Supplements: What Works and What Does Not Work

The Best Alternative Medicine
by Kenneth R. Pelletier

(Page 4 of 5)

Recently, the Third National Health and Nutrition Examination Survey showed that supplement use among adults ranges from about 36 to 51 percent. Furthermore, about 48 percent of children ages three to five take supplements. Currently, there are about six hundred supplement manufacturers in the United States, producing approximately four thousand products, with total annual sales of at least $4 billion and rising rapidly. Surveys indicate that consumers most often take supplements for disease prevention, boosting immunity, increasing energy, improving fitness, increasing alertness and mental activity, reducing stress, and treating medical problems.

For some time, the U.S. government has been concerned that consumers may be taking supplements for reasons that are not justified by scientific research. However, consumers are, for the most part, protected from unsafe products, because the government can remove supplements from the market if they present a significant or unreasonable risk of illness if used as recommended on the label.

Until recently, the literature used by distributors of dietary supplements was not allowed to contain health claims. A 1994 federal law changed this, and now publications that are reprinted in their entirety, and are not misleading, may be used in retail settings. Restrictions on labels are even more stringent; only a limited number of health claims is permitted on labels. Only four of these claims have been approved, including those dealing with the relationship between dietary calcium and osteoporosis; between folate and neural tube defects; between soluble fiber from whole oats and coronary heart disease; and between sugar alcohols and dental caries. Thus, the government remains conservative in its attitude toward supplements.

Among the supplements currently on the market are a number of controversial substances whose health benefits have not been definitively proven by RCTs. Some of the new substances have been popularized by special interest groups, such as bodybuilders, and by the lay press. Published research on such substances may lie outside mainstream medical literature.

Following is an analysis of some of the most popular of these substances. This analysis attempts to objectively assess the best existing research.

Selenium. Selenium is a trace mineral that has been the subject of extensive research and controversy. Found in brown rice, seafood, enriched white rice, whole wheat flour, and Brazil nuts, it is a powerful antioxidant, and is also a component of glutathione peroxidase, an antioxidant enzyme that helps to protect against free radical damage.

Much of the world's soil is deficient in selenium, which leads to low selenium intake. According to epidemiological studies, this accounts for an increased risk in certain regions of many kinds of cancer, including breast and colon cancer, and increased heart disease in certain regions. For example, people in selenium-depleted north-central China suffer some of the world's highest rates of esophageal and stomach cancer. However, these rates declined when some inhabitants were given selenium and vitamin E.

People need very little selenium to protect their health. For men, the RDA is 70 mcg (micrograms, or millionths of a gram), and for women it is 55 mcg. Many authorities now advise 200 to 400 mcg per day. However, 700 to 800 mcg a day may be toxic. Chronic ingestion of 5,000 mcg a day has been reported to result in fingernail changes, hair loss, nausea, abdominal pain, diarrhea, nerve problems, fatigue, and irritability. Because vitamin E enhances the effects of selenium, it can increase this possible toxicity.

Among the claims made for selenium are that it protects against cancer, improves immunity, protects against oxidative stress, prevents and treats AIDS-related pathology, and treats infertility. In actuality, though, RCTs present rather sketchy evidence of most of these claims.

• High blood pressure in pregnancy. According to a 1994 Chinese study by Han, pregnant women at risk for high blood pressure showed reduction and prevention of hypertension.

• Cancer. In 1996, an eight-year study by Dr. Larry C. Clarke at the University of Arizona revealed significant reductions in cancer mortality among people taking 200 mcg daily. However, an analysis of Dutch cancer patients indicated that cancer patients did not have low levels of selenium in their bodies. Thus, selenium's role in cancer is unproven.

• HIV. A 1996 study of HIV patients by Delmas-Beauvieux showed that those receiving selenium had higher glutathione peroxidase activity, suggesting increased immune function.

Other conditions that showed an inconclusive reaction to selenium were myotonic dystrophy, asthma, and infertility. Also, selenium showed no ability to reduce oxidative stress in children with cystic fibrosis.

People with special antioxidant needs may benefit from moderate selenium supplementation, but most claims about selenium remain unproven.

Chromium. Chromium is necessary for insulin to function properly in the human body. Insulin not only helps to metabolize sugars, but is also involved in the body's use of protein and fats. Borderline chromium deficiency may help to trigger adult-onset diabetes, but is not the underlying cause of diabetes, so chromium cannot cure the disease.

A majority of the American population takes in less than the RDA of chromium. Estimates are that 50 percent of the American population has a marginal or serious chromium deficiency, especially the elderly, pregnant women, and athletes. Therefore, supplementation with 50 to 200 mcg may be prudent.

Chromium supplementation does present some dangers. Excess dietary chromium may accumulate in the tissues and cause chromosome damage, which may contribute to cancer. Daily supplementation of 200 mcg or more of chromium picolinate, an organic form of chromium, has been linked to iron deficiencies because chromium competes with iron for transport and distribution. Trivalent chromium, the form found in the diet, has very low toxicity and a great margin of safety, but hexavalent chromium is toxic, and long-term occupational exposure can lead to skin problems, perforated nasal septum, and lung cancer.

Among the claims made for chromium are that it promotes an increase in lean body mass, increases strength during resistance training, stabilizes blood sugar levels, and lowers cholesterol. Following is an examination of these claims.

• Strength and lean body mass. A 1989 study by Dr. Kenneth Cooper reported that football players were able to increase their muscle mass after taking 1.6 mg of chromium picolinate for two weeks, with total body fat decreasing from about 16 to 12 percent. This is a relatively high intake of chromium picolinate; some athletes take as little as 600 mcg a day (which is still equivalent to the dosage level that has produced chromosome damage in animals).

  However, two recent studies have contradicted the findings of this 1989 study. In a 1996 study reported in the American Journal of Clinical Nutrition, muscle mass increased with resistance training, regardless of chromium supplementation. In a 1994 University of Massachusetts study, the strength and body fat of athletes was unaffected by the supplementation.

  In a recent review of the clinical literature, Dr. Pamela Peeke, a National Institutes of Health researcher, failed to establish any beneficial effects of chromium supplementation on lean body mass and enhancement of strength. It appears as if the beneficial effects of chromium supplementation may occur only in individuals with impaired chromium status.

• Weight loss. Despite the negative findings of research on athletes, chromium supplementation was found in a recent study to help overweight people lose body fat and improve the ratio of lean to fat tissue. In a 1996 study by Dr. Gilbert R. Kaats, chromium supplementation at both 200 and 400 mcg daily resulted in significant fat loss.

• Glucose tolerance. Equivocal findings exist in studies that examine whether chromium helps to normalize blood sugar levels. Chromium supplementation can improve or normalize impaired glucose tolerance, but normal glucose tolerance is not further improved with chromium supplementation, according to studies by Anderson in 1991 and Abraham in 1992.

• Blood lipids. Some researchers have found no improvement in blood lipids with chromium supplementation, while others, including Press in 1990, have obtained more positive results. Many nutritional factors influence lipid metabolism, and it may be that only certain cases are related to a low chromium status because of impairment of glucose tolerance. These cases would be expected to improve with chromium supplementation.

In conclusion, because chromium deficiency seems to be widespread in the U.S. diet, individuals with impaired glucose tolerance or lipid metabolism may benefit from chromium supplementation, especially if testing shows low blood levels of chromium. For other people, it is probably wiser to rely on nutritional sources.

Chromium can be obtained in the diet from whole grains, brewer's yeast, wheat germ, liver, broccoli, prunes, nuts, cheese, and fortified cereals. One form of yeast, known as chromium-enriched yeast, has an even higher chromium content than brewer's yeast. Both of these forms of yeast contain GTF (glucose tolerance factor) chromium, which is much better absorbed by the body than the other forms.

Coenzyme Q₁₀. Coenzyme Q₁₀, also known as ubiquinone, acts like a vitamin in the body and works as a catalyst in chemical reactions, even though it is not actually an enzyme. It is found in every cell in the body. It has also shown potential as an antioxidant, helping to protect against free radicals. Its primary function in the body is to help convert food into energy.

Studies have suggested that coenzyme Q₁₀ might be useful in protecting against tissue damage in heart disease, deterioration of the retina, breast cancer, and other illnesses. However, there have not yet been many large, well-designed studies on coenzyme Q₁₀.

Claims that have been made for coenzyme Q₁₀ include that it slows aging by supporting immune functioning, prevents heart disease through its antioxidant action, and improves physical performance. No adverse effects have been reported.

• Protection against tissue reperfusion, or restoration of blood flow, injury. Coenzyme Q₁₀ has shown promising results in protecting against injury from reperfusion, or rapid restoration of blood flow, to tissues after the blood supply has been stopped, as in heart attack or cardiac surgery. In a 1994 clinical trial in Italy by Chello, forty coronary artery bypass surgery patients who received 150 mg of Q₁₀ a day for seven days before the operation showed less evidence of damage and a lower incidence of ventricular arrhythmias during the recovery period. However, when used just twelve hours before surgeries, Q₁₀ showed no positive effect. Therefore, this application will remain a "gray area" until more large-scale studies are done.

• Congestive heart failure. Coenzyme Q₁₀ has proven beneficial in patients with congestive heart failure. In a 1993 Italian study by Lampertico, supplementation produced improvement in a number of indicators of heart and lung function. However, the study had problems both in design and in the brevity of the treatment period. In another 1993 Italian RCT, this one by Morisco, patients using coenzyme Q₁₀ required less hospitalization for worsening heart failure, and episodes of pulmonary edema or cardiac asthma were significantly reduced. Research in this area is still in the early stages, and it remains uncertain.

• Muscle dystrophies. Coenzyme Q₁₀ was shown in two successful, small double-blind trials, both by Folkers in 1995, to improve physical performance in patients with a variety of muscular dystrophies and neurogenic atrophies. In both studies, definite improvement in physical performance was found in the patients receiving coenzyme Q₁₀. However, these were very small studies, performed by an ardent supporter of the nutrient.

• Sports performance. There have been claims that coenzyme Q₁₀ can improve sports performance, but the evidence has largely been negative. In a 1991 study by Braun, triathletes and cyclists were not found to perform better after taking 100 mg a day of Q₁₀ for four to eight weeks.

• Cancer. Coenzyme Q₁₀'s antioxidant activity has led to suggestions that it might be beneficial in the treatment of cancer. In one 1994 study by Lockwood, none of the patients in the supplemented group died, versus the predicted or expected mortality of four; none had further metastases; and six showed apparent partial remission. However, because a number of antioxidants were used, the results cannot be attributed to Q₁₀ alone. Thus far, nothing definitive has been proven.

• Gum disease. In a study cited by Cooper in 1996, Japanese researchers reported in 1994 that coenzyme Q₁₀ was used successfully in adult periodontitis, both as a treatment in itself and in combination with standard nonsurgical treatment. However, in 1995, researchers disputed this success in the British Dental Journal.

In conclusion, although research on coenzyme Q₁₀ has yielded positive findings in some areas, its most promising applications appear to be in medical situations where the supervision of a physician is required. It has not been demonstrated that coenzyme Q₁₀ is appropriate for use as a daily nutritional supplement among healthy people.

It is preferable to get coenzyme Q₁₀ from food sources, which include spinach, sardines, and peanuts. However, some of these foods are high in fat.

Superoxide Dismutase (SOD). Superoxide dismutase, or SOD, is an extremely potent antioxidant that protects cells against damage from free radicals. It is one of the three main antioxidant enzymes found in our cells.

Human clinical studies of SOD are still at a very early stage, but some researchers claim it slows the aging process and has potential in treating Alzheimer's disease.

SOD supplements are sold in oral form, but consumers should be aware that oral SOD products are completely destroyed in the gut. Benefits of SOD come from injectable forms.

• Skin problems and postradiation damage. Although research is limited, a promising application of SOD is for severe skin diseases and radiation damage either from prolonged sun exposure or due to radiation treatment. One researcher, Michelson, has found SOD useful in treating various skin disorders, including a very severe case of scleroderma, an autoimmune disease. He also treated severe postradiation damage with two injections weekly for three months, with substantial improvement evident in two weeks. French and Japanese researchers have also reported positive results in treating scleroderma.

• Arthritis. SOD injections are used in Europe to treat musculoskeletal inflammation and osteoarthritis. Bovine SOD, injected into the joint, has been found beneficial in controlled double-blind studies in treating osteoarthritis of the knee. However, treatment of rheumatoid arthritis has been disappointing, according to Flohe in 1988.

• Reperfusion or restoration of blood flow damage. As with coenzyme Q₁₀, SOD is being investigated for its ability to protect against free radical damage, reducing injury to the brain and other organs caused by reperfusion, oxygen deprivation, drops in blood pressure, and increased cranial pressure after trauma.

  Based on a 1993 study by Marzi of patients with multiple injuries, SOD helped to mitigate cardiovascular and lung failure, and reduced intensive care treatment and inflammation.

  In a 1993 study of patients with severe head injuries, Muizelaar found that far fewer patients on high dosages of SOD died or lapsed into a vegetative state. Lower dosages did not help.

  While SOD has shown exciting potential in this specialized medical application, results are not yet conclusive.

• Anti-aging. Despite claims, there is no evidence that SOD delays aging in humans. However, in animals, when both SOD and catalase are increased, maximum life span is significantly increased, according to a 1994 literature review by Warner.

Copyright © 2000 by Dr. Kenneth R. Pelletier, Inc.

About the Author

Dr. Kenneth R. Pelletier is a clinical professor of medicine at the University of Maryland and the University of Arizona Schools of Medicine. He is a medical and business advisor to NIH, the World Health Organization (WHO), and major corporations, including American Airlines, Medtronic, Disney, Merck, Ford, Microsoft, Blue Cross, Blue Shield, and United Healthcare. As director of the American Health Association, he is the author of more than two hundred professional papers, and he was previously a clinical professor of medicine at the Stanford University School of Medicine.