A recent report from the National Academy of Sciences Institute of Medicine recommended modest increases in dietary antioxidants but stopped far short of prescribing megadoses of vitamins and minerals to prevent cancer and other chronic diseases.
The April 2000 report highlights the chasm of uncertainty between the laboratory and epidemiologic evidence suggesting the benefits of antioxidants on one hand, and the lack of a scientific basis for specific recommendations on the other. So the most consistent advice remains: Eat fruits and vegetables.
The third in a series on dietary recommendations for U.S. and Canadian residents, the report expands on the Recommended Dietary Allowances that NAS has set since 1941. In some ways, it reflects a new approach to prescribing nutrient intake. The dietary reference intakes for the first time include not only RDAs (the amount of a nutrient needed to meet nutritional requirements), but also AIs (adequate intake) and ULs (tolerable upper intake levels).
AIs are a less precise measure, used when there is insufficient evidence to determine the RDA. ULs represent the maximum intake that is likely to pose no health risks for most people. The setting of ULs is meant to alert the public that too much of a good thing can be harmful: Huge doses of some nutrients can cause symptoms ranging from diarrhea to hair loss to hemorrhage.
For vitamin C, the new recommended intakes are 75 milligrams per day for women and 90 mg for men (up from 60 for both men and women), with smokers advised to get an additional 35 mg. The daily UL for vitamin C is 2,000 mg per day. For vitamin E, the recommended adult dose is 15 mg and the UL is 1,000 mg; and for seleniuma component of oxidant defense enzymes produced by the bodythe RDA is 55 micrograms and the UL is 400 micrograms.
The panel noted that most people can easily reach these RDA values from foods, making dietary supplements unnecessary. The report does not recommend daily intake levels or ULs for beta carotene and other carotenoids, citing a lack of evidence. But it cautions against taking them in high doses and suggests that beta-carotene supplementation should be used only to prevent or correct vitamin A deficiency.
"A direct connection between the intake of antioxidants and the prevention of chronic disease has yet to be adequately established," said Norman I. Krinsky, Ph.D., chair of the NAS Panel on Dietary Antioxidants and Related Compounds, and a professor of biochemistry at Tufts University School of Medicine, Boston. "We do know, however, that dietary antioxidants can in some cases prevent or counteract cell damage that stems from exposure to oxidants. But much more research is needed to determine whether dietary antioxidants can actually stave off chronic disease."
Visible Departure
Suzanne Murphy, Ph.D., a nutritionist at the Cancer Research Center of Hawaii who chairs an NAS subcommittee on the uses of dietary reference intakes, said that increasing the recommended intake of vitamin C is the panels "most visible departure" from the conventional thinking that set RDAs at the minimum needed to prevent deficiency diseases. The new recommendation, substantially higher than what is needed to prevent scurvy, is based on 80% saturation of leukocytes, a level that some scientists feel may have wider preventive benefits.
Although a tentative step, "it is at least going in the direction of thinking about chronic disease prevention," Murphy said. "The panel, I think, was breaking new ground, trying to look at requirements in a whole new way." The problem is the lack of solid data on which to base recommended intake. For instance, she said, the 80% figure is somewhat arbitrary, and other nutrition experts feel the panel might have selected other percentages instead.
In contrast to the government advisory panel, marketers of dietary supplements do not hesitate to link their product to health benefits. One company touts lycopene (a carotenoid found in tomatoes) on the Internet to prevent prostate cancer. They cite, among other antioxidant studies, one that was published in the Journal of the National Cancer Institute in 1995. Yet the study, like most others in the field, examined consumption of foods, not pills.
The lead author of that study, Edward L. Giovannucci, D.Sc., M.D., of Harvard Medical School in Boston, said such sales pitches are "premature and not based on evidence. There is very little epidemiologic evidence on supplement intake." Lycopene, like a number of other antioxidants, is a promising lead, he said, but far from being ready for recommendation as a supplement. He said further studies with biomarker end points are needed to guide the design of clinical prevention trials.
With the vast number of potential interactions among dietary constituents, some still unknown, Giovannucci said, "its really going to be an enormous task to figure out what are the specific chemical constituents that confer the benefit . . . its going to be almost impossible to distill that into a pill."
Prevention Studies
It is for that reason that Kedar N. Prasad, Ph.D., of the Center for Vitamins and Cancer Research at the University of Colorado, Denver, believes prevention studies have taken the wrong tack by focusing on single antioxidants. The most informative trial, he said, would be one that combines moderate doses of multivitamins, a low-fat, high-fiber diet, lifestyle changes such as exercise, and is designed to test the individual as well as synergistic effects of those three components.
"I believe these three are equally importantif you ignore one, you will not get the maximum benefit," Prasad said. "But no such clinical trial has yet been performed." Previous trials have suggested that single micronutrients in large doses may actually stimulate cancer growth, he said. But in combination, they each exert unique antioxidant effects as well as acting as checks on one anothers harmful effects.
A recent study led by the National Cancer Institutes Arthur Schatzkin, M.D., Dr.P.H., may lend support to this whole-diet approach. In the study of 42,254 women, published in the April 26 Journal of the American Medical Association, Schatzkin and colleagues found that women who ate the largest amounts of healthy foods (fruits, vegetables, whole grains, low-fat dairy products, and lean meats and poultry) had death rates from cancer, heart disease, and stroke about 30% lower than those consuming very little of these foods.
"The lesson we have learned is that there is more to foods than the individual nutrients that we have been studying," said Murphy.
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