FitSugar

Dietitian vs. Nutritionist

FitSugar — Fri, 28 Sep 2007 09:30:00 -0700

A dietitian is an expert in food and nutrition. They give dietary advice, help promote healthy eating habits, develop specific diets for people, and participate in nutrition research. In the U.S., nutrition professionals include the registered dietitian (RD), and the dietetic technician, registered (DTR). They are regulated by the American Dietetic Association (ADA). They must meet strict educational and professional prerequisites and pass a national exam before they are registered dietitians.

Nutritionists are health specialists who are interested in food and nutritional science, preventative nutrition, diseases related to nutrient deficiencies, and the use of food and nutrients to cure disease and ailments.

They also are not regulated. They have varying degrees of education in nutrition – some have very little and some have a masters or phD. Since the term "nutritionist" isn't regulated, anyone can call themselves a nutritionist and dispense nutritional information without having any education whatsoever - they even write books.

Fit's Tips: If you want advice on your diet, food, or nutrition, I'd see a dietitian unless a nutritionist could prove to you how much education they've had.

Source

Fiber

FitSugar — Wed, 08 Oct 2008 17:35:33 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Overview

Dietary fiber, found in the walls of plant cells, cannot be digested by enzymes in the human digestive tract but plays an essential role in human health. It is found in all plant-based foods, with most whole foods containing a combination of the two types of fiber, including soluble and insoluble fiber. Both types of fiber help maintain the health of the intestinal tract and promote regular elimination of stool.

Soluble fiber attracts water and forms a gel in the digestive tract. This slows digestion and lowers the rate of nutrient absorption (such as starch and sugars) from the stomach and intestine. The result is a significant reduction in cholesterol levels over time, which may help prevent heart disease and stroke. Intake of soluble fiber may also improve glucose tolerance in people with diabetes. Psyllium husk, pectin, and the soft parts of fruits, dried beans, and peas are examples of soluble fiber.

Insoluble fiber, on the other hand, is the portion of plant cells that gives the wall its structural integrity. Insoluble fiber can be found in the peels of fruit, such as apples, blueberries, and grapes. It acts as a natural laxative that speeds the passage of foods through the stomach. It also gives stool its bulk and helps it move quickly through the gastrointestinal tract.

Dietary fiber has been shown to play a role in the treatment of conditions such as gastrointestinal disease, constipation, hemorrhoids, high cholesterol, heart disease, and diabetes. However, most Americans consume only 11 - 13 grams of dietary fiber per day -- less than half the amount recommended by health care professionals. It has been recommended that Americans should strive to achieve a total dietary fiber intake of 25 - 30 grams daily, preferably from foods and not supplements.

Uses

Constipation

Many well-designed clinical studies have concluded that fiber relieves constipation. Clinical studies have used wheat bran and psyllium primarily. Fiber is believed to relieve constipation by adding bulk to stool and speeding its transit through the gastrointestinal tract.

Diarrhea

When recommended by a health care provider, fiber can be used to relieve mild-to-moderate diarrhea. Soluble fiber soaks up a significant amount of water in the digestive tract, thereby making stool firmer and slower to pass.

Irritable bowel syndrome (IBS)

Several well-designed clinical studies have found that soluble fiber helps regulate stool frequency and consistency in people with IBS.

Hemorrhoids

Soluble fiber may be recommended by a doctor to help soften stool and reduce the pain associated with hemorrhoids.

Inflammatory bowel disease (IBD)

In a clinical study of people with ulcerative colitis (a type of IBD), psyllium seeds were as effective as the prescription drug mesalamine in reducing recurrences of the disease. In addition, a doctor may recommend the use of fiber as a bulking agent for mild-to-moderate cases of diarrhea from either ulcerative colitis or Crohn's disease (another important type of IBD).

Diverticulosis

Patients with diverticulosis are often given fiber supplements to increase the tone of their digestive tract. The American Dietetic Association (ADA) recommends 25 - 30 grams per day. Some nutritionally-oriented doctors may recommend even more. Care should be taken to discuss the appropriate type of fiber for each individual patient as certain types of fiber may actually aggravate diverticulosis. In particular, avoidance of nuts, pumpkin, caraway, and sesame seeds is recommend out of concern that the small particles may get lodged in the diverticula and cause infection and irritation.

High cholesterol

Soluble fibers, such as those in psyllium husk, guar gum, and oat bran, have a cholesterol-lowering effect when added to a low-fat, low-cholesterol diet. Clinical studies have shown psyllium, in particular, to be quite effective in lowering total as well as low density lipoprotein (LDL or "bad") cholesterol levels.

Diabetes

Clinical studies suggest that a high-fiber diet may help prevent type 2 diabetes, lower insulin and blood sugar levels, and improve cholesterol and triglyceride levels in people with diabetes. In addition, one well-designed clinical study suggests that pregnant women with type 1 diabetes are able to lower the amount of insulin they use if they eat a high fiber diet.

A clinical study compared patients with type 2 diabetes who were consuming 50 grams of fiber daily with patients following the American Diabetes Association’s recommendation of 24 grams of fiber daily. After 6 weeks, patients on the higher fiber diet had substantially better control of blood glucose, insulin, and blood lipids. In another clinical study, a group of men with type 2 diabetes who took psyllium twice daily experienced significant improvements in blood glucose and lipid values compared to a control group taking a placebo.

Obesity

Clinical studies and human case reports suggest that soluble fiber (such as psyllium, pectin, and guar gum) may enhance the sensation of fullness and reduce hunger cravings. For these reasons, incorporating soluble fiber into the diet may aid weight loss.

High blood pressure

Although not entirely conclusive, the addition of fiber (namely, 12 grams of soluble fiber per day) may help lower blood pressure (also called hypertension).

Heart disease

Incorporating high-fiber foods (such as oatmeal, oat bran, psyllium, and legumes) into the diet may help lower heart disease risk.

Colon cancer

Although initial clinical reports were promising, studies investigating the value of a high-fiber diet for colorectal cancer have been conflicting. While some clinical studies evaluating groups of people have suggested that fiber protects against the development of colorectal cancer, most large, better-designed clinical studies have found only a minimal association between fiber intake and colorectal cancer risk. In addition, fiber does not appear to protect against the recurrence of colorectal cancer in people who have already been treated for the condition.

Other types of cancer

Preliminary clinical evidence suggests that a diet high in fiber (in conjunction with lifestyle changes and conventional medication) may help protect against the development of certain types of cancer such as prostate, breast, and lining of the uterus. Further studies are needed to confirm these findings, however.

Dietary Sources

Soluble fiber is found in dried beans and peas, oats, barley, fruits, and psyllium seed husks.

Insoluble fiber is found primarily in fruits and vegetables, whole-grain products, whole grain cereals, and wheat and corn bran.

Available Forms

Dietary fiber is available as a supplement in several forms, including fiber tablets, capsules, and powders. Fiber is also available as bulk fiber laxatives, including psyllium.

How to Take It

The National Academy of Sciences' Institute of Medicine, which provides science-based advice on matters of medicine and health, gives the following daily fiber recommendations for adults:

Pediatric

Infants and children under 18 years of age: There is no specific dietary amount established for pediatric fiber intake. Children with specific fiber needs should increase the daily intake of fibrous foods slowly over a period of days. Fiber supplements should only be taken under the guidance of a qualified health care practitioner.

Adults

For adult males ages 19 - 50: The recommended daily fiber intake amount is 38 grams.

For adult females ages 19 – 50: The recommended daily fiber intake amount is 25 grams.

For adult males ages 51 and older: The recommended daily fiber intake amount is 30 grams.

For adult females ages 51 and older: The recommended daily fiber intake amount is 21 grams.

If you are not getting enough fiber each day, you may need to boost your fiber intake in the diet. Choose whole-grain products, raw or cooked fruits and vegetables, dried beans, and dried peas. Refined or processed foods, including fruit juices, white breads, pastas, and rice, and non-whole-grain cereals, are lower in fiber content. The grain-refining process removes the outer coat (bran) from the grain, which lowers its fiber content. Similarly, removing the skin from fruits and vegetables decreases their fiber content.

Precautions

Because supplements may have side effects or interact with medications, they should be taken only under the supervision of a knowledgeable health care provider.

In general, fiber supplements may reduce or delay the absorption of certain medications. For this reason, it is best to refrain from taking fiber supplements at the same time as other medications. Instead, medications should be taken at least 1 hour before or between 2 - 4 hours after taking fiber.

Fiber should always be taken with a full 8 oz glass of water. It is also important to drink at least 6 - 8 full glasses of water throughout the day or constipation may develop. Taking fiber supplements without adequate liquids may cause it to swell and, in extreme cases, cause choking. Do not take this product if you have difficulty swallowing. People with esophageal stricture (narrowing of the esophagus) or any other narrowing or obstruction of the gastrointestinal tract should not take fiber supplements.

If you experience chest pain, vomiting, or difficulty swallowing or breathing after taking fiber supplements, seek immediate medical attention.

A potential side effect from any fiber product is gas and bloating.

Although very uncommon, allergic reactions (even anaphylaxis) to soluble fiber may develop in people who consume these types of supplements over a long period of time.

Possible Interactions

If you are currently being treated with any of the following medications, you should not use fiber supplements without first talking to your health care provider.

Antidepressant medications (Tricyclic antidepressants) -- Dietary fiber has been reported to lower the blood levels and effectiveness of tricyclic antidepressant medications, such as amitriptyline (Elavil), doxepin (Sinequan), and imipramine (Tofranil), in several patients. Reduced dietary fiber intake increased the blood levels and improved symptoms in these patients. Individuals currently taking tricyclic medications should consult a health care provider before increasing fiber intake.

Diabetes medications -- While fiber supplements may help to regulate blood sugar levels, they may also interfere with the absorption of anti-diabetic medications, specifically glyburide (Diabeta) and metformin (Glucophage). Therefore, fiber supplements should not be taken at the same time as these medications.

Carbamazepine -- Taking soluble fiber such as psyllium with carbamazepine (Tegretol), a medication used to treat seizure disorders, may decrease the absorption and effectiveness of carbamazepine. A health care provider should close monitor blood levels of anyone taking both soluble fiber and carbamazepine.

Cholesterol-lowering medications -- Combining psyllium or other soluble fibers with cholestyramine (Questran) or colestipol (Colestid), two types of cholesterol-lowering medications known as bile acid sequestrants, may be beneficial in lowering cholesterol levels. Individuals taking these medications should consult a health care provider to determine whether psyllium is safe and appropriate.

Fiber in the form of pectin (from fruit) and oat bran reportedly reduces the body's ability to absorb cholesterol-lowering medications known as "statins," including lovastatin (Mevacor) and atorvastatin (Lipitor), and could lead to decreased effectiveness of these medications.

Digoxin -- Fiber supplements may reduce the body's ability to absorb digoxin (Lanoxin), a medication used to regulate heart function. Therefore, fiber supplements should not be taken at the same time as this medication.

Lithium -- Clinical reports suggest that psyllium or other soluble fibers may lower lithium levels in the blood, reducing the effectiveness of this medication. Lithium levels should be monitored very closely by a health care provider, particularly if there is any significant change in fiber intake.

Penicillin -- In one clinical study, the fiber supplement guar gum reduced blood levels of penicillin. Therefore, it would be best not to take penicillin at the same time as fiber supplements.

Supporting Research

Alabaster O, Tang ZC, Frost A, Sivapurkar N. Potential synergism between wheat brain and psyllium: enhanced inhibition of colon cancer. Cancer Lett. 1993;75:53–58.

Alberts DS, Martínez ME, Roe DJ, et al. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. N Eng J Med. 2000;342(16):1156-1162.

American Diabetes Association. Nutrition recommendations and principles for people with diabetes mellitus. Diabetes Care. 1999;22(1):S42-S45.

Anderson JW, Allgood LD, Lawrence A, et al. Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials. Am J Clin Nutr. 2000;71:472-479.

Anderson JW, Allgood LD, Turner J, Oeltgen PR, Daggy BP. Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia. Am J Clin Nutr. 1999;70:466-473.

Appel LJ. Nonpharmacologic therapies that reduce blood pressure: a fresh perspective. Clin Cardiol. 1999;22(Suppl. III):III1-III5.

Ashraf W, Park F, Lof J, Quigley EM. Effects of psyllium therapy on stool characteristics, colon transit and anorectal function in chronic idiopathic constipation. Aliment Pharmacol Ther. 1995;9:639–647.

Bazzano LA, He J, Ogden LG, Loria C, Vupputuri S, Myers L, Whelton PK. Legume consumption and risk of coronary heart disease in US men and women: NHANES epidemiologic follow-up study. Arch Intern Med. 2001;161(21):2573-2578.

Bonithon-Kopp C, Kronborg O, Giacosa A, Rath U, Faivre J. Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group. Lancet. 2000;356(9238):1286-1287.

Botterweck AA, van den Brandt PA, Goldbohm RA. Vitamins, carotenoids, dietary fiber, and the risk of gastric carcinoma: results from a prospective study after 6.3 years of follow up. Cancer. 2000;88(4):737-748.

Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nut. 1999;69(1):30-42.

Burke V, Hodgson JM, Beilin LJ, Giangiulioi N, Rogers P, Puddey IB. Dietary protein and soluble fiber reduce ambulatory blood pressure in treated hypertensives. Hypertension. 2001;38(4):821-826.

Chandalia M, Garg A, Lutjohann D, von Bergmann K, Grundy SM, Brinkley LJ. Beneficial effect of high dietary fiber intake in patients with type 2 diabetes mellitus. N Eng J Med. 2000; 342:1392-1398.

Cohen LA. Dietary fiber and breast cancer. Anticancer Res. 1999;19(5A):3685-3688.

Compher CW, Frankel WL, Tazelaar J, Lawson JA, McKinney S, Segall S, et al. Wheat bran decreases aberrant crypt foci, preserves normal proliferation, and increases intraluminal butyrate levels in experimental colon cancer. JPEN: J Paren Enteral Nutr. Sep-Oct 1999;23(5):269-277.

Etman MA. Effect of a bulk forming laxative on the bioavailability of carbamazepine in man. Drug Dev Ind Pharm. 1995;21(16):1901-1906.

Ettinger AB, Shinnar S, Sinnett MJ, Moshe SL. Carbamazepine-induced constipation. J Epilepsy. 1992;5(3):191-193.

Fernandez-Banares F, Hinojosa J, Sanchez-Lombrana JL, et al. Randomized clinical trials of Platago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Am J Gastroenterol. 1999;94:427–433.

Gallaher DD, Schneeman BO. Dietary fiber. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington, DC: International Life Sciences Institute; 1996:87-94.

Gin H, Orgerie MB, Aubertin J. The influence of guar gum on absorption of metformin from the gut in healthy volunteers. Horm Metab Res. 1989;21(2):81-83.

Goodman MT, Wilkens LR, Hankin JH, Lyu LC, Wu AH, Kolonel LN. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol. 1997;146(4):294-306.

Gray DS. The clinical uses of dietary fiber. Am Fam Physician. 1995;51(2):419-426.

Hayes RB, Ziegler RG, Gridley G, et al. Dietary factors and risks for prostate cancer among blacks and whites in the United States. Cancer Epidemiol Biomarkers Prev. 1999;8(1):25-34.

Hermansen K, Sondergaard M, Hoie L, Carstensen M, Brock B. Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects. Diabetes Care. 2001;24(2):228-233.

Hillemeier C. An overview of the effects of dietary fiber on gastrointestinal transit. Pediatr. 1995:997-999.

Howard BV, Manson JE, Stefanick ML, et al., Low-fat dietary pattern and weight change over 7 years: the Women's Health Initiative Dietary Modification Trial. JAMA. 2006;295(1):39-49.

Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med. 2001;345(11):790-797.

Huupponen R, Seppala P, Iisalo E. Effect of guar gum, a fibre preparation, on digoxin and penicillin absorption in man. Eur J Clin Pharmacol. 1984;26(2):279-281.

Jänne PA, Mayer RJ. Chemoprevention of colorectal cancer. N Engl J Med. 2000;342(26):1960-1968.

Jenkins DJ, Kendall CW, Vuksan V. Viscous fibers, health claims, and strategies to reduce cardiovascular disease risk. Am J Clin Nut. 2001;73(3):653-654.

Jenkins DJ, Popovich DG, Kendall CW, Vidgen E, Tariq N, Ransom TP, et al. Effect of a diet high in vegetables, fruit, and nuts on serum lipids. Metabol. 1997;46(5):530-537.

Johnson BF, Rodin SM, Hoch K, Shakar V. The effect of dietary fiber on the bioavailability of digoxin in capsules. J Clin Pharmacol. 1987;27(7):487-490.

Kalkwarf HJ, Bell RC, Khoury JC, Gouge AL, Miodovnik M. Dietary fiber intakes and insulin requirements in pregnant women with type 1 diabetes. J Am Diet Assoc. 2001;101(3):305-310.

Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. AHA Scientific Statement: AHA Dietary guidelines Revision 2000: A statement for healthcare professionals from the nutrition committee of the American Heart Association. Circulation. 2000;102(18):2284-2299.

Kritchevsky D. Dietary fibre and cancer. Eur J Cancer Prev. 1997;6:435-441.

Kurtz RC, Zhang ZF. Gastric cardia cancer and dietary fiber. Gastroenterology. 2001;120(2):568-70

Lantner RR, Espiritu BR, Zumerchik P, Tobin MC. Anaphylaxis following ingestion of a psyllium-containing cereal. JAMA. 1990;264(19):2534-2536.

Le Marchand L, Wilkens LR, Hankin JH, Kolonel LN, Lyu LC. Independent and joint effects of family history and lifestyle on colorectal cancer risk: Implications for prevention. Cancer Epidemiol Biomarkers Prevent. 1999;8:45-51.

Liu S, Manson JE, Stampfer MJ, Hu FB, Giovannucci E, Colditz GA, et al. A prospective study of whole-grain intake and risk of type-2 diabetes mellitus in women. Am J Pub Health. 2000;90:1409-1415.

Lu LJ, Anderson KE, Grady JJ, Kohen F, Nagamani M. Decreased ovarian hormones during a soya diet: implications for breast cancer prevention. Can Res. 2000;60(15):4112-4121.

Ludwig DS, Pereira MA, Kroenke CH, Hilner JE, Van Horn L, Slattery ML, Jacobs DR Jr. Dietary fiber, weight gain, and cardiovascular disease risk factors in young adults. JAMA.1999:282(16):1529-1546.

Marlett JA, et al. Mechanism of serum cholesterol reduction by oat bran. Hepatology. 1994;20:1450-1457.

Mayne ST, Risch HA, Dubrow R, Chow WH, Gammon MD, Vaughan TL, et al. Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev. 2001;10(10):1055-1062.

McGuffin M, ed. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, 1997.

McRorie JW, Daggy BP, Morel JG, Diersing PS, Miner PB, Robinson M. Psyllium is superior to docusate sodium for treatment of chronic constipation. Aliment Pharmacol Ther. 1998;12:491–497.

Michels KB, Giovannucci E, Joshipura KJ, Rosner BA, Stampfer MJ, Fuchs CS, et al. Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers. J Natl Cancer Inst. 2000;92(21):1740-1752.

Murray MT, Pizzorno JE. Role of dietary fiber in health and disease. In: Pizzorno JE, Murray MT, eds. Textbook of Natural Medicine. Vol 1. 2nd ed. Edinburgh: Churchill Livingstone; 1999:507-516.

National Cholesterol Education Program. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-2497.

Perlman BB. Interaction between lithium salts and ispaghula husk [letter]. Lancet. 1990;355:416.

Persson PG, Ahlbom A, Hellers G. Diet and inflammatory bowel disease: a case-control study. Epidemiol. 1992;3(1):47-52.

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Richter WO, Jacob BG, Schwandt P. Interaction between fibre and lovastatin. Lancet. 1991;338;706.

Rodrigues-Moran M, Guerrero-Romero F, Lazcano-Burciaga G. Lipid- and glucose-lowering efficacy of Plantago Psyllium in type II diabetes. J Diabetes Complications. 1998;12:273–278.

Schatzkin A, Lanza E, Corle D, Lance P, Iber F, Caan B, et al. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. N Engl J Med. 2000;342(16):1149-1155.

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Tariq N, Jenkins D, Vidgen E, Fleshner N, Kendall CW, Story JA, et al. Effect of soluble and insoluble fiber diets on serum prostate specific antigen in men. J Urol. 2000;163:114-118.

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Toutoungi M, Schulz P, Widmer J, et al. Probable interaction of psyllium and lithium. Therapie. 1990;45(4):358-360.

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Review Date:
5/25/2007
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and 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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adam.com

Weight control and diet

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

In This Report

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer and Weight Control:

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

Drug Warning:

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

New Over-the-Counter Medication:

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

Research News:

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

Effects of Obesity on the Body:

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

Introduction

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Biological and Medical Causes

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

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

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

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

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

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

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

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

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

Genetics also determine the number of fat cells a person has. Some people are simply born with more. It should be noted that even when genetic factors are present, a person can still control their diet.

The Thrifty Gene. Some experts think the existence of a so-called "thrifty" gene regulates changes in hormone levels, to accommodate seasonal changes. Theoretically, it works in the following manner:

In certain populations, hormones are released during seasons when food supplies have traditionally been low. This leads to insulin resistance and increased fat storage.
The process is reversed in seasons when food is readily available.
Because modern industrialization has made high carbohydrate and fatty foods available all year long, the gene no longer serves a useful function. Fat, originally stored for famine situations, is not used.

This theory could explain why the previously nomadic Native American tribes who now have Western dietary habits have such high rates of Type 2 diabetes and obesity. In the past, the traditional low-fat, high-fiber foods tribe members ate may have protected them from obesity and type 2 diabetes. Today, these tribes' diet consists of more Western foods, which are higher in fat. Furthermore, these foods are readily available year-round, and many members of the tribe are sedentary. The result is a very high incidence of Type 2 diabetes and obesity. Although genetic abnormalities may make it harder or easier to lose weight, the occurrence of obesity has dramatically increased over the past two decades, and genes cannot have changed within that short amount of time. Our ability to use the food that we eat evolved so that our body could conserve energy and store fat during times of famine. Most cases of obesity now occur in people with normal body function who live in industrialized nations, where there is more than enough food.

A number of medical conditions may contribute to being overweight, but rarely are they a primary cause of obesity.

Hypothyroidism is sometimes associated with weight gain. But, patients with an underactive thyroid generally show only a moderate weight increase of five to 10 pounds.
Very rare genetic disorders, including Froehlich's syndrome in boys, Laurence-Moon-Biedl, and the Prader-Willi syndromes, cause obesity.
Abnormalities or injury to the hypothalamus gland can cause hypothalamic obesity.
Cushing's disease is a rare condition caused by high levels of steroid hormones. It results in obesity, a moon-shaped face, and muscle wasting.
Obesity is also linked to polycystic ovarian syndrome, a hormonal disorder in women.

Click the icon to see an image of polycystic ovaries.

Some prescription medications contribute to weight gain, usually by increasing appetite. Such drugs include the following:

Corticosteroids
Female hormone treatments, including some oral birth control pills (effect is usually temporary), and certain progestins (such as Megestrol) used to treat cancer
Antidepressants and anti-psychotic drugs, including lithium and valproate
Insulin and insulin-stimulating drugs used to treat diabetes often lead to weight gain, a particularly unfortunate conflict of interest for obese individuals with type 2 diabetes

You should not stop taking any medications without your doctor's knowledge.

Cultural and Emotional Causes

Enough food is produced in the US to supply 3,800 calories every day to each man, woman, and child in the country, far more than the average person needs to sustain life. In a 2002 study, participants carefully recorded everything they ate and drank, and all activities and psychological factors surrounding the eating events. The people who gained weight ate more and their portions were larger than those who did not. This may be an obvious conclusion, but the public press often plays up biologic factors involved with obesity and overlooks the simple notion that Americans eat too much and exercise too little.

Obesity is dramatically increasing not only in American children and adults, but also in every country that has adopted similar cultural habits. The World Health Organization now considers obesity to be a global epidemic and a public health problem as more nations become "Westernized." In spite of the proven health risks of obesity, the government, insurance companies, and the medical profession do not spend nearly enough money to balance the commercial and cultural pressures that are producing millions of overweight people.

In 2007, the Robert Wood Johnson Foundation sounded a positive note with the announcement of a $500 million initiative, aimed at “reversing the childhood obesity epidemic by 2015.” The money will be used for research, education, and activities that promote healthy eating among America’s children.

Perhaps the primary reason for the dramatic rise in obesity is the sedentary (inactive) lives led by most Americans, including children and young people. In a 2003 study comparing modern life to the past, researchers found that labor saving devices had reduced a person's energy use by 111 calories a day -- adding up to an extra 11 pounds a year. Half the difference in energy use was due to less walking. At the same time, according to the U.S. Centers for Disease Control and Prevention, between 1970 and 2000 the typical American man increased his caloric intake by 168 calories a day (good for 17 pounds a year) while the average woman added 335 calories a day.

Regular television watching has been singled as the most hazardous pastime. According to a major 2003 study, for every 2 hours a person spends in front of the TV each day, the risk for obesity increases by 23% and for type 2 diabetes by 14%. In the study, TV watching produced the lowest metabolic rates compared to sewing, playing board games, reading, writing, and driving a car. Just the act of watching TV encourages unhealthy snacks and eating patterns. In addition, the advertising on the television complicates the problem by promoting fast foods, cereal, and snack products that are high in salt, fats, and carbohydrates. Even worse, much of these advertisements are directed at children -- the most vulnerable group.

People are not only eating more food than they did 20 years ago, they are also replacing home cooking with packaged foods, fast food, and dining out. This behavior, according to studies, places people at higher risk for obesity. Fast foods may be more harmful than restaurant cooking. These foods tend to be served in larger portions. They generally contain more calories and unhealthy fats, and less nutritious ingredients, than homemade or restaurant meals. Snack foods and sweet beverages, including juice and soft drinks, are specific problems that add to the increasing rates of obesity. Frequent small, healthy meals (instead of two or three large daily meals) have been associated with lower weights.

People react differently to stress. Some overeat and gain weight and others stop eating and lose weight. People who gain weight in response to stress often overeat foods high in sugar, fats, and salt. A 2003 study on rats suggested that stress hormones increase the pleasure of eating such so-called "comfort foods." Furthermore, the study supported previous research showing that stress-related eating was connected to the unhealthy accumulation of abdominal fat.

Risk Factors

Where you live plays a role in your risk for obesity. Simply living in the United States makes a person more susceptible to obesity. The prevalence of obesity in America has risen dramatically over the past few years and continues to increase.

According to the latest figures available, 32.2% of American adults (aged 20 and older) are obese (BMI over 30) -- up from about 23% in the early 1990s.
The number of Americans aged 20 - 74 who were overweight also increased -- from about 44.8% in 1960 to 65.2% in 2002.
The rate of extreme obesity (BMI > 40) increased from 0.8% in 1960 to 4.9% in 2002.
Obesity has increased in every state, in both men and women, across all age groups, and in every ethnic group, although some groups may face slightly higher risks than others.

Fat tends to settle in certain regions, depending on gender. Women gain fat predominantly in the stomach, hips and thighs, while men tend to gain fat in the belly and waist.

Risk by Age. People of any age are at risk for obesity. More children and adolescents are overweight in America than ever before. Gaining some weight is inevitable with age and adding about 10 pounds to a normal base weight over time is not harmful. The current weight gain in American adults over 50, however, is significant. By age 55, the average American has added nearly 40 pounds of fat during the course of adulthood. This condition is made worse by the fact that muscle and bone mass decrease with age.

Risk by Gender. In men, BMI tends to increase until age 50 and then it levels off. In women, weight tends to increase until age 70 before it plateaus. A 2000 study found that there are three high-risk periods for weight gain in women.

The first is at the onset of menstruation, particularly if it is early. In fact, a study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9. This, in turn, increases the risk for more weight gain as girls enter puberty.
The second is after pregnancy, with higher risk for women who are already overweight.
Finally, many women gain weight after menopause.

These findings are significant because they may allow women to target high-risk times, and consequently prevent unnecessary weight gain.

Risk by Economic Group. Obesity is more prevalent in lower economic groups. One 2002 study reported that women who reported that they did not have enough food were more likely to be overweight than those who said they had sufficient food. Researchers discovered that the low-income women tended to have fewer fruits and vegetables but were actually taking in more calories a day than higher-income women. However, obesity is increasing in young adults with college education as well as in other groups.

Ethnic Groups. Among ethnic groups in general, African-American women are more overweight than Caucasian women but African-American men are less obese than Caucasian men. (Currently, 80% of African-American women are overweight.) Hispanic men and women tend to weigh more than Caucasians.

US Regions. Regionally, the prevalence of obesity is lowest in the Western states and highest in the South.

A number of dietary habits put people at risk for becoming overweight:

Night-Eating Syndrome. Night-eating syndrome is defined as having no appetite in the morning, insomnia, and consuming more than half of daily food intake after 6:00 PM. It is associated with obesity and is difficult to treat. Stress reduction and relaxation techniques may be helpful.
Binge Eating and Eating Disorders. About 30% of people who are obese are binge eaters who typically consume 5,000 - 15,000 calories in one sitting. To be diagnosed as a binge eater, a person has to binge at least twice a week for 6 months. Many experts believe that binge-eating carbohydrates causes an increase in a natural opiate leading to dependence on carbohydrates. Therefore, this condition should be treated as an addiction. Other eating disorders are bulimia and anorexia. Bulimia is binge eating followed by purging in order to lose weight. Anorexia nervosa is a mental illness in which the person refuses to maintain weight at the normal level. The patient with anorexia has a terrible fear of getting fat, and an abnormal perception of what his or her body looks like. Both conditions pose risks for serious medical problems, and anorexia nervosa can be life-threatening. A combined approach using behavioral therapy and antidepressants may help these individuals. [See In-Depth Report #49: Eating disorders.]
Restrained Eating. Some people, mostly middle-aged women who have normal weight, have a pattern referred to as restrained eating. This pattern requires a high level of conscious control and usually maintains a lower weight. However, such restraint places these individuals at higher risk for loss of control and subsequent overeating.
Infrequent Eating. There is some evidence to suggest that eating small frequent meals uses more calories than infrequent large meals. It should be strongly noted, however, that packaged snack foods add calories and some do not produce a feeling of being full, so that people simply eat more than they should.

Anyone with Sedentary Lifestyles. Office workers, drivers, and anyone whose lifestyle involves sitting for long periods are at higher risk for obesity.

Ex-Smokers. The trend toward weight increase has followed the trend for quitting smoking. Nicotine increases the metabolic rate, and quitting, even without eating more, can cause weight gain, which may be considerable. It is important to note that weight control is not a valid reason to smoke. People in previous centuries did not smoke cigarettes, nor were they usually obese.

Shift-Workers. A recent study found that individuals who work late shifts (between 4 p.m. and 8 a.m.) tend to eat more and take longer naps than day workers and are more likely to gain excess weight.

People with Disabilities. Obesity rates are higher than average in people with physical or mental disabilities. Those with disabilities in the lower part of the body, such as the legs, are at highest risk.

Overweight in children and adolescents is rising at an alarming rate. In 2004, 19% of young children aged 6 - 11 were overweight, an increase of 8% from 1994. Among children aged 25, 13.9% were overweight in 2004, up from 7.2% 10 years earlier.

Definition of Overweight in Children

Children and adolescents are considered to be overweight if their BMI is above 95% of the children in their age and sex categories. Ethnic variations, timing of growth spurts, and higher normal fat levels around puberty can affect these measurements.

Causes and Risk Factors for Overweight in Children

Lifestyle Factors. Without educational or parental guidance, children are extremely vulnerable to the intense cultural pressures that are largely responsible for the obesity epidemic. The following are some specific problems created by the culture:

Excessive television watching plays a critical role in obesity in children. Not only is it a sedentary activity, but television also offers innumerable temptations with its advertisements for fast foods, sugar cereals, and unhealthy snacks. In one study obesity rates were lowest in children who watched television 1 hour or less a day and highest in those who watched 4 or more hours.
Sugar, particularly from soda, other sweetened beverages, and fruit juice, may be the major contributor to childhood obesity. One study reported that drinking soda regularly increases a child's risk for obesity by 60%. The average American adolescent consumes 15 - 20 extra teaspoons of sugar a day just from soda and sugary drinks. (Juice, while better than soda, is still filled with sugar.)
Less physical exercise and greater sedentary activities play another significant role in obesity in children. A high level of physical activity -- not just using up energy -- is important for weight control in young people. Unfortunately, according to one study, the annual distance walked by children has fallen by nearly 30% since 1972, partially because more parents are driving their children to school out of fear of abduction, molestation, and traffic accidents. Schools are also offering fewer opportunities for daily physical activities than in the past.

Neither the media nor the educational system has strong well-financed programs that encourage healthy alternatives, including exercise and healthy foods.

Family History. Parental obesity more than doubles the risk that a young child, whether thin or overweight, will become obese as an adult. In older children and teenagers, obesity in parents starts to count less as a predictor for body weight than their own weight. The risk for obesity may be due to environmental or genetic factors, or both.

Ethnic and Socioeconomic Factors. As in adult populations, children from lower socioeconomic groups and minority populations are at higher risk for obesity. For example, among young Mexican Americans and African-Americans, there has been an increase in overweight prevalence of about 13% to over 23%.

Factors Surrounding Birth. The following factors surrounding birth are associated with a child's weight:

Low birth weight is a risk factor for later obesity and diabetes. One theory is that humans have a "thrifty gene" that produces metabolic changes in infants with low birth weight. Such changes affect insulin and fat accumulation, in order to produce a "catch-up" weight in these young children as quickly as possible. This rapid weight gain in infancy increases the risk for obesity in children and young adults.
In a study of African-American children, having an overweight pregnant mother increased the risk for later weight gain, but low birth weight did not.

Although some small studies have reported protection against obesity from breastfeeding, evidence is weak. In a 2003 study, for example, children who were breast fed for 3 - 5 months had a lower risk for obesity, but prolonged breastfeeding had no effect. Nevertheless, given the healthful effects of breast feeding and the possibility that it may have even a slight impact on childhood obesity, it is highly recommended.

Biological Effect of Childhood Overweight on Adult Weight

Achieving a healthy weight becomes more difficult as children get older. The odds of obesity persisting into adulthood ranges from 20% in 4 year olds to 80% in teenagers. One reason for the persistence is biological. The fat cells change in number or mass depending on a person's age:

Fat cells themselves multiply during two growth periods: early childhood and adolescence. Overeating during those times increases the number of fat cells. Some people are also just born with more fat cells.
After adolescence, fat cells tend to increase in mass rather than quantity, so that adults who overeat and gain weight tend to have larger fat cells, not more of them. This growth in mass may be responsible for the greater risk of persistent obesity among teenagers compared to small children who are overweight. Losing weight after adolescence reduces the size of the fat cells but not their number, so weight loss becomes much more difficult.

Health Consequences of Childhood Overweight

Children and adolescents who are overweight have poorer health than other children. Studies are reporting unhealthy cholesterol levels and high blood pressure in overweight children and adolescents. Of great concern is the dramatic increase in type 2 diabetes in young people, which is largely due to the increase in overweight children. Overweight in children is also linked to asthma, gallbladder problems, sleep apnea, and liver abnormalities. Overweight girls are more likely to enter puberty early, according to a new study, and subsequently be at higher risk for breast cancer.

It is not clear yet how many of these childhood problems persist in people who achieve normal weight as adults. Staying overweight into adulthood certainly carries health risks.

Managing Overweight Children

Childhood obesity is best treated by a non-drug, multidisciplinary approach including diet, behavior modification, and exercise. Evidence suggests that reducing calories by only 200 - 260 per day would prevent weight gain in most overweight children. Here some tips for children who are overweight:

Limit (or avoid, if possible) take out, fast foods, high-sugar snacks, commercial packaged snacks, soda, and sugar-sweetened beverages (including too much juice).
Let children snack but make sure the snacks are healthy. Eating small frequent healthy meals (instead of two or three large ones) has been associated with being thinner and having a better cholesterol profile.
Let children choose their own food portions. One study indicated that children naturally ate 25% less when they chose their own portion size. When they were given larger portions their bite sizes were larger and they ate more.
Do not criticize a child for being overweight. It does not help and such attitudes could put children at risk for eating disorders, which are equal or even greater dangers to their health.
Limit television, video games, and computer use to a few hours a week. This can contribute significantly to weight control, regardless of diet and physical activity.
For young children, try the traffic-light diet. Food is designated with stoplight colors depending on their high caloric content: Green for go (low calories); yellow for "eat with caution" (medium calories); red for "stop" (high calories).
Try a low glycemic index diet. This may be as beneficial, and possibly more, than a standard reduced-fat diet in overweight children. Such a diet focuses on certain carbohydrates (for example, dried beans and soy), which raise blood sugar more slowly than other types of carbohydrates. This diet is sometimes used in diabetes, and as a dietary approach in overweight adults. [See In-Depth Report #42: Diabetes diet.]

Click the icon to see an image about TV watching.

Click the icon to see an image of childhood overweight.

Complications

General Adverse Effects of Obesity. Obesity, defined as a BMI of 30 or over, accounts for nearly 300,000 deaths in the U.S. each year. It is associated with more chronic health problems than smoking, heavy drinking, or poverty. Furthermore, given the current increase in obesity, it will surpass smoking as the most important preventable cause of death in America.

Some studies indicate the following health risks by body mass:

The lowest risks for heart disease, diabetes, and some cancers are in people with BMI values of 21 - 25.
The risks increase slightly when BMI values are between 25 - 27.
The risks are significant in BMIs between 27 - 30.
The same risks are dramatic at BMIs over 30.

Anyone with chronic health problems such as heart or lung disease, stroke, or arthritis, should be concerned about extra weight. This same concern also applies to people with known risk factors for such conditions.

Metabolic Changes. As fat stores increase, the fat cells themselves enlarge and produce chemicals that increase the risk for several diseases. Such diseases may include diabetes, high blood pressure, gallbladder disease, and some cancers.
Increased Mass. The increased body weight itself causes problems that result in injury and diseases, including osteoarthritis and sleep apnea.
Harmful Fat Cell Types. Weight concentrated around the abdomen and in the upper part of the body (the apple shape) poses a higher health risk than fat that settles around the hips and flank (the pear shape). Fat cells in the upper part of the body appear to have different qualities from those found in the lower parts. In fact, studies suggest a higher risk for diabetes in people with the "apple shape" and lower risk in those who are "pear shaped."

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

General Adverse Effects of Being Overweight (Not Obese). It is still not clear if being overweight (a BMI of 25 - 29.9) hurts healthy people with no risk factors for serious illnesses.

According to one 2001 study, just being overweight increased the risk for developing diabetes, gallstones, hypertension, heart disease, stroke, and colon cancer. The risk rose according to how much the individuals were overweight. In any case, adults who are overweight in middle age face a poor quality of life as they age, with the quality declining the greater the weight. One study suggested, however, that being over 65 and overweight (but not obese) is not associated with higher mortality rates.

Some experts argue, in fact, that in anyone who is not severely obese, it is the unhealthy diet and sedentary lifestyle that causes harm -- not weight per se. In support of this argument, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Being somewhat overweight may also have some benefits under specific circumstances:

In older women, some excess fat may produce extra estrogen that helps slow down bone loss, and insulates bones from fall-related injuries. It should be strongly noted, however, that when older overweight women lose weight they report less pain, improved vitality, and improved physical function. The same positive effect of overweight does not appear to hold in older men.
Conditioned athletes may have high BMIs because of very dense muscle tissue. Being fit in general may protect many overweight people.
Some evidence suggests that Caucasians have the lowest mortality with BMIs of 24.3 - 24.7 while African-Americans are better off in the range of 26.8 - 27.1.
Children may have higher normal fat levels during growth spurts and around puberty.

Individuals with a BMI of at least 30 have a 10 - 50% increased rate of death from all causes, compared with individuals with a BMI of 20 - 25. Mortality rates from many causes are higher in obese people, but heart disease is the primary cause of death. People who are obese have almost three times the risk for heart disease as people with normal weights. Being physically unfit adds to the risk.

Weight concentrated around the abdomen and in the upper part of the body (apple shape) is particularly associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Fat that settles in a pear shape around the hips and lower body appears to have a lower association with these conditions.

Obesity poses many dangers to the heart and circulatory system.

Damage in the Blood Vessels. As people age, changes in body fat (particularly increasing abdominal fat) seem to cause stiffness in the aorta, the major blood vessel leading from the heart. Studies are finding higher levels of a factor called C-reactive protein (CRP) in people with obesity and abdominal fat. CRP is now considered to be a marker for inflammation and damage in the arteries. (Losing weight reduces CRP levels.)

High Blood Pressure. High blood pressure is the health problem most commonly associated with obesity, and the greater the weight, the greater the risk. High blood pressure carries serious risks of stroke, heart attack, and heart failure. The link between obesity and high blood pressure is complex, and may be a combination of genetic, population, and biological factors. Many studies have reported that modest weight loss is beneficial for reducing existing high blood pressure. [See In-Depth Report #14: High blood pressure.]

Heart Failure. An important 2002 study reported that obesity might account for 11% of heart failure cases in men and 14% in women. This link existed independently of other risk factors, such as high blood pressure, sleep apnea, and diabetes, which are also associated with obesity. The biologic mechanisms involved in obesity that lead specifically to heart failure are not clear. [See In-Depth Report #13: Heart failure.]

Unhealthy Cholesterol Levels and Lipid Levels. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels (the major form of fat storage in the body) are usually high, while HDL levels (the "good" cholesterol) tend to be low. Both conditions are risk factors for heart disease. [See In-Depth Report #23: Cholesterol.]

Click the icon to see an image of coronary artery disease.

Stroke. Obesity is also associated with a higher risk for stroke. [See In-Depth Report #45: Stroke.]

Type 2 Diabetes and Insulin Resistance. Most people with type 2 diabetes are obese and, in fact, studies strongly suggest that weight loss may be the key in controlling the current epidemic of type 2 diabetes. The common factor appears to be insulin resistance. Insulin is a critical hormone in the use of sugar. In type 2 diabetes, different factors cause the body to become insulin resistant -- that is, the body can no longer respond properly to insulin. This has the effect of increasing sugar levels in the blood, the hallmark of diabetes. Both obesity and insulin resistance, at different phases, are marked by high levels of certain chemicals. It is not known yet if the higher levels are simply a product of obesity, or play some role in causing diabetes.

Insulin resistance is also associated with high blood pressure and abnormalities in blood clotting. Some research indicates that obesity, in fact, is the one common element linking insulin resistance, diabetes type 2, and high blood pressure. [See In-Depth Report #60: Diabetes - type 2.]

Metabolic Syndrome. Metabolic syndrome (also called syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome. A combination of weight loss and exercise is an effective treatment for this syndrome.

The American Cancer Society released new cancer prevention guidelines in September 2006. The guidelines stress the importance of keeping a healthy weight throughout life. The Society indicates that healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Obesity has been associated with a higher risk for cancer in general and specific cancers in particular. Studies have also suggested that restricting calories reduces the risk for cancer. Some experts believe that effective weight control for children and adults could reduce cancer rates by 30 - 40%. One way obesity may increase the risk for cancer is its association with high levels of hormones called growth factors, which can trigger rapid cell production leading to cancer.

Uterine Cancers. The risk of uterine cancer in obese women appears to be two or three times higher than in thinner women.

Prostate Cancer. New studies from 2005 and 2006 report that obesity is associated with an increase in prostate cancer mortality, although not with the risk for less aggressive forms of prostate cancer.

Click the icon to see an image of prostate cancer.

Breast Cancer. Studies are mixed on the association between obesity and breast cancer. A number of studies have linked obesity to breast cancer in postmenopausal women, particularly in women who begin to gain weight after age 18.

Click the icon to see an illustrated series detailing a breast cancer surgery (mastectomy).

Gallbladder Cancer. Obese women are at higher risk for gallbladder cancer.

Gastrointestinal Cancers. A number of cancers in the gastrointestinal tract have been associated with obesity:

Cancer of the esophagus may be due to a higher incidence of gastroesophageal reflux disorder (heartburn) in people who are overweight.
Colon cancer has been linked to increased body mass in both men and women.
Pancreatic cancer and obesity have been weakly linked, with one study reporting a lower risk in overweight people who are physically active.

Click the icon to see an illustrated series detailing a colon cancer surgery.

Muscles and Bones

Obesity places stress on bones and muscles. Studies report that the incidence of osteoarthritis is significantly increased in people who are overweight. People who are obese are also at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands. It should be noted that some weight may be protective against osteoporosis (loss of bone thickness).

Obesity increases the risk for the following mouth and eye disorders:

Gum disease
Cataracts
Maculopathy, an eye disease related to aging

Infertility. Abnormal amounts of body fat, either 10 - 15% too high or too low, can contribute to infertility in women. Obesity is specially related to certain infertility problems, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.

Effect on Pregnancy. Obesity has many dangerous effects on pregnancy. These include high blood pressure, gestational diabetes (diabetes, usually temporary, that occurs during pregnancy), urinary tract infections, blood clots, prolonged labor, and higher fetal death rate in late stages of pregnancy. Obesity is also associated with increased rates of cesarean delivery. Infants of women who are obese are also at higher risk for neural tube birth defects, which affect the brain or spine. Folic acid supplements, ordinarily effective in preventing these conditions, may not be as protective in overweight women.

Obesity is thought to be a risk factor for symptoms of adult-onset asthma. Though there is evidence that obesity causes wheezing and shortness of breath, it does not appear to be strongly associated with the disease mechanisms in the lungs that cause true asthma.

Obesity also puts people at risk for hypoxia, a condition in which there is not enough oxygen to meet the body's needs. Obese people need to work harder to breathe. They tend to have breathing muscles and lungs that do not work as well as those in thinner people.

The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Nonalcoholic Fatty Liver Disease. People with obesity, particularly if they also have type 2 diabetes, are at higher risk for a condition called nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH). This condition causes liver damage that is similar to liver injury seen in alcoholism. In some cases, it can be very serious and require liver transplantation. It occurs in about half of people with diabetes, and 20 - 50% of obese people, depending on how severe their obesity is. NASH can also occur in overweight children.

Gallstones. The incidence of gallstones is significantly higher in obese women and men. The risk for stone formation is also high if a person loses weight too quickly. In people on ultra-low calorie diets, gallstones may be prevented by taking ursodeoxycholic acid (Actigall).

Click the icon to see an image of gallstones.

People who are obese and nap tend to fall asleep faster and sleep longer during the day. At night, however, it takes them longer to fall asleep, and they sleep less than people with normal weights. In an apparent vicious circle, studies have suggested that obesity not only interferes with sleep but that sleep problems may actually contribute to obesity.

Sleep Apnea. Obesity, particularly the apple shape, is strongly associated with sleep apnea, which occurs when the upper throat relaxes and collapses from time to time during sleep. This collapse temporarily blocks the passage of air. Sleep apnea is increasingly being viewed as a potentially serious health problem, which may lead to complications such as heart disease and stroke. Some studies suggest that among overweight people, those who have sleep apnea have a greater risk of heart disease than those without it. In one study, the more obese a person with sleep apnea was, the higher the pressure on the airway, and therefore the greater the obstruction of the airway. Obstructive sleep apnea may also add to obesity, however, as sleepy people tend to be sedentary. Some studies indicate that treating sleep apnea may help people lose abdominal fat.

Narcolepsy. A small European study found a link between narcolepsy (a sleep disorder characterized by excessive daytime sleepiness with frequent daily sleep attacks) and high BMI.

Depression. A number of studies have reported an association between depression and obesity, particularly in obese women. There may be a number of factors to explain the link. In some cases of atypical depression, people overeat and may gain weight. Overweight people may also become depressed because of social problems and a poor self-image. In these cases, depression usually disappears when people lose weight.

There is evidence, however, that obesity itself may impair levels of tryptophan -- a chemical needed to make serotonin, a brain chemical associated with mental well-being. In one study, even after people lost weight, tryptophan levels were lower than normal.

There does not appear to be any association between depression and obesity in men.

Social Problems. One long-term study reported that overweight young women completed fewer years of school, were 20% less likely to be married, and had 10% higher rates of household poverty than their thinner peer. Obese young men were also less likely to be married, and their incomes were lower than their thinner peers. Nevertheless, studies consistently show that overweight males (both boys and men) are not as severely emotionally affected as females of any age. Women and girls tend to blame themselves for being heavy, while males tend to blame being overweight on outside factors.

Weight Loss and Maintenance

Even modest weight loss can reduce the risk factors for heart disease and diabetes. The simplest (but still difficult) approach to weight loss is reducing calories and exercising at least 150 minutes a week. Behavioral and mental changes in eating habits, physical activity, and attitudes about food and weight are also essential to weight management. For people who are very overweight and cannot lose weight through lifestyle changes, a number of effective weight-loss medications are available. For those with severe obesity, surgical procedures are proving to be very beneficial.

Some Tips for Losing Weight. The following are some general suggestions for dieters:

Start with realistic goals. Diet failure is extremely common, and the odds of significant weight loss are low, particularly in people with the highest weights. People who are able to restrict calories, engage in an exercise program, and get help in making behavioral changes can expect to lose between 5 - 10% of their current body weight. That is generally all that is needed to achieve meaningful health changes. Certainly, the distorted image of a super-thin female shape should not be anyone's goal.
Maintain a regular exercise program, assuming you have no health problems that will stop you. Choose a program that you enjoy. Check with your doctor about any health considerations. [See In-Depth Report #29: Exercise.]
Do not use hunger pangs as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat and start by recording all calories in writing. Studies suggest that when many people report their own calories intake they significantly underestimate their consumption of high-calorie and over-estimate the low-calorie foods. People who do not carefully note everything they eat tend to take in too many calories when they believe they are dieting.
Observe weekend eating. People tend to eat more on the weekends. If it is difficult to monitor all meals during the week, it be may be useful to at least track eating habits during the weekends.
Once the pounds are lost, do your best to keep the healthier weight. Make daily, even hourly, conscious decisions about eating and exercising activities. Such thinking, in many cases, can become automatic and not painful.
Don't give up, even after repeated weight loss failures. Most studies indicate that yo-yo dieting or weight cycling have no bad psychological or physical effects. Repeated dieting also does not harm the body's ability to burn calories efficiently.
Weight loss, in any case, should not be the only or even the primary goal for people concerned about their health. The success of weight loss efforts should be evaluated according to improvements in disease risk factors or symptoms, and by the adoption of healthy lifestyle habits, not just by the number of pounds lost.


Lifestyle	Reduce rate of eating. Keep food records. Eliminate environmental triggers to eating. Identify high-risk situations for overeating. Separate eating from other activities.
Exercise	Face up to emotional barriers to exercise. Understand the link between exercise and weight control. Establish reasonable exercise goals. Develop a plan for regular activity. Add increased activity into daily lifestyle.
Attitudes	Develop reasonable weight-loss goals. Avoid "all or none" thinking. Focus attention away from the scale and toward behavior. Uncouple weight from self-esteem. If you "fall off the wagon," take steps to ensure the situation does not repeat (recover from lapses with constructive action).
Relationships	Understand the key role of social support to health. Identify supportive others. Match personal style to support-seeking activities. Be specific in making support requests. Be assertive but reinforcing in drawing help from others.
Nutrition	Resist the temptation of popular fad diets. Eat with your health in mind; do not concentrate on what should be "off-limits." Eat with moderation in mind. Maximize fiber. Develop a tailored plan.
From Brownell KD. The LEARN Program for Weight Control. 7th ed. Dallas, Tex: American Health Publishing Company; 1998.

Weight Management

There are many approaches to dieting and many claims for great success with various fad diets. To date, although many diets achieve effective immediate weight loss, none has emerged as an effective tool for maintaining healthy weight. The only definite recommendation that can be made about any diet plan is to be sure it includes an exercise program, assuming there are no health problems to forbid it.

The original food pyramid, with four food groups, has been replaced with an updated food guide called "My Pyramid." This illustrates the relative proportions of different foods that make up a nutritious, well-balanced diet and includes exercise.

Calorie restriction has been the cornerstone of obesity treatment. The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories. A person could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine your daily calories requirements, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Extreme diets of less than 1,100 calories carry health risks. They are also often followed by bingeing or overeating, and a return to the obese state. Such diets often do not have enough vitamins and minerals, which must then be taken as supplements. Most of the initial weight loss is in fluids. Later, fat is lost, but so is muscle, which can account for more than 30% of the weight loss. No one should be on severe diets for longer than 16 weeks, or fast for more than 2 or 3 days. Severe dieting has unpleasant side effects including fatigue, intolerance to cold, hair loss, gallstone formation, and menstrual irregularities. There have been rare reports of death from heart arrhythmias when liquid formulas did not have sufficient nutrients. Pregnant women who excessively diet during the first trimester put their unborn children at risk for birth defects. Of note, those whose diets include a high intake of fluids and much reduced protein and sodium are at risk for hyponatremia, which can cause fatigue, confusion, dizziness, and in extreme cases, coma and death.

This dietary approach requires counting only grams of fat with the goal of achieving 30% or fewer calories from fat. One gram of fat contains nine calories, while one gram of carbohydrates or protein has only four calories. Fat in your diet converts more readily to fat in the body, compared with carbohydrates or proteins. Simply switching to low-fat or skimmed dairy products may be enough for some people.

There are possible drawbacks to this approach:

Some people who reduce their fat intake may not get enough basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low-fat diets should eat a wide variety of foods and take a multivitamin supplement, if appropriate. Calcium deficiencies may be particularly harmful in women at risk for osteoporosis.
Many people start eating foods with too many carbohydrates, believing that they are not adding calories. No one should use a low-fat diet as an excuse for eating too many carbohydrates, particularly starchy foods and sugar. A high-calorie diet from any source will add pounds.
A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets that had varying amounts of fat and carbohydrates in each. The diets contained the same amount of calories, but differed in the percentage and type of fat. People on the low-fat, high-carbohydrate diet reported more anger and depression compared with the other two diets.
Replacing fatty foods, such as cakes, cookies, and chips, with their commercial "low-fat" counterparts does not constitute a low-fat diet. These foods generally contain more sugar and hence calories, not to mention other ingredients, which have virtually no nutritional value. In fact, a 2002 study suggested that increasing sugar may, over time, reduce levels of HDL ("good") cholesterol.
Very low-fat diets may increase the risk for stroke from hemorrhage in the brain.

Some fat in a diet is essential. It should come from plant oils and fish, however, and not from animal products or hardened oils, such as margarine. Trans-fatty acids, found in hardened oils, are actually more of a risk factor for obesity than saturated fats from animal products, although both should be avoided.

Fiber and Complex Carbohydrates. In all cases, complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Fiber is an important component of many complex carbohydrates. Fiber is almost always found only in plants, particularly vegetables, fruits, whole grains, nuts, and legumes (beans and peas). One exception is chitosan, a dietary fiber made from shellfish skeletons. Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, and fruit and vegetable peels) has been associated with weight loss. Studies also suggest that diets rich in fiber from whole grains reduce the risk for type 2 diabetes.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly benefiting blood pressure as well. Simply adding breakfast cereal to a diet appears to reduce cholesterol levels. People who increase their levels of soluble fiber should also increase water and fluid intake.

High-protein, low carbohydrate diets, such as the Atkins and South Beach diets, have been touted as effective ways to produce short-term weight loss. Because of their emphasis on fats and proteins, many experts are concerned about long-term health problems. A report in the March 2006 Lancet linked the Atkins diet to life-threatening complications that caused the death of one woman. The 40-year-old woman had a deadly buildup of acids called ketones in her blood, a condition called ketoacidosis. Ketoacidosis can cause coma and death. Ketones are a known by-product of high protein, low carbohydrate diets. At low levels they can cause nausea, lightheadedness, and bad breath.

The long-term effects of these diets are still unknown. For example, the Atkins diet restricts some vegetables and most fruits, which are known to protect against serious diseases such as heart problems and cancer. The diet may also cause too much calcium to build up in the urine. This can increase the risk for kidney stones and osteoporosis. In addition, high-protein intake, particularly from meat, can be harmful in people with kidney problems. Individuals at risk for kidney stones, or those who have other kidney problems, should not go on high-protein diets without talking to their doctor first. Unfortunately, many people with diabetes are at risk of kidney problems, which could reverse any possible benefits a high-protein diet may bring them. Eating a lot of meat has also been associated with certain common cancers, notably prostate and colon cancers. A 2002 study suggested that such diets during pregnancy may increase the risk for high blood pressure in the child.

Still, significant studies say that such diets improve cholesterol and blood sugar levels. Studies in 2002 and 2003 have indicated that these diets lower blood glucose levels, which can be important in people who are diabetic. The diets also reduce triglyceride levels (unhealthy fat molecules) and increases HDL (" good") cholesterol levels. High triglyceride and low HDL levels are important risk factors for heart disease, and are common in people with type 2 diabetes. Studies are mixed on whether this type of diet reduces overall cholesterol or LDL ("bad") cholesterol levels.

Experts that promote the low carbohydrate approach argue that heart problems from obesity are due to insulin disturbances from sugar imbalances. Therefore, they believe that restricting carbohydrates is the best approach for obesity -- especially for overweight people with diabetes. More research is needed, however, to determine the long-term impact of such diets on health.

High-protein, low-carbohydrate diets include Atkins, Protein Power, Sugar Busters, and Dr. Stillman. The Atkins diet is one of the most popular and has a four-phase program:

Induction. For the first 2 weeks, individuals consume no more than 20 grams of carbohydrates a day. The diet consists of pure protein and fats. There is no fruit, bread, grains, starchy vegetables, or dairy products other than cheese, cream, or butter. This phase is not suitable for children, pregnant women, or anyone with kidney disease.
On-going Weight Loss. After the first phase, individuals continue to lose weight while they increase carbohydrate levels by five grams each day.
Premaintenance. When individuals get close to their weight goal, they add another 10 grams of carbohydrates per day as long as they do not begin to gain weight. Weight loss is very slow at this time, but the individual is now getting used to maintenance.
Maintenance. Lifetime maintenance is usually between 40 and 100 grams of carbohydrates a day, depending on steady weight level.

Anyone who chooses this diet should prefer fish or soy products to meat as protein sources. Fish may reduce leptin, a hormone associated with fat storage and heart diseases, and would be the best protein source. People on this diet should also choose monounsaturated fats (as in olive oil) over saturated fats or trans-fatty acids fat. Patients often need supplements, at least a multivitamin and possibly calcium, chromium, omega-3 fatty acids (found in fish oil), and other supplements.

The South Beach and Zone diets encourage healthy fats. They also allow certain carbohydrates. For example the Zone uses healthy carbohydrates (vegetables and dried beans) and unsaturated fats. The South Beach diet uses carbohydrates that have a lower impact on blood sugar levels. This is called a low-glycemic index. Low-glycemic foods include barley, dried bean and peas, milk, strawberries, and apples. High-glycemic foods include refined grains, white bread, white potatoes, and bananas and other tropical fruits. The glycemic index was developed for use in diabetes -- not for weight loss. Nevertheless, there is some evidence that foods with low glycemic indexes may produce a feeling of fullness and so discourage further eating. As with any high-protein diets, people at risk for kidney stones, or those who have other kidney problems, should avoid these plans.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In fact, in one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat substitute (derived from oats) as part of a low-calorie diet. At the end of the 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from a diet can be harmful to general health.

Fat substitutes include the following:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand, as part of a low-fat, diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that the use of stanols can allow lower doses of statins (cholesterol lowering medications). Stanols do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Note that simply adding snacks containing olestra does not appear to have any effect on cholesterol or weight loss.) Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The side health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (e.g., Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-substitutes are also available. Although studies to date are not showing any significant side effects, these products' effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners and reduced their sugar intake weighed less over time than those who took in similar types and amounts of drinks and food containing sugar. It should be noted that using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain, as long as the total amount of calories in the diet is under control. There is some public concern about chemicals used to produce many of these sweeteners, and the side effects seen in studies using rats. Natural low-calories sweeteners are available that may be more acceptable to many people.

Saccharin (Sugar Twin, Sweet n' Low, Sucaryl, and Featherweight). Saccharin has been used for years. Some studies found that large amounts of saccharin cause bladder cancer in rats. However, the rats were fed huge amounts that do not apply to human diets. Currently there is no evidence that saccharin causes cancer in humans.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of nervous system disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing part of the sugar with chlorine. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period, with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the U.S. since 1988 with no reported side effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame, but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced-calorie sweetener is made from lactose, which is the sugar found in dairy products and other foods. It may be especially beneficial for people with type 2 diabetes. It may also have additional benefits that help the intestinal tract.
Alitame (Aclame) is formed from amino acids, the building blocks of proteins. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been carefully tested.

Other sugar substitutes being investigated include glycyrrhizin (derived from licorice) and dihycrochalcone (derived from citrus fruits).

Some studies have reported good success with meal replacement beverages (Slim-Fast, Sweet Success). They contain major nutrients needed for daily requirements. Each serving typically contains between 200 - 250 calories and replaces one meal. (Note: Using them for all meals reduces calories to a severe extent and can be harmful.)

One study reported that most subjects who had undergone a 12-week weight loss program and then used Ultra Slim Fast supplements as directed for maintenance kept off more than half their weight loss after more than 3 years. A quarter of the subjects were still losing weight.

Medical evidence suggests that a diet rich in magnesium could reduce a person's risk of metabolic syndrome, a cluster of problems including obesity, high blood pressure, and high cholesterol. Metabolic syndrome can lead to diabetes and heart disease. A long-term study of thousands of Americans found that the risk for metabolic syndrome decreased in those who consumed the most magnesium from meals. The findings were published in the journal Circulation.

Commercial and Non-Profit Support Programs for Weight Loss. There are many different types of weight-loss program. (This report cannot address all of the many commercial and nonprofit weight-loss programs currently available, nor can it assess their claims.)

Taking off Pounds Sensibly (TOPS), a nonprofit support organization with many local chapters, is one of the least expensive programs, costing $20 a year.

Most of the commercial programs such as Weight Watchers, Jenny Craig, and NutriSystem offer individual or group support, lifestyle changes and packaged meals. These programs tend to be expensive. There are few well-conducted studies on these programs. One 2003 study reported modest weight loss over 2 years with Weight Watchers compared to a self-help program. There were no differences in heart risk factors.

Cognitive Behavioral Approaches. Most support programs use some form of cognitive-behavioral methods to change the daily patterns associated with eating. They are very useful for preventing relapse after initial weight loss. The following is a typical approach:

The patient first records in a diary all activity related to eating patterns, including the times of day, length of meal, emotional states, companions, and, of course, the kind and amounts of food eaten. Most people -- even professional dieticians, according to one study -- tend to underreport their daily calorie intake. However, writing it down is still a good method for increasing a person's awareness of eating patterns. (One patient said that recording circumstances surrounding relapses was a particularly valuable guide for understanding the stresses leading to her own eating behaviors.)
The patient reviews the diary with a therapist or group to set realistic goals and identify patterns that the patient can change. For instance, if food is normally eaten while watching television, then the patient may be advised to eat in another room instead.
Good eating habits are reinforced by rewards. These rewards are other pleasures that substitute the high calorie consumption and sedentary activities.

Behavioral modification has been shown to be helpful particularly for people who have an overly strong response to the taste, smell, and appearance of food. It also may be useful for binge eaters.

Stress-Reduction Techniques. Stress reduction and relaxation techniques may be helpful for some people with obesity, such as those whose weight is related to night-eating syndrome. [See In-Depth Report #31: Stress.]

Changing Sedentary Habits. Making even small changes in physical activity can expend energy. For example, simply getting up to turn the TV on and off instead of using the remote, and standing (instead of sitting) while talking on the phone may help a person lose up to five pounds a year. Other suggestions include cooking one's own food (instead of eating take-out or fast food), walking to as many places as possible, using stairs instead of escalators or elevators, and gardening. Even fidgeting may be helpful in keeping pounds off, and, in one study, chewing gum increased energy expenditure.

No one should rely on such mild activities, however, for serious weight loss. Only high levels of physical activity -- not just using up energy -- help prevent obesity.

Approach to Exercise. Exercise, which replaces fat with muscle, is the critical companion for any weight control program. In a one-year study, women who regularly averaged 3.5 days (176 minutes) of exercise each week lost significantly more weight than women who did not exercise regularly. Women who exercised more than 195 minutes a week lost nearly 7% of their abdominal fat.

People who exercise are more apt to stay on a diet plan. Exercise improves psychological well-being and replaces sedentary habits that usually lead to snacking. Exercise may even act as a mild appetite suppressant. Moreover, exercise improves overall health even with modest weight loss. In support of this, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Be aware, however, that the pounds won't melt off magically. Losing significant weight requires both intensive exercise and calorie restriction. In addition, if a person exercises but doesn't diet, any actual pounds lost may be minimal, because denser and heavier muscle mass replaces fat. Nonetheless, regardless of weight loss, a fit body will look more toned and be healthier. In addition, exercise benefits the heart even with modest weight loss.

The following are some suggestions and observations on exercise and weight loss:

The more strenuous the exercise, the better the chances for short-term and long-term success. With intense exercise, the metabolism continues to burn calories before returning to its resting level. This state of elevated metabolism can last for as little as a few minutes after light exercise to as long as several hours after prolonged or heavy exercise.
Of the standard aerobic machines, the treadmill burns the most calories. It may be particularly effective when used in short multiple bouts during the day. In fact, frequent exercise sessions as short as 10 minutes in duration (about four times a day) may be the most successful exercise program for obese people.
Resistance, or strength, training is excellent for replacing fat with muscles. It should be performed two or three times a week.
As people slim down, their initial level of physical activity becomes easier and they burn fewer calories per mile of walking or jogging. The rate of weight loss slows down, sometimes discouragingly so, after an initial dramatic head start using diet and exercise combinations. People should be aware of this phenomenon and keep adding to their daily exercise program.
As people age, they also need to exercise more to keep off the same amount of weight.
Changes in fat and muscle distribution may differ between men and women as they exercise. Men tend to lose abdominal fat (which lowers their risk for heart disease faster than reducing general body fat). Exercise, however, does not appear to have the same effect on weight distribution in women. In one interesting study, women in aerobic and strength training programs lost fat in their arms and trunk, but did not gain muscle tissue in these regions.

Warning Note. Because obesity is one of the risk factors for heart disease and diabetes, anyone who is overweight must discuss their exercise program with a doctor before starting. Sudden demanding exercise, in such cases, can be very dangerous. [See In-Depth Report #29: Exercise.]

Medications

There are several different drugs used for weight loss. Unless specifically instructed by a doctor, people should use non-drug methods for losing weight. Except under rare circumstances, pregnant or nursing women should never take diet medications of any sort, including herbal and over-the-counter remedies.

A 2001 study reported that 7% of American adults use nonprescription weight-loss products. People must be cautious when using any weight-loss medications, including over-the counter diet pills and herbal or so-called natural remedies. Buying unverified products over the Internet can be particularly dangerous.

Green tea. Perhaps the best alternative advice for people who are overweight is to drink tea. Studies have indicated that regular tea drinking is associated with lower weight, particularly in people who drink it for years. Green tea specifically has been associated with increased energy expenditure. One study reported that people who took a green tea extract (Exolise) lost weight and reduced their waist size. Better evidence is needed to confirm the results on this supplement.

Thermogenic Approach to Weight Loss. An approach to weight loss called thermogenic (also hepatothermic) therapy is based on the idea that certain natural compounds have properties that enable the liver to increase energy in the cells and stimulate the metabolism. Theoretically, the result would be fat loss. Among the natural substances used in such products are EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aloe vera, aspartate, chromium, coenzyme Q10, green tea polyphenols, aloe vera, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs.

Nearly all the current over-the-counter dietary aids contain some combination of these ingredients. There is no evidence that any of these ingredients can produce weight loss, and some may even have harmful effects.

Chromium is a common ingredient in many diet supplements (e.g., Xenadrine, Dexatrim, Acutrim Natural, Twinlab Diet Fuel). It is claimed to specifically promote fat loss, rather than lean muscle loss. Some evidence suggests that niacin-bound chromium may improve insulin sensitivity. On the negative side, animal studies have suggested that chromium may have damaging effects on genetic materials in cells. This could cause sterility.

Ephedra, Ephedrine, and Ma Huang. The FDA does not allow the sale of drugs that contain ephedrine. In May 2004, the FDA banned the sale of dietary supplements that contain ephedra (also called Ma Huang). Ephedra has been linked to serious side effects, including strokes and heart attacks.

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

Conjugated Linoleic Acid (CLA). Conjugated linoleic acid is found in many dietary products (e.g., Biosculpt Liquid, Body Success, GNC Optibolic Body Answers Dietary Formula). There is no evidence that it produces weight loss. Furthermore, there is some concern that CLA might increase insulin resistance and a dangerous inflammatory response in people with obesity.

Tiratricol. Over-the-counter products containing tiratricol, a thyroid hormone, have been sold for weight loss. Such products may increase the risk for thyroid disorders, heart attack, and stroke.

Laxative Actions in Natural Substances. Many dietary herbal teas contain laxatives, which can cause gastrointestinal distress, and, if overused, may lead to chronic pain, constipation, and dependency. In rare cases, dehydration and death have occurred. Some laxative substances found in teas include senna, aloe, buckthorn, rhubarb root, cascara, and castor oil.

Guar Gum. Some fiber supplements containing guar gum have also caused obstruction of the gastrointestinal tract.

Chitosan. Chitosan, a dietary fiber from shellfish, prevents a small amount of fat from being absorbed in the intestine. Well-conducted studies, however, have not found it to be effective. Products containing it include Cheat & Lean Fat Blocker, Natrol, Chroma Slim, and Enforma. People who are allergic to shellfish should not take these supplements.

Plantain. Dietary remedies that list the ingredient plantain may contain digitalis, a powerful chemical that affects the heart. NOTE: This substance should not be confused with the harmless banana-like plant also called plantain.

Orlistat (Xenical) can help about one-third of obese patients with modest weight loss, and can assist in long-term maintenance of weight loss. It works by slowing the absorption of fat (by about 30%) in the intestine. Studies indicate that between 50 - 80% of patients can achieve weight loss of 5% or greater, depending on other lifestyle changes. However, many people regain a significant portion of this weight back within 2 years. It does not work for all patients, however. In one survey of patients who took it, 10% gained weight or did not lose any, and 43% lost less than 5%. Nevertheless, orlistat may delay or even prevent the onset or progression of diabetes and improve cholesterol levels, regardless of weight loss.

The drug can cause gastrointestinal problems and may interfere with absorption of the fat-soluble vitamins A, D, and E and other important nutrients. The most unpleasant side effect is oily leakage of feces from the anus. Restricting fats can reduce this effect. People with bowel disease should probably avoid it. In spite of these side effects, most patients are able to tolerate this agent.

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

Sibutramine (Meridia) helps balance the brain chemicals serotonin and norepinephrine. This helps increase metabolism, causes a feeling of fullness, and increases energy levels. It may be particularly useful for binge-eaters. Studies indicate that sibutramine is effective in achieving weight loss, although the weight loss slows considerably after the first 3 months. The drug also appears to improve cholesterol and lipid (fat) levels, and may have other effects that benefit the heart.

Side effects of sibutramine are common. They include dry mouth, constipation, and insomnia. In one study, almost half the patients dropped out as a result of these side effects. There have been reports of increases in heart rate and blood pressure while taking this medication, although a 2001 study indicates that blood pressure stabilizes over time.

At this time, people who have a history of high blood pressure, stroke, heart disease, or arrhythmias should not take this drug. People taking decongestants, bronchodilators (such as for asthma), monoamine oxidase inhibitors, or serotonin reuptake inhibitors should also avoid sibutramine.

Phentermine and Other Sympathomimetics. Sympathomimetics are drugs that act like the stress hormone (and chemical messenger) norepinephrine. These medications act as stimulants in the brain. Some are approved for treating obesity, but only for short-term use. They include:

Phentermine (Ionamin, Adipex-P, Fastin)
Benzphetamine (Didrex)
Phendimetrazine (Adipost, Bontril, Melfiat, Plegine, Prelu-2, Statobex)

Phentermine is the most commonly prescribed appetite suppressant, and is less expensive than orlistat or sibutramine. Its effects are not long lasting, however. It can also raise blood pressure. In addition, phentermine is associated with depression, which is already a problem in many cases of obesity. A combination (Phen-Pro) containing phentermine and the antidepressant fluoxetine (Prozac) is being investigated to help reduce this problem. Note: Neither phentermine nor such combinations are associated with the heart problems linked to the previous phentermine combination known as Fen-Phen (phentermine and fenfluramine).

Amphetamines. The amphetamines dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), and phenmetrazine (Pleudin) are powerful stimulants. They were used most often in the past but are no longer prescribed for weight loss. These drugs improve mood and produce some modest weight loss over the short term, but carry serious risks of addiction, agitation, and insomnia.

Rimonabant. Rimonabant (Accompli) belongs to a new class of drugs called selective CB1 blockers. The drug is designed to block receptors in the brain associated with the regulation of eating. Rimonabant also targets receptors in fat tissue. The Rimonabant in Obesity-Lipids (RIO-Lipids) study looked at how rimonabant affected metabolic risk factors in high-risk overweight or obese patients with blood fat disorders. The study involved more than 1,000 participants. The findings, published in the November 2005 New England Journal of Medicine, said that people who took the drug significantly reduced their body weight and size of their waist.

Earlier studies involving the drug reported that obese patients treated with 20 mg of rimonabant lost significantly more weight and inches from their waist than patients who received placebo. The drug also appeared to have beneficial effects on raising HDL ("good") cholesterol levels.

Note: Fake rimonabant has been found for sale on several web sites. Patients should be aware that this drug is still experimental, and rimonabant is not available for sale. Buying and taking counterfeit drugs can have serious health consequences. In addition, an FDA advisory panel in April 2007 rejected the drug, citing fears it may cause psychiatric problems and seizures in some patients.

Axokine. Axokine is a type of drug called a ciliary neurotrophic factor. It signals the brain to suppress one's appetite. It is proving to be effective in achieving weight loss, and also improves cholesterol, lipid, and glucose levels regardless of food intake. It could be particularly helpful for people with type 2 diabetes. Early study results found that severely obese patient who took the drug lost more weight than those who took a dummy pill (placebo). Nearly half (46%) of patients who took the drug lost at least 10 pounds, compared to 5% of those who received the placebo. Study participants tolerated the drug well. There were no reports of serious side effects.

Zonisamide. Zonisamide (Zonegran) is an anti-seizure medication that is also being investigated for weight loss. In one study, patients who took it lost more weight than those on placebo. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Other side effects include dizziness, forgetfulness, headache, and nausea.

Topiramate. Topiramate (Topamax) is another anti-seizure medication being investigated for weight reduction. Three clinical trials have reported that patients given topiramate lost more weight than those receiving placebo. Weight loss was sustained for up to 1 year. The drug is also being studied for binge-eating disorders associated with obesity.

Other Treatments

Surgical procedures for obesity may be appropriate for some dangerously obese people, and may reduce heart problems and many of the risks associated with obesity. These risks include high blood pressure, sleep apnea, and diabetes. In fact, some evidence suggests that surgery may provide much greater control of weight and diabetes than nonsurgical weight-loss methods. Studies are reporting significant reductions in diabetes, and the need for diabetic medications, after surgery. Other medical conditions that often improve after surgery include heartburn, arthritis, and other joint and circulation problems.

Bariatric surgeries produce weight loss through one of two approaches:

Restrictive Banding Procedures. These procedures restrict the amount of food by closing off parts of the stomach with bands.
Malabsorptive Bypass Procedures. This approach restricts the amount of food and also reduces absorption by using a bypass of parts of the intestine.

The malabsorptive procedures are more successful in achieving weight loss than the banding approach, but they carry a greater risk for nutritional deficiencies.

Most people who have bariatric surgery lose about two-thirds of excess weight within 2 years. In addition, diseases associated with obesity (such as diabetes, high blood pressure, sleep apnea, joint pain, and incontinence) often improve.

Researchers at the Mayo Clinic looked at records from patients who had the surgery between 1990 and 2003. They found that those who had bariatric surgery reduced their risk of cardiovascular events such as a heart attack much more than those who lost weight without surgery. The findings were published in the September 2005 Mayo Clinic Proceedings.

Other studies have shown that even though most patients maintain significant weight loss, the majority regain about to 10% of their weight. Patients must still develop a healthy life style and be calorie conscious after the operation. Follow-up must be life-long.

Any surgical candidate must have failed consistently in losing weight through less invasive methods. Experts recommend bariatric surgery only for the following:

Those whose BMI is above 40 (about 100 pounds overweight)
Those with BMIs of over 35 who have type 2 diabetes or serious obesity-related medical problems
Those with severe obesity that interfered with employment, normal physical activity (e.g., walking), and important relationship

About a third of people who undergo these procedures achieve normal weight, and 80% experience some weigh loss. They are less successful than the bypass procedures, but carry a lower risk of nutritional deficiencies.

Vertical Banded Gastroplasty. Vertical banded gastroplasty (VBG) was the most common restrictive procedure. It involves creating a hole through both stomach walls and sealing the edges with a staple. This narrows the stomach, similar to a funnel, and allows only small amounts of food to pass through.

Laparoscopic Gastric Banding. Laparoscopic gastric banding (the Lap-Band) usually does not require a major incision and avoids some of the major complications of gastric bypass:

It employs an adjustable silicone band that is placed around the upper part of the stomach.
A small balloon-like reservoir attached to the band under the abdominal skin contains saline, which can be added or removed to tighten or loosen the band.
The procedure restricts the amount of food a person can eat and gives the feeling of fullness.

The band is removable, if necessary. Studies to date indicate that the intestinal tract returns to normal afterward. Studies, including those done in the elderly, have reported significant weight loss and improved quality of life with the procedure.

Malabsorptive procedures produce greater weight loss than restrictive procedures. Patients generally achieve about two-thirds of their weight loss within 2 years. Furthermore, in a 2003 study, after standard bypass surgery, 83% of patients with type 2 diabetes experienced normal blood glucose levels and the rest had significant reductions.

Roux-en-Y Gastric Bypass Procedure. This is the most common and successful malabsorptive surgery in the United States. It involves creating a small stomach pouch that serves as a reservoir and restricts food intake. The pouch eventually holds up to 3 ounces of food and has a small outlet that delays emptying and causes a feeling of fullness. Then the surgeon creates a Y-shaped section in the small intestine that attaches to the pouch. This section allows food to bypass the lower stomach and upper part of the intestine. One 2003 study reported that this procedure was associated with significant weight loss, and 80% of patients with type 2 diabetes were able to reduce their medications. A more recent study, published in the March 14, 2006, issue of Archives of Surgery, found that gastric bypass surgery also helps lower the blood pressure of very obese patients.

The procedure produces greater and more sustained weight loss than banding procedures, but it is also more complicated, and carries a higher risk of nutritional deficiencies. Laparoscopy techniques, which are less invasive, are now preferred over open surgery. They achieve equally good results with fewer complications.

Biliopancreatic Diversion. This procedure is more complicated and removes portions of the stomach. The pouch that is created attaches directly to the lower part of the small intestine. It poses a higher risk for nutritional deficiencies than other procedures and is not used as often.

Click the icon to see an image of gastric bypass surgery.

General Side Effects and Complications. Side effects and complications of bariatric procedures are common, and up to 25% of patients require corrective or repeat procedures. After any of these procedures people must chew all their food carefully, and they cannot eat large amounts of food at one time. If patients do not follow these guidelines, they will experience nausea, abdominal distress, or both.

Complications from any bariatric procedure includes the following:

Vomiting: This is the most common complication, and it is most common with banding procedures.
Nutritional deficiencies: There is a strong risk of nutritional deficiencies, particularly with malabsorptive operations. This complication can lead to anemia and increase the risk of bone loss and osteoporosis. Taking enough mineral and vitamin supplements is important after bariatric surgery.
Deep-vein thrombosis: There is a significant risk for deep-vein thrombosis (blood clots in the veins).
Abdominal hernia: This is another common complication. Newer, laparoscopic techniques do not carry this risk, but not all individuals are candidates for this less-invasive approach.
Rapid weight loss after surgery: This complication puts people at high risk for gallstones.
Women who wish to be pregnant should wait until their weight has stabilized. Rapid weight loss and nutritional deficiencies can harm the fetus.

People at highest risk for complications are those with heart or lung problems, severe obesity, and a history of abdominal surgeries. The mortality rate from bariatric surgeries is 0.2%, which is lower than the morality rates from severe obesity itself. Other surgical variations and less invasive techniques using laparoscopy have been developed.

Specific Complications of Restrictive Banding Procedures. Nausea, vomiting, or both occurs in half the patients, and severe heartburn occurs in a third. Device-related complications include band slippage, pouch dilation (widening), or both in nearly a quarter of patients, and obstruction in 12% of patients. Very serious complications are rare, but include blood clots, bleeding, infection, pneumonia, and perforation (tearing) of the stomach.

Specific Complications of Malabsorptive Bypass Procedures. Vomiting often occurs. Nutritional deficiencies occur more often in these procedures. The so-called dumping syndrome is a common unpleasant side effect, which occurs when food waste moves too quickly through the intestine. Symptoms include nausea, weakness, sweating, and faintness (particularly after eating sweets).

Spot Exercising. Anyone seeking to lose weight must expect that the results may not be as cosmetically satisfying as one would wish. Spot exercising (training particular areas of the body) is ineffective in reducing fat in specific locations because exercise draws on fat stores throughout the body. Gimmicky devices such as bust developers, vacuum pants, and exercise belts do absolutely nothing to reduce fat or add bulk in specific locations. Electrical pads wrapped around the waist, arms, or thighs were reported to cause burns and fires.

Cellulite-Removal Creams. Many women try to reduce fat in their thighs (cellulite) with creams that contain aminophylline (Skinny Dip, Thermojetics Body Toning Cream, Smooth Contours). Studies provide no evidence that these creams are effective. Their apparent effect on fat may simply be from narrowing blood vessels and forcing water from the skin, which could be dangerous for people with blood flow problems.

Endermologie. Endermologie uses motorized rollers and regulated suction to smooth out cellulite. In one study, about 28.6% of patients reported improved appearance after using it.

Liposuction. Liposuction eliminates fat in specific areas, such as the abdomen, thighs, buttocks, or knees. Special instruments are inserted through the skin into the pockets and suction is used to move the fat, break it up, and remove it. Small tubes may be used to drain blood and fluid during the first few days. The pain after the operation can be severe and often the skin does not contract, resulting in a flabby look. Complications can include burns from the vibrators, bruising, blood clots, and bleeding. Weight gain generally tends to develop in other locations after the operation. Some doctors are using this procedure in overweight people with diabetes to remove abdominal fat. Although there is no proof that it has an effect on diabetes, some experts believe the procedure deserves attention.

Liposuction is not recommended for major weight loss.

Resources

www.healthierus.gov/dietaryguidelines -- Dietary Guidelines for Americans 2005
www.naaso.org -- North American Association for the Study of Obesity
www.eatright.org -- American Dietetic Association
www.nutrition.gov. -- Nutrition.gov
www.asbs.org -- American Society for Bariatric Surgery
www.cnpp.usda.gov -- Center for Nutrition Policy and Promotion
http://fnic.nal.usda.gov -- Food and Nutrition Information Center
www.americanheart.org -- American Heart Association
www.nationaleatingdisorders.org -- National Eating Disorders Organization
www.aabt.org -- Association for Advancement of Behavior Therapy
www.fda.gov -- Food and Drug Administration
http://win.niddk.nih.gov -- Weight-Control Information Network

References

US Food and Drug Administration FDA Approves Orlistat for Over-the-Counter Use. Rockville, MD: National Press Office; February 7, 2007.

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. Journal of the American Medical Association. 2006; 295:1549-1555.

National Center for Health Statistics. Chartbook on Trends in the Health of Americans. Health, United States, 2005. Hyattsville, MD: Public Health Service. 2005

National Institute of Diabetes and Digestive and Kidney Diseases - Weight-control Information Network. Statistics Related to Overweight and Obesity. Available online.

National Center for Health Statistics. Prevalence of Overweight Among Children and Adolescents: United States, 2003-2004.

Morino M, Toppino M, Bonnet G, Rosa R, et al. Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of efficacy. Surg Endosc. 2002 Nov;16(11):1566-72.

Brethauer SA, Schauer PR, Chand B. Risks and benefits of bariatric surgery: Current evidence. Cleveland Clinic Journal Of Medicine. 2006 Nov; 73(11): 993-1007.

Rosenthal RJ, Szomstein S, Kennedy CI, et al. Laparoscopic surgery for morbid obesity: 1,001 consecutive bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Obes Surg. 2006 Feb;16(2):119-24.

He K, Liu K, Daviglus ML, et al. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation. 2006: Published online before print. March 27, 2006.

Chen TY, Smith W, Rosenstock JL, Lessnau KD. A life-threatening complication of Atkins diet. Lancet. 2006 Mar 18;367(9514):958.

Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc. 2005 Sep;80(9):1157-62.

Sidhaye A, Cheskin LJ. Pharmacologic treatment of obesity. Adv Psychosom Med. 2006;27:42-52.

Fernstrom JD, Courcoulas AP, Houck PR, Fernstrom MH. Long-term changes in blood pressure in extremely obese patients who have undergone bariatric surgery. Arch Surg. 2006 Mar;141(3):276-83.

Despres JP, Golay A, Sjostrom L; Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005 Nov 17;353(20):2121-34.

Lanningham-Foster L, Nysse LJ, Levine JA. Labor saved, calories lost: the energetic impact of domestic labor-saving devices. Obes Res. 2003 Oct;11(10):1178-81.

Review Date:
6/14/2007
Reviewed By:
A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (4/30/2007).

A.D.A.M. Copyright

adam.com

Colon and rectal cancers

FitSugar — Wed, 08 Oct 2008 17:35:05 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Dietary Factors
Prevention
Diagnosis
Staging
Prognosis
Surgery
Medications
Radiation Treatment
Follow-up Testing
Treatment for Metastasized ...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In September 2006, the Food and Drug Administration approved panitumumab (Vectibix) for the treatment of patients with colorectal cancer that has spread to other parts of the body following chemotherapy. Like cetuximab (Ertibux), panitumumab targets the epidermal growth factor receptor (EGFR) on cancer cells. Panitumumab is the first new colorectal cancer drug approved since 2004. The FDA granted accelerated approval to panitumumab based on a clinical trial of patients with metastatic cancer. The average time to disease progression or death was 96 days in patients treated with panitumumab compared to 60 days in patients who received standard care.

Diet and Colorectal Cancer Recurrence

Evidence indicates that diet plays a role in colorectal cancer prevention. Now, a 2007 study in the Journal of the American Medical Association (JAMA) suggests that dietary factors also affect the risk of cancer recurrence. Patients with stage III colorectal cancer who ate lots of red meat, refined grains, and sweets had a higher risk of cancer recurrence and death than patients whose diets were high in fruits and vegetables, poultry, and fish.

Folic Acid No Good for Prevention?

Many experts have long believed that folic acid supplements may help protect against colorectal cancer. But according to a 2007 JAMA study, high-dose folic acid supplements may not prevent colorectal cancer and may actually increase the risk for adenomatous polyp formation. Adenomatous polyps are benign colorectal tumors that can potentially become cancerous. In the study, patients who took folic acid supplements had a greater risk of developing new, more numerous, and larger adenomatous polyps than patients who did not take the supplements.

NSAIDS Not Recommended for Colorectal Cancer Prevention

In March 2007, the U.S. Preventive Services Task Force (USPSTF) recommended against the routine use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent colorectal cancer in people who are at average risk for this disease. Several recent studies have indicated that aspirin, and NSAIDs such as celecoxib (Celebrex), can help prevent colorectal cancer. But the USPSTF notes that the risks of these drugs outweigh the benefits. Long-term daily use of NSAIDs increases the risk for gastrointestinal bleeding, kidney function problems, and heart attack and stroke.

Introduction

Cancers of the colon and rectum, often referred to collectively as colorectal cancer, are life-threatening tumors that develop in the large intestine.

More than 80% of colorectal tumors evolve from adenomatous polyps. These gland-like growths develop on the mucous membrane that lines the large intestine. They are usually either:

Tubular polyps, which protrude mushroom-like
Villous adenomas, which are flat and spreading and are more apt to become malignant (cancerous)

Polyps are very common and almost always benign. Their numbers increase with age. Polyps are found in about 25% of people by age 50, and 50% of people by age 75. Fewer than 1% of polyps under 1 centimeter (slightly less than half an inch) become cancerous. About 10% of larger polyps become cancerous within 10 years, and about 25% of these larger polyps become cancerous after 20 years. Certain inherited polyps can become cancerous more rapidly.

Digestion takes place in the gastrointestinal (GI) tract, essentially a long tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach. Food then travels through the small and large intestines before being excreted through the rectum and out the anus.

The esophagus, stomach, large and small intestine -- aided by the liver, gallbladder, and pancreas -- convert the nutritive components of food into energy and break down the non-nutritive components into waste to be excreted.

The esophagus is a narrow muscular tube, about 9 1/2 inches long that begins below the tongue and ends at the stomach.

In the stomach, acids and stomach motion break food down into particles small enough so that the small intestine can absorb nutrients.

Click the icon to see an image of stomach anatomy.

The small intestine, despite its name, is the longest part of the gastrointestinal tract, extending for about 20 feet. Food passes from the stomach through its three parts: first the duodenum, then the jejunum, and finally the ileum. Most of the digestive process occurs in the small intestine.

Click the icon to see an image of small intestine anatomy.

Undigested material, such as plant fiber, is passed next to the large intestine, mostly in liquid form. The large intestine is wider than the small intestine but only about 6 feet long. It is the final portion of the digestive tract and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections.

Click the icon to see an image of large intestine anatomy.

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they are passed through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Causes

In most cases of colon or rectal cancers, the cause or causes are unknown. Defects in genes that normally protect against cancer play the major role in causing polyp cells to continuously spread and become cancerous. Some of these cases are caused by inherited genetic defects, and such patients usually have family histories of colorectal cancer. Most of the genetic mutations involved in colon cancers, however, appear to arise spontaneously (no strong family history) rather than being inherited. In such cases, environmental or other factors trigger genetic changes in the intestine that lead to cancer.

About 6% of cases of colon cancer are due to inherited factors.

APC Gene and Familial Adenomatous Polyposis (FAP). When the adenomatous polyposis coli (APC) gene is normal, it helps suppress tumor growth. In its defective form, it permits high levels of the protein beta-catenin to accumulate, which accelerates cell growth leading to polyps. Various genetic mutations that affect the APC gene directly or indirectly have been identified:

Familial adenomatous polyposis (FAP) is a rare and serious disorder in which the patient inherits an adenomatous polyposis coli (APC) mutation from either parent. It occurs in about 1 in 8,000 people. During early adulthood, hundreds to thousands of polyps grow in the colon. FAP causes less than 1% of all cases of colorectal cancer, but if untreated, virtually everyone who inherits this condition develops cancer before the age of 40. Many of the deaths attributed to FAP can be prevented with early and aggressive surgical treatment.
Non-inherited mutations of the APC gene have been detected in nearly all patients with spontaneous colon cancers.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, accounts for at least half of colorectal cancers that run in families. (However, only 3% or less of all colorectal cancers are due to this problem). About 50 - 80% of people who inherit the abnormal gene will develop colon cancer. HNPCC tends to develop in the right side of the colon, often in young individuals. (Left-sided cancers can still occur as well.)

People who inherit HNPCC and other defects are prone to other cancers, including uterine and ovarian cancers, as well as cancers of the small intestine and kidney system (very rare). HNPCC is highly associated with genes containing an abnormality called microsatellite instability (MSI), which is a sign of defective DNA repair. Testing tumors for MSI in people with newly diagnosed colon cancer who also have a family history of the disease may prove to be an effective method for identifying patients with hereditary nonpolyposis colorectal cancer. Tests are being developed that can detect the actual HNPCC genetic abnormality (mutation) that was inherited from a father or mother. The two most commonly affected genes are MSH2 and MLH1.

Cyclooxygenases and Prostaglandins. Cyclooxygenase 1 and 2 (COX-1 and COX-2) are enzymes involved in the production of prostaglandins, substances produced by the body that cause inflammation, widen and narrow blood vessels, control muscle contractions, and inhibit hormones that regulate fat metabolism. COX-2, but not COX-1, appears to play a role in the development and spread of colorectal tumors. COX-2 increases the levels of prostaglandin E2 (PGE2), which, in turn, stimulates factors that inhibit apoptosis, the natural process whereby all cells, including cancerous ones, self-destruct. It also activates interleukin-6 (IL-6), a factor in the immune system that is associated with cancer cell invasion.

C-Reactive Protein (CRP). CRP is another indicator of inflammation. In a 2004 study published in the Journal of the American Medical Association, elevated CRP levels predicted the development of colon -- but not rectal -- cancer.

Bile Acid Salts. Deoxycholic acid, which is found in the fat-digesting bile salts released by the gallbladder, appears to have carcinogenic properties. Its effects are now believed to play a role in some cases of colon cancer. Levels of the acid can rise as a result of high-fat diets or certain diseases.

Growth Factors. Chronically higher circulating levels of growth factors, including insulin-like growth factor, have been associated with colorectal cancer.

Inflammatory bowel diseases include Crohn's disease and ulcerative colitis. These chronic disorders cause persistent injuries in the intestinal tract that can, in some cases, produce cancerous changes.

Symptoms

It is possible to have colon or rectal cancer without symptoms. Many patients are free of symptoms until their tumors are quite advanced.

Weight loss and changes in bowel movements are general symptoms for colon cancer, but these symptoms also occur in many other diseases.

Blood in the stools is a common sign of many intestinal cancers. It may appear red if it is fresh or black if it is old. It should be reported to a doctor immediately, even though it is often caused by conditions other than cancer, including:

Hemorrhoids
Minor tears around the rectal or anal areas
Diverticulosis

In addition, stool can change color by:

Eating certain red foods, such as beets or red licorice (red)
Taking iron supplements and medications that have bismuth subsalicylate, most commonly Pepto-Bismol (black)

Nevertheless, blood in the stools is an abnormal finding that should never be ignored. Always report it to your doctor for further advice.

Symptoms of colorectal cancer vary widely depending on the location of the cancer within the large intestine.

Tumors in the Cecum and Ascending Colon (Right Colon). The waste matter in the first portion of the colon is in liquid or semi-liquid form. Tumors that develop here do not change bowel habits or stool formation, but they may cause intermittent or chronic bleeding. Although the stools look normal, patients may develop symptoms of anemia from iron deficiency. Such symptoms include weakness, fatigue, heart palpitations, shortness of breath, and exercise intolerance.

Tumors in the Transverse Colon. As waste material passes across the upper quadrants of the abdomen (the transverse colon), the intestine absorbs water, and the waste matter becomes more solid. In addition to bleeding, tumors here may cause cramps, gas, partial or complete obstruction, and even perforation of the bowel. Anemia can also occur.

Tumors in the Descending Colon and Rectum (Left Colon). When tumors partially block the lower intestine, thin, pencil-shaped stools may form. Bowel habits can change. Tumors in the rectum and lowest part of the intestine can cause pain and a feeling of fullness. Defecation may be painful, or patients may feel the urge to defecate but nothing happens. Bleeding from these locations may be brisk and bright red or maroon, but cancer is often detected before symptoms of chronic anemia develop.

Risk Factors

Colorectal cancer is the third most common cancer in the U.S., with Americans facing a lifetime chance of 5.5 - 6% for this cancer. In 2007, colorectal cancer was expected to cause 153,760 new cases and 52,180 deaths in the United States. About 73% of cancers occur in the colon and 27% in the rectum.

The lifetime risk of cancer of the colon or rectum is 5.9% for men and 5.5% for women.

Colorectal cancer risk increases with age. More than 90% of these cancers occur in people over age 50. The rate of colorectal cancer in patients under 20 years is less than 1 in 100,000 per year. At age 50 about 1 in 2,000 people per year will develop colorectal cancer. After age 65, this rate increases to almost 3 in 1,000.

African-Americans have the highest risk of being diagnosed with, and dying from, colorectal cancer. Among Caucasians, Jews of Eastern European (Ashkenazi) descent have an elevated rate of colorectal cancer. Asian Americans/Pacific Islanders, Hispanics/Latinos, and American Indians/Alaska Natives have a lower risk than Caucasians.

About 20 - 25% of colorectal cancers occur among people with a family history of the disease. (Seventy-five percent of cases are due to other causes.) People who have more than one first-degree relative (sibling or parent) with the disease are especially at high risk. The risk is even higher if the relative was diagnosed with colorectal cancer before the age of 60.

About 5 - 10% of patients with colorectal cancer have an inherited genetic abnormality that causes the disease. Genetic mutations associated with colorectal cancer include familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.

The risks for colon cancer are far higher in industrialized nations than less developed countries. A Western lifestyle, being sedentary, smoking, and having excess weight have all been associated with increased risk for colorectal cancer. (However, about 75% of cases occur without a known predisposing factor.)

Dietary Factors. Eating a lot of red meat increases the risk for colorectal cancer. Other types of animal protein (low-fat dairy products, fish, poultry) may decrease the risk of developing polyps and colorectal cancer. Studies on fruits, vegetables, and fiber are mixed. Some evidence suggests that diets very low in fruits and vegetables may increase the risk. In any case, eating a variety of fruits and vegetables should be part of a healthy diet.

A 2007 study in the Journal of the American Medical Association suggested that diet may play a role in colorectal cancer recurrence, as well as prevention. The study evaluated patients with stage III colon cancer who had been treated with surgery and chemotherapy. Patients who ate diets high in red and processed meats, refined grains, and sweets had a higher risk of cancer recurrence and poorer survival than patients whose diets were high in fruits and vegetables, poultry, and fish.

Alcohol and Smoking. Alcohol use and smoking increase the risk for colorectal cancer. Patients who smoke and drink may also be diagnosed with colorectal cancer at a younger age than non-drinkers and non-smokers. Several studies suggest that women who smoke are at especially high risk of developing colorectal cancer.

Obesity. There is a demonstrated link between body mass and colon cancer risk for both men and women. The Centers for Disease Control and Prevention has reported that the risk of colon cancer rises as body mass index increases. Obesity has been associated biologically with higher circulating levels of insulin and a hormone called insulin-like growth factor. Chronically high levels of these substances may increase colorectal cancer risk.

Physical Inactivity. More than 50 studies from around the world suggest that physical activity helps prevent colon cancer. In contrast, exercise does not protect against rectal cancer.

Crohn's disease and ulcerative colitis are chronic afflictions of the large intestine known as inflammatory bowel diseases (IBD). Both have been linked to increased risk for colorectal cancer. (Patients with ulcerative colitis have a higher risk than those with Crohn's disease.) Family histories are helpful in determining risk associated with inflammatory bowel disease. Some studies suggest the following:

Patients with IBD who have a family history of colorectal cancer face up to a five-fold risk of colon cancer themselves.
Individuals without IBD who have relatives who suffered from both IBD and colorectal cancer may face a higher risk for developing colorectal cancer themselves.
Individuals without IBD but with a family history of IBD and no colon cancer most likely face no higher risk for cancer themselves.

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines that is usually confined to the terminal portion of the small intestine, the ileum. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other inflammatory bowel diseases have been linked with an increased risk of colorectal cancer.

Polyps. Polyps are tissue growths, usually benign, that develop in the color or rectum, most often in patients over 50 years of age. When pathologists examine polyps removed from the colon, they classify them as either hyperplastic or adenomatous. Both types are benign, but some adenomas will become malignant. As a preventive measure, polyps should be removed (polypectomy).

Ureterosigmoidostomy. People who have had ureterosigmoidostomy, a surgical procedure to correct a birth defect in the bladder or to treat some bladder cancers, may develop tumors near the site of the defect, which is chronically exposed to urine and feces. Such patients have a 5 - 10% chance of developing colon cancer 15 - 30 years after the operation.

Diabetes. Many studies have identified an association between type 2 diabetes and colon cancer. Both diseases share common risk factors of obesity and physical inactivity, but diabetes itself is a risk factor for colorectal cancer. Both men and women who have diabetes are at risk.

Heart Disease. Coronary artery disease (CAD) increases the risk for colorectal cancer. Both CAD and colorectal cancer share important risk factors, including smoking, high fat diet, sedentary lifestyle, and obesity.

Dietary Factors

Some, but not all, studies have suggested that a high intake of fruits and vegetables can lower the risk for colorectal cancer. One study, for example, reported that these foods do not prevent polyps from forming but may help prevent them from becoming cancerous.

Phytochemicals. Many studies have demonstrated the cancer-fighting effects of plant chemicals called phytochemicals. Fruits and vegetables that contain phytochemicals can often be identified by colors:

Dark green (broccoli, spinach, kale, collard greens, mustard greens). These vegetables contain chemicals called isothiocyanates, which have been associated with a lower risk for cancer in general.
Red (red pepper, tomatoes, watermelon, raspberries, pink grapefruit). Lycopene is a chemical found in these foods that may have strong cancer-protective properties. Cooking tomatoes appears to increase their benefits.
Yellow-orange (carrots, pumpkin, sweet potatoes, oranges, tangerines). The colors in these foods are due to carotenoids. Carotenoids have been associated with health protection, although they may not have much effect on colon cancer itself.
Blue-black (many berries). Dark berries appear to have potent antioxidant chemicals that may be protective against cancer.

Organosulfurs are important food chemicals that are part of the allium family. Studies have reported health benefits from foods containing them. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots. A review of 300 studies concluded that people who eat raw or cooked garlic regularly experience about two-thirds the risk of colorectal cancer as people who eat little or none. Another analysis, however, found the available evidence about garlic to be inconclusive. Garlic supplements, in any case, do not appear to be protective.

Fiber. Studies have been mixed on whether fiber (found in fruits, vegetables, and whole grains) protects the colon from cancer. For example, three major studies in 2002 and 2003 reported no difference in the development of colorectal polyps or cancer recurrence with high intake of fiber. On the other hand, results of the 2003 European Prospective Investigation into Cancer and Nutrition (EPIC) -- the largest study ever conducted on the role of diet in the development of cancer -- suggested that fiber is protective regardless of its source. However, in the study, the greatest benefits were observed for the left side of the colon and the least for the rectum. In any case, fiber, which is only found in plant products, may be beneficial for the heart and have other health advantages.

The role of fats in inflammatory bowel disease is complex and not fully known. A 2006 study from the Women’s Health Initiative found that a low-fat diet did not help reduce the risk for colorectal cancer. However, the study did not distinguish between types of fat.

Monounsaturated fats (olive, peanut, canola oils; avocados, nuts) and omega-3 polyunsaturated fats (fish, flaxseed oil, walnuts) are the healthiest types of fats.
Saturated fats (red meat, butter, high-fat dairy products) and trans-fats (hydrogenated fat found in snack foods, fried foods, commercial baked goods) are unhealthy types of fats.

Dietary guidelines recommend that adults limit the total fat in their diet to 25 - 35% of total daily calories. Saturated fat intake should be less than 7%, and trans fats less than 1%, of total daily calories. (Patients with heart disease or diabetes may need to limit unhealthy fat in their diet even further.) Most fats should come from polyunsaturated and monounsaturated fat sources.

[See In-Depth Report #43: Heart healthy diet; and #42: Diabetes diet.]

Evidence strongly suggests that red meat raises the risk for colon cancer development, and perhaps also recurrence. Red meat contains dietary iron, which has been associated with a higher risk for colon cancer.

High-temperature cooking (grilling, broiling, or pan-frying) has been specifically associated with increased risk for colon polyps and colon cancer. Overcooking meat increases the amount of carcinogens called heterocyclic amines, which has been associated with cancerous changes.

Milk, Lactose, and Probiotics. In one study, adults who drank the most milk had the lowest risk for colon cancer. A 2004 study published in the Journal of the National Cancer Institute supported this conclusion. In this review of 10 epidemiologic studies that included more than 500,000 people, those who consumed more milk and calcium had a lower risk of developing colorectal cancer. Milk contains not only calcium but also other compounds, such as lactose, that may help protect against colon cancer.

Yogurt specifically has been associated with a lower risk for colon cancer if it contains live active bacterial cultures, such as Lactobacillus acidophilus, that are called probiotics. These "friendly bacteria" appear to protect the colon from cancerous changes. (Acidophilus and other probiotic capsules are also available in health food stores.)

Calcium. Calcium, which is found in dairy products, is associated with colon cancer protection. Many studies have shown a possible protective effect from either high-calcium diets or calcium supplements. However, a 2006 study from the Women’s Health Initiative found that calcium and vitamin D supplements do not reduce women’s colorectal cancer risk. Many doctors still recommend that postmenopausal women take these supplements for bone health.

Obesity has been associated with colon cancer. In some studies of people under 67 years old, the amounts of fat and protein were less important than the total number of calories consumed: the higher the energy intake, the greater the risk for developing colon cancer. In older adults, high calorie intake did not make any significant difference. Other studies have indicated that eating too much sugar may increase the risk for colon cancer.

Studies conducted in several countries have found that drinking four or more cups of coffee a day is associated with a lower risk for colorectal cancer. Green tea may have also beneficial properties, but more research is needed in both of these areas.

Folate and B Vitamins. For years, many doctors have believed that the B vitamin folate (called folic acid) may help protect against colorectal cancer, particularly for people who are genetically predisposed to this disease. Folate is found in beans, citrus fruits, and green vegetables, but some studies have indicated that the greatest protective benefits come from taking supplements.

However, an important study published in 2007 in the Journal of the American Medical Association challenged this assumption. The study suggested that high-dose folic acid supplements do not prevent colorectal cancer, and may actually increase the risk for developing certain types of colorectal tumors. The study evaluated over 1,000 men and women who had a recent history of non-cancerous colorectal polyps. (Adenomatous polyps, also called colorectal ademomas, are the most common type of polyp found in colorectal cancer screenings.) The results indicated that patients who took 1 mg/day of folic acid supplements were more likely to develop new adenomatous polyps than patients who did not take supplements. Patients in the folic acid supplement group were also more likely to have advanced adenomas and more numerous adenomas.

Adenomatous polyps are benign tumors, but they can potentially develop into cancerous tumors. Researchers are continuing to investigate the role that folic acid plays in colorectal cancer risk and prevention. It is possible that folic acid may help prevent the initial appearance of adenomatous polyps, but increase the risk for additional polyp formation once they have begun to occur.

Antioxidant Supplements. Antioxidants are chemicals that help eliminate harmful particles called oxygen-free radicals that have been associated with cancerous changes. Some studies have associated supplements of the antioxidants selenium and vitamins A, C, D, and E with lower colon cancer risk, but most studies have found no protective effect.

Prevention

Studies indicate that daily exercise is one of the best ways to reduce the risk of colorectal cancer. The more vigorous the activity, the greater the benefit, but even moderate exercise (walking, stair-climbing) can help reduce colorectal cancer risk. The American Cancer Society (ACS) recommends that people engage in at least moderate exercise for 30 minutes or more at least 5 days a week. The ACS also notes that 45 minutes or more of moderate-to-vigorous activity at least 5 days a week may help further reduce cancer risk.

Some studies also suggest that regular exercise may be beneficial for patients who have been diagnosed with colorectal cancer. Two 2006 studies indicated that exercise may reduce the risk of colorectal cancer recurrence and death for patients with stage I - III cancer.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very common pain relievers that are available over-the-counter and by prescription. They include aspirin, ibuprofen (Motrin), naproxen (Aleve), and the COX-2 inhibitor celecoxib (Celebrex). Several studies have reported that NSAIDs help reduce the risk of colorectal cancer. However, regular use of NSAIDs, even in low doses, can increase the risk of gastrointestinal bleeding and stomach ulcers. Long-term use of NSAIDs can also increase the risk for heart attack and stroke, especially in people who have a history of heart disease. Several 2006 and 2007 studies in the New England Journal of Medicine reported that celecoxib prevented precancerous polyps, but the drug more than doubled patients’ risk for heart attack and other cardiovascular events.

A 2005 Nurse’s Health Study found that aspirin, but not other NSAIDs, does provide protection against colorectal cancer. However, the risk was only reduced for women who took 2 aspirin a day for more than 10 years. In addition, this dose level greatly increases the risk for gastrointestinal bleeding. Furthermore, a 2007 study in the New England Journal of Medicine suggested that aspirin’s protective effects may only apply to some types of colorectal cancer tumors. Another 2007 study, published in the Lancet, indicated that long-term daily use of aspirin can protect against polyps and colorectal cancer, but experts agree that aspirin’s risks do not outweigh its benefits for most people. (Some people who are at high risk for developing colorectal cancer may benefit from aspirin therapy.)

In March 2007, the U.S. Preventive Services Task Force (USPSTF) recommended against the routine use of aspirin and other NSAIDs to prevent colorectal cancer in people at average risk for this disease. (This recommendation does not apply to people who have a family history of colorectal cancer or who are at high risk for developing colorectal cancer due to other risk factors.) Long-term use of NSAIDs can increase the risk for gastrointestinal bleeding, kidney function problems, and heart problems. Aspirin can also increase the risk for hemorrhagic stroke. Due to these risks, the American Cancer Society and other professional associations also recommend against the use of NSAIDs or other types of medications for colorectal cancer prevention.

Medications containing 5-aminosalicylate (5-ASA) are sometimes given to patients with ulcerative colitis to help control inflammation. These drugs, which include sulfasalazine and mesalamine, are chemically related to aspirin. A 2005 review of clinical trials found that patients with ulcerative colitis who used 5-ASA were 49% less likely to develop colorectal cancer than patients who did not use these drugs

Some studies have suggested that cholesterol-lowering statin drugs may help reduce colorectal cancer risk. A 2006 study in the Journal of the National Cancer Institute did not find any protective benefit for statins.

Estrogen has been associated with a lower risk for colon cancer, perhaps because of specific enzymes that prevent cell proliferation. Drugs containing estrogen, then, may help high-risk women:

There is some evidence that hormone replacement therapy (HRT) reduces the risk of colon cancer in postmenopausal women. It carries other risks, however, including a higher risk for breast and uterine cancer and blood clots. A 2004 New England Journal of Medicine study found that while short-term use of estrogen plus progestin reduced the risk of developing colon cancer, combination HRT users who were diagnosed with the disease had more advanced forms of the cancer. Older women who are at higher risk for colon cancer might discuss risks and benefits of HRT with their doctor.
Oral contraceptives may reduce younger women's risk of colon cancer. Duration of use does not seem to be associated with decreased risk, but protection appears stronger for women who have more recently used oral contraceptives.

Diagnosis

Colon and rectal cancers are diagnosed using the screening tests discussed below. These tests can detect precancerous polyps and colorectal cancers at stages early enough for complete removal and cure.

Unfortunately, only 30 - 40% of adults over 50 years old (mostly in the upper socioeconomic group) have regular screening tests that could detect a cancer early enough for curative treatment. A survey reported that many people are not screened because they are too embarrassed. Those who had already had the tests were willing to have them again if they saved one additional day of their lives.

There is some debate about what is the best screening method. Current screening guidelines offer several different options for patients. Doctors agree that not enough people are screened and that these tests, if adopted with the same regularity as such screening tests as Pap smears, would save many lives. It is especially important for anyone at increased risk or with symptoms, such as rectal bleeding or ulcerative colitis, to have testing at an earlier age.

There is also debate about when people should stop being screened. A 2006 study in the Journal of the American Medical Association indicated that screening provides little benefit for elderly people, especially because colorectal cancers grow very slowly. The researchers suggest that doctors should carefully consider the risks versus benefits of screening patients age 80 and older.

Individuals should discuss with their doctors the risks and benefits of all screening procedures. Some controversy exists over how often people without risk factors for cancer should be screened and which detection method should be used for them.

Guidelines for Adults Age 50 and Over with Average Risk. The following are the five screening options recommended for people age 50 and over who have no symptoms and no family history of colon cancer:

Fecal occult blood test (FOBT) or fecal immunochemical test (FIT) every year
Flexible sigmoidoscopy every 5 years
FOBT or FIT every year plus sigmoidoscopy every 5 years
Double-contrast barium enema every 5 years
Colonoscopy every 10 years

Choosing between Colonoscopy and Sigmoidoscopy. The choice between colonoscopy and sigmoidoscopy for routine screening for older adults with average risk is an area of intense debate. The issues are as follows:

Sigmoidoscopy is less costly, less invasive, quicker, and safer than colonoscopy. Although it allows inspection of only the left side of the colon, any abnormal findings from sigmoidoscopy trigger a full colonoscopy. Therefore, experts estimate that sigmoidoscopy can detect 80% of all significant problems.
Colonoscopy is more sensitive than any other current screening method for detecting colon cancer. It can find 75 - 90% of colorectal cancers. If the goal were to reduce the number of cancer cases, regardless of cost, colonoscopy would be the preferred approach. Colonoscopy, however, is more expensive than sigmoidoscopy and has a slightly higher risk for complications (bowel tears or bleeding when a polyp is removed).

There are 3 basic tests for colon cancer: a stool test (to check for blood), sigmoidoscopy (inspection of the lower colon), and colonoscopy (inspection of the entire colon). All 3 are effective in catching cancers in the early stages, when treatment is most beneficial.

Screening, particularly with colonoscopy, in increased- and high-risk populations can save lives. The most important risk factors are a family history of colorectal cancer and personal history of colorectal cancer, polyps, or chronic inflammatory bowel disease. People with these risk factors should be screened before age 50 and may need more frequent screenings.

Guidelines for Increased-Risk Groups. Anyone with first-degree relatives diagnosed with colon cancer younger than 60, or with two relatives who have been diagnosed with colon cancer at any age, should consider beginning the standard screening regimen with a colonoscopy every 5 years, beginning at age 40 or 10 years before the youngest case in the family (whichever is earlier).

Men of African descent are also considered to be at increased risk for colon cancer and should discuss similar screening guidelines with their doctors.

Guidelines for High-Risk Groups. The following guidelines may be useful for specific high-risk groups.

People who have the mutated hereditary nonpolyposis colorectal cancer gene (MSH2 or MLH-). Frequent colonoscopy (for instance, every 1 - 2 years) beginning in their early 20s. (Regular screening for other cancers, such as uterine cancer, is also reasonable.)
People who have the mutated familial adenomatous polyposis (FAP) gene. Frequent screening with endoscopy (flexible sigmoidoscopy or colonoscopy) beginning in early puberty. Genetic testing is now recommended for family members of people with known FAP.
People with predisposing intestinal problems, such as widespread and active ulcerative colitis or Crohn's disease. Annual screening with colonoscopy with biopsies of suspicious areas.

Guidelines for Follow-Up After Detection of Precancerous Polyps. Patients who have had a previous examination in which polyps were detected (and removed) should have a repeat colonoscopy 1 - 3 years later, depending on the size, number, and type of polyps removed.

The digital rectal examination is used to detect tumors in the rectum, lower intestine, and prostate gland. The doctor inserts a lubricated-gloved finger into the patient's rectum and feels for lumps or other abnormalities. The exam is quick and painless but embarrassing for some. Fewer than 10% of colon cancers develop within the region that can be evaluated by a DRE, so it is not useful as a sole screening test.

Blood in bowel movements is not always visible, in which case it is called occult (hidden) blood. Fecal occult blood tests (FOBTs) are used to detect this hidden blood. The most common FOBT method is called the guaiac-based test. The patient is asked to supply up to six stool specimens in a specially prepared package. A small quantity of feces is smeared on specially treated paper, which reacts to hydrogen peroxide. If blood is present, the paper turns blue.

Accuracy. FOBTs can miss more than 75% of advanced cancers. Nevertheless, large studies have indicated that this simple test, performed annually, saves lives and may reduce the risk of dying from colon cancer by 15 - 33%. The following factors may affect its accuracy:

The levels of iron in the blood can affect results. Patients should not take iron supplements or eat red meats several days before the test.
Certain raw fruits and vegetables that contain the chemical peroxidase (cauliflower, horseradish, radishes, melons, and turnips) can cause a positive test reaction even if no blood is present.
Aspirin and NSAIDs are anticoagulants that can cause minor bleeding. They should not be taken for a week before the test. However, a 2005 study suggested that the prescription anticoagulant warfarin does not affect FOBT results.
Vitamin C and foods rich in this vitamin may cause a false negative reaction and should be avoided a few days before the test.
Bleeding from other causes, such as menstruation, hemorrhoids, gingivitis, or urinary infections, can produce blood in the stools and affect results.

Even if none of these conditions is present, a test that shows hidden blood does not necessarily mean that cancer is present. About 20 - 30% of people with occult blood have noncancerous polyps or other conditions, such as gastritis, and only 5 - 10% actually have cancer. Any abnormal result, however, requires further testing, such as colonoscopy.

Lack of Compliance. Compliance is a major problem. Patients are asked to perform the tests at home and send the test cards to the laboratory. Only 35 - 50% of patients actually follow through. Occult-blood tests that give results at home are available but are extremely inaccurate. In one large study, these tests failed to detect advanced cancer in about 62% of cases, although they may detect some early cancers.

If a digital rectal exam (DRE) or fecal occult blood test (FOBT) shows signs of trouble, several methods to visualize the colon are available. They include colonoscopy, sigmoidoscopy, and double-contrast barium enema. They have the following similarities and differences:

Sigmoidoscopy can only view the rectum and the left side of the colon, while colonoscopy and barium enemas allow a view of the entire large intestine.
Both flexible sigmoidoscopy and colonoscopy involve snaking a fiber optic tube through regions of the rectum and colon to view the walls of the intestine. The tube contains a tiny camera that transmits the image to a video screen. The use of an ultrasound (sound wave) scanner is proving to enhance viewing quality. Barium enemas simply use x-rays.
During either sigmoidoscopy or colonoscopy, the doctor is able to remove polyps or other abnormalities revealed by these procedures with surgical instruments inserted through the tube. It is not possible to remove polyps with a barium enema, which is not invasive.

Sigmoidoscopy. Sigmoidoscopy examines the rectum and the lower two feet of the colon. It cannot, however, detect the roughly half of cancers that occur in the right colon. Right-sided cancers are more common in older people.

The procedure uses a flexible fiber optic tube (it is thus referred to as flexible sigmoidoscopy) that contains a tiny camera and surgical instruments.
It lasts about 10 minutes and may be mildly uncomfortable, but it is not painful and is generally very safe. In one study, 70% of patients reported that the procedure was far less unpleasant than they had expected.

This procedure has been found to reduce the risk of fatal cancers in the rectal and sigmoid area by 60%. If polyps are detected, a colonoscopy is then used.

Colonoscopy. Colonoscopy is the most accurate testing method and can reduce cancer incidence by up to 90%. It is clearly indicated for anyone with an increased risk for colorectal cancer, including those with a personal or family history of the disease. As with sigmoidoscopy, a colonoscopy uses a flexible tube, but it is snaked through the entire large intestine.

For about a day before the procedure the patient eats nothing and drinks a laxative solution that cleans out the colon. The taste of the solution is unpleasant, although it has improved in recent years.
The procedure typically uses a sedative that produces a "twilight" sleep and often makes the procedure more comfortable than sigmoidoscopy.
Air may be introduced into the intestine to widen it and allow the tube to navigate curves. A colonoscopy avoids the risk of radiation associated with a barium enema, but it is important to note that even a colonoscopy does not detect all cancers.

Complications are rare, but include the following:

Hyponatremia. Hyponatremia is a low concentration of sodium in the blood. The complication may be caused by the effects of bowel cleaning before the procedure that can result in water retention and reductions in sodium. When severe, it can cause temporary neurological symptoms, such as confusion, lethargy, unsteadiness, and slurred speech. Researchers suggest that sodium concentrations be measured in patients who develop such symptoms after colonoscopy.
Bowel perforation (very low risk, about 2 in 1,000 procedures). The risk for bowel perforation is greater with colonoscopy than flexible sigmoidoscopy.
Bleeding at the site of biopsy or polyp removal.

Overall, colonoscopy is a safe procedure. However, according to a 2006 study in the Annals of Internal Medicine, serious complications occur in about 5 of every 1,000 colonoscopies. Most of these complications occurred when a biopsy or polyp removal was performed. (The risk for complications without biopsy or polyp removal is about 1 in every 1,000 colonoscopies.) This study looked at colonoscopies in general, including those that are done to diagnose the causes of a patient's symptoms. The risk may be lower for colonoscopies performed solely to screen for colorectal cancer.

Barium Enema. The double-contrast barium enema, which uses an x-ray image, is the less expensive alternative for viewing the entire colon. It is not as accurate as colonoscopy, and if any polyps or abnormalities are revealed on x-ray, a colonoscopy is then required to remove suspicious tissue, so it is now recommended much less often than in the past.

The barium enema is a valuable diagnostic tool that helps detect abnormalities in the large intestine (colon). The barium enema, along with colonoscopy, remains the standard in the diagnosis of colon cancer, ulcerative colitis, and other diseases of the colon.

Screening for familial adenomatous polyposis. Genetic screening for familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC) is now available and may be recommended for high-risk patients. The test for FAP detects a mutation in the adenomatous polyposis coli in up to 90% of people who carry it. Testing for HNPCC mutation is somewhat more complex.

Screening for insulin-like growth factor. A gene that regulates insulin-like growth factor (IGF-2) is functional during fetal development and then becomes inactive. Some evidence now suggests that people who have IGF-2 in adulthood have a higher risk for colon cancer. Blood tests for detecting IGF-2, then, may be helpful in identifying patients who should have more intensive screening. Currently, however, this is only used as a research tool.

Stool DNA Testing. A promising technique for colorectal cancer screening is the detection of altered DNA in cancer cells that have shed from the colon and are excreted in the stool. Such tests may prove to detect both inherited and noninherited genetic mutations. This may become a widely used tool in the future. However, larger clinical studies are needed.

Virtual Colonoscopy. A promising experimental technique called virtual colonoscopy allows three-dimensional imaging of the colon without using invasive instruments. As with standard colonoscopy, the patient takes a laxative first to clear out the intestine. The procedure itself involves pumping air into the colon and scanning the intestine using computed tomography (CT). It is very safe and takes about only 10 minutes. The procedure is similar in accuracy to conventional colonoscopy for detection of larger polyps (6 mm or more in diameter) and is also potentially less expensive. Colonoscopy is required, however, if suspicious areas are found, which may occur frequently with the CT procedure, since it erroneously identifies a high number of nonexistent polyps.

A study published in April 2004 in the Journal of the American Medical Association compared results of standard colonoscopy versus virtual colonoscopy in over 600 patients at nine major medical centers. Virtual colonoscopy had much lower rates of successfully finding polyps than standard colonoscopy. Virtual colonoscopy detected polyps of at least 6 mm in 39% of patients and polyps of at least 10 mm in 55% of patients. By contrast, standard colonoscopy detected 99% of polyps of at least 6 mm, and 100% of polyps of at least 10 mm. In addition, accuracy rates varied widely among the different hospitals. The authors advised that until more improvement in training and technique is achieved, virtual colonoscopy "is not yet ready for widespread clinical application."

Magnetic Resonance Colonography. Magnetic resonance colonography (MRC) is another non-invasive technique for visualizing the colon. The patient receives an enema containing a contrast substance, and then magnetic resonance images are taken. MRC is fast, comfortable, and less invasive than colonoscopy. Currently, however, there is a poor detection rate for flat tumors and for polyp tumors less than 10 mm in diameter.

Staging

A diagnosis of cancer will lead to staging and other tests to help determine the outlook and the appropriate treatments.

The large intestine is a long hollow organ lined with mucous membrane (mucosa). Muscle layers wrap around the entire length and help move food material through to the rectum.

Unlike many other cancers, the size of the tumor is not a major factor in determining the outcome of colorectal cancer. Of greater importance is how far the cancer has spread. To determine this, doctors will assign a stage to the tumor. There are several methods for staging. The older system, known as Dukes', categorizes four basic stages: A, B, C, and D. A more recent system refers to these stages as I, II, III, and IV but divides the categories slightly differently. The term "5-year survival" means that patients have lived at least 5 years since diagnosis. Most patients who live 5 years without a recurrence are considered to be cured of their disease.


Stage	Condition	5-Year Survival
A or I	Tumor superficially involves the inner lining of the intestine.	More than 90%
B or II	Tumor has penetrated through the muscle wall of the intestine but has not reached the lymph nodes.	70 - 85%
C or III	Lymph nodes are involved.	65% or below
D or IV	Tumor has spread to other organs (metastasized), usually the liver first.	5 - 9%

Click the icon to see an image of the stages of cancer.

Researchers are continually seeking to identify tumor markers, substances (usually found in blood samples) that will assist in the diagnosis of cancer and in monitoring effects of treatment.

Carcinoembryonic Antigen. High blood levels of a protein called carcinoembryonic antigen (CEA) sometimes indicate the presence of colon cancer. Unfortunately, it is also elevated in other cancers and in some noncancerous conditions. CEA is not effective as a screening tool for healthy people, but might eventually be helpful for patients with cancer.

An advanced diagnostic technique called polymerase chain reaction (PCR) can detect genetic evidence of CEA. One study indicated that when these microscopic footprints of colon cancer are detected in the lymph nodes of patients with Stage II cancer (whose lymph nodes otherwise appear to be not involved with cancer), the outlook is similar to that of patients with Stage III cancer. Patients without this so-called micrometastasis have a very favorable prognosis. Further research is needed, however, before PCR can be used in widespread practice.
In patients with a history of, or active, colon cancer, follow-up measuring of blood CEA levels may be helpful in detecting recurrence of the cancer and effectiveness of treatments.

Defective P53 Gene. The presence of a defective p53 gene is a marker for very poor prognosis in patients with advanced colon cancer. In its normal state, the gene is important for regulation of cell growth. Testing for this abnormality, however, is not widely done because it is not clear how to use this information.

Other Tumor Markers. Other tumor markers under investigation include a protein called GLUT1, cancer antigen 19-9 (CA 19-9), matrix metalloproteinase-9 (MMP-9) RNA, HER-2/neu oncoprotein, transforming growth factor beta-1 (TGF-beta-1), and CD44.

Click the icon to see an image of drawing blood for culture.

A technique known as a sentinel node biopsy is increasingly performed by experienced surgeons in selected patients. This procedure is used to determine if cancer has spread beyond the nodes, possibly reducing the need for complete axillary lymphadenectomies. It involves the following:

The procedure uses an injection of a tiny amount of a tracer, either a radioactively-labeled substance (radioisotope) or a blue dye, into the tumor site.
The tracer or dye then flows via the lymphatic system into the so-called sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If they do not show any signs of cancer, it is highly likely that the remainder of the lymph nodes will be cancer free, and further surgery becomes unnecessary.

It is still not known if the sentinel node biopsy has any survival advantages compared to the standard procedures with lymph nodes removal. However, one study indicated that careful and complete removal of potentially cancerous lymph nodes is still very important for improving survival in patients with Stage II and III colorectal cancer.

Whole-body imaging scans that combine positron emission tomography (PET) and computed tomography (CT) may be helpful in accurately staging colorectal cancer, according to preliminary research published in 2006 in the Journal of the American Medical Association.

Prognosis

Survival rates for colorectal cancer have been rising in recent years. The 5-year survival rate is as high as 90% for cancer that has not spread to the lymph nodes (localized cancer). When cancer has spread to lymph nodes and other parts of the body, survival rates drop to 65% and below. Because many cancers are detected at later stages, the overall survival rate is currently about 60%. African-Americans and other minorities tend to have lower survival rates than Caucasians. Studies suggest, however, these higher mortality rates are largely due to less access to optimal health care, including appropriate surgical care and aggressive treatments.

In most cases, age is not a factor in treatment success. Good survival rates are achieved in the elderly as well as in young people. Chances for survival are less in Stage II cancers if the intestine is obstructed or perforated. If cancer has spread to lymph nodes (Stage III), the outlook is better if three or fewer lymph nodes are involved. Treatment can prolong life even when cancer has spread.

Surgery

Surgical removal of the tumor ("resection") along with any affected surrounding tissue is the standard initial treatment for potentially curable colorectal cancers (cancers that have not spread beyond the colon or lymph nodes). Drug and radiation therapy are often used for advanced cancers and are continuously being tested with surgery in different combinations and sequences.

Although choosing a qualified surgeon is critical, choosing a hospital experienced in procedures is also important. The more often colon cancer surgery is performed at a given hospital, the lower the mortality rate at that hospital is likely to be.

Unless cancer is very advanced, most tumors are removed by an operation known as colectomy:

Colectomy involves removing the cancerous part of the colon and nearby lymph nodes.
The surgeon then reconnects the intestine.
If the surgeon cannot reconnect the intestine, usually because of infection or obstruction, the surgeon will perform a colostomy. The need for colostomies is higher after surgery for rectal cancer. In most cases of colon cancer, colostomies are not needed. [See "Colostomy" below.]

Click the icon to see an illustrated series detailing colon cancer treatment.

The Surgical Approach. The standard technique for a colectomy is open, invasive surgery. Laparoscopy, sometimes called “keyhole surgery,” is a less invasive method. Laparoscopy is still considered an investigational technique for treating colon cancer, but it is gaining more acceptance and showing good results in clinical trials.

Open Surgery:

Open surgery uses a wide incision to open the patient's abdomen. The surgeon then performs the procedures with standard surgical instruments. This is the usual method for performing colectomy.

Laparoscopy:

Laparoscopy uses a few small incisions through which the surgeon passes a fiber optic tube (laparoscope) containing a small camera or tiny instruments. It is generally used for early colon cancer (for tumors less than 2 centimeters or for well-defined tumors less than 3 centimeters).
A 2004 New England Journal of Medicine study found that patients who received laparoscopic colectomy had similar rates of surgical complications, cancer recurrence, and survival as those who received traditional open surgery. However, the patients who had laparoscopy recovered faster and did not need as many narcotic painkillers.
Several 2005 studies indicated that laparoscopy works as well as conventional surgery for treatment of colon cancer. However, laparoscopy does not appear to be as effective for rectal cancer.

Click the icon to see an image detailing pelvic laparoscopy.

Click the icon to see an illustrated series detailing a resection of the large intestine.

Other Investigational Measures. Researchers are testing expandable metal tube-like devices called stents to keep the intestine open. Stents may be used before a procedure to allow bowel cleansing or for long-term use to keep open colons that can't be operated on.

A colostomy is performed in order to bypass or remove the lower colon and rectum. The procedure generally involves creating a passage, called a stoma, through the abdominal wall that is connected to the colon. The feces pass through this passage and are eliminated. Patients must learn how to care for the stoma and keep the area sanitary.

A colostomy usually will have one opening (single-barreled), or there may be two loops opening through the skin (double-barreled).

Usually the colostomy is temporary and can be reversed by a second operation after about 3 - 6 months. It the rectum and sphincter muscles in the rectum need to be removed, the colostomy is permanent. Permanent colostomies are more common when the cancerous regions are within 2 - 3 centimeters of the anus. Fortunately, surgical advances and knowledge of the extent of safe margins are reducing the need for permanent colostomies.

Click the icon to see an illustrated series detailing a colostomy procedure.

Managing Permanent Colostomies. In cases where the colostomy is permanent, the patient must wear a colostomy pouch, which sticks to the skin using a special glue. Pouches are available as one- or two-piece systems. The one-piece system is simpler, but the two piece system allows replacement of the pouch without removing the tape.

For best results, the pouch should be emptied when about one-third full. It should be replaced 1 - 2 times a week, depending on signs of leakage (itching or burning of the skin near the stoma). The pouches are odor proof.

Surgical treatments for cancer in the rectum are complex since they involve muscles and tissue that are critical for urinary and sexual function.

Local Excision or Polypectomy for Early Stages. In order to preserve the function of the anal sphincter and prevent the need for colostomy, Stage I and Stage II tumors may be removed by local excision, sometimes followed by chemotherapy and radiation. In this procedure, the tumor is cut out without removal of a major section of rectum. In some cases cancer recurs, but a second operation may be possible. Another treatment for early-stage rectal cancer, called electrocoagulation, destroys tumors using a high frequency electric current. It is being tested in clinical trials.

Radical Resection. In about a third of cases of rectal cancer, the cancer occurs in the lower part of the rectum, where between 70 - 80% of cancers have spread beyond the rectal wall. These patients need a radical resection, in which surrounding structures, including the sphincter muscles that control bowel movements, must often be removed.

The use of chemotherapy and radiation prior to surgery may prevent the need for permanent colostomy in some patients. This is an active area of clinical research, and trials are under way to address this issue. Another technique, called coloanal anastomosis, reconstructs the area to avoid the need for colostomy, and may be appropriate in some patients.

Total Mesorectal Excision. Total mesorectal excision (TME) involves dissection and removal of the entire cancerous area of the rectum along with surrounding fatty regions where the lymph nodes are located (the mesorectum). When successful, TME preserves the sphincter muscle, reducing the need for a permanent colostomy. Increasing use of this procedure is resulting in lower recurrence rates, lower levels of impotence and incontinence, and better overall survival rates compared to other resection techniques. Some experts now recommend it as a first choice for certain patients with locally advanced rectal cancer.

Combining chemotherapy and radiation either before or after TME is yielding promising long-term results and a low risk for local recurrence. There are many questions, however, and it is not clear which approach is better for specific patients.

Side effects of colon surgery include:

Sexual dysfunction. This is of particular concern. In general, colostomy does not usually affect sexual function. However, wide rectal surgery can cause short- or long-term sexual dysfunction. Sildenafil (Viagra) may help men who experience this after surgery.
Irregular bowel movements.
Gas and flatulence. Pouching filters are available to reduce gas. Certain foods produce more gas than others -- usually within 6 - 8 hours after ingestion for colostomy patients. They include beans, oat bran, most fruit, and certain vegetables (cabbage, cauliflower, Brussels sprouts, broccoli, and asparagus). To prevent swallowing air, patients should avoid sipping through straws, chewing gum, and chewing with their mouths open.
Diarrhea.
Bladder complications.
Sense of urinary urgency.
Fecal incontinence. Patients with rectal surgery have a higher risk for bowel dysfunction than those who had a colostomy.
Complications in or around the stoma. These can occur early after surgery to many years after the procedure. They include skin infection or breakdown, hernias, narrowing of the stoma, bleeding, and collapse.

There are no dietary restrictions, although many patients avoid foods that can produce gas. Everyone should drink plenty of fluids and get sufficient fiber.

The potential side effects of sexual and bowel dysfunction for colorectal surgical patients can be devastating, although many patients do very well and live normal productive lives. Positive emotions play a strong role in recovery. Patients who are depressed should discuss with a doctor all aspects of treatment that affect the quality of life, and consider seeking support groups.

Medications

Chemotherapy uses drugs that kill cancer cells throughout the body. There are two situations in which chemotherapy is used:

The adjuvant setting. Adjuvant refers to the use of chemotherapy after surgery in patients with Stage III tumors and selected patients with high-risk Stage II tumors (disease that is potentially curable). The goal of this therapy is to eliminate any cancer cells that surgery may have missed, thereby preventing recurrence and increasing the chance of cure. Patients of all ages, including the elderly, can benefit.
In metastatic disease. In patients with metastatic disease (where the cancer has spread to other parts of the body) the goal of chemotherapy is to shrink tumors, improve symptoms and quality of life, and lengthen life.

In the adjuvant setting, there are some differences in chemotherapy treatments between colon and rectal cancers:

Chemotherapy for Stage II is considered standard care for Stage II rectal cancer but is under debate for colon cancer.
Chemotherapy is standard for patients with Stage III colon cancer. Chemotherapy is also standard for patients with Stage III rectal cancer but is used in combination with radiation.

Chemotherapy for Stage II Colon Cancer. Adjuvant chemotherapy for Stage II colon cancer is controversial. Such patients tend to have a good outcome after surgery, and the positive effects of chemotherapy have been difficult to demonstrate. To date, the survival advantage of adjuvant chemotherapy in this group has been reported to be only in the range of 2%. However, better trials are still needed to confirm or refute the benefits in specific patient groups.

Although not yet known with certainty, some data suggest that certain patients with Stage II cancer may be at higher risk of recurrence and would theoretically benefit from adjuvant therapy. These include patients with cancers that have:

Obstructed the bowel
Perforated the wall of the colon
Adhered to structures outside the intestine

Advanced diagnostic techniques are under investigation for helping to select appropriate candidates for adjuvant therapy. None of these methods, however, are ready to be used routinely to help make treatment decisions. The decision whether to pursue chemotherapy for Stage II disease should be made after careful discussion between the patient and their oncologist, especially after features, such as bowel perforation or obstruction, are taken into account.

Chemotherapy for Stage III Colon Cancer. Since the early 1990s, adjuvant chemotherapy with 5-FU and leucovorin has been the standard of care for Stage III colon cancer. In recent years, the FOLFOX (5-FU, leucovorin, oxaliplatin) regimen has also been used for chemotherapy following surgery. Numerous trials have shown that adjuvant chemotherapy in this setting reduces the absolute risk of death from colon cancer by about one-third and improves survival by 10%. Clinical trials are also investigating combinations of other drugs.

Chemotherapy for Advanced Colorectal Cancer. Chemotherapy is either given directly into the arteries of the liver or intravenously (through a vein) with 5-FU and leucovorin. Oxaliplatin is sometimes added, but recent evidence suggests that the targeted therapy biologic drug bevacizumab may be a better addition. Other alternative chemotherapy choices are capecitabine, or irinotecan combined with cetuximab. Radiation therapy may be used in place of chemotherapy or in combination with it. Studies indicate that chemotherapy offers only a modest improvement in survival, but may help reduce symptoms.

Seven drugs are currently approved for colorectal cancer chemotherapy:

5-fluorouracil (5-FU, Adrucil), which is often given in combination with leucovorin (Wellcovorin). Leucovorin is a vitamin that helps boost the effectiveness of 5-FU.
Capecitabine (Xeloda)
Oxaliplatin (Eloxatin)
Irinotecan (Camptosar)
Bevacizumab (Avastin)
Cetuximab (Erbitux)
Panitumumab (Vectibix)

Capecitabine is a pill form of 5-FU. The other drugs are administered intravenously. Many of these drugs are given in combination with each other. Common chemotherapy combination regimens include:

5-FU / LV (5-FU and leucovorin)
FOLFOX (5-FU with leucovorin and oxaliplatin)
FOLFORI (5-FU with leucovorin and irinotecan)
IFL (Irinotecan, 5-FU, leucovorin)
XELOX (Capecitabine and oxaliplatin)

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Because cancer cells grow and divide rapidly, anticancer drugs work by killing fast-growing cells. This means that healthy cells that multiply quickly can also be affected. The fast-growing normal cells most likely to be affected are blood cells forming in the bone marrow, and cells in the digestive tract, reproductive system, and hair follicles. Nausea and vomiting is a very common side effect, but drugs such as ondansetron (Zofran) can help provide relief. In general, side effects are nearly always temporary, and medications can help manage them. Most patients are able to continue with normal activities for all but perhaps 1 - 2 days a month.

5-Fluorouracil (5-FU) with Leucovorin. Adjuvant therapy using 5-fluorouracil, either alone or with leucovorin (5-FU/LV), is the standard treatment for patients with high-risk colon cancer (Stage III or select patients with Stage II tumors). Leucovorin, also called folinic acid, is a form of the B vitamin folic acid, which helps increase 5-FU’s effectiveness. Patients are given a series of cycles that usually continue for at least 6 months.

There are many different ways of giving 5-FU, including intravenously over several hours once a week, intravenously daily for 5 consecutive days every month, or as continuous infusion with a portable pump.

The side effects can be quite different, depending on the way 5-FU is given, and women may be more susceptible than men. In one analysis, 53% of women and 40% of men experienced severe side effects, while response rates and survival were similar for both sexes. Many patients, however, tolerate 5-FU with leucovorin well, with manageable side effects. The most common side effects include nausea and vomiting, diarrhea, loss of appetite, hair loss, swelling of hands and feet, rashes, and mouth sores.

Irinotecan. Irinotecan (Camptosar) blocks an enzyme essential for cell division. Irinotecan can be given alone or in combination with 5-FU and leucovorin. This combination therapy (irinotecan plus 5-FU/LV) is also referred to as the "Salz regimen," or IFL. When it was approved in the mid 1990s, irinotecan was the first new drug developed for colon cancer in over 30 years. Studies have shown that irinotecan combined with 5-fluorouracil and leucovorin (5-FU/LV) significantly delays the time at which tumors progress and improves survival in metastatic cancer compared to 5-FU/LV alone. While the survival advantage is small, the combination has become the standard of care for metastatic cancer. Of concern, however, are studies that have reported an increased risk of death from toxic effects with the use of the three-drug combination. These deaths appeared to be related to blood-clotting complications. Doctors should carefully monitor dosages. Diarrhea is a common side effect of irinotecan.

Capecitabine. Capecitabine (Xeloda), an oral form of 5-FU, was approved in 2001 as a treatment for metastatic colorectal cancer. It is the only pill approved for colorectal cancer. A major 2005 study, published in the New England Journal of Medicine, found that capecitabine works as well as the standard 5-FU/LV regimen and causes significantly fewer side effects. The study involved patients with Stage III colon cancer who had undergone surgical removal of the tumor. In 2005, capecitabine was approved for postsurgical treatment of patients with Dukes’ C colon cancer. Capecitabine is also showing promise in combination with radiation therapy for rectal cancers.

Oxaliplatin. Oxaliplatin (Eloxatin) is related to cisplatin, a widely used platinum-based chemotherapy drug. Oxaliplatin is used in combination with 5-FU and leucovorin. (This triple combination therapy is called the FOLFOX regimen.) Oxaliplatin was first approved in 2002 for use in combination with 5-FU and leucovorin as a second-line treatment for cancer that has progressed after initial therapy.

Since 2002, oxaliplatin has received additional approvals as a first-line treatment for advanced colorectal cancer, and as a post-surgical treatment for patients who have undergone tumor resection.

Oxaliplatin can cause pain and tingling sensations in the hands and feet (neuropathy) that is worsened by exposure to cold. Recent research suggests that adding xaliproden (Xaprila) to the FOLFOX regimen may help reduce the frequency of neuropathy without interfering with the benefits of chemotherapy. Xaliproden is a drug used to treat the neurological disease amyotrophic lateral sclerosis (also known as Lou Gehrig's disease).

Bevacizumab. Bevacizumab (Avastin) was approved in February 2004 as a first-line treatment for patients with metastatic colorectal cancer (advanced cancer that has spread in the body). It is used in combination with IFL (irinotecan, 5-FU, leucovorin). Bevacizumab is a genetically engineered monoclonal antibody that targets and inhibits vascular endothelial growth factor (VEGF), a protein that regulates angiogenesis (the development of new blood vessels that feed a tumor's blood supply). It is the first anti-angiogenic therapy approved for the treatment of colorectal cancer.

In a study of 800 patients with metastatic colorectal cancer, bevacizumab administered intravenously along with IFL extended survival by about 5 months longer than IFL alone. Common side effects of bevacizumab include nosebleeds, fatigue, diarrhea, and high blood pressure. Less common side effects include stroke, heart attacks, angina, and formation of holes in the colon and stomach (gastrointestinal perforation).

Cetuximab. Cetuximab (Erbitux) was approved in February 2004 for the treatment of metastatic colorectal cancer. This monoclonal antibody drug targets epidermal growth factor receptor (EGFR), a protein required by cancer cells in order to proliferate. It can be used either in combination with irinotecan or alone for patients who have not responded to irinotecan. Studies of the cetuximab-irinotecan combination suggest it can help in tumor shrinkage. It has a modest effect on survival, prolonging patients’ lives by about an additional month.

Panitumumab. Panitumumab (Vectibix) was approved in September 2006 for treatment of colorectal cancer that has metastasized following standard chemotherapy. Like cetuximab, panitumumab is a monoclonal antibody drug that targets EGFR. In clinical trials, panitumumab helped delay disease progression and prolong survival by about 3 months. About 8% of patients experienced tumor shrinkage. Common side effects of this drug include skin rash, fatigue, abdominal pain, nausea, and diarrhea or constipation. Serious side effects include pulmonary fibrosis, severe skin rash, and skin reactions at the infusion site.

One of the most promising recent developments in cancer treatment research has been the emergence of so-called "targeted therapies." Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells their generalized toxicity can cause severe side effects. Targeted therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division. Because they selectively target cancerous cells, they may induce less severe side effects. In addition, these drugs hold the promise of creating options for more individualized cancer treatment based on a patient's genotype. In the future, diagnostic tests may help doctors identify which patients are more likely to respond successfully to specific drugs.

Biologic therapies use the body's immune system to attack the cancer (immunotherapy). These drugs are derived from biological sources and include vaccines, monoclonal antibodies (MAbs), and gene therapies. Many targeted therapies are classified as biologics. Bevacizumab (Avastin), cetixumab (Erbitux), and panitumumab (Vectibix) are currently the three biologic drugs approved for colorectal cancer treatment, but many other drugs are in development.

Targeted therapies involve many different types of drugs and molecular pathways. These include:

Angiogenesis Inhibitors. Anti-angiogenesis drugs inhibit the formation of new blood vessels that supply tumors with the blood, oxygen, and nutrients vital to tumor growth. Angiogenesis inhibitors, such as the monoclonal antibody bevacizumab (Avastin), target vascular endothelial growth factor (VEGF). Cediranib (Recentin), formerly AZD2171, is a new angiogenesis inhibitor that is in Phase III clinical trials for treatment of colorectal cancer.

Tumor Growth Factor Inhibitors. Tumor growth factors, such as epidermal growth factor, stimulate cell growth. Cetixumab (Erbitux) and panitumumab (Vectibix) are the two currently approved colorectal cancer drugs that target the epidermal growth factor receptor (EGFR). Nimotuzumab (TheraCIM) is currently being studied in combination with irinotecan in Phase III trials.

Tyrosine Kinase Inhibitors. Tyrosine kinase is an enzyme associated with EGFR that is involved with the signaling mechanisms that prompt cell growth. The EGFR/tyrosine kinase inhibitor erlotinib (Tarceva), which is approved for the treatment of pancreatic and lung cancers, is being investigated as an adjuvant treatment for metastatic colorectal cancer. Sunitinib (Sutent), which is approved for renal cell carcinoma, is another tyrosine kinase inhibitor in Phase III trials for colorectal cancer.

Radiation Treatment

Radiation therapy uses x-rays to kill cancer cells that might remain after an operation or to shrink large tumors before an operation so that they can be removed surgically. The object of radiation therapy is to damage the tumor as much as possible without harming surrounding tissues. Radiation may be administered in the following ways:

Externally by an x-ray machine (external beam radiation).
By passing radioactive pellets through thin plastic tubes inserted into the intestine.
By implanting tiny radiation seeds directly into the tumor (brachytherapy).
Computer imaging techniques providing 3-dimensional pictures of the cancerous area are allowing precise targeting of radiation to the tumor.

Postoperative radiation treatment combined with chemotherapy is common practice for patients with rectal cancer in Stages II and III. Such patients are at risk of recurrence both at the site of their original tumor and elsewhere in the body. Although there can be significant long-term side effects, the combination of 5-FU and radiation is still considered standard after surgery.

The standard procedure in the U.S. is to apply radiation after surgery (postoperative). Pre-operative chemotherapy and radiation, however, are sometimes used to preserve sphincter-muscle function and reduce the chance that a patient will need a colostomy. Furthermore, some studies suggest that the use of radiation before surgery reduces the likelihood of recurrences and may slightly prolong survival in some patients with rectal cancer. (It has no additional advantages, however, if the subsequent surgery does not completely remove the cancerous regions.) Studies comparing preoperative and postoperative chemotherapy and radiation are currently under way.

Radiation therapy can also be used during surgery (a procedure called intra-operative radiotherapy). It allows the surgeon to move healthy tissue out of the path of the radiation beam.

Short-term side effects of radiation include:

Diarrhea
Skin irritation around the anus
Incontinence
Fatigue
Bowel movement problems

Longer-term complications may include:

Incontinence
Hip and pelvic fractures
Diarrhea
Increased risk for bowel obstruction

Follow-up Testing

The American Society of Clinical Oncology (ASCO) sets guidelines for follow-up testing to detect recurring cancer after the completion of treatment. The following guidelines are based on ASCO’s 2005 updated recommendations.

Most colorectal cancer recurrences happen within 3 years after surgery. American Society of Clinical Oncology recommends that a colorectal cancer patient sees their doctor for a physical examination every 3 - 6 months for the first 3 years, every 6 months for the fourth and fifth years, and at the doctor's and patient's discretion during subsequent years.

Patients should have a colonoscopy 3 years after surgery. If the results are normal, patients should then receive a colonoscopy every 5 years. Some patients with hereditary types of colorectal cancer may need more frequent screenings.

A flexible sigmoidoscopy is recommended every 6 months for 5 years for patients with Stage II or III rectal cancer who did not receive radiation therapy.

Carcinoembryonic antigen (CEA) levels should be measured every 3 months after surgery for 3 years in patients with Stage II or III cancer. High CEA levels in the blood may indicate that the cancer has spread to other parts of the body.

Patients at high risk for cancer recurrence should receive an annual computerized tomography (CT) scan for the first 3 years after treatment. The CT scan can help determine if cancer has spread to the lungs or liver. Patients who have had rectal cancer, and did not have radiation therapy, should receive a pelvic CT scan. The scan is not recommended for most lower-risk patients with Stage I or II colorectal cancer.

American Society of Clinical Oncology does not recommend other follow-up blood tests such as complete blood count, liver function tests, fecal occult blood tests. There appears to be no additional benefit for these tests.

Treatment for Metastasized Colorectal Cancer

The liver is the most frequent site for colorectal cancers to spread (metastasized). Here, treatments may slow the spread of cancer and even prolong survival. Cure is very rare.

When cancer has spread, surgery to remove or bypass obstructions in the intestine may be performed. In these circumstances, surgery is considered palliative in that it may improve symptoms but will not lead to cure. In rare cases, metastatic colon cancer may be cured with surgical removal of tumors in areas to which the cancer has spread, such as the liver, ovaries, and lung. The liver is the most common site of spread. Only selected patients may be eligible for such surgery, but in these patients, 5-year survival has been 25% or higher.

Chemotherapy may help improve symptoms and possibly prolong survival in metastasized colorectal cancers. Several investigational drugs are being tested. Doctors are also testing chemotherapy administered directly into the liver -- a treatment called hepatic arterial infusion (HAI). A 2006 study found that hepatic arterial infusion improves survival and quality of life for patients whose cancer has spread to the liver. The study indicated that HAI works better for these patients than chemotherapy delivered intravenously.

Other investigative techniques used to destroy liver tumors include:

Cryosurgery. This approach freezes the tumor or surrounding tissue.
Embolization. Embolization employs a catheter to deliver substances into the liver that block blood vessels and therefore starve the tumor. Chemotherapy is often administered during this procedure.
Radiation.

For end-stage cancer, hospice care is a compassionate option.

Resources

www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.oncolink.org -- OncoLink cancer information
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.nccn.org -- National Comprehensive Cancer Network
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med. 2007 May 24;356(21):2131-42.

Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6;297(21):2351-9.

Flossmann E, Rothwell PM; British Doctors Aspirin Trial and the UK-TIA AspirinTrial. Effect of aspirin on long-term risk of colorectal cancer: consistent evidencefrom randomised and observational studies. Lancet. 2007 May 12;369(9573):1603-13.

Kerr DJ, Dunn JA, Langman MJ, Smith JL, Midgley RS, Stanley A, et al. Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med. 2007 Jul 26;357(4):360-9.

Levin TR, Zhao W, Conell C, Seeff LC, Manninen DL, Shapiro JA, Schulman J. Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med. 2006 Dec 19;145(12):880-6.

Meyerhardt JA, Niedzwiecki D, Hollis D, Saltz LB, Hu FB, Mayer RJ, et al. Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA. 2007 Aug 15;298(7):754-64.

U.S. Preventive Services Task Force. Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2007 Mar 6;146(5):361-4.

Veit-Haibach P, Kuehle CA, Beyer T, Stergar H, Kuehl H, Schmidt J, et al. Diagnostic accuracy of colorectal cancer staging with whole-body PET/CT colonography. JAMA. 2006 Dec 6;296(21):2590-600.

Review Date:
9/8/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Diet and disease

admin — Thu, 04 Sep 2008 18:51:41 -0700

Overview

Definition
Information

Illustrations

Osteoporosis

Cholesterol producers

Phytochemicals

Selenium - antioxidant

Diet and disease prevention

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

There are nutritional and dietary elements that have proven relationships to certain diseases or conditions. For additional information on FDA-approved health claims, refer to nutrition labeling.

Information

This article addresses the following:

Calcium and osteoporosis
Fiber and cancer
Fruits, vegetables, and cancer
Fiber and coronary heart disease
Fat and cancer
Saturated fat, cholesterol, and coronary heart disease
Sodium and hypertension
Alcohol
Nitrates and cancer

1. CALCIUM AND OSTEOPOROSIS:

Calcium is one of the most important minerals for human life. The body uses it to form and maintain healthy bones and teeth. Calcium also plays a vital role in nerve conduction, muscle contraction, and blood clotting.

Osteoporosis is a disease in which the calcium content of bones is very low. In this disease, calcium and phosphorus, which are normally present in the bones, become reabsorbed back into the body. This process results in brittle, fragile bones that are easily broken.

Getting enough calcium in the diet throughout childhood and puberty is one key to preventing osteoporosis. A person who does not get enough calcium growing up will not have sturdy bones. An older person who consumes a low-calcium diet is also at great risk for osteoporosis.

The recommended dietary allowances (RDA) for calcium are based on age, gender, and hormonal factors. Many foods, such as some vegetables, contain calcium. However, milk and dairy products are some of the best food sources. Calcium may also be obtained by taking supplements.

2. FIBER AND CANCER:

Dietary fiber is found in plant foods, where it occurs in two forms: soluble and insoluble. Soluble fiber attracts water and turns to gel during digestion. This process slows digestion and the rate of nutrient absorption from the stomach and intestine.

Soluble fiber is found in oat bran, barley, nuts, seeds, dried beans and legumes, lentils, peas, and some fruits and vegetables. Insoluble fiber also adds bulk (fiber) to the stool. It is found in wheat bran, vegetables, and whole grains.

A diet high in fiber is thought to reduce the risk of cancers of the rectum and colon.

3. FRUITS, VEGETABLES, AND CANCER:

Eating more fruits and vegetables helps provide a good supply of fiber, vitamin A, vitamin C, beta carotene and other carotenoids, and valuable substances called phytochemicals. Studies have shown that a diet high in these nutrients and fiber can reduce the risk of developing cancers of the stomach, colon rectum, esophagus, larynx, and lung.

Vitamin C and beta carotene, which forms vitamin A, are antioxidants. As such, they protect body cells from oxidation, a process that can lead to cell damage and may play a role in cancer.

In addition to nutrients that are needed for normal metabolism, plant foods also contain phytochemicals, plant chemicals that may affect human health. There are hundreds of phytochemicals, and their exact role in promoting health is still uncertain. However, a growing body of evidence indicates that phytochemicals may help protect against cancer.

To get these benefits, eat more fruits and vegetables that contain vitamins A and C and beta carotene. These include dark-green leafy vegetables such as spinach, kale, collards, and turnip greens. Citrus fruits, such as oranges, grapefruit, and tangerines are also high in antioxidants. Other red, yellow, and orange fruits and vegetables, or their juices are also healthful choices. Note: Juicing removes the fiber.

4. FIBER AND CORONARY HEART DISEASE:

Some fiber, especially soluble fiber, binds to lipids such as cholesterol. The fiber then carries the lipids out of the body through the stool. This lowers the concentration of lipids in the blood and may reduce the risk of coronary heart disease.

5. FAT AND CANCER:

A diet high in fat has been shown to increase the risk of cancers of the breast, colon, and prostate. A high-fat diet does not necessarily cause cancer. Rather, it may promote the development of cancer in people who are exposed to cancer-causing agents.

A diet high in fat may promote cancer by causing the body to secrete more of certain hormones that create a favorable environment for certain types of cancer. Breast cancer is one of these hormone-influenced cancers. High-fat diets also may change the characteristics of the cells to make them more vulnerable to cancer-causing agents.

To reduce fat in the diet, choose lean cuts of beef, lamb, and pork as well as skinless poultry and fish. Baking, broiling, poaching, and steaming are recommended cooking methods. Choose skim or low-fat milk and dairy products, as well as low-fat salad dressings.

6. SATURATED FAT, CHOLESTEROL, AND CORONARY HEART DISEASE:

Eating too much saturated fat is one of the major risk factors for heart disease. A diet high in saturated fat causes cholesterol, a soft, waxy substance, to build up in the arteries. Eventually, the arteries harden and narrow. The result is an increased pressure in the arteries as well as strain on the heart to maintain adequate blood flow throughout the body.

Because of its high calorie content, too much dietary fat also increases the risk of heart disease in that it increases the likelihood that a person will become obese. Obesity is another risk factor for heart disease.

7. SODIUM AND HYPERTENSION:

Sodium is a mineral that helps the body regulate blood pressure. Sodium is also commonly known as salt. It also plays a role in the proper functioning of cell membranes, muscles, and nerves. Sodium concentration in the body is mainly controlled by the kidneys, adrenal glands, and the pituitary gland in the brain.

The balance between dietary intake and kidney excretion through urine determines the amount of sodium in the body. Only a small amount of sodium is lost through the stool or sweat. The amount of sodium in urine is controlled by the steroid hormone aldosterone. Water and sodium are also related. Retention of more sodium is followed by retention of more fluid, and vice versa.

Sodium-sensitive individuals may experience high blood pressure from too much sodium in the diet. The American Heart Association has developed specific guidelines for sodium intake. Dietary changes may be helpful. Sodium intake may have little effect in persons without high blood pressure, but it may have a profound effect in sodium-sensitive individuals. Blood pressure is often controlled by diuretics that cause sodium excretion in the urine.

8. ALCOHOL:

Alcohol use increases the risk of liver cancer. When combined with smoking, alcohol intake also increases the risk of cancers of the mouth, throat, larynx, and esophagus. In addition, alcohol intake is associated with an increased risk of breast cancer in women.

Alcohol is processed by the liver into energy for the body. Continued and excessive use of alcohol can damage the liver in various ways, including the development of a fatty liver. A fatty liver can lead to cirrhosis of the liver.

Alcohol can damage the lining of the small intestine and stomach, where most nutrients are digested. As a result, alcohol can impair the absorption of essential nutrients. Alcohol also increases the body's need for some nutrients, and interferes with the absorption and storage of other nutrients.

Continued and excessive use of alcohol can result in an increase in blood pressure. Chronic heavy drinking also can cause damage to the heart muscle (cardiomyopathy). In addition, stroke is associated with both chronic heavy drinking and binge drinking.

If you choose to drink alcohol, do so in moderation -- no more than 2 drinks per day for a man, 1 per day for a woman.

9. NITRATES AND CANCER:

Countries in which people eat a lot of salt-cured, smoked, and nitrite-cured foods have a high rate of cancer of the stomach and esophagus. Examples of such foods include bacon, ham, hot dogs, and salt-cured fish.

Eat salted, smoked, or cured foods only on occasion.

RESOURCES:

The American Cancer Society is an excellent source of information on cancer prevention. www.cancer.org
The American Dietetic Association provides sound dietary advice on a wide range of topics. www.eatright.org
The American Heart Association provides dietary guidelines aimed at reducing the risk of heart disease and certain contributors to heart disease, such as high cholesterol, high blood pressure, and obesity. www.americanheart.org
The National Cancer Institute's CancerNet is a government gateway to the latest, most accurate information on cancer prevention. www.cancer.gov
The National Heart, Lung, and Blood Institute provides trustworthy information on preventing heart disease and cardiovascular risk factors. www.www.nhlbi.nih.gov/
The National Osteoporosis Foundation is a good source of information on osteoporosis prevention. www.nof.org

Review Date: 8/8/2007

Reviewed By: Cynthia Dennison Haines, MD, family physician specializing in nutrition, fitness, and preventive health, St. John's Mercy Medical Center, St. Louis, MO, and Assistant Clinical Professor, St. Louis University's School of Medicine, Department of Community and Family Medicine.

A.D.A.M. Copyright

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Source Doc: 1_002096

Cirrhosis

FitSugar — Wed, 08 Oct 2008 17:35:41 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Lifestyle Changes
Abdominal Infections
Encephalopathy
Ascites
Bleeding Episodes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration approved HepaGram B, an injectable immune globulin that can help prevent recurrence of hepatitis B following liver transplantation.

Primary Biliary Cirrhosis

Primary biliary cirrhosis is an autoimmune liver disease that increases the risk for liver cancer. According to a 2007 study, specific risk factors may help predict which patients with primary biliary cirrhosis are at particularly high risk of developing liver cancer. These risk factors include older age, being male, history of blood transfusion, and any signs of portal hypertension (high pressure of the blood in the portal vein, which leads to the liver) or cirrhosis.

Hepatitis C and Cirrhosis

Patients with cirrhosis who are infected with a particular hepatitis C genotype (1b) have a high risk of developing liver cancer, indicates a 2007 study. These patients should receive regular monitoring so that liver cancer can be detected in its earliest stages.
Interferon drug therapy can help reduce -- but not entirely eliminate -- the risk of liver cancer developing in patients with hepatitis C-related cirrhosis.

Hemochromatosis

Hemochromatosis, also called “iron overload,” is an iron disorder that increases the risk for cirrhosis. Hereditary hemochromatosis is one of the most common genetic diseases in the United States, and experts have debated whether all people should get screened for it. In 2006, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines concerning hemochromatosis screening. The USPSTF does not recommend routine screening in the general population. However, people who have family histories of hemochromatosis, or who show signs or symptoms of this disorder, should get tested.

Encephalopathy

Lactulose, a drug that helps remove ammonia from the body, can help improve cognitive function and quality of life for people with hepatic encephalopathy, suggests a 2007 study. Hepatic encephalopathy, a complication of liver disease, affects the brain and nervous system.

Introduction

Cirrhosis is an irreversible result of various disorders that damage liver cells over time. Eventually, damage becomes so extensive that the normal structure of the liver is distorted and its function is impaired.

Cirrhosis is a chronic liver disease that causes damage to liver tissue, scarring of the liver (fibrosis - nodular regeneration), progressive decrease in liver function, excessive fluid in the abdomen (ascites), bleeding disorders (coagulopathy), increased pressure in the blood vessels (portal hypertension), and brain function disorders (hepatic encephalopathy). Excessive alcohol use is the leading cause of cirrhosis.

The disease process often takes the following path:

Scarring. The main damage in cirrhosis is triggered by scarring (fibrosis) that occurs from injuries due to alcohol, viruses, or other assaults. Normal clumps and form nodules around the scarred areas. The scar tissue and regenerated nodules act like small dams and alter the flow of blood and bile in and out of the liver.

Altered Blood and Bile Flow. The changes in blood and bile flow have significant consequences, with both the liver and other organs responding to the altered flow:

The spleen overproduces nitric oxide, a gas that causes blood vessels in the spleen to relax and open.
The small blood vessels and bile ducts in the liver itself, however, narrow (constrict). (Blood vessels in other organs, including the kidney, also narrow.)
Blood flow coming from the intestine into the liver is slowed by the narrow blood vessels. It backs up through the portal vein and seeks other routes.
New, abnormally twisted and swollen veins called varices form in the stomach and lower part of the esophagus in order to compensate for the backup blood.
Bile also builds up in the bloodstream, resulting in high levels of bilirubin, which causes a yellowish cast in the skin called jaundice.
Fluid buildup also occurs in the abdomen (called ascites), and swelling in the arms and legs is common.

Changes in Liver Size. The liver enlarges in the first phases of the disease. In advanced stages, the liver sometimes shrinks, a condition called postnecrotic cirrhosis.

The liver is the largest organ in the body. In the healthy adult, it weighs about 3 pounds. The liver is wedge-shaped, with the top part wider than the bottom. It is located immediately below the diaphragm and occupies the entire upper right quadrant of the abdomen.

Vital Functions. The liver performs over 500 vital functions. Damage to the liver can impair these and many other processes. Among them are the following:

Processing Healthful Nutrients. It processes all of the nutrients the body requires, including proteins, glucose, vitamins, and fats.

Bile Production. The liver produces bile, a green-colored fluid that helps the body absorb fats and fat-soluble vitamins. Bile is formed from bilirubin, a yellow-green pigment produced from the breakdown of hemoglobin, the oxygen-carrying component in red blood cells. Bile contains bile salts, fatty acids, cholesterol, and other substances. Bile travels from the liver to the gallbladder, where it is stored until after a meal. It is then secreted into the intestines where it helps digest fat.

Eliminating Toxins. One of the liver's major functions is to render harmless potentially toxic substances, including alcohol, ammonia, nicotine, drugs, and harmful by-products of digestion.

Recycling Blood. The liver and spleen removes old red blood cells from the blood. The iron contained in them is recycled in the bone marrow to make new red blood cells.

The Liver's Architecture. The vital processes the liver performs rely on well-organized liver architecture.

The Building Blocks. The basic building blocks of the liver are the following structures:

Bile ducts
Blood vessels
Working liver tissue (called the parenchyma)
Supportive (connective) tissue

The Architecture. The liver is a built on a framework of lobes:

The lobes. The liver is divided into two major lobes, a right and a smaller left, that are separated by tough, fibrous connective tissue.
The lobules. The liver's two major lobes contain about 100,000 smaller lobes, called lobules. Each lobule contains microscopic columns of liver cells and blood vessels. Bracing the corners of each lobule column are an artery and a vein that carry blood and a bile duct that drains bile.
The arteries and veins. The arteries bring oxygen-rich blood to nourish the liver cells. The veins supply the liver cells with blood containing the nutrients and toxins that the liver cells process. A central vein runs through each column and collects the processed blood from both sources. These veins join to form the hepatic vein.
The bile ducts. The bile ducts in the column corners collect bile draining from tiny canals around the liver cells. These ducts eventually join to form the large common bile duct that leads from the liver to the gallbladder.

The Liver's Blood Supply. The liver is rich in blood. It holds about a pint, or 13% of the body's supply. It is furnished with blood from two large vessels, the hepatic artery and the portal vein, and is drained of blood by the hepatic vein. (The word "hepatic" derives from the Latin word for liver.)

The hepatic artery. This artery supplies blood from the heart directly to the liver. This blood nourishes the liver.

The portal vein. The portal vein carries to the liver blood that has been circulating through the stomach, spleen, and intestine. The liver processes this blood, extracting nutrients and toxins.

The hepatic vein. This vein carries blood from the liver and connects to the inferior vena cava, a large vein that carries blood back to the heart.

Click the icon to see an image of the liver.

Causes

Several processes can lead to cirrhosis.

Alcoholism particularly endangers the liver. Alcoholic cirrhosis (also sometimes referred to as portal, Laennec's, nutritional, or micronodular cirrhosis) is the primary cause of cirrhosis in the U.S. It is estimated to be responsible for 44% of deaths from cirrhosis in North America. Some experts believe this estimate is low. One Canadian study found alcohol to be the major contributor in 80% of all cirrhosis deaths.

The relationship between alcohol and cirrhosis is generally as follows:

Alcohol is absorbed from the small intestine, and the blood carries it directly into the liver, where it becomes the preferred energy source.
In the liver, alcohol converts to toxic chemicals, such as acetaldehyde (AcH), which trigger the production of powerful immune factors called cytokines. These molecules in large amounts can cause inflammation and tissue injury. They are proving to be major culprits in the destructive process in the liver. AcH is particularly being researched because it plays a role in most actions of alcohol, including damaging effects on the liver that may lead to cirrhosis.
The injured liver eventually is unable to break down fatty acids, compounds that make up fat. Over time, then, fat accumulates, further impairing the liver's ability to absorb oxygen and increasing its susceptibility to injury. During the initial phase, the fat-laden liver becomes greatly enlarged, but it eventually shrinks as cirrhosis develops.

Chronic hepatitis, both hepatitis B and hepatitis C, is the second leading cause of cirrhosis. Chronic hepatitis C is the more dangerous form and accounts for one-third of all cirrhosis cases. About 5 - 20% of patients with chronic hepatitis C, and 5 - 10% of patients with chronic hepatitis B, eventually develop cirrhosis over the course of several decades. The longer a patient has had chronic hepatitis, the greater the risk for eventually developing cirrhosis. A 2005 study indicated that cirrhosis develops in 70% of patients who have had hepatitis C for more than 60 years.

The hepatitis virus can produce inflammation in liver cells, causing injury or destruction. If the condition is severe enough, the cell damage becomes progressive, building a layer of scar tissue over the liver. In advanced cases, as with alcoholic cirrhosis, the liver shrivels in size, a condition called postnecrotic or posthepatic cirrhosis.

Hepatitis C is a virus-caused liver inflammation which may lead to jaundice, fever, and cirrhosis. The people most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs and health care workers or emergency workers who may be exposed to contaminated blood.

Autoimmune liver diseases include autoimmune hepatitis and primary biliary cirrhosis. Like other autoimmune disorders, these conditions most likely develop because a genetically defective immune system attacks the body's own cells and organs. People who have one of these liver diseases also often have other autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, scleroderma, inflammatory bowel disease, glomerulonephritis, and hemolytic anemia.

Autoimmune Hepatitis. Autoimmune chronic hepatitis occurs when an abnormal immune response causes an attack on the liver cells. It accounts for about 20% of all chronic hepatitis cases. Autoimmune chronic hepatitis typically occurs in women age 20 - 40 who have other autoimmune diseases. Some research indicates that the postmenopausal period may be another peak in incidence of AIH among women. About 30% of patients are men, however, and in both genders there is often no relationship to another autoimmune disease. In general, no major risk factors have been discovered for this condition.

Suspects for triggering this hepatitis include the measles virus, a hepatitis virus, or the Epstein-Barr virus, which causes mononucleosis. It is also possible that a reaction to a drug or other toxin that affects the liver also triggers an autoimmune response in some people.

Click the icon to see an image of mononucleosis.

Primary Biliary Cirrhosis. Up to 95% of primary biliary cirrhosis (PBC) cases occur in women, usually around age 50. In people with PBC, the immune system attacks and destroys cells in the liver’s bile ducts. Like many autoimmune disorders, the causes of PBC are unknown. Recent research indicates the following risk factors:

Family history of PBC
Family history of Sjögren syndrome (another autoimmune disorder)
Individual history of urinary tract infections (UTI)
History of smoking
History of nail polish use
Hormone replacement therapy
Exposure to toxins from hazardous waste sites

This research suggests that environmental factors (chemicals, cigarette smoke) or infectious organisms (bacteria that causes UTI) may trigger PBC in patients who are genetically susceptible to the disease. Women who have never been pregnant appear less likely to develop PBC.

Nonalcoholic fatty liver disease (NAFLD) resembles alcoholic liver disease, but it occurs in people who do not drink a lot of alcohol. Obesity and type 2 diabetes are the two main causes of a fatty liver. Some evidence suggests that insulin resistance (the primary problem in type 2 diabetes) is a major factor in development of a fatty liver. A diet high in fatty foods may also be a risk factor, as dietary fat accumulates in the liver. Due to the recent rise in childhood obesity, NAFLD is increasingly occurring in children. In fact, NAFLD is now the most common liver disease in American children.

Nonalcoholic fatty liver disease can lead to nonalcoholic steatohepatitis (NASH). Liver inflammation and injury, as well as a fatty liver, characterize NASH. NASH occurs in about half of people with diabetes and up to 75% of obese people.

Nonalcoholic fatty liver disease is usually benign and very slowly progressive. But, in certain patients it can lead to cirrhosis, liver failure, or liver cancer. About 8 - 20% of people with nonalcoholic steatohepatitis go on to develop cirrhosis. A 2006 study indicated that NASH-related cirrhosis causes fewer deaths than cirrhosis that is caused by chronic hepatitis C. However, many patients with NASH have coronary artery disease and heart failure and have a high risk of dying from heart disease.

Weight reduction and diabetes and cholesterol management are the primary approaches to controlling these diseases.

Hemochromatosis is a disorder of iron metabolism. This disease interferes with the way the body normally gets rid of iron. People with hemochromatosis absorb too much more iron from the food that they eat. The iron overload accumulates in organs in the body. When excess iron deposits accumulate in the liver, they can cause cirrhosis.

There are two main forms of hemochromatosis:

Primary hemochromatosis, also called hereditary hemochromatosis, is an inherited genetic disease.
Secondary hemochromatosis results from other conditions, such as anemia and alcoholism.

Hereditary hemochromatosis is one of the most common genetic diseases, especially among Caucasians. About 1 in every 200 Americans carries the gene that causes this disease. Although experts do not recommend that everyone get screened for hemochromatosis, people who have a family history of this disease, or who show symptoms (joint pain, fatigue, abdominal pain), should get tested. Left untreated, hemochromatosis can lead to serious damage of the liver, heart, and pancreas.

Hemochromatosis is treated with phlebotomy, a procedure that involves removing about a pint of blood once or twice a week. Starting phlebotomy treatment before organ damage occurs can help prevent cirrhosis. If, however, cirrhosis has already developed, patients have a high risk for developing liver cancer even if iron levels are normalized.

Inherited Diseases. Cirrhosis can be caused by several inherited diseases, including:

Cystic fibrosis
Alpha-1 antitrypsin deficiency
Galactosemia
Glycogen storage diseases
Wilson's disease

Other Rare Causes. Rare causes of cirrhosis include:

Schistosomiasis, caused by a parasite found in the Far East, Africa, and South America.
Small intestine bypass surgery (rarely, if ever, performed anymore).
Long-term or high level exposure to certain chemicals and drugs can cause cirrhosis, including arsenic, methotrexate, and toxic doses of vitamin A.

Cancers that have metastasized to the liver, blood clots in the hepatic or portal vein, or obstructions in the bile duct can cause changes that resemble cirrhosis.

Risk Factors

Cirrhosis affects about 3 million Americans a year. However, because about 2.7 - 4 million people harbor hepatitis C, the rates of cirrhosis could dramatically increase over the next few years.

Only 10% of heavy drinkers develop advanced liver disease. Not eating when drinking and consuming a variety of alcoholic beverages are factors that increase the risk for liver damage. Still, the amount of alcohol consumed and the patterns of drinking are only weak predictions of risk. Other risk factors have been identified that may increase the danger to the liver:

Obesity is a major factor for all stages of liver disease.
Women develop liver disease at lower quantities of alcohol intake than men. The reason for this may be due to women's inability to metabolize alcohol as quickly as men, so it stays in the bloodstream longer.
Genetic factors that regulate the immune responses in the intestine also play a role in increasing the risk for liver injury from alcoholism.

Risk Factors for Developing Cirrhosis from Hepatitis C. Overall, between 10 - 15% of patients with chronic hepatitis C develop cirrhosis. The risk varies widely, however. The following conditions put people with hepatitis C at higher risk for liver damage:

Overall the risk for progression is highest in men -- particularly African-Americans -- who were older at the time of infection. The risk is much lower in women and children (2 - 4%).
Moderate-to-heavy alcohol users. (Even one or two alcoholic drinks a day increase the risk for liver injury in hepatitis C patients.)
Having a specific genetic type of the virus. There are six main genetic types and more than 90 subtypes, which can differ significantly in their effects and response to treatment. Genotype 1 is the most serious and is the cause of up to three quarters of the cases in the U.S. The other common forms are types 2 (15%) and 3 (7%), which pose less danger.
Co-infection with hepatitis B. Co-infection with B significantly affects the outcome of these patients and may be more common than previously believed. This co-condition may cause superinfections with very serious consequences, reduce these patients' responses to interferon therapy, and increase their risk of liver cancer. Patients with hepatitis C should be immunized against hepatitis B.
Co-infection with HIV.
A history of transfusions. (In one report, the risk in middle-aged patients with a history of transfusions was 20 - 30%).
Being diabetic and overweight, particularly if fat is distributed in the abdomen (an apple-shape). This condition poses a higher risk for nonalcoholic fatty liver disease (NASH), which in turn is apt to become scarred and cirrhotic.

Having large iron stores in the liver.
High exposure to toxic chemicals or environmental contaminants.

Because there are millions of Americans now infected with chronic hepatitis C, doctors have been justifiably concerned that there will be a significant number of cases of liver failure and liver cancer in the coming years. Computer analyses have suggested that mortality rates from hepatitis C-related cirrhosis or liver cancer will double or triple over the next 20 years. Fortunately, improved therapies may significantly reduce these discouraging estimates.

Researchers are working on developing a genetic test to identify patients with chronic hepatitis C who are most at risk of developing cirrhosis. In 2007, scientists announced they had made progress on a test that measures variations in seven genes to calculate a “Cirrhosis Risk Score.” The researchers hope that this experimental test may eventually help doctors decide which patients should receive early treatment with alpha-interferon and ribavirin.

Risk Factors for Developing Cirrhosis from Hepatitis B. The great majority of people with chronic persistent hepatitis B have a good long-term outlook. Between 5 - 10%, however, become carriers of the virus, and 5 - 10% of these individuals eventually develop cirrhosis. The addition of hepatitis D is a particular danger and increases the risk for cirrhosis. Seven genetic types of hepatitis B virus (designated A to G) have now been identified, which may help researchers determine the patients who may have a better outlook than others. Genotype C is the most common form and is more aggressive than genotype B, which also responds better to treatment.

Primary biliary cirrhosis accounts for only 0.6 - 2% of deaths from cirrhosis. In patients with chronic persistent autoimmune hepatitis, the outlook is very favorable, and survival rates are equal to the general population. If it becomes active, it must be treated. Left untreated, the 5-year survival rates of primary biliary cirrhosis are 50%.

Obesity increases the risk for nonalcoholic fatty liver disease (NAFLD), a condition that can lead to nonalcoholic steatohepatitis (NASH). Studies estimate that 8 - 20% of people with NASH eventually develop cirrhosis. A 2006 study found that people with NAFLD and elevated liver enzymes have a high risk of developing end-stage liver disease. People with NASH had an especially poor prognosis for survival. Losing weight is important for overweight people with NASH and may help to delay disease progression. A 2003 study of more than 11,000 patients indicated that obesity increases the risk of death from cirrhosis in people who drink little or no alcohol, but not among those who drink alcohol.

Symptoms

Many people experience few symptoms at the onset of cirrhosis.

Early symptoms include:

Fatigue and loss of energy.
Loss of appetite and nausea.
Spider angiomas may develop on the skin. These are pinhead-sized red spots from which tiny blood vessels radiate.

Patients in later stages may develop the following symptoms:

Jaundice. This yellowish cast to the skin and eyes occurs because the liver cannot process bilirubin for elimination from the body.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

The palms of the hands may be reddish and blotchy, a condition known as palmar erythema.
Loss of body hair.
Abnormalities in hormone-affected organs. In men with alcoholic cirrhosis, the testicles may atrophy, and their breasts may become swollen, sometimes painfully.
Ascites. A swollen belly is a sign of ascites, the most common major complication of cirrhosis, which occurs when fluid accumulates in the abdomen. Fever, abdominal pain, and tenderness when the belly is pressed indicate that the fluid is infected, but infection can occur without any symptoms.
Fluid buildup and swelling (edema) in legs.

People with primary biliary cirrhosis may have severe generalized itching and often develop small fatty yellow lumps called xanthomas on the eyelids, hands, and elbows. They may have an unpleasant condition called steatorrhea, in which the feces contain excessive fat, causing them to float and to be very foul smelling.

Click the icon to see an image of a xanthoma.

Complications

Cirrhosis is the eleventh leading cause of death by disease in the United States, killing more than 25,000 people each year. A damaged liver affects almost every bodily process, including the functions of the digestive, hormonal, and circulatory systems. The most serious complications are those associated with so-called decompensation, which occur when cirrhosis progresses. They include the following:

Bleeding and fluid buildup (ascites).
Infections.
Damage to the brain (encephalopathy). Impaired brain function occurs when the liver cannot detoxify harmful substances.

Liver cancer is also a long-term risk with cirrhosis.

Cirrhosis is irreversible, but the rate of progression can be very slow, depending on its cause and other factors. Five-year survival rates are about 85% and can be lower or higher depending on severity.

For example, alcoholics with cirrhosis who abstain can have a 5-year or more survival rate of as high as 85%. For those who continue drinking, the chance for living beyond 5 years is no higher than 60%.
In patients with hepatitis B or C, the 5-year survival rate after a diagnosis of cirrhosis is 71 - 85%.
About two-thirds of patients with primary biliary cirrhosis never develop symptoms and can have a normal lifespan. Once symptoms of liver damage, such as jaundice, occur, however, the average survival time declines. In one study of women diagnosed with primary biliary cirrhosis, about 36% developed symptoms over an 11-year period, and 11% either died or required liver transplantation.

Unfortunately, doctors are usually unable to determine when cirrhosis first occurred, which makes it difficult to determine prognosis.

In cirrhosis, liver cell damage slows down blood flow. This causes a backup of blood through the portal vein, a condition called portal hypertension. The effects of portal hypertension can be widespread and serious, including fluid buildup and bleeding.

Ascites and Fluid Buildup. Ascites is fluid buildup in the abdomen. It is uncomfortable and can reduce breathing function and urination. Ascites is usually caused by portal hypertension, but it can result from other conditions. Swelling can also occur in the arms, legs, and spleen. Although ascites itself is not fatal, it is a marker for severe progression. Once ascites occurs, only half of patients survive after 2 years. Some doctors refer to the phases of cirrhosis as preascitic and ascitic. Some doctors even believe that ascites signals the need for liver transplantation, particularly in alcoholic cirrhosis.

Variceal Bleeding. One of the most serious repercussions of portal hypertension is the development of varices, blood vessels that enlarge to provide an alternative pathway for blood diverted from the liver. In about two-thirds of patients, they form in esophagus. Varices pose a high risk for rupture and bleeding because of the following characteristics:

They are thin-walled.
They are often twisted.
They are subject to high pressure.
Internal bleeding from these varices (variceal bleeding) occurs in 20 - 30% of patients with cirrhosis. The risk of death from a single episode can reach 70%.

Bleeding commonly recurs within 2 weeks of the first episode, but after 6 weeks, the risk for recurrence is the same as for patients who have not had a bleeding event.

Factors that predict variceal bleeding include:

Ascites
Encephalopathy
Large veins

Factors that can increase the danger for a bleeding episode in high-risk individuals include the following:

Moderate-to-intense exercise
Bacterial infection
Certain times of the day. Eating increases portal pressure, and there is a greater risk for bleeding in the evening. A lesser but still significant risk occurs in the early morning.

It is important for patients to be screened for esophageal varices and treated with preventive beta blockers if they show signs of risk. Between 30 - 40% of patients with cirrhosis have bleeding. The risk of dying from this complication is 20 - 35%. Some doctors recommend that all newly diagnosed patients be screened using endoscopy. Screening should also be considered for all previously diagnosed patients who have not been screened but would benefit from preventive treatments.

Portal hypertension can cause several secondary complications, including kidney failure. Non-steroidal anti-inflammatory drugs, such as naproxen, may increase the risk for kidney failure.

Gastrointestinal bleeding can occur from abnormal blood clotting, which can be a result of a combination of complications associated with cirrhosis. They include vitamin K deficiencies and thrombocytopenia -- a drop in platelets (the blood cells that normally initiate the clotting process). Some research now suggests that thrombocytopenia itself may be associated with more advanced liver failure.

Bacterial infections are very common in advanced cirrhosis, and may even increase the risk for bleeding. Most bacterial infections, including those in the urinary, respiratory, or gastrointestinal tracts, develop when patients are in the hospital. Abdominal infections are a particular problem in cirrhosis and occur in up to 25% of patients with cirrhosis within a year of diagnosis.

Mental impairment is a common event in advanced cirrhosis. In severe cases, the disease causes encephalopathy (damage to the brain), with mental symptoms that range from confusion to coma and death. A combination of conditions associated with cirrhosis causes this serious complication:

Buildup in the blood of harmful intestinal toxins, particularly ammonia.
An imbalance of amino acids that affect the central nervous system.

Encephalopathy is often triggered by certain conditions, including:

Gastrointestinal bleeding
Constipation
Excessive dietary protein
Infection
Surgery
Dehydration

Alcoholics with cirrhosis are believed to be at higher risk for this complication than are nonalcoholic cirrhosis, but one study suggested that alcoholics simply tend to have more severe cirrhosis. Even minimal hepatic encephalopathy (MHE) can have detrimental effects on functional ability. One study suggested that MHE impairs the ability to safely drive a car, and that all patients with cirrhosis be tested for MHE.

Symptoms of Encephalopathy. Early symptoms of hepatic encephalopathy include forgetfulness, unresponsiveness, and trouble concentrating. Sudden changes in the patient's mental state, including agitation or confusion, may indicate an emergency condition. Other symptoms include bad fruity-smelling breath and tremor. Late stage symptoms of encephalopathy are stupor and eventually coma.

Hepatorenal syndrome occurs if the kidneys drastically reduce their own blood flow in response to the altered blood flow in the liver. It is a life-threatening complication of late-stage liver disease that occurs in patients with ascites. Symptoms include dark colored urine and a reduction in volume, yellowish skin, abdominal swelling, mental changes (delirium, confusion), jerking or coarse muscle movement, nausea, and vomiting.

People with cirrhosis have an increased risk for liver cancer. Hepatitis B and C themselves increase the risk for liver cancer, regardless of the presence of cirrhosis. Hepatitis B infection is the leading cause of liver cancer.

For hepatitis C-related cirrhosis, a 2007 study indicated that patients with cirrhosis who are infected with genotype 1b hepatitis C have a greater risk of developing liver cancer than patients infected with other types of hepatitis C genotypes. (Genotype 1 is the most common type of hepatitis C in the United States.)

People with primary biliary cirrhosis also face a high risk of liver cancer. According to a 2007 study, several factors can indicate the increased likelihood of developing liver cancer. These factors include older age, male gender, history of blood transfusion, and signs of portal hypertension or cirrhosis.

About 30% of patients with chronic liver disease develop osteoporosis (loss of bone density), which is twice the usual incidence. Patients with primary biliary cirrhosis have a particularly high risk for osteoporosis. Treating osteoporosis in patients with cirrhosis can be complicated. One study found that calcitriol (a form of vitamin D) is especially helpful in preventing bone loss in patients with cirrhosis.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements may reduce and even reverse loss of bone density.

Nearly all patients with cirrhosis are insulin resistant. Insulin resistance is a primary feature in type 2 diabetes and occurs when the body is unable to use insulin. This hormone is important for delivering blood sugar and amino acids into cells and helps determine whether these nutrients will be burned for energy or stored for future use.

One study reported that nearly a quarter of patients with cirrhosis had gallstones.

Click the icon to see an image of gallstones.

They may also face a higher than average risk for certain abnormal heart rhythms. Peptic ulcers, sleep disorders, and respiratory problems are also more common in people with cirrhosis than in the general population.

Diagnosis

A physical examination may reveal the following in a patient with cirrhosis:

The cirrhotic liver is firm and often enlarged. The liver may feel rock-hard. (In advanced stages of cirrhosis, the liver may become small and shriveled.)
The left side can often be felt by the doctor when pressing on the abdomen.

If the abdomen is swollen, the doctor will check for ascites by tapping the flanks and listening for a dull thud and feeling the abdomen for a shifting wave of fluid.

Measuring Liver Enzymes (Aminotransferases). Enzymes known as aminotransferases, including aspartate (AST) and alanine (ALT), are released when the liver is damaged. Measurements of these enzymes, particularly ALT, are the least expensive and most noninvasive tests for determining severity of the underlying liver disease and monitoring treatment effectiveness. Enzyme levels vary, however, and are not always an accurate indicator of disease activity. (For example, they are not useful in detecting progression to cirrhosis.)

Radioimmunoassays. To identify a particular virus that may be causing hepatitis, blood tests called radioimmunoassays are performed. Typically, radioimmunoassays identify particular antibodies, which are molecules in the immune system that attack specific antigens. (Antigens are any molecules that the body considers threatening or dangerous, and can be targeted by antibodies.)

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

Some of these tests can pinpoint hepatitis antigens directly. These tests, however, have limitations:

There may not be enough antibodies for blood tests to detect for up to weeks or months after hepatitis develops. Blood tests that are taken too early, then, may miss these signs of infection.
Antibodies also persist after patients recover, so a positive antibody test can indicate a previous infection but does not necessarily determine if the infection is active.

The assays for individual hepatitis viruses may differ.

Polymerase Chain Reaction. In some cases of hepatitis C, a polymerase chain reaction (PCR), may be performed. A PCR is able to make multiple copies of the genetic material (the RNA) of the virus to the point where it is detectable.

Screening for Hepatitis C Virus. In 2004, the U.S. Preventive Services Task Force (USPSTF) recommended against routine screening for the hepatitis C infection in the general population due to low prevalence of the disease. In addition, it "found no evidence that screening for HCV infection in adults at high risk leads to improved long-term health outcomes" and found insufficient evidence to recommend for or against such screening. However, the USPSTF did advise testing in those with signs or symptoms of liver disease. The failure to recommend testing in the high-risk population goes against current recommendations made by the Centers for Disease Control and Prevention, the National Institutes of Health, and other professional organizations. In response to the study, published in the Annals of Internal Medicine, the American Association for the Study of Liver Diseases issued a statement saying that halting such screening would be a "terrible mistake with grave consequences," pointing out that the study itself underscored some key infection-related data that strongly emphasizes the need for screening in high-risk populations.

A liver biopsy is the only definite method for diagnosing cirrhosis. It also helps determine its cause, treatment possibilities, the extent of damage, and the long-term outlook. For example, hepatitis C patients who show no significant liver scarring when biopsied appear to have a low risk for cirrhosis.

The biopsy may be performed using various approaches, including:

Percutaneous Liver Biopsy. This approach uses a needle inserted through the abdomen to obtain a tissue sample from the liver. Various forms of needles are used, including those that use suction or those that cut out the tissue. If cirrhosis is suspected, a cutting needle is the better tool. This approach should not be used in patients with bleeding problems, and it must be used with caution in patients with ascites or severe obesity.

Click the icon to see an image of liver biopsy.

Transjugular Liver Biopsy. This approach uses a catheter (a thin tube) that is inserted in the jugular vein in the neck and threaded through the hepatic vein (which leads to the liver). A needle is passed through the tube, and a suction device collects liver samples. This procedure is risky but may be used for patients with severe ascites.
Laparoscopy. This procedure requires a small abdominal incision through which the doctor inserts a thin tube that contains small surgical instruments and a tiny camera to view the surface of the liver. This is generally reserved for staging cancer or for ascites with unknown causes.

Biopsies can be dangerous, so they cannot be performed on patients who have test results that indicate clotting problems, on those who have had previous liver biopsies, or who have ascites.

Certain blood tests are used to determine liver function. They include the following:

Serum albumin concentration. Serum albumin measures protein in the blood (low levels indicate poor liver function).
Prothrombin time (PT). The PT test measures in seconds the time it takes for blood clots to form (the longer it takes the greater the risk for bleeding).
Bilirubin. One of the most important factors indicative of liver damage is bilirubin, a red-yellow pigment that is normally metabolized in the liver and then excreted in the urine. In patients with hepatitis, the liver cannot process bilirubin, and blood levels of this substance rise, sometimes causing jaundice.

The results of these tests along with the presence of specific complications (ascites and encephalopathy) are used for calculating the Child-Pugh Classification. This is a staging system (A to C) that helps doctors determine the severity of cirrhosis.

Very high levels of serum alkaline phosphatase, an enzyme produced in the liver, and high levels of immune factors called mitochondrial antibodies are usually present in blood tests of patients with primary biliary blood cirrhosis. Bilirubin measurements appear to be important factors in determining its severity.

Fatty liver is suspected when a patient has elevated liver enzymes. The doctor will take imaging tests of the liver using ultrasound, computed tomography, or magnetic resonance imaging. A liver biopsy is the standard test for confirming a diagnosis of fatty liver disease and for distinguishing NAFLD from nonalcoholic steatohepatitis (NASH). Several studies in 2006 and 2007 suggested that a blood test for cytokeratin-18 (CK-18), a protein found in liver cells, may be an effective noninvasive approach for diagnosing NASH. Doctors hope that this simple blood test may eventually be able to replace liver biopsy.

Several imaging tests can be used to diagnose cirrhosis and its complications.

Imaging Techniques. Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound are all imaging techniques that are useful in detecting and defining the extent of cirrhosis. Such tests can reveal ascites, an enlarged spleen, an irregular liver surface, reversed portal vein blood flow, and liver cancer. Sometimes they can even detect abnormally large blood vessels in the liver. In some cases, images from ultrasound and CT can be misinterpreted as cancer. MRI is most useful for ruling out or confirming cancer.

Click the icon to see an image of an MRI scan.

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

Liver Scans. Sometimes liver scans are performed using a small radioactive tracer and a special camera that records information provided by the tracer as it passes through the liver:

Arteriography uses dye injected into the hepatic arteries that show up on x-ray.
Splenoportography uses dye injected into the spleen, which allows the doctor to measure portal vein pressure. This procedure is risky.

Hepatic vein wedge pressure involves insertion of a catheter into the hepatic veins. The blood pressure in the veins of the liver is then measured. The result is an indicator of portal vein pressure. If pressure is high, cirrhosis is likely. A low measurement is a favorable sign.

Endoscopy. Some doctors recommend endoscopy for patients newly diagnosed with mild-to-moderate cirrhosis in order to screen for esophageal varices. (These are abnormal blood vessels in the esophagus that increase the risk for bleeding). In this test, a fiber optic tube is inserted down the throat. The tube contains tiny cameras to view the inside of the esophagus, where varices are most likely to develop. Endoscopy is the only procedure for detecting varices, but it is not clear if screening for varices in patients without severe cirrhosis is any more beneficial than simply putting them immediately on preventive drugs -- whether or not varices have been identified.

Paracentesis. If ascites is present, paracentesis is performed to determine its cause. This procedure involves using a thin needle to withdraw fluid from the abdomen. The fluid is tested for different factors to determine the cause of ascites:

Bacteria cultures and white blood cell counts. (These are used to determine the presence of infection.)
Protein levels. Low levels of protein in the fluid plus a low white blood cell count suggest that cirrhosis is the cause of the ascites.

The appearance of the fluid is helpful in determining problems:

A cloudy fluid plus a high white blood cell count means an infection is present.
Bloody fluid suggests the presence of a tumor.

Screening for Liver Cancer. Patients with cirrhosis are usually screened for liver cancer using ultrasound and tests for a substance called alpha-fetoprotein (AFP). It is not known whether such screening has much impact on survival, because it is not very sensitive and has a high rate of false positives (suggesting the presence of cancer when it is not actually present). Screening is not necessary in patients without cirrhosis.

Treatment

The only treatment for alcoholic cirrhosis is to stop drinking. Individuals with alcoholic cirrhosis are typically malnourished and require increased calories and rigorous nutritional support, which can improve survival rates.

Interferons Alone and in Combination with Ribavirin. Pegylated interferon combined with ribavirin is the gold standard treatment for chronic hepatitis C in both adults and children. It achieves response rates of up to 50% for patients infected with HCV genotype 1 (the most common genotype form in the U.S.) and up to 80% for patients infected with genotypes 2 or 3. Interferon alone is usually reserved for patients who cannot tolerate ribavarin.

A 2005 clinical trial of patients with chronic hepatitis C and cirrhosis found that interferon treatment reduced the risk of liver cancer and significantly improved chance of survival. The study emphasizes the importance and substantial benefits of interferon therapy. A 2007 study of patients with hepatitis C-related cirrhosis also indicated that interferon therapy can help reduce the risk of liver cancer and overall risk of death from liver disease.

A number of natural and synthetic interferons are available:

Natural interferons include interferon alfa-2a (Intron) and interferon alfa-2b (Roferon).
Pegylated interferons (PegINF) are long-acting formulations of interferon. They include alfa-2b (Peg-Intron) or alfa-2a (Pegasys). These drugs are used in combination with ribavarin (Copegus, Rebetol).
Alfacon-1 (Infergen), also called consensus interferon, is a genetically modified interferon. A combination of alfacon-1 with ribavirin is proving to help some patients who had been resistant to ribavirin with interferon.

A 2005 study suggested that some patients with hepatitis C genotypes 2 or 3 may be able to benefit from a shorter course of combination treatment (12 weeks) than the standard 24-week treatment duration. A shorter treatment time may reduce the risk of side effects. However, a 2007 study in the New England Journal of Medicine found that 16 weeks of combination therapy in patients with these genotypes did not work as well as the 24-week regimen. Given the significant side effects associated with combination pegylated interferon and ribavarin treatment, particularly anemia, researchers are actively investigating how to identify which patients may be able to succeed with shorter treatment duration.

PegINF combinations are proving to slow progression of scarring, and have even achieved improvement in some patients who already have cirrhosis. Whether the combination treatment protects against future liver cancer is still unclear. (A higher total dose, rather than a longer duration of treatment, may be the critical factor for protection.)

Side Effects of Combination Treatment. The side effects of the combination include those of both interferon and ribavirin. Interferon side effects may occur more often in the combination treatment. Combination treatment side effects may include:

Anemia occurs in about 22% of patients who take combination treatment versus 1% who take interferon alone. This complication is reversible and usually stabilizes after 1 - 2 months of treatment. However, some patients may become so anemic that they have to stop the medication. Since anemia can worsen heart disease, patients with a history of significant heart problems should not be treated with ribavirin. Other nucleoside analogues are being investigated that may have a lower risk for anemia than ribavirin.
Flu-like symptoms, such as fever, headaches, and muscle aches, are the most common side effect.
Reduced white blood cell count.
Skin disorders, such as dry skin and rash.
Coughing and shortness of breath.
Gastrointestinal symptoms (nausea, indigestion, lack of appetite).
Emotional and psychological symptoms, such as severe sleep disturbances, depression, irritability, and anxiety.
Combination treatment in pregnant women poses a very high risk for birth defects.

The current drugs used for hepatitis C still do not meet the needs of all patients. They are expensive, have significant side effects, do not work in half the patients who take them, and are unsuitable in many others. Investigation is ongoing to find better solutions. Drugs showing promise include:

Albinterferon alfa-2b (Albuferon). This long-acting form of interferon-alfa may have fewer side effects and require less dosing than pegylated interferons. It is currently being tested in combination with ribavarin in Phase II trials for patients with genotype 1 chronic hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a peptide derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It is being used for hepatitis B and is under investigation for hepatitis C in combination with interferon.
Celgosivir. Celgosivir is a new type of antiviral drug, which blocks alpha-glucosidase, an enzyme involved in viral replication. Celgosivir is being studied in combination with pegylated interferon alfa-2b and ribavirin. The drug is derived from the Australian chestnut tree.
Eltrombopag (Revolade). Thrombocytopenia, reduced production of blood platelets, is a condition that affects patients with hepatitis C and cirrhosis. Patients with thrombocytopenia cannot tolerate standard antiviral therapy. Researchers hope that eltrombopag, a drug that stimulates platelet production, may help normalize platelet levels so that they can start antiviral drug treatment.
Statins. Statin drugs are used for the treatment and management of cholesterol. Researchers are studying whether they may help improve liver enzyme levels in patients with hepatitis C.

Of interest are studies using phlebotomy (which is simply drawing blood) to reduce iron levels. In one study, maintenance therapy with this procedure reduced liver inflammation and possibly slowed progression of cirrhosis.

An ounce of prevention is worth a pound of cure, and the phrase resoundingly holds true in the case of hepatitis B. Today, a vaccine against hepatitis B is available. It can prevent hepatitis B and, therefore, also prevent liver cancer. The American Academy of Pediatrics and the Centers for Disease Control and Prevention currently recommend that all babies born in the United States receive a hepatitis B vaccine at birth.

Six drugs are currently approved in the United States for treatment of chronic hepatitis B:

Peginterferon alfa-2a (Pegasys)
Interferon-alfa-2b (Intron)
Adefovir (Hepsera)
Lamivudine (Epivir)
Entecavir (Baraclude)
Telbivudine (Tyzeka)

These drugs block the replication of hepatitis B in the body. Some also help boost the immune system. A doctor will decide which drug to prescribe based on a patient’s age, disease severity, and other factors. Each drug has various advantages and disadvantages in terms of cost, efficacy, side effects, and likelihood of drug resistance. A combination of drugs may also be prescribed.

Peginterferon alfa-2a. Peginterferon alfa-2a (Pegasys) was approved in 2005 for treatment of chronic hepatitis B. (Peginterferon is also called pegylated interferon.) The drug was previously approved in 2002 for treatment of chronic hepatitis C. Pegasys prevents the hepatitis B virus from replicating and also helps boost the immune system. It is given as a weekly injection. Peginterferon is sometimes prescribed in combination with lamivudine (Epivir).

Interferon Alpha. For many years, interferon alfa-2b (Intron) was the standard drug for hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to help hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs in almost all cases, although this recurring mutation may be weaker than the original strain. Administering the drug for longer periods may produce sustained remission in more patients while still being safe. Interferon is also effective in eligible children, although long-term effects are unclear.

Lamivudine, Entecavir, and Telbivudine. These drugs are classified as nucleoside analogs. Lamivudine (Epivir or 3TC) is an antiretroviral drug that is used to treat human immunodeficiency virus (HIV) as well as hepatitis B. Studies suggest that lamivudine reduces viral count in over half of hepatitis B patients who take it as sole therapy for about a year. It is less expensive than interferon-alfa and has fewer side effects, but may not work as well as interferon-alfa for long-term therapy. A major problem with lamivudine is the development of mutated viral strains that become resistant to the drug, particularly in areas where the virus is common. About 20% of patients who take lamivudine develop drug resistance.

In 2005, the Food and Drug Administration (FDA) approved entecavir (Baraclude) for treatment of adults with chronic hepatitis B. In clinical trials, entecavir worked better than lamivudine for treating hepatitis B. Entecavir appears to have less risk of drug resistance than lamivudine. Studies also suggest that it may be a good alternative treatment for patients who have developed resistance to lamivudine. Questions have been raised about the drug’s possible cancer risks. Ongoing studies are evaluating this risk.

In 2006, the FDA approved telbivudine (Tyzeka), the newest nucleoside analog drug, for treatment of chronic hepatitis B.

Adefovir. Adefovir (Hepsera) belongs to a class of antiviral drugs called nucleotide analogs. (Nucleotides are related to nucleosides but have a slightly different chemical structure.) Nucleotide analogs block an enzyme involved in the replication of viruses. Adefovir costs more than lamivudine, but may be effective against lamivudine-resistant strains of hepatitis B. The drug must be taken on a long-term basis. A 2006 study indicated that when patients stopped taking adefovir after 48 weeks, the hepitatis B virus resumed replication. Patients who took the drug for a longer period (144 weeks) continued to benefit from treatment. Another 2006 study indicated that for some patients, adefovir remains effective for up to 5 years, although resistance occurs in about 20% of patients.

Drug Warnings. In 2004, the FDA issued two drug warnings for patients with hepatitis B. The HIV drug tenofovir (Viread) should not be used to treat patients with HIV who are co-infected with hepatitis Bas the drug may increase hepatitis severity. The lymphoma drug rituximab (Rituxan) may reactivate hepatitis B. Patients with lymphoma should be screened for hepatitis B. In 2007, the FDA revised the label for entecavir (Baraclude); patients who are co-infected with hepatitis Band HIV should take entecavir only if they are also taking antiviral HIV drugs.

Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic hepatitis B.
Pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys) are approved for treatment of chronic hepatitis C. They are being investigated alone and in combination with other drugs, such as ribavirin (Copegus, Rebetol), for treatment of hepatitis B. The combination of pegylated interferon and ribavirin is the standard treatment for hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a substance derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It appears to be safe for hepatitis B patients when used alone or in combination with interferon. It is approved in many countries, but not the United States.

Ursodeoxycholic Acid (UDCA) and Drugs Used to Slow Progression. At this time no medication can cure primary biliary cirrhosis. Ursodiol, ursodeoxycholic acid (Actigall), or UDCA has been the standard drug used for primary biliary cirrhosis. Several studies have reported that it slows progression and helps prevent the need for liver transplantation.

It has no effect on symptoms, including itching and fatigue. Some drugs, such as colchicine, corticosteroids, or immunosuppressants, are being investigated for use in combination with UDCA. Long-term controlled trials are needed to determine the value of UDCA alone or with other drugs.

Drugs for Itching. Itching is a major problem with this disease. Cholestyramine, taken with meals, is the first choice for relieving itching. Several other drugs have been used or investigated, including low doses of the drug naltrexone and phototherapy.

Drugs for Impaired Fat Absorption. Because primary biliary cirrhosis affects fat absorption, patients may need high doses or injections of important fat-soluble vitamins, including K, D, A, and E.

Treatment of Nonalcoholic Fatty Liver Disease. Weight loss is the most important method for managing nonalcoholic fatty liver disease (NAFLD) and preventing progression to nonalcoholic steatohepatitis (NASH) and, eventually, cirrhosis. Diabetes and cholesterol control are also important. Investigators are studying whether various drugs used to treat type 2 diabetes may help treat NAFLD and NASH.

Other research is focusing on antioxidant vitamins, such as vitamin E.

In 2005, the National Institutes of Health launched two trials to study treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitisin adults and children. Children with NAFLD will receive vitamin E, metformin, or placebo. In the adult trial, patients with NASH will receive vitamin E, pioglitazone, or placebo.

Secondary Biliary Cirrhosis. Secondary biliary cirrhosis caused by blockage in the bile ducts can be relieved by surgery.

Autoimmune Hepatitis. Autoimmune hepatitis is treated with the corticosteroid prednisone and also sometimes immunosuppressants, such as azathioprine (Imuran).

Hemochromatosis. For hemochromatosis, weekly bleedings (phlebotomies) may be performed until iron levels are normal, then repeated as needed. If treatment is given before cirrhosis develops, life expectancy may be normal.

Wilson's Disease. D-penicillamine is the drug most used for Wilson's disease.

There are no current safe and effective therapies for liver scarring (fibrosis). However, recent insights into the cellular and molecular mechanisms responsible for scarring have led to the development of specific, antifibrotic drugs that target the primary injury and inhibit abnormal cell mechanisms. Such drugs, now in very early testing, could one day help prevent or reduce the progression of liver scarring or the progression to liver cancer.

Liver transplantation may be indicated for the following:

Patients who have developed life-threatening cirrhosis and who have a life expectancy of more than 12 years.
Patients with liver cancer that has not spread beyond the liver.

Survival rates after transplantation are similar among those who have hepatitis B, hepatitis C, or alcoholic liver disease. Current 5-year survival rates after liver transplantation are about 75%. Patients also report improved quality of life and mental functioning after liver transplantation. Patients should seek medical centers that perform more than 50 transplants per year and produce better-than-average results.

Unfortunately, there are many more patients waiting for liver transplants than there are available organs. Fortunately, more procedures are now being performed using liver tissue from a living donor. In these cases, surgeons replace the patient’s diseased liver with a part of the liver taken from a donor. The donor’s liver regenerates to full size within a few weeks of surgery, and the recipient’s liver also regrows.

Transplantation surgery generally takes 4 - 12 hours to perform, and patients stay in the hospital for up to 3 weeks after the surgery. Most patients return to normal or near-normal activities 6 - 12 months following the transplant. For the rest of their lives, patients need to take immunosuppressive medication to prevent rejection.

Liver Transplantation in Patients with Hepatitis. One of the primary problems with many hepatitis patients is recurrence of the virus after transplantation.

One study of patients with hepatitis C reported 5-year risks of 80% for viral recurrence and 10% for cirrhosis. A 2004 study found that the hepatitis C virus recurs with more severity with liver donations from living donors than livers taken from cadavers.
Viral recurrence is also high in patients with hepatitis B. In 2007, the FDA approved HepaGram B, an immune globulin, to prevent recurrence of hepatitis B after transplantation. Patients need to receive HepaGram B injections on a lifelong basis.

Liver Transplantation in Autoimmune Liver Diseases. Patients who require transplantation for primary biliary cirrhosis are those who develop major complications of portal hypertension and liver failure or who have poor quality of life and short survival without the procedure. Survival rates after transplantation are excellent.

The outlook is also good for patients who have autoimmune hepatitis who require a transplant. Survival rates are about 90% after 1 year, and 70 - 80% after 5 years. Rejection usually occurs in those patients whose immune systems are very compromised.

Liver Transplantation in Alcoholism. There is considerable controversy over whether liver transplantation should be performed in alcoholics with cirrhosis who are unlikely to abstain. One French study reported no differences in survival, transplant rejection, and other indicators of success and failure after transplantation between alcoholics and non-alcoholics and between alcoholics who abstained and those who relapsed after the procedure.

Click the icon to see an illustrated series detailing a liver transplant.

Lifestyle Changes

A healthy lifestyle is particularly important for people with cirrhosis.

Healthy Foods. Because important antioxidant vitamins are depleted in the cirrhotic liver, patients should maintain a diet rich in fresh fruits, vegetables, and whole grains.

Coffee and Tea. Coffee appears to help lower the risk of cirrhosis, especially among heavy drinkers. A 2006 study indicated that people who drank 1 - 3 cups of coffee a day reduced their risk of alcoholic cirrhosis by 40%. Those who drank 4 or more cups reduced their risk by 80%. Researchers think that there is some ingredient in coffee (other than caffeine) that is responsible for this apparent protection. Studies on tea have been mixed. Some studies report that tea also lowers the risk of chronic liver disease, while others have found no effect.

Antioxidant Supplements. There is some preliminary laboratory evidence that various antioxidant supplements -- including vitamin E, selenium, and S-adenosylmethionine (SAMe) -- may help protect against liver damage and cirrhosis. Supplements, however, are not recommended for people with liver disease except with the advice of a doctor. Some vitamins, such as vitamins D and A, are metabolized in the liver and can be toxic.

Iron Restrictions. Elevated iron levels have been associated with cirrhosis from many causes. Patients should avoid iron-rich foods, such as red meats, liver, and iron-fortified cereals, and should avoid cooking with iron-coated cookware and utensils.

Supplemental Nutritional Products. Supplemental nutritional beverages may be helpful, particularly for patients with both alcoholism and cirrhosis. In one study, patients with both alcoholism and cirrhosis drank Ensure every day as a supplement to their regular diet. After 6 months they showed significant improvement in many signs of overall health compared to those who did not consume the beverage.

Vitamin B1 (Thiamine). Thiamine binds to iron and helps reduce iron load in the liver. One small study suggested it may be helpful for patients with chronic hepatitis B. It is not known if it has any benefit for cirrhosis. Pork is high in the vitamin, but more healthful sources include dried fortified cereals, oatmeal, corn, nuts, cauliflower, sunflower seeds and vitamin pills.

Like most vitamins, vitamin B1 may be obtained in the recommended amount with a well-balanced diet, including some enriched or fortified foods.

Omega-3 Fatty Acids. Some research suggests that supplements of omega-3 fatty acids (found in fish oil and evening primrose oil) may help protect the diseased liver.

Click the icon to see an image of omega-3 fatty acids.

Protein and Soy. High-quality dietary protein may be especially helpful for patients with ascites and for repairing muscle mass, but excessive protein loads may trigger encephalopathy. Protein solutions have been devised that provide beneficial amino acids without including those that increase this risk. There is no limit on vegetable proteins, such as those from soy.

Salt Restriction. Restricting salt consumption to less than 2,000 mg a day is particularly important for patients with ascites. The less salt the better.

Zinc. In some studies, taking zinc supplements have lowered ammonia levels in some patients who were zinc-deficient, a common problem in cirrhosis. Zinc replacement may reduce frequency and severity of muscle cramps and may even help protect against encephalopathy.

Fluid restriction is not usually necessary, but patients with severe ascites should discuss limiting fluid with their doctors.

Exercise increases the risk for portal pressure and variceal bleeding. One study reported that taking a beta-blocker may reduce this risk, although patients should discuss this with their doctor.

Infections can have a severe impact on the liver. Although most respiratory infections generally affect only the lungs, one small study suggested influenza may directly affect the liver in patients with cirrhosis and exacerbate the disease process. Researchers in the study advise annual flu shots for people with cirrhosis.

Patients should be aware that manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Among the natural substances being investigated for liver disease are ginseng, glycyrrhizin (a compound in licorice), catechin (found in green tea), SAMe, and silymarin (found in milk thistle).

Silymarin. Silymarin is a chemical found in the milk thistle herb. It is one of the most popular, and most studied, herbal remedies for liver disease. Some studies have indicated that silymarin may help improve liver enzyme levels. However, a 2005 review found that milk thistle did not help reduce deaths from liver disease caused by alcohol or hepatitis.

S-adenosylmethionine. S-adenosylmethionine (SAMe) is a chemical found in all parts of the body, which declines with age. It has been investigated for years in Europe for arthritis, depression, and liver disease. Some preliminary studies suggest it may provide some protection against liver damage and scarring and may improve survival rates in alcoholic patients with cirrhosis. It is very expensive, however, and as with all unregulated products, long-term side effects, drug interactions, and other factors are not fully known.

The following warnings are of particular importance for people with liver disease:

Kava kava (an herb used for anxiety and tension) can be toxic to the liver and cause severe hepatitis and even liver failure if taken excessively.

Abdominal Infections

Antibiotics are administered when fluid examination and tests for ascites indicate infection. For a first episode, the antibiotic cefotaxime is typically administered intravenously, requiring hospitalization. Treatment usually lasts 10 days, but research indicates that 5 days may be sufficient for certain patients. Some research indicates that the oral antibiotic ofloxacin may work as well with fewer complications, allowing patients to be treated at home.

In advanced cirrhosis, the risk for serious abdominal infection is high, and the antibiotic norfloxacin is often prescribed preventively against specific organisms that infect the abdominal cavity. One study reported, however, that patients who took norfloxacin became susceptible to Staphylococcal infections. Long-term treatments with norfloxacin or similar antibiotics may increase the risk for fungal infections after liver transplantation.

Encephalopathy

The first step in managing encephalopathy (damage to the brain) is to treat any precipitating cause, such as:

High ammonia levels
Bleeding
Low oxygen
Dehydration
Infection
Use of sedatives

Some studies indicate that manganese poisoning may be partially responsible for encephalopathy in cirrhosis. Studies are needed to determine if drugs that remove manganese improve this complication.

Ammonia is the leading toxin in causing encephalopathy related to cirrhosis. Mild encephalopathy is managed by directing therapy toward eliminating ammonia in the intestine:

The first step is to restrict animal protein, substituting meats and dairy products with vegetable protein, such as soy, and amino acid supplements.
Enemas, which clean out the intestine, may be effective.
Lactulose (Cephulac, Chronulac, Constulose, Duphalac, Enulose) and lactitol, known as disaccharides, help lower blood ammonia levels and have been shown to be effective in improving cognitive function and quality of life in people with mild encephalopathy.
Antibiotics, such as metronidazole, rifamycin, or neomycin, are effective in reducing levels of ammonia-producing bacteria in the intestine, although long-term use of these drugs can cause toxic side effects. Rifaximin (Xifaxan), another antibiotic, was approved in 2005 for treatment of hepatic encephalopathy.
L. acidophilus is the probiotic found in live culture yogurt. Researchers are studying whether L. acidophilus food or supplements can aid in improving liver and cognitive functions.
Researchers are investigating whether exercise can help remove ammonia from the body and improve encephalopathy.

Investigational Drugs. Certain drugs, such as rifaximin (Xifaxan) and flumazenil (Mazicon, Romazicon), are under investigation for treating encephalopathy. Flumazenil is typically administered to counteract the effects of sedatives.

Ascites

Nearly all patients with ascites (fluid accumulation in the abdomen) can benefit from the following measures:

Abstaining from alcohol. (Sometimes abstaining from alcohol is enough to improve this complication.)
Restricting salt.
Taking diuretics, usually spironolactone (Aldactone) and furosemide (Lasix). Previously, spironolactone was usually given alone, but experts now use it by itself only in patients with minimal fluid buildup. Patients should be monitored carefully for excessive and too-fluid loss, which can set off complications, including hypokalemia (dangerously low potassium levels), kidney failure, or encephalopathy. Weight loss from diuretics usually should not exceed 1 - 2 pounds per day, but there is no limit for patients with massive swelling.

Doctors often recommend bed rest for patients with ascites, but studies do not support its benefits. Restricting fluid is not usually necessary unless sodium levels in the blood are very low.

Patients with recurring ascites, or ascites that does not respond to standard diuretics after a month (refractory ascites), may require procedures to reduce fluid.

Large-Volume Paracentesis. Large-volume paracentesis is the current standard procedure and involves the following:

Large volumes of fluid are removed through a tube in the abdomen. Research indicates that 4 - 6 liters are usually effective and safe.
Albumin (protein) may be administered intravenously. This helps prevent a sudden drop in blood flow in the arteries. One study suggested that terlipressin, a drug that constricts blood vessels, may be as effective.
If the ascites does not respond to treatments, the patient may need paracentesis every 2 weeks or more frequently, and up to 10 liters may need to be removed.

Patients who need this procedure are probably not complying with dietary requirements.

Transjugular Intrahepatic Portosystemic Shunt. Studies have been mixed on whether transjugular intrahepatic portosystemic shunt (TIPS) improves survival without transplantation compared to large-volume paracentesis. An important 2003 study reported that although TIPS reduced the number of paracenteses, there was no improvement in survival rates. In addition, patients who were given TIPS had a higher risk for encephalopathy than those given large-volume paracentesis. In general, TIPS should be a second-line option for ascites that does not respond to diuretics.

Peritoneovenous Shunting. Peritoneovenous shunting is an older, more invasive, procedure involving insertion of a tube, or shunt, under the skin that routes the fluid from the abdomen into the jugular vein. The procedure can have serious complications, including infection, blood clots, encephalopathy, and rupture of blood vessels in the esophagus. It is now generally reserved for patients who are not candidates for repeat paracentesis or liver transplantation.

Hepatorenal syndrome can occur in patients with ascites. This is a life-threatening condition in which the kidneys fail in trying to compensate for altered blood flow in the liver. Studies suggest that terlipressin may be an effective treatment in combination with albumin for hepatorenal syndrome.

Researchers are testing certain drugs that may correct the imbalances in circulation that lead to portal hypertension and ascites. Of particular interest are drugs called nonpeptide vasopressin antagonists, also referred to as aquaretics. They may reverse the dilation in blood vessels that lead to salt and fluid retention.

The prognosis for patients with ascites is poor, even with intensive procedures. Liver transplantation should be considered for patients when ascites does not respond to treatments and when poor liver function or other complications, such as peritonitis or kidney failure, are present.

Bleeding Episodes

Preventing an Initial Bleeding Episode. About half of patients with mild-to-moderate cirrhosis have esophageal varices (enlarged veins in the esophagus). In such patients, the risk for bleeding within 2 years is as high as 35%. Bleeding is fatal in half of these patients. In general, experts recommend preventive drugs for such patients, even if they have not been screened with endoscopy -- the procedure needed to actually detect varices. Beta-blockers are the only medications to date that have some preventive effects, but others are under investigation.

Guidelines for Treating Bleeding Episodes. The doctor should first be certain that bleeding is caused by portal hypertension and ruptured varices and not by other conditions. For example, patients with cirrhosis are also at higher than average risk for bleeding peptic ulcers.

Saline or Ringers solution (a fluid and electrolyte replenisher) followed by red blood cells and plasma is administered immediately to replace lost blood.

The next step is to immediately achieve normal blood clotting (hemostasis) in order to stop the current bleeding episode and prevent early recurrence, which typically occurs 3 - 5 days after a bleeding episode.

In general it is a two-pronged approach using drugs and endoscopy procedures.

Drugs. Either octreotide or vasopressin are typically used to reduce portal pressure and blood flow.
Endoscopy. Endoscopy involves insertion of a thin tube containing a tiny camera followed by surgery to make repairs. Endoscopic sclerotherapy is the most common procedure. Emergency sclerotherapy is often used as first-line therapy for variceal bleeding, but a major 2002 analysis suggested that it is no more effective than drugs for stopping bleeding, and it has potentially serious adverse effects.

A combination of drugs and endoscopy is the best approach for stopping bleeding compared to endoscopy alone. It is not clear if there is any difference in long-term survival, however.

Prevent Bleeding Recurrence. Rebleeding is common after an episode. Beta-blocker drugs are typically used, although they are not effective for many patients.

Preventing Complications. The patient who is experiencing a bleeding episode is at high risk for other complications, including pneumonia, bacterial infections, and hepatic encephalopathy. Bacterial infections can also impair blood clotting. Preventive oral antibiotics are often problematic in these patients. One study suggested that intravenous ciprofloxacin may be helpful.

Beta-Blockers. Beta-blockers, typically propranolol (Inderal) or nadolol (Corgard), reduce the heart rate and can lower portal vein pressure in many patients and so reduce variceal bleeding. Carvedilol (Coreg), a newer drug, may be even more effective, but more research is needed. Beta-blockers are also used as a primary approach for prevention of recurring bleeding. Nevertheless, they fail to reduce portal pressure in nearly 40% of patients with cirrhosis. They may not be appropriate for patients with type 1 diabetes, asthma, emphysema, and chronic bronchitis. They must be taken for at least 2 years and most likely longer to sustain a survival advantage.

Other Drugs. Other drugs are being used or investigated, mostly in combination with beta-blockers, to reduce recurrence rates.

Isosorbide mononitrate is a nitrate, a type of drug commonly used for angina. Combinations with beta-blockers appear to prevent rebleeding more effectively than beta-blockers alone. It is not clear if the combination improves any other aspects of the disease. The nitrate may also be an alternative drug for patients who cannot tolerate beta-blockers. Studies have failed to show any survival advantage, however, when isosorbide mononitrate is used alone.
The diuretic spironolactone may be helpful in combination with a beta-blocker for reducing both ascites and rebleeding after an initial episode.
Angiotensin II receptor antagonists, including losartan (Cozaar), are being studied for lowering portal pressure.

Somatostatinand Similar Drugs. Somatostatin is a natural hormone that constricts blood vessels. This drug or synthetic derivatives (octreotide and vapreotide) may be more effective than the common procedure, endoscopic sclerotherapy, for controlling bleeding. No single drug is more effective than another. Their benefits for improving overall survival, however, are still uncertain, and a major analysis of current studies found no effects on survival rates with either octreotide or somatostatin.

Somatostatin, the natural hormone, controlled variceal bleeding in 87% of patients in one study, but it is short acting.
Octreotide (Sandostatin) is a derivative of somatostatin and is longer acting. It has largely replaced the older drug. It is very safe, even for heart patients, and has few serious side effects.
Vapreotide (Octastatin) also resembles somatostatin. One study concluded that a combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone for controlling bleeding, but the combination therapy did not improve mortality rates at 42 days. The study suggested that these drugs should be taken for 5 days.

Vasoconstrictors. Vasoconstrictors narrow the blood vessels and reduce flow in the spleen. They are particularly effective when used with nitroglycerin.

Vasopressin (Pitressin) is the most commonly used vasoconstrictor. It poses a risk to the heart, however, and it is not clear whether it is actually helpful.
Terlipressin is a synthetic version of vasopressin that is proving to be as effective as sclerotherapy in controlling bleeding. It also lacks vasopressin's side effects and may prove to prolong survival and serve as a bridge for patients waiting for liver transplantation.

Endoscopic procedures use a tube inserted down through the esophagus, containing microcameras and tiny instruments. Endoscopy is used both to diagnose the disease and stop bleeding. The two standard procedures are band ligation and sclerotherapy. In general, a combination of drug therapies and an endoscopic procedure is the usual approach for preventing a bleeding recurrence.

Endoscopic Band Ligation. In endoscopic band ligation, latex bands are wrapped around the bleeding varices, shutting off the blood supply. It is the method of choice to control of bleeding and, in weekly sessions, to prevent rebleeding, because it has a lower risk for complications than sclerotherapy. Recurrence rates are higher with band ligation, however. Studies are mixed on whether weekly treatments with band ligation are any more effective in preventing rebleeding than beta-blockers plus isosorbide mononitrate. A combination of medications plus band ligation is under investigation.

Investigators are studying argon plasma coagulation (APC) after band ligation to prevent variceal recurrence and rebleeding. This procedure uses argon gas to deliver electric currents that coagulate and stop bleeding.

Endoscopic Sclerotherapy. Endoscopic sclerotherapy is only effective against bleeding in the esophagus. The endoscopic tube is inserted through the mouth. A sclerosant (a solution that toughens the tissue around the variceal blood vessels) is injected to stop the bleeding. The procedure is repeated over a period of 2 - 3 months. Repeat treatments appear to reduce rebleeding and death. Minor complications (usually ulcers in the mucus membranes) are common, and serious complications can occur (narrowing or perforation of the esophagus and leakage at the injection site.)

Balloon tamponade has been available for years, but it is now used only for bleeding that cannot be controlled by drugs or endoscopy. It uses a tube inserted through the nose and down through the esophagus until it reaches the upper part of the stomach. A balloon at the tube's end is inflated and positioned tightly against the esophageal wall. It is usually deflated in about 24 hours. Serious complications can occur, the most dangerous being rupture of the esophagus. Recurrence of bleeding is common.

Shunts are used for patients who are still bleeding in the esophagus after endoscopic sclerotherapy or who are bleeding in the stomach. Choices include the following:

Transjugular intrahepatic portosystemic shunt (TIPS)
A surgical shunt

Shunt operations usually eliminate variceal bleeding, but encephalopathy and shunt failure are frequent complications. Doctors do not recommend shunts as elective surgery for high-risk patients who are candidates for liver transplantation, since shunts make this operation more difficult.

Transjugular Intrahepatic Portosystemic Shunt.A transjugular intrahepatic portosystemic (or portal-systemic) shunt (TIPS) involves the following:

The patient only requires a local anesthetic and a sedative.
A long needle is inserted into the jugular vein in the neck and passed down through the vena cava, a large vein that conducts blood back to the heart. This serves to widen the vein.
The surgeon makes an incision in the hepatic vein in the liver and creates a connection to the portal vein.
A cylindrical wire-mesh stent is inserted into this connecting vein.
The stent now acts as a shunt, which reroutes blood around the scarred liver.

TIPS is a good choice for bleeding that is not controlled by endoscopy, particularly when it is performed shortly after a bleeding episode. It also reduces ascites.

It is not useful as the first choice for stopping an initial bleeding episode or for preventing rebleeding, however, since it poses a high risk for encephalopathy. This complication outweighs its benefits compared to endoscopy for initial treatment and to beta-blockers for preventing recurrence. Blockage or closure of the shunt can develop over time.

TIPS is generally recommended for only patients who:

Cannot tolerate sclerotherapy
Are unlikely or unable to comply with the repeated procedures necessary for sclerotherapy
Have poor blood circulation

Surgical Shunts. There are two types of surgical shunts:

A portal shunt, or portal systemic shunt. It was introduced in 1945 and was the first significant treatment for bleeding varices. It relieves pressure in the portal vein by surgically joining it to the inferior vena cava, a large vein that conducts blood back to the heart. It poses a high risk for encephalopathy and does not appear to improve survival, so is not used often.
A variation called the H-graft portacaval shunt is a partial shunt that is proving to be effective for treating bleeding. It controls bleeding in 90% of patients and has a lower encephalopathy rate than the complete portal shunt or TIPS. In fact, early studies report that it may have lower rates for transplantation and death than TIPS.
A distal splenorenal shunt (DSRS) preserves blood flow through the portal vein while relieving pressure on the varices by joining the left kidney vein to the splenic vein. (The splenic vein returns blood from the spleen and is one of two veins that form the portal vein.) Studies show that DSRS has similar mortality rates compared to the portal shunt but lower rates of encephalopathy afterwards. Patients with alcoholic cirrhosis fare worse with DSRS than nonalcoholic patients. It is probably best used as an elective operation in patients with good liver function who continue to bleed in spite of endoscopy.

Resources

www2.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.aasld.org -- American Association for the Study of Liver Diseases
www.liverfoundation.org -- American Liver Foundation
www.gastro.org -- American Gastrointestinal Association
www.cdc.gov/ncidod/diseases/hepatitis -- Centers for Disease Control and Prevention, Hepatitis
www.hepfi.org -- Hepatitis Foundation International
www.pbcers.org -- Primary Biliary Cirrhosis Organization
www.organdonor.org -- National Transplant Society
www.unos.org -- United Network for Organ Sharing
www.organdonor.gov -- US government organ donor site

References

Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: A seventeen-year prospective cohort study. Hepatology. 2007 Aug 6; [Epub ahead of print]

Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnu L, Mazzella G, et al. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007 Mar;45(3):579-87.

Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865-73.

Huang H, Shiffman ML, Friedman S, Venkatesh R, Bzowej N, Abar OT, et al. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. Hepatology. 2007 Aug;46(2):297-306.

Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life inpatients with cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007 Mar;45(3):549-59.

Suzuki A, Lymp J, Donlinger J, Mendes F, Angulo P, Lindor K. Clinical predictors for hepatocellular carcinoma in patients with primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2007 Feb;5(2):259-64. Epub 2006 Dec 15.

U.S. Preventive Services Task Force. Screening for hemochromatosis: recommendation statement. Ann Intern Med. 2006 Aug 1;145(3):204-8.

Whitlock EP, Garlitz BA, Harris EL, Beil TL, Smith PR. Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2006 Aug 1;145(3):209-23.

Review Date:
8/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Asthma in adults

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

In This Report

Highlights
Introduction
Symptoms
Causes
Prognosis
Risk Factors
Diagnosis
Treatment
Quick-Relief Medications...
Long-Term Relief Medication...
Other Treatments
Managing Asthma
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

In 2007, the FDA requested the manufacturers of omalizumab (Xolair) to include a “boxed warning” emphasizing that this drug may cause a severe and life-threatening allergic reaction (anaphylaxis). Omalizumab is approved for patients who have moderate-to-severe asthma related to allergies and whose symptoms are not controlled by inhaled corticosteroids. It is given by injection in a doctor’s office every 2 - 4 weeks. The warning indicates that patients may develop anaphylaxis after any dose of omalizumab, even if they had no reaction to the initial shot. Health care providers need to observe patients carefully for 2 hours after they receive an omalizumab injection. However, because an allergic reaction can occur up to 24 hours after the injection, patients need to know the signs and symptoms of anaphylaxis and how to self-administer emergency treatment.

Anaphylaxis symptoms include:

Difficulty breathing
Chest tightness
Dizziness
Fainting
Itching and hives
Swelling of the mouth and throat

Drug Approval

In 2006, the FDA approved budesonide/formoterol (Symbicort). Symbicort combines a corticosteroid and a long-acting beta2-agonist into a single inhaler.

Long-Acting Beta2-Agonists

Long-acting beta2-agonist drugs, such as salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer), may worsen asthma symptom severity and increase the risk for asthma-related death, indicates a 2006 review in the Annals of Internal Medicine.
Products that contain salmeterol and formoterol now have strengthened warning labels detailing these risks.

Asthma and Heartburn

Studies have suggested an association between heartburn, also known as gastroesophageal reflux disease (GERD), and asthma that gets worse at night (nocturnal asthma). A 2006 study tested whether a proton pump inhibitor drug might help improve morning breathing in patients who suffer from these two conditions. The results suggested that the drug provided only a moderate benefit.

Introduction

The word asthma originates from an ancient Greek word meaning panting. Essentially, asthma is an inability to breathe properly. When any person inhales, the air travels through the following structures:

Air passes into the lungs and flows through progressively smaller airways called bronchioles. The lungs contain millions of these airways.
All bronchioles lead to alveoli, which are microscopic sacs where oxygen and carbon dioxide are exchanged.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Asthma is a chronic condition in which these airways undergo changes when stimulated by allergens or other environmental triggers. Such changes appear to be two specific responses:

The hyperreactive response (also called hyperresponsiveness)
The inflammatory response

These actions in the airway cause patients to cough, wheeze, and experience shortness of breath (dyspnea), the classic symptoms of asthma.

In the hyperreactive response, smooth muscles in the airways of the lungs constrict and narrow excessively in response to inhaled allergens or other irritants. Everyone's airways respond by constricting when exposed to allergens or irritants, but a special hyperreactive response occurs in people with asthma:

When people without asthma breathe in and out deeply, the airways relax and open to rid the lungs of the irritant.
When people with asthma try to take those same deep breaths, their airways do not relax and narrow, causing patients to pant for breath. Smooth muscles in the airways of people with asthma may have a defect, perhaps a deficiency in a critical chemical that prevents the muscles from relaxing.

The hyperreactive stage is followed by the inflammatory response, which generally contributes to asthma in the following way:

In response to allergens or other environmental triggers, the immune system delivers white blood cells and other immune factors to the airways.
These so-called inflammatory factors cause the airways to swell, to fill with fluid, and to produce a thick sticky mucus.
This combination of events results in wheezing, breathlessness, inability to exhale properly, and a phlegm-producing cough.

Click the icon to see an image of a normal bronchiole versus an asthmatic bronchiole.

Inflammation appears to be present in the lungs of all patients with asthma, even those with mild cases, and plays a key role in all forms of the disease.

Symptoms

Asthma symptoms vary in severity from occasional mild bouts of breathlessness to daily wheezing that persists despite taking large doses of medication. After exposure to asthma triggers, symptoms rarely develop abruptly but progress over a period of hours or days. Occasionally, the airways have become seriously obstructed by the time the patient calls the doctor.

The classic symptoms of an asthma attack include:

Wheezing when breathing out is nearly always present during an attack. Usually the attack begins with wheezing and rapid breathing, and, as it becomes more severe, all breathing muscles become visibly active.
Shortness of breath (dyspnea). Shortness of breath is a major source of distress in patients with asthma. However, the severity of this symptom does not always reflect the degree to which lung function is impaired. Some patients are not even aware that they are experiencing shortness of breath. Such patients are at particular risk for very serious and even life-threatening asthma attacks, since they are less conscious of symptoms. Those at highest risk for this effect tend to be older, female, and to have had the disease for a longer period of time.
Coughing. In some people, the first symptom of asthma is a nonproductive cough. Some patients find this cough even more distressing than wheezing or sleep disturbances.
Chest tightness or pain. Initial chest tightness without any other symptoms may be an early indicator of a serious attack.
Neck muscles may tighten, and talking may become difficult or impossible.
Rapid heart rate.
Sweating.
Chest pain occurs in about 75% of patients. It can be very severe, although the pain's intensity is not necessarily related to the severity of the asthma attack itself.

The end of an attack is often marked by a cough that produces thick, stringy mucus. After an initial acute attack, inflammation lasts for days to weeks, often without symptoms. (The inflammation itself must still be treated, however, because it usually causes relapse.)

Causes

Asthma has dramatically risen worldwide over the past decades, particularly in developed countries, and experts are puzzled over the cause of this increase. The mechanisms that cause asthma are complex and vary among population groups and even from individual to individual. Many asthma sufferers have allergies, and some researchers are targeting common factors in both these conditions. Not all people with allergies have asthma, however, and not all cases of asthma can be explained by allergic response.

Asthma is most likely to be caused by a convergence of factors that can include genes and various environmental and biologic triggers (infections, dietary patterns, hormonal changes in women, and allergens).

Nearly half of adults with asthma have an allergy-related condition, which, in most cases developed first in childhood. (In patients who first develop asthma during adulthood, the allergic response usually does not play a strong causal role.) Important irritants or allergens include:

Dust mites, specifically mite feces, which are coated with enzymes that contain a powerful allergen. These are the primary allergens in the home.
Animal dander.
Pollen. An asthma attack from an allergic response to pollen is more likely to occur during extreme air changes, such as thunderstorms. Major weather changes, such as El Nino, can affect the timing of allergy seasons. For example, in 1998, when the effects of El Nino were very strong, allergy and asthma attacks occurred earlier and were markedly increased.
Molds. A 2002 study suggested that molds might produce a worse asthma attack in adults than other allergens.
Fungi.
Cockroaches. Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.
Fossil Fuels. Certain chemicals may trigger allergic rhinitis. Some experts believe that refined fossil fuels, such as diesel fuel and particularly kerosene, may be important triggers for allergic rhinitis. And, in people who already have allergies or asthma, exposure to such fossil fuels may worsen symptoms.

The Allergic Process. The allergic process, called atopy, and its connection to asthma is not completely understood. It involves various airborne allergens or other triggers that set off a cascade of events in the immune system leading to inflammation and hyperreactivity in the airways. One description is as follows:

The conductor in an orchestra of immune factors that contribute to allergies and asthma appears to be a category of white blood cells known as helper T cells, in particular a subgroup called Th2 cells.
Th2 cells overproduce interleukins (ILs), immune factors that are molecular members of a family called cytokines, which are involved in the inflammatory process.
Interleukins 4, 9, and 13 may be responsible for a first-phase asthma attack. These interleukins stimulate the production and release of antibody groups known as immunoglobulin E (IgE). (People with both asthma and allergies appear to have a genetic predisposition for overproducing IgE.)
During an allergic attack, these IgE antibodies can bind to special cells in the immune system called mast cells, which are generally concentrated in the lungs, skin, and mucous membranes. This bond triggers the release of several active chemicals, importantly potent molecules known as leukotrienes. These chemicals cause airway spasms, overproduce mucus, and activate nerve endings in the airway lining.
Another cytokine, interleukin 5, appears to contribute to a late-phase inflammatory response. This interleukin attracts white blood cells known as eosinophils. These cells accumulate and remain in the airways after the first attack. They persist for weeks and mediate the release of other damaging particles that remain in the airways.

The Immune Response. Researchers are investigating the role that T cells play in asthma. T cells are white blood cells that are involved in the immune response. Researchers had focused on the T cell called type 2 helper (Th2) cells. However, a 2006 breakthrough study in the New England Journal of Medicine suggested that a different type of T cell may play a stronger role in asthma than previously thought.

Researchers discovered that these cells, called natural killer T cells, are far more common in the lungs of people with asthma than in the lungs of healthy people. Natural killer T cells are very rare, but researchers found them in 60% of people with moderate-to-severe persistent asthma. While this research is preliminary, it may explain why corticosteroid drugs do not work well for some patients with asthma: Steroid drugs target Th2 and other inflammatory cells, not natural killer T cells. Researchers think that further investigation of natural killer T cells may lead the way to new types of asthma drugs. If these cells prove to be involved in asthma, then drugs that eliminate them might become an important new treatment.

Over the course of years the repetition of the inflammatory events involved in asthma can cause irreversible structural and functional changes in the airways, a process called remodeling. The remodeled airways are persistently narrow and can cause chronic asthma. Researchers are trying to determine how this process occurs:

Interleukins. Some researchers are looking at potent immune factors, including interleukins 11 and 13. They have been linked to a number of processes possibly involved in remodeling, including scarring in the airways and overgrowth of cells in the smooth muscles that line the airways.

Growth Factors. Compounds known as vascular endothelial growth factor (VEGF) have been observed in the airways of patients with asthma. VEGF is a powerful promoter of cell growth in blood vessel linings, and some researchers believe it may be major factor in remodeling.

About one-third of all persons with asthma share this condition with another member of their immediate family. Asthma may be more likely to pass to children from their mother than from their father. Both allergies and asthma are strongly associated with hereditary factors, sharing certain genetic markers, but they are not always inherited together.

Research on the genetics of these conditions is confusing. Of some significant promise, researchers have identified a gene (ADAM33), which has been linked to asthma. The gene regulates one of the enzymes called metalloproteases, which are involved with the smooth muscle in the airway. A mutation of this gene could play a role in airway changes that occur after inflammation.

Hormones or changes in hormone levels appear to play a role in the severity of asthma in women.

Menstrual-Related Asthma. Between 30 - 40% of women with asthma experience fluctuations in severity that are associated with their menstrual cycle. One study indicated that women with menstrually associated asthma tend to have the following characteristics:

Older age
Had asthma for a long time
Had severe asthma attacks that were likely to occur 3 days before and 4 days into the menstrual period

Oral contraceptives (OCs) theoretically should help asthma sufferers by leveling out hormonal changes, but they do not appear to have much effect. (There have been a few reports of asthma exacerbation with OCs, but these are uncommon events.)

Asthma during Pregnancy. During pregnancy, one-third of women with asthma suffer more from the condition, one-third suffer less, and one-third experience no difference in severity. Some studies suggest that expectant mothers carrying a female baby tend to have more severe asthma symptoms than do those who are bearing a male.

Menopause and Asthma. Around the time of menopause (called perimenopause) when estrogen declines, the risk for hospitalization in women with asthma increases fourfold compared to previous years. Studies have not demonstrated that hormone replacement therapy (HRT), which contains estrogen, has much benefit.

About 10% of adults and some fewer children have aspirin-induced asthma (AIA). With this condition, asthma gets worse when patients take aspirin. Aspirin is one of the drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs). Although aspirin is used to reduce inflammation in other disorders, it appears to have the opposite effect in many asthma cases. It is not wholly known why this occurs. AIA often develops after a viral infection. It is a particularly severe asthmatic condition, associated with up to 25% of asthma-related hospitalizations. In about 5% of cases, aspirin is responsible for a syndrome that involves multiple attacks of asthma, sinusitis, and nasal congestion. Such patients also often have polyps (small benign growths) in the nasal passages.

Patients with aspirin-induced asthma (AIA) should avoid aspirin and most likely other NSAIDs, including ibuprofen (Advil) and naproxen (Aleve).

Acetaminophen (Tylenol) has been the traditional alternative for relief of minor pain for patients who are aspirin-sensitive. Unfortunately, recent evidence has muddied these recommendations. Some asthmatic episodes have been linked to high consumption of acetaminophen among adults.

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath.

Asthma occurs primarily at night (nocturnal asthma) in as many as 75% of patients with asthma. Attacks often occur between 2 and 4 a.m. Factors that might play role in nocturnal asthma may include one or more of the following:

Chemical and temperature changes in the body during the night that increase inflammation and narrowing of the airways
Delayed allergic responses from exposure to allergens during the day
The wearing off of inhaled medications toward the early morning
An increase in acid reflux (back up of stomach acid) that causes airways to narrow
Postnasal drip that occurs during sleep
Conditions relating to sleep, such as sleep apnea or sleeping on one's back, which may worsen any asthma attack that occurs at night

Some experts believe that nocturnal asthma may actually be a unique form, with its own specific biologic mechanisms that occur only at night and which reduce natural steroid hormones (which block inflammation).

Infections. The role of infections in asthma is complicated. Respiratory infections may play a role in some cases of adult-onset asthma, but may be protective against asthma in small children. (In both children and adults with existing allergic asthma, however, an upper respiratory tract infection often worsens an attack.)

Researchers are particularly interested in the organisms Chlamydiapneumoniae and Mycoplasmapneumoniae adenovirus. They are major causes of both mild and serious respiratory infections and are becoming important suspects in many cases of severe adult asthma. (If such respiratory infections occur in young children, they are unlikely to affect adult-onset asthma.)

In one study, patients whose asthma occurred after infections had more severe conditions than those whose asthma was due to other causes. The infection-initiated asthma, however, lasted only 5.6 years compared to 13.3 years in the non-infection group.

In any age group, respiratory infections worsen existing asthma in people who have it already. Rhinovirus (the common cold virus) has been reported to be the most common infection associated with asthma attacks. In one study, it was associated with 61% of asthma exacerbations in children and 44% in adults. Some research suggests that colds promote allergic inflammation and increase the intensity of airway responsiveness for weeks.

GERD. At least half of patients with asthma have gastroesophageal reflux disease (GERD), the cause of heartburn. It is not entirely clear which condition causes the other or whether they are both due to common factors.

Heartburn is a condition where the acidic stomach contents back up into the esophagus causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux that causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.

Some theories for the causal connection between GERD and asthma are:

Acid leaking from the lower esophagus in GERD stimulates the vagus nerve, which runs through the gastrointestinal tract. This stimulated nerve triggers the nearby airways in the lung to constrict, causing asthma symptoms.
Acid backup that reaches the mouth may be inhaled into the airways (aspirated). Here, the acid triggers a reaction in the airways that cause asthma symptoms.

GERD is sometimes hard to detect and might be a contributor in the following patients:

Those who do not respond to asthma treatments
Those whose asthma attacks follow episodes of heartburn
Those whose attacks worsen after eating or exercise
Those whose coughs follow episodes of acid reflux. (One study found that GERD was associated with about half of the episodes of coughs and wheezes in patients with asthma.)

Treating GERD symptoms with anti-acid drugs may resolve asthma in some (but not all) patients who share both conditions. A small 2005 study found that while GERD was common in patients with asthma, treatment of GERD had no effect on asthma symptoms. A 2006 study indicated that the proton pump inhibitor esomeprazole (Nexium) slightly helped patients who had both GERD and asthma symptoms that occurred at night. [See In-Depth Report #85: Heartburn and gastroesophageal reflux disease.]

Sinusitis. Almost half of children and adults with allergic asthma have sinus abnormalities, and in various studies, between 17 - 30% of patients with asthma develop true sinusitis. The presence of sinusitis, however, does not appear to increase the severity of asthma.

Click the icon to see an image of sinusitis.

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath. This condition generally occurs in children and young adults, most often during intense exercise in cold dry air. Symptoms are generally most intense about 10 minutes after exercising and then gradually resolve.

EIA is triggered only by exercise and is distinct from ordinary allergic asthma in that it does not produce a long duration of airway activity, as allergic asthma does. (It should be noted that some people have both forms of asthma.) People who have only EIA do not appear to require long-term maintenance therapy. A study of military recruits with EIA also reported that the condition does not hinder a person's overall physical performance.

Medications

Cromolyn, a mild anti-inflammatory drug, or short-acting beta2-agonists have been the treatments of choice for preventing EIA. Newer approaches for people who work out regularly include pretreatment with long-acting beta2-agonists, such as salmeterol (Serevent), or the regular use of inhaled corticosteroids.

Hints for Reducing EIA

EIA occurs only after exercise and is more likely to occur with regularly paced activities in cold, dry air. The following are some suggestions for reducing its impact:

Warm-up and cool-down periods are important.
Patients with EIA might do better with activities that involve short bursts of exercise (tennis, football) than with exercises involving long-duration regular pacing (cycling, soccer, and distance running).
Breathing through a scarf or through the nose helps warm up the airways.
Some evidence suggests that restricting dietary salt might help reduce EIA.

Click the icon to see an image of exercise-induced asthma.

Prognosis

About 450,000 American adults are admitted to an emergency room with asthma each year. The number of deaths from asthma increased from about 2,900 in 1908 to a high of 5,667 in 1996. The numbers appear to be declining slightly, and in 2002 about 4,260 people died because of asthma. Death from asthma is still a very uncommon event, considering that an estimated 20 million people in the U.S. have this condition. Most deaths from asthma, even when they occur in elderly adults, are preventable. It is very rare for a person who is receiving proper treatment to die of asthma. And, studies suggest that the use of inhaled corticosteroids can reduce the risk for death by 90%. In spite of this and similar research, these important drugs are greatly underused.

About 55% of U.S. deaths from asthma occur among the elderly (over age 65), and an estimated 25% occur in adults aged 45 - 64. Women have a higher risk for fatal asthma than men. Being poor is also a significant risk factor for severe asthma. Hispanics and African Americans are at higher risk for death from asthma than Caucasians. Other specific risk factors for fatal asthma include:

Previous history of respiratory failure
Frequent visits to the emergency room
Lack of continuous care and poor compliance with medications
Having stopped treatment, particularly withdrawal from corticosteroids
Having an emotional or psychiatric disorder. (Some evidence suggests that depression, anxiety, and stressful life situations can worsen asthma.)
Being a drug abuser
Being in a lower socioeconomic and educational group

The following signs and symptoms may indicate a life-threatening situation:

As the chest labors to bring enough air into the lungs, breathing often becomes shallow.
Lacking sufficient oxygen, the skin becomes bluish.
The flesh around the ribs of the chest appears to be sucked in.
The patient may begin to lose consciousness.

Asthma often progresses very slowly to a serious condition or may develop to a fatal or near-fatal attack within a few minutes. It is very difficult to predict when an attack will become very serious.

It should strongly be noted that early symptoms or lack thereof do not always reflect the ultimate severity of an attack. In fact, some studies suggest that people at high risk for fatal or near-fatal asthma attacks are those with poor awareness of their own reduced ability to breathe and who are therefore slow in seeking help. Those at highest risk for this effect tend to be older, female, and have had the disease for a longer period of time. Monitoring peak flow rates is an important management component since it provides a more accurate assessment of lung function than symptoms alone.

The severity of asthma is graded using the following categories: mild intermittent and mild, moderate, and severe persistent. A patient in any of these categories, even mild intermittent, can still experience a severe and even life-threatening attack. In fact, according to one report, 30% of asthma deaths occur in patients with mild asthma.

Asthma is usually chronic, although it occasionally goes into long periods of remission. Long-term outlook generally depends on severity:

In mild-to-moderate cases, asthma can improve over time, and many adults even become symptom free.
Even in some severe cases, adults may experience improvement depending on the degree of obstruction in the lungs and the timeliness and effectiveness of treatment.
In about 10% of severe persistent cases, changes in the structure of the walls of the airways lead to progressive and irreversible problems in lung function, even in aggressively treated patients.

Lung function declines faster than average in people with asthma, particularly in those who smoke and in those with excessive mucus production (an indicator of poor treatment control). Overall, one study reported that 72% of men and 86% of women with asthma had symptoms 15 years after an initial diagnosis. Only 19% of these people, however, were still seeing a doctor, and only 32% used any maintenance medication.

Patients who develop occupational asthma often experience asthmatic symptoms for years, even after avoiding the harmful triggers. Improvement does occur over time in most people who leave such jobs.

Emotional Problems. Even when it is not life-threatening, asthma is debilitating and frightening. It significantly lowers the quality of life.

Sleep Disorders. Sleeplessness and daytime sleepiness are common problems. Studies indicate that between 80 - 93% of people with asthma have sleeping problems about three times a week. In one poll, 40% missed work an average of 11 days a year because of sleep disturbance. Asthma has been associated with snoring and obstructive sleep apnea, a condition in which blockage of the upper airway causes the sleeper to temporarily stop breathing, then resume with a gasp, often many times during each hour of sleep.

Asthma and Pregnancy. Uncontrolled asthma in pregnant women puts them at higher risk for complications that can include early labor, hypertension, gestational diabetes, and hemorrhage. Asthma also places the babies at risk for lower birth weight and breathing disorders. Teenage mothers with asthma face higher risks than older women. Fortunately, studies indicate that most asthma drugs are safe to take during pregnancy, and good control of asthma reduces these risks to normal levels.

New guidelines released in 2005 by the National Asthma Education and Prevention Program (NAEPP) emphasize that most asthma medications are safe for pregnant women. The guidelines recommend that pregnant women with asthma have albuterol available at all times. Inhaled corticosteroids should be used for persistent asthma. Patients whose persistent asthma does not respond to standard dosages of inhaled corticosteroids may require a higher dosage or the addition of a long-acting beta agonist to their drug regimen. For severe asthma, oral corticosteroids may be required. The NAEPP notes that while it is not clear if oral corticosteroids are safe for pregnant women, uncontrolled asthma poses an even greater risk for a woman and her fetus.

Heart Disease. There have been some reports of an association between asthma and a heightened risk for heart disease. Some experts believe that the inflammatory process may be the common factor linking the two conditions, although there is no evidence to date confirming any causal association.

Risk Factors

According to a major national 2001 survey, American adults have a 10% lifetime risk for developing asthma. As of 2002, an estimated 20 million adults had the disorder. Between 1980 - 1996 the prevalence of asthma increased by nearly 74%, but it may be stabilizing. Other respiratory diseases, sinusitis, and ear infections are also on the rise, suggesting that airborne or environmental factors may be at work that affects all of these conditions, including asthma.

Before puberty, asthma occurs more often in males, but after adolescence, it appears to be more common in females. In adults with similar cases of actual airway obstruction, women are likely to report more severe symptoms than men are. In addition, women may be at much greater risk of death from asthma than men.

In both adults and children, the incidence of obesity and asthma has been increasing in parallel over recent years. Studies report a strong association between the two conditions. Some experts suggest that excess weight pressing on the lungs may trigger the hyperreactive response in the airways typical of asthma. Others believe that asthma leads to obesity by inhibiting physical activity, although several studies have found no difference in activity levels between people with or without asthma. Some studies suggest that many obese people may be misdiagnosed as having asthma when in fact they are simply short of breath, possibly because of the increased effort required for breathing.

In any case, there is evidence that losing weight can relieve asthma symptoms. Some evidence also suggests that people who are overweight (body mass index greater than 25) have more difficulty getting their asthma under control. Weight loss in anyone who is obese and has asthma or shortness of breath reduces airway obstruction and improves lung function. [See In-Depth Report #53: Weight control and diet.]

In one study of elderly people with severe adult-onset asthma, smoking was the most significant risk factor for developing this condition. Smoking, in any case, contributes to decline in lung function in everyone.

Urban Life and Poverty. African Americans have higher rates of asthma than Caucasians or other ethnic groups. They are also more likely to die of the disease. Ethnicity and genetics, however, are less likely to play a role in these differences than socioeconomic differences, such as having less access to optimal health care. Poverty is a consistent risk factor in most studies. Both the elderly and the urban poor have the highest risk for severe asthma and death. Urban life, in fact, has been associated with a higher risk for asthma in all income groups and among both children and adults. Twin studies also suggest that people who have lower educational levels (as well as those who exercise less) are at higher risk for adult-onset asthma, further suggesting a link to lower economic status.

Geographical Differences. Asthma rates vary widely among different populations regardless of socioeconomic or other factors. For example, asthma and hospitalization rates are dramatically higher in New York Puerto Ricans than in Hispanic Americans who live in Los Angeles or the Southwest. Among the U.S. states, rates are lowest in Louisiana and highest in Maine.

There are significant differences among nations. In a 2001 study of 22 nations, the countries with the highest asthma rates were Britain, Ireland, Australia, New Zealand, and the U.S. (According to another study, asthma rates are also significantly higher in Canadian adults than they are in comparable European groups.) Low rates were reported in Iceland, Norway, Spain, Germany, Italy, Algeria, India, and Eastern European nations. The reasons for these variations are still unknown.

Diagnosis

When asthma is suspected, the patient should describe for the doctor any pattern related to the symptoms and possible precipitating factors, including:

Whether symptoms are more frequent during the spring or fall (allergy seasons).
Whether exercise, a respiratory infection, or exposure to cold air has ever triggered an attack.
Any family history of asthma or allergic disorders, such as eczema, hives, or hay fever.
Any occupational or long-term exposure to chemicals. Early detection of occupational asthma is very important. If symptoms improve on weekends and vacation and are worse at work, the job is likely to be the source of the asthma, although this is not always the case. Asthma is common, and exacerbation at work may be coincidental.

A number of disorders may cause some or all of the symptoms of asthma:

Asthma and chronic obstructive lung diseases (chronic bronchitis and emphysema) affect the lungs in similar ways and, in fact, may all be present in the same person. Unlike other chronic lung conditions, asthma usually first appears in patients younger than age 30 and with chest x-rays that are normal. Still, it may be difficult to distinguish these disorders in some adults with late onset asthma.
Panic disorder can coincide with asthma or be confused with it.
Gastroesophageal reflux disorder (GERD) is a common companion in asthma and may affect treatment.
Other diseases that must be considered during diagnosis are pneumonia, bronchitis, severe allergic reactions, pulmonary embolism, cancer, heart failure, tumors, psychosomatic illnesses, and certain rare disorders (such as tapeworm and trichomoniasis).

If symptoms and a patient's history suggest asthma, the doctor will usually perform tests known as pulmonary function tests to confirm the diagnosis and determine the severity of the disease.

Using a spirometer, an instrument that measures the air taken into and exhaled from the lungs, the doctor will determine several values:

1. Vital capacity (VC), which is the maximum volume of air that can be inhaled or exhaled.

2. Peak expiratory flow rate (PEFR), commonly called the peak flow rate, which is the maximum flow rate that can be generated during a forced exhalation.

3. Forced expiratory volume (FEV1), which is the maximum volume of air expired in one second.

Spirometry is a painless study of air volume and flow rate within the lungs. Spirometry is frequently used to evaluate lung function in people with obstructive or restrictive lung diseases such as asthma or cystic fibrosis.

If the airways are obstructed, these measurements will fall. Depending on the results, the doctor will take the following steps:

If measurements fall, the doctor typically asks the patient to inhale a bronchodilator. This drug is used in asthma to open the air passages. The measurements are taken again. If the measurements are more normal, the drug likely has cleared the airways and a diagnosis of asthma is strongly suspected.
If measurement results fail to show airway obstruction, but asthma is still suspected, the doctor may perform a challenge test. This involves administering a specific drug (histamine or methacholine) that usually increases airway resistance only when asthma is present. The challenge test may be quite useful in ruling out occupational asthma. It is not always accurate, particularly in patients whose only symptom is persistent coughing.
Administering cold air is another method for inducing airway resistance. This test is very accurate for ruling out asthma, but it is not sensitive enough to accurately identify adults who actually have asthma.

The patient may be given skin or blood allergy tests, particularly if a specific allergen is suspected and available for testing. Allergy skin tests may be the best predictive tests for allergic asthma, although they are not recommended for people with year-round asthma.

Click the icon to see an image of allergy testing.

Tests that either rule out other diseases or obtain more information about the causes of asthma include:

A complete blood count.
Chest and sinus x-rays.
Computed tomography (CT) scans. CT scans may be helpful in certain cases, such as for determining wall thickness in airways in patients who are difficult to treat, which could signify a higher risk for lung damage.
Examination of the patient's sputum for eosinophils (white blood cells that in high levels are associated with severe allergic asthma). One 2002 study suggested that treatment goals based on achieving a normal eosinophil count might effectively manage asthma.
Researchers are investigating measurements of certain chemicals in sputum or exhaled air that indicate airway inflammation. Such chemical markers include nitric oxide and hydrogen peroxide. For example, high levels of nitric oxide in exhaled air is proving to be a simple and noninvasive way of diagnosing asthma.
If aspirin-induced asthma (AIA) is suspected, a non-invasive test called acoustic rhinometry may be useful. A solution of lysine acetylsalicylic acid (L-ASA) is instilled into the patient's nostril. Patients who experience symptoms such as sneezing, itching, congestion, and secretion are likely to have AIA.

Treatment

Treating an Acute Attack in the Hospital. An acute attack may require hospitalization. Laboratory tests, an electrocardiogram (ECG), and a chest x-ray are performed to determine lung function, oxygen levels, and other indications of severity or rule out other causes. Depending on the results, the following treatments may be given:

Beta2-agonists are the standard therapy. They may be administered with a nebulizer (a device that administers the drug in a fine spray) or given hourly with an inhaler. Studies are suggesting the use of an inhaler is equally or possibly more effective than a nebulizer. Intravenous delivery is not recommended in most cases.
A corticosteroid (commonly called a steroid) given within the first hour helps reduce the need for hospitalization. Steroids are typically administered intravenously or as an injection in adults. Lower doses work as well as higher ones in these situations.
Intravenous magnesium opens airways and is an important emergency treatment for patients with very severe asthma.
Oxygen is usually administered, and can be life-saving in severe cases.
In life-threatening situations, the patient may require mechanical ventilation.
Antibiotics are not useful for asthma attacks if there is no strong evidence of the presence of a bacterial infection. (Viral infections, most often colds and the flu, are more likely to trigger an asthma attack. In such cases, antibiotics do not appear to be beneficial and may have adverse effects.)

Discharge and Relapse After Hospitalization. It typically takes 3 - 4 hours to determine if a patient can be safely sent home or if they need to stay in the hospital. Patients are generally discharged under the following circumstances:

When symptoms are gone or are minimal, and
The peak expiratory flow rate is 70% or more of the predicted rate

Discharged patients generally take oral corticosteroids for 5 - 7 days. Despite reasonable precautions, about 20% of patients relapse within 2 weeks, although the risk is very low if they keep taking their medication after they leave.

Avoiding allergens, following appropriate drug treatments, and home monitoring are key elements in preventing dangerous asthma attacks and hospitalization. A combination of medications is important for both treating and preventing asthma attacks. In addition, good communication between the doctor and patient is a key factor in a successful management program. Written action plans, which instruct individual patients how to properly respond to changes in their unique symptoms, are a very important element in successful self-management of asthma.

Medications for asthma fall into two categories:

Rescue Medication. Medications that open the airways (bronchodilators, or inhalers) are used to quickly relieve any moderate or severe asthma attack. These drugs are usually short-acting beta-adrenergic agonists (beta2-agonists). Other drugs used in special cases include corticosteroids taken by mouth and anticholinergic drugs. None of these drugs have any effect on the disease process itself. They are only useful for treating symptoms.
Maintenance Medication. Simply coping with asthma symptoms without also controlling the damaging inflammatory response is a common and serious error. For adults and children over age 5 with moderate-to-severe persistent asthma, experts now recommend inhaled corticosteroids and long-acting beta2-agonists.

Patients can greatly reduce the frequency and severity of asthma attacks by understanding the difference between coping with asthma attacks and controlling the disease over time. Unfortunately, many patients do not understand the difference between medications that provide rapid short-term relief and those that are used for long-term symptom control. Many patients with moderate or severe asthma overuse their short-term medications and underuse their corticosteroid medications. The overuse of bronchodilators can have serious consequences; not using steroids can lead to permanent lung damage.

Patients need to understand that asthma symptoms can change quickly over time and that treatment strategies may need to change. In 2005, the two leading U.S. allergy associations published joint guidelines on controlling asthma. The guidelines emphasize that asthma treatment decisions need to be made on an individual basis. It is important that patients have a close relationship with their doctor. The doctor needs to evaluate a patient’s asthma symptoms at each and every visit to determine if there should be any changes in medication.

According to the guidelines, asthma management is classified as either “well-controlled” or “not well-controlled.” Your doctor may need to change some of your medications, or increase or decrease the dosage, depending on whether your asthma is well-controlled or not well-controlled.

These are the signs of well-controlled asthma:

Asthma symptoms occur twice a week or less
Rescue bronchodilator medication is used twice a week or less
Symptoms do not cause nighttime or early morning awakening
Symptoms do not limit work, school, or exercise activities
Peak flow meter readings are normal or the patient’s personal best
Both the doctor and the patient consider the asthma to be well controlled

Most asthma drugs are inhaled using various forms of inhalers or nebulizers. Inhaled drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. The basic devices are the metered-dose inhaler (MDI), breath-actuated inhalers, dry powder inhalers, and nebulizers.

MDIs have used chlorofluorocarbons (CFCs) as their propellants. CFCs are damaging to the environment. CFCs are now being replaced with other propellants (such as hydrofluoroalkane) that are equally effective to CFCs, are environmentally safe, and do not chill the device as CFCs do. Devices that don't use propellants at all are also now available.

Metered-Dose Inhaler. The standard device for administering any asthma medication has been the metered-dose inhaler (MDI). This device, particularly when used with a holding chamber, allows precise doses to be delivered directly to the lungs.

Click the icon to see an image of a holding chamber.

MDI-delivered drugs must be used regularly as prescribed, and the patient carefully trained in their use, for the drugs to be effective and safe. Some patients hold the MDI too close to their mouths, or even inside them. Others may exhale too forcefully before inhalation. The holding chamber, or spacer, allows the patient additional time to inhale the medication, improving delivery. They vary, however, in their ability to deliver medication. Often MDIs continue to deliver propellant after the drug has been used up. Patients should track their medicine and throw the device away when the last dose has been administered.

Click the icon to see an illustrated series detailing metered dose inhaler use.

Breath-Actuated Inhalers. Breath-actuated rotary inhalers (Easi-Breathe and Autohaler) deliver the drug directly to the back of the throat as the user inhales. Their primary advantage over the MDI is their ease of use. They also do not use CFCs as propellants. In comparison studies, patients have been very successful with the breath-actuated inhalers.

Dry Powder Inhalers. Dry powder inhalers (DPIs) deliver a powdered form of beta2 agonists or corticosteroids directly into the lungs. They also do not use CFCs. Such devices include Rotahaler, Spinhaler, Turbohaler, Clickhaler, Easyhaler, Diskhaler, Discus, Twisthaler, Spiros, and others. DPIs are as effective as the older devices, and generally have a better taste and are easier to manage. They may differ among themselves, however, in their ability to deliver drugs into the airways. In one study, for example, the Turbohaler was easier to use than the Diskhaler, achieving better delivery. The Discus is another effective DPI. It has a dose counter and protects against exhalation effects.

Humidity or extreme temperatures can affect these inhalers' performance, so they should not be stored in humid places (bathroom cabinets) or locations subject to high temperatures (glove compartments during summer months).

Dry-powder may cause tooth erosion, and children are advised to rinse their mouths out right after using a DPI and to brush twice a day with a fluoride toothpaste.

Other Hand-Held Inhalers. Respimat delivers a fine-mist spray that is created by forcing the liquid medication through nozzles. It does not use any propellant.

Nebulizers. A nebulizer is a device that administers the drug in a fine spray that the patient breathes in. They are mostly used in hospital settings or when the patient cannot use an inhaler. Nebulizers may be important for delivering newer drugs used in asthma treatment.

Click the icon to see an illustrated series detailing nebulizer use.

People who self-manage their asthma using daily monitoring of peak air flow and adjusting their medications as needed have fewer hospitalizations, fewer unplanned doctors visits, and, generally, a better quality of life than those who rely only on the occasional doctor or emergency room visit to control symptoms. Doctors recommend that patients with even mild asthma monitor their own conditions.

In general, monitoring involves the following steps:

A peak flow meter is the standard monitoring device for measuring peak expiratory flow rate (PEFR).

Click the icon to see an image of a peak flow meter.

Patients with severe asthma should take PEFR readings two or three times a day. The overall goal should be to achieve less than a 20% (and ideally only 10%) variation in readings between evening and morning rates. For mild-to-moderate asthma, a single determination each morning usually suffices, but patients should check with their doctors.
It is important to use the meter at the same times each day and to stand or sit in the same position to keep an accurate record.
Patients should keep an ongoing record of their peak flow readings to help them detect worsening of their condition.
They should also record attacks, exposure to any allergens or triggers, and medications taken.
After about 2 months, patients and doctors can use the recorded data for administering medications effectively and to recognize problems before they become serious.

In general, many people fail to monitor their asthma. Experts believe that, ideally, portable monitors should be available to measure forced expiratory volume (FEV1), a more accurate gauge of lung function, and the results should be electronically transmitted to the doctor.

New monitoring devices are showing promise in accomplishing one or more of these goals, although they are not covered by most insurers. For example, the AirWatch is a handheld digital monitor that measures and displays the rate of airflow and compares it to the rates from previous days. Once a month, or whenever there is a problem, the patient plugs the device into a standard telephone jack, and the daily readings are sent to an automated data center that creates tables and charts for the patient and the doctor.


Medication Purpose	Drug Class	Generic Name	Brand Names	Administration
Quick-Relief Medications (control acute attacks)	Short-Acting Beta2 Agonists	Albuterol	Proventil, Ventolin, AccuNeb	Inhaler, nebulizer
		Levalbuterol	Xopenex	Nebulizer
		Metaproterenol	Alupent	Inhaler
		Pirbuterol	MaxAir	Inhaler
		Ipratropium / Albuterol	Combivent	Inhaler
	Anticholinergics	Ipratropium	Atrovent	Inhaler
		Tiotropium	Spiriva	Inhaler
	Systemic Corticosteroids	Cortisone	Cortone	Pill
		Dexamethasone	Decadron	Pill
		Hydrocortisone	Cortef	Pill
		Methylprednisolone	Medrol	Pill
		Prednisolone	Orapred, Prelone	Syrup
		Prednisone	Various	Pill
		Triamcinolone	Aristocort	Pill
Long-Term Relief Medications (prevent attacks and control chronic symptoms)	Inhaled Corticosteroids	Beclomethasone	QVAR	Inhaler
		Budesonide	Pulmicort	Inhaler, nebulizer
		Budesonide / Formoterol	Symbicort	Inhaler
		Flunisolide	AeroBid	Inhaler
		Fluticasone	Flovent	Inhaler
		Fluticasone / Salmeterol	Advair	Inhaler
		Mometasone	Asmanex	Inhaler
		Triamcinolone	Azmacort	Inhaler
	Long-Acting Beta2-Agonists	Formoterol	Foradil	Inhaler
		Salmeterol	Serevent	Inhaler
	Anti-inflammatories	Cromolyn	Intal	Nebulizer
		Nedocromil	Tilade	Inhaler
	IgE-inhibitor	Omalizumab	Xolair	Injectable
	Leukotriene Modifiers	Montelukast	Singulair	Pill
		Zafirlukast	Accolate	Pill
		Zileuton	Zyflo	Pill
	Methylxanthine	Theophylline	Uniphyl, Quibron, Theo-24	Pill, syrup

Quick-Relief Medications

These medications quickly control acute asthma attacks.

Beta2-agonists do not reduce inflammation or airway responsiveness but serve as bronchodilators, relaxing and opening constricted airways during an acute asthma attack. They are used alone only for patients with mild and intermittent asthma. Patients with more severe cases should use them in combination with other drugs.

Asthma is a disease in which inflammation of the airways causes airflow into and out of the lungs to be restricted. When an asthma attack occurs, mucus production is increased, muscles of the bronchial tree become tight, and the lining of the air passages swells, reducing airflow and producing the characteristic wheezing sound.

Specific short-acting beta2-agonists include:

Albuterol (Proventil, Ventolin), called salbutamol outside the U.S., is the standard short-acting beta2-agonist in America. Other similar beta2-agonists are isoproterenol (Isuprel, Norisodrine, Medihaler-Iso), metaproterenol (Alupent, Metaprel), pirbuterol (Maxair), terbutaline (Brethine, Brethaire, Bricanyl), and bitolterol (Tornalate). Isoetharine (Bronkometer, Bronkosol) is available in nebulizers.
Newer beta2-agonists, including levalbuterol (Xopenex), have more specific actions than the standard drugs. Studies have indicated that levalbuterol is as effective as albuterol with fewer side effects. The original formulation of Xopenex was administered with a nebulizer. A new metered-dose inhaler formulation became available in late 2005.

Short-acting bronchodilators are generally administered through inhalation and are effective for 3 - 6 hours. They relieve the symptoms of acute attacks, but they do not control the underlying inflammation. If asthma continues to worsen with the use of these drugs, patients should discuss corticosteroids or other drugs to treat underlying inflammation.

Side Effects of Beta2-Agonists. Side effects of all beta2-agonists include the following:

Anxiety
Tremor
Restlessness
Headache
Fast and irregular heartbeats. A doctor should be notified immediately if this side effect occurs, particularly in people with existing heart conditions. Such patients face an increased risk for sudden death from cardiac related causes. This risk is higher with oral or nebulized drugs, but there have also been reports of heart attacks and angina in some patients using inhaled beta2-agonists.

Beta2-agonists have serious interactions with certain other drugs, such as beta-blockers, and patients should tell the doctor about any other medications they are taking. Individuals with diabetes, existing heart disease, high blood pressure, hyperthyroidism, an enlarged prostate, or a history of seizures should take these drugs with caution.

Loss of Effectiveness and Overdose. There has been some concern that short-acting beta2-agonists become less effective when taken regularly over time, increasing the risk for overuse. Over time some patients may become tolerant to many effects of short-acting beta2-agonists. The degree to which this affects the airways is uncertain. In some studies, the duration of action has declined but the peak effect appears to be preserved, making these drugs still useful for acute attacks. Regular use of long-acting beta 2-agonists may reduce the effect of short-acting forms.

A 2005 landmark study suggested that patients’ differing clinical response to albuterol may be based on their genotype. Albuterol targets the beta-adrenergic receptor. In the Beta-Adrenergic Response by Genotype (BARGE) trial, researchers studied the effects of albuterol on patients with two different forms of this receptor. The results suggested that patients with the arginine form of the receptor did not respond to albuterol. These patients’ asthma symptoms actually improved when albuterol was not used. By contrast, patients with the glycine form of the receptor had improved asthma control with albuterol.

Patients who perceive beta2-agonists as being less effective may overuse them. Overdose can be serious and in rare cases even life-threatening, particularly in patients with heart disease.

Inhaled ipratropium bromide (Atrovent) acts as a bronchodilator over time. Ipratropium bromide alone is only modestly beneficial for acute asthma attacks. Moreover, the drug is not approved specifically for asthma. It may, however, have benefits in certain cases:

It may be useful for certain older patients with asthma who also have emphysema or chronic bronchitis.
A combination with a beta2-agonist might be helpful for patients who do not initially respond to treatment with a beta2-agonist alone.

Common oral corticosteroids include prednisone, prednisolone, methylprednisolone, and hydrocortisone. They very effectively reduce inflammation but are generally used only after hospitalization for an acute attack. In some severe cases, they may be used as maintenance.

Adverse effects of prolonged use of oral steroids include cataracts, glaucoma, osteoporosis, diabetes, fluid retention, susceptibility to infections, weight gain, hypertension, capillary fragility, acne, excess hair growth, wasting of the muscles, menstrual irregularities, irritability, insomnia, and psychosis. Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, bisphosphonates, or hormone replacement therapy in post-menopausal women.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

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

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

Long-Term Relief Medications

These medications are taken on a regular basis to prevent asthma attacks and control chronic symptoms.

Corticosteroids, also called glucocorticoids or steroids, are powerful anti-inflammatory drugs. Steroids are not bronchodilators (they do not relax the airways) and have little effect on symptoms. Instead, they work over time to reduce inflammation and prevent permanent injury in the lungs. They can also help prevent asthma attacks from occurring. Many studies have shown that the use of inhaled corticosteroids in patients with moderate-to-severe asthma significantly reduces the rate of rehospitalizations and deaths from asthma.

Inhalation of corticosteroids makes it possible to provide effective local anti-inflammatory activity in the lungs with minimal systemic effects. (By contrast, steroids taken by mouth have considerable side effects throughout the body.) Inhaled corticosteroids are recommended as the primary therapy under the following circumstances:

For any asthmatic condition more serious than occasional episodes of mild asthma. (Low-doses of inhaled steroids may even be safe and effective for some people with mild asthma, particularly those who find themselves using beta2-agonists daily.)
When treatment with bronchodilators is not effective.

Examples of inhaled corticosteroids:

The most recent generation of inhaled steroids include fluticasone (Flovent), budesonide (Pulmicort), triamcinolone (Azmacort and others), and flunisolide (AeroBid). In general, these newer steroids are more powerful than the older generation of inhaled drugs. These steroids are sometimes combined with a long-acting beta2-agonist in a single inhaler.
The FDA approved a new inhaled corticosteroid, mometasone furoate (Asmanex) in 2005.
The older corticosteroid inhalants are beclomethasone (Beclovent, Vanceril) and dexamethasone (Decadron Phosphate Respihaler and others). They are less powerful than the newer steroids when delivered with standard inhalers. New inhaler systems include QVAR, which uses extra fine formulations of beclomethasone to allow deep delivery into the lungs. Such systems may prove to be as effective as the newer, more potent steroids. Beclomethasone is believed to be safe during pregnancy.
Inhalers that combine both long-acting beta2-agonists and corticosteroids are also available. These include Symbicort (budesonide/formoterol), which in 2006 was approved for patients ages 12 years and older.

Traditionally, patients have been advised to take corticosteroids on a daily basis. However, a 2005 study suggested that intermittent corticosteroid therapy may be appropriate for some patients with mild persistent asthma. In the Improving Asthma Control Trial (IMPACT), researchers found that patients with mild persistent asthma who used an inhaled corticosteroid (budesonide) on an as-needed basis to control acute symptoms had similar lung function and quality of life outcomes as patients who used the drug daily. The researchers emphasize that patients with severe asthma should adhere to a daily dosage schedule, and that all patients with asthma should consult with their doctor to discuss any changes in medication regimen.

Optimal timing of the dose is important and may vary depending on the medication. Most of the newer inhaled steroids and even some older ones are now available as a single daily dose.

Inhaled steroids are generally considered safe and effective and only rarely cause any of the more serious side effects reported with prolonged use of oral steroids. Side effects of inhaled steroids are the following:

The most common side effects are throat irritation, hoarseness, and dry mouth. These effects can be minimized or prevented by using a spacer device and rinsing the mouth after each treatment.
Rashes, wheezing, facial swelling (edema), fungal infections (thrush) in the mouth and throat, and bruising are also possible but not common with inhalators.
A 2001 study reported a higher risk for cataracts in patients over age 40. (No higher risk was observed in younger people.)
Some studies report a higher risk for bone loss in patients who take inhaled steroids regularly, a side effect which is known to occur with oral steroids. A number of bone-preserving medications are now available that might safely offset this effect.
There is some concern that the more potent drugs, particularly fluticasone, suppress the adrenal system (which secretes natural steroids) to a greater degree than other steroid inhalants. (This is a serious side effect of oral steroids.)

Long-acting beta2-agonists are used in combination with inhaled corticosteroids for treating patients with moderate-to-severe asthma. These drugs include salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer). Combination single inhalers are available. One combines salmeterol and the corticosteroid fluticasone (Advair Diskus), and another combines formoterol and the corticosteroid budesonide (Symbicort).

Long-acting beta2-agonists are used for preventing an asthma attack (not for treating attack symptoms). The effects of one dose of a long-acting beta2-agonist last for about 12 hours, so these medicines are particularly effective during the night. These drugs also may be used for prevention of exercise-induced asthma in people and to protect against aspirin-induced asthma.

However, research indicates that long-acting beta2-agonists can worsen asthma by increasing symptom severity. These drugs may also increase the risk for asthma-related deaths. Experts are still trying to determine when long-acting beta2-agonists should be added to an asthma treatment plan. If your symptoms do not improve or if symptoms worsen with this type of drug, your doctor will recommend discontinuing it. Do not, however, stop taking this drug or other asthma medications without first talking with your doctor.

Side Effects. Side effects of long-acting beta2-agonists are similar to the short-acting drugs.

Specific Warning on Salmeterol and Formoterol. In 2003, a "black box" warning was added to product packaging for drugs that contain salmeterol, including Serevent Diskus, and Advair Diskus. The warning was based on a study that demonstrated more serious and even fatal asthma episodes in patients who used the drug than in patients who used a placebo. The risk for serious asthma episodes with salmeterol appears to be highest in African Americans and elderly patients with severe asthma.

In 2006, the FDA updated the warning to include formoterol (Foradil Aerolizer). Warnings for salmeterol and formoterol products emphasize that these medicines can increase the risk of severe asthma episodes. If these episodes occur, they can be fatal. Long-acting beta2-agonists require up to 20 minutes to achieve effectiveness, and there is a danger of overdose if a patient is not aware of this delay and takes additional doses to achieve faster relief. The FDA recommends that patients:

Use long-acting beta2-agonists only if other medicines (such as steroids) have not helped control asthma.
Use a short-acting bronchodilator, not a long-acting beta2-agonist, to treat sudden wheezing.
Do not use long-acting beta2-agonists to treat wheezing that is getting worse. Call your doctor if this situation occurs.
Do not stop using any asthma medicines without first talking to your doctor.

Cromolyn sodium (Intal) is both an anti-inflammatory drug and has antihistamine properties that block asthma triggers such as allergens, cold, or exercise. Nedocromil (Tilade) is similar to cromolyn. A cromolyn nasal spray called NasalCrom has been approved for over-the-counter purchase, but only to relieve nasal congestion caused by allergies. Patients should not use it for self-medication without the advice of a doctor.

Candidates. Cromolyn is often used in children with allergic asthma, but it has also been an important treatment for exercise-induced asthma (EIA) in all age groups, for pregnant women, and possibly for preventing allergic asthma in adults as well as children. Both cromolyn and nedocromil appear to be useful for patients with aspirin-induced asthma. These drugs do not effectively treat asthma once an attack is underway. They also have very little long-term benefits on lung function compared to inhaled corticosteroids.

Side Effects. Side effects of cromolyn include nasal congestion, coughing, sneezing, wheezing, nausea, nosebleeds, and dry throat. Nedocromil has an unpleasant taste, and some people have complained of nausea, headache, and spasms in the airways, but no serious side effects have been reported.

Leukotriene-antagonists (also called anti-leukotrienes or leukotriene modifiers) are oral medications that block leukotrienes. Leukotrienes are powerful immune system factors that, in excess, produce a battery of damaging chemicals that can cause inflammation and spasms in the airways of people with asthma. As with other anti-inflammatory drugs, leukotrienes are used for prevention and not for treating acute asthma attacks.

Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These drugs are proving to be effective for long-term prevention of asthma, including exercise-induced asthma and aspirin (or NSAID)-induced asthma. Most studies to date still report better success with inhaled corticosteroids than with the leukotriene-antagonists. Their anti-inflammatory actions are different from those of steroids, however, and combinations of the two drugs are being tried. A 2002 analysis of 13 studies, however, reported only modest benefits when anti-leukotrienes were added to corticosteroids. The combination did improve asthma control in some of the studies, but they did not reduce corticosteroid use. (In all but one of these studies the subjects were adults.)

Side Effects and Complications. Gastrointestinal distress is the most common side effect of leukotriene-antagonists. Very few other side effects have been reported. In general, these drugs appear to be safe and well tolerated.

Of some concern are reports of Churg-Strauss syndrome in a few people taking zafirlukast or montelukast. Churg-Strauss syndrome is very rare, but it causes blood vessel inflammation in the lungs and can be life threatening. Oral steroids quickly resolve the problem. Usually the syndrome has occurred in patients who were tapering off steroids and changing over to the leukotrienes-antagonists. Some experts believe that, in such cases, the steroids may simply have masked the presence of the disorder, which then developed when the steroid drugs were withdrawn. Symptoms include severe sinusitis, flu-like symptoms, rash, and numbness in the hands and feet.

Other concerns are indications of liver injury in patients taking zileuton and zafirlukast when taken at higher than standard doses. No adverse effects on the liver have been reported to date with montelukast.

Theophylline. Theophylline (Theo-Dur, Theolair, Slo-Phyllin, Slo-bid, Constant-T, Respbid) relaxes the muscles around the bronchioles and also stimulates breathing. One study reported that it may also have anti-inflammatory qualities even in low doses. Available in tablet, liquid, and injectable forms, some theophylline sustained-release tablets and capsules have a long duration of action and can, therefore, be taken once or twice a day with good results.

If theophylline is not taken exactly as prescribed, an overdose can easily occur. Toxicity can cause nausea, vomiting, headache, insomnia, and, in rare cases, disturbances in heart rhythm and convulsions. Contact a doctor immediately if any of these side effects occur.

The risks for these adverse effects are small if the drug is taken exactly as prescribed, but the following precautions should be noted:

Chronic smokers metabolize theophylline much more quickly and require higher doses of the drug than nonsmokers; prolonged-release versions are helpful for such people.
Too much caffeine can increase the concentration of this drug and the amount of time it stays in the body.
Theophylline also interacts with many other drugs that are taken for other common medical conditions, including asthma. Exercise caution when using beta2-agonists and theophylline together.
No one with a peptic ulcer should take theophylline. The elderly and anyone with heart disease, liver disease, hypertension, seizure disorders, or heart failure, should take theophylline with caution. Of special note, people with heart conditions who take theophylline orally face an increased risk for sudden death from heart-related causes.

Omalizumab (Xolair) is FDA-approved for patients age 12 and older who have moderate-to-severe persistent asthma related to allergies. The first drug of this type to be approved for asthma, omalizumab is a monoclonal antibody (MAb), a genetically developed drug designed to attack very specific targets. Omalizumab is administered by injection every 2 - 4 weeks. It is used only to treat patients whose symptoms are not controlled by inhaled corticosteroids.

Omalizumab prevents the antibody immunoglobulin E (IgE) from triggering the inflammatory events that lead to asthmatic attacks. Studies have shown excellent benefits of the drug, including a reduced need for corticosteroids, fewer hospitalizations, and significant symptomatic improvements.

However, about 1 in 1,000 patients who take omalizumab develop anaphylaxis (a life-threatening allergic reaction). In 2007 the FDA requested the manufacturers of omalizumab put a “boxed warning” on the medicine’s label emphasizing the drug’s risk for anaphylaxis. The boxed warning notes that patients can develop anaphylaxis after any dose of omalizumab, even if they had no reaction to a first dose. Anaphylaxis may occur up to 24 hours after the dose is given.

The FDA recommends that health care providers observe patients for at least 2 hours after an injection. Patients should also carry emergency self-treatment for anaphylaxis (such as an Epi-Pen) and know how to administer it. With an Epi-Pen, or similar auto-injector device, patients can quickly give themselves a life-saving dose of epinephrine.

Anaphylaxis symptoms include:

Difficulty breathing
Chest tightness
Dizziness
Fainting
Itching and hives
Swelling of the mouth and throat

Other Treatments

Various drugs are being investigated for asthma treatment. Some of these drugs have anti-inflammatory effects, which may help reduce dependence on corticosteroids. For example, etanercept (Enbrel), which blocks the inflammatory protein called tumor necrosis factor alpha, is being investigated for patients whose asthma has not responded to other drugs. The humanized monoclonal antibody daclizumab has also improved asthma control in patients with treatment-resistant asthma, as well as patients with moderate to severe chronic persistent asthma. Certain antibiotics, such as clarithromycin (Biaxin), may improve lung function in patients with asthma who show evidence of infection with the bacterial organisms Mycoplasma or Chlamydiapneumoniae. Dapsone, a drug known as a sulfone, is also under investigation.

Alternative therapies are being widely used by children, adolescents, and adults with asthma. In one study, nearly half of asthma or allergy sufferers resorted to alternative treatments. To date, however, evidence does not support any value from most alternative therapies, including high-dose vitamins, urine injections, homeopathic remedies, and most herbal remedies.

Relaxation and Stress-Reduction Techniques. Patients report benefits from many stress reduction techniques, such as acupuncture, hypnosis, breathing relaxation techniques, massage therapy, and meditation practices.

Acupuncture, hypnosis and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

The Buteyko Breathing Method. The Buteyko breathing method is an experimental approach designed to increase levels of carbon dioxide in the body. To do this, patients are trained to reduce their volume of breath and to avoid hyperventilation (over-breathing). Some studies have reported that patients using this method reduce their use of medications and improve their quality of life. The system originated in Australia and is not yet widely available in the U.S.

Probiotics. Probiotics are beneficial bacteria that may help protect against allergies and asthma. Antibiotic over-use and modern hygiene may specifically be reducing these helpful organisms. Probiotics can be obtained in active yogurt cultures and in supplements, which are being studied for protection.

Herbal Remedies. There have been few rigorous studies on herbal remedies for asthma. Butterbur (also known as Petasites hybridus, butter dock, blatterdock, bog rhubarb, and exwort) is one traditional herbal remedy used for treating seasonal allergies and asthma. In a 2002 study, it appeared as effective and less sedating than a commonly prescribed antihistamine for treating seasonal allergies over a 2-week period, but there has been little research on its effect on asthma.

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

Managing Asthma

Avoidance or control of the triggers that lead to asthma attacks is as much a priority as treatment of the disease.

Controlling Pets. Patients who already have pets and are not allergic to them probably have a low risk for developing allergies. If pets trigger asthma, however, they should be kept outside. If this isn't possible, they should at least be confined to carpet-free areas outside the bedroom. Cats harbor significant allergens, which can even be carried on clothing; dogs usually present fewer problems. Washing animals once a week can reduce allergens. Dry shampoos, such as Allerpet, are now available for both cats and dogs that remove allergens from skin and fur and are easier to administer than wet shampoos.

Controlling for Dust. Spray furniture polish is very effective for reducing both dust and allergens. Air cleaners, filters for air conditioners, and vacuum cleaners with High Efficiency Particle Arresting (HEPA) filters can help remove particles and small allergens found indoors. Neither vacuuming nor the use of anti-mite carpet shampoo, however, is effective in removing mites in house dust. In fact, vacuuming stirs up both mites and cat allergens. If possible, avoid carpets and rugs.

A HEPA (High Efficiency Particle Arresting) filter can remove the majority of harmful particles, including mold spores, dust, dust mites, pet dander and other irritating allergens from the air. Along with other methods to reduce allergens, such as frequent dusting, the use of a HEPA filtration system can be a helpful aid in controlling the amount of allergens circulating in the air. HEPA filters can be found in most air purifiers, which are usually small and portable.

Bedding and Curtains. Many experts recommend reducing exposure to dust mites by enclosing mattresses and pillows in semipermeable coverings. (Vinyl mattress covers limit airflow and may also worsen, or even cause, asthma in children. Synthetic pillows may pose a significantly higher risk for severe asthma attacks in children than feather or no pillows.) However, several 2005 studies suggested that such covers do not prevent asthma or allergies. Replace curtains with shades or blinds, and wash bedding using the highest temperature setting.

Reducing Humidity in the House. Although warm, moist air from vaporizers can greatly ease and moderate asthma attacks, living in a damp house is counterproductive. Dust mites thrive in humidity and damp houses increase the risk for mold, so on-going humidifiers can be unuseful. If they are used, humidity levels should not exceed 40% and they should be cleaned daily with a vinegar solution.

Gas Stoves, Kerosene, and Cooking. People with asthma should choose electric ovens rather than gas, which release nitrogen dioxide, a substance that can aggravate asthma symptoms. Even smoky cooking can worsen asthma. Kerosene (used in space heaters and lamps) may also produce allergic reactions.

Exterminating Pests (Cockroaches and Mice). Use a professional exterminator to eliminate cockroaches. (One study reported that ridding a home of cockroaches and cleaning the house using standard housecleaning techniques failed to eliminate the cockroach allergens themselves.) Exterminate mice and attempt to remove all dust, which might contain mouse urine and dander.

Avoiding Smoking and Cigarette Smoke. Cigarette smoke can accelerate the decline in lung function related to asthma. Even exposure to secondhand smoke can double the risk of asthma-related emergency room visits. In one study, it was the most frequently cited trigger of asthma symptoms. Everyone should quit smoking and encourage others around them to quit. [For help in quitting, see In-Depth Report # 41: Smoking.]

Click the icon to see an image of common asthma triggers.

Avoiding Outdoor Allergens. The following are some recommendations for avoiding allergens outside:

Avoid scheduling camping and hiking trips during times of high pollen count (generally, May and June for grass pollen and mid-August to October for ragweed).
Avoid strenuous activity when ozone levels are highest, which usually occur in early afternoon, particularly on hot hazy summer days. Levels are lowest in early morning and at dusk.
Asthma attacks are often higher during thunderstorms. It is not clear why. Some evidence points to a build-up of ozone that accompanies such storms. One study suggested that changing airflow patterns bring a sudden downdraft of air containing concentrations of pollens, small particles and allergens.
Patients who are allergic to mold should avoid barns, hay, raking leaves, and mowing grass. Exposure to automobile fumes may worsen asthma. Fungi in car air conditioners can also be a problem.

Click the icon to see an image of fungus.

Reducing Exposure to Air Pollution. A number of studies have linked air pollution to asthma. An important 2000 study found a strong association between higher mortality rates from heart and lung diseases and high levels of specific pollutants (ozone, carbon monoxide, sulfur dioxide, and nitrogen dioxide). Some experts point out that asthma rates in North America have increased over recent years while the prevalence of many common air pollutants have declined. Nevertheless, evidence strongly suggests that air pollution can worsen existing asthma and patients should take precautions if they are exposed to polluted air.

A number of studies have estimated that between 2 - 26% of adult-asthma cases are related to work history. Some experts encourage doctors to suspect occupational factors in all cases of adult-onset asthma. Although workers who have allergies, who smoke, or both are at higher risk than others, any worker exposed to occupational triggers may be at risk for asthma.

Work-related asthma is one of two types:

Work-aggravated asthma, in which existing asthma symptoms are triggered by irritants at the workplace
Occupational asthma, which is new-onset asthma strongly associated with conditions at work

Occupational asthma is further categorized as:

Nonlatent (symptoms occur right after exposure to an irritant, usually high concentrations of gas, fumes, dust, or chemicals)
Latent (symptoms develop after prolonged exposure to substances in the workplace)

Occupational Triggers. Over 250 substances have been identified as potential occupational triggers of asthma, and the list is growing. A few of these chemicals and substances include:

Isocyanates used in the manufacture of polyurethane, paints, steel, and electronics
Trimellitic anhydrides (TMA) used in many plastics and epoxies
Western red cedar, oak, redwood, and mahogany
Metal salts (platinum, nickel, and chrome) and metal working fluids
Vegetable dusts (soybeans, grains, flour, cotton, and gums)
Biologic organisms (Bacillus subtilis, pancreatic enzymes)
Xylanase used in the baking industry
Pharmaceuticals (penicillin, phenylglycine acid chloride)
Glutaraldehyde used to sterilize medical equipment
Red dye made from the cochineal insect
Diacetyl, the main chemical in artificial butter flavoring used in popcorn

Workers in these industries and others, including farmers, hairdressers, and those who work in the garment industries are at risk for asthma.

Preventing Occupational Asthma. In people whose asthma is caused by workplace conditions, improved ventilation or face masks may help.

Sometimes, however, even low levels of chemical substances can trigger an asthma attack. In such cases, leaving the job is the only way to prevent the condition from getting worse. Because such a step can be emotionally and financially threatening, workers should be sure that occupational substances are the cause of the asthma by having a complete check-up by a lung specialist.

If the diagnosis of occupational asthma is certain, patients should obtain advice on available compensation plans for disability. The effects of workplace asthma can be permanent. However, in one study, 70% of people with asthma experienced significant improvement in symptoms after leaving the job.

Patients with asthma and chronic allergic rhinitis may require daily medications. Patients with severe seasonal allergies may be advised to start medications a few weeks before the pollen season, and to continue medicine until the season is over.

Immunotherapy ("allergy shots") may help reduce asthma symptoms, and the use of asthma medications, in patients with known allergies. They may also help prevent the development of asthma in children with allergies. Immunotherapy poses some risk for severe allergic reactions, however, especially for children with poorly controlled asthma.

[See In-Depth Report #77: Allergic rhinitis; and Report #5: Asthma in children and adolescents.]

Preventing and Treating Respiratory Infections. Respiratory infections, including the common cold, can act with allergies to worsen asthma. People with asthma should try to minimize their risk for respiratory tract infections. Washing hands is a very simple but effective preventive measure.

Patients with asthma should ask their doctors about the flu vaccine and also whether they should receive the vaccination against pneumococcal pneumonia.

Zanamivir, a new drug used for treating influenza, is considered safe for patients with asthma 12 years of age or older. In one study, patients with asthma who were treated with zanamivir experienced fewer flu symptoms and had improved lung function. [See In-Depth Report #94: Colds and influenza.]

Managing Hormonal-Related Asthma. Women who suspect that menstrual-related changes may influence asthma severity should keep a diary recording their menstrual dates and times of asthma attacks. In some cases, adjusting medications in anticipation of menstruation may help prevent attacks. Some small studies have suggested that hormonal drugs called gonadotropin-releasing hormone (GnRH) analogues may help women with severe premenstrual asthma. Such drugs reduce or suppress estrogen levels, however, and can have severe side effects. More research is needed to determine if the disadvantages outweigh the benefits.

Weight Loss. People who have asthma and who are overweight may help reduce asthma symptoms with weight loss.

Fruits, Vegetables, and Whole Grains. Healthy foods are important for lung function. Specific foods that may be important for healthy lungs contain antioxidants (deep green and yellow-orange fruits and vegetables), selenium (fish, red meat, grains, eggs, chicken, liver, garlic), plant chemicals called flavonoids (apples, onions), and magnesium (green leafy vegetables, nuts, whole grains, milk, and meats).

Vitamin D. There may be an association between a lack of vitamin D and asthma. Some research suggests that children are less likely to develop asthma at a young age if their mothers consume a high intake of vitamin D during pregnancy. Vitamin D is available from dietary sources or vitamin supplements.

Fish Oil. Omega-3 fatty acids, found in cold water oily fish and in supplements (preferably DHA-EPA, which are the important compounds in fish oil) have anti-inflammatory effects. Some evidence suggests they may be helpful for people with asthma, although it is weak.

Caffeine. Caffeine has properties that are similar to theophylline, a drug used to treat asthma. A major analysis of studies reported that caffeine improved lung function for up to 4 hours after consumption. (People who are going to have their lung function tested should avoid drinking coffee, tea, or other caffeinated beverages for at least 4 hours beforehand.)

Alcohol. In adults, some research suggests that alcohol intake may influence allergy severity. One study found that as little as one drink a day is enough to worsen dust mite allergies.

Role of Food Allergies. Although 67% of people with asthma believe their symptoms are aggravated by food allergies, studies indicate that this belief may be true in only 5% of cases. The primary suspects are monosodium glutamate, or MSG (found in some canned soups, cheese, and certain vegetables), and sulfites (preservatives in wine and foods that include processed frozen potatoes and tuna). Contrary to what many people believe, dairy products do not appear to worsen asthma symptoms in people who are not already allergic to them.

Asthma is no reason to avoid exercise. Historically, about 10% of Olympic athletes have asthma. Some studies indicate that long-term exercise even helps control asthma and reduce hospitalization. Patients should consult their doctors before embarking on any exercise program, however. Uncontrolled asthma can be dangerous and, in rare cases, can be fatal for athletes, even some with mild asthma. Use of the inhaler is extremely important.

People who enjoy running should probably choose an indoor track to avoid pollutants. Swimming is excellent for people with asthma. Yoga practice, which uses both stretching, breathing, and meditation techniques, may have particular benefits. One study reported that two-thirds of patients who practiced yoga regularly were able to reduce or stop taking their asthma medications.

Exercise-induced asthma is a limited condition that has specific recommendations.

People with asthma have no higher rate of anxiety or depression than the general population. However, such emotions interact with the effects of asthma and its treatments in important ways:

Negative emotions can discourage compliance with medication and the ability to cope
Poor control of asthma symptoms, in turn, increases the risk for negative emotions
Stress and depression have been associated with more severe symptoms and even an increased risk of fatal asthma attacks

Some evidence suggests that stress reduction techniques, a positive attitude and relaxation techniques can be very helpful in the long-term management of asthma. [See In-Depth Report #31: Stress.]

Resources

www.lungusa.org -- The American Lung Association
www.acaai.org -- American College of Allergy, Asthma & Immunology
www.aaaai.org -- American Academy of Allergy, Asthma & Immunology
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
http://asthma.nationaljewish.org -- National Jewish Medical and Research Center
www.aafa.org -- Asthma and Allergy Foundation of America
www.aarc.org -- American Association for Respiratory Care

References

Glassroth J. The role of long-acting ß-agonists in the management of asthma: Analysis, meta-analysis, and more analysis. Ann Intern Med 2006 Jun 20; 144:936-7.

Kiljander TO, Harding SM, Field SK, Stein MR, Nelson HS, Ekelund J, et al. Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2006 May 15;173(10):1091-7.

National Asthma Education and Prevention Program Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics -- 2002. Rockville, MD. National Heart, Lung, and Blood Institute, US Dept of Health and Human Services; 2003. NIH publications 02-5074.

Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006 Jun 20;144(12):904-12.

Review Date:
3/27/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Depression

FitSugar — Wed, 08 Oct 2008 17:34:54 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Depression is a mood disorder in which feelings of loss, anger, sadness, or frustration interfere with everyday life. Depression affects about 17 million Americans each year. It can be mild, moderate, or severe and occur as a single episode, recurring episodes, or chronic depression (lasting more than 2 years).

The primary types of depression include:

Major depression -- five or more symptoms must be present. An episode must last at least 2 weeks, but tends to continue for 20 weeks. (A mood disorder is classified as minor depression if less than five depressive symptoms are present for at least 2 weeks.)
Dysthymia-- a chronic, generally milder form of depression. Symptoms are similar to major depression but more mild in degree.
Atypical depression-- depression accompanied by unusual symptoms, such as hallucinations, delusions, and physical rigidity

Other common forms of depression include:

Postpartum depression-- experienced by 8 - 20% of women following delivery
Premenstrual dysphoric disorder (PDD)-- experienced by 3 - 8% of women. Depressive symptoms occur 1 week prior to menstruation and disappear following menstruation.
Seasonal affective disorder (SAD)-- experienced by 5% of adults, the majority of whom are women. It occurs during the fall-winter season and disappears during the spring-summer season.

Depression may also occur with mania (known as manic-depression or bipolar disorder). In this condition, moods cycle between mania and depression.

Signs and Symptoms

While it is normal for most people to feel "down in the dumps" on occasion, someone with major depression feels significantly depressed for a prolonged period of time, has difficulty enjoying acts that were once pleasurable, and experiences at least five of the following symptoms for 2 weeks or more:

Sleep disturbances -- at least 90% of people with depression have either insomnia (sleeplessness) or hypersomnia (excessive sleeping).
Significant change in appetite (often resulting in either weight loss or weight gain)
Fatigue and loss of energy
Feelings of worthlessness, self-hate, and inappropriate guilt
Extreme difficulty concentrating
Either agitation, restlessness, and irritability or inactivity and withdrawal
Recurring thoughts of death or suicide
Feelings of hopelessness

Although not generally considered to be defining characteristics of depression, many people with the condition report a lack of sex drive and sudden bursts of anger.

Causes

The causes of depression are complex and involve a combination of biologic, genetic, and environmental factors. People with depression may have abnormal levels of certain brain chemicals, including serotonin, acetylcholine, and catecholamines (such as dopamine). The following may alter the levels of these brain chemicals and contribute to development of depression:

Heredity -- a recently identified gene called SERT that regulates the brain chemical serotonin has been linked to depression.
Chronic stress (such as from loss, abuse, or deprivation in early childhood)
Amount of exposure to light
Sleep disturbances
Social isolation
Nutritional deficiencies
Serious medical conditions, such as heart attack or cancer
Certain medications, including those for high blood pressure, high cholesterol, or irregular heartbeat

Risk Factors

Although depression is a condition that can affect anyone, regardless of age, race, or gender, the following factors may increase your risk for an initial or recurrent episode of depression:

Prior episodes of depression
Family history of depression
Suicide attempt -- a previous attempt of suicide during a major depressive episode increases the likelihood of another episode of depression.
Female gender -- the incidence of depression appears to be greater in women than in men. Some researchers speculate, however, that women may simply report their symptoms more frequently than men, and that men may be more apt to mask their depressive symptoms with alcohol. Therefore, it is still unclear whether women truly have a greater risk for depression.
Young adulthood or middle age -- the highest occurrence of depression is between the ages of 25 - 44. The elderly are also at particular risk due to death of loved ones, physical illness, and loss of independence.
Stressful life events (such as the death of a loved one), particularly if the event occurs at a young age
Postpartum period
Chronic medical or psychological conditions, including autoimmune diseases (such as lupus), cancer, heart disease, chronic headaches, chronic pain, anxiety, obsessive-compulsive disorder, and borderline personality disorder. Medical conditions that cause shifts in hormones, such as thyroid disorders or menopause, may also contribute to depression.
History of abuse (such as mental, physical, or sexual)
Lack of social support system (such as a network of close friends or family)
Current or past alcohol or drug abuse -- 25% of people with addictions have depression.

Diagnosis

If feelings of depression or any of the related symptoms are present, it is important to address them with a doctor or someone who can help direct care appropriately. Unfortunately, many people with depression tend to refrain from disclosing any or all of their symptoms in this setting. Occasionally, even when the symptoms are discussed during an appointment, a doctor may try to treat them individually, rather than recognizing the complete picture of depression. Working together with a primary care doctor is extremely important because they are often the health care providers who make a referral to a psychiatrist who, in turn, makes a definite diagnosis of depression. Proper diagnosis of depression is the first step toward proper treatment.

Only psychiatrists can prescribe medication, but psychologists and social workers, as well as psychiatrists, use psychotherapy as an important mode of treatment. These specialists will often administer a screening test, such as the Beck Depression Inventory or the Hamilton Rating Scale, which consists of about 20 questions that assess an individual's risk for depression. Even before these psychological screening tests, however, several blood tests will be performed to determine whether nutrient deficiencies or underlying medical conditions (such as a thyroid disorder) may be causing or contributing to depression.

Although the vast majority of people with depression are treated as outpatients, hospitalization is necessary for people who intend to, or do, attempt suicide, and may be necessary under other circumstances as well.

Preventive Care

The following steps can help prevent depression or decrease the chances of relapse:

Adequate sleep, regular exercise, and a balanced, healthy diet may help prevent depression and diminish symptoms of this mood disorder.
Mind-body techniques, such as biofeedback, meditation, and tai chi, are effective ways to prevent or reduce symptoms associated with depression.
Psychotherapy directed at coping skills generally helps prevent relapse.
Family therapy may prevent children or teens of depressed parents from becoming depressed later in life.
Compliance with the prescribed treatment regimen decreases the chance of relapse.

Treatment Approach

People with depression have several options for treatment, but a combination of psychotherapy and antidepressant medications is the regimen of choice, particularly for people with major depression. Cognitive-behavioral therapy appears to be the most effective type of psychotherapy, particularly for adolescents and people with atypical or postpartum depression. As many as 90% of people with depression improve from a combination of psychotherapy and antidepressants. However, adverse side effects from certain medications make it difficult for many to take their medications. Some complementary and alternative therapies may be helpful in reducing the side effects from such medications, while other complementary and alternative therapies may actually diminish the symptoms of depression.

Lifestyle

Exercise

Studies have consistently shown that regular exercise (either aerobic or strength and flexibility training) significantly reduces depressive symptoms in people with mild to moderate depression and improves the mood of people with major depression. Some even suggest that exercise may be as effective as psychotherapy for people with mild-to-moderate depression, although additional research is needed. In the meantime, exercise can be used safely in conjunction with medication for those with depression.

Medications

Antidepressant medications are very effective; reports indicate that they are 90% successful in treating depression. In general, medications are taken for at least 4 - 6 months to assure complete and effective treatment. However, antidepressants often cause adverse side effects, making it difficult for some people to comply with taking their medications. Medications must not be stopped before first talking with a physician. Most antidepressants cause withdrawal symptoms if they are not discontinued slowly over time with guidance from a physician.

There are several classes of antidepressant medications, including:

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs increase the activity of a chemical in the brain called serotonin. Most health care providers will prescribe SSRIs before any other antidepressant medication for depression, in part because the side effects associated with SSRIs are generally fewer than for other classes of antidepressants. Typical side effects caused by SSRIs include stomach upset, weight gain or loss, drowsiness, sexual dysfunction (such as impotence, decreased libido, and diminished orgasm), headache, jaw grinding, and apathy. Very unusual side effects from this class of prescription drugs include extreme agitation, impulsivity, tremors, and insomnia. People who discontinue taking SSRIs due to side effects usually attribute their discontent to sexual dysfunction.

Drugs classified as SSRIs include:

Fluoxetine
Sertraline
Paroxetine -- most likely in this class to cause sexual dysfunction
Fluvoxamine
Citalopram -- least likely in this class to cause sexual dysfunction

Another group of antidepressant medications (which are similar to SSRIs, but target other brain chemicals in addition to serotonin) may cause fewer negative sexual side effects. These include:

Bupropion -- should not be used if there is history of or risk for seizure
Nefazodone -- no sexual dysfunction reported. It begins to work very quickly and may cause a decrease in blood pressure when going from lying or sitting to standing.
Venlafaxine -- may impair sexual function and is not recommended in the elderly. It may improve quality of life more effectively than other antidepressants, but can cause irregular heart rhythm. Withdrawal from the medication is difficult.
Mirtazapine -- may be particularly effective if feelings of anxiety are also present. It helps with insomnia but may cause drowsiness, blurred vision, weight gain, and damage to production of cells in the bone marrow (very rare).
Maprotiline -- may cause dry mouth, drowsiness, sensitivity to the sun, and seizures

Tricyclic Antidepressants

Tricyclics increase the activity of the brain chemicals serotonin and norepinephrine. They are as effective as SSRIs, but are usually prescribed only to those who do not respond well to SSRIs because side effects are quite common and are usually less tolerable. Tricyclic antidepressants include:

Amitriptyline
Amoxapine -- increases risk of seizure in those who are prone to have a seizure
Clomipramine -- used for obsessive-compulsive disorder
Desipramine
Doxepin -- may help with insomnia
Imipramine -- may cause a rare lung disorder called idiopathic pulmonary fibrosis
Nortriptyline -- less risk of irregular heart rhythm than others in this class
Protriptyline -- less drowsiness than others in this class and may even cause weight loss and sun sensitivity
Trimipramine -- high risk for irregular heart rhythm

Side effects of tricyclics may include:

Dry mouth
Blurred vision
Constipation
Sexual dysfunction
Weight gain
Dizziness
Drowsiness
Urinary urgency (a sense that one has to urinate even when the bladder is empty)
Drop in blood pressure when going from lying or sitting to standing (causes dizziness and lightheadedness)
Irregular heart rhythm

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs boost levels of norepinephrine, dopamine, and serotonin in the brain. MAOIs are generally prescribed only when other antidepressants have not been effective, which may occur in people with atypical depression. People who take MAOIs may experience a sharp increase in blood pressure after consuming food or drink containing the amino acid tyramine (found in such foods as aged cheeses and red wine). MAOIs also negatively interact with other medications, including Ritalin (used for attention deficit hyperactivity disorder) and pseudoephedrine (decongestant in many over-the-counter and prescription medications), and should not be taken with other classes of antidepressants.

MAOIs include:

Phenelzine -- should be avoided by people with a history of seizures or bipolar disorder (manic-depression)
Isocarboxazid -- side effects include drowsiness, sexual dysfunction, weakness, trembling, and blurred vision.
Tranylcypromine -- should not be used if there is any history of kidney disease or bipolar disorder

Surgery and Other Procedures

Electroconvulsive Therapy (ECT) for depression is usually reserved for when all other therapies have been unsuccessful. In this procedure, a small electrical current induces a seizure lasting approximately 40 seconds. A muscle relaxant and mild sedative are administered prior to the procedure. ECT is generally repeated every 2 - 5 days for a total of six treatments. It may cause temporary confusion, memory impairment, headache, muscle aches, irregular heart rhythm, or nausea.
Magnetic Resonance Imaging (MRI)-Guided Cingulotomy involves the application of an electrical current to a specific part of the brain. The MRI is used as a guide for an exact placement. Long-term improvement has been reported using this technique in over 50% of people with depression who have not responded to other treatment methods.

Nutrition and Dietary Supplements

A comprehensive treatment plan for depression may include a range of complementary and alternative therapies. Preliminary studies suggest that nutritional supplements may reduce the symptoms of some depression. Ask your team of health care providers about the best ways to incorporate these therapies into your overall treatment plan. Always tell your health care provider about the herbs and supplements you are using or considering using.

Following these nutritional tips may help reduce symptoms:

Try to eliminate potential food allergens, including dairy, wheat (gluten), corn, preservatives, and food additives. Your health care provider may want to test for food sensitivities.
Eat antioxidant foods, including fruits (such as blueberries, cherries, and tomatoes), and vegetables (such as squash and bell peppers).
Eat foods high in B-vitamins and calcium, such as almonds, beans, whole grains (if no allergy), dark leafy greens (such as spinach and kale), and sea vegetables such as kelp and dulce.
Avoid refined foods, such as white breads, pastas, and especially sugar.
Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy), or beans for protein.
Use healthy oils for cooking, such as olive oil or vegetable oil.
Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
Avoid coffee and other stimulants, alcohol, and tobacco.
Drink 6 - 8 glasses of filtered water daily.
Exercise at least 30 minutes daily, 5 days a week.

You my address nutritional deficiencies with the following supplements:

A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals such as magnesium, calcium, zinc, and selenium.
Omega-3 fatty acids, such as fish oil, one to two capsules or one tablespoonful oil one to three times daily, to help decrease inflammation and help with mental balance.
Vitamin C, 500 - 1000 mg one to three times daily, as an antioxidant and for immune support.
Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant, immune, and muscular support.
5-hydroxytryptophan (5-HTP), 50 mg two to three times daily, for mood stabilization. Ask your health care provider about potential prescription interactions.
Probiotic supplement (containing Lactobacillus acidophilus and other species), 5 - 10 billion CFUs (colony forming units) a day, for maintenance of gastrointestinal and immune health. You should refrigerate your probiotic supplements for best results.
SAMe (s-adenosyl-L-methionine), 100 - 200 mg before breakfast daily, for mood improvement.
Dihydroepiandosterone (DHEA), start at 5 mg three times a day and work up to 100 mg per day for 7 - 12 months. It is recommended to use DHEA under the supervision of a qualified health care provider. If adverse effects develop, discontinue use.
L-theanine, 200 mg one to three times daily, for nervous system support.
Melatonin, 2 - 5 mg one hour before bedtime, for sleep and immune protection. Ask your health care provider about potential prescription interactions.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day. You may use tinctures alone or in combination as noted.

St. John's wort (Hypericum perforatum) standardized extract, 300 mg two to three times per day, for depression. Check with your health care provider if you are taking prescription medications.
Kava kava (Piper methysticum) standardized extract, 100 - 250 mg one to three times daily, as needed for symptoms of stress and anxiety. Talk with your health care provider before taking kava kava if you have an unhealthy liver.
Ginkgo (Ginkgo biloba) standardized extract, 40 - 80 mg three times daily, for blood flow and depression.
Green tea ( Camellia sinensis) standardized extract, 250 - 500 mg daily, for antioxidant and general health effects. Use caffeine-free products. You may also prepare teas from the leaf of this herb.
Rhodiola ( Rhodiola rosea ) standardized extract, 100 - 600 mg daily, for antioxidant and anti-stress activity.

Acupuncture

Two randomized, controlled, clinical trials suggest that electroacupuncture may reduce symptoms of depression as effectively as amitriptyline, a tricyclic antidepressant medication. Electroacupuncture involves the application of a small electrical current through acupuncture needles. Other studies suggest that acupuncture may be effective for people with mild depression and for those with depression related to a chronic medical illness. Further research is warranted in this area.

Homeopathy

Although very few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies to alleviate the symptoms of depression based on their knowledge and experience.

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 treatment for each individual. A few homeopathic remedies that may work for depression include:

Ignatia -- for a sudden sense of grief or disappointment following the death of a loved one, the end of a romantic relationship, or an unexpected loss of one's job
Natrum muriaticum -- for grief following the death of a loved one or sadness from the end of a romantic relationship

Massage and Physical Therapy

Studies of formerly depressed adolescent mothers, children hospitalized for depression, and women with eating disorders, suggest that massage decreases stress hormone levels, feelings of anxiety, and symptoms of depression. Giving massage may also be beneficial for people who are depressed. Elderly volunteers with depression showed notable improvement in their symptoms when they massaged infants.

Aromatherapy, or the use of essential oils in massage therapy, may also be of value as a supplemental treatment for depression. Theoretically, the smells of the oils elicit positive emotions through the limbic system (the area of the brain responsible for memories and emotions). However, the benefits of aromatherapy appear to be related to the relaxation effects of the treatment as well as to the recipient's belief that the treatment will be beneficial. Essential oils used during massage for depression are quite varied and include:

Lavender ( Lavandula officinalis)
Basil (Ocimum basilicum)
Orange (Citrus aurantium)
Sandalwood (Santalum album)
Lemon (Citrus limonis)
Jasmine (Jasminum spp.)
Sage (Salvia officinalis)
Chamomile (Chamaemelum nobile)
Peppermint (Mentha piperita)
Rosemary (Rosmarinus officinalis)

Mind-Body Medicine

Mind-body therapies and techniques that may be useful as a part of an overall treatment regimen for depression include:

Psychotherapy

Cognitive-behavioral therapy is a type of psychotherapy in which individuals learn to identify and change distorted perceptions about themselves and adapt new behaviors to better cope with the world around them. This therapy is frequently considered the treatment of choice for people with mild-to-moderate depression, but it may not be recommended for those with severe depression. Studies of people with depression indicate that cognitive-behavioral therapy is at least as effective as tricyclic antidepressants. Compared to those treated with antidepressants, people treated with cognitive-behavioral therapy demonstrated similar, or better, results and lower relapse rates.

Other therapeutic approaches that may be applied by a psychiatrist, psychologist, or social worker include:

Psychodynamic psychotherapy -- based on Freud's theories about unresolved conflicts in childhood and depression as a grief process
Interpersonal therapy -- acknowledges childhood roots of depression, but focuses on current problems contributing to depression and is considered very effective treatment for depression
Supportive psychotherapy -- nonjudgmental advice, attention, and sympathy, and this approach may improve compliance with taking medication

Relaxation

One study suggests that relaxation techniques, such as yoga and tai chi, may improve symptoms of depression in people with mild depression.

Meditation

Some researchers believe that mindfulness meditation may prevent depression from recurring in people who once had the condition.

Other Considerations

Pregnancy

Postpartum depression is experienced by 8 - 20% of women following delivery.
The safety of SSRIs and tricyclic antidepressant medications during pregnancy remains uncertain. The physician will provide guidance regarding use or avoidance of antidepressants during pregnancy. The risks and benefits to the mother and the fetus must be weighed in each individual case in order to determine the most appropriate regimen during pregnancy. MAOIs cause birth defects and should be avoided during pregnancy.
Many of the dietary supplements and herbs mentioned here have not been tested for safety during pregnancy. Talk with your doctor or pharmacist.

Warnings and Precautions

People with Parkinson's disease should avoid SSRIs.
People with coronary artery disease should avoid tricyclic antidepressants.
Several herbal remedies and supplements should not be combined with antidepressant medications. Be sure to inform your health care provider of all herbs and supplements you take to avoid adverse interactions.

Prognosis and Complications

Depression is a serious condition that can have a devastating effect on people's lives. It can directly and indirectly contribute to chronic medical conditions, such as heart disease and stroke, because depressed people with these conditions are less likely to engage in healthy behaviors (such as exercise) and more likely to engage in unhealthy behaviors (such as smoking). Suicide is a significant factor in depression. About 15 % of people with a major depressive disorder commit suicide. Depression also significantly shortens the lifespan of the elderly and is associated with the development of memory impairment and dementia.

When left untreated, depression can last up to 2 years. Rates of recurrence are variable: 50% of people who have had one depressive episode will have a second major depressive disorder, 70% will have a third, and 90% will have a fourth. Symptoms of depression usually disappear after menopause in women with premenstrual dysphoric disorder or seasonal affective disorder. Fortunately, there are several treatment options available for people with depression, and the prognosis improves tremendously for those who seek treatment and comply with their regimen.

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Review Date:
11/6/2006
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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DrSugar Answers: Are Herbal Supplements Safe?

DrSugar — Fri, 08 May 2009 08:00:00 -0700

DrSugar is in the house and he's answering your health questions.

Dear DrSugar,
I've never taken herbal supplements, but I know many people do. I read about herbal supplements that reduce body fat, specifically belly fat, and possibly stress. I was wondering if you could answer a few questions for me? What do you think of herbal supplements in general? How does someone find quality herbal supplements . . . do you recommend any? I would love some advice on the matter.
- Herb Curious

This is an increasingly popular subject. Learn what the doctor has to say on the matter when you read more.

There is a tremendous amount of misinformation out there surrounding the use and efficacy of herbal supplements. If you go to a local herbal supplement store, as I have recently, and read the bottle labels, you will see a wide variety of claims such as "stress reducer," "sexual enhancer," "ultra fat burner," and more. Most of these claims have not been validated by scientific studies and compared with a placebo. In some instances, product claims have been completely debunked. Vitamin E, for instance, has been proven to not reduce the risk of cancer despite its antioxidant content. Regarding supplements claiming to reduce belly fat and stress: if they really worked and were safe, who wouldn’t be taking them? Can you imagine a safe pill that took five pounds off the belly and relieved stress? If it sounds too good to be true, it probably is.

Some supplements and vitamins are effective and safe. Calcium supplements and vitamin D promote long-term bone health and can reduce risks of developing osteoporosis. Fish oil has been shown to have beneficial effects on lowering cholesterol. St. John's Wort has provided some benefits in treating mild depression, but not severe depression. A multivitamin can be beneficial for people who do not eat a well rounded diet due to dietary restrictions or other health problems. The list goes on.

The key is to be skeptical of herbal supplements claims and to research specific supplements from a reputable source. The Mayo Clinic's Drugs and Supplement site has an extensive review of supplements and highlights the supporting data (or lack of) for each use. Keep in mind that not all supplements are safe. Heavily advertised Hydroxycut, for example, was recently pulled from shelves for causing liver problems. Other "fat burners" were just stimulants and were pulled off the market for causing heart problems. Many herbal medicines can also interact with traditional medicines, so always talk to your doctor first if you’re already on other medicines.

DrSugar's posts are for informational purposes only and should not be considered medical advice, diagnosis, or treatment recommendations. Click here for more details.

DrSugar Answers: Antidepressant, IBS, and Weight Gain?

DrSugar — Thu, 21 May 2009 03:30:00 -0700

 DrSugar is in the house and he's answering your health questions.

Dear DrSugar, 
I've recently been diagnosed with probable irritable bowel syndrome that is exacerbated by anxiety and depression. My doctor prescribed the antidepressant Citalopram to decrease my abdominal pain and stabilize my mood. I've read multiple reports about the correlation between antidepressant medication and weight gain. I was an overweight teenager with poor eating habits and have finally managed to lose a great deal of weight in the past year. I'd rather not pile it back on as a result of a pill. Is it true that Citalopram is likely to make me put on weight? Are there any other remedies that might help abdominal pain from IBS? Thank you.
- Concerned about Citalopram

This is a complicated issue and worthy of investigation, so to see what the doctor has to say on this matter, just read more.

Controlling the symptoms of irritable bowel syndrome (IBS) can be very difficult, and getting a handle on anxiety and depression is a great place to start. Unfortunately, many antidepressants are associated with weight gain. The antidepressant Citalopram is classified as a selective serotonin reuptake inhibitor (SSRI). While this class of medication is less likely to cause weight gain than older antidepressants, SSRIs still have about a 25 percent incidence of weight gain. Weight gain when starting an SSRI is not inevitable, but it is still a possibility. Alternative antidepressants not associated with weight gain, like buproprion and venlafaxine, have not been as thoroughly researched for effectiveness in treating IBS as the drug you were prescribed.

There are some simple IBS therapies, including dietary modifications and medication for constipation or diarrhea, that may help with your abdominal pain as well. Regular exercise can also help to relieve symptoms of constipation and uncomfortable bloating. If anxiety and depression are the main issues exacerbating your IBS, an antidepressant, like an SSRI, is probably your best option. Remember that if you begin to rapidly gain weight once you begin taking an SSRI, you can consult your doctor for other options. Good luck!

Have a question for DrSugar? Send it by private messaging me here, and I will forward it to the good doctor.

DrSugar's posts are for informational purposes only and should not be considered medical advice, diagnosis, or treatment recommendations. Click here for more details.