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


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


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.


CONCLUSIONS
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.
Bischoff-Ferrari
H A
HA
Centre on Aging and Mobility, Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Gloriastrasse 25, 8091, Zurich, Switzerland. Heike.Bischoff@usz.ch
Shao
A
A
Dawson-Hughes
B
B
Hathcock
J
J
Giovannucci
E
E
Willett
W C
WC
D000058:Accidental Falls / Q000517:prevention & control; D000368:Aged; D002118:Calcium / Q000097:blood; D019587:Dietary Supplements / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D014807:Vitamin D / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood
D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002118:Calcium