Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL

Arterioscler Thromb Vasc Biol. 2001 Aug;21(8):1320-6. doi: 10.1161/hq0801.095151.


One strategy for treating coronary artery disease (CAD) patients with low HDL cholesterol (HDL-C) is to maximally increase the HDL-C to LDL-C ratio by combining lifestyle changes with niacin (N) plus a statin. Because HDL can prevent LDL oxidation, the low-HDL state also may benefit clinically from supplemental antioxidants. Lipoprotein changes over 12 months were studied in 153 CAD subjects with low HDL-C randomized to take simvastatin and niacin (S-N), antioxidants (vitamins E and C, beta-carotene, and selenium), S-N plus antioxidants (S-N+A), or placebo. Mean baseline plasma cholesterol, triglyceride, LDL-C, and HDL-C levels of the 153 subjects were 196, 207, 127, and 32 mg/dL, respectively. Without S-N, lipid changes were minor. The S-N and S-N+A groups had comparably significant reductions (P</=0.001) in plasma cholesterol, triglyceride, and LDL-C. However, increases in HDL-C, especially HDL(2)-C, were consistently higher in the S-N group than in the S-N+A group (25% vs 18% and 42% vs 0%, respectively). With S-N, but not with S-N+A, there was a selective increase in apolipoprotein (apo) A-I (64%) in HDL particles containing apo A-I but not A-II [Lp(A-I)] and their particle size. Thus, in CAD patients with low HDL-C, S-N substantially increased HDL(2)-C, Lp(A-I), and HDL particle size. These favorable responses were blunted by the antioxidants used owing to a striking selective effect on Lp(A-I). This unexpected adverse interaction between antioxidants and lipid therapy may have important implications for the management of CAD.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology
  • Cholesterol, HDL / chemistry
  • Cholesterol, HDL / metabolism*
  • Cholesterol, LDL / metabolism
  • Coronary Disease / drug therapy*
  • Coronary Disease / metabolism
  • Dietary Supplements
  • Drug Interactions
  • Female
  • Humans
  • Hypolipidemic Agents / pharmacology*
  • Hypolipidemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Niacin / pharmacology*
  • Niacin / therapeutic use
  • Particle Size
  • Selenium / pharmacology
  • Simvastatin / pharmacology*
  • Simvastatin / therapeutic use
  • Vitamin E / pharmacology
  • beta Carotene / pharmacology


  • Antioxidants
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hypolipidemic Agents
  • beta Carotene
  • Vitamin E
  • Niacin
  • Simvastatin
  • Selenium
  • Ascorbic Acid