BY HOWARD F. BERLIN, MD, FACC

Patients frequently ask what supplemental vitamins they should take. This topic has become part of the medical landscape, and as a physician, I am concerned about what advice to give patients safely. Patients are bombarded by advertising, testimonial support, and peer pressure to take supplemental vitamins. The makers and sellers of these products also suggest that patients consult with their physician before taking vitamins or dietary supplements. This puts physicians in a very uncomfortable position.

This article provides a basic understanding of vitamins and further reinforces the recommendations from the National Institutes of Health (NIH) and the American Heart Association (AHA) about vitamins and dietary supplements for healthy adults. Vitamins are organic compounds required in tiny amounts for essential metabolic reactions in a living organism. These do not include minerals, fatty acids, or amino acids, nor do they encompass the large number of other nutrients that promote health but are not essential for life.

Vitamins

Vitamins act both as catalysts and substrates in chemical reactions. When acting as a catalyst, vitamins are bound to enzymes called cofactors. For example, vitamin K is part of the proteases involved in blood clotting. Vitamins also act as coenzymes to carry chemical groups between enzymes. For example, folic acid carries various forms of the carbon group in the cell — methyl, formyl, and methylene.

Until the 1900s, we obtained vitamins solely through food. Changes in diet could occur during a particular growing season that could alter the types and amounts of vitamins ingested. Vitamins have been produced as commodity chemicals and made widely available as inexpensive pills for several decades to allow supplementation of dietary intake.

The U.S. Food and Drug Administration (FDA) is largely responsible for our current predicament, in part because of the way it regulates vitamins. The Office of Dietary Supplements of the NIH has stated:
“Research studies in people to prove that a dietary supplement is safe are not required before the supplement is marketed, unlike for drugs. It is the responsibility of dietary supplement manufacturers/distributors to ensure that their products are safe and that their label claims are accurate and truthful. If the FDA finds a supplement to be unsafe once it is on the market, only then can it take action against the manufacturer and/or distributor, such as by issuing a warning or requiring the product to be removed from the marketplace.”

So, manufacturers do not have to prove that a supplement is effective but can claim that the product addresses a nutrient deficiency, supports health, or reduces the risk of developing a health problem — if true. When manufacturers make such claims, this message must follow the claim: “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.”

In essence, the multibillion-dollar supplements industry has the legal right to market vitamins without proof of efficacy. Only if the product is found to be unsafe after it is on the market can action be taken.

Dietary supplements

Dietary supplements are not intended to treat, diagnose, mitigate, prevent, or cure disease. Sometimes dietary supplements may have unwanted effects, especially if taken before surgery or with other dietary supplements or medicines or by people with certain health conditions. Whatever your choice, supplements should not replace prescribed medications or the variety of foods important to a healthful diet.

There are many examples of scientific findings that contradict certain claims or assumptions about the value of vitamin supplementation. For example, the Agency for Healthcare Research and Quality has issued a consensus document, “Effect of Supplemental Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cardiovascular Disease — October 2003.” This document concludes:

“The available scientific studies offer little evidence that supplementation with vitamin C, vitamin E, or coenzyme Q10 has any benefit on cardiovascular disease prevention or treatment. Indeed, for vitamin E and vitamin C there is good evidence that supplementation at the doses tested provides no benefit, in that large placebo controlled, randomized studies have reported no benefit in terms of all cause mortality, cardiovascular mortality, myocardial infarction, or blood lipids (e.g., the MRC/BHF trial, GISSI, HOPE, PPP, and ATBC). Isolated examples of possible benefit for vitamin E or vitamin C supplementation reported for specific outcomes in certain trials failed to be supported by other outcomes in the same trials (for example, the statistically significant beneficial effect of vitamin E supplementation on incidence of nonfatal myocardial infarction observed in the CHAOS trial must be balanced against the nonsignificant increase in fatal myocardial infarction with vitamin E in the same trial) or be confirmed in other trials. This lack of consistency in the evidence casts doubt on any of the reported associations being causal.

“There is good evidence that vitamin E supplementation has no clinically important effect on lipid levels. Regarding coenzyme Q10, the available evidence is much less, in terms of large randomized trials, than for vitamins C or E. Therefore, our conclusions are less definitive. The reported results have been mixed, with a meta-analysis and some individual studies reporting improvements in measures of cardiac function, but other studies reporting no such benefit. The more recent randomized trials report smaller benefits, if any, than older trials. The most that can be concluded at this point is that there is no conclusive evidence either supporting or refuting an effect of coenzyme Q10 on cardiovascular disease.”

Here is another example of findings that question or challenge some popular thinking about vitamin supplementation. The AHA has issued an evidence-based, scientific position paper that states:
“We recommend that healthy people get adequate nutrients by eating a variety of foods in moderation, rather than by taking supplements. An exception for omega-3 fatty acid supplements is explained below.

“The Dietary Recommended Intakes (DRIs) published by the Institute of Medicine are the best available estimates of safe and adequate dietary intakes. Almost any nutrient can be potentially toxic if consumed in large quantities over a long time. Interactions between dietary supplements and prescription drugs and among several dietary supplements taken at the same time may occur. Too much iron can increase the risk of chronic disease, and too much vitamin A can cause birth defects.

“There aren’t sufficient data to suggest that healthy people benefit by taking certain vitamin or mineral supplements in excess of the DRI. While some observational studies have suggested that lower rates of cardiovascular disease and/or lower risk factor levels result in populations who use vitamin or mineral supplements, it isn’t clear if this is due to the supplements. For example, supplement users may be less overweight and more physically active.”

In 2004, AHA’s Council on Nutrition, Physical Activity, and Metabolism summarized findings about vitamin supplementation and its affect on cardiovascular disease (CVD). It said, “No consistent data suggest that consuming micronutrients at levels exceeding those provided by a dietary pattern consistent with AHA dietary guidelines will confer additional benefit with regard to CVD risk reduction.”

	Patients are bombarded by advertising, testi-monial support, and peer pressure to take supplemental vitamins.

Antioxidant vitamin supplements

The AHA also has examined the role of antioxidant vitamins, which some studies indicated might contribute to cardiovascular health. The association noted that studies of healthy adults taking large doses of Vitamins A, C, and E did not establish a cause-and-effect relationship between vitamin intake and any observed changes in cardiovascular health. The AHA added, “Scientific evidence does not suggest that consuming antioxidant vitamins can eliminate the need to reduce blood pressure, lower blood cholesterol, or stop smoking.”
So, while there is no conclusive proof that increased antioxidant vitamin intake may have an overall cardiovascular benefit, antioxidant food sources — especially plant-derived foods such as fruits, vegetables, whole-grain foods, and vegetable oils — are recommended.

Omega-3 fatty acid supplements

Fish consumption has been linked to lower risk of heart disease. AHA recommends that patients without documented heart disease eat a variety of fish, preferably containing omega-3 oil, at least twice a week. Preferred species include salmon, herring, and trout.

AHA also recommends that patients with documented heart disease consume about 1 gram of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are types of omega-3 fatty acids. The preferred source for these acids is by eating fish, although physicians may consider recommending EPA and DHA supplements. Finally, AHA recommends people with high triglycerides consume 2 to 4 grams of EPA and DHA per day in the form of capsules as directed by physicians.

For more information on omega-3, see volume 110 of Circulation, pages 637 to 641.

Vitamin E and beta carotene

The Cleveland Clinic Foundation published results of its analysis of seven randomized trials of vitamin E supplementation, alone or in combination with other antioxidants, and eight trials of beta carotene supplements. The research involved 81,788 patients taking vitamin E and 138,113 taking beta carotene. Vitamin E did not lower mortality and did not significantly decrease the risk of cardiovascular death or stroke. Beta carotene produced a small but significant increase in death from all causes and a slight increase in cardiovascular death. The study, reported in The Lancet in 2007, discouraged use of beta carotene supplements because of the risk of death.

At this time, the totality of information indicates that there is no substitute for good eating habits and that a Mediterranean diet, aerobic exercise, weight loss, and smoking cessation are favorable steps to reduce the risk of cardiovascular disease. Research is ongoing and may yet reveal significant benefits from vitamin supplementation. But physicians must practice evidence-based medicine. We need to try to curb our patients’ current enthusiasm for vitamins until we are sure of the benefits and possible risks.