Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer. The Women’s Health Study:
A Randomized Controlled Trial (Juli 2005)
Lee, I.M. et al.,
JAMA 294, 2005: 6th July 2005
Objective
Evaluate the benefits and risks of vitamin E supplementation (600 IU every other day) in the primary prevention of cardiovascular disease and cancer among healthy women.
Design
Randomized, placebo-controlled
Almost 40.000 healthy women (45 years of age and older) randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2x2 factorial design
Intervention dose: 600 IU vitamin E (RRR-alpha tocopherol) on alternate days
Mean duration: 10.1 years of follow-up
Primary endpoints
First major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death
Total invasive cancer
Results
Significant 24% reduction (relative risk, 076; 95% confidence interval, 0.59-0.98; P=.03) for cardiovascular death
Non-significant 7% risk reduction (relative risk, 0.93; 95% confidence interval, 0.82-1.05; P=.26) related to cardiovascular events in the vitamin E group
No significant effects on incidences of myocardial infarction (relative risk, 1.01; 95%, confidence interval, 0.82-1.23; P=.96) or stroke (ischemic or haemorrhagic) (relative risk, 0.98; 95%, confidence interval, 0.82-1.17; P=.82)
No significant effect on incidence of total cancer (relative risk, 1.01; 95%, confidence interval, 0.94-1.08; P=.87) or breast (relative risk, 1.00; 95%, confidence interval, 0.90-1.12; P=.95) or lung (relative risk, 1.09; 95%, confidence interval, 0.83-1.44; P=.52) or colon cancers (relative risk, 1.00; 95%, confidence interval, 0.77-1.31; P=.99)
No significant effect on total mortality (relative risk, 1.04; 95%, confidence interval, 0.93-1.16; P=.53)
Author’s Conclusion
600 IU of vitamin E taken every second day provided no major benefit for major cardiovascular events or cancer, did not effect total mortality, but decreased cardiovascular mortality in healthy women.
The data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women.
GVF Comment
The study confirmed that vitamin E is safe, reporting that taking 600 IU1 of vitamin E supplements every other day did not increase total mortality in healthy women. This supports a recent review paper where the authors concluded from clinical trial evidence that vitamin E supplements appear safe for most adults in amounts < 1600 IU . The confirmation of the safe use of vitamin E in the Women’s Health Study contradicts the recent meta-analysis from Miller et al.2 that reviewed studies of people already ill with cancer, heart disease or other serious medical conditions.
The possible adverse effects of 400 IU of vitamin E on heart failure reported recently in the HOPE-TOO trial3 could not be confirmed in the Women’s Health Study. However, it was not specified as an endpoint, but self-reported information has been collected that could not demonstrate any association between vitamin E use and heart failure.
Although the study did not showed benefit of vitamin E on the primary endpoints major cardiovascular events and total invasive cancer, a significant 24% reduction in the secondary endpoint of cardiovascular deaths among the nearly 20,000 women who took vitamin E supplements over a 10-year period compared with the nearly 20,000 other study participants who were given placebo was observed. For the subgroup of women aged at least 65, the study reported that taking vitamin E supplements reduced the risk of major cardiovascular events significantly by 26%. Among that population, there was a 49% reduction in cardiovascular death and a 34% reduction in myocardial infarction. The study’s authors stated that this finding of decreased cardiovascular deaths could be due to chance. However, they acknowledged that it was significant and deserved further study.
References
Hathcock et al., Vitamins E and C are safe across a broad range of intakes, Am J Clin Nutr. 2005 Apr;81(4):736-45
Miller et al., Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46
Lonn et al. , Effects of Long-Term Vitamin E Supplementation on Cardiovascular Events and Cancer - A Randomized Controlled Study (The HOPE Study Extension) = HOPE-TOO JAMA 2005; 293, 1338-1347