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American Journal of Clinical Nutrition, Vol. 81, No. 4, 736-745, April 2005
© 2005 American Society for Clinical Nutrition

REVIEW ARTICLE

Vitamins E and C are safe across a broad range of intakes1,2

John N Hathcock, Angelo Azzi, Jeffrey Blumberg, Tammy Bray, Annette Dickinson, Balz Frei, Ishwarlal Jialal, Carol S Johnston, Frank J Kelly, Klaus Kraemer, Lester Packer, Sampath Parthasarathy, Helmut Sies and Maret G Traber

1 From the Council for Responsible Nutrition, Washington, DC (JNH and AD); the University of Bern, Bern, Switzerland (AA); Tufts University, Boston, MA (JB); Oregon State University, Corvallis, OR (TB, BF, and MGT); the University of California, Davis, Davis, CA (IJ); Arizona State University, Mesa, AZ (CSJ); King's College, London, United Kingdom (FJK); BASF, Ludwigshafen, Germany (KK); the University of Southern California, Los Angeles, CA (LP); Louisiana State University, Baton Rouge, LA (SP); and Heinrich Heine University, Dusseldorf, Germany (HS).

A robust database shows that dietary supplements of vitamins E and C are safe for the general population. Because these nutrients supply antioxidant and other functions for homeostasis and protection against free radical damage, supplementation has been intensively studied. Because of perceived benefits, many persons consume quantities of vitamins E and C well above the recommended dietary allowances. As safety guidance, tolerable upper intake levels have been established by the Food and Nutrition Board, Institute of Medicine, at 1000 mg for vitamin E and 2000 mg for vitamin C in adults. Many clinical trials with these vitamins have involved subjects with various diseases, and no consistent pattern of adverse effects has occurred at any intake. Numerous studies of vitamin C supplementation have provided no pattern of evidence to support concerns about safety other than occasional gastrointestinal upset or mild diarrhea resulting from the osmotic effects of unabsorbed quantities of vitamin C. Evidence of bleeding effects and other potential adverse effects of high vitamin E intakes in humans is not convincing. Evidence of adverse effects of vitamin C that result from its effects on iron absorption and metabolism has not been confirmed in clinical trials. Thus, we conclude from clinical trial evidence that vitamin E supplements appear safe for most adults in amounts ≤1600 IU (1073 mg RRR-{alpha}-tocopherol or the molar equivalent of its esters) and that vitamin C supplements of ≤2000 mg/d are safe for most adults.

Key Words: Vitamin E • {alpha}-tocopherol • tocopherol • vitamin C • ascorbic acid • risk assessment • safety • clinical trials




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