Antioxidants and Cholesterol:
Need for a Balanced View of the Evidence

WASHINGTON, D.C., August 15, 2001—Last week, the media spread a story on antioxidants that did not fairly reflect the research on which the story was based. The damage to consumer perceptions has been done, but the actual facts still deserve full consideration, and the whole story needs to be put into perspective. The key facts are these:

A recently published study demonstrates that the main effects of cholesterol-lowering drugs are not inhibited by antioxidants. These include lowering total cholesterol, lowering triglycerides, lowering LDL ("bad" cholesterol), and improving the LDL/HDL ratio. Questions are raised about the impact on HDL cholesterol, and especially on one subfraction of HDL.

Vitamin E, vitamin C, and other antioxidants can benefit heart health in ways that are quite separate from the effects of cholesterol-lowering drugs. The new study provides no basis for the antioxidant-bashing that has occurred.

The full story is somewhat complicated. A group of researchers at the University of Washington has been investigating the effects of two cholesterol-lowering treatments (simvastatin and niacin), with and without added antioxidants, as compared to antioxidants alone or a placebo. The antioxidant "cocktail" included in this study consisted of 1000 mg of vitamin C, 800 IU of vitamin E, 25 mg of beta-carotene, and 100 mcg of selenium. The cholesterol-lowering treatments were expected to lower total cholesterol, lower triglycerides, lower LDL cholesterol ("bad" cholesterol), and raise HDL cholesterol ("good" cholesterol).

The simvastatin-niacin treatments did in fact accomplish all these things. When the treatments were given in combination with antioxidants, however, the researchers said the antioxidants "modestly blunted" one of the expected effects, namely the increase in HDL cholesterol. They cautiously refer to this as an "unexpected adverse interaction." The headline of the article assertively announced that antioxidants "block the response of HDL" to the drug treatment. This was the message carried by the media to every corner of the globe, although the data provided in the article do not support this assertion.

The tables in the article show that the primary results of the cholesterol-lowering treatments, with or without antioxidants, were strikingly positive. In both groups, total cholesterol was reduced, triglycerides were lowered, LDL cholesterol was reduced, and HDL cholesterol was increased. The tables show that there was no statistically significant difference between the responses of the two groups, in terms of these effects. These main effects are shown in the table below. The LDL to HDL ratio also was markedly improved in both groups, from a ratio of more than 4 at the beginning of the study to a ratio of about 2 by the end of the study.

When subfractions of HDL were examined by the researchers, total HDL was divided into two fractions -- one fraction accounting for 85% or more of the total and another fraction accounting for 15% or less of the total. The major fraction increased in both groups. The minor fraction increased in the drug group but did not increase in the drug+antioxidant group. The authors are legitimately concerned about the reasons for this difference, and more research is needed. However, there is no consensus on the health significance of changes in the subfractions of HDL, and these subfractions are not the subject of current national cholesterol-lowering guidelines. The findings with respect to these subfractions certainly should not be allowed to overshadow the main effects.

An editorial accompanying this article concludes that physicians should not recommend antioxidants in excess of the Recommended Dietary Allowances and should "advise their patients that the use of antioxidants could be hazardous, especially in conjunction with lipid-lowering drugs." This is pure hyperbole and is not justified by the actual results of the study.

Antioxidants are much more likely to provide additional benefit with respect to heart health than to present cause for concern. The Food and Nutrition Board of the National Academy of Sciences released its completely updated report on recommended dietary allowances for antioxidants in 2000. The report says "there is reason to expect that the antioxidant vitamins should decrease the risk of cardiovascular disease." The report points out that the dominant theory about the development of cardiovascular disease is that oxidized LDL sets off a chain of events that damage the blood vessel. Vitamin E has been shown to inhibit the oxidation of LDL. In addition, the report notes that vitamin E could affect the development of atherogenesis by other mechanisms such as inhibiting platelet aggregation, inhibiting adhesion of monocytes to the vessel walls, stimulating dilation of the vessels, and inhibiting protein kinase C.

There is strong evidence from some large epidemiologic studies that people with higher dietary intakes of vitamin E or people who used vitamin E supplements did in fact have a

lower risk of heart disease than non-supplement users or people with lower intakes. The results of clinical trials in people at high risk or people with existing heart disease have been disappointing, but the overall evidence is still sufficiently positive to justify several ongoing studies in healthy populations using levels of vitamin E far beyond RDA levels.

"The ongoing studies need to be carried to their conclusion, and scientists as well as journalists need to keep an open mind and present a balanced view of the totality of the evidence," said Annette Dickinson, Ph.D., Vice President for Scientific and Regulatory Affairs for the Council for Responsible Nutrition (CRN).

The Council for Responsible Nutrition (CRN) is a science-based, trade association founded in 1973 and represents more than 110 companies in the dietary supplement industry, including ingredient suppliers and manufacturers. CRN members adhere to a strong code of ethics, comply with dosage limits and manufacture dietary supplements to high quality standards under good manufacturing practices.