How do antioxidant vitamins block the high density lipoprotein-cholesterol response to lipid therapy for heart disease?

Amir Zeki, Marian Cheung, Xue Qiao Zhao, Drew Poulin, Joseph Davis, Alice Dowdy, B. Greg Brown

Research output: Contribution to journalArticlepeer-review


Low levels of HDL (high density lipoprotein) cholesterol are associated with an increased risk of CHD (coronary heart disease), the major cause of premature death in the United States. Therapeutic approaches to increase HDL levels are limited. Niacin (nicotinic acid) is the most effective agent currently available, and has helped reverse CAD (coronary artery disease) in recent studies. The current best therapy to raise HDL includes exercise, weight loss, and niacin, often with a 'statin' added for LDL-lowering. However, recently it was confirmed that a combination of supplemental antioxidants that is widely used in the U.S. reduces the rise in HDL by 50% to 65%. This rise in HDL usually occurs in response to lipid therapy with niacin and simvastatin. Consumption of a combination of vitamins E, C, beta-carotene, and selenium, taken at the high doses commonly used by Americans as nutritional supplements, nearly completely inhibits the desirable 30% increase in HDL-cholesterol. This increase normally occurs in response to treatments aimed at improving abnormal lipid levels in individuals at a very high risk of developing CHD. Specifically, the niacin-induced rise in HDL-2 cholesterol and apolipoprotein A-I levels (the HDL components most clearly associated with protection against heart disease) are selectively blocked by the vitamins. However, LDL lowering was equivalent with or without the use of antioxidants. Since both vitamin E and beta-carotene have been shown to affect gene regulation, these two components are the most likely cause of this new and important observation. Another ongoing study suggests the role of one of these possible antioxidants. Earlier data from an ongoing lipid-lowering study (FATS or Familial Atherosclerosis Treatment Study, B. Greg Brown et al), suggest that antioxidants have an identical effect in subjects with normal HDL levels, and suggest that the effect may be due to beta-carotene. The goal of this study, a sub-study of the original HATS project (HATS or HDL Atherosclerosis Treatment Study, B. Greg Brown et al), is to determine conclusively which component of the antioxidant combination is responsible for the detrimental effect on HDL levels. Since both niacin and these antioxidant supplements are readily available without prescription, it is important to identify the culprit vitamin. This issue is of immense public health importance in view of the vast number of Americans who consume large quantities of supplemental antioxidants.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Issue number2
StatePublished - Feb 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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