FitSugar

Forget the Scale, How About a Bod Pod?

FitSugar — Tue, 22 May 2007 14:30:00 -0700

If you have a hard time stepping onto the scale, imagine stepping into the Bod Pod...

The Bod Pod is the latest in measuring body composition. Instead of underwater weighing, skin fold and circumference measuring or even a scale, your doctor (or personal trainer) may ask you to step inside the Bod Pod. This futuristic contraption will measure your body composition (fat mass and lean mass) in about 5 minutes flat.

There is something about this that totally reminds me of that look into the future ride at Epcot circa 20 years ago and I can't stop saying the name, Bod Pod, Bod Pod... However, this is actually a great device for fitness professionals. Don't be replacing your bathroom scale/body fat measurer just yet, because aside from the fact that it is absolutely huge, the Bod Pod is a bit on the pricey side. About $42,000 on the pricey side. Yikes -- I'll be sticking to the old fashioned ways myself, but you can check it out at BodPod.com.

Swimming For Weight Loss?

FitSugar — Tue, 13 Oct 2009 13:30:25 -0700

Swimming has gotten a bad rap as an exercise for weight loss. Unlike running, which curbs your appetite, swimming seems to increase it.

Studies comparing swimming with walking and cycling weight-loss programs found that swimmers gained five pounds on average, while the other two groups lost between 17 and 19 pounds. The culprit seems to be the increased appetite that follows working out in water, since swimming lowers your body temp and the body crave calories to help heat it back up. Plus the swimmers weight gain could be attributed to an increase in lean muscle mass, which would have changed their body composition without weight loss.

See how I think you can make swimming part of your weight-loss plan, when you read more.
If you are swimming for weight loss, I don't believe you should give up on the pool entirely - swimming is a great full-body exercise. I do think you should add some cardio training on land. I am a firm believer in cross-training, so adding strength training and walking or running will help burn calories as well as build bone density, which is another benefit of weight-bearing exercises that you miss out on when swimming. When you do finish a swim workout, take a sauna, a steam, hot tub, or a hot shower to help heat your body. Also try sipping on some hot herbal tea as a post-workout drink.

The Skinny On: Measuring Body Fat Percentage

FitSugar — Thu, 20 Aug 2009 05:50:09 -0700

If you're in the business of trying to lose weight, the best way to monitor your progress isn't by stepping on a scale. Since a basic bathroom scale measures your entire body weight, it doesn't take into consideration how much of you is made up of fat, and how much is made of healthy stuff like bones, muscle, blood, and organs. For a more accurate picture of your body composition, it's best to measure your body fat percentage, and here are the many ways it's calculated.

Home scales that measure body fat. They use the Bioelectrical Impedance Analysis method to measure body fat percentage. It sends a low level and harmless electrical current through your feet and uses the data to determine how much of you is fat. They are fairly accurate and easy to use, as long as you follow the directions. A scale like this will cost between $50 and $100.
DEXA (dual energy X-ray absorptiometry) scan. This test is normally used to measure bone density to check for osteoporosis, but it can also measure fat percentage. It uses two different low-dose X-rays to figure out bone mass and soft tissue mass. Even though it's super accurate and considered the "gold standard" for measuring body fat, it's also super pricey, about $100 or more.

To see the other methods, read more.

Skin fold calipers (pinch test). You can buy a set to do on your own, or have a professional take your measurements. It basically squeezes your skin folds and measures how thick you are. This test is low in cost but tends to be less accurate than the DEXA scan.
Hydrostatic weighing (underwater weighing). You sit on a scale in a tank of water, blow out all your air, and then are dunked completely underwater. The more fat you have, the more you'll float. This test is very accurate, but it can be scary for some people to submerge themselves underwater. It costs around $50.

Do you have a scale that measures body fat?

You Asked: Increased Cardio but Gaining Weight

FitSugar — Fri, 31 Jul 2009 08:00:42 -0700

Dear Fit,
I've been increasing my cardio workouts to help me drop the seven pounds I gained after losing my job. Previously I was doing 30 minutes twice a week, but over the last three weeks, I've been doing 30 minutes five or six times a week. I alternate between running, biking, and hiking. I lost a pound in the first week, but now I'm slightly heavier than I was when I started this new routine! When I look in the mirror, I do notice that my muscles have more definition, but the scale is not making me happy. My diet hasn't changed at all, so what gives? Does muscle weigh more than fat, or am I doing something wrong?
- Frustrated About Fat

Losing weight takes a lot of hard work, so it's completely understandable that the scale is upsetting you. To hear what I have to say about this read more.

When it comes to losing weight, try to think about it this way. You want to lose fat, but that doesn't necessarily translate to losing pounds as measured by a scale. Muscle doesn't weigh more than fat, it's just more dense and not as bulky and lumpy as fat. That means a pound of muscle takes up less room than a pound of fat. So by increasing your cardio workouts, you're probably gaining muscle and decreasing your overall body fat. You can tell by how you look in the mirror or by the way your clothes fit.

I know you want to see the number decrease on the scale, but remember that weight isn't an accurate way to determine how healthy and fit you are. Think about your body composition instead, meaning your percentage of body fat. Exercising will make you stronger, so you'll have more muscle and less fat, which is what you want. My advice is to keep up your fitness routine and your healthy diet, and forget about watching the scale. Keep an eye on how lean and toned you look, and that's a much better indication of your progress.

Obesity

FitSugar — Wed, 08 Oct 2008 17:35:32 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Being overweight or obese puts you at risk for a number of diseases, including heart disease, diabetes, high blood pressure, stroke, gallbladder disease, osteoarthritis, and respiratory disorders. The risk of developing these diseases is even higher when weight is concentrated near the waist.

Obesity is an increasing problem. According to the National Institutes of Health, 60% of American adults are overweight and 25% are considered obese, while about 25% of American children are overweight or obese. And the numbers are rising. Taking weight off, and keeping it off, is difficult. Many people who lose weight later gain back some or all of the excess pounds.

Despite growing research on obesity, there are no medications, herbs, or supplements that can help you lose a significant amount of weight, and all have some side effects. The only way to lose weight is to reduce the amount of calories you eat and increase the time and intensity of your exercise. These actions have many health benefits in addition to helping you lose weight.

Signs and Symptoms

Obesity is usually determined by body mass index, or BMI, using a formula that calculates a ratio of your height to your weight.

BMI 25 - 29.9 (overweight)
BMI 30 and above (obese)

A high waist to hip ratio (indicating that fat is centered around the waist) increases the risk for developing serious, even life-threatening conditions associated with obesity. Generally, for men a ratio of .90 or less is considered safe. For women, .80 or less is considered safe.

Conditions that may accompany obesity include:

High cholesterol (including high triglyceride levels)
Diabetes
High blood pressure
Sleep apnea (episodes when a person stops breathing while asleep)
Osteoarthritis
Gallstones

What Causes It?

A number of factors contribute to obesity.

Diet: Eating high-fat, high-calorie foods causes weight gain.
Lack of exercise: Sedentary people don't burn as many calories as active people.
Genetics: Your genes may influence how much fat your body stores and where it store it, although genes alone do not mean you will be obese.
Age: People gain weight as they get older, because they tend to be less active and to lose muscle mass.
Psychological issues: Some people overeat when they are upset or stressed.
Medications: Some drugs, such as corticosteroids, blood pressure medication, and tricyclic antidepressants, can cause you to gain weight.
Medical problems: Rarely, obesity is due to a medical problem such as Cushing's syndrome (where the adrenal glands produce too much hormone) or hypothyroidism (where the thyroid gland doesn't produce enough hormone). Conditions such as osteoarthritis cause people to be less active, which can lead to weight gain.

Risk Factors

The following factors may increase an individual's risk for becoming obese:

Living in an industrialized country, especially the United States
Having family members who are overweight or obese
Not being physically active
Overeating
Eating a high-fat diet
Taking certain prescription medications (see "Causes")
Having a hormone disorder, such as Cushing's syndrome or hypothyroidism (underactive thyroid)
Being emotionally stressed (from the death of a loved one, for example), which may cause a person to overeat

Preventive Care

The best way to prevent obesity and maintain a normal weight is to eat a healthy diet and exercise daily. Keeping a food and exercise journal, where you record what you eat and how long you exercise, is an excellent way to get started.

Organizations such as the American Diabetes Association, the American Heart Association, and the American Dietetic Association have developed guidelines that promote weight loss and healthy eating. These guidelines recommend that no more than 30% of a person's total calorie intake should come from fats. Overall, you should eat a wide variety of foods, especially fruits and vegetables, in order to stay healthy and maintain proper weight.

Many studies show that exercise -- from moderate to intense -- helps prevent obesity. The Centers for Disease Control and Prevention and the American Academy of Sports Medicine recommend at least 30 minutes of moderate aerobic activity (such as a brisk walk) at least 5 days a week. You don't have to exercise for 30 minutes at a time; 10 minutes, done three times a day, is also effective. In fact, any exercise -- from taking the stairs to cleaning the house or working in the garden -- is beneficial.

What to Expect at Your Provider's Office

Health care practitioners use BMI to diagnose obesity. To determine BMI, weight in kilograms is divided by height in meters, squared. You can find online BMI calculators that do the math for you. As previously noted in the "Signs and Symptoms" section, the following BMI ranges are most often used as indications that a person is overweight or obese:

BMI 25 - 29.9 (overweight)
BMI 30 and above (obese)

Your doctor may also measure your blood pressure and percentage of body fat, and may order blood tests to check cholesterol levels and determine how well your thyroid is functioning.

Treatment Options

Losing weight -- and then maintaining a healthy weight -- involves a combination of diet, exercise, and other lifestyle modifications. Although some medications, herbs, and supplements may help you lose a little weight, you still must eat fewer calories and exercise more to see any real effect. For severe obesity, bariatric surgery (which physically restricts the amount of food a person can eat) may be an option.

Lifestyle

To lose weight, you must eat fewer calories and increase your physical activity to burn more calories. The key to losing and keeping off weight is to set realistic weight loss goals that are achievable. The changes you make to your eating and exercise habits will need to last throughout your life.

Exercise

Exercise can help you lose weight, especially in the first six months, and to maintain your desired weight in the long-term. Exercise not only contributes to weight loss, it also decreases abdominal fat and increases heart health, lowers blood pressure, and helps keep blood sugar in check.

If you are not used to exercising, start slowly and build up to the goal of 30 minutes a day for at least 5 days a week. An ideal exercise program includes aerobic activity (walking, swimming, biking), strength training (lifting weights), and flexibility (stretching). If you are severely obese or have other medical problems, talk to your doctor before starting a new exercise program.

You may be sore at first. Some muscle soreness is normal. However, if you experience pain that lasts more than 2 hours after your workout, see your doctor before continuing.

Drug Therapies

Some medications help promote weight loss, but there are no drugs to cure obesity. Weight loss medications should be used in addition to diet, exercise, and other lifestyle modifications. Many of these drugs are available by prescription only and some have serious side effects.

Over-the-counter Medications

Orlistat (Alli) -- The FDA has approved Alli as the only over-the-counter weight loss drug. It reduces the amount of fat your body can absorb from foods. Side effects include oily stools, flatulence, and diarrhea. Alli also blocks you body from absorbing some vitamins and nutrients, so you should take a multivitamin daily.

Prescription Medications

Sibutramine (Meridia) -- boosts metabolism, enhances energy level, and promotes a feeling of fullness. Side effects include dry mouth and insomnia; cannot be taken by people with a history of stroke, seizures, or heart, liver, or kidney diseases. Meridia is moderately effective; studies show that people who take Meridia lost about 10 pounds more than those who just followed a low-calorie diet.
Orlistat (Xenical) -- reduces the absorption of fat from foods; side effects include oily stools, flatulence, and diarrhea. Recently approved for over-the-counter sale in the U.S.
Phentermine -- suppresses appetite; serious potential side effects include pulmonary hypertension and heart valve defects. Phentermine is similar to an amphetamine and should not be taken by people with high blood pressure, heart disease, glaucoma, or those taking antidepressant medications

Surgical Procedures

Bariatric or weight-loss surgery may be considered in cases where people are severely obese and lifestyle changes have not worked. Physicians carefully select individuals for surgery, and patients must undergo psychological testing and counseling. Bariatric surgery reduces the amount of food that can be taken into the stomach. People who have had bariatric surgery must be monitored by their doctor afterward to make sure they get enough essential nutrients. Procedures include:

Roux-en Y procedure (gastric bypass) -- permanently reduces the size of the stomach; vomiting is the most common side effect
Gastric banding -- An adjustable silicone band is placed around the stomach, decreasing the amount of food that can be eaten. The band can be adjusted or removed.

Complementary and Alternative Therapies

Diet

Diet plans are enormously popular. They range from traditional low-fat, high-carbohydrate diets to high-protein, high-fat, low-carbohydrate diets. The truth is, no specific diet works for everyone, and no diet works without the other essential components of weight loss -- exercise and stress management.

The U.S. Department of Health and Human Services says a healthy diet

Emphasizes fruits, vegetables, whole grains, and fat-free or low-fat dairy products
Includes lean meats, poultry, fish, beans, eggs, and nuts
Is low in saturated fats, trans fats, cholesterol, salt, and added sugar

Among many weight-loss plans available, the ones that generally result in a balanced diet include the Weight Watchers plan, the South Beach Diet, and the American Heart Association No Fad Diet. Beware of diets that promise quick, substantial weight loss; they often don't contain enough of the nutrients your body needs to stay healthy, and you're more likely to go off the diet and engage in binge eating, gaining the weight back. Weight loss of about 1 to 2 pounds per week is considered safe and sustainable. Before attempting any diet, it is important to consult a healthcare practitioner to determine which plan is right for you.

Nutrition and Supplements

Most evidence for using these supplements in weight loss is either scant or mixed. None of these supplements will work for significant weight loss without changes to diet and exercise habits. Talk to your healthcare provider before using these supplements.

5-Hydroxytryptophan (5-HTP) (600 - 900 mg per day) -- 5-HTP is thought to reduce hunger cravings by boosting serotonin levels in the central nervous system, which may reduce appetite and lessen food cravings. However, 5-HTP has been associated with eosinophilia myalgia syndrome (EMS), a rare and potentially fatal blood disorder, although it isn't clear whether 5-HTP actually contributes to developing the disorder. In addition, people who take antidepressants or herbs and supplements with antidepressant effects (such as St. John's wort and SAMe) should avoid 5-HTP. Talk to your doctor before taking 5-HTP.

Fiber -- may help lower insulin levels (insulin controls the amount of sugar in the blood) and help you feel fuller.

Conjugated linoleic acid (CLA) -- Preliminary human and animal studies suggest that CLA may help control weight by reducing body fat and enhancing lean body mass. However, the benefit appears to be slight, there is some question as to whether CLA can increase insulin resistance in overweight people (a precursor to developing diabetes), and studies show mixed results for weight loss.

Zinc (15 - 20 mg per day) -- may increase lean body mass and decrease or keep stable the amount of fat. The reason may be that zinc increases levels of leptin, a hormone in the body that helps you feel full.

Chitosan (1,500 mg three times per day) -- Chitosan is a fiber-like supplement made from the shells of crustaceans such as shrimp and crab. While some studies have found that chitosan (in addition to a low-calorie diet) reduces weight, it is unclear whether the supplement itself, the low-calorie diet, or a combination of both led to the weight loss. Other studies have shown mixed results.

Pyruvate (22 - 44 g per day) -- Pyruvate is a substance that occurs naturally in the body, where it is converted to lactic acid. There is some evidence that it may help reduce body fat, possibly by increasing the body's metabolic rate. Other studies show no effect.

Hydroxycitric acid (HCA) (2.5 g per day) -- This substance, extracted from the fruit Garcinia cambogia, is similar to citric acid (found in oranges and citrus fruits). In test tubes, HCA stops carbohydrates from being stored as fat, and some animal tests indicate HCA can suppress appetite. However, studies in humans show mixed results.

7-keto or 7-keto-DHEA (3-acetyl-7-oxo-dehydroeplandrosterone) (100 mg two times per day) -- 7-keto is a substance related to DHEA, a substance in the body that is the precursor to male and female hormones. DHEA has been studied as a weight-loss supplement, but results are mixed and there is some concern over DHEA's hormone-like effects on the body. One preliminary trial suggested that 7-keto may help enhance weight loss for people who are already dieting and exercising, without risk of the side effects of DHEA (7-keto is not converted to hormones in the body). However, more studies are needed to determine whether 7-keto has any real effect on weight loss. People who have had or are at risk of hormone-related cancers should not take 7-keto without their doctor's supervision.

Chromium (600 mcg per day) -- Chromium or chromium picolonate is a popular supplement among bodybuilders and those trying to lose weight and build more lean muscle mass. However, results from scientific studies have been mixed, and its effects are small compared to those of exercise and a well-balanced diet. Chromium may improve blood sugar (also a risk factor for heart disease), particularly in those with diabetes and glucose intolerance, but should not be taken for that purpose without a doctor's supervision. In addition, large doses of chromium can cause kidney damage.

Glucomannan (1 g three times per day, 1 hour before each meal) -- Glucomannan is a kind of insoluble fiber that appears to reduce blood sugar levels and may help to promote weigh loss. People with diabetes should not take glucomannan without their doctor's supervision.

Herbs

Psyllium (Plantaginis ovatae) -- Psyllium, a kind of soluble fiber, may reduce hunger cravings by making you feel full. For this reasons, incorporating psyllium and other sources of fiber into your diet may aid weight loss.

Green tea (Camellia sinensis) -- Researchers have theorized that polyphenols (chemical substances found in plants that have antioxidant properties, protecting cells in the body against damage) found in green tea extract may boost metabolism and help burn fat. However, studies have shown mixed results so far. In addition, the extracts used in the studies have contained caffeine, which could be responsible for increasing metabolism and promoting weight loss. If you are sensitive to caffeine or have anxiety or heart problems, you may want to limit how much green tea you consume.

Guggul (Commiphora mukal, 25 mg of guggulsterones three times per day) -- a common ingredient in several Ayurvedic medicines used to treat obesity. Studies suggest that overweight people who take these Ayurvedic remedies lose slightly more weight compared to those who do not take them. Guggul can cause mild diarrhea and nausea, and may interact with the following medications: blood-thinning drugs (anticoagulants), birth control pills, thyroid hormone, tamoxifen, and estrogens. People who take these medications should not take guggul. In addition, people who have or have had hormone-sensitive cancers (breast, ovarian, or prostate cancer) should not take guggul.

Cayenne or capsaicin (Capsicum frutescens, 6 - 10 g per meal) -- Preliminary evidence indicates that capsaicin (the substance that makes chili peppers taste hot) may reduce hunger and help the body burn fat, particularly when eating a high-fat diet. More research is needed to confirm these early findings, however.

Hoodia (Hoodia gordonii) -- A number of media reports on hoodia have suggested it could be an effective weight-loss supplement. However, the only evidence that exists is a single, unpublished study funded by the manufacturer of the supplement, so no one knows whether hoodia works or even whether it is safe. In addition, news reports now suggest that most hoodia supplements on the market today contain little if any of the actual herb. Until more research is done and trusted sources exist to provide the herb, hoodia is best avoided.

Homeopathy

Few studies have examined the effectiveness of specific homeopathic remedies, and there is no single or combination homeopathic remedy that will help all people lose weight. However, individualized homeopathic therapy can be designed to aid weight loss by addressing metabolism, digestion, and elimination. Before prescribing a remedy, homeopaths take into account a person's constitutional type -- your physical, emotional, and intellectual makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for an individual.

Acupuncture

Many studies have found both acupuncture and acupressure can improve weight loss slightly. Acupuncture is believed to promote weight loss by stimulating points on the body that boost serotonin levels. (Elevated serotonin levels are thought to suppress appetite.) One well-designed study found that people who received electrical acupuncture of the ear (auricular acupuncture) reduced their appetite.

Cognitive Behavioral Therapy

Besides changing diet and exercise habits, successful weight loss often requires additional behavioral adjustments to keep the weight off. That might include setting reasonable weekly or monthly goals -- how much exercise or how much weight loss is desired, for instance -- and finding ways to reward yourself for successes that don't involve food. Working with both a dietician and a behavioral specialist can help you put these practices into play.

It also helps to reduce the stress that leads to overeating by practicing relaxation exercises, such as yoga, meditation, or tai chi.

Finally, it is hard to lose weight without support. Support groups such as Overeaters Anonymous or Weight Watchers can help you stay focused on your goals and allow members to share success and encourage each other.

Hypnosis

Although studies are mixed, some evidence indicates that hypnosis (especially when used in combination with cognitive behavioral therapy, exercise, and a low-fat diet) may help overweight or obese people lose weight.

Other Considerations

Pregnancy

Pregnant women should not take any herbal remedies or over-the-counter or prescription medications for weight loss.

Obese women who become pregnant are at an increased risk for the following:

Gestational diabetes -- a diabetic condition that appears during pregnancy and usually goes away after the birth of the baby
High blood pressure
Preeclampsia -- a potentially fatal condition causing high blood pressure, fluid retention, and protein in the urine; may cause abdominal pain and vomiting
Caesarean sections
Fetal distress -- a condition in which the baby does not receive enough oxygen

Prognosis and Complications

People who are overweight or obese increase their risk for developing the following conditions:

Type 2 diabetes
High blood pressure
Coronary artery disease
High cholesterol
High levels of triglycerides (fat) in the blood
Heart failure
Respiratory problems (such as sleep apnea)
Circulatory problems (such as varicose veins)
Gallbladder disease
Breast cancer (after menopause) and endometrial cancer
Prostate cancer
Colorectal cancer
Osteoarthritis

Eating and exercise habits are hard to change. Many people are able to lose at least 20 pounds with diet and exercise plans, but only about 10 - 20% can maintain that weight loss for a long period of time. Losing just 15 - 20 pounds, however, can reduce the risk of serious complications, such as diabetes and heart failure, by 10 - 25%.

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Review Date:
3/24/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

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Kidney stones

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

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Diagnosis
Treatment
Medications
Other Treatments
Complications
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Research:

Patients who have the most common type of gastric bypass surgery, the Roux-en-Y, are at increased risk for kidney stones, beginning 6 months after surgery, according to a study published in 2006.

Causes of Kidney Stones:

Calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of this imbalance is unknown.
Having acidic urine or too much uric acid in the body leads to the formation of uric acid stones.
Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes.
Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Treatments:

In about 85% of patients, the kidney stones are small enough that they pass through normal urination, usually within 2 - 3 days.
Certain medications can prevent recurrence of stones in people who are at high risk.
Extracorporeal shock wave lithotripsy (ESWL) is a technique that uses sound waves (ultrasound) to break up simple stones in the kidney or upper urinary tract. The shock waves are delivered from outside the body.
Surgery may be necessary if the stone or stones are too big to pass, and cannot be broken down through ESWL.
A change of diet and increased drinking of fluids, especially water, will help prevent a recurrence.

Introduction

Kidney stones are hard, solid rocks that form in the urinary tract. In many cases, the stones are very small and can pass out of the body without any problems. However, if a stone (even a small one) blocks the flow of urine, excruciating pain may result, and prompt medical treatment may be needed.

The process of urination begins in the kidneys. The kidneys filter out fluids and waste from the body, producing urine. The two kidneys are located deep behind the abdominal organs, below the ribs and toward the middle of the back.

Each kidney contains over a million nephrons. These are the tiny filtration units of the kidney.
Each nephron is composed of a tiny group of blood vessels (a glomerulus) enclosed in a funnel-like structure called Bowman's capsule.
Each glomerulus filters waste products, water, and salts out of the liquid part of the blood (plasma) that has entered the kidney.
About 1% of the plasma is converted into urine. The rest returns into the blood to prevent dehydration. Urine is primarily made of acids, urea, and creatinine (nitrogen compounds).
Urine passes from Bowman's capsule into tiny tubules, which lead to large collecting tubes in the center of the kidney. As the urine passes through this network, it becomes more concentrated.
Urine then flows from the kidney through thin tubes called ureters into the bladder.
The bladder's stretchy walls expand to store the incoming urine until it leaves the body through a tube called the urethra.

The kidneys are responsible for removing wastes from the body, regulating electrolyte balance and blood pressure, and stimulating red blood cell production.

Click the icon to see an image of the urinary tract.

Occasionally, various salts build up on the inside surfaces of the kidney and form crystals. Eventually these crystals become large enough to form stones in the kidney, a condition called nephrolithiasis. Kidney stones (renal calculi) may also form in the ureter or the bladder. Combinations of minerals and other chemicals, some derived from a person's diet, make up the salts in these stones.

Click the icon to see an image of the kidney stones.

Calcium Stones. About 70 - 90% of all kidney stones are made of calcium, usually combined with oxalate, or oxalic acid. A number of common vegetables, fruits, and grains contain oxalate.

About 6% of calcium stones are made of calcium phosphate (called brushite).

Uric Acid Stones. Uric acid is responsible for close to 10% of kidney stones. It is the breakdown product of purines, nitrogen compounds found in our bodies and in certain foods. The breakdown of purines to uric acid occurs in the liver, and from there uric acid enters the bloodstream, most of it passing into the kidneys. From the kidneys, uric acid leaves the body in the urine. Often, uric acid stones occur with calcium stones.

Struvite Stones. Struvite stones are made of magnesium ammonium phosphate. They are almost always associated with certain urinary tract infections. Worldwide, they make up to 30% of all kidney stones. In the United States, however, less than 15% of all stones are struvite. Most struvite stones occur in women. The rate of these stones may be declining in America, perhaps because of better control of urinary tract infections.

Cystine Stones. A build-up of the amino acid cystine, a building block of protein, causes 1% of kidney stones in adults and up to 8% of stones in children. The tendency to form these stones is inherited. Cystine stones are marked by rapid growth and recurrence, which, if not treated promptly, can eventually lead to kidney failure.

Xanthine Stones. Other kidney stones are composed of xanthine, a nitrogen compound. These stones are extremely uncommon and usually occur as a result of a rare genetic disorder.

Click the icon to see an animation about kidney stones.

Causes

The key process in the development of kidney stones is supersaturation.

The urine carries salts, including calcium oxalate, uric acid, cystine, or xanthine.
These salts can become extremely concentrated if there is not enough urine, or if unusually high amounts of crystal-forming salts are present.
When salt concentration levels reach the point at which they no longer dissolve, these salts form crystals.

Different factors may be involved in either reducing urine amount, or increasing the levels of the salts.

Deficiencies in Protective Factors. Normally, urine contains substances that may protect against stone formation, including:

Magnesium
Citrate
Pyrophosphate
Enzymes

These substances:

Allow salt in the urine to be at higher-than-normal concentrations without forming crystals
Prevent crystal formation
Coat the crystals and prevent them from sticking to the surface of kidney tubes

Not having enough of these protective substances can cause stones.

Changes in the Acidity of the Urine. Changes in the acid balance of the urine can affect stone formation.

Uric acid and cystine stones mainly form in acidic urine.
Calcium phosphate and struvite stones increase in alkaline urine.

Factors that Bind Crystals to the Kidney Tubules. Researchers are studying the cells lining the kidney tubules in order to understand how and why early crystals bind to the tubes long enough to form stones. Under investigation are elevated levels of substances that either cause crystals to stick to the tubes or deficiencies in those that prevent them from sticking.

In general, calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of calcium stones is not known, and the condition is then called idiopathic nephrolithiasis. Research suggests that nearly all stones result from problems in the breakdown and absorption of calcium and oxalate. Genetic factors may play a role in about half of these cases. A number of medical conditions and drugs can also affect digestion and intestinal absorption.

Excess Calcium in the Urine (Hypercalciuria). Hypercalciuria (too much calcium in the urine) is responsible for as much as 70% of calcium-containing stones. A number of conditions may produce hypercalciuria. Many are due to genetic factors, but most cases are idiopathic (due to unknown causes).

The following can lead to hypercalciuria and calcium stones:

Too much calcium absorption in the intestines: In most of these conditions, genetic factors lead to increased calcium absorption in the intestine. Researchers are investigating a possible defective gene that regulates calcitriol, a form of vitamin D, which, in excess levels, may increase intestinal absorption of calcium.
Excessive chloride: Chloride has a negative charge, and calcium has a positive one, so they balance each other in the body. Excess chloride may lead to excess calcium. A gene known as CLCN5, which regulates chloride in the urine, is defective in many patients with calcium stones.
Renal calcium leak: In this condition, the filtering processes in the kidney fail, causing an increase of calcium in the urine.
Excessive sodium: High urinary levels of sodium result in increased levels of calcium. Certain defects in the kidney tubules transport system, which cause imbalances in sodium and phosphate, can lead to high calcium levels in the urine. A diet high in salt can also produce this effect.

Excess Oxalate in the Urine (Hyperoxaluria). Oxalate is the most common stone-forming compound. Excessive oxalate in the urine (hyperoxaluria) is responsible for up to 60% of calcium stones and is a more common cause of stones than too much calcium in the urine.

Hyperoxaluria can be either primary or secondary.

Primary hyperoxaluria is an inherited disorder in which too much oxalate in the urine is the main problem.
Secondary hyperoxaluria results from specific conditions that cause high levels of urinary oxalate.

Secondary hyperoxaluria is usually caused by too much dietary oxalates (found in a number of common vegetables, fruits, and grains) or by problems in the body's breakdown of oxalates. Such defects may be due to various factors:

Severe vitamin B6 deficiencies (usually due to genetic disorders)
Deficiencies in Oxalobacter formigene, an intestinal bacteria that breaks down oxalate
Short bowel syndrome, a condition that makes the intestines unable to properly absorb fat and nutrients; calcium may bind to unabsorbed fat instead of oxalates, which causes a buildup of oxalate
Androgens (male hormones)

Female hormones (estrogens) actually lower the risk of hyperoxaluria. Estrogen may help prevent the formation of calcium oxalate stones by keeping urine alkaline, and raising protective citrate levels.

A study published in 2006 found that patients who undergo the most common gastric type of bypass surgery, the Roux-en-Y, were at increased risk for calcium oxalate kidney stones, beginning 6 months after surgery. The study found that patients who underwent the procedure developed hyperoxaluria, and the condition was common 12 months after surgery. The authors also noted an increased number of kidney stone incidents in this patient group.

Excessive Calcium in the Bloodstream (Hypercalcemia). Hypercalcemia generally occurs when bones break down and release too much calcium into the bloodstream. This is a process called resorption. It can occur from a number of different diseases and events:

Hyperparathyroidism: Overactive parathyroid glands cause about 5% of calcium stones. People with this disorder have at least a 20% chance of developing kidney stones. Women are more likely to have this disorder than men.
Immobilization: Lack of movement can lead to kidney stones.
Renal tubular acidosis: This disorder causes acidic and alkaline imbalance. Renal tubular acidosis not only increases calcium levels in the bloodstream but also reduces protective citrate levels.

Hyperuricosuria is a condition of high levels of uric acid in urine. It occurs in between 15 - 20% of people (mostly men) with calcium oxalate stones. Urate, the salt formed from uric acid, creates the center of a crystal (nidus), around which calcium oxalate crystals form and grow. Such stones tend to be severe and recurrent. They appear to be strongly related to a high intake of protein. (Hyperuricosuria also plays a major role in some uric acid stones.)

Low Urine Levels of Citrate (Hypocitraturia). Citrate is the main substance in the body that is responsible for removing excess calcium. It also blocks the process that turns calcium crystals into stones. Low levels of citrate in the urine (hypocitraturia) is a significant risk factor for calcium stones. In addition, hypocitraturia also increases the risk for uric acid stones. This condition most likely contributes to about a third of all kidney stones.

Many conditions can reduce citrate levels. Some causes include:

Renal tubular acidosis
Potassium or magnesium deficiency
Urinary tract infection
Kidney failure
Chronic diarrhea

Often, however, the cause of hypocitraturia-related stones is unknown.

Low Levels of Other Stone-Blocking Compounds. Several other compounds in the urine, including magnesium and pyrophosphate, also prevent the formation of calcium stones. If any of these compounds are lacking, stones may develop.

Nanobacteria Infection. Nanobacteria are tiny infectious organisms that can pass from the blood into urine. They coat themselves with mineral deposits that resemble the composition of kidney stones. Cells infected with these bacteria develop mineral deposits on the inside and outside. Researchers believe that nanobacteria may form the cores of the kidney stones in many people.

Human body tissues, certain foods, and certain alcoholic drinks contain substances called purines. Purine-containing foods include dried beans, peas, and liver. When the body breaks down purines, it produces uric acid. The presence of a certain level of uric acid in the body is normal.

The following conditions are usually seen in patients with uric acid stones:

Too much acid in the urine for a long period (the most important cause of uric acid stones)
Lower than normal amounts of urine produced.
Hyperuricosuria, a metabolic disorder that leads to high levels of uric acid in the urine

Note: Hyperuricosuria can also trigger calcium stones. Therefore, a combination of calcium and uric acid stones may be present in patients with hyperuricosuria.

A number of conditions and other factors may contribute to, or cause, uric acid stones:

Gout: Uric acid and other kidney stones develop in up to 25% of patients with primary gout, a painful form of arthritis that occurs when uric acid in the blood forms crystals in one or more joints.
Diabetes: New research has shown that people with type 2 diabetes have highly acidic urine that can lead to kidney stones, particularly uric acid stones. The findings were published in the May 2006 Journal of the American Society of Nephrology.
Insulin resistance: People with insulin resistance are at an increased risk for uric acid stones. The reason is unknown but may be related to the transport of certain salts through the kidneys. This transport changes in patients with insulin resistance.
Kidney abnormalities: Kidney problems that reduce the production of ammonia, particularly in people with diabetes or insulin resistance, may lead to uric acid stones.
Genetic factors: Genetic factors can increase a person's risk for uric acid stones.
Hypocitraturia: Hypocitraturia is a low amount of citrate in the urine.
Diet: Eating too much animal protein increases the risk of forming uric acid stones.

Other risk factors include:

Certain medications (chemotherapy drugs, diuretics, and salicylates)
Binge drinking
Not eating for long periods of time (fasting)
Lead poisoning
Blood cancers (leukemia, multiple myeloma, and lymphomas)
Some rare types of anemia (low levels of red blood cells in the blood)
Chronic diarrhea

Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes. These enzymes raise the concentration of ammonia in the urine. Ammonia makes up the crystals that form struvite stones. The stone-promoting bacteria are usually Proteus, but may also include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci. Women are twice as likely to have struvite stones as men.

Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Causes of Cystine Stones. Cystine stones develop from genetic defects that cause abnormal transport of amino acids in the kidney and gastrointestinal system leading to a build-up of cystine, one of these amino acids. Researchers have identified two genes responsible for this condition: SLC3A1 and CLC7A9.

Causes of Xanthine Stones. In some cases, xanthine stones may develop in patients being treated with allopurinol for gout.

Risk Factors

Kidney stones are one of the most common disorders of the urinary tract. They are an ancient health problem. Evidence of kidney stones has been found in an Egyptian mummy estimated to be more than 7,000 years old.

An estimated 1.3 million Americans seek medical help for kidney stones each year. At this time, studies suggest kidney stones affect over 5% of Americans and that the rate has increased since the 1970s, perhaps because of increases in animal and dietary protein intake.

Men. The risk of kidney stones increases in a man's 40s and continues to rise until age 70. Caucasian men are at higher risk than other groups.

Women. The risk of kidney stones peaks in a woman's 50s. In younger women, stones are more likely to develop during the late stages of pregnancy. Pregnant women tend to have a higher calcium intake, but their kidneys do no handle the calcium as well as they did prior to pregnancy. Kidney stones are still a rare occurrence during pregnancy, however, affecting only 1 in 1,500 pregnancies.

Risk Factors in Children. Stones in the urinary tract in children are usually due to genetic factors. Most of the time, the cause is too much calcium in the urine (hypercalciuria). Deformities in the urinary tract pose a significant risk for kidney stones in children. Children with low birth weight who need to be fed intravenously are also at risk for stones.

Obesity and weight gain are both associated with an increased risk of kidney stones.

Men who weigh more than 220 lbs are 44% more likely to develop kidney stones than men who weigh less than 150 lbs.
Women who are obese are 90% more likely to develop kidney stones than women with a lower body mass index (BMI).

Higher BMIs and larger waist circumferences are both risk factors for kidney stones. Researchers think that there may be a link between fat tissue, insulin resistance, and urine composition. People with larger body sizes may excrete more calcium and uric acid, which increase the risk of kidney stone formation.

A family history of kidney stones increases one's risk for the condition. Researchers are looking into markers or other factors that might predict kidney stones in relatives, although none has yet been clearly identified. One report found that among the siblings of patients with calcium stones, sisters with higher urinary calcium levels and more acidic urine were more likely to develop stones. Brothers with high urinary calcium, low urinary potassium, and older age were more likely to have the problem. A family history of gout may also make a person vulnerable to stones.

According to a 2003 study of American ethnic groups, Caucasians have the highest incidence of kidney stones (5.9%) followed by Mexican Americans (2.6%). African-Americans have the lowest risk (1.7%).

Dietary factors, minerals in local water, or both may contribute to geographic differences that have been observed in the occurrence of kidney stones. Studies have reported the highest occurrence of kidney stones in the southern region of the United States and the lowest in the west. One study suggested that the higher risk may be due to a higher rate of high blood pressure in the southern states and certain dietary habits, particularly lower intake of magnesium and low use of calcium supplements.

Specific Foods. In general, certain foods increase the risk for stones only in people who have genetic or medical vulnerability. People whose diets are high in animal protein and low in fiber and fluids may be at higher risk for stones. A number of foods contain oxalic acid, but there is no proof that such foods make any major contribution to calcium oxalate stones in people without other risk factors. However, several studies have shown that increasing dietary calcium and restricting salt, animal protein, and foods rich in oxalate can help prevent calcium oxalate stones from returning.

Stress. One study reported that people who had a major, stressful life experience were more likely to develop stones than those who had not. Some experts speculate that this increased risk may be due to a hormone called vasopressin, which is released in response to stress. Vasopressin also increases the concentration of urine.

Sleep Position. Sleeping in the same position consistently may influence risk. A 2001 study reported that in people who had a history of kidney stones, recurrences tended to occur on the same side that people slept on. An earlier study suggested that people who had kidney stones were more apt to sleep on their stomachs. Movement during sleep did not appear to affect the risk.

Being Bedridden. Any medical or physical condition that keeps a person in bed or immobile increases blood levels of calcium from bone breakdown, thereby posing a risk for stone formation.

Gout. Patients with gout are at a high risk of uric acid stones. These patients have very acidic urine, and a 2002 study suggested that the two disorders may have a common source.

High Blood Pressure. Persons with high blood pressure are up to three times more likely to develop kidney stones. It is not entirely clear whether having high blood pressure increases the risk for a stone, whether stones lead to high blood pressure, or if there is an action linking both.

Inflammatory Bowel Disease: Crohn's disease and ulcerative colitis cause problems in absorption of substances in the intestines. These problems significantly increase the risk for kidney stones, particularly in men.

Urinary Tract Infections (UTIs): Urinary tract infections are almost always the cause of struvite stones.

Hyperparathyroidism: The parathyroid glands regulate calcium levels in the body through the parathyroid hormone. In hyperparathyroidism, one or more of these glands makes too much parathyroid hormone. Some people with hyperparathyroidism develop kidney stones. Surgery to remove the hyperactive parathyroid gland in such patients reduces the risk for stone formation, but the risk still remains high for some time after surgery.

Other Medical Conditions. Kidney disease, chronic diarrhea, certain cancers (such as leukemia and lymphoma), and sarcoidosis put people at higher risk for stones.

AIDS medications. Over 10% of persons with AIDS who take the medicine indinavir develop stones. The risk is even higher in patients with AIDS who also have hepatitis B, hepatitis C, or hemophilia, as well as those who are very thin or who take the antibiotic combination TMP-SMX. In one study of persons with AIDS who took a combination of indinavir, zidovudine, and lamivudine, 36% developed kidney stones.

Other Drugs. Kidney stones are a rare side effect of thyroid hormones and loop diuretics (drugs that increase urination). In fact, diuretics are also used to prevent calcium stones. Certain cancer chemotherapies can also cause kidney stones. Long-term use of medications, such as antacids, which change the acidic content of urine, may increase the risk for kidney stones.

Symptoms

In many cases, kidney stones do not produce symptoms. However, if a stone becomes stuck in the ureter (the thin tube between the bladder and the kidney), symptoms can be very severe. Often, they vary depending on the stone's location and its progress.

Kidney stone attacks tend to be most common late at night or in the early morning, possibly because of minimal urine output or constriction of the ureters during the early morning hours. Kidney stone attacks are least common during the late afternoon

Pain usually begins abruptly on one side and then usually continues as intense, constant pain. (In some cases it persists for a few minutes, disappears, and then returns after about 10 minutes.)
The patient cannot become comfortable and usually stands, sits, paces, or reclines in a vain search for a position that will bring relief.
If the stone is in the kidney or upper urinary tract, the pain usually starts in one flank area (to the side of the back near the waist). It typically moves to the groin as the stone passes down.
If the stone is too large to pass easily, the pain follows the muscle contractions in the wall of the ureter as they try to squeeze the stone along into the bladder.
Nausea and vomiting may occur.
Blood in the urine may be present.
As the stone passes down the ureter closer to the bladder, a person may feel the need to urinate more often or a burning sensation during urination.
If fever and chills accompany any of these symptoms, an infection may be present.

The size of the stone does not necessarily predict the severity of the pain; a very tiny crystal with sharp edges can cause intense pain while a larger round stone may not be as distressing. Struvite stones can often occur without symptoms.

Diagnosis

The doctor will perform a physical exam. This includes pressing against abdominal areas for tender locations that might indicate the presence of the stone.

The patient's age is a significant factor. Kidney stones that occur in children and young patients are more apt to result from inherited problems that cause cystine, xanthine, or, in some cases, calcium oxalate stones. In adult patients, calcium stones are most common.

A medical history may help predict which crystal has formed the stone. The doctor will need to know the following:

Any previous kidney stone attacks
Histories of cancer, sarcoidosis, or small bowel disease
Any medications being taken, including non-prescription substances, particularly high doses of vitamins D or C and calcium-containing antacids

Many conditions can cause symptoms similar to kidney stones. Usually the diagnosis is easily made because of the specific nature of the symptoms, but it is not always clear. Urinary tract infections can cause similar, but usually less intense, pain. In fact, infection may be present with a kidney stone. Other causes of pain that may mimic kidney stones include:

Gallstones
Diverticulitis (infection or irritation of abnormal pockets in the intestines)
Intestinal blockage
Blood clots
Irritable bowel syndrome
Appendicitis
Stomach ulcers
Hiatal hernia (when the upper part of the stomach bulges into the chest, through an opening in the diaphragm)
Pancreatitis (inflammation of the pancreas)
Hepatitis
Pelvic inflammatory disease
Inflammatory bowel disease (Crohn's and colitis)
Heart attack

Various imaging techniques are helpful in determining the presence of kidney stones. The best approach uses spiral (or helical) computed tomography scans. If it is not available, the patient will need ultrasound or standard x-rays. If no stones show up, but the patient has severe pain that suggests the presence of kidney stones, the next step is an intravenous pyelogram.

X-Rays. A standard x-ray of the kidneys, ureters, and bladder may be a good first step for identifying many stones, since many are visible on x-rays. Calcium stones can be identified on x-rays by their white color. Cystine crystals can also show up on x-rays.

Spiral (or Helical) Computed Tomography. A type of computed tomography (CT) scan, called a spiral or helical CT scan, is currently the best method for diagnosing stones in either the kidneys or the ureters. This test is fast, does not require instruments or foreign chemicals to enter the body, and provides detailed accurate images of even very small stones. If stones are not present, a spiral CT scan can often identify other causes of pain in the kidney area. It is better than x-rays, ultrasound, and intravenous pyelogram -- the previous standard test for detecting kidney stones. Experts hope spiral CT will eventually be able to identify the chemicals present in a stone.

Ultrasound. Ultrasound can detect clear uric acid stones and obstruction in the urinary tract. It is not useful for finding very small stones, but some research indicates that it may be a useful first diagnostic step in the emergency room to help predict the likelihood of a stone, including suspected stones in children.

Intravenous Pyelogram. With intravenous pyelogram (IVP), the doctor injects a special dye into the patient. A technician will then take x-rays as the dye enters the kidneys and travels down the urinary tract. IVP is invasive but, until recently, was the most cost-effective method for detecting stones. Where it is available, spiral CT is now preferred, since it gives a faster diagnosis, is more accurate, is safer, and is similar in cost.

In any case, IVP should not be used on patients with kidney failure. There is also a risk for an allergic reaction to standard dyes, although newer less allergenic ones are becoming available.

In the procedure intravenous pyelogram (IVP), the patient is injected with dye. X-rays are taken as the dye travels through the urinary tract. This procedure is done to confirm the presence of kidney stones, although some stones may be too small to see.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) techniques are showing promise for diagnosing urinary tract obstruction but do not yet accurately reveal small stones, or ones that do not cause a blockage. Because no radiation is involved with MRI, however, it may prove to be a good option for pregnant women.

Urine samples are required to evaluate features of the urine, including its acidity and the presence of:

Red or white blood cells
Infection
Crystals
High or low levels of chemicals that inhibit or promote stone formation

Clean-Catch Urine Sample for Culturing. After determining that a kidney stone is present, the health care provider usually gives the patient a collection kit, including filters, to try to catch the stone or gravel as it passes out. The urine may also be tested (cultured) for the presence of infection-causing organisms. A clean-catch urine sample is almost always required for culturing. To provide a clean catch, do the following:

First, wash your hands thoroughly, then wash the penis or vulva and surrounding area four times with downward strokes, using a new soapy sponge each time.
Begin urinating into the toilet and stop after a few drops.
Position the container to catch the middle portion of the urine stream. Ideally, this urine will contain only the bacteria and other evidence of the stone.
Urinate the remainder into the toilet.
Tighten the cap on the container securely, being careful not to touch the inside of the rim.

Click the icon to see an image of a calcium urine test.

Twenty-Four Hour Urine Collection. A 24-hour urine collection may be needed to measure urine volume and levels of acidity, calcium, sodium, uric acid, oxalate, citrate, and creatinine.

You should not change any of your usual eating or drinking patterns when performing this test.
Discard the first urination on the day of the test.
Afterward all urine passed over the next 24 hours is collected, including the first urination on the morning of day two.
A second 24-hour urine collection may be needed to determine if treatment is working or if the first analysis was not conclusive and the doctor suspects a less common stone, such as a cystine or xanthine stone.

Click the icon to see an image of a uric acid urine test.

Urine tests that are used to determine the specific chemical and biological factors causing the stone should be performed about 6 weeks after the attack, since the attack itself may change the levels of such substances, including calcium, phosphate, and citrate. It should be noted that calcium levels in the urine may be abnormal even in many people without stones. In addition, high urinary concentrations of calcium may pose a greater or lesser risk depending on age. (In one 2001 study, middle-aged adults with high urinary calcium concentrations had a much greater risk than older adults with high levels.)

The kidney stones obtained from the urine sample are examined under a microscope. The crystal formations are often specific enough so that the doctor is able to identify the substance causing the stone.

Calcium oxalate crystals are eight-sided, while calcium phosphate crystals tend to have irregular shapes.
Uric acid stones are sometimes described as pear-shaped or diamond-shaped.
Some struvite stones have very specific shapes commonly described as "coffin lids." Struvite crystals may also occur in a formation known as a staghorn, which can be large and damaging to the kidney.

Testing whether urine is acidic or alkaline helps to identify the specific type of stone. The levels of acidity or alkalinity in any solution, including urine, are indicated by the pH scale:

A pH value of 7.0 is neutral.
A solution with a low pH (below 7.0) is acidic. (A low pH favors uric acid and cystine stones.)
A solution with a high pH is alkaline. (A high pH favors calcium phosphate and struvite stones.)

A dipstick test for blood in the urine (called hematuria) is typically performed when patients appear in the emergency room with flank pain (the primary symptom of kidney stones). About a third of kidney stone patients, however, do not show blood in the urine, so other tests may be needed.

Blood Tests for Stone Factors. Blood and urine tests help determine what substances form the crystals. This allows the doctor to determine the appropriate treatment and preventive measures.

Blood tests may help determine blood levels of urea nitrogen, creatinine, calcium, phosphate, and uric acid for patients with known or suspected calcium oxalate stones. Doctors will usually schedule these tests about 6 weeks after the attack, in order to measure these substances when the stone has been passed, and the patient has been stabilized. This is particularly true in patients with recurrent stones.

Parathyroid Tests. Tests to detect parathyroid hormone levels are given if the doctor suspects hyperparathyroidism, based on other signs and symptoms.

Tests for Infection. A test result that shows a high white blood cell count might indicate infection. Such results, however, could be misleading, since the number of white blood cells could also increase in response to the extreme physical stress of a kidney stone attack.

Tests for Metabolic Problems. About half of children with stones have an identifiable metabolic disorder, which increases their risk of stone recurrence five-fold. Experts argue whether tests for metabolic disorders are routinely needed once the stone composition has been determined. Studies suggest the following:

People with recurrent calcium stones have a wide range of irregular blood or urine test results, indicating a variety of possible metabolic disorders. For example, calcium stones in middle-aged women may be due to parathyroid abnormalities.
Calcium phosphate stones most likely result from renal tubular acidosis.
People with non-calcium stones generally have identifiable metabolic disorders.
Determining the stone composition may be sufficient for treatment, and may help avoid unnecessary metabolic tests.

Treatment

When tests show there is a kidney stone, the next step is to determine treatment. The patient should be admitted to the emergency room if they have severe vomiting, fever, or symptoms of infection.

Strong opioid painkillers, such as meperidine (Demerol), are often required for a severe kidney stone attack. However, doctors will usually not give such drugs until they confirm the presence of a kidney stone on an x-ray. In some cases, powerful nonsteroidal anti-inflammatory drugs (NSAIDs) may work just as well as opioids, and they have fewer side effects. However, they do take longer to work.

In about 85% of patients, the kidney stones are small enough that they pass through normal urination, usually within 2 to 3 days. In some cases, a stone may take weeks to months to pass, although pain usually goes away before that.

The patient should drink plenty of water (two to three quarts a day) to help move the stone along, and take painkillers as needed. The doctor usually provides a collection kit with a filter and asks the patient to save any passed stones for testing.

If the stone has not passed in 2 - 3 days, the patient will need additional treatments. In some severe cases, hospitalization may be necessary.

Specific procedures vary depending on the size of the stone or complexity of the situation. Noninvasive procedures are proving to be very beneficial in eliminating stones, and have largely replaced invasive surgeries.

For small stones that are lodged in the lower part of the ureter, ureteroscopy or shock wave lithotripsy are the procedures of choice.
For larger stones, ureteroscopy, percutaneous nephrolithotomy, and shock wave lithotripsy are all potentially useful. The choice of any of these procedures depends on a number of factors, including location of the stone and the presence of any problems that caused the stone in the first place.
In some complicated cases, standard open surgical procedures (called nephrolithotomy) may be required.

See "Other Treatments" section for more information on kidney stone surgery.


Stone Type	Diet and Lifestyle	Medications	Procedures
Calcium Oxalate	Plenty of fluids. (Choose water, lemon juice. Avoid grapefruit, apple, and cranberry juice.) Limit the amount of protein and salt in the diet. Increase fiber. Limit the amount of fats in the diet, particularly in people who have short bowel syndrome. Balance normal calcium intake with potassium- and phosphate-rich foods. Limit the amount of calcium in the diet (only in people who have genetic abnormalities that cause high intestinal absorption of calcium). Limit the amount of foods high in oxalates (only in patients with rare intestinal conditions that cause hyperoxaluria).	Diuretics ("water pills"), Citrate salts, phosphates, cholestyramine.	Lithotripsy, uteroscopy, percutaneous nephrolithotomy, open surgery.
Uric Acid	Plenty of fluids. (Choose water, blackcurrant juice. Avoid cranberry juice.) Increase calcium intake (be sure well-balanced with potassium and phosphates). Reduce protein and other foods with high-purine content.	Potassium citrate, sodium bicarbonate, allopurinol.	Lithotripsy, uteroscopy, percutaneous nephrolithotomy, open surgery.
Struvite stones	Plenty of fluids (water, cranberry juice). Reduce proteins.	Antibiotics to eliminate any infection. Acetohydroxamic acid (AHA) may be helpful in combination with antibiotics. In some cases, organic acids given through urinary tract.	May respond poorly to most lithotripsy procedures and require open surgery. Newer procedures may be helpful.
Cystine stones	Very high fluid intake (four quarts a day). Limit the amount of protein in the diet.	Alkalizing agents (such as bicarbonate). Sometimes d-penicillamine, tiopronine, or captopril useful for lowering cystine levels.	May respond poorly to most lithotripsy procedures and require open surgery. Newer procedures may be helpful.

Medications

Diuretics. Diuretics are medicines commonly used to treat high blood pressure and other disorders. They remove fluid and sodium from the body. Low doses of a class of diuretics known as thiazides are sometimes used to reduce the amount of calcium released by the kidneys into the urine. Thiazides include:

Hydrochlorothiazide (Esidrix, HydroDiuril)
Chlorothiazide (Diuril)
Trichlormethiazide (Metahydrin, Naqua)
Chlorthalidone (Hygroton)

However, thiazides also cause potassium loss, which reduces citrate levels and can increase the risk for stones. Patients taking thiazide pills should also take potassium citrate, to prevent citrate loss. Amiloride (Midamor) is a potassium-sparing diuretic, which may be used if a thiazide does not work.

Citrates. Citrate salts are often given to people with calcium oxalate or uric acid stones:

Potassium magnesium citrate is available over the counter. It is proving to be very beneficial in preventing kidney stones. In one study, potassium magnesium citrate reduced the risk for kidney stone recurrence by 85%.
Potassium citrate (K-Lyte, Polycitra-K, Urocit-K) is given as the only treatment to people with normal urine calcium levels. Between 70 - 75% of patients with recurrent stones have ongoing remission (no stone recurrence) with potassium citrate treatment. However, some people cannot tolerate potassium citrate because of side effects (stomach problems).
Magnesium citrate (Citroma, Citro-Nesia) may help people who develop calcium stones from impaired intestinal absorption due to short bowel disease.

None of these products should be used by people with struvite stones, urinary tract infections, bleeding disorders, or kidney damage. Patients who take citrate supplements containing potassium should not take any other medications that either contain this mineral or prevent its loss (such as so-called potassium-sparing diuretics). People with peptic ulcers should avoid citrate supplements, or discuss using non-tablet forms with their doctor.

Phosphates. Phosphates help reduce the breakdown of bone that releases calcium into the bloodstream. They are also involved in the kidney's reabsorption of calcium from the urine.

Phosphate compounds:

Neutral (nonacidic) sodium or potassium phosphate (K-Phos, Neutral, Neutra-Phos) is usually taken four times a day after meals to prevent kidney stones unless otherwise directed by the doctor. Diarrhea is a possible side effect.
Cellulose phosphate (Calcibind) is recommended only for severe hypercalciuria that is associated with recurrent calcium stones and is caused by excessive absorption of calcium from the intestines. However, this drug may increase oxalate levels and decrease magnesium levels, which can lead to different stones. Taking magnesium supplements and reducing dietary oxalates, calcium, and ascorbic acid may help offset these risks. Cellulose phosphate may also cause bloating.

Avoid acidic forms of phosphate, since they increase the risks for both hypocitraturia and hypercalciuria.

Cholestyramine (Questran, Questran Light) is a drug used to reduce cholesterol levels. However, it also binds with oxalate in the intestine, so it is also used to reduce high oxalate levels in urine (hyperoxaluria). The drug usually comes in a powder that is dissolved in liquid.

Bloating and constipation are common side effects of this drug. Cholestyramine also interferes with other medications, including digoxin (Lanoxin) and warfarin, and may contribute to calcium loss and osteoporosis. In order to prevent such interactions, take other drugs 1 hour before, or 4 - 6 hours after, taking cholestyramine.

Long-term use of cholestyramine may cause deficiencies of vitamins A, D, E, and K. Vitamin supplements may be necessary.

Sodium Bicarbonate. Patients whose persistently acidic urine causes uric acid stones may take sodium bicarbonate to reduce urine acidity. Patients taking sodium bicarbonate must test their urine regularly with pH paper, which turns different colors depending on whether the urine is acidic or alkaline. Too much sodium bicarbonate can cause the urine to become too alkaline. This increases the risk for calcium phosphate stones. Patients who need to reduce the amount of sodium they take in (as a result of other medical conditions) should not use sodium bicarbonate.

Potassium Citrate. Potassium citrate, which restores citrate to the urine, is useful for patients with high levels of uric acid in the urine.

Allopurinol. Allopurinol (Lupurin, Zyloprim) is very effective in reducing high levels of uric acid, and may be helpful for patients with uric acid stones. Allopurinol will not prevent calcium stones from forming. There is also a slight risk for the formation of xanthine stones with this drug. Side effects include diarrhea, headache, and fever. More severe complications include blood disorders that may produce fatigue, bleeding, or bruising. The drug may also increase the risk for cataracts.

About 2% of patients experience an allergic reaction to allopurinol that causes a rash. In rare cases, the rash can become severe and widespread enough to be life threatening. Allergic individuals who have experienced only a mild rash to sodium bicarbonate may be able to build up their tolerance for allopurinol by undergoing a desensitization process. In this process, patients start with small doses of allopurinol and gradually increase them, if no reaction develops.

Allopurinol reduces uric acid levels rapidly, so it may trigger an attack of gout in vulnerable people. To prevent this problem, patients taking allopurinol should also take a nonsteroidal anti-inflammatory drug (NSAID) for 2 or 3 months. Aspirin should not be taken, since it increases uric acid levels. Patients should discuss the appropriate NSAID choice with their doctor.

Before patients can receive any medical treatment for struvite stones, they must have surgery to completely remove the stones.

Antibiotics for Eliminating Infection. Persons with struvite stones receive ongoing treatment with antibiotics to keep the urine free of the bacteria that cause urinary tract infections. Careful follow-up and urine testing is extremely important. A high-pH urine indicates low acidity and an increased risk of infection.

Acetohydroxamic Acid (AHA). Acetohydroxamic acid (AHA or Lithostat) is beneficial when used with long-term antibiotics. AHA blocks enzymes that bacteria release, and has been effective in preventing stones even when bacteria are present. Side effects, however, can be severe. The drug reduces iron levels in the body, so anemia is a common problem. Patients may need to take iron supplements. Other side effects include nausea, vomiting, depression, anxiety, rash, persistent headache, and, rarely, small blood clots in the legs.

Experts recommend this drug only for patients with healthy kidneys who have chronic diseases caused by specific struvite-causing organisms.

Patients taking this medicine should avoid alcohol. Pregnant women should not take acetohydroxamic acid.

Organic Acids. Medical treatments to dissolve stones may be useful in patients who do not respond to other medications, or in combination with surgeries. Acidic urine dissolves struvite stones, so the doctor may wash the urinary tract with a solution of organic acids (such as Renacidin). Candidates for such washes must have sterile urine (no bacteria or other organisms in the urine) and healthy kidney function. In surgical patients, the wash is performed 4 or 5 days after the operation. The wash starts with saline (salt solution) for 1 - 2 days and, if there are no problems, the organic acid solution follows for another 1 or 2 days, until all stones dissolve. Regular urine tests are necessary to ensure that the bacteria do not return.

Aluminum Hydroxide Gel. An aluminum hydroxide anti-acid gel may reduce phosphate levels that are important in struvite stone formation, but it has a long-term risk of causing aluminum toxicity. Long-term reduction of phosphorus can also increase the risk for calcium oxalate stones. Experts recommend limiting phosphorus through a low-protein diet, rather than through the use of this gel.

The first-line treatment for cystine stones is increasing the alkalization of urine so the stones can dissolve. If alkalization fails, drug treatments may include d-penicillamine, alpha-mercaptopropionylglycine (tiopronine), or captopril. These medications lower cystine concentration.

Patients with cystine stones must drink plenty of fluids, much more than patients with other stones. The patients should drink at least four quarts of water over a 24-hour period.

Other Treatments

Surgery is usually needed if the stone is too large to pass on its own, if there are signs that the stone is growing, or if the stone is blocking the urine flow and causing a urinary tract infection or kidney damage.

Until recently, the procedure to remove a stone was a very painful, major surgery, requiring 4-6 weeks of recovery. Today, treatments for stones are much less invasive. Major surgery is performed in less than 2% of patients.

Stone removal procedures:

Extracorporeal shock wave lithotripsy (ESWL) is used for small stones (less than one centimeter, or slightly less than half an inch) that occur in the upper part of the ureter and do not pass on their own. One study indicated lithotripsy might even be safe and effective for patients whose stones are associated with malformed kidneys, although such patients are at higher risk for stone recurrence and should be carefully monitored.
Percutaneous nephrolithotomy (PNL). PNL can be used for very large stones in the upper urinary tract, when ESWL fails, for kidney transplant patients, or when the kidneys or surrounding areas are malformed. PNL is the preferred procedure for drug-resistant cystine stones, which are usually also resistant to shock wave therapy.
Ureteroscopy. For stones in the lower tract, ureteroscopy is generally the best procedure, although lithotripsy is also usually feasible and patients ordinarily prefer it.
Standard open surgery (nephrolithotomy) may be required if any of these procedures fail or are not appropriate, or in special cases, such as when the patient is very obese.

Most procedures are more effective for calcium and uric acid stones and less effective for struvite and cystine stones, although new techniques may be improving their effects on all stones.

Extracorporeal shock wave lithotripsy (ESWL) is a technique that uses sound waves (ultrasound) to break up simple stones in the kidney or upper urinary tract. ("Extracorporeal" means "outside the body," and "lithotripsy" means stone-breaking.) ESWL is not used for cystine stones. The procedure generally does not work for stones larger than three centimeters in diameter (which is slightly over an inch). There are several variations of ESWL. The following is a typical procedure:

Most ESWL procedures use some anesthesia, although they are often done on an outpatient basis.
The patient is positioned in a water bath. (In some procedures the patient lies on a soft cushion.)
The procedure uses ultrasound to generate shock waves that travel through the skin and body tissues until they hit the dense stones. (The doctor pinpoints the stone during treatment by using x-rays or ultrasound.)
The shock waves crush the stones into tiny sand-like pieces that usually pass easily through the urinary tract.
The shattered stone fragments may cause discomfort as they pass through the urinary tract. In such cases, the doctor may insert a small tube called a stent through the bladder into the ureter to help the fragments pass. This practice, however, has not proved to speed up passage of the stones in most cases and is not used routinely.

Extracorporeal shock wave lithotripsy (ESWL) is a procedure used to shatter simple stones in the kidney or upper urinary tract. Ultrasonic waves are passed through the body until they strike the dense stones. Pulses of sonic waves pulverize the stones, which are then more easily passed through the ureter and out of the body in the urine.

Success rates of ESWL range from 50 - 90%, depending on the location of the stone and the surgeon's technique and level of experience. Recovery time is short, and most people can resume normal activities in a few days.

Complications. Complications may include the following:

The most common complication is blood in the urine, which lasts for a few days after treatment. To reduce the chances of bleeding, doctors usually tell patients to avoid taking aspirin and other NSAIDs, which can promote bleeding, for 7 - 10 days before the treatment.
Bruising and minor discomfort due to the shock waves are common in the back or abdomen.
Sometimes the stone does not completely break up with one treatment, and additional treatments may be required. Inability to pass stone fragments may also be a particular problem in patients who have cysts or other kidney problems.
Higher risk for diabetes later. A 2006 study published in the journal Urology found that 17% of patients who received shock-wave lithotripsy developed diabetes later in life. The diabetes risk was related to the number and intensity of shocks.
Higher risk for hypertension (high blood pressure). The same study that linked ESWL to diabetes also showed that people who received shock-wave lithotripsy treatment were 47% more likely to develop high blood pressure than those who had their stones treated without surgery.

ESWL appears to be safe for children, although a 2001 study reported temporary damage in the kidney tubules after treatment. It is unclear if this complication has any long-term consequences. Experts recommend using the least amount of shocks and impact possible in young people. If more than one treatment is needed, there should be a waiting period of at least 15 days between treatments.

Percutaneous nephrolithotomy may be used when ESWL is not available or effective (such as if the stone is very large, in an inaccessible location, or is a cystine stone). It is also preferred over ESWL for stones that have remained in the ureter for more than 4 weeks.

It is more effective than ESWL for patients with severe obesity, and appears to be safe for the very elderly and the very young. Success rates are nearly 98% for kidney stones and 88% for ureteral stones. They may vary by the technique used and the specific patients. For example, success rates are slightly lower in children, although the procedure can be done safely in young patients. Long-term effects are unknown.

A typical procedure is as follows:

The surgeon makes a tiny incision in the back and creates a tunnel directly into the kidney.
The surgeon then inserts an instrument called a nephroscope through the tunnel.
The stone is located and removed. If it is large, it is destroyed using ultrasound, lasers, or other devices. The surgeon then removes the fragments. An advantage of percutaneous nephrolithotomy over ESWL is that the surgeon is able to remove the stone fragments directly, instead of relying on their natural passage from the kidney.
Generally, patients stay in the hospital for 5 or 6 days and may need a small device called a nephrostomy tube left in the kidney during the healing process.

Devices Used to Destroy Stones. For large stones, some type of energy-delivering device may be needed to break the stone into small pieces. They are referred to as intracorporeal lithotripsy devices (meaning stone breakers within the body). The device may be one of the following:

Ultrasound is currently the preferred method. It results in a stone-free rate of 94%. A rigid nephroscope delivers the ultrasound waves.
Pneumatic (compressed air) lithotripsy uses a probe that comes in direct contract with a stone. Compressed air causes a piston to collide rapidly with the probe, and the result is a "jackhammer" action against the stone, causing the stone to break up. This method, however, can send stone fragments into other parts of the urinary tract.
A more recent device uses a combination pneumatic probe and ultrasound, with stone-free rates of 80 - 89%. It may prove to be superior to ultrasound alone and be effective against stones of all types.
The holmium laser literally melts the stones and destroys up to 100% of stones of any composition. It uses a flexible nephroscope and has an excellent safety record. It should be used sparingly, however, with particular caution against large uric acid stones until more is understood about its effect. Another device, the erbium: YAG laser, although showing promise in lithotripsy, is not currently practical.

Complications. Complication rates are about 3%. Major complications occur in about 1% of cases. These complications may include scarring of the tissue, but studies indicate that it does not impair kidney function, even if the patient requires repeat surgery. There is also a risk for blood loss during and after the procedure, which, in some cases, can be significant.

Because the procedure requires large volumes of fluid, fluid overload is a potential problem, particularly in children or patients with heart disease.

In some cases, infection may result. Other complications may include a collapsed lung and injuries to areas outside the kidney (but within the operative area), such as the abdomen or chest.

Ureteroscopy may be used for stones in the middle and lower ureter. With the arrival of smaller instruments, this procedure can be done successfully in children as well. The procedure involves the following:

The patient receives a general anesthetic, though no incision is required for the procedure.
The surgeon passes a small fiberoptic instrument called a ureteroscope through the urethra and bladder into the ureter.
The surgeon locates the stone or stones.
The surgeon can remove smaller stones by grasping them with small forceps. A laser or pneumatic device breaks up large stones.
The surgeon may decide to leave a small tube, or stent, in the ureter for a few days after treatment, to help the lining of the ureter heal.

Complication rates range from 10 - 20%, with major problems occurring in up to 6% of patients. In some cases, large stones are not broken up into small enough pieces. This can result in blockage of the urinary tract and possible kidney damage.

Imaging tests, such as ultrasound or spiral CT, are useful within 3 months to check for residual stones, and a second procedure may be required. The risk of complications is highest when the procedure is performed by less experienced surgeons, or if stones are found in the kidney. The risk for perforation of the ureter increases the longer the procedure takes.

Open surgery involves incisions through the patient's flank and into the kidney. The surgeon will cool the kidneys using ice. X-rays during the procedure help locate the stone. At the beginning of the surgery, the surgeon will isolate the arteries supplying the kidneys, ensuring they are not harmed during the surgery. The surgeon will then locate and remove the stone. The surgeon will also correct any blockage in the affected area. The surgery, called nephrolithotomy, is very invasive and is restricted to the following:

Patients with very large or complex stones that cannot be removed using less invasive measures
Very obese patients

Some centers report success with extracorporeal shock wave lithotripsy, however, in patients who would normally be nephrolithotomy candidates. Therefore, even these patients should discuss other options with their surgeon.

The procedure is not appropriate for patients with:

Bleeding or clotting disorders
Untreated widespread infection
Severe and chronic kidney insufficiency (unless removing the stone will improve kidney function)

Complications

Between 70 - 90% of crystals remain tiny enough so that they can travel through the urinary tract and leave the body in the urine without being noticed. When they do cause symptoms, however, kidney stones have been described as one of the most painful disorders to afflict humans. The pain they cause is sometimes called renal colic. ("Renal" means "kidney.")

Obstruction and Infection. Although kidney stones often lead to obstruction (blockage) of the urinary tract, the blockage is usually temporary and causes no lasting damage. In some cases, however, particularly if the obstruction progresses with no symptoms, infection may occur, which can be serious and need immediate attention.

Kidney Failure. It is very rare for kidney stones to cause kidney failure, although some people have risk factors that make them more vulnerable to this serious complication. Risk factors include the following:

Very frequent recurrences (such as in people with cystine stones or other inherited forms of kidney stone disorders)
Accompanying episodes of urinary tract infections with obstruction, a particular risk with struvite stones
A history of multiple urologic procedures for kidney stones
Greater size of the kidney stone gravel

Without preventive treatment, calcium stones recur in 10% of patients within a year of the first attack, and in half of patients within 5 - 7 years. Individual risk for recurrence, however, varies depending on the stone and the underlying condition. For example, a 15-year-old with inherited cystine stones has a very high risk for recurrence, while a middle-aged man with a first calcium oxalate stone has a good chance of never passing another.

Prevention

All individuals who have experienced kidney stones should take some specific preventive measures to prevent recurrence. The following are some general observations:

The most important dietary recommendations for reducing the risk for calcium stones are increasing fluid intake, restricting sodium, and reducing protein intake.
A lower risk for calcium stones is also associated with higher potassium intake.
A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids and dietary potassium and phosphate. (Increasing calcium alone may pose a modest risk for stones.)
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine, which promote stone formation.

Because different kidney stone types may require specific dietary changes, patients should work with their doctors to develop an individualized plan. It is important to note that nutritional considerations are very important in preventing recurrence, and patients should be vigilant in complying with the proper diet.

Good voiding habits, particularly frequent urination, are important. Therefore, of all the preventive recommendations, drinking enough fluids is the most important guideline for people with any type of kidney stones.

In general, patients with calcium or uric acid stones should drink at least 10 full glasses of fluid each day (at least half should be water). This includes one with each meal and drinking fluids at night, even if it means getting up from sleep. Fluid intake should produce at least two and a half quarts of urine each day.
To prevent cystine stones, patients should drink even more water -- over a gallon, or 16 8-ounce cups, every day. Patients should drink this amount at regular intervals throughout the night and day.

In all cases, patients need more fluid after exertion and during times of stress. If they drink enough, the urine should be pale and almost watery, not dark and yellow.

Water. Although water is best, it may vary depending on its source. Variations in water itself may have different impacts. One study reported that drinking hard tap water increased urinary calcium concentration by 50% compared to soft bottled water. On the other hand, mineral water containing both calcium and magnesium may reduce several risk factors for both calcium and uric acid stone formation.

Juices and Specific Effects. Other beverages have various positive or negative effects, depending on the type of stone:

Lemon Juice: Drinking one-half cup of pure lemon juice (enough to make eight glasses of lemonade) every day raises citrate levels in the urine, which might protect against calcium stones. (While orange juice also increases citrate levels, it does not lower calcium and it raises oxalate levels. Therefore, it is not recommended.)
Cranberry and Apple Juice: Apple and cranberry juice contain oxalates, and both have been associated with a higher risk for calcium oxalate stones. Cranberry juice has properties that may increase the risk for both calcium oxalate and uric acid stones. On the other hand, cranberry juice helps prevent urinary tract infections and so may be helpful for reducing the risk for struvite and brushite stones. (These stones are far less common, however.)
Black Currant Juice: In one study, black currant juice reduced urine acidity and was associated with protection against uric acid stones.
Grapefruit Juice: A number of studies have found a risk for stones from drinking grapefruit juice. In one study, just one 8-ounce cup of grapefruit juice per day increased the risk for forming stones by 44%.

Other Beverages and Their Effects on Stone Formation.

Soft Drinks. Patients with stones should avoid cola drinks, since they can severely reduce citrate levels in the urine. Many soft drinks contain phosphoric acid, which increases the risk for stones. Some research shows that drinking one quart (less than three 12-ounce cans) of soda per week may increase a person's risk of developing stones by 15%.
Alcohol. Wine may be protective against kidney stones. A study conducted in Finland, suggests that the risk of developing stones also decreases with beer consumption. However, it is important to remember that beer is high in oxalates. Beer and other alcoholic beverages also contain purines, which may increase the specific risk for the less common uric acid stones in susceptible people. Binge drinking, in any case, increases uric acid and the risk for stones.
Coffee and Tea. Some research reported a lower risk for stones in people who drink tea and both regular and decaffeinated coffee.

A long-term 2002 study followed men with calcium oxalate stones and high levels of urinary calcium. The study found that a low-sodium, low-protein diet, containing normal levels of calcium, dramatically reduced the recurrence of stones compared to a diet that was simply low in calcium.

Salt Restriction. Because salt intake increases the amount of calcium in urine, patients with calcium stones should limit their sodium intake. Sodium may also increase levels of urate, the crystalline substance that can trigger formation of recurrent calcium oxalate stones. Although the relative contribution of limiting sodium intake has not been confirmed, some researchers believe that restricting sodium along with increasing fluid intake is the most important dietary measure for preventing stones.

Protein Restriction. Protein increases uric acid, calcium, and oxalate levels in the urine, and reduces citrate levels. Diets high in protein, particularly meat protein, have been consistently connected with kidney stones. (Meat protein has a higher sulfur content and produces more acid than vegetable protein.) A 2002 study of those following a high-protein, low-carbohydrate diet (such as the Atkins diet, for example), found dramatically increased levels of urinary uric acid and calcium after just several weeks. These effects put patients at higher risk for not just kidney stones, but possibly osteoporosis as well. According to Swiss studies, about a third of people at risk for calcium stones may have a sensitivity to meat proteins that causes mild hyperoxaluria.

Whether restricting meat protein alone has any protective value without restricting sodium as well is unknown. Most studies to date have found no difference in stone development between people with low and normal meat protein diets over four years. A 2000 study reported that only dramatic reductions in meat protein had any preventive effect against stone recurrence.

Although the precise role of dietary protein in kidney stones needs further clarification, it is reasonable for everyone to consume meat protein in moderation. People with struvite stones, who need to reduce phosphates in their diets, should also cut down on proteins.

Calcium from Foods. Dietary calcium recommendations for kidney stone prevention need to be determined on an individual basis. A doctor will suggest calcium guidelines based on a patient's age, gender, body size, and type of stone. Most studies indicate that dietary calcium (found in milk, yogurt, and cheese) protects against many types of calcium oxalate stones. Large studies of both men and women found that those with the highest intake of calcium from foods had a much lower risk for stones than those who had little calcium in their diets. A diet containing a normal amount of calcium, but reduced amounts of animal protein and salt, may protect against stones better than a low-calcium regimen. However, calcium metabolism changes as people age. Some studies suggest that a high calcium intake protects against kidney stones in men younger than age 60, but not in older men.

Dietary calcium may actually bind the oxalate in foods, preventing it from being absorbed into the blood and excreted into the urine. In a normal healthy diet, dairy products supply almost 80% of the daily calcium requirement. For people who have calcium stones associated with resorption (the breakdown of bone that releases calcium into the bloodstream), limiting calcium intake could cause further bone loss.

Calcium Supplements. Evidence on calcium supplements is mixed, although in general many studies suggest that they reduce oxalate levels and so help prevent calcium oxalate stones. One study suggested that taking 500 mg of calcium supplements a day regularly may "reprogram" the intestines to absorb less calcium and may therefore be protective. Experts generally agree that calcium supplementation within dosage recommendations (about 1,200 mg per day) remains safe. In one study, however, women who took calcium supplements had a 20% higher risk for stones. Research indicates that dosages of calcium above 2,000 mg per day are clearly associated with the formation of stones. Some experts speculate that this higher risk may occur because supplements are often taken in the morning, either without food or with breakfast, which is typically low in oxalates. Taking supplements with later meals may not produce the same risk.

Calcium Restriction in Certain Cases. Some patients, such as those whose stones are caused by genetic defects in which the intestine absorbs too much calcium, may need to limit calcium intake. More studies are needed to define this group precisely.

Fiber may be beneficial for people with kidney stones. In addition, some fiber-rich foods may contain compounds that help protect against kidney stones. A wide variety of high-fiber plant foods contain a compound called phytate (also called inositol hexaphosphate, InsP6, or IP6), which appears to help prevent crystallization of calcium salts, both oxalate and phosphate. Phytate is found in legumes and wheat and rice bran. (Soybeans are also rich in phytate but they are also very high in oxalates, so the overall effects of soy on kidney stones are not clear.)

A high intake of purines can increase the amount of uric acid in the urine. Those at risk for uric acid stones should reduce their intake of foods and beverages that contain purines. These include beer and other alcoholic beverages, anchovies, sardines, yeast, organ meats (such as liver and kidneys), legumes (including dried beans, peas, and soybeans), mushrooms, spinach, asparagus, cauliflower, and poultry.

Most people with calcium oxalate stones should not avoid oxalate-rich foods unless the doctor specifically recommends a restrictive diet. Oxalate binds with calcium in the intestine, which may actually reduce calcium absorption. Some studies, in fact, indicate that eating foods containing oxalates and calcium together may reduce the risk of stones. Most of the foods that contain oxalates are very important for good health. Limiting oxalates may be particularly harmful in people with bowel disorders marked by malabsorption.

Foods high in oxalic acid include beets, soy, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard.
Foods containing moderate amounts of oxalates include beans (green and wax), blackberries, blueberries, carrots, celery, coffee (roasted), concord grapes, currants, dandelion greens, endive, gooseberries, lemon peel, okra, green onions, oranges, green peppers, black raspberries, strawberries, and sweet potatoes.

Certain fats may play a beneficial or harmful role in specific cases of kidney stones.

Restricted Fats in Patients with Stones Associated with Bowel Disease. Patients who have stones associated with short-bowel syndrome should eat foods with lower amounts of fats and oxalates. If patients with short-bowel syndrome eat too much fat, calcium may bind to unabsorbed fat instead of to oxalates. This increased oxalate levels, resulting in increased risk of stone formation.

Fish Oil. Omega-3 fatty acids, found in oily fish like mackerel, salmon, and albacore tuna, have many health benefits, but the most current evidence suggests they do not help prevent kidney stones. A 2005 study of over 200,000 adults found that increased omega-3 fatty acid intake did not reduce kidney stone risk.

Vitamin B6. Vitamin B6, or pyridoxine, is used to treat people with primary hyperoxaluria, a severe inherited disorder. Patients should not try to treat themselves with vitamin B6. Very high doses (500 to 2,000 mg daily over long periods) can cause nerve damage, with loss of balance and numbness in the feet and hands. Food sources of vitamin B6 include meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.

Vitamin C. Ascorbic acid (vitamin C) may change in the body to tiny crystals, called oxalates. These crystals do not dissolve. People with hyperoxaluria (too much oxalate in the urine) should avoid vitamin C supplements. Even for men with normal oxalate levels, higher consumption of vitamin C (more than 1,000 mg a day) may increase kidney stone risk.

Magnesium and potassium may help reduce the risk for kidney stones in men.

Because of an association between stress and kidney stones, relaxation and stress management techniques may also be beneficial.

Dietary Considerations. People with kidney stones appear to be more sensitive to certain foods than people who do not form kidney stones. Therefore, vulnerable people should make specific changes in their diet. They should work with their doctors to develop a dietary plan that fits their individual situation. Drinking plenty of fluids is important for preventing recurrence of any kidney stone.

Indications for Drug Treatments. If dietary treatments fail, drug therapy may be helpful. A number of drugs are available to prevent recurrences of calcium oxalate and other stones. Medications that inhibit the formation of stones include allopurinol, thiazide, potassium citrate, and potassium-magnesium citrate. In addition, drug treatments can sometimes also help prevent other complications related to stones, such as osteoporosis.

Correcting Underlying Conditions Known to Cause Kidney Stones. It is also important to treat and correct, if possible, any underlying disorder that may be causing stones to form. Such disorders include distal renal tubular acidosis, hyperthyroidism, sarcoidosis, and certain cancers. To prevent calcium stones that form in hyperparathyroid patients, a surgeon may remove the affected parathyroid gland (located in the neck). In most cases, only one of the glands is enlarged. Removing it ends the patient's problem with kidney stones.

Resources

www.kidney.niddk.nih.gov -- National Kidney and Urologic Diseases Information Clearinghouse
www.urologyhealth.org -- American Urological Association
www.kidney.org -- National Kidney Foundation
www.ohf.org -- Oxalosis and Hyperoxaluria Foundation

References

Cameron MA, Maalouf NM, Adams-Huet B, Moe OW, Sakhaee K. Urine composition in type 2 diabetes: predisposition to uric Acid nephrolithiasis. J Am Soc Nephrol. 2006 May;17(5):1422-8. Epub 2006 Apr 5.

Curhan GC, Willett WC, Knight EL, Stampfer MJ. Dietary factors and the risk of incident kidney stones in younger women: Nurses' Health Study II. Arch Intern Med. 2004;164(:885-891.

Finkielstein VA. Strategies for preventing calcium oxalate stones. CMAJ. 2006;174(10); 1407-1409.

Krambeck AE, Gettman MT, Rohlinger AL, Lohse CM, Patterson DE, Segura JW. Diabetes mellitus and hypertension associated with shock wave lithotripsy of renal and proximal ureteral stones at 19 years of followup. J Urol. 2006;175(5):1742-7.

Sinha MK, Collazo-Clavell ML, Rule A, et al. Hyperoxaluric nephrolithiasis is a complication of Roux-en-Y gastric bypass surgery. Kidney International. 2007;72:100-107.

Straub M, Hautmann RE. Developments in stone prevention. Curr Opin Urol. 2005;15(2):119-126.

Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol. 2004;15(12):3225-3232.

Taylor EN, Stampfer MJ, Curhan GC. Fatty acid intake and incident nephrolithiasis. Am J Kidney Dis. 2005;45(2):267-274.

Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005;293(4):455-462.

Taylor EN, Stampfer MJ, Curhan GC. Diabetes mellitus and the risk of nephrolithiasis. Kidney Int. 2005 Sep;68(3):1230-5.

Wasserstein AG. Nephrolithiasis. American Journal of Kidney Diseases. 45(2);2005:422-28.

Review Date:
7/24/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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

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Weingärtner J, Lotz K, Fanghänel J, Gedrange T, Bienengräber V, Proff P. Induction and Prevention of Cleft Lip, Alveolus and Palate and Neural Tube Defects with Special Consideration of B Vitamins and the Methylation Cycle. J Orofac Orthop. 2007; 68(4):266-277.

Wierzbicki AS. Homocysteine and cardiovascular disease: a review of the evidence. Diab Vasc Dis Res. 2007;4(2):143-50.

Zeisel SH. The fetal origins of memory: the role of dietary choline in optimal brain development. J Pediatr. 2006;149(5 Suppl):S131-136.

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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

Losing Weight vs. Gaining Muscle

FitSugar — Mon, 09 Mar 2009 04:30:00 -0700

Spring is around the corner and so is bikini season. This time of year is when I receive queries from readers concerned that they are not losing very much weight, even though they are dieting and exercising after hibernating on the couch for the dark months of Winter. In the questions on this subject I have received recently, the Sugar readers have all noticed that their clothes are looser and their body's are firmer, but their scales have barely budged. Although they're frustrated, I must say they are doing the right thing - dieting and working out.

They may not be losing much weight, but they are losing fat while gaining muscle, which is great. Muscle tissue is more dense than fat tissue, so it takes up less space. When you lose fat and gain muscle your body measurements will change, like waist circumference, even though your weight doesn't.

To see how muscle mass helps when losing weight, read more.
Muscle also requires more energy and therefore burns more calories than fat. Meaning the more muscle mass you have the faster your metabolism, which is great. If you're looking to lose weight, I think you should alter your goal to change your body composition. Keep on exercising and counting calories, since that is how you effectively lose weight. Make sure to keep your caloric intake above 1200 calories, because if you go under your body goes into famine mode and holds onto fat. Measure your progress by how your clothes feel and remember, the slower you lose weight - two pounds maximum a week - the higher the chances you will keep it off.

Source

Non-Hodgkin's lymphoma

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

In This Report

Highlights
Introduction
Risk Factors
Symptoms
Diagnosis
Outlook
Staging and Treatment Guide...
Chemotherapy
Biologic Therapy (Immunothe...
Radiation
Transplantation
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

Chemotherapy can cause anemia, a drop in red blood cell (hemoglobin) levels. Erythropoiesis-stimulating drugs, which boost the production of red blood cells, are administered to counteract this complication. However, these drugs, which include epoietin alfa (Epogen, Procrit) and darbepoietin alfa (Aranesp), can also cause serious side effects and adversely affect survival when hemoglobin levels are raised too high.

In 2007, the U.S. Food and Drug Administration (FDA) made several changes to the prescribing labels for erythropoiesis-stimulating drugs. The new labels have stronger warnings and updated dosing-related safety information.

The FDA advises that for treating anemia associated with chemotherapy, dosing should increase hemoglobin levels to no more than 12 g/dL. Treatment with these drugs should stop as soon as the chemotherapy course is completed. Erythropoiesis-stimulating drugs are not safe or appropriate for all patients undergoing chemotherapy. Patients should discuss the risks and benefits with their oncologists. The FDA is currently reviewing additional data concerning the safety of these drugs.

Positron Emission Tomography (PET) Scans and Lymphoma

PET scans are used to help diagnose and stage lymphoma, and they may also be helpful in assessing treatment outcomes for some types of lymphoma. In 2007, an international team of cancer specialists drew up new guidelines for evaluating how well lymphoma responds to treatment in clinical trials. The guidelines now recommend that PET scans be used to help determine if a patient has achieved remission.

Introduction

Lymphomas are malignancies of the lymph system that are generally subdivided into two groups, Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Hodgkin's disease accounts for about 15% of all lymphomas. [For more information, see In-Depth Report #83: Hodgkin's disease.]

Non-Hodgkin's lymphomas is a term for malignancies that range from a very slow disease to an extremely aggressive but curable condition. They have certain features in common.

The lymphatic system filters fluid from around cells. It is an important part of the immune system. When people refer to swollen glands in the neck, they are usually referring to swollen lymph nodes. Common areas where lymph nodes can be easily felt, especially if they are enlarged include the groin, armpits (axilla), above the clavicle (supraclavicular), in the neck (cervical), and the back of the head just above hairline (occipital).

Lymphomas, such as non-Hodgkin's lymphomas and Hodgkin's disease, represent tumors of the lymphatic system. This system is a network of organs, ducts, and nodes. The system interacts with the blood's circulatory system to transport a watery clear fluid called lymph throughout the body. The lymphatic system contains lymphocytes, important cells involved in defending the body against infectious organisms. This system also restores 60% of the fluid that leaks out from blood capillaries back into circulation, and its ducts provide transportation for fats, proteins, and other substances collected from the body's tissues.

Lymphocytes. The lymphatic system is involved in the production and transportation of lymphocytes, white blood cells that are a primary component of the immune system. Among other vital functions, certain lymphocytes are responsible for producing antibodies, factors that can target and attack specific foreign proteins (antigens). To understand the lymphatic system, it is helpful to track part of the life cycle of these lymphocytes:

Lymphocytes develop in the bone marrow or thymus gland and are therefore categorized as either B cells (bone marrow-derived cells) or T cells (thymus gland-derived cells).
B cells complete their structural growth and definition (known as differentiation) and mature in the bone marrow.
T cells also start out in the bone marrow but differentiate and mature in the thymus gland, located beneath the breastbone (sternum). This small gland is active mostly in the fetal stage through the first 10 years of life, after which it atrophies (shrinks).
B-cell and T-cell lymphocytes leave these organs through the bloodstream, which eventually branches out into the tiny blood vessels called capillaries.
Some lymphocytes, along with fluid, proteins, and other substances, migrate out of the capillaries into the surrounding tissues. A proportion of these lymphocytes and other substances then enter the lymphatic vessels.
Lymphatic vessels begin as tiny, blind-ended tubes and lead to larger lymphatic ducts and branches until they drain into two ducts in the neck, where the fluid re-enters the bloodstream.
Along the way, the fluid passes through lymph nodes, oval structures composed of lymph vessels, connective tissue, and white blood cells. Here, the lymphocytes are either filtered out or added to the contents of the node.

Lymph Nodes. In the lymph node, lymphocytes receive their initial exposure to foreign substances (antigens), such as bacteria or other microorganisms, activating the lymphocytes to perform their immune functions. The size of a lymph node varies generally from that of a pinhead to a bean. Most nodes are in clusters located throughout the system. Important node clusters are found in the neck, lower arm, armpit, and groin.

Other Structures in the Lymphatic System. The tonsils and adenoids are secondary organs composed of masses of lymph tissue that also play a role in the lymphatic system. The spleen is another important organ that processes lymphocytes from incoming blood.

Click the icon to see an animation about lymph nodes.

Click the icon to see an image of lymph nodes in the head and neck.

Click the icon to see an image of the immune system structures.

Non-Hodgkin's lymphomas occur most often in lymph nodes in the chest, neck, abdomen, tonsils, and the skin. NHLs may also develop in sites other than lymph nodes such as the digestive tract, central nervous system, and around the tonsils.

About 85% of non-Hodgkin's lymphomas (NHLs) arise in B cells; the rest occur in T cells. Activation of a gene called BCL-2 is believed to be partly responsible for many B-cell lymphomas. This defect prevents apoptosis (a natural process whereby cells self-destruct) in the lymphoma cells.

There are more than 20 distinct types of non-Hodgkin's lymphomas. Most first arise in the lymph nodes, but about 20 - 30% of cases are now found outside the nodes, most often in the stomach, small intestine, skin, and brain.

Even experts disagree about the exact groupings. Lymphomas are categorized in a number of ways.

Classification by Cell Type, Appearance, and Genetic Make-up: The REAL System. Different classification systems for lymphoma have been proposed. The system used in this report is called REAL (Revised European-American Lymphoma Classification). It classifies all lymphomas by appearance, cell type, and genetic make-up:

Non-Hodgkin's lymphomas are first grouped as B cell or T cell.
Next, they are categorized by whether the B-cell and T-cell lymphomas were derived from immature (precursor) cells or mature (peripheral) cells.
The peripheral B and T cells are then classified by their appearance, genetic make-up, and specific chemical "markers," which further identify them.

T-cell lymphomas, Hodgkin's disease, and certain leukemias and aggressive lymphomas are covered in the REAL classification but are not discussed in any depth in this report.

Groups by Slow or Fast Growth. Each non-Hodgkin's lymphoma is further defined by its grade, or how aggressive it is:

Indolent (slow-growing), also called low-grade
Aggressive (fast-growing), also called intermediate- or high-grade

According to one report, half of new cases are now intermediate-grade lymphomas. Low-grade makes up 30%, while high-grade makes up 10% of all lymphomas.

Groups by Properties. Lymphomas are also grouped by certain properties:

Size (large versus small)
Shape (round versus irregular)
Whether they are or resemble blood plasma cells
Whether they are follicular (organized in round clusters) or diffuse (spread evenly throughout the lymph node)

Staging. Staging the disease is the next important step in classifying lymphomas. The stage (I - IV) of an NHL is determined by the number of tumors and whether they are still localized or have spread beyond the lymph node. In general, the higher the stage, the poorer the outcome, but other factors are important for a precise prognosis.

Indolent (Slow-Growing) Lymphomas (also Called Low-Grade Lymphomas)

Follicular lymphomas (FLs). Follicular small cleaved cell lymphoma (grade I) and follicular mixed small and large cell lymphoma (grade II). FLs account for 70% of indolent tumors and 20% of all NHLs in industrialized countries. It is very rare in developing countries and in Asia.

Lymphoplasmacytoid/Waldenstrom's macroglobulinemia. Often found in bone marrow, lymph nodes, and spleen. Can cause blood to become viscous and "sticky."

Marginal zone lymphomas (MZL). MZLs often occur as a result of a pre-existing disorder such as hepatitis C, bacterial infection in the stomach (H. pylori ), or an autoimmune disorder (Sjögren syndrome in the salivary glands or Hashimoto's thyroiditis in the thyroid gland). They may be classified as:

Monocytoid B-cell lymphoma, which involves only lymph nodes
Splenic marginal zone lymphoma, which affects the spleen, blood, and bone marrow
Mucosa-associated lymphoid tissue (MALT) lymphoma, which usually involves the gastrointestinal tract, thyroid, lung, breast, or skin

There is some controversy over whether MALT is a variation of MZL or a completely separate type of lymphoma that is more suitably classified as a separate low-grade lymphoma. At this time, it is classified as an MZL.

Aggressive Lymphomas (also Called Intermediate- and High-Grade Lymphomas)

Diffuse large-cell lymphomas (DL). DLs are the most common NHLs, accounting for about 40% of all cases. Subtypes include the following:

Primary mediastinal large B-cell lymphoma
Follicular large cell lymphoma
Anaplastic large cell lymphoma
T-cell lymphomas (not covered in this report)

In about 40% of cases, these DL lymphomas appear in areas outside lymph nodes, including digestive tract, skin, bone, thyroid, and testes.

Burkitt's lymphoma/diffuse, small noncleaved cell lymphoma. This is the most common childhood NHL. In African children, it often involves facial bones and is associated with Epstein-Barr infection.

Mantle cell lymphoma. Mantle cell lymphomas are found in lymph nodes, the spleen, bone marrow, blood, and sometimes the gastrointestinal system (lymphomatous polyposis). This lymphoma is similar to indolent lymphomas at the time of diagnosis, but it is more aggressive.

Lymphoblastic lymphoma. This lymphoma often occurs in young people. It is associated with a large mediastinal mass (occurring in chest cavity between the lungs) and carries a high risk for spreading to bone marrow and central nervous system.

Risk Factors

About 63,000 Americans were diagnosed with non-Hodgkin's lymphomas in 2007, and nearly 19,000 people died of the disease. For the past 25 years, the incidence in NHL has increased continuously. Most of this increase has occured in people over age 65.

Part of the reason for the dramatic rise was AIDS, which increases the risk for high-grade lymphomas. However, even after eliminating changes in diagnosing NHLs and known causes (such as AIDS), the incidence over the past 40 years is 40% higher. The number of cases in which lymphomas first occur outside the lymph nodes has also increased compared to those limited to the nodes. (This observed increase, however, may in large part be due to different methods of diagnosing lymphomas).

The cancer can develop in people at all ages, including children, although it is most common in those ages of 45 - 60. In general, the incidence of NHL is 50% higher in men than in women. This higher rate has been observed in many countries. Nevertheless, recent reports suggest that the rate is leveling off or even declining in men, but is increasing in women, particularly African-American women. Overall, the risk is slightly higher in Caucasians than in African-Americans.

The risks for NHL among men versus women and among African-Americans versus Caucasians may vary by lymphoma subtype. For example, follicular lymphomas were significantly higher in Caucasians than in African-Americans, and there was little gender difference. High-grade lymphomas were the most rapidly increasing type, particularly among men, with follicular lymphomas increasing most rapidly in African-American men.

Other studies have also reported ethnic differences by specific lymphoma subtypes. For example, follicular lymphomas constitute 20% of all NHLs in Western nations but are very uncommon in Asia and in developing countries.

The brother or sister of a person with the disease has more than twice the risk of developing NHL than the general population. Some cases of NHL in such cases are due to inherited disorders of the immune system. Studies suggest, however, that such family clusters are more likely to be due to environmental conditions that trigger the genetic factors.

Because of the rapid rise in NHL, investigators are looking for lifestyle factor that may contribute to this increase. No real association between lymphomas and body weight or shape or amounts of exercise has been found.

A number of reports suggest an influence of diet in the development of non-Hodgkin's involvements. However, for the most part a strong association remains speculative. Some of the possible dietary risk factors include:

A number of studies have observed an association between an increased risk for non-Hodgkin's lymphomas and high consumption of red meat (beef, pork, and lamb).
A higher risk for lymphoma has also been suggested for trans fatty acids (hydrogenated polyunsaturated fats, which are contained in hard margarines and commercial baked goods and fast foods). There appears to be no higher risk with natural polyunsaturated fats (found in most vegetable and fish oils).
Fish may be protective.
Some evidence suggests that milk may also be protective.
One major study observed a reduction in risk with high intake of vegetables. Another found no protection from vegetables, but did with diets rich in fruit.
Vitamin supplements have no effect on NHL.

Despite these kinds of reports, the influence of diet on the development of non-Hodgkin's lymphomas remains speculative.

Alcohol Use. Studies on alcohol have been mixed, with some showing a higher risk, some a lower risk, and some no difference at all.

Smoking. There is no evidence that smoking increases the risk for NHL itself, although it has been linked with high-grade and follicular NHLs in people with lymphomas.

Viruses or other microorganisms also play a role in some lymphomas. A number are being investigated:

Epstein-Barr virus, the cause of mononucleosis, is highly associated with Burkitt's disease and NHLs associated with immunodeficiency diseases. It is also a risk factor for Hodgkin's disease
Adult T-cell leukemia-lymphoma, which appears to be caused by a virus known as HTLV-I, has been found in southwestern Japan, the Caribbean, and the southeastern United States.
People who have stomach inflammation due to Helicobacter pylori or H. heilmannii bacteria are at increased risk for mucosa-associated lymphoid tissue lymphomas (MALT). (The use of antibiotics to get rid of the bacteria may cause remission in some patients who have an early stage form of lymphoma in an early stage.)
Human herpes virus 8 has been associated with NHL.
Borrelia burgdorferi, the bacteria that causes Lyme disease, has been associated with primary B-cell lymphoma.
Heavy antibiotic use during adulthood may increase risk. A 2005 study found that adults who used antibiotics more than 10 times had 1.8 times the risk of developing NHL than nonusers. However, researchers were not certain if antibiotics themselves, or the underlying infections they treated, were responsible for the increased risk.

Click the icon to see an image of Lyme disease.

Studies are reporting a higher prevalence of viral hepatitis C and B in patients with lymphomas, although such viruses do not appear to play a major role in triggering lymphoma.

Patients with diseases or conditions that affect the immune system may be at higher risk for lymphomas:

HIV-positive patients and those with full-blown AIDS are at higher risk for NHL, and the disease is more likely to be widespread in these patients than in those without the immune disease. Most AIDS-related NHLs are high-grade lymphomas. Burkitt's lymphoma is often seen in patients with AIDS. Although these patients have had a very poor prognosis, advances in antiviral therapy for HIV now allow better management of NHL with some success in achieving favorable outcomes. Part of the dramatic increase in NHL incidence over the past decades can be traced to AIDS.
Patients with a history of autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus, Hashimoto's thyroiditis, Crohn's disease, and Sjögren syndrome, are at an increased risk for certain NHLs, such as marginal zone lymphomas.
People who have organ transplants are at higher risk for NHL, probably due to multiple factors, including the drugs used to suppress the immune system and the transplanted organ itself.
Patients who have had high-dose chemotherapy with stem-cell transplantation are at higher risk.
Other immunodeficiency syndromes that put people at risk for NHL include Chediak-Higashi syndrome, ataxia-telangiectasia, B-cell lymphoproliferative syndrome, Bruton agammaglobulinemia, common variable immunodeficiency, and Wiskott-Aldrich syndrome.

Note on Allergies: There appears to be no association between NHL and allergies, overactive responses of the immune system. Allergies are the most common immune disorder.

Overexposure to a number of industrial and agricultural chemicals has been frequently linked to an increased risk for lymphomas. The data, however, are not consistent.

Organochlorines are chemicals produced when solid waste is burned. These by-product chemicals include dioxin, polychlorinated biphenyls (PCBs), and furans. Many studies have indicated that exposure to these chemicals increases the risk of developing NHL.
A number of studies have found an association between NHL and certain pesticides and herbicides, although more research is needed to confirm any definitive risk.
White spirits, thinners, phenoxy herbicides, wood preservative, aviation gasoline, plastic, and rubber chemicals have been associated with a higher risk for lymphomas. Specifically, in one study, painters and lumberjacks had a higher risk for NHL, while office and house workers had a lower risk.
Some studies have found an association with long duration and early use of permanent dark hair dyes. There is no consistent evidence, however, that hair dye increases the risk for lymphomas.

Symptoms

The most common first sign of lymphomas is painless enlargement of one or more lymph node, usually in the neck, armpits, or groin. Patients should see their doctors if these symptoms do not go away within 2 - 3 weeks.

The most common lumps or swellings in the neck are enlarged lymph nodes. They can be caused by bacterial or viral infections, cancer, and other rare causes.

Lymphomas sometimes cause systemic symptoms -- symptoms that affect the whole body, rather than a specific location. Some systemic symptoms are referred to as B symptoms. Patients who have B symptoms have a more severe condition than asymptomatic patients with the same cancer stage or tumor location or size.

B systemic symptoms include:

Drenching night sweats and weight loss
Fever (may occur sporadically and only at night)

Other systemic symptoms include:

Itching all over the body caused by the release of histamines, substances ordinarily triggered by an allergic response. In the case of NHL, this is due to abnormalities in the immune system. Although this is a systemic symptom, it is not usually considered a B symptom if other systemic symptoms are not also present.
In late stages, some patients develop a skin rash.
Tumor masses in the chest can cause coughing or breathlessness.
Lymphomas in the stomach can cause nausea and vomiting.

Many patients seek medical help for abnormally swollen lymph nodes (commonly referred to as "swollen glands"). Swollen glands can be caused by many conditions, most often infections, and are rarely serious.

Infections. In the great majority of cases, swollen glands are caused by an infection:

Enlarged lymph nodes in the neck are much more likely to be a sign of strep or other throat infection than NHL.
Infectious mononucleosis (caused by the Epstein Barr virus) is a common cause of swollen lymph nodes in young people.
Travel, particularly to countries with a high incidence of tropical diseases, can trigger similar symptoms.
Other infections that cause swollen glands include cat scratch fever, Lyme or other tick-borne disease, HIV, tularemia, tuberculosis, syphilis, herpes simplex virus, cytomegalovirus, and hepatitis.

Hodgkin's Disease. Although both Hodgkin's disease and non-Hodgkin's lymphomas are malignancies of the lymph nodes, they can usually be distinguished by certain characteristics. It is extremely important to differentiate between Hodgkin's lymphomas and non-Hodgkin's lymphomas, since the treatments for these two conditions differ. In particular, a subtype of lymphoma called anaplastic large-cell lymphoma (ALCL) might be confused with Hodgkin's disease under some circumstances. [For more information, see In-Depth Report #83: Hodgkin's disease.]


Characteristics	Hodgkin's Disease	Non-Hodgkin's Lymphomas
Age and Prevalence	Average age is 28 with two age peaks, the major one occuring between 15 - 24, anda lesser peak after age 55. It is less common than NHL.	Average age is about 67. It is more common than HD.
Location	In both malignancies, the disease occurs most often in lymph nodes above the collarbone. However, in HD it is also more likely to appear in the chest cavity between the lungs (the mediastinum), particularly in younger patients. Only about 15 - 20% of cases are found in areas below the diaphragm. Disease occurs outside the nodes in about 4% of cases.	In both malignancies, the disease occurs most often in lymph nodes above the collarbone. In NHL, however, it is also more likely to appear in the nodes in the abdomen (called the mesenteric nodes). The disease occurs in the chest cavity in less than 40% of patients. (An exception, lymphoblastic lymphoma, which is seen most often in young people, is likely to first appear in the chest.) Disease occurs outside the nodes in about 23% of patients. Slow-growing lymphomas are common in the liver and bone marrow.
Symptoms	More likely than NHL (40%) to have systemic symptoms (such as fever and night sweats) at the time of diagnosis.	Less likely to have systemic symptoms (27%) at the time of diagnosis.
Progression	Less likely than NHL to be diagnosed in stage IV (10%). Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site. If it spreads below the diaphragm, it usually reaches the spleen first; the disease then may spread to the liver and bone marrow. If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs.	More likely than HD to be diagnosed in stage IV (36%). The lymphomas are less predictable in their course than Hodgkin's disease and they are more apt to spread.

Other Cancers or Serious Conditions in the Lymphatic System. Other cancers that can travel to lymph nodes include breast cancer and leukemia.

Very serious causes of enlarged lymph nodes include disorders of the lymph system, such as Castleman's disease, lymphomatoid granulomatosis, and angioimmunoblastic lymphadenopathy. These lymph system disorders, although noncancerous, involve abnormal lymph cells. They are often fatal and can be very difficult to distinguish from lymphomas. Many of the other serious illnesses involving diseased lymph nodes develop simultaneously at multiple sites, while Hodgkin's nearly always starts at one location before spreading to nearby nodes. [For more information, see In-Depth Report #83: Hodgkin's disease or Report #86: Acute lymphocytic leukemia.]

Exposure to Medications. Exposure to certain medications such as phenytoin (Dilantin) may cause enlarged nodes. Other drugs, such as cephalosporins, penicillins, or sulfonamides, can cause enlarged nodes and other symptoms, including fever and rash, which may resemble Hodgkin's disease.

Diagnosis

The doctor will first ask questions about the patient's medical history and perform a physical examination to detect any node enlargements. If these steps point to lymphoma, additional tests will be done to rule out other diseases or to confirm the diagnosis and extent of the lymphoma.

It is sometimes reasonable to wait a little while for the swelling and symptoms to go away before deciding that additional testing is necessary. In some cases, lymph node swelling may be due to a temporary infection. However, some lymphomas cause off and on lymph node swelling. This is particularly true with small cleaved cell lymphoma (the most common NHL). Lymph nodes should be checked periodically for any return of swelling.

The doctor will examine not only the affected lymph nodes but also the surrounding tissues and other lymph node areas for signs of infection, skin injuries, or tumors. The consistency of the node sometimes indicates certain conditions. For example, a stony, hard node is often a sign of cancer, usually one that has metastasized (spread to another part of the body). A firm, rubbery node may indicate lymphoma. Soft nodes suggest infection or inflammatory conditions.

Blood tests help rule out infection and other diseases. Such tests include those blood counts and blood chemistries for kidney and liver function, uric acid, calcium, and phosphate levels. In a patient already diagnosed with lymphoma, blood tests that measure the enzyme lactate dehydrogenase are important in determining the prognosis. High levels indicate bulkier tumors. The presence of anemia may indicate specific NHLs, such as diffuse, small lymphocytic lymphoma.

A biopsy is the most important test for diagnosing lymphomas and can be used to tell the difference between non-Hodgkin's and Hodgkin's disease. A biopsy has risks and should be performed only by a qualified and experienced doctor. Sometimes a doctor may choose to wait and observe the involved lymph nodes, which will usually go away on their own if a temporary infection is causing the swelling. (However, some lymphomas may go away and appear to be benign, only to reappear at a later time.)

The Procedure. The doctor removes the node and checks the surrounding areas. The tissue in the node is then examined under a microscope for signs of infection and abnormalities indicating cancer or other conditions.

Results. Even if biopsies do not show any problems, disease may still be present in some cases. The doctor should continue to observe the patient until swelling or other signs of disease are gone. Biopsied tissue samples should be frozen in case special tests are later required. Such tests may include detection of particular antibodies, genetic and immune factors, and certain markers (substances that may indicate disease) located on the surface of the cells. If lymphoma has been diagnosed, the tissue will be examined for its histology, the cellular structures that will determine the lymphoma type.

Bone marrow aspirate and biopsy are routinely performed to determine whether the disease has spread. With bone marrow aspirate, bone marrow cells are sucked out through a special needle. A biopsy may be performed before or after the aspiration. In this procedure, a special needle removes a core of the marrow that is structurally intact.

Click the icon to see an image of bone marrow aspiration.

Chest X-Ray. A chest x-ray shows the lymph nodes in the chest and neck area. It is particularly useful in detecting Hodgkin's disease and enlarged lymph nodes.

Click the icon to see an image of an x-ray machine.

Computer Tomography. Computed tomography (CT) scans are more accurate than x-rays. They can detect abnormalities in the chest and neck area, as well as revealing the extent of the cancer and whether it has spread. CT scans are used to evaluate symptoms and help diagnose lymphomas, help with staging of the disease, monitor response to treatment, and evaluate when the symptoms occur. A CT scan is also often used in detecting lymphomas in the abdominal and pelvic areas, the brain, and chest area.

Click the icon to see an image of a CT machine.

Magnetic Resonance Imaging (MRI). MRIs may be used to detect the spread of the disease to the brain, spine, chest, pelvis, and abdomen.

Click the icon to see an image of a MRI machine.

Positron Emission Tomography (PET). PET scans can help tell whether or not an enlarged lymph node is benign or cancerous. PET scans are more accurate than CT scans or other imaging tests for staging lymphomas. PET scans may also help doctors determine how well a patient has responded to treatment, if any residual cancer exists, and if a patient has achieved remission.

Tests of lymphoma's DNA are in use or are being developed to detect particular genetic abnormalities that help determine outlook and may eventually lead to new treatments. Examples of such abnormal genetic arrangements are those that affect normal cell death, resist chemotherapy, or trigger aggressive cancer growth.

An advanced approach called the microarray technique uses chips that contain up to thousands of DNA sequences that represent specific normal and abnormal genes. Such sequences have been compiled for lymphomas. Eventually, experts may be able to match a patient's DNA to these patterns and identify specific subtypes.

Biologic markers, also called biomarkers, are high levels of substances released by tumors. They indicate the level of cancer activity. Biomarkers can be found in sputum, blood, and tissue samples. Biomarkers can be enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), and growth factors. Some under investigation include:

CD44. This molecule binds to the surface of cells and may be involved in metastasis. High levels of this molecule may suggest a more aggressive disease.
BCL-6. This cancer gene is implicated in diffuse large B-cell lymphoma. High levels of this gene in these patients indicate a better outlook after treatment.

Outlook

Five-year survival rates for NHL range from 20 - 95%, depending on the lymphoma type, stage, age of the patient, and other variables. Because the outlook varies so widely, making a definite prognosis is very difficult. For example, patients with very slow growing (indolent) lymphomas can live many years. However, they are usually diagnosed at a late stage, after the cancer has spread, thus reducing the survival rate. Aggressive lymphomas are more likely to cause rapid death, but they are also often curable. New drugs that target specific factors in the tumor cells are improving survival rates.

Follicular lymphomas, the most common indolent (slow-growing) NHLs, are potentially curable in early stages I and II. Unfortunately, however, these slow-growing malignancies produce no symptoms until they are in advanced stages. In most cases, these lymphomas are not diagnosed until they have spread to other sites, including the spleen and bone marrow. In such cases, they are difficult to cure. Predicting outcome for indolent follicular lymphomas is more difficult than for aggressive lymphomas. Even if treatment achieves a response, these tumors almost always recur. Even after relapse, however, the tumors can be treated again if they are still very slow-growing.

In general, the average survival rate for follicular lymphoma is 7 - 10 years, depending on other risk factors. New drug treatments, particularly monoclonal antibodies, have significantly improved survival rates. According to a 2005 study, 91% of patients with follicular lymphoma now survive the first 4 years after diagnosis, compared with 69% of patients treated in the past with older types of drugs. The research team found the best 4-year survival rates for patients treated with the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy regimen followed by monoclonal antibody biologic drugs (rituximab or iodine-131 tositumomab).

Factors for Predicting Outlook in Indolent Lymphomas. Six risk factors are proving to be useful for predicting outlook:

Being male
Being older
Having stage III or IV disease
Elevated levels of the enzyme lactate dehydrogenase (LDH)
The presence of B symptoms
Erythrocyte sedimentation rate over 30

Patients with a good chance for a positive outcome (65% chance for survival rates of 10 years or greater) have one or none of these factors. Those with intermediate risk (23%) have two factors, and those likely to have a poor outcome (11%) have three or more factors. MALT lymphomas generally have a good prognosis. Primary gastric lymphomas have a 3-year survival rate of 89%.

High-grade aggressive lymphomas are often symptomatic early on and are potentially curable with aggressive treatments. Diffuse large-cell lymphomas, the most common aggressive non-Hodgkin's lymphomas, while fatal if not treated, are often curable with intensive chemotherapy combinations. If relapse occurs after chemotherapy, it usually does so within 2 years.

Most other aggressive lymphomas respond to aggressive chemotherapy. Mantle cell lymphoma is less responsive to chemotherapy. The average survival time is 3 - 5 years.

Factors for Predicting Outlook in Aggressive Lymphomas: A scoring system called the International Prognostic Index has proved to be fairly accurate for predicting outcome in patients with most aggressive B-cell lymphomas. It uses five risk factors to help predict whether the disease will be aggressive:

Being older than 60 -- this age group tends to have other medical conditions, which contribute to the poorer prognosis
Having a disseminated tumor (stage III or IV)
Disease that has spread to more than one site beyond the lymph nodes
A poor performance status
Having elevated levels of lactate dehydrogenase (LDH)

Having one or none of these risk factors indicates the best outlook. Two factors indicate a low-to-intermediate likelihood of a poor outlook. Three factors predict an intermediate-to-high likelihood of poor outlooks. Finally, four or five factors pose the highest likelihood of poor survival.

Lymphoma can spread to the central nervous system, or it can appear there first. Called primary CNS lymphomas (PCNSL), this condition is a very serious, particularly if it occurs at relapse.

The central nervous system is comprised of the brain and spinal cord. The peripheral nervous system includes all peripheral nerves.

Risk Factors for CNS Involvement After a Diagnosis of NHL. AIDS-related lymphomas often involve the central nervous system (CNS), including the brain and spinal column. CNS involvement also occurs with aggressive lymphomas, such as Burkitt’s lymphoma.

Risk Factors of Primary CNS Lymphomas. PCNSL used to account for only about 2% of lymphomas, but the incidence is on the rise in all age groups and in both. The reason for the increase is not known.

Medical Problems. The radiation and chemotherapies used in treating NHL can have long-term effects on many organs in the body and can increase the risk for serious illnesses, including heart disease and certain cancers.

Negative Emotional Problems. Depression and anxiety are common in survivors, particularly those who suffer additional medical conditions. Many patients also suffer from fatigue and aches and pains, called somatic symptoms, which have no apparent physical basis. In one study, such symptoms were more highly associated with intensive chemotherapy. Women and people in lower social and economic groups are at higher risk for depression and somatic symptoms -- just as they are in the general population.

Staging and Treatment Guidelines

Treatment for non-Hodgkin's lymphoma is highly specific for each patient and is determined by the tumor classification. It includes the following factors:

Stage
Grade
Histologic type (cellular structure)
Location
Other factors, such as blood levels of lactate dehydrogenase

Treatment for lymphomas has been primarily dependent on chemotherapy (particularly intensive regimens using several drugs) or a combination of chemotherapy and radiation. For advanced or refractory lymphomas and for relapse, patients may undergo bone marrow or stem cell transplantation. New treatments, especially those known as immunotherapies, or biological response modifier (BRM) therapies, are showing promise. Some experts recommend that patients ask their doctors about getting into well-designed clinical trials as early as possible.

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

In assessing the success of a clinical trial, experts often refer to the tumor response. A complete response, for example, means that there is no longer any evidence at all of the disease by examination, blood tests, or x-ray studies. It does not necessarily mean, however, that the disease is cured. It may still recur later on.

In judging the success of a treatment for NHL, the most important criteria are overall survival and the duration of time until the disease progresses or the patient dies.

In Stage I, lymphoma is found in only one lymph node area or in only one area or organ outside the lymph nodes. Either of the following indicates stage II:

Lymphoma is found in two or more lymph node areas on the same side of the diaphragm.
Lymphoma is found in only one area or organ outside the lymph nodes and in the lymph nodes around it. Other lymph node areas on the same side of the diaphragm may also have lymphoma.

Early Stage Indolent (Low-Grade) Lymphoma. Below are the general treatment options:

Radiation therapy. Radiation to local areas can achieve a cure in 40 - 50% of patients.
Chemotherapy. Chemotherapy uses drugs to kill cancer cells.
Watchful waiting. Patients who choose watchful waiting must be aware of signs and conditions indicating the need for treatment. These include B symptoms, endangered organs, massive bulky tumors, or a steady progression that lasts at least 6 months.
Investigative treatments, such as conjugated and unconjugated monoclonal antibodies or radiation plus chemotherapy. In one study, a combination of therapies worked better than radiation alone.

The following are treatment options for some specific low-grade lymphomas:

Mucosa-associated lymphoid tissue (MALT) lymphoma. When disease is in the stomach (gastric MALT) and the patient is infected with H. pylori bacteria, antibiotics can cause regression in a significant number of patients with stage I lymphoma. In certain patients where antibiotics fail, or are not appropriate, radiation alone can achieve significant cure rates. Surgery with or without radiation, or chemotherapy with or without radiation, are possible options. Treatment options for patients with MALT localized in other sites depend on the location of the specific disease and range from radiation to chemotherapy to biologic therapies, such as interferon.
Primary gastric lymphoma (indolent). Radiation is the typical treatment for this lymphoma, which is located only in the stomach, small intestine, or other nearby regions. Surgery is being reconsidered since it seems to offer no advantage.

Click the icon to see an image of the digestive system.

Early Stage Aggressive (Intermediate- to High-Grade) Lymphomas. Treatment options include:

Chemotherapy alone
Combinations of chemotherapy (usually CHOP) plus radiation therapy
Radiation alone (rarely)
Chemotherapy alone or with surgery for lymphoma in the gastrointestinal region
Immunotherapies (rituximab, Bexxar) with or without chemotherapy (usually CHOP), or high dose chemotherapy and bone marrow or stem cell transplantation

In stage III, lymphoma is found in lymph node areas on both sides of the diaphragm (for instance, in both the chest and the abdomen). The lymphoma may also have spread to the spleen. In stage IV, lymphoma has spread via the bloodstream to organs outside the lymph system, such as the bone marrow or brain. Lymphoma cells may or may not be in the lymph nodes near these organs.

Advanced Stage Indolent (Low-Grade Lymphomas). Treatment options are controversial because of the low-cure rate and yet slow-growing nature of these lymphomas. Patients without symptoms are often managed by watchful waiting, in which the disease is monitored closely for development of symptoms or bulky tumor masses, particularly if they threaten major organs. At such times, treatment is started. Treatment may include:

Chemotherapy combinations (CHOP, CVP, CMOPP)
Nucleoside analogs (for example, fludarabine) alone or with chemotherapy
Oral alkylating chemotherapy drugs such as cyclophosphamide or chlorambucil with or without steroids
Monoclonal antibodies (MAbs) such as rituximab alone or in combinations with CHOP or nucleoside analogs
Chemotherapy plus interferon
Clinical trials involving intensive chemotherapy and radiation followed by bone marrow or stem cell transplantation

Advanced Stage Aggressive (Intermediate- to High-Grade) Lymphomas. Treatment options may include:

Doxorubicin-based combination chemotherapy with or without rituximab
Chemotherapy plus radiation therapy
Immunotherapies with or without chemotherapy
Treatments to prevent disease from spreading to the central nervous system in high-risk patients
Clinical trials for patients at high risk for relapse, involving intensive chemotherapy, high dose chemotherapy, and bone marrow or stem cell transplantation

Indolent-Lymphomas Relapses. Nearly all patients with indolent lymphomas relapse after initial treatment, with length of remission after a first treatment averaging 18 - 50 months. Successful retreatment is often possible, but disease-free periods become increasingly shorter with each subsequent treatment.

Older patients may choose watchful waiting. Other treatment options may include:

Radiation alone or with chemotherapy -- in one study low-dose involved-field radiotherapy was very effective in recurring indolent lymphoma
Chemotherapy
High-dose chemotherapy with autologous stem cell transplant
Clinical trials involving monoclonal antibodies, radioimmunotherapy, nucleoside analogues alone or in combination with other drugs, or stem cell transplantation followed by biologic therapies

Aggressive Lymphomas Relapse. After initial treatment, more than half of patients with aggressive lymphomas are cured, while about 20% progress, and the other 30% relapse after a disease-free period. Among those who relapse, many can still be cured with aggressive treatments.

Treatment options:

Bone marrow or peripheral stem cell transplantation
Bone marrow transplantation with radiation
Clinical trials that involve continuous infusion chemotherapy, biologic therapies (monoclonal antibodies) alone or in combination with transplantation

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

Treating Lymphoma Restricted to the Central Nervous System. Treatment options may include:

High-dose methotrexate regimens alone or in combination with radiation
Corticosteroids and radiation
Clinical trials that involve biologic therapies, such as rituximab or interferon alpha administered directly into the spinal fluid (intrathecal administration) for meningitis related to central nervous system lymphoma

Preventing (Prophylactic Treatment) Lymphomas in High-Risk Patients. Treatment to prevent the spread of NHL to the central nervous system may be appropriate in some patients. It is not recommended for patients with low-grade NHL. Preventive treatment may be appropriate for certain patients with high-grade NHL, such as those with lymphoblastic and Burkitt's lymphoma or if they have 4 - 5 of the following risk factors: Elevated levels in the blood of the enzyme acetate dehydrogenase and albumin (a common protein), being older than 60, and having lymph nodes beyond the peritoneum (the lining of the abdomen) and involvement of more than one site outside a lymph node.

Chemotherapy

Chemotherapy plays a role in the treatment of nearly all lymphoma patients and has achieved remarkable results, even in late stages. It uses drugs to kill cancer cells. Such drugs are called cytotoxic drugs. Chemotherapy is referred to as bodywide or systemic therapy because the drugs travel throughout the bloodstream to the entire body.

Studies indicate that chemotherapy as sole treatment is adequate for most children and young adults in early, and perhaps in many advanced, stages. (Radiation has been commonly used for these patients but can be particularly dangerous for children.)

A chemotherapy cycle is usually 21 - 28 days. Patients take the drugs for a few days, then have a period of rest. The drugs may be taken by mouth or given by injection. Chemotherapy is injected into the spinal fluid if the cancer has spread to the brain. This is called intrathecal chemotherapy. Intrathecal chemotherapy is also used as a preventive measure in patients at high risk for central nervous system involvement. Chemotherapy may be administered at a medical center or in a doctor's office. Some patients receiving chemotherapy need to remain in the hospital for several days so the effects of the drug can be monitored. Patients with lymphoblastic lymphoma may need long-term maintenance chemotherapy. Such therapy does not seem to benefit patients with small-noncleaved-cell and large-cell lymphomas.

CHOP. The current standard chemotherapy regimen for NHL is CHOP. CHOP is a combination of cyclophosphamide, doxorubicin hydrochloride (Adriamycin), vincristine (Oncovin), and prednisone. It is proving to be particularly effective for many stages of lymphoma when used in combination with rituximab (Rituxan), a monoclonal antibody. (See Biologic Therapy section.) Some studies of this combination in low-grade lymphomas have reported response rates of 70 - 100%. CHOP alone is still preferred for HIV patients, who tend to have a toxic response to rituximab.

CVP. This stands for cyclophosphamide, vincristine, and prednisone. It may be used with CHOP in certain cases.

Fludarabine and Nucleoside Analogues. Fludarabine (Fludara) is a type of drug called a nucleoside analogue. It is one of the most active drugs for treating low-grade lymphomas and may be effective for other NHLs, including mantle cell lymphomas. Promising regimens containing fludarabine are under investigation. For example, FND (fludarabine, mitoxantrone, and dexamethasone) may be helpful in combination with rituximab for certain patients, including those with indolent NHL. Other nucleoside analogues include gemcitabine and cladribine. Toxicities and infection rates from high dose nucleoside analogues have been high. Fludarabine also has been associated with a risk for leukemia.

Bendamustine. This potent drug has shown to be effective for indolent NHLs and possibly aggressive lymphomas. One study suggested that a single dose of low-dose etoposide, taken by mouth, may be beneficial for elderly patients.

Antibiotics. Antibiotics, such as doxycycline, may cure or put into complete remission about half of mucosa-associated lymphoid tissue (MALT) lymphoma cases. MALT lymphoma is a type of lymphoma that sometimes affects the eyes. It is associated with the bacterium Helicobacter pylori (H. pylori ), which also causes stomach ulcers. Recent studies indicate that antibiotics are a good alternative to chemotherapy or radiation for patients with this type of lymphoma. Patients most likely to respond positively to antibiotics are those with MALT lymphoma in its early stages.

Vorinostat. Vorinostat (Zolinza) was approved in 2006 for treatment of cutaneous T-cell lymphoma (CTCL), a rare form of NHL.

Side effects and complications of any chemotherapeutic regimen are common. They are more severe with higher doses. Side effects may increase over the course of treatment.

Common Side Effects. Common side effects include:

Nausea and vomiting -- Drugs known as serotonin antagonists, such as ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs and in most patients who take more powerful drugs.
Diarrhea
Hair loss
Weight loss
Depression

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps a few days a month.

Serious Side Effects. Serious chemotherapy side effects can also occur and may vary depending on the specific drugs used. They include:

Neutropenia is a severe drop in white blood cells. Neutropenia increases the chance for infection from suppression of the immune system and is a potentially life-threatening condition. Drugs known as granulocyte colony stimulating factor (G-CSF) are used to help boost white blood cell count. These drugs, which include filgrastim (Neupogen) and pegfilgrastim (Neulasta), can help lessen the risk for neutropenia occurrence and, if neutropenia does occur, to reduce its length and severity.
Anemia is a lack of red blood cells. Erythropoietin stimulates red blood cell (hemoglobin) production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). In 2007, the FDA released strict dosing guidelines for these drugs. In patients with cancer, they should be used to treat only anemia associated with chemotherapy and to increase hemoglobin levels to no more than 12 g/dL. Treatment should stop as soon as chemotherapy is complete. These drugs may not be safe or appropriate for all patients.
Liver and kidney damage
Abnormal blood clotting (thrombocytopenia)
Allergic reaction

Long-Term Complications.

Fatigue and Somatic Symptoms. Chemotherapy has been associated with long-term somatic symptoms, which are general conditions, such as fatigue and aches and pains that have no apparent physical basis. Fatigue is especially common after chemotherapy and can even last for years.
The most serious long-term complications from chemotherapy are secondary cancers, particularly in people over age 40.
Infertility is a risk, particularly with the use of cyclophosphamide.
Some patients get osteoporosis (bone thinning) and damage in bone cells.
Regimens containing certain drugs, particularly doxorubicin or mitoxantrone, increase the risk for future heart failure.

Click the icon to see an image of the uterus and ovaries.

In general, these serious late side effects are dependent on the cumulative drug dose and rate of administration.

Doctors are particularly concerned about the effects of combinations of chemotherapy with radiation, especially leukemia and heart problems. Interestingly, in one study on patients with intermediate- and high-grade NHL, those on chemotherapy alone had more toxic effects than those on combined modality, most likely because it employed fewer cycles of chemotherapy. Better radiation techniques are also reducing the risks of combined modality treatments.

Biologic Therapy (Immunotherapy)

Biological response modifier therapy, also called immunotherapy, uses the body's own immune system to fight cancer using natural or laboratory-developed factors. These drugs are often combined with other treatments.

Monoclonal antibodies (MAbs) are designed in the laboratory to produce the same effects as natural antibodies and are exciting new weapons in the anti-cancer armament. They bind to specific proteins called antigens and make them vulnerable to attack by other factors in the immune system. Lymphomas carry antigens that provoke strong immune responses and so are believed to be particularly good candidates for MAb therapy.

MAbs are called either unconjugated or conjugated, depending on how they are designed to destroy the cancer cell.

Unconjugated monoclonal antibodies rely on a strong natural immune system. The antibody builds up at the tumor site until it is able to trigger an immune response against the cancer. A possible downside to this form is the potential development of tolerance to the antibody so that it loses its effectiveness. Rituximab is an unconjugated form and the first MAb to be approved for any cancer.
Conjugated monoclonal antibodies are linked to a plant or bacterial toxin or radioisotope. The antibody specifically attacks the antigen on the lymphoma cell, and the toxin or radioactive material from the isotope kills it.

Unconjugated MAbs (Rituximab). Rituximab (Rituxan) was the first monoclonal antibody approved for cancer. This drug targets the CD-20 antigen, which is found on most B-cell lymphomas.

First approved in 1997 for treatment of relapsed or refractory NHL, rituximab has received several expanded indications since that time. As of 2006, rituximab is approved for:

Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell, NHL
First-line treatment of diffuse large B-cell (DLBC), CD20-positive, NHL in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens
First-line treatment of follicular, CD20-positive, B-cell NHL in combination with CVP (cyclophosphamide, vincristine and prednisolone) chemotherapy
Low-grade, CD20-positive, B-cell NHL in patients with stable disease or patients who have been partially or completely helped by first-line treatment with CVP chemotherapy

Rituximab in combination with CHOP (a regimen called R-CHOP, or CHOP-R) is used for first-line treatment for aggressive lymphomas, with studies reporting 3-year event-free survival of 53% compared to 35% with CHOP alone. A 2006 study also indicated that rituximab provides benefits when used as maintenance treatment after CHOP or R-CHOP induction therapy. Rituximab plus CHOP is also showing promise as a first-line treatment for mantle cell lymphoma.

Rituximab is given by infusion. The treatment has mild-to-moderate short-term side effects, including nausea, fever, chills, hives, dizziness, and headache. Uncommon and more serious side effects are severe allergic reactions, very low blood pressure, blood abnormalities, wheezing, infections, and sudden heart events.

Rituximab has also been associated with cases of progressive multifocal leukoencephalopathy (PML), a rare and potentially deadly brain infection. Patients who experience any of the following symptoms should immediately contact their doctors:

Vision problems or unusual eye movements
Confusion
Dizziness or loss of balance
Difficulty talking or walking

Patients who have previously had hepatitis B, or who are at high-risk for this viral infection, should be tested before taking rituximab because the drug has been linked to reactivation of the hepatitis B virus. Patients who are HIV-positive may experience more adverse effects from rituximab than with CHOP.

Conjugated Monoclonal Antibodies with Radioimmunotherapy. Conjugated MAbs with radioimmunotherapy contain tiny amounts of radioactive materials. When the drug is injected, the monoclonal antibody targets an antigen (protein) on the surface of the tumor. The radioisotope is then delivered directly into the tumor where it kills the cancer. Ibritumomab and tositumomab both target the CD-20 antigen. Treatment with these drugs takes about 7 - 9 days to complete, compared to several months for traditional chemotherapy treatments.

Ibritumomab (Zevalin) is approved for patients with relapsed or refractory low-grade, follicular or transformed B-cell NHL. It is also approved for patients with follicular NHL who have not responded to rituximab (Rituxan). Research indicates it may also be safe for patients with advanced NHL who have had stem cell transplantation. Zevalin uses an yttrium-90 (90-Y) radioactive isotope.
Tositumomab and Iodine I-131 (Bexxar) combines the monoclonal antibody tositumomab with the radioisotope I-131. The Bexxar treatment is approved for treatment of relapsed or refractory low-grade, follicular, or transformed B-cell NHL. Overall response rates of 56% have been reported with Bexxar, with up to 30% being complete responses (no evidence of cancer). Recent studies suggest that when Bexxar is used as a first treatment, it may produce long-term complete remission in patients with advanced stage follicular lymphoma. In a 2005 New England Journal of Medicine study, 95% of previously untreated patients with advanced follicular lymphoma responded to Bexxar, and 75% had complete responses. Seventy percent who had complete responses from Bexxar treatment were still disease-free 4 - 7 years later.

In general, these drugs cause fewer side effects than traditional chemotherapy. However, serious complications may include skin infections, severe allergic reactions, and temporary lowering of blood counts.

Other Monoclonal Antibodies. Other MAbs are being developed that target other antigens on lymphomas. For example, epratuzumab targets CD-22 and is showing promise in early studies. Some are being studied in both conjugated and unconjugated forms and also in combination with MAbs that target different antigens.

Interferon alpha (Intron A) is used as an antiviral drug that also has properties that are effective against some common forms of NHL, particularly low-grade, follicular NHL in advanced stages. It is usually combined with chemotherapy regimens such as CHOP that contain an anthracycline drug (usually doxorubicin). The combination is toxic, however, and outcomes vary. Interferon is also being studied for lymphomas in the central nervous system. It may be useful after autologous stem cell transplantation.

Side Effects. Side effects of interferon include flu-like symptoms, severe depression, irritability, weight loss, vomiting, general weakness and loss of strength, and fever. About a third of patients have a severe drop in white blood cells. About 10% of patients cannot tolerate the drug's side effects.

Cytotoxic Deoxyguanosine Analogue Prodrugs. Nelarabine (Arranon) is approved for treating T-cell lymphoblastic lymphoma (T-LBL). T-LBL is a rare form of lymphoma that accounts for less than 2% of all cases of NHL.

Proteasome Inhibitors. In 2006, bortezomib (Velcade) was approved for treatment of mantle cell lymphoma in patients who have received at least one prior therapy.

Cyclin-Dependent Kinase Inhibitors. Flavopiridol, a drug known as a cyclin-dependent kinase inhibitor, is showing some effect in patients with mantle-cell lymphoma. This drug is designed to block enzymes that regulate cell cycles and help block their growth.

Vaccines. Although still experimental, lymphoma vaccines are used to treat -- not prevent -- cancer. They are part of an immunotherapy approach called personalized medicine; each vaccine is individually tailored to the genetic composition of the patient’s tumor. The vaccine is usually given a few months after a patient receives chemotherapy. Several different vaccines, including the BiovaxID and MYVax, are in late-stage clinical trials.

Radiation

Radiation is commonly used to treat indolent lymphomas. The dose administered ranges from 35 - 50 Gy and depends on a number of factors: The type of lymphoma, the age of the patient, whether the intent is to cure or relieve symptoms, how close sensitive organs are to the diseased area, and whether radiation is being combined with chemotherapy.

Radiation is tailored to the individual and usually limited to the diseased areas and possibly nearby regions:

If the lymphoma is confined to tissues above the diaphragm, radiation is delivered to the neck, chest, and under arms (called the mantle-field) and sometimes to lymph nodes in the upper abdomen or spleen or both.
If the lymphoma is below the diaphragm, subtotal nodal radiation may be used, which is directed to other regions, including lymph nodes in the upper abdomen, spleen, and pelvis, in addition to the mantle-field.
Radiation to the brain is called cranial radiation.
Total body irradiation is sometimes performed, although it is not clear whether its high toxicity outweighs any advantages.

Devices called planning simulators allow doctors to plan x-ray treatments that accurately conform to the patient's anatomy so that protective shields can be created to precisely protect the regions outside the treatment areas.

Side effects and complications of radiation generally depend on the target site in the body. They include:

Dental problems
Inflammation in the lungs -- with carefully conducted therapy, the risks for lung complications are small. Lung impairment may not even be evident, and the lungs usually recover after 2 - 3 years.
Hypothyroidism
Infections
Long-term risk for heart disease
Long-term risk for certain cancers -- of particular concern is a possible increased risk for breast cancer. Studies indicate that young women and adolescent girls are at highest risk, with the incidence increasing significantly 15 years after treatment. The risk is greater in those who had higher radiation doses. Radiation may also increase the risk over time for other cancers, including lymphoma and thyroid, lung, and colon cancers, although the risk is still low. Smoking, of course, increases the risk for lung cancer. Radiation of bone marrow increases the risk for leukemia.
Impaired bone growth -- children and adolescents are at special risk for bone problems caused by radiation. Experts are finding that radiation for many children and young adults in early stages or NHL is no more effective and has more serious long-term effects than chemotherapy. Some believe that radiation should play no role in the treatment of young people, except in special cases, such as lymphomas that require radiation to the brain.
Infertility -- the negative effects on fertility may be worse in women than in men; sperm usually recover within 5 years. To protect the ovaries, a technique called ovarian transposition is sometimes used. Transposition may sometimes be performed through a laparoscope, a thin tube containing tiny instruments and cameras, which is introduced through a small incision. The doctor uses the laparoscope to move the ovaries out of the range of areas being treated with radiation.

Click the icon to see an image of the lungs.

Click the icon to see an image of hypothyroidism.

Click the icon to see an image of the uterus and ovaries.

Transplantation

Stem cell procedures have proven to produce long-term survival and even cures in some patients with intermediate- and high-grade non-Hodgkin's lymphomas.

Stem cell transplantation involves removing and replacing stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments harm growing cells as well as cancer cells, and so the healthy stem cells must be replaced by transplanting them from the donor into the patient.

Sources of Cells. Stem cells must first be collected in one of the following ways:

Directly from blood, called peripheral blood stem cell transplantation
From bone marrow, called bone marrow transplantation
From umbilical cords or placentas -- this procedure uses donor cells, but has a lower risk for immune system rejection of the cells than with a standard donor transplant. It takes longer to restore blood cells with this process, so it is generally used for children and sometimes adults with low weight.

Some evidence suggests that both stem cell and bone marrow procedures produce similar benefits in terms of response rates and duration of remission. However, in one study, stem cell transplantation was associated with better overall survival rates. It also seems to be superior in terms of cost, quality of life, and the need for less supportive care.

Donor or Patient Cells. The marrow or blood stem cells can be taken from the patient (autologous) or from a matched donor (allogeneic):

In an autologous transplant, the marrow or blood cells used for replacement are taken from the patient. There is some danger, however, that these cells may contain tumor cells, and that the cancer can regrow. It is unclear if this approach improves survival compared to standard chemotherapy for newly diagnosed disease. However, it clearly has benefits in the treatment of some forms of relapsed non-Hodgkin's lymphomas. There is also a higher risk for leukemia. (This risk is lower in peripheral stem cells transplants than in bone marrow transplants.)
In an allogeneic transplant, bone marrow or stem cells are taken from a donor. Siblings are the best donors. Relapse rates can be very low with this approach, and cure may be possible in some cases. However, it is highly toxic and donor and recipient must be matched as closely as possible to avoid rejection by the immune system, a serious complication called graft-versus-host disease. Advances in techniques are reducing the toxicities associated with this approach. Older patients who cannot tolerate the preparatory treatment required for a standard allogeneic transplant may be able to receive a non-myeloblative transplant (“mini-transplant), which uses lower doses of chemotherapy and radiation.

The Blood Stem Cell Collection Procedure. With peripheral blood stem cell transplantation:

The donor is usually given a drug called granulocyte colony-stimulating factor, or G-CSF (filgrastim, lenograstim, pegfilgrastim) to stimulate stem cell growth.
The patient (or donor in an allogeneic procedure) then undergoes apheresis. With this process the blood is withdrawn from one of the patient's veins, then passes through a machine that filters out the white cells and platelets, which contain the stem cells. The blood is returned through another vein. The entire procedure takes 3 - 4 hours but needs to be repeated several times.
The stem cells are treated to remove contaminants and then are frozen to keep them alive until the patient is ready to receive them back.

Blood is the only fluid tissue in the body. Blood transports oxygen and nutrients to body tissues, and returns waste and carbon dioxide. Blood distributes nearly everything that is carried from one area in the body to another place within the body. For instance, blood helps transport hormones from the endocrine organs to their target organs. Blood also helps maintain body temperature. The protective functions of blood include clot formation and the prevention of infection.

Allogeneic transplants are preceded by chemotherapy treatment known as conditioning. The point of this treatment is to inactivate the immune system and to kill any residual malignant cells. It is extremely toxic since it also destroys non-malignant marrow cells. Drugs used are typically cyclophosphamide, carmustine, and etoposide. Alternative conditioning to reduce toxicity includes total-body radiation plus drugs. Monoclonal antibodies, such as rituximab, are promising drugs, since they have low toxicity and may add benefits for all stages of transplantation.
A few days after treatment, the patient given the stored stem cells, which are administered through a vein. This may take several hours. Patients may have a fever, chills, hives, shortness of breath, or a fall in blood pressure during the procedure.
The patient may be treated with granulocyte colony-stimulating factor after chemotherapy. The goal is to stimulate the growth of infection-fighting white blood cells. Adding thrombopoietin may help enhance stem cell production.
The patient is kept in a protected environment to minimize infection. Patients who have received an allogeneic transplant may need blood cell replacement, nutritional support, and drugs to treat graft-versus host disease. They usually can leave the hospital within 3 - 5 weeks.

Candidates. These procedures are typically used for patients with relapsed aggressive lymphoma who are still sensitive to the effects of chemotherapy. The procedures do not work for patients whose tumors are not responsive to drugs. Some evidence suggests that certain primary (non-relapsed) lymphomas initially unresponsive to a first round of chemotherapy but who respond to a second round may benefit from combination of high-dose chemotherapy and radiation followed by transplantation. Transplantation is also being investigated as first-line therapy for patients with aggressive lymphomas, although at this time evidence does not support its use.

Success Rates. Success rates vary depending on many factors. The following are survival rates reported by a few studies of patients with different lymphomas:

In patients with refractory or relapsed intermediate grade NHL who received autologous transplantation, 5-year survival rates averaged 34%.
In a study of allogeneic bone marrow transplantation, 58% of patients with late-stage low-grade lymphoma had survived after an average of 29 months.
Patients with anaplastic large-cell lymphoma were treated with autologous stem cell transplantation with intensified chemotherapy as first line-therapy. Survival rates were 87% at 5 and more years afterward. (Survival was much lower with other lymphomas.)
Patients with diffuse aggressive NHL who did not achieve a first remission but who are still sensitive to chemotherapy achieved a 5-year survival rate of up to 37% after autologous stem cell transplantation.
In one study, 35% of patients with an initial poor prognosis were still alive 5 years after an allogeneic stem cell transplantation, although mortality probability from the treatment itself was very high (48%).

Common side effects include nausea, vomiting, fatigue, mouth sores, and loss of appetite.

The procedures themselves are fairly dangerous and carry a small risk for death. When it was first used, transplantation procedures had 10 - 25% morality rates. Now mortality rates are below 5%.

Infection resulting from a weakened immune system is the most common side effect. Because the stem cell procedure is done more swiftly, the risk period is shorter than with bone marrow transplantation. The risk for infection is most critical during the first 6 weeks following the transplant, but it takes 6 - 12 months post-transplant for a patient’s immune system to fully recover. Immune systems of patients with graft-versus-host disease can take even longer to function normally.

Many patients develop severe herpes zoster virus infections (shingles) or have a recurrence of herpes simplex virus infections (cold sores and genital herpes). Pneumonia, cytomegalovirus, aspergillus (a type of fungus), and Pneumocystis carinii (a protozoan) are among the most important life-threatening infections.

It is very important that patients take precautions to avoid infections. Guidelines for post-transplant infection prevention include:

Discuss with your doctor what vaccinations you need and when you should get them.
Avoid crowds, especially during cold and flu season.
Be diligent about handwashing and make sure that visitors wash their hands.
Avoid eating raw fruits and vegetables -- food should be well cooked. Do not eat foods purchased at salad bars or buffets. In the first few months after the transplant, be sure to eat protein-rich foods to help restore muscle mass and repair cell damage caused by chemotherapy and radiation.
Boil tap water before drinking it.
Dental hygiene is very important, including daily brushing and flossing. Schedule regular visits with your dentist.
Do not sleep with pets. Avoid contact with pets’ excrement.
Avoid fresh flowers and plants as they may carry mold. Do not garden.
Swimming may increase exposure to infection. If you swim, do not submerge your face in water. Do not use hot tubs.
Report to your doctor any symptoms of fever, chills, cough, difficulty breathing, rash or changes in skin, and severe diarrhea or vomiting. Fever is one of the first signs of infection. Some of these symptoms can also indicate graft-versus-host disease.
Report to your ophthalmologist any signs of eye discharge or changes in vision. Patients who undergo radiation or who are on long-term steroid therapy have an increased risk for cataracts.

Graft-versus-host disease (GVHD) is a serious attack by the patient's immune system triggered by the donated new marrow in allogeneic transplants. Mild cases of GVHD can actually be helpful as they can cause graft-versus-lymphoma where the immune system kills remaining lymphoma cells. Still, severe GVHD can pose serious complications.

To reduce the risk for GVHD, doctors remove some immune T-cells from the donor’s stem cells before the transplant. Researchers are investigating new techniques to refine this process of T-cell depletion.

Acute GVHD occurs in 30 - 50% of allogeneic transplants, usually within 25 days. Its severity ranges from very mild symptoms to a life-threatening condition (more often in older patients). The first sign of acute GVHD is a rash, which typically develops on the palms of hands and soles of feet and can then spread to the rest of the body. Other symptoms may include nausea, vomiting, stomach cramps, diarrhea, loss of appetite and jaundice (yellowing of skin and eyes). To prevent acute GVHD, doctors give patients immune-suppressing drugs such as steroids, methotrexate, cyclosporine, tacrolimus, and monoclonal antibodies.

Chronic GVHD can develop 70 - 400 days after the allogeneic transplant. Initial symptoms include those of acute GVHD. Skin, eyes, and mouth can become dry and irritated, and mouth sores may develop. Chronic GVHD can also sometimes affect the esophagus, gastrointestinal tract and liver. Bacterial infections and chronic low-grade fever are common. Chronic GVHD is treated with similar medicines as acute GVHD.

Too much sun exposure can trigger GVHD. Be sure to always wear sunscreen (SPF 15 or higher) on areas of the skin that are exposed to the sun. Stay in the shade when you go outside.

Secondary cancers. There is a small long-term risk for leukemia after transplantation in young people. Use of newer chemotherapeutic drugs, however, may not pose as high a danger as older treatments.

Other potentially serious complications include:

Bleeding because of reduced platelets (highest risk within the first 4 weeks); blood transfusions may be required
Infertility
Organ complications to the liver, heart, kidney, or lungs
Failure of the transplant
Muscle problems including stiffness, cramps, and joint pain
Frequent urination and bladder control problems
Older patients should be screened for osteoporosis (bone thinning) and hypothyroidism (underactive thyroid)

Surgery

Surgery is sometimes used to remove as much malignant tissue as possible before administering chemotherapy. This is particularly useful for bulky tumors that occur in the stomach.

Surgery is sometimes performed for primary gastric lymphoma, but its advantages are uncertain. Some studies indicate that chemotherapy alone or with radiation may be sufficient and could spare many patients from surgery.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.leukemia.org -- The Leukemia and Lymphoma Society
www.canceradvocacy.org -- National Coalition for Cancer Survivorship
www.marrow.org -- National Marrow Donor Program
www.asco.org -- American Society of Clinical Oncology
www.lymphoma.org -- Lymphoma Research Foundation
www.plwc.org -- People Living with Cancer
www.oncolink.org -- Cancer information
www.fhcrc.org/science/clinical/ltfu/patient -- Fred Hutchinson Cancer Research Center -- Transplant Infection Guidelines for Patients
www.lymphomainfo.net -- Lymphoma Information Network
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Boffetta P, de Vocht F. Occupation and the risk of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2007: 16(3):369-72.

Ferrara JL. Novel strategies for the treatment and diagnosis of graft-versus-host-disease. Best Pract Res Clin Haematol. 2007. 20(1):91-7.

Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10;25(5):571-8. Epub 2007 Jan 22.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin’s Lymphoma. V.3.2007.

Seam P, Juweid ME, Cheson BD. The role of FDG-PET scans in patients with lymphoma. Blood. 2007 Nov 15;110(10):3507-16. Epub 2007 Aug 20.

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

adam.com

Weight management

admin — Thu, 04 Sep 2008 18:49:43 -0700

Overview

Definition
Information

Illustrations

Calculating body frame size

Hunger center in brain

Muscle cells vs. fat cells

Yo-yo dieting

Weight loss

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Weight management means keeping your body weight at a healthy level.

Information

Regular exercise and a healthy diet are crucial when it comes to controlling your weight. A weight management plan depends on whether you are overweight or underweight.

An easy way to determine your own desirable body weight is to use the following formula:

Women: 100 pounds for the first 5 feet of height plus 5 pounds for each additional inch.
Men: 106 pounds of body weight for the first 5 feet of height plus 6 pounds for each additional inch.
For a small body frame, 10% should be subtracted. For a large frame, 10% should be added.

Body fat and body mass measurements are used to determine whether a person is under- or overweight. A registered dietitian or exercise physiologist can help you calculate your body fat. The recommended amount of body fat differs for men and women.

For women:

The recommended amount of body fat is 20 - 21%.
The average American woman has approximately 22 - 25% body fat.
A woman with more than 30% body fat is considered obese.

For men:

The recommended amount of body fat is 13 - 17%.
The average American man has approximately 17 - 19% body fat.
A man with 25% body fat or higher is considered obese.

Body mass index (BMI) is an indirect measurement of your body composition. It takes into consideration both your weight and height. BMI helps determine your risk for certain diseases, including diabetes and hypertension.

It is important to note that the terms "overweight" and "obesity" do NOT mean the same thing.

Weight management for people who have been overweight involves continued physical activity and monitoring the amount of food eaten.

UNDERWEIGHT

Anorexia nervosa and bulimia are eating disorders associated with a negative body image. Anorexia nervosa is a disorder in which people extremely limit their food intake. This results in dangerously quick weight loss, to the point of starvation. This disorder is most commonly found in adolescent females, but may also occur in males, children, and adults.

Bulimia is binge eating followed by self-induced vomiting. It's often associated with anorexia nervosa. Many people with bulimia don't lose a lot of weight, and may not get medical attention until they seek help.

Excessive intentional weight loss can cause a person to be dangerously underweight. To maintain their weight, people with eating disorders must eat enough food to prevent them from losing the weight they have gained.

CALORIES FOR WEIGHT MAINTENANCE

To maintain your weight, you can use the following formula:

10 calories per pound of desirable body weight if you are sedentary or very obese
13 calories per pound of desirable body weight if your activity level is low, or if you are over age 55
15 calories per pound of desirable body weight if you regularly do moderate activity
18 calories per pound of desirable body weight if you regularly do strenuous activity

Activity levels:

Low activity: No planned, regular physical activity; occasional weekend or weekly activity (such as golf or recreational tennis) is the only type of physical activity
Moderate activity: Participating in physical activities such as swimming, jogging, or fast walking for 30 - 60 minutes at a time
Strenuous activity: Participating in vigorous physical activity for 60 minutes or more at least 4 - 5 days per week

A BALANCED DIET

Do not eat meat more than once a day. Eat fish and poultry more often than red or processed meats because they are less fattening.
Avoid frying food. Fried food absorbs the fats from the cooking oils, increasing your dietary fat intake. Instead, bake or broil food. If you do fry, use polyunsaturated oils, such as corn oil.
Cut down on your salt intake. Limit table salt, or flavor intensifiers that contain salt, such as monosodium glutamate (MSG).
Include adequate fiber in your diet. Fiber is found in green leafy vegetables, fruit, beans, bran flakes, nuts, root vegetables, and whole-grain foods.
Do not eat more than 4 eggs per week. Although they are a good source of protein, and they're low in saturated fat, eggs are very high in cholesterol.
Choose fresh fruit for dessert, rather than cookies, cake, or pudding.
Eat a well-balanced diet. Too much of anything -- calories or a particular type of food -- has its drawbacks.
Follow the recommendations of the food guide pyramid.

RECOMMENDATIONS FOR WEIGHT MANAGEMENT

To successfully manage your weight, follow these basic guidelines:

Eat a healthy, well-balanced diet.
Balance physical activity with diet to maintain your desired weight. Aerobic exercise will help increase muscle tissue and burn calories.
Gradually adjust your eating habits to encourage a permanent lifestyle change. You may need counseling and behavior modification to change your diet.
Avoid alcohol, or drink in moderation.

RESOURCES

A registered dietitian is an excellent resource for individualized weight management. The registered dietitian can provide information on classes and programs available in your community.

The Federal Trade Commission offers consumer brochures that evaluate commercial weight management programs.

Note: 1 calorie equals 1000 calories or 1 kilocalorie.