Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials.
BACKGROUND
Oxidised LDL is thought to play an important part in the pathogenesis of atherosclerosis. Observational studies have associated alpha tocopherol (vitamin E), beta carotene, or both, with reductions in cardiovascular events, but not clinical trials. We did a meta-analysis to assess the effect of these compounds on long-term cardiovascular mortality and morbidity.


METHODS
We analysed seven randomised trials of vitamin E treatment and, separately, eight of beta carotene treatment; all trials included 1000 or more patients. The dose range for vitamin E was 50-800 IU, and for beta carotene was 15-50 mg. Follow-up ranged from 1.4 to 12.0 years.


RESULTS
The vitamin E trials involved a total of 81788 patients and the beta carotene trials 138113 in the all-cause mortality analyses. Vitamin E did not provide benefit in mortality compared with control treatment (11.3 vs 11.1%, odds ratio 1.02 [95% CI 0.98-1.06] p=0.42) or significantly decrease risk of cardiovascular death (6.0 vs 6.0%, p=0.86) or cerebrovascular accident (3.6 vs 3.5%, p=0.31). Beta carotene led to a small but significant increase in all-cause mortality (7.4 vs 7.0%, 1.07 [1.02-1.11] p=0.003) and with a slight increase in cardiovascular death (3.4 vs 3.1%, 1.1 [1.03-1.17] p=0.003). No significant heterogeneity was noted for any analysis.


CONCLUSIONS
The lack of a salutary effect was seen consistently for various doses of vitamins in diverse populations. Our results, combined with the lack of mechanistic data for efficacy of vitamin E, do not support the routine use of vitamin E.
Vivekananthan
Deepak P
DP
Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Penn
Marc S
MS
Sapp
Shelly K
SK
Hsu
Amy
A
Topol
Eric J
EJ
D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D002423:Cause of Death; D006801:Humans; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D024502:alpha-Tocopherol / Q000627:therapeutic use*; D019207:beta Carotene / Q000009:adverse effects / Q000627:therapeutic use*
D000975:Antioxidants; D019207:beta Carotene; D024502:alpha-Tocopherol