High intakes of vitamin A and/or beta-carotene seem to not increase fracture risk

According to a new Australian study, regular long-term intake of high-dose vitamin A and beta-carotene supplements does not increase the risk of any fracture or osteoporotic fracture; beta-carotene may even have a preventive effect.

This intervention trial documented cases of fractures among 2,322 adults who had been previously exposed to asbestos (1). Initially, they received either 25,000 IU of vitamin A (retinyl palmitate) per day (7.5 mg retinol equivalents, RE), 30 mg beta-carotene per day, or 0.75 mg beta-carotene per day for six years; after that, all participants received 25,000 IU of vitamin A per day for 10 years. The study results showed that participants who took high doses of vitamin A for up to 16 years had no increased risk of fractures or any osteoporotic fracture risk. However, a decreased risk of fracture was associated with a greater duration of beta-carotene supplementation in men.

The researchers commented that, although both vitamin A and beta-carotene (a precursor of vitamin A) contribute to vitamin A intake, not all beta-carotene is converted to retinol, and so beta-carotene and vitamin A do not necessarily have the same effect on bone. Two observational studies have suggested that there is a protective relationship between beta-carotene and fracture risk, possibly through beta-carotene’s antioxidant capability (2, 3).

Observational studies examining vitamin A supplement use in relation to fracture risk have been mixed so far. A slightly increased risk for self-reported hip fracture, but not all fractures, was suggested among vitamin A supplement users in the Iowa Women’s Health Study, which followed over 34,000 post-menopausal women for an average of 9.5 years (4). However, no dose-response relationship was demonstrated, and hip fracture was not associated with dietary or total retinol intake. On the other hand, the Women’s Health Initiative Observational Study, which included over 75,000 post-menopausal women, the total retinol intake (from food and supplements) for an average of 6.6 years was not associated with risk for any fracture or hip fracture (5). To date, all of the observational studies in this field have included women only, with the majority focusing on post-menopausal women, while the present study included both men and women of a wide range of ages.

1. Ambrosini G. L. et al. No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene. Osteoporos Int. 2013; 24:1285–1293./
2. Sahni S. et al. Protective effect of total carotenoid and lycopene intake on the risk of hip fracture: a 17-year follow-up from the Framingham Osteoporosis Study. J Bone Min Res. 2009; 24:1086–1094.
3. Zhang J. et al. Antioxidant intake and risk of osteoporotic hip fracture in Utah: an effect modified by smoking status. Am J Epidemiol. 2006; 163:9–17.
4. Lim L. S. et al. Vitamin A intake and the risk of hip fracture in postmenopausal women: the Iowa Women’s Health Study. Osteopor Int. 2004; 15:552–559.
5. Caire-Juvera G. et al. Vitamin A and retinol intakes and the risk of fractures among participants of the Women’s Health Initiative Observational Study. Am J Clin Nutr. 2009; 89:323–330.