Vitamin A and retinol intakes and the risk of fractures among participants of the Women's Health Initiative Observational Study

Background: Excessive intakes of vitamin A have been shown to have adverse skeletal effects in animals. High vitamin A intake may lead to an increased risk of fracture in humans. Objective: The objective was to evaluate the relation between total vitamin A and retinol intakes and the risk of incident total and hip fracture in postmenopausal women. Design: A total of 75,747 women from the Women's Health Initiative Observational Study participated. The risk of hip and total fractures was determined using Cox proportional hazards models according to different intakes of vitamin A and retinol. Results: In the analysis adjusted for some covariates (age; protein, vitamin D, vitamin K, calcium, caffeine, and alcohol intakes; body mass index; hormone therapy use; smoking; metabolic equivalents hours per week; ethnicity; and region of clinical center), the association between vitamin A intake and the risk of fracture was not statistically significant. Analyses for retinol showed similar trends. When the interaction term was analyzed as categorical, the highest intake of retinol with vitamin D was significant (P = 0.033). Women with lower vitamin D intake (<= 11 mu g/d) in the highest quintile of intake of both vitamin A (hazard ratio: 1.19; 95% CI: 1.04, 1.37; P for trend: 0.022) and retinol (hazard ratio: 1.15; 95% CI: 1.03, 1.29; P for trend: 0.056) had a modest increased risk of total fracture. Conclusions: No association between vitamin A or retinol intake and the risk of hip or total fractures was observed in postmenopausal women. Only a modest increase in total fracture risk with high vitamin A and retinol intakes was observed in the low vitamin D-intake group. Am J Clin Nutr 2009; 89: 323-30.