Submitted to: Osteoporosis International
Publication Type: Book / Chapter
Publication Acceptance Date: 10/27/2009
Publication Date: 7/7/2010
Citation: Bischoff-Ferrari, H.A., Shao, A., Dawson-Hughes, B., Hathcock, J., Giovannucci, E., Willett, W.C. 2010. Benefit-risk assessment of vitamin D supplementation. In: Reichrath,J., Editor. Osteoporosis International. Austin, TX: Landes Bioscience. p.55-71. Interpretive Summary:
Technical Abstract: The current intake recommendations of 200 to 600 IU vitamin D/d may be insufficient for important disease outcomes reduced by vitamin D. The purpose of this study was to assess the benefit of higher dose and higher achieved 25-hydroxyvitamin D levels (25(OH)D) versus any associated risk. Based on double-blind RCTs, 8 for falls (n=2426) and 12 for non-vertebral fractures (n= 42,279), there was a significant dose-response relationship between higher dose and higher achieved 25(OH)D and greater fall and fracture prevention. Optimal benefits were observed at the highest dose tested to date for these endpoints, 700 to 1000 IU vitamin D/d, or mean 25(OH)D between 75 to 110 nmol/l (30-44 ng/ml). Prospective cohort data on cardiovascular health and colo-rectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median levels between 75 and 110 nmol/l). In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000 IU /d or achieved 25(OH)D up to 643 nmol/l. Mean levels of 75 to 110 nmol/l were reached in most RCTs with 1800 IU to 4000 IU vitamin D/d without risk. Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimal benefits without increasing health risks. These levels can be best obtained with oral doses in the range of 1800 to 4000 IU vitamin D/d; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the population.