The relationship between vitamin A and risk of fracture: meta-analysis of prospective studies

J Bone Miner Res. 2014 Sep;29(9):2032-9. doi: 10.1002/jbmr.2237.


Osteoporotic fracture is a significant cause of morbidity and mortality and is a challenging global health problem. Previous reports of the relation between vitamin A intake or blood retinol and risk of fracture were inconsistent. We searched Medline and Embase to assess the effects of vitamin A (or retinol or beta-carotene but not vitamin A metabolites) on risk of hip and total fracture. Only prospective studies were included. We pooled data with a random effects meta-analysis with adjusted relative risk (adj.RR) and 95% confidence interval (CI). We used Q statistic and I(2) statistic to assess heterogeneity and Egger's test to assess publication bias. Eight vitamin A (or retinol or beta-carotene) intake studies (283,930 participants) and four blood retinol level prospective studies (8725 participants) were included. High intake of vitamin A and retinol were shown to increase risk of hip fracture (adj.RR [95% CI] = 1.29 [1.07, 1.57] and 1.40 [1.03, 1.91], respectively), whereas beta-carotene intake was not found to increase the risk of hip fracture (adj.RR [95% CI] = 0.82 [0.59, 1.14]). Both high or low level of blood retinol was shown to increase the risk of hip fracture (adj.RR [95% CI] = 1.87 [1.31, 2.65] and 1.56 [1.09, 2.22], respectively). The risk of total fracture does not differ significantly by level of vitamin A (or retinol) intake or by blood retinol level. Dose-response meta-analysis shows a U-shaped relationship between serum retinol level and hip fracture risk. Our meta-analysis suggests that blood retinol level is a double-edged sword for risk of hip fracture. To avoid the risk of hip fracture caused by too low or too high a level of retinol concentration, we suggest that intake of beta-carotene (a provitamin A), which should be converted to retinol in blood, may be better than intake of retinol from meat, which is directly absorbed into blood after intake.


Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoporotic Fractures / blood*
  • Osteoporotic Fractures / epidemiology*
  • Prospective Studies
  • Publication Bias
  • Risk Factors
  • Vitamin A / blood*


  • Vitamin A