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Vitamin-D supplementation with or without Calcium does not reduce skeletal or non-skeletal outcomes by more than 15%


Vitamin-D insufficiency is associated with many disorders, leading to calls for widespread supplementation. Some investigators suggest that more clinical trials to test the effect of Vitamin-D on disorders are needed.

A trial sequential meta-analysis of existing randomised controlled trials of Vitamin-D supplements was done, with or without Calcium, to investigate the possible effect of future trials on current knowledge.
Researchers have estimated the effects of Vitamin-D supplementation on myocardial infarction or ischaemic heart disease, stroke or cerebrovascular disease, cancer, total fracture, hip fracture, and mortality in trial sequential analyses using a risk reduction threshold of 5% for mortality and 15% for other endpoints.

The effect estimate for Vitamin-D supplementation with or without Calcium for myocardial infarction or ischaemic heart disease ( 9 trials, 48647 patients ), stroke or cerebrovascular disease ( 8 trials 46431 patients ), cancer ( 7 trials, 48167 patients ), and total fracture ( 22 trials, 76497 patients ) lay within the futility boundary, indicating that Vitamin-D supplementation does not alter the relative risk of any of these endpoints by 15% or more.

Vitamin D supplementation alone did not reduce hip fracture by 15% or more ( 12 trials, 27834 patients ). Vitamin-D co-administered with Calcium reduced hip fracture in institutionalised individuals ( 2 trials, 3853 patients ) but did not alter the relative risk of hip fracture by 15% or more in community-dwelling individuals ( 7 trials, 46237 patients ).

There is uncertainty as to whether Vitamin-D with or without Calcium reduces the risk of death ( 38 trials, 81173 ).

The findings suggest that Vitamin-D supplementation with or without Calcium does not reduce skeletal or non-skeletal outcomes in unselected community-dwelling individuals by more than 15%.
Future trials with similar designs are unlikely to alter these conclusions. ( Xagena )

Bolland MJ et al, The Lancet Diabetes & Endocrinology 2014; 2: 307-320

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