Dietary Vitamin A May Increase Postmenopausal Fracture Risk

BOSTON--An analysis of the Nurses' Health Study (NHS) has uncovered data indicating that high intakes of dietary retinol may lead to higher risk for bone fractures in postmenopausal women, according to a study published in the Jan. 2 issue of the Journal of the American Medical Association (JAMA) (287,1: 47-54, 2002) (www.jama.com). Researchers from Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School reviewed NHS data for 72,337 postmenopausal women aged 34 to 77 years and identified 603 incident hip fractures resulting from low or moderate trauma between 1980 and 1998. Those in the highest quintile for vitamin A intake (3,000 mcg/d of retinol equivalents) had a significantly elevated risk of fracture as compared to women in the lowest quintile of intake.

Researchers attributed increased risk primarily to retinol intake, as beta-carotene does not contribute to serum retinol concentrations and was not shown to significantly increase fracture risk. In addition, researchers noted that the association of high retinol intake with hip fracture was less among women using postmenopausal estrogens. Among women not taking supplemental vitamin A, retinol from food was significantly associated with fracture risk. Researchers concluded that long-term intake of a diet high in retinol may promote the development of osteoporotic hip fractures in women.

An editorial submission was also printed in the Jan. 2 issue of JAMA in response to the vitamin A study. According to Margo Denke, M.D., "the human diet is biased against excessive production of retinoic acid because of the paucity of sources for dietary retinol . The human body has adapted to major day-to-day variation in retinol intake by creating tightly regulated storage pools for dietary retinol in the plasma and liver." In addition, 12 mcg beta-carotene or 24 mcg of other provitamin A carotenoids are considered equivalent to 1 mcg of all-trans retinol.

Denke continued, stating that there are a few aspects of the investigation that need clarification. First, she cited the fact that a food frequency questionnaire would have provided a "superior" estimate of what the women's true intake of vitamin A was. Second, Denke stated, "despite the relative homogeneity of the study cohort, which may more easily permit detection of an untoward effect of dietary retinol, some confounding could occur." She explained that alcohol is known to enhance the effects of retinol deficiency as well as toxicity, and it was unstated whether the researchers considered the reported J-shaped association between alcohol intake and fracture.

The Council for Responsible Nutrition (CRN) issued a press release in response to this study, stating that the Upper Limits (UL) for vitamin A, which were set by the Institute of Medicine (IOM), are appropriate for assuring safety in supplementing with vitamin A. "The findings of the Nurses' Health Study on hip fractures must be evaluated within the context of the totality of credible science on vitamin A safety," said John Cordaro, president and chief executive officer of CRN. "Vitamin A has long been established as a vitally important human nutrient, essential for growth, immune function, reproduction and vision, and it may also help reduce the risk of some cancers. This recent study does not change these facts and does not warrant policy changes."

"This study cannot serve as the basis for policy on vitamin A limit because it is contradicted by other powerful studies," added John Hathcock, Ph.D., vice president of nutritional and regulatory science at CRN. "IOM should continue to evaluate all the scientific evidence and not change its UL of 3,000 mcg, equivalent to 10,000 IU, unless there is a sufficient scientific reason to do so."

The Consumer Healthcare Products Association (CHPA) also issued a statement in response to the JAMA study, pointing out that by contrast, the NHANES III study (National Health and Nutrition Examination Survey III) showed no association between vitamin A intake (serum retinyl esters) and bone mineral density or osteoporosis in a large sample of U.S. adults, including postmenopausal women. "Clearly consumers need scientifically sound answers before they make any drastic changes to their self-care practices," said R. William Soller, Ph.D., senior vice president and director of science and technology at CHPA. "Typically our industry has let evolving science shape the future of our products. If and when a new lower daily intake level of vitamin A is finalized by IOM and adopted by [the Food and Drug Administration], that recommendation would in turn be incorporated into our members' product formulations and labeling."

Share this article: Email, Slashdot, Digg, Del.icio.us, Yahoo!MyWeb, Windows Live Favorites, Furl
Add this article feed to: RSS, My Yahoo, Newsgator, Bloglines