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Vitamin E Supplementation Does Not Improve Cardiovascular Events and May Increase the Risk for Heart Failure 

March 23, 2005

Ontario, Canada- Cultural tendencies and animal model studies believe vitamins are beneficial to all people and illnesses, but a recent study by Eva Lonn, MD et al, from the Health Research Institute and McMaster University in Ontario, Canada published an article in the March 16, 2005 issue of JAMA showing that vitamin E had no beneficial effect on heart disease or cancer. In fact, this study showed that in patients with vascular disease or diabetes mellitus, long term Vitamin E supplementation does not only lack preventative mechanisms for cancer and major cardiovascular events, it increases the risk for heart failure. 

The predominant and active form of Vitamin E is a-Tocopherol which is a major antioxidant in lipid phases. The Heart Outcomes Prevention Evaluation (HOPE) and HOPE-The Ongoing Outcomes (HOPE-TOO) designed a randomized, double-blind, placebo-controlled international trial to evaluate whether long-term supplementation with vitamin E decreases the risk of cancer and major cardiovascular events. The patients were at least 55 years old with vascular disease or diabetes mellitus and participated in the study spanning from 1993 to 2003. In the HOPE study, patients were given ramipril vs. placebo and vitamin E vs. placebo. In the HOPE-TOO study participants continued to take daily vitamin E (400 IU) or matching placebo.  

Among all HOPE patients, there were no significant differences in the primary analysis. For cancer incidence, there was a RR 0.94; 95% confidence interval, 0.84-1.06; p=0.3. For cancer deaths, RR, .88; 95% CI 0.71-1.09; p=.24. For major cardiovascular events, 1022 (21%) patients in the vitamin E group vs. 985 (20.6%) patients in the placebo group (RR, 1.04, 95% CI, 0.96-1.14; p=.34). Patients in the vitamin E group had a higher risk of heart failure (RR, 1.21; 95% CI,1.0-1.47; 1.01-1.26; p=0.03) and higher hospitalization for heart failure (RR, 1.21; 95% CI, 1.00-1.47; p=0.045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there is no difference in cancer incidence, cancer deaths, and major cardiovascular events. In the HOPE-TOO analysis of study patients with longest duration of treatment and observation, the increase in risk was 19% in heart failure events (p=0.007) and 40% increase in the risk of hospital admission for heart failure (p= 0.002). 

The major finding for the HOPE and HOPE-TOO trial is the lack of benefit for vitamin E in preventing cancer or major cardiovascular events after prolonged period of treatment and observation. Furthermore, there may be a higher risk of heart failure with prolonged use of vitamin E. The mechanism for the deleterious effect of vitamin E is not clear but the study suggested vitamin Es potential to become pro-oxidant and depress myocardial function or the reduction of HDL cholesterol with vitamin E.  

Thus, this study indicates that in conjunction with its lack of efficacy, the potential for harm suggests that vitamin E supplements should not be used in patients with vascular disease or diabetes mellitus.  

Co-authors: Jackie Bosch, MSc, Salim Yusef, MBBS, Dphil, Patrick Sheridan, MSc, Janice Poque, MSc, J. Malcom O. Arnold, MD, Andrew Arnold, MBBS, Peter Sleight, MD, DM, Jeffrey Probstfield, MD and Gilles R. Dagenais MD.  


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