22. Describe the controversy around the effects of combining statin drugs with antioxidant supplements containing beta-carotene?
A 3-year randomized controlled trial in 160 patients with documented coronary heart disease and low serum high density lipoprotein (HDL) concentrations found that a combination of simvastatin (Zocor) and niacin increased HDL2 levels, inhibited the progression of coronary artery stenosis, and decreased the frequency of cardiovascular events, including MI and stroke (89). Surprisingly, when an antioxidant combination (1,000 mg of vitamin C, 800 IU of alpha-tocopherol, 100 mcg of selenium, and 25 mg of beta-carotene daily) was taken with the simvastatin-niacin combination, the protective effects were diminished. Since the antioxidants were taken together in this trial, the individual contribution of beta-carotene cannot be determined. In contrast, a much larger randomized controlled trial of simvastatin and an antioxidant combination (600 mg of vitamin E, 250 mg of vitamin C, and 20 mg of beta-carotene daily) in more than 20,000 men and women with coronary artery disease or diabetes found that the antioxidant combination did not diminish the cardioprotective effects of simvastatin therapy over a 5-year period (90), suggesting that the antioxidant combination may have interfered with the HDL-raising effect of niacin in the former trial. Further research is needed to determine potential interactions between antioxidant supplements and cholesterol-lowering agents, such as niacin and HMG-CoA reductase inhibitors (statins).