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

Abstract. Salonen JT, Nyyssönen K, Salonen R, Lakka H‐M, Kaikkonen J, Porkkala‐Sarataho E, Voutilainen S, Lakka TA, Rissanen T, Leskinen L, tuomainen T‐P, Valkonen V‐P, Ristonmaa U (University of Kuopio, Finland), Poulsen HE (University of Copenhagen, Copenhagen, Denmark). 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. J Intern Med 2000; 248: 377–386. Objectives. To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis, hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins. Design and subjects. Double‐masked two‐by‐two factorial trial, randomization in four strata (by gender and smoking status) to receive twice daily either 91 mg (136 IU) of d‐α‐tocopherol, 250 mg of slow‐release vitamin C, a combination of these or placebo for three years. A randomized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45–69 years with serum cholesterol ≥ 5.0 mmol L –1 were studied. Setting. The population of the city of Kuopio in Eastern Finland. Intervention. Twice daily either a special formulation of 91 mg of d‐α‐tocopherol, 250 mg of slow‐release vitamin C, a combination of these (CellaVie ® ) or placebo for three years. Measurements. Atherosclerotic progression, defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima–media thickness (IMT), was calculated over semi‐annual assessments. Results. The average increase of the mean IMT was 0.020 mm year –1 amongst men randomized to placebo and 0.018 mm year –1 in vitamin E, 0.017 mm year –1 in vitamin C and 0.011 mm year –1 in the vitamin combination group ( P = 0.008 for E + C vs. placebo). The respective means in women were 0.016, 0.015, 0.017 and 0.016 mm year –1 . The proportion of men with progression was reduced by 74% (95% CI 36–89%, P = 0.003) by supplementation with the formulation containing both vitamins, as compared with placebo. Conclusions. Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow‐release vitamin C can retard the progression of common carotid atherosclerosis in men. This may imply benefits with regard to other atherosclerosis‐based events.