Osteoporosis International

, Volume 21, Issue 7, pp 1121–1132 | Cite as

Benefit–risk assessment of vitamin D supplementation

  • H. A. Bischoff-FerrariEmail author
  • A. Shao
  • B. Dawson-Hughes
  • J. Hathcock
  • E. Giovannucci
  • W. C. Willett



Current intake recommendations of 200 to 600 IU vitamin D per day may be insufficient for important disease outcomes reduced by vitamin D.


This study assessed the benefit of higher-dose and higher achieved 25-hydroxyvitamin D levels [25(OH)D] versus any associated risk.

Methods and results

Based on double-blind randomized control trials (RCTs), eight 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 700 to 1000 IU vitamin D per day or mean 25(OH)D between 75 and 110 nmol/l (30–44 ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median 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 per day or achieved 25(OH)D up to 643 nmol/l. Mean levels of 75 to 110 nmol/l were reached in most RCTs with 1,800 to 4,000 IU vitamin D per day without risk.


Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000 IU vitamin D per day; 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.


Falls Fractures Hypercalcemia Recommendations Risk Vitamin D 


Conflicts of interest



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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2009

Authors and Affiliations

  • H. A. Bischoff-Ferrari
    • 1
    • 2
    • 1
    Email author
  • A. Shao
    • 3
  • B. Dawson-Hughes
    • 4
  • J. Hathcock
    • 3
  • E. Giovannucci
    • 5
  • W. C. Willett
    • 5
  1. 1.Centre on Aging and Mobility, Department of Rheumatology and Institute of Physical MedicineUniversity Hospital ZurichZurichSwitzerland
  2. 2.Department of Rheumatology and Institute of Physical MedicineUniversity Hospital ZurichZurichSwitzerland
  3. 3.Council for Responsible NutritionWashingtonUSA
  4. 4.USDA Human Nutrition Research Center on AgingTufts UniversityBostonUSA
  5. 5.Department of NutritionHarvard School of Public HealthBostonUSA

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