arthritis-Vitamins-C-and-E-Slow-Progression-of-Atherosclerosis

Vitamins C and E Slow Progression of Atherosclerosis
in Adults with Hypercholesterolemia

Reference:
Salonen R, Nyssonen K, Kaikkonen J, et al. Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression. Circulation 2003;107:947-53.

Design: Randomized, double-blind, placebo-controlled.

Participants: Five hundred and twenty smoking and nonsmoking men and postmenopausal women (ages 45-69 years) with hypercholesterolemia defined as serum cholesterol = 5.0 mmol/L (193 mg/dL).

Study Medication and Dosage:
The study consisted of an 8-week dietary counseling and placebo run-in period, a 3-year double-blind treatment period, and a 3-year open treatment period. After the placebo run-in period, subjects were randomly assigned to receive one of the following with meals twice daily: (1) 136 IU d-alpha-tocopherol (vitamin E); (2) 250 mg time released ascorbic acid (vitamin C); (3) both d-a-tocopherol and time released vitamin C at the doses above (in a single tablet); or (4) placebo. After the three-year, double-blind period, the study was continued for an additional three years during which all subjects previously taking active supplements, received the vitamin E and vitamin C combination and the placebo subjects continued taking the placebo medication.

Duration: Six years

Outcome Measures:
Subjects were randomized separately into the following four strata: (1) smoking (> 5 cigarettes/day) men; (2) nonsmoking men; (3) smoking postmenopausal women; (4) nonsmoking menopausal women. Follow-up visits occurred at 6, 12, 18, 24, 30, 36 and 72 months from baseline. Ultrasonographic assessment of the common carotid artery (CCA) and intima-media thickness (IMT) was performed at these visits. The linear regression slope of the mean CCA-IMT over all points of follow-up was used as the primary outcome measure.

Key Findings:
Four hundred and forty subjects completed the trial. Supplementation reduced the slope of mean CCA-IMT by 33% in men (p = 0.014) and by 14% in women (p = 0.024). In a covariance analysis of both sexes, supplementation reduced the CCA-IMT by a significant 26% (p = 0.014). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented group and 0.010 mm in the supplemented group (p = 0.034). The treatment effect was 54% in subjects who already had at least one plaque obstructing > 20% of arterial luminal diameter. In addition, the treatment effect was also larger and mainly confined to participants who had a baseline plasma vitamin C level below median (< 71.25 mmol/L). There was no significant difference in treatment effect between smokers and nonsmokers.

Practice Implications:
Known as the "Antioxidant Supplementation in Atherosclerosis Prevention" study, this important trial clearly demonstrates the protective effects of long-term, on-going use of vitamins C and E against atherosclerosis in adults with hypercholesterolemia. Previous concern has been expressed about the potential interaction of statin drugs with antioxidant supplements. However, this was largely dispelled by the large Heart Protection Study. The treatment effect in this 6-year trial is very significant and rivals the findings with cholesterol-lowering medications, but with fewer side effects. It's interesting to note that while a 4-year trial with garlic found the most significant treatment effect in postmenopausal women, this trial found the greater effect in men. The results of this trial suggest that vitamins E and C should join garlic as safe and effective prevention of progression of atherosclerosis.