Of course, purity is not the only important quality. The question that is much harder to answer is: Will this supplement actually improve the health of the general population? The National Cancer Institute studies led by Omenn and his colleagues suggest that some supplements are not only ineffective, but can actually be harmful. A small subset of studies, however, suggests that supplements may be beneficial for preventing certain conditions. (INFOGRAPHIC 12.7)

Question 12.6

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For instance, in 1997, researchers at Harvard University and its affiliated hospitals and schools began a clinical trial as part of the Physicians Health Study II to test whether moderate doses of multivitamins might prevent cancer or heart disease. “When you think about individual vitamin supplements tested in trials, there’s been an emphasis on high doses,” explains Howard Sesso, one of the study’s leaders and an associate professor of epidemiology at the Harvard School of Public Health. “We thought it would be interesting to have the opposite approach: It might be more appropriate to test a standard common multivitamin that has all the essential vitamins and minerals in combination, but in lower, more usual, doses that you would get in your diet.”

To do this, the Harvard researchers tracked the health of nearly 15,000 physicians older than 50 years who had been randomly assigned to take either a standard multivitamin or a sugar pill every day for an average of 11 years. Although the multivitamin takers did not end up with a reduced risk for heart disease, they were 8% less likely to develop cancer during the follow-up period than the doctors who did not take multivitamins. A separate arm of the study that evaluated the effects of taking 400 mg vitamin C every day and 400 IU vitamin E every other day did not, however, find that the two vitamins reduced cancer risk. It seemed to be the combination of many vitamins, at lower doses, that made a positive difference.

Sesso and his colleagues were very pleased with their study results, “But what we were immediately trying to think through was: How do you explain the findings?” Indeed, one major question is exactly how vitamins may protect against cancer. Another question is whether a person is better off getting vitamins through whole foods or through pills. “I think a lot of people would argue that the natural approach through food is the way to go,” Sesso says, but more research is needed to prove this point.

Supplements seem to pose the highest risks when they are what are known as “high-potency supplements,” which include one or more nutrients or ingredients in amounts significantly in excess of recommendations. These supplements include the mega-doses of beta-carotene (30 mg) and vitamin A (25,000 IU) that the participants were taking as part of Omenn’s CARET trial. Sometimes, these supplements also exceed the established Tolerable Upper Intake Limit (UL), the maximum level of daily intake that is likely to cause no risk of adverse health effects to almost all individuals in the population. No laws establish or cap potency for any supplements, except potassium. But high doses of some supplements can cause fatigue, diarrhea, hair loss, kidney stones, liver and nerve damage, and birth defects. They can lead to nutrient imbalances or interactions, reducing the absorption and utilization of other nutrients. And taking high doses of many minerals—as well as the fat-soluble vitamins A, D, and E—can be toxic. Even high doses of the water-soluble vitamin B₆ are toxic, potentially causing permanent nerve damage. It’s important to remember that even if you don’t exceed the UL for a nutrient through supplement use, you may exceed it when you combine the amount you’re getting from a supplement with the amount you’re getting from food. (INFOGRAPHIC 12.8)

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