Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3‐year progression of carotid atherosclerosis

Randomized, placebo-controlled trial in adults aged 45 to 69 years with hypercholesterolemia in Kuopio, Eastern Finland. Participants included smoking and nonsmoking men and postmenopausal women, stratified by sex and smoking status and followed with carotid ultrasound measurements over 36 months.

Adults were randomized to oral vitamin E 91 mg d-alpha-tocopherol twice daily, vitamin C 250 mg slow-release ascorbic acid twice daily, both vitamins in a single tablet, or placebo for 3 years. The combined regimen provided vitamin E plus vitamin C at the same doses given as the single-agent arms.

Combined vitamin E plus slow-release vitamin C supplementation slowed common carotid atherosclerosis progression in men, with the clearest benefit among smokers; no substantial preventive effect was seen in postmenopausal women. In men, mean carotid IMT progression over 36 months was 0.011 mm/year with both vitamins versus 0.020 mm/year with placebo, and covariate-adjusted IMT increase was 50.9% less than in other men (0.009 vs. 0.018 mm/year, P = 0.044) and 45.0% less than placebo (P = 0.049). The odds ratio for progression versus placebo in men receiving both vitamins was 0.26 (0.11, 0.64), P = 0.003, whereas single vitamins showed weaker or non-significant effects. In women, progression did not differ significantly across groups.

The main benefit was confined to a male subgroup, especially smokers, which limits generalizability. Single-vs-combination and sex-specific analyses increase the risk of chance findings from multiple comparisons, and the trial was not powered to show uniform benefit across all groups. Arm-specific ethnicity data were not reported, and some adverse events and dropouts differed by arm.