Vitamins E and C supplements not effective for prevention of cardiovascular disease in men

11 nov 2008--Neither vitamin E nor vitamin C supplements reduced the risk of major cardiovascular events in a large, long-term study of male physicians, according to a study in the November 12 issue of JAMA. The article is being released early online November 9 to coincide with the scientific presentation of the study findings at the American Heart Association meeting.

Most adults in the United States have taken vitamin supplements in the past year, according to background information provided by the authors. "Basic research studies suggest that vitamin E, vitamin C, and other antioxidants reduce cardiovascular disease by trapping organic free radicals, by deactivating excited oxygen molecules, or both, to prevent tissue damage." Some previous observational studies have supported a role for vitamin E in cardiovascular disease prevention. Some previous observational studies have also shown a role for vitamin C in reducing coronary heart disease risk.

In this study, known as the Physicians' Health Study II, Howard D. Sesso, Sc.D, M.P.H., and colleagues from Brigham and Women's Hospital, Harvard Medical School and School of Public Health and VA Boston Healthcare System, Boston, assessed the effects of vitamin E and vitamin C supplements on the risk of major cardiovascular disease events among 14,641 male physicians. These physicians were 50 years or older and at low risk of cardiovascular disease at the beginning of the study in 1997, and 754 (5.1 percent) had prevalent cardiovascular disease. The study participants were randomized to receive 400 IU of vitamin E every other day or a placebo and 500 mg of vitamin C daily or a placebo.

"During a mean (average) follow-up of 8 years, there were 1,245 confirmed major cardiovascular events," the researchers report. There were 511 total myocardial infarctions (heart attacks), 464 total strokes, and 509 cardiovascular deaths, with some men experiencing multiple events. A total of 1,661 men died during follow-up. Compared with placebo, neither vitamin E nor vitamin C had an effect on the prevention of major cardiovascular events. "Neither vitamin E nor vitamin C had a significant effect on total mortality, but vitamin E was associated with an increased risk of hemorrhagic stroke."

In conclusion the authors write: "In this large, long-term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men."

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JAMA. 2008;300[18]:2123-2133. Available pre-embargo to the media at www.jamamedia.org.

Optimal dose of vitamin E maximizes benefits, minimizes risk

Corvallis, Oregon – 31 oct 2008 -- Vitamin E has been heralded for its ability to reduce the risk of blood clots, heart attack, and sudden death. Yet in some people, vitamin E causes bleeding. Scientists have known for more than 50 years that excess vitamin E promotes bleeding by interfering with vitamin K, which is essential in blood clotting. However, they haven't been able to pinpoint how the two vitamins interact. Nutrition researcher Maret Traber of Oregon State University reviews studies of possible explanations of the interaction in an article published recently in Nutrition Reviews.
One of the most compelling studies of the benefits of vitamin E is the Women's Health Study, in which 40,000 healthy women, 45 and older, took 600 IU vitamin E supplements or a placebo every other day for 10 years. Women taking the supplements had 24 percent fewer deaths from heart disease. Vitamin E's protective effect appeared even stronger in women 65 and older. Those taking the vitamin experienced a 26 percent reduction in cardiovascular events and a 49 percent reduction in cardiovascular deaths.
"That's a significant benefit," Traber said. Yet, she added, "In some people high doses of vitamin E increase the tendency to bleed. Women enrolled in the study had an increase in nose bleeds."
To lessen the bleeding risk, the U.S.-based Food and Nutrition Board in 2000 set the upper tolerable limit for daily vitamin E intake at 1500 I.U.
Research Traber reviewed suggests that a shared metabolic pathway in the liver causes vitamins E and K to interact. Vitamin K in the liver appears to diminish as vitamin E increases.
"Several different explanations could account for the interaction between the two vitamins," Traber said. "We need more research to understand the delicate balance between vitamins E and K."
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This study is published in the November 2008 issue of Nutrition Reviews. Media wishing to receive a PDF of this article may contact professionalnews@bos.blackwellpublishing.net.
To view the abstract for this article, please click here.

Low Serum Concentration of Vitamin E Linked to Physical Decline in Older Persons

Laurie Barclay
January 22, 2008 — Low serum concentration of vitamin E, an indicator of poor nutrition, is associated with subsequent physical decline among community-dwelling older adults, according to the results of a study reported in the January 23 issue of the Journal of the American Medical Association.
"Maintaining independence of older persons is a public health priority, and identifying the factors that contribute to decline in physical function is needed to prevent or postpone the disablement process," write Benedetta Bartali, RD, PhD, from Cornell University in Ithaca, New York, and colleagues. "The potential deleterious effect of poor nutrition on decline in physical function in older persons isunclear. . . . The purpose of this study was to determine whether a low concentration of specific micronutrients is associated with subsequent decline in physical function."
The investigators analyzed data from a longitudinal study of 698 community-dwelling persons 65 years or older who were randomly selected from a population registry in Tuscany, Italy. Baseline evaluation was performed from November 1, 1998, through May 28, 2000, and the 3-year follow-up evaluations from November 1, 2001, through March 30, 2003.
Decline in physical function during the 3-year follow-up was defined as a loss of 1 or more points in the Short Physical Performance Battery score. With the top 3 quartiles of each nutrient combined as the reference group, odds ratios were calculated for the lowest quartile. To confirm the validity of these results, the study authors used 2 additional and complementary analytical approaches.
Mean decrease in the Short Physical Performance Battery score was 1.1 point. Only a low concentration of vitamin E (< 1.1 μg/mL [< 24.9 μmol/L]) was significantly associated with subsequent decline in physical function, based on a logistic regression analysis with adjustment for potential confounders. Odds ratio for the association of lowest alpha-tocopherol quartile with at least a 1-point decline in physical function was 1.62 (95% confidence interval, 1.11 - 2.36;P = .01).
Baseline concentration of vitamin E was significantly associated with the Short Physical Performance Battery score at follow-up, in a general linear model with vitamin E analyzed as a continuous measure, after adjustment for potential confounders and baseline Short Physical Performance Battery score (β =.023; P = .01).
The strongest predictors of decline in physical function were age older than 81 years and vitamin E (in participants aged 70 - 80 years), based on classification and regression tree analysis. Physical decline occurred in 84% and 60%, respectively (misclassification error rate, 0.33).
"These results provide empirical evidence that a low serum concentration of vitamin E is associated with subsequent decline in physical function among community-living older adults," the study authors write.
Limitations of the study include bias by loss to follow-up, use of an Italian population–based sample limiting generalizability, vitamin D associated with decline in physical function in bivariate analysis but not in adjusted analyses, possible false-positive results because 6 micronutrient levels were tested, and possibly inadequate adjustments for multiple potential confounders.
"Although the findings from this epidemiological study cannot establish causality, they provide a solid base that low concentration of vitamin E contributes to decline in physical function," the study authors conclude. "Clinical trials may be warranted to determine whether optimal concentration of vitamin E reduces functional decline and the onset of disability in older persons with a low concentration of vitamin E."
The Invecchiare in Chianti study was supported by the Italian Ministry of Health and in part by the National Institute on Aging, National Institutes of Health. Funding for vitamin E assessment was provided by Bracco Imaging SpA, Italy. Some of the study authors have disclosed various financial relationships with the National Institute on Aging, the Yale Claude D. Pepper Older Americans Independence Center, and Yale University School of Medicine. The remaining study authors have disclosed no relevant financial relationships.
JAMA. 2008;299:308-315.