Do Antioxidants Contribute to Heart Disease?

Study Shows Vitamins Raise Levels of Bad Cholesterol in Mice

May 3, 2004 --Taking antioxidant vitamins, a practice done daily by millions of Americans in hopes of preventing heart disease, may actually contribute to it by boosting production of "bad" cholesterol.

New research on rodents shows that high doses of the much ballyhooed antioxidant nutrients -- vitamins C, E, and beta-carotene -- stimulate their liver's production of very low density lipoproteins (VLDL), which convert in the bloodstream to low-density lipoprotein (LDL), the so-called "bad" cholesterol that accumulates along artery walls and leads to atherosclerosis, or hardening of the arteries.

This suggests that getting doses of antioxidants usually found in vitamin supplements -- but not what is found in food -- may be "potentially harmful" for the heart, says researcher Edward A. Fisher, MD, PhD, director of the Lipid Treatment and Research Center at New York University Medical Center.

"If you're concerned about heart disease, our study offers another reason not to take them," he tells WebMD. "But it's not as simple as whether you should take, or not take, vitamin E or other antioxidants. What our study shows is that in some situations, oxidative stress might be good and in others it is bad."

Until now, "oxidative stress" was considered to be all bad -- the process in which "free radicals," or unstable molecules, damages cells and contribute to scores of disease.

Antioxidants prevent oxidative stress and have been thought to help reduce risk of cancer, diabetes, Alzheimer's disease, and other conditions. This is one reason why fruits and vegetables, which are generally rich sources of these nutrients, are universally recommended. But the role of higher-dose vitamin supplements is less established, particularly in preventing heart disease.

Some studies show that antioxidant supplements are helpful. Antioxidants are thought to prevent the changes that turn cholesterol molecules in the blood into substances that can form plaques in artery walls, blocking blood flow. But other studies indicate these supplements may be wasted money because they offer no benefit -- and may even boost heart disease risk.

Antioxidants Boost LDL Cholesterol

In his study, Fisher's team found that vitamin E, a well-known antioxidant, prevented the normal breakdown of fats in rat and mouse liver cells. In other words, these antioxidants prevented the liver from destroying fats such as VLDL, the precursor to "bad" LDL cholesterol. The antioxidants caused more VLDL to be present.

His research, published in the Journal of Clinical Investigation, is reportedly the first to link antioxidant vitamins with increased VLDL production. And that's what it makes it important, says one expert.

"The bottom line of this paper is that you shouldn't assume that taking antioxidant vitamins is only going to have beneficial effects on cardiovascular disease," says Ronald M. Krauss, MD, director of atherosclerosis research at Children's Hospital Oakland Research Institute, who was not involved in Fisher's study but wrote an accompanying editorial to it.

"There is no human clinical information -- the research was done on animals -- so this study doesn't offer a recommendation of whether or not you should take antioxidant vitamins," Krauss tells WebMD. "But it provides good background into what may be occurring when one does take antioxidants and help explain some previous findings."

Two years ago, a study of 20,000 people -- already with heart disease risks such as diabetes or blood vessel damage -- showed that taking daily supplements of vitamins C, E, and beta-carotene produced small but noticeable increases in heart disease risk factors such as higher levels of LDL cholesterol and triglycerides, a blood fat linked to heart disease. This study also linked these supplements to lower levels of "good" HDL cholesterol.

"The changes experienced were modest but consistent with mechanisms identified in this paper," Krauss tells WebMD. He says a previous study showed that giving an antioxidant cocktail to people with heart disease reduced the benefits of some cholesterol-lowering drugs.

Last June, after reviewing 15 previous studies involving more than 15,000 people, Cleveland Clinic researchers reported in The Lancet that taking vitamin E did not help prevent heart disease and that taking high levels of beta-carotene supplement actually caused a slight increase in risk of heart attack or stroke. Two weeks later, the U.S. Preventive Services Task Force published its own paper in Annals of Internal Medicine showing there was no evidence that antioxidants, or folic acid, protected against heart disease -- and the agency even warned against taking beta-carotene supplements, which have previously been linked to increased lung cancer risk in smokers.

Does this mean that antioxidant supplements should be avoided? Not necessarily, says Krauss.

"There is evidence that supplements are beneficial for other conditions. And there is the suggestion that if you start taking them early in life, before atherosclerosis develops or there are significant signs of heart disease, these vitamins might be protective, rather than waiting until the disease has come into the picture. What this study shows is that despite popular belief that antioxidants are all good, they might have their downside as well, at least as it pertains to heart disease."

Show Sources

SOURCES: Pan, M. Journal of Clinical Investigation, May 2004; vol 113: pp 1277-1287. U.S. Preventative Services Task Force, Annals of Internal Medicine, July 1, 2003; vol 139: pp 51-55. Vivekananthan, D. The Lancet, June 14, 2003. Heart Protective Study Collaborative Group, The Lancet, July 6, 2002, vol 360: pp 23-33. Edward A. Fisher, MD, PhD, director, Lipid Treatment and Research Center; Leon H. Charney Professor of Cardiovascular Medicine; professor of cell biology, New York University Medical Center, New York. Ronald M. Krauss, MD, director of atherosclerosis research, Children's Hospital Oakland Research Institute, Oakland, Calif.
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