the corpus luteum degenerates into a form called the corpus albicans, and estrogen and progesterone levels drop. Finally, the endometrial lining sloughs off and is shed during menstruation.


Menstrual Phases	Typical No. of Days	Hormonal Actions
Follicular (Proliferative) Phase	Cycle Days 1 - 6: Beginning of menstruation to end of blood flow.	Estrogen and progesterone start out at their lowest levels. FSH levels rise to stimulate maturity of follicles. Ovaries start producing estrogen and levels rise, while progesterone remains low.
	Cycle Days 7 - 13: The endometrium (the inner lining of the uterus) thickens to prepare for the egg implantation.
Ovulation	Cycle Day 14:	Surge in LH. Largest follicle bursts and releases egg into fallopian tube.
Luteal (Secretory) Phase, also known as the Premenstrual Phase	Cycle Days 15 - 28:	Ruptured follicle develops into corpus luteum, which produces progesterone. Progesterone and estrogen stimulate blanket of blood vessels to prepare for egg implantation.
	If fertilization occurs:	Fertilized egg attaches to blanket of blood vessels that supplies nutrients for the developing placenta. Corpus luteum continues to produce estrogen and progesterone.
	If fertilization does not occur:	Corpus luteum deteriorates. Estrogen and progesterone levels drop. The blood vessel lining sloughs off and menstruation begins.

Onset of Menstruation (Menarche). Previous evidence had set the onset of menstruation, called the menarche, at an average age of 12 or 13. Recent studies, however, set the time of onset earlier by about 1 year in Caucasian girls and 2 years in African-American girls. Currently, the youngest possible age for normal puberty is 7 years old for Caucasians and 6 years old for African-Americans, down from a previous low of 8 years for both.

Evidence is pointing to the increasing incidence of childhood obesity as a major cause of the trend in earlier menarche onset. (Obesity is also highly associated with hormonal disorders in girls entering puberty at young ages.) Environmental estrogens found in chemicals and pesticides are also suspects.

Length of Monthly Cycle. The menstrual cycle can be very irregular for the first 1 - 2 years, usually being longer than the average of 28 days. The length then generally stabilizes to an average of 28 days, although the cycle length may range from 20 - 45 days and still be considered normal. A variation of 10 days or more -- either more or fewer days -- may have an impact on fertility, however. When a woman reaches her 40s the cycle lengthens, reaching an average of 31 days by age 49. Several factors can affect cycle length at any age.


Risk Factors for Shorter Cycles	Risk Factors for Longer Cycles
Regular alcohol use	Being under 21 and over 44
Stressful jobs	Being very thin (also at risk for short bleeding periods)
	Competitive athletics (also at risk for short bleeding periods)

Length of Periods. Periods average 6.6 days in young girls. By the age of 21, menstrual bleeding averages 6 days until women approach menopause. However, about 5% of healthy women menstruate less than 4 days, and 5% menstruate more than 8 days.

Normal Absence of Menstruation. Normal absence of periods can occur in any woman under the following circumstances:

Menstruation stops during the duration of pregnancy. Some women continue to have irregular bleeding during the first trimester. This bleeding may indicate a threatened miscarriage and requires immediate attention by the doctor.
When women breastfeed they are unlikely to ovulate. After that time, menstruation usually resumes, and they are fertile again.
Perimenopause starts when the intervals between periods begin to lengthen, and it ends with menopause itself (the complete cessation of menstruation). Menopause usually occurs at about age 51, although smokers often go through menopause earlier.

Risk Factors

In the U.S., an estimated 10.2% of women ages 15 - 44, or about 6.1 million women, have impaired fertility, and the incidence is increasing. About 25% of women experience some period of infertility during their reproductive years.

As a woman ages, her chances for fertility decline. Infertility in older women appears to be mostly due to a higher risk for chromosomal abnormalities that occur in her eggs as they age. Older women are also more likely to have health problems that may interfere with fertility. If fertilization occurs, older, healthy women can usually successfully bear a fetus to term, although they have a higher risk for miscarriage. Using population studies, experts have come up with estimated odds for pregnancy at different ages, given no fertility intervention. One analysis of pregnancy rates based on conception on the day of ovulation suggested that women ages 19 - 26 have twice the pregnancy rates as those ages 35 - 39.


Age	Fertility %
Up until age 34	90%
By age 40	Declining to 67%
By age 45	Declining to 15%

Although most of a woman's estrogen is manufactured in her ovaries, 30% is produced in fat cells by a process that transforms circulating adrenal male hormones into estrogen. Because a normal hormonal balance is essential for the process of conception, it is not surprising that extreme weight levels, either high or low, can contribute to infertility.

Being Overweight. Being overweight or obese (fat levels that are 10 - 15% above normal) can contribute to infertility in various ways. Obesity is highly associated with polycystic ovarian syndrome (PCOS), which is the cause of infertility in some cases. In one study, overweight women without PCOS were classified in one of five grades, depending on the severity of the obesity. The risk for irregular or absent periods increased two-fold by each increase in grade. In this group, amenorrhea (absent periods) was also highly associated with type 2 diabetes and blood sugar abnormalities.

Being Underweight. Body fat levels 10 - 15% below normal can completely shut down the reproductive process. Women at risk include:

Women with eating disorders, such as anorexia or bulimia.
Women on very low-calorie or restrictive diets are at risk, especially if their periods are irregular.
Strict vegetarians might have difficulties if they lack important nutrients, such as vitamin B12, zinc, iron, and folic acid.
Marathon runners, dancers, and others who exercise very intensely. (Lower body fat contributes to menstrual irregularities in competitive athletes, but other mechanisms are also involved.)

Exposure to environmental hazards (herbicides, pesticides, industrial solvents) may affect fertility. Estrogen-like hormone-disrupting chemicals are of particular concern for infertility in men and for effects on offspring of women.

Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Specific phthalates of special concern include dibutyl phthalate (DBP) and others found in many products, including cosmetics and clay products sold to children (Fimo, Sculpey). Animals exposed to phthalates have significantly impaired sperm count and abnormalities in reproductive structures, such as the testes. In addition, there is some concern that exposure in pregnant women may affect the offspring.

Neurotransmitters (chemical messengers) act in the hypothalamus gland, which controls both reproductive and stress hormones. Severely elevated levels of stress hormone can, in fact, shut down menstruation. Whether stress has any significant effect on fertility or fertility treatments is unclear. One 2005 study found that psychological stress does not affect the success or failure of in vitro fertilization.

Click the icon to see an image of the hypothalamus.

Causes

Causes of infertility can be found in about 90% of infertility cases but, despite extensive tests, about 10% of couples will never know why they cannot conceive. Between 10 - 30% of cases of infertility have more than one cause. Male or female infertility each account for about 30 - 40% of cases. In men, sperm defects (their quality and quantity) are usually responsible. Female infertility is more complex.

Pelvic inflammatory disease (PID) is the major cause of female infertility worldwide. PID comprises a variety of infections caused by different bacteria that affect the reproductive organs, appendix, and parts of the intestine that lie in the pelvic area. The sites of infection most often implicated in infertility are in the fallopian tubes, a specific condition referred to as salpingitis.

Causes of PID. PID may result from many different conditions that cause infections. Among them are:

Sexually transmitted diseases (cause of most PIDs). Chlamydia trachomatis is an infectious organism that causes 75% of infertility in the fallopian tubes. Gonorrhea is responsible for most of the remaining cases.
Pelvic tuberculosis (a growing global problem as tuberculosis cases increase)
Nonsterile abortions
Ruptured appendix
Herpes virus (suggested for some cases, but not confirmed as a cause).

Symptoms of PID. The infection may be subclinical (occurring without any symptoms), or there may be fever, chills, or pelvic pain indicating inflammation of the entire pelvic area.

Effects of PID. Severe or frequent attacks of PID can eventually cause scarring, abscess formation, and tubal damage that result in infertility. About 20% of women who develop symptomatic PID become infertile. PID also significantly increases the risk of ectopic pregnancy (fertilization in the fallopian tubes). The severity of the infection, not the number of the infections, appears to pose the greater risk for infertility.

Endometriosis may account for as many as 30% of infertility cases. Some evidence suggests that between 30 - 50% of women with endometriosis are infertile. Often, however, it is difficult to determine if endometriosis is the primary cause of infertility, particularly in women who have mild endometriosis. Endometriosis rarely causes an absolute inability to conceive, but, nevertheless, it can contribute to it both directly and indirectly.

Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body causing pain and irregular bleeding.

Direct Effect of Endometrial Cysts. Endometrial cysts may directly cause infertility in several ways:

If implants occur in the fallopian tubes, they may block the egg's passage.
Implants that occur in the ovaries prevent the release of the egg.
Severe endometriosis can eventually form rigid webs of scar tissue (adhesions) between the uterus, ovaries, and fallopian tubes, thereby preventing the transfer of the egg to the tube.

Immune Factors and the Inflammatory Response. Researchers are focusing on defects in the immune system that not only may be responsible for endometriosis in the first place but may also cause the infertility associated with endometriosis. Even in early stage endometriosis, investigators have observed increased immune system activity.

Other Conditions Linking Endometriosis and Infertility. Researchers have sometimes noted unusually low levels of specific substances that enable a fertilized egg to adhere to the uterine lining. (Such abnormalities are more often a factor in infertility in women with mild-to-moderate endometriosis than in those with severe cases.)

One study found that the eggs in women with endometriosis appeared to have more genetic abnormalities than those in women without the disorder.

Polycystic ovarian syndrome (PCOS) is a condition in which the ovaries produce high amounts of androgens (male hormones), particularly testosterone. PCOS occurs in about 6% of women, and amenorrhea or oligomenorrhea (infrequent menses) is quite common. According to one study, nearly 30% of obese women with PCOS had amenorrhea. (The rate was lower -- 4.7% -- in women with normal weight.)

Click the icon to see an image of polycystic ovarian syndrome.

In PCOS, increased androgen production produces high luteinizing hormone (LH) levels and low follicle-stimulating hormone (FSH) levels, so that follicles are prevented from producing a mature egg. Without egg production, the follicles swell with fluid and form into cysts. Every time an egg is trapped within the follicle, another cyst forms, so the ovary swells, sometimes reaching the size of a grapefruit. Without ovulation, progesterone is no longer produced, whereas estrogen levels remain normal.

The elevated levels of androgens (hyperandrogenism) can cause obesity, facial hair, and acne, although not all women with PCOS have such symptoms. Other male characteristics, such as deepening voice and clitoral enlargement, are rare.

PCOS also poses a high risk for insulin resistance, particularly in women who are also obese. Insulin resistance is associated with diabetes type 2, in which insulin levels are normal or high but the body cannot use this hormone efficiently. About half of PCOS patients, in fact, also have diabetes.

Premature ovarian failure is the early depletion of follicles before age 40, which, in most cases, leads to premature menopause. It affects about 1% of women and is typically preceded by irregular periods, which might continue for years. In this condition, follicle-stimulating hormone (FSH) levels are elevated, as they are during perimenopause. Premature ovarian failure is a significant cause of infertility, and women who have this condition have only a 5 - 10% chance to conceive without fertility treatments.

Causes of Premature Ovarian Failure. There are numerous causes of premature ovarian failure. Often the cause of this disorder or other causes of premature ovarian failure is unknown. In some cases, premature ovarian failure may represent an acceleration of the aging process.

The following conditions may produce premature ovarian failure:

Adrenal, pituitary, or thyroid gland deficiencies.
Genetic factors related to the X chromosome. A woman needs two functioning X chromosomes for normal reproduction. When one is abnormal, ovarian function fails. The most severe example is Turner syndrome, a genetic condition, in which one of the two X-chromosomes is missing or malfunctioning. Milder cases of ovarian failure can occur in fragile X syndrome and other rare inherited conditions that cause partial X-chromosome abnormalities.
Cancer treatments (radiation, chemotherapy, or both). Women who are undergoing cancer treatments and who want to become pregnant should see a reproductive specialist to discuss their options. According to the American Society of Clinical Oncology's 2006 guidelines, the fertility preservation method with the best chance of success is embryo cryopreservation. This procedure involves harvesting a woman's eggs (oocytes), followed by in vitro fertilization and freezing of embryos for later use. Other treatments under investigation include egg preservation, collecting and freezing unfertilized eggs, removing and freezing a part of the ovary for later reimplantation, and using hormone therapy to protect the ovaries during chemotherapy. Women may be able to access these investigational approaches through enrolling in clinical trials.
Autoimmunity. Autoimmune diseases -- including type 1 diabetes, systemic lupus erythematosus, autoimmune hypothyroidism, and autoimmune Addison's disease -- are associated with a higher risk for early menopause. Autoimmunity, however, may also play a role in some cases of premature ovarian failure without the presence of specific autoimmune diseases. In such cases, antibodies specifically attack the cells that secrete reproductive hormones thus causing ovarian failure.
Other causes of premature ovarian failure include sarcoidosis, mumps, some sexually transmitted diseases, and tuberculosis. Women with epilepsy are at higher risk for premature ovarian failure.

Idiopathic hypogonadotropic hypogonadism is a rare condition in which follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are underproduced, preventing the development of functional ovaries. There are no other abnormalities in the hypothalamus-pituitary axis (such as tumors or abnormal stress hormones or prolactin). In most cases, the causes of hypergonadotropic hypogonadism are unknown. Genetic factors, including Kallman syndrome, have been identified in about 20% of these cases.

Functional hypothalamic amenorrhea (FHA) is the absence of menstruation due to disturbances in the thyroid gland and hypothalamus-pituitary-adrenal (HPA) system, which regulates reproduction and other important functions. The eating disorders anorexia and bulimia are most often associated with FHA. FHA may be due to other different factors, most unknown.

Luteal phase defect is a general term referring to problems in the corpus luteum that result in inadequate production of progesterone. Because progesterone is necessary for thickening and preparing the uterine lining, the ovum fails to successfully implant in the endometrium. Between 25 - 60% of women who have recurrent miscarriages may have a luteal phase defect. A luteal phase defect, however, can also occur in fertile women, so other factors may be responsible for implantation failure.

Benign fibroid tumors in the uterus are extremely common in women in their 30s. The effect of fibroids on fertility is controversial. One analysis suggested that they may account for infertility in only 1 - 2.4% of women who are having trouble conceiving.

Large fibroids may cause infertility impairing the uterine lining, by blocking the fallopian tube, or by distorting the shape of the uterine cavity or altering the position of the cervix.

Some evidence suggests that even small fibroids may reduce the chances of pregnancy in women who are undergoing assisted reproductive techniques. Treatments to reduce fibroids may be helpful in such women, although there has been little research on this subject.

Click the icon to see an image of uterine fibroids.

Prolactin is a hormone produced in the pituitary gland that stimulates breast development and milk production in association with pregnancy. High levels of prolactin (hyperprolactinemia) reduce gonadotropin hormones and inhibit ovulation. Hyperprolactinemia in women who are not pregnant or nursing can be caused by hypothyroidism or pituitary adenomas. (These are benign tumors that secrete prolactin. They can cause headache and visual problems as well as breast secretions.) Some drugs, including oral contraceptives and some antipsychotic drugs, can also elevate levels of prolactin.

Secretions from the breast not related to pregnancy or nursing (called galactorrhea) are a telltale symptom of high prolactin levels and should be investigated.

Inborn Abnormalities. Inborn genital tract abnormalities may cause infertility. Mullerian agenesis is a specific malformation in which no vagina or uterus develops. Even in these cases, some women can become mothers by undergoing in vitro fertilization and having the fertilized egg implanted in another woman who is willing and able to carry the pregnancy (a surrogate mother).

Uterine or Abdominal Scarring. Bands of scar tissue that bind together after abdominal or pelvic surgery or infection (called adhesions) can restrict the movement of ovaries and fallopian tubes and may cause infertility. Asherman syndrome, for example, is scarring in the uterus that can cause obstructions and secondary amenorrhea. It may be caused by surgery, repeated injury, or unknown factors. Laparoscopic surgery is less likely to cause adhesions than standard open surgery.

In some of these cases, surgery may be helpful. One technique, called pressure lavage under ultrasound guidance (PLUG), may prove to be useful for treating some cases of mild scarring in the uterus (intrauterine adhesions). This technique is based on transvaginal sonohysterography, which uses ultrasound along with saline infused into the uterus to enhance visualization. Continuous accumulation of saline in the procedure is used to break up the scars.

Ectopic Pregnancies. Ectopic pregnancies increase the risk for infertility, although subsequent pregnancy rates are quite variable. Ectopic pregnancies that terminate without treatment appear to pose a lower risk for future infertility. Even a ruptured tube does not appear to reduce the chance for a future pregnancy in most women. Such an event however can be dangerous and even life threatening for the woman. Laparoscopic surgery to remove a fallopian tube affected by an ectopic pregnancy may preserve fertility better than traditional abdominal surgery.

Click the icon to see an image of an ectopic pregnancy.

Medications. Among the medications that can cause temporary infertility are those used to treat chronic disorders, as well as antidepressants, hormones, painkillers, and antipsychotic drugs.

Inflammatory Bowel Disease. Inflammatory bowel disease (particularly Crohn's disease or surgery for ulcerative colitis) can affect fertility.

Click the icon to see an image of Crohn's disease.

Celiac Sprue. Celiac sprue is a disease in which the patient cannot tolerate gluten, a common food chemical. The disorder is also highly associated with infertility in men and women, possibly through multiple effects on nutrition, immune factors, and hormones. The mechanisms are not altogether clear, but infertility is usually reversible with strict dietary control.

Click the icon to see an image of celiac sprue.

Iron Intake. Nutritional iron deficiency may contribute to female infertility. According to a 2006 study, women who take iron supplements are 40% less likely to experience ovulatory infertility than women who do not take iron supplements. Some researchers suggest that screening for iron deficiency should be part of the standard work-up of infertility tests.

Epilepsy. In one study of women with epilepsy, fertility rates were 33% lower than among women in the general population, perhaps due to certain antiepileptic drugs that increase the risk for birth defects. The social effects of epilepsy may also lead to marriage at an older age, which can be associated with delayed attempts to get pregnant and thereby affect fertility.

Thyroid Problems. Thyroid problems, either too much thyroid hormone (hyperthyroidism) or too little (hypothyroidism), can interrupt cycles.

Click the icon to see an image of hyperthyroidism.

Click the icon to see an image of hypothyroidism.

Metabolic Syndrome (also Called Syndrome X). Doctors diagnose this condition when at least three of the following abnormalities are present:

Abdominal obesity
Low HDL (good) cholesterol levels
High triglyceride levels
High blood pressure
Insulin resistance

Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease. One study reported that, as with polycystic ovarian syndrome, women with metabolic syndrome have higher levels of male hormones and are therefore at risk for infertility. Another study estimated that 24% of the population now has this condition.

Other Medical Conditions. Medical conditions associated with delayed puberty and amenorrhea (absence of periods) include Cushing's disease, sickle cell disease, HIV, kidney disease, and diabetes. Genetic mutations that affect luteinizing hormone may also be responsible for some cases of light or absent menstruation. Other rare genetic disorders, such as Kallman syndrome, cause abnormalities in the hypothalamus of the brain.

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. Fertility testing should be done earlier if a woman is over 35 years old or if either partner has known risk factors for infertility. An analysis of the man's semen should be performed before the female partner undergoes any invasive testing.

The first step in any infertility work up is a complete medical history and physical examination. Sexual technique and timing, menstrual history, lifestyle issues (such as smoking and drug, alcohol, and caffeine consumption), any medications being taken, and a profile of the patient's general medical and emotional health can help the doctor decide on appropriate tests.

Before embarking on an expensive fertility work-up, the following steps are free or low-cost and can be helpful:

Monitor basal body temperature. This is accurate in determining if ovulation is actually taking place.
Test the consistency of your cervical mucus. Collect some mucus between your two fingers and stretch it apart. If you are near the time of ovulation, the mucus will stretch more than 1 inch before it breaks. As an alternative, at-home kits can test saliva as substitute for checking cervical mucus.
Take an over-the-counter urine test for detecting luteinizing hormone (LH) surges. This helps determine the day of ovulation.
Fertell is the first at-home test kit for couples that is approved by the Food and Drug Administration. Women can test their urine for levels of follicle-stimulating hormone (FSH), while men can test their semen for sperm motility (ability of sperm to move). Fertell became available online and in some pharmacies in June 2007.

Several laboratory tests may be used to detect the cause of infertility and monitor treatments:

Hormonal Levels. Blood and urine tests are taken to evaluate hormone levels. Hormonal tests for ovarian reserve (the number of follicles and quality of the eggs) are especially important for older women.

Examples of possible results include:

High follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and low estrogen levels suggest premature ovarian failure or hypogonadotropic hypogonadism.
High LH and low FSH may suggest polycystic ovary syndrome or luteal phase defect.
High FSH and high estrogen levels on the third day of the cycle predicts poor success rates in older women trying fertility treatments.
LH surges indicate ovulation.
Blood tests for prolactin levels and thyroid function are also measured. These are hormones that may indirectly affect fertility.

Clomiphene Challenge Test. Clomiphene citrate (Clomid, Serophene), a standard fertility drug, may be used to test for ovarian reserve. With this test, the doctor measures FSH on day 3 of the cycle. The woman takes clomiphene orally on days 5 and 9 of the cycle. The doctor measures FSH on the tenth day. High levels of FSH either on day 3 or day 10 indicate a poor chance for a successful outcome.

Tissue Samples. To rule out luteal phase defect, premature ovarian failure, and absence of ovulation, the doctor may take tissue samples of the uterus 1 - 2 days before a period to determine if the corpus luteum is adequately producing progesterone. Tissue samples taken from the cervix may be cultured to rule out infection.

Tests for Autoimmune Disease. Tests for autoimmune disease, such as hypothyroidism and diabetes, should be considered in women with recent ovarian failure that is not caused by genetic abnormalities.

If an initial fertility work-up does not reveal abnormalities, as happens in about 40% of cases, more extensive tests will reveal abnormal tubal or uterine findings. The three major approaches for examining the uterus are ultrasound (particularly a variation called saline-infusion sonohysterography), hysterosalpingography, and hysteroscopy. Although combinations of these diagnostic approaches are often used to confirm diagnoses, one study indicated that with the introduction of saline-infusion sonohysterography, all are equally accurate and combinations do not increase accuracy. Furthermore, the ultrasound procedure is significantly less painful than the other two, suggesting that this should be the procedure of choice, if available.

Ultrasound and Sonohysterography. Ultrasound is the standard imaging technique for evaluating the uterus and ovaries, detecting fibroids, ovarian cysts and tumors, and also obstructions in the urinary tract. It uses sound waves to produce an image of the organs and entails no risk and very little discomfort.

Transvaginal sonohysterography uses ultrasound along with saline infused into the uterus, which enhances the visualization of the uterus. This technique is proving to be more accurate than standard ultrasound in identifying potential problems. It is currently the gold standard for diagnosing polycystic ovaries.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) gives a better image of any fibroids that might be causing bleeding, but it is expensive and not usually necessary.

Hysteroscopy. Hysteroscopy is a procedure that may be used to detect the presence of endometriosis, fibroids, polyps, pelvic scar tissue, and blockage at the ends of the fallopian tubes. Some of these conditions can be corrected during the procedure by cutting away any scar tissue that may be binding organs together or by destroying endometrial implants. (It may miss cases of uterine cancer, however, and is not a substitute for more invasive procedures, such as dilation and curettage ( D&C) or endometrial biopsy, if cancer is suspected.)

It is done in the office setting and requires no incisions. The procedure uses a long flexible or rigid tube called a hysteroscope, which is inserted into the vagina and through the cervix to reach the uterus. A fiber optic light source and a tiny camera in the tube allow the doctor to view the cavity. The uterus is filled with saline or carbon dioxide to inflate the cavity and provide better viewing. This frequently causes cramping.

There are small risks of bleeding, infection, and reactions to anesthesia. Many patients experience temporary discomfort in the shoulders after the operation due to residual carbon dioxide that puts pressure on the diaphragm. The wound itself is minimally painful.

Hysterosalpingography. Hysterosalpingography is performed to discover possible blockage in the fallopian tubes and abnormalities in the uterus:

The doctor inserts a tube into the cervix through which a special dye is injected. (The patient may experience some cramping and discomfort.)
The dye passes into the uterus and up through the fallopian tubes.
An x-ray is taken of the dye-filled uterus and tubes.
If the dye is seen emerging from the end of the tube, no blockage is present. (In some cases, hysterosalpingography may even restore fertility by clearing away tiny tubal blockages.)
If results show blockage or abnormalities, the test may need to be repeated. In case of blockage, hysterosalpingography may reveal a number of conditions, including endometrial polyps, fibroid tumors, or structural abnormalities of the uterus and tubes.

The test has significant rates of false diagnoses, both positive and negative. There is a small risk of pelvic infection, and antibiotics may be prescribed prior to the procedure. One study suggested that flushing the tubes with an oil-based fluid (lipiodol) during this procedure may improve fertility rates in women with infertility of unknown causes.

As women age, the number of follicles (and therefore their egg supply) declines. Researchers are developing tests that may help determine how many are left. Such tests include the following:

Calculating the volume of the ovaries. In general, the smaller the ovaries, the fewer the remaining eggs.
Counting antral follicles. Antral follicles are those that develop but do not become dominant follicles. Instead, they form a fluid-filled space called an antrum. Women who have fewer than three to five antral follicles appear to have a poor chance of fertility.
Measuring inhibin B. Inhibin B is a growth factor produced in the ovaries. Low levels suggest fewer eggs.

Eventually these markers may be useful for determining which women need more aggressive treatments.

Genetic testing may be warranted in cases of male infertility or when genetic factors may be causing pregnancy failure in the woman. If genetic abnormalities are suspected in either partner, counseling is recommended.

A technique called preimplantation genetic diagnosis (PGD) is now available in some centers that can examine all the chromosomes in a human embryo. It helps identify abnormalities that increase the risk for infertility, treatment failures, or genetic defects in the offspring.

Treatment

Some doctors recommend that if a couple fails to conceive after 1 - 2 years of frequent unprotected sex, they should consult a fertility expert. Women who are 35 or older, however, may want to begin exploring their options if they do not become pregnant within 6 months to a year.

Several approaches can treat infertility, depending on the cause:

Lifestyle measures (healthy lifestyle, planning sexual activity with ovulation cycle, managing stress and emotions)
Treatments for endometriosis, fibroids, or menstrual disorders
Use of anti-estrogen drugs, such as clomiphene, to induce ovulation in women with ovarian dysfunction
Surgery (standard or laparoscopic) to unblock fallopian tubes
Use of hormone treatments (clomiphene or progestins) for luteal phase defect
Assisted reproductive technologies (ART) such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)

Choosing a good fertility clinic is important. Those offering assisted reproductive techniques are not always regulated by the government, 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 offer such gimmicks.


Causes of Infertility	Treatments
Endometriosis	Conservative surgery (typically laparoscopy) is the appropriate approach for restoring fertility. GnRH agonists or progestins, used to treat endometriosis itself, have no effect on fertility. Possible exceptions are GnRH agonists used after surgery. In one study, this treatment helped improve conception rates in women who subsequently underwent assisted reproductive techniques. Assisted reproductive technologies (ART). (Fertility drugs alone have no effect.) It is not clear, in any case, whether either laparoscopy for removing endometrial implants or ART has additional advantages in many of these women compared to simply trying to become pregnant through non-aggressive means.
Hyperprolactinemia	Dopamine agonists, including bromocriptine (Parlodel) or cabergoline (Dostinex). Surgery in some cases.
Luteal phase defect	Clomiphene or superovulation drugs (FSH drugs or hMG).
Hyperprolactinemia (elevated prolactin)	Bromocriptine, cabergoline to shrink tumors that result in over secretion of prolactin. Cabergoline is more effective, but bromocriptine has been used longer. Once ovulation starts, women who want to become pregnant should stop cabergoline one month before attempting conception. Surgery may be needed for women who do not respond to medications or who have large tumors.
Hypogonadotropic Hypogonadism	Fertility drugs (hMG preferable to FSH alone) with or without assisted reproductive technologies.
Pelvic Inflammatory Disease	Screening high-risk women for the presence of Chlamydia trachomatis and treating the organism before it causes symptoms could reduce the risk of PID by almost 60%. If any sexually transmitted infection is detected, both partners should receive antibiotics, even if there are no symptoms. If PID symptoms develop, particularly lower abdominal pain, fertility can be preserved if women receive antibiotics within 2 days. A delay significantly increases the risk for scarring.
Polycystic Ovarian Syndrome	Lifestyle changes (weight loss and exercise in women who are overweight.) Clomiphene is the standard first-line treatment for polycystic ovarian syndrome (PCOS)-related infertility. Although some research has indicated that the diabetes drug metformin (Glucophage) might help treat infertility in women with PCOS, a 2007 study in the New England Journal of Medicine indicated that clomiphene is much more effective.
Premature Ovarian Failure	Assisted reproductive technologies with donor eggs.
Preserving fertility after cancer treatments	Removal and freezing (called cryopreservation) of ovarian tissue containing embryos or freezing immature and unfertilized eggs to use for later reimplantation. (Freezing before cancer treatment appears to offer the best chance.) Under investigation: Ovarian transplantation procedures and gonadotropin-releasing hormone analogues, which put women in a temporary pre-pubescent state during chemotherapy and may preserve fertility.
Fallopian tubal blockage	Surgical procedures (laparoscopy or salpingostomy) to clear the tubes. (Average pregnancy rate after salpingostomy is about 30%, but they can vary widely.) Flushing the tubes with an oil-based fluid (lipiodol) during hysterosalpingography (investigative). In a 2002 study, this procedure improved pregnancy rates in women with infertility of unknown causes. Assisted reproductive technologies.
Unexplained infertility	Lifestyle measures. Fertility drugs. Assisted reproductive technologies.

Lifestyle Changes

Although there are no dietary or nutritional cures for infertility, a healthy lifestyle is important. Ovulatory problems are reversible by changing behavioral patterns. Such conditions include:

Maintain a healthy weight. Women who are either over- or underweight are at risk for fertility failure, including a lower chance for achieving success with fertility procedures. Everyone should have a diet rich in fresh fruits and vegetables and whole grains and low in saturated fats.
Stop smoking. Smoking increases the risk for infertility in both men and women, and poses a future health risk for the mother and infant. Everyone should quit.
Avoid caffeine and alcohol.
Avoid excessive exercise if it causes menstrual irregularity. However, moderate and regular exercise is essential for good health. Few women exercise to the extent that their periods are affected. For those who do, one study found that simply adding calories can restore menstruation in many cases.
Don't use electric blankets. In one study, a 74% higher incidence of spontaneous abortion was associated with using an electric blanket during the month of conception. There was no association with heated waterbeds or electromagnetic waves.
Avoid any unnecessary medications.

There is no evidence of harm to a developing fetus from low exposure to microwaves or electromagnetic waves. Women who remain anxious may derive comfort by avoiding some of these devices (such as cellular phones or electric blankets) and remaining a foot or so away from others (such as computers or microwave ovens).

Both male and female hormone levels fluctuate according to the time of day, and they 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. (Sexual interest also tends to be higher 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.

Each morning before rising, the woman takes her temperature with a specialized basal body thermometer and marks the result on a graph-paper chart.
The woman also notes the days of menstruation and sexual activity.
The so-called "fertile window" is 6 days long, starts 5 days before ovulation, and ends the day of ovulation.
The chances for fertility are considered to be highest between days 10 and 17 in the menstrual cycle (with day 1 being the first day of the period, and ovulation occurring about 2 weeks later). However, cycles vary from woman to woman. Researchers suggest that women track the length of their cycles, which can run anywhere from between 19 and 60 days. A long cycle, for example, suggests a delayed ovulation date.
Immediately after ovulation the body temperature increases sharply in about 80% of cases. (Some women can be ovulating normally yet not show this temperature pattern.)

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. 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 (ClearBlue) are also available. They are less costly than the saliva test but are messier. Monitoring hormones 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 doctors say that having sex more than 2 days a week adds no benefits. Moreover, frequent sexual activity lowers sperm count per ejaculation. Other 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.

The fertility process is a roller coaster of emotions that are present throughout and in 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. A successful pregnancy often depends on repeated attempts.
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 can be viewed as important as medical treatment. The following are some ways women reduce stress while trying to conceive:

Talking to one's spouse, family, and friends is very beneficial. The best support comes from the spouse. Studies suggest that a positive attitude on the husband's part is essential for enabling his wife to deal effectively with either the success or failure of fertility treatments. Men and women may cope differently with the stress, and each should understand the other's special needs. Women tend to want greater personal space and also to want to share the burden with their husbands. Men tend to cope by seeking to improve themselves (for example being strong, or being the "best").
Almost half of women seeking fertility treatments practice good-luck rituals, including praying and wearing charms or special jewelry. No evidence exists that these practices increase fertility, but they may help reduce anxiety and enhance a sense of control.
Cognitive-behavioral therapy, which uses methods that include relaxation training and stress-management, have been associated with higher pregnancy rates. (In one study, 42% became pregnant without medical intervention.)
Attending support groups or counseling services before and after treatment helps many women endure the process and ease the grief should treatment fail. One study indicated that pregnancy rates were twice as high in women who coped with their depression by reaching out to others rather than repressing guilt or rage. (These results held only in cases in which women, not their mates, were infertile.)
Acupuncture may help some women. Some evidence suggests that this alternative treatment has beneficial effects on chemicals in the brain involved with stress and reproduction. Acupuncture is safe, but studies have been mixed on whether it can help improve pregnancy rates. One study indicated that women who received acupuncture achieved significantly higher success rates during fertility treatments (42.5%) than those who did not receive it (26.3%). Several 2006 studies suggested that acupuncture may improve pregnancy success for women who undergo in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) procedures. One of these studies found that acupuncture had a positive effect if it was given during the luteal phase (post-ovulatory period of menstrual cycle.) Another study suggested that acupuncture should be given on the day of embryo transfer.

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

Effects of Failure. 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 Successful Treatments. Some studies have indicated that even if successful, some women experience higher stress and fear of failure during pregnancy. According to one study, however, women who achieved pregnancy using fertility treatments felt increasingly better and had higher self esteem and less anxiety as the pregnancy progressed than women whose pregnancies were not due to medical intervention.
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.

Medications

Fertility drugs are often used alone as initial treatment to induce ovulation. If they fail as sole therapy, they may be used with assisted reproductive procedures or artificial insemination to produce multiple eggs, a process called superovulation.

Clomiphene citrate (Clomid, Serophene) is usually the first fertility drug of choice for women with infrequent periods and long cycles. Unlike more potent drugs used in superovulation, clomiphene is gentler and works by blocking estrogen, which tricks the pituitary into producing

follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This boosts follicle growth and the release of the egg. Clomiphene can be taken orally, is relatively inexpensive, and the risk for multiple births (about 5%, mostly twins) is lower than with other drugs.

Women with the best chances for success with this drug are those who have the following conditions:

Polycystic ovarian syndrome (PCOS)
Ability to menstruate but irregular menstrual cycle

Women with poorer chances of success with this drug have the following conditions:

Infertility but with normal ovulation
Low estrogen levels
Premature ovarian failure (early menopause)

One or two tablets are taken each day for 5 days, usually starting 2 - 5 days after the period starts. If successful, ovulation occurs about a week after the last pill has been taken. If ovulation does not occur, then a higher dose may be given for the next cycle. If this resgimen is not successful, treatment may be prolonged or additional drugs may be added. Doctors usually do not recommend more than 6 cycles.

Clomiphene often reduces the amount and quality of cervical mucus and may cause thinning of the uterine lining. In such cases, other hormonal drugs may be given to restore thickness. Other side effects of clomiphene include ovarian cysts, hot flashes, nausea, headaches, weight gain, and fatigue. There is a 5% chance of having twins with this drug, and a slightly increased risk for miscarriage.

If clomiphene does not work or is not an appropriate choice, gonadotropin drugs are a second option. Gonadotropins include several different types of drugs that contain either a combination of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), or only FSH. Clomiphene works indirectly by stimulating the pituitary gland to secrete FSH, which prompts follicle production. In contrast, the gonadtropin hormones directly stimulate the ovaries to produce multiple follicles.

Gonadotropins are given in a shot. (Your doctor may show you how to self-administer the injection.) Gonadotropins include:

Human Menopausal Gonadtropins (hMG), also called menotropins
Human Chorionic Gonadotropins (hCG)
Urofollitropin and Follitropin, natural and synthetic forms of FSH
Gonadotropin-releasing hormone (GnRH) analogs, which include GnRH agonists and GnRH antagonists

Gonadotropin drugs are either natural compounds extracted from urine or synthetic compounds that are genetically engineered in a laboratory using recombinant DNA.

Human Menopausal Gonadotropin (hMG). HMG drugs, also called menotropins, contain a mixture of both FSH and LH. These drugs (Pergonal, Repronex, Metrodin, Humegon) are all derived from the urine of postmenopausal women. HMG is administered as a series of injections 2 - 3 days after the period starts. Injections are usually given for 7 - 12 days, but the time may be extended if ovulation does not occur. In such cases, a shot of human chorionic gonadotropin (hCG) may trigger ovulation.

Human Chorionic Gonadotropin (hCG). Human chorionic gonadotropin (hCG) is similar to LH. It mimics the LH surge, which stimulates the follicle to release the egg. Natural hCG drugs, derived from the urine of pregnant women, include Pregnyl, Profasi, Novarel, APL, Chorex, and Follutein. Ovidrel is the only available genetically modified hCG drug. Ovidrel has fewer side effects at the injection site, and its quality can be better controlled than the natural drugs. It is generally used after hMG or FSH to stimulate the final maturation stages of the follicles. Ovulation, if it occurs, does so about 36 - 72 hours after administration.

Urofollitropin and Follitropin. Urofollitropin (Bravelle, Fertinex) is a purified form of FSH, derived from the urine of postmenopausal women. Follitropin drugs (Gonal-F, Follistim) are synthetic versions of FSH. These FSH drugs are sometimes given in combination with an hCG drug.

GnRH Analogs (Agonists or Antagonists). Gonadotropin-releasing hormone (GnRH) is a hormone produced in the hypothalamus part of the brain. GnRH stimulates the pituitary gland to produce LH and FSH. GnRH analogs are synthetic drugs that are classified as either agonists or antagonists. They are similar to natural GnRH but have very different actions. While natural GnRH stimulates LH and FSH, these drugs actually prevent the LH and FSH surge that occurs right before ovulation. This action helps prevent the premature release of the eggs before they can be harvested for assisted reproductive technologies.

GnRH agonists include leuprolide (Lupron), nafarelin (Synarel), and goserelin (Zoladex).
GnRH antagonists include ganirelix (Antagon) and cetrorelix (Cetrotide). GnRH antagonists suppress FSH and LH more than GnRH agonists, and they may require fewer injections.

Women with endometriosis often have an especially hard time getting pregnant. A 2006 review suggested that GnRH agonists may help women with endometriosis quadruple their chances of becoming pregnant when the drug is used 3 - 6 months prior to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). [See In-Depth Report #74: Endometriosis.]

Multiple Births. Overproduction of follicles can lead to ovarian enlargement. This event increases the risk for multiple births. There is a 25% chance of multiple births (about 17% for twins and 8% for triplets and or more).

Ovarian Hyperstimulation Syndrome. The most serious complication with superovulation is ovarian hyperstimulation syndrome (OHS), which is associated with the enlarged ovary (although the precise cause is unknown). This can result in dangerous fluid and electrolyte imbalances and endanger the liver and kidney. OHS is also associated with a higher risk for blood clots. In rare cases, it can be fatal. Symptoms include abdominal bloating, nausea, vomiting, and shortness of breath.

Bleeding and Rupture of Ovarian Cysts. Overproduction of follicles, if unchecked, may result in bleeding and rupture of ovarian cysts.

Cancer Concerns. There has been concern that clomiphene and gonadotropins may increase the risks for ovarian and breast cancer. Most evidence to date does not indicate that ovulation-stimulating drugs increase the risks for these types of cancers. However, more research needs to be done. Some studies suggest that clomiphene, which is chemically related to the breast cancer drug tamoxifen, may actually decrease the risk for breast cancer.

Progesterone. Progesterone is a hormone that is produced by the body during the menstrual cycle. Progesterone drugs are sometimes given to women who have experienced frequent miscarriages (a possible sign of progesterone deficiency). A progesterone drug may also be given after egg retrieval during an in vitro fertilization (IVF) cycle to help thicken the uterine lining (endometrium) so it can better hold the egg following implantation.

Aromatase Inhibitors. 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). These drugs are used for treating breast cancer and are being investigated for stimulating ovulation in infertile women. Although letrozole is not approved for treatment of infertility, it has become widely used for this purpose in recent years. Some doctors were concerned that letrozole could increase the risk of birth defects. However, a major 2006 study indicated that letrozole does not increase risk to the fetus. The study compared the rate of birth defects among babies whose mothers conceived with letrozole and those who used clomiphene (the standard first-line fertility drug). Researchers found no differences in birth outcomes between the two groups.

Tamoxifen. Tamoxifen (Nolvadex) is a drug known as a selective estrogen-receptor modulator (SERM). It is used to prevent breast cancer in high-risk women. Studies suggest that it may equal clomiphene in its ability to induce ovulation. It may be especially useful when used along with IVF for preserving fertility in breast cancer patients. This drug is less expensive than clomiphene, but it poses some health hazards, including a risk for blood clots and uterine cancer.

Glucocorticoids. Glucocorticoids are steroid hormones that are sometimes used in combination with IVF and intracytoplasmic sperm injection (ICSI). It is thought that anti-inflammatory effect of these drugs can help make the lining of the uterus more responsive to egg implantation. However, a 2007 review indicated that glucocorticoids do not help improve pregnancy success rates and should not be used routinely with assisted reproductive technologies.

Regimens to induce ovulation vary widely according to individual need. A typical procedure, involving superovulation and in vitro fertilization (IVF) may be as follows:

Doctors make sure that the patient is not pregnant or in the luteal phase of her menstrual cycle (the premenstrual period).
Injections of either human menopausal gonadtropins, which contains luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or pure FSH are administered daily 2 - 4 days after day 1 of the next cycle. Either drug may be used.
After 4 - 8 days of treatment, estrogen levels are monitored. Increasing levels on the fourth day of treatment may be strong indicators of success. If estrogen levels indicate that ovaries are responding, ultrasound is then performed to detect possible overproduction of follicles. Such evaluation should then be conducted every 1 - 2 days and dosages adjusted accordingly.
Gonadotropin-releasing hormone analogs are used to prevent a premature release of LH hormone (and therefore ovulation). GnRH agonists are typically administered either early on or a few days after ovulation in the cycle previous to the one planned for IVF. This approach is referred to as the long protocol, and it serves to suppress the pituitary gland and allows time for the eggs to mature before harvesting. Other protocols using GnRH antagonists are under investigation, but to date the long protocol has the best pregnancy rates.
When at least three follicles have reached a diameter of 18 mm, human chorionic gonadotropins (hCG) is typically administered to release the egg. It is not given if there are signs of overproduction of follicles, which suggests a risk for ovarian hyperstimulation syndrome (OHS), a dangerous complication. (One study reported that giving high doses of progesterone to high-risk women the day of hCG administration may prevent OHS.)
Egg retrieval may be performed about 36 hours following hCG administration, with the transfer of the embryo (the fertilized egg) back into the woman 2 - 3 days after retrieval.
Embryos are transferred to the uterus through a small tube. This process does not require an anesthetic, although the procedure can cause cramping.

Natural (Unstimulated) In Vitro Fertilization Cycles. An alternative to superovulation for some couples is natural in vitro fertilization (IVF) cycles. It allows multiple, consecutive cycles of treatment. Natural IVF is far less expensive than standard hyperstimulation methods and avoids their risks, including multiple births and ovarian hyperstimulation syndrome (OHS).

The process involves ultrasound and hormonal monitoring starting 5 days before the estimated ovulation day.
No superovulation drugs are used, such as follicle-stimulating hormone (FSH) and human menopausal gonadtropins (hMG). The doctor, however, may administer an injection of human chorionic gonadotropins (hCG) to stimulate the luteinizing hormone (LH) surge.
The egg retrieval timing is based on detecting LH surge.
A single egg is retrieved. The procedure that follows is similar to other IVF cycles.

The basic disadvantage to this approach is that the eggs may be released before there is a chance for them to be harvested. Women report far lower stress levels with this approach, however, even though it requires more treatment cycles. In one study, the live-birth rate was 32%. Not all women are appropriate candidates, however. Women should have regular menstrual cycles and infertility of unknown cause or associated with problems in the fallopian tubes. Pregnancy rates are still very low in older women.

Clomiphene. Another gentler alternative to superovulation is the use of clomiphene before IVF, which works slightly better than unstimulated IVF.

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% between 1996 and 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.

Artificial insemination (AI) is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. AI 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 AI 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
When unexplained infertility exists in both partners

Those in whom AI 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 IVF 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 AI 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 ovulation.

About 71% of assisted reproductive technologies (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 usually 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.)

In 2002, more than 45,000 American babies were born using in vitro fertilization (IVF). Success rates have increased in all age groups (although they are still considerably lower in older than in younger women). Chances for assisted reproductive technologies (ART) 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). 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 a 2002 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 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.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main problem. 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, then it 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 some studies have shown a higher number of birth defects in children conceived with ICSI, experts think that this may have more to do with the genetic background of the parents than ICSI itself. Recent research suggests that ICSI children develop normally. A 2006 study of 8-year-old children conceived with ICSI 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. Doctors caution that 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.

In Vitro Maturation. A 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. At this time, 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 is currently conducted outside the U.S.

Complications of Assisted Reproductive Technologies

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.
In vitro fertilization. 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, 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 infertility 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.

ART remains a good option for many infertile couples. The likelihood of having a healthy single child of normal birth weight using ART is about 94%. The likelihood of having a child free of major birth defects is about 91%. Frozen eggs do not appear to pose any higher risk for developmental problems.

Preimplantation genetic diagnosis (PGD) is now available in some 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. Researchers 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 also reduces the chance for successful outcome.
Blastocyst transfer may help reduce the chances for multiple births.

Resources

www.resolve.org -- National Infertility Association
www.asrm.org -- American Society for Reproductive Medicine
www.theafa.org -- American Fertility Association
www.endometriosisassn.org -- The Endometriosis Association
www.acog.org -- American College of Obstetricians and Gynecologists
www.endo-society.org -- The Endocrine Society
www.aace.com -- American Association of Clinical Endocrinologists
www.cdc.gov/reproductivehealth/index.htm -- Centers for Disease Control: Assisted Reproductive Technology Reports

References

Boomsma CM, Keay SD, Macklon NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005996.

Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Iron intake and risk of ovulatory infertility. Obstet Gynecol. 2006 Nov;108(5):1145-52.

Dieterle S, Ying G, Hatzmann W, Neuer A. Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study. Fertil Steril. 2006 May;85(5):1347-51.

Hvidtjorn D, Grove J, Schendel DE, Vaeth M, Ernst E, Nielsen LF, et al. Cerebral palsy among children born after in vitro fertilization: the role of preterm delivery--a population-based, cohort study. Pediatrics. 2006 Aug;118(2):475-82.

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.

Jensen A, Sharif H, Svare EI, Frederiksen K, Kjaer SK. Risk of breast cancer after exposure to fertility drugs: results from a large Danish cohort study. Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1400-7. Epub 2007 Jun 21.

Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006 Jun 20;24(18):2917-31.

Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007 Feb 8;356(6):551-66.

Mackay AP, Berg CJ, King JC, Duran C, Chang J. Pregnancy-Related Mortality Among Women With Multifetal Pregnancies. Obstet Gynecol. 2006 Mar;107(3):563-568.

Ombelet W, Martens G, De Sutter P, Gerris J, Bosmans E, Ruyssinck G, et al. Perinatal outcome of 12,021 singleton and 3108 twin births after non-IVF-assisted reproduction: a cohort study. Hum Reprod. 2006 Apr;21(4):1025-32.

Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004635.

Shevell T, Malone FD, Vidaver J, Porter TF, Luthy DA, Comstock CH, et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol. 2005 Nov;106(5 Pt 1):1039-45.

Smith C, Coyle M, Norman RJ. Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer. Fertil Steril. 2006 May;85(5):1352-8.

Terry KL, Willett WC, Rich-Edwards JW, Michels KB. A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med. 2006 Dec 11-25;166(22):2484-9.

Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Jun;85(6):1761-5.

Westergaard LG, Mao Q, Krogslund M, Sandrini S, Lenz S, Grinsted J. Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective, randomized trial. Fertil Steril. 2006 May;85(5):1341-6.

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:
10/29/2007
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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