In subgroup analyses , all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation ( P for interaction=0.04 ) ; neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality .
CONCLUSIONS Vitamin D supplementation alone was not associated with  all cause mortality in adults compared with placebo or no treatment .
Vitamin D supplementation reduced the risk of cancer death by 16 % .
Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality .
OBJECTIVE To investigate whether vitamin D supplementation is associated with lower mortality in adults .
Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis: A Randomized Clinical Trial.
IMPORTANCE Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis , but current trial evidence is contradictory . OBJECTIVE To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels . DESIGN , SETTING , AND PARTICIPANTS A multicenter r and omized , double-blind , placebo-controlled clinical trial in Tasmania and Victoria , Australia . Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D ( 12.5 - 60 nmol/L ) were enrolled from June 2010 to December 2011 . The trial was completed in December 2013 . INTERVENTIONS Participants were r and omly assigned to receive monthly treatment with oral vitamin D3 ( 50,000 IU ; n = 209 ) or an identical placebo ( n = 204 ) for 2 years . MAIN OUTCOMES AND MEASURES Primary outcomes were change in tibial cartilage volume ( assessed using magnetic resonance imaging [ MRI ] ) and change in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) pain score ( 0 [ no pain ] to 500 [ worst pain ] ) from baseline to month 24 . Secondary outcomes were cartilage defects and bone marrow lesions ( assessed using MRI ) . RESULTS Of 413 enrolled participants ( mean age , 63.2 years ; 50 % women ) , 340 ( 82.3 % ) completed the study . The level of 25-hydroxyvitamin D increased more in the vitamin D group ( 40.6 nmol/L ) than in the placebo group ( 6.7 nmol/L ) ( P < .001 ) over 2 years . There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score . There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions . Adverse events ( ≥ 1 per patient ) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group ( P = .04 ) . [ table : see text ] . CONCLUSIONS AND RELEVANCE Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels  , vitamin D supplementation , compared with placebo , did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years . These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01176344 ; anzctr.org.au Identifier : ACTRN12610000495022
In subgroup analyses , all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation ( P for interaction=0.04 ) ; neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality .
CONCLUSIONS Vitamin D supplementation alone was not associated with  all cause mortality in adults compared with placebo or no treatment .
Vitamin D supplementation reduced the risk of cancer death by 16 % .
Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality .
OBJECTIVE To investigate whether vitamin D supplementation is associated with lower mortality in adults .