The vast majority of studies reported inverse associations between 25(OH)D concentration and all-cause mortality .
This association appeared to be non-linear , with progressively lower mortality with increasing 25(OH)D up to a point , beyond which there was no further decrease .
There is moderate evidence that vitamin D status is inversely associated with cancer mortality and death due to respiratory diseases , while for cardiovascular mortality , there is weak evidence of an association in observational studies , which is not supported by the data from intervention or Mendelian r and omization studies .
Epidemiological evidence suggests that vitamin D deficiency is associated with increased mortality , but it is unclear whether this is explained by reverse causation , and if there are specific causes of death for which vitamin D might be important .
Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial
Importance Previous r and omized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence . Objective To examine whether high-dose vitamin D supplementation received monthly , without calcium , is associated with a reduction in  cancer incidence and cancer mortality in the general population . Design , Setting , and Participants This is a post hoc analysis of data from the Vitamin D Assessment ( ViDA ) study , a r and omized , double-blind , placebo-controlled trial that recruited participants from family practice s and community groups in Auckl and , New Zeal and , from April 5 , 2011 , through November 6 , 2012 , with follow-up completed December 31 , 2015 . Participants were adult community residents aged 50 to 84 years . Of 47 905 adults invited from family practice s and 163 from community groups , 5110 participants were r and omized to receive vitamin D3 ( n = 2558 ) or placebo ( n = 2552 ) . Two participants withdrew consent , and all others ( n = 5108 ) were included in the primary analysis . Data analysis was by intention to treat . Interventions Oral vitamin D3 , in an initial bolus dose of 200 000 IU and followed by monthly doses of 100 000 IU , or placebo for a median of 3.3 years ( range , 2.5 - 4.2 years ) . Main Outcomes and Measures Post hoc primary outcome was the number of all primary invasive and in situ malignant neoplasms ( excluding nonmelanoma skin cancers ) diagnosed from r and omization until the study medication was discontinued on July 31 , 2015 . Results Of the 5108 participants included in the analysis , the mean ( SD ) age was 65.9 ( 8.3 ) years , 58.1 % were male , and 4253 ( 83.3 % ) were of European or another race/ethnicity , with the remainder being Polynesian or South Asian .  Mean ( SD ) baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 ( 9.0 ) ng/mL. In a r and om sample of 438 participants , the mean follow-up 25-hydroxyvitamin D concentration consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group . The primary outcome of cancer comprised 328 total cases of cancer ( 259 invasive and 69 in situ malignant neoplasms ) and occurred in 165 of 2558 participants ( 6.5 % ) in the vitamin D group and 163 of 2550 ( 6.4 % ) in the placebo group , yielding an adjusted hazard ratio of 1.01 ( 95 % CI , 0.81 - 1.25 ; P = .95 ) . Conclusions and Relevance High-dose vitamin D supplementation prescribed monthly for up to 4 years without calcium may not prevent cancer . This study suggests that daily or weekly dosing for a longer period may require further study . Trial Registration anzctr.org.au Identifier :
The vast majority of studies reported inverse associations between 25(OH)D concentration and all-cause mortality .
This association appeared to be non-linear , with progressively lower mortality with increasing 25(OH)D up to a point , beyond which there was no further decrease .
There is moderate evidence that vitamin D status is inversely associated with cancer mortality and death due to respiratory diseases , while for cardiovascular mortality , there is weak evidence of an association in observational studies , which is not supported by the data from intervention or Mendelian r and omization studies .
Epidemiological evidence suggests that vitamin D deficiency is associated with increased mortality , but it is unclear whether this is explained by reverse causation , and if there are specific causes of death for which vitamin D might be important .