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Plasma retinol and total carotenes and fracture risk after long term supplementation with high doses of retinol

DOI: 10.1016/j.nut.2013.10.007
  • Retinol
  • Vitamin A
  • Carotene
  • Fractures
  • Intervention Study
  • Plasma
  • Biomarkers
  • Medicine


Abstract Objective Observational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an ageing population, make this a potentially important association. This study investigated plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta carotene in 998 adults between 1990 and 2007. Research methods Subjects were 663 men and 335 women in a cancer prevention program who were initially randomised to a retinol (7.5mg RE/d) or beta carotene (30mg/d) supplement between 1990 and 1996. After 1996, all subjects received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self report in 2007. The risk for any fracture or osteoporotic fracture was modelled using Cox proportional hazard models. Results Over a median follow up of 7.8 years, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (HR=0.86 per μmol/L, 95% CI 0.65-1.14) or osteoporotic fracture (HR=0.97 per μmol/L, 95% CI 0.66-1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR=0.85 per μmol/L, 95% CI 0.71-1.01). Conclusions This study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation.

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