Human Intervention Trials on Effects of Antioxidant Supplements on Risk or Progression of Coronary Heart Disease

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A number of studies show that vitamin E decreases the oxidative susceptibility of LDL. Animal investigations as well as human epidemiological data show that antioxidants decrease the risk or progression of coronary heart disease.

Intervention trials will be now discussed aiming to assess the effects of antioxidant supplements on risk or progression of heart disease in various groups.

A randomized nutrition intervention trial provided daily multiple vitamin-mineral supplementation in 29,584 adults from Linxian, China. The largest reductions were for cerebrovascular disease mortality (at doses of one to two times the U.S. recommended dietary allowances) mortality from cerebrovascular disease over a 5-year period. Mortality was 10% lower among subjects supplemented with /3-carotene, vitamin E, and selenium (Blot etal, 1995).

A randomized, double-blind, placebo-controlled primary prevention trial (the ATBC study) was primarily aimed to determine whether daily supplementation with a-tocopherol, /3-carotene, or both would reduce the incidence of lung cancer and other cancers. A total of 29,133 male smokers (21 cigarettes a day for 36 years) 50-69 years of age were given a-tocopherol (50 mg per day) and/or 20 mg synthetic /3-carotene for 5-8 years. Thirty-five fewer deaths from ischemic heart disease and 11 fewer deaths from ischemic stroke, but 22 more deaths from hemorrhagic stroke among men who received vitamin E supplements were counted. Fewer cases of prostate cancer were diagnosed among those who received a-tocopherol than among those who did not. a-Tocopherol had no apparent effect on total mortality, although more deaths from hemorrhagic stroke were observed among men who received this supplement than among those who did not (Albanes et al., 1995).

A large double-blind trial (the CARET study) in the United States evaluated the effects of combined daily supplementation of 30 mg synthetic /3-carotene and 25,000 IU vitamin A or placebo on the incidence of cancer and cardiovascular disease. Objects of the study were 18,314 smokers, former smokers, and workers exposed to asbestos over an average follow-up period of 4 years. In the supplemented group, the relative risk of death from cardiovascular disease was 26% higher than in the group on placebo. Researchers observed that favorable effects of antioxidants may be particularly difficult to achieve with continuing cancer-promoting and atherosclerosis-promoting assaults in smokers (Omenn, 1996).

In the Physicians' Health Study, 22,071 healthy male physicians 40-84 years of age in the United States received either 50 mg /3-carotene or a placebo on alternate days for a period of 12 years. There were no significant differences in the overall incidence of deaths from cardiovascular disease or in the number of men who suffered a stroke or myocardial infarction in the /3-carotene-supplemented group compared to the placebo group. In current and former smokers, those assigned to receive /3-carotene supplements had no significant increase or decrease in the risk of cardiovascular disease (Hennekens et al., 1996). In a subgroup analysis of 333 physicians with a history of stable angina pectoris and/or coronary revascularization, the ยก3-carotene-supplemented group had a significant 51% reduction in the risk of major coronary events. The beneficial effect of /3-carotene first appeared during the second year of supplementation (Gaziano, 1994).

The last randomized trial studied the effect of vitamin E supplementation (400 or 800IU per day) on the risk of myocardial infarction in 2002 patients with angiographic evidence of coronary atherosclerosis. Results of the Cambridge Heart Antioxidant Study (CHAOS) demonstrate that vitamin E supplementation significantly decreased the risk of cardiovascular disease and nonfatal myocardial infarction by 47%. After 200 days of treatment, vitamin E produced a 77% decrease in the risk of nonfatal myocardial infarction alone. Total mortality from cardiovascular disease was not significantly lower in the vitamin E-supplemented group, with most of the deaths occurring during the first 200 days of follow-up (Stephens et al., 1996).

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