Dietary Vitamin A May Increase Postmenopausal Fracture Risk

Dietary Vitamin A May Increase Postmenopausal Fracture Risk

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

Researchers attributed increased risk primarily to retinol intake, asbeta-carotene does not contribute to serum retinol concentrations and was notshown to significantly increase fracture risk. In addition, researchers notedthat the association of high retinol intake with hip fracture was less amongwomen using postmenopausal estrogens. Among women not taking supplementalvitamin A, retinol from food was significantly associated with fracture risk.Researchers concluded that long-term intake of a diet high in retinol maypromote the development of osteoporotic hip fractures in women.

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

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

The Council for Responsible Nutrition (CRN) issued a press release inresponse to this study, stating that the Upper Limits (UL) for vitamin A, whichwere set by the Institute of Medicine (IOM), are appropriate for assuring safetyin supplementing with vitamin A. "The findings of the Nurses' Health Studyon hip fractures must be evaluated within the context of the totality ofcredible science on vitamin A safety," said John Cordaro, president andchief executive officer of CRN. "Vitamin A has long been established as avitally 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 policychanges."

"This study cannot serve as the basis for policy on vitamin A limitbecause it is contradicted by other powerful studies," added John Hathcock,Ph.D., vice president of nutritional and regulatory science at CRN. "IOMshould continue to evaluate all the scientific evidence and not change its UL of3,000 mcg, equivalent to 10,000 IU, unless there is a sufficient scientificreason to do so."

The Consumer Healthcare Products Association (CHPA) also issued a statementin response to the JAMA study, pointing out that by contrast, the NHANES IIIstudy (National Health and Nutrition Examination Survey III) showed noassociation between vitamin A intake (serum retinyl esters) and bone mineraldensity or osteoporosis in a large sample of U.S. adults, includingpostmenopausal women. "Clearly consumers need scientifically sound answersbefore they make any drastic changes to their self-care practices," said R.William Soller, Ph.D., senior vice president and director of science andtechnology at CHPA. "Typically our industry has let evolving science shapethe future of our products. If and when a new lower daily intake level ofvitamin A is finalized by IOM and adopted by [the Food and Drug Administration],that recommendation would in turn be incorporated into our members' productformulations and labeling."