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Vitamin E or vitamin C supplements did not differ from placebo for major cardiovascular events and mortality
  1. Lynne E Young
  1. University of Victoria School of Nursing Victoria, British Columbia, Canada

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H D Sesso

Dr H D Sesso, Brigham and Women’s Hospital, Boston, MA, USA; hsesso{at}


In men at lower risk of cardiovascular disease (CVD), do vitamin E and vitamin C supplements reduce major CVD events?



randomised placebo controlled trial (Physicians’ Health Study II). NCT00270647.


unclear allocation concealment.


blinded (patients, clinicians, and outcome assessors)

Follow-up period:

⩽10 years (mean 8 y).




14 641 male physicians ⩾50 years of age (mean age 64 y). Men with a history of myocardial infarction (MI), stroke, or cancer were included. Exclusion criteria were history of cirrhosis, active liver disease, anticoagulant use, or serious illness. 5.1% of men had prevalent CVD.


after stratification for age, previous cancer or CVD diagnosis, and previous β-carotene assignment, men were allocated to vitamin E, 400 IU every other day (n = 3659); vitamin C, 500 mg/day (n = 3673); vitamin E plus C (n = 3656); or placebo (n = 3653). Matching placebos were used.


a composite end point of non-fatal MI, non-fatal stroke, and CVD mortality. Secondary outcomes included all-cause mortality.

Patient follow-up:

95% (intention-to-treat analysis).


Vitamin E and vitamin C did not differ from placebo for major CVD events or all-cause mortality (table). The study had 80% power to detect a 16% relative reduction in the primary outcome at the 5% significance level.


Supplementation with vitamin E or vitamin C did not differ from placebo for major cardiovascular events and mortality in men.

A modified version of this abstract appears in ACP Journal Club.


Sesso HD, Buring JE, Christen WG, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA 2008;300:2123–33.

Vitamin E or vitamin C v placebo in male physicians*

Clinical impact ratings: Cardiology 6/7; Family/general practice 5/7


Antioxidants scavenge oxygen free radicals (OFRs), which are linked to cancer and CVD.1 Thus, consumers take vitamins to reduce health risks, and 57% of first-time consumers do so for specific health issues (eg, heart health). Advice from physicians motivates about 12% of these consumers.2 Evidence about the safety and effectiveness of vitamin supplements influences the advice given by health professionals.3

The methodological rigour of the study by Sesso et al is commendable, but the study raises some questions. The vitamin doses were lower than those used in previous cohort studies, which found that vitamin C was associated with a 25% reduction in CVD.4 However, similar to other studies,1 Sesso et al found that vitamin E supplements did not prevent CVD. Rather, at a dose of about half the usual dose of vitamin E, Sesso et al reported an increased risk of haemorrhagic stroke.

What might influence these discrepant findings? The explanation must lie with the reliability of study design to determine cause and effect. Large trials, such as that by Sesso et al, offer more reliable evaluations of the effects of antioxidants than cohort designs or even meta-analyses of cohorts.

How then are nurses to advise patients? The study by Sesso et al does not support the use of 500 mg of vitamin C or vitamin E to prevent CVD. Nurses should follow the recommendations of the American Heart Association5 and the Mayo Clinic6,7 that antioxidants be obtained from a well-balanced, antioxidant-rich diet, not supplements, which appear at best to be ineffective and, at worst, may increase risk of harm.



  • Source of funding: National Institutes of Health and BASF Corporation.