Lancet Diabetes Endocrinol 2014 Jan 24;[EPub Ahead of Print], MJ Bolland, A Grey, GD Gamble, IR Reid
Research · February 17, 2014
TAKE-HOME MESSAGE
- Results of this large systematic review and meta-analysis indicate that vitamin D supplementation does not reduce incidence of any of the following diseases by more than 15% (the threshold set for risk reduction in this study): myocardial infarction/ischemic heart disease; stroke/cerebrovascular disease; cancer; total fractures/hip fractures.
- In two studies, vitamin D plus calcium supplementation reduced the risk of hip fracture in institutionalized patients. It’s unclear whether vitamin D, supplemented with or without calcium, has an effect on mortality.
Commentary By: Peter Lin MD, CCFP
Vitamin D supplementation: Is it beneficial?
The authors concluded that vitamin D with or without calcium had no benefit relative to myocardial infarction (MI), stroke, cancer, total fracture, hip fracture, or mortality. They also stated that future studies are not likely to change the conclusions that they have reached, suggesting the futility of further research. Is this true?
Let us take a closer look—at first glance, the data from the 40 trials with > 40,000 patients that they analyzed look very impressive. But some studies were as short as 12 weeks, and only a few were 5 years in duration. Also, the dose of vitamin D ranged from 200 IU per day to 500,000 IU per year. In other words, the studies were heterogeneous in their treatments and may not have been of long enough duration to be able to detect any benefit.
In addition, the threshold that the authors set was a 15% reduction in any of the endpoints of MI, stroke, cancer, or fractures. That is a very high bar to set for the definition of success. They wanted a 5% death reduction before they would say vitamin D worked. Does that mean that a 3% mortality reduction or a 10% reduction in MI is not worthwhile? It is important that we see the kinds of studies from which the authors drew their conclusions, and we must consider what they mean by “failed to show benefit.” Meantime, let us be reasonable with the bar that we set for vitamin D and continue to recommend it appropriately.
ABSTRACT
BACKGROUND
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.
METHODS
We did a trial sequential meta-analysis of existing randomised controlled trials of vitamin D supplements, with or without calcium, to investigate the possible effect of future trials on current knowledge. We 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.
FINDINGS
The effect estimate for vitamin D supplementation with or without calcium for myocardial infarction or ischaemic heart disease (nine trials, 48 647 patients), stroke or cerebrovascular disease (eight trials 46 431 patients), cancer (seven trials, 48 167 patients), and total fracture (22 trials, 76 497 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, 27 834 patients). Vitamin D co-administered with calcium reduced hip fracture in institutionalised individuals (two trials, 3853 patients) but did not alter the relative risk of hip fracture by 15% or more in community-dwelling individuals (seven trials, 46 237 patients). There is uncertainty as to whether vitamin D with or without calcium reduces the risk of death (38 trials, 81 173).
INTERPRETATION
Our 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.
Lancet Diabetes Endocrinol 2014 Jan 24;[EPub Ahead of Print], MJ Bolland, A Grey, GD Gamble, IR Reid