Research Linking Vitamin E Supplementation and All-Cause Mortality is Inconclusive

November 11, 2004; Parsippany, NJ – At this year’s American Heart Association annual meeting, researchers from Johns Hopkins presented data on a new meta-analysis of 19 earlier published vitamin E studies with diverse primary objectives that investigated the impact of this antioxidant on a variety of chronic diseases, including cardiovascular disease, cancer, age-related eye diseases, Parkinson’s and Alzheimer’s Disease. The authors conducted the analysis to look at all-cause mortality among those taking vitamin E. This new analysis came to the same conclusion as three previously published meta-analyses – vitamin E was neither beneficial nor harmful. None of the studies originally found any significant impact of vitamin E supplementation on all-cause mortality reported.

A subgroup analysis was performed on all-cause mortality based on a dose-response relationship of vitamin E. This analysis suggested that high dose vitamin E (≥ 400 IU/day) may increase all-cause mortality (an additional 34 deaths per 10,000); while low dose vitamin E was found to lower the risk of total mortality (33 fewer deaths per 10,000). The statistical model used in the subgroup analysis differed from the first and tends to be biased toward the risk of harm rather than the potential benefit. Different models could have produced different results.

By combining the results of 19 studies, the authors have theoretically increased the statistical power of their analysis. However, the studies chosen represent a diversity of study participants (suffered from chronic disease; at high risk for disease or malnourished), disease conditions, treatments and durations of intervention (ranging from 1.4 to 8.2 years). Given the difference between all the studies, the authors concede that the findings cannot be generalized to a healthy adult population.

The all-cause mortality outcome may not be suitable given that none of the 19 studies analyzed originally had this outcome as a primary endpoint. In fact, a number of the studies in this meta-analysis have shown positive results on the primary outcomes selected. These studies include AREDS (reduced progression of advanced age-related macular degeneration); REACT (reduced occurrence of cataract); ADCS (slowed progression of Alzheimer’s Disease); CHAOS (lower incidence of non-fatal MI) and ASAP (in conjunction with vitamin C, a slower progression of atherosclerosis).

Therefore, issues with the health of the study population, the appropriateness of the outcome selected and the disparate results from the two analyses raise questions about the relevance of these findings to the scientific understanding of the role of vitamin E in chronic disease.

DSM Nutritional Products, Inc., the global leader in nutritional fortification, offers the industry’s most extensive portfolio of Vitamin E ingredients in both natural and synthetic forms. DSM is the world’s largest nutritional ingredient supplier to producers of foods, beverages and dietary supplements. The company has an international network of technical service, production and distribution facilities as well as sales and marketing presence in more than 100 countries. In addition to its vast ingredient portfolio, DSM provides unparalleled processing and manufacturing expertise in developing innovative formulations that provide optimum performance and health appeal.

For further information, please contact DSM Nutritional Products, Inc. at 45 Waterview Boulevard, Parsippany, New Jersey, 07054-1293. Phone: 1-800-526-0189. Website:


Michael Gaziano, MD, MPH
Chief, Division of Aging, Brigham & Women’s Hospital
Associate Professor, Harvard Medical School

Jeffrey Blumberg, PhD
Associate Director and Chief, Antioxidants Research Laboratory
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University

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