Another meta-analysis has been published in Lancet claiming vitamin D does not help non-skeletal outcomes. The paper drew widespread publicity:
The paper was a metanalysis of many randomized controlled trials of vitamin D. The authors concluded that vitamin D did not help (by more than 15%) myocardial infarction (nine trials of 48,647 patients), stroke or cerebrovascular disease (eight trials of 46,431 patients), cancer (seven trials of 48,167 patients), total fracture (22 trials of 76,497 patients) or hip fracture (12 trials of 27,834 patients). They stated vitamin D may or may not slightly reduce overall mortality.
Mark J Bolland, Andrew Grey, Greg D Gamble, Ian R Reid The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. The Lancet Diabetes & Endocrinology 24 January 2014 (Article in Press DOI: 10.1016/S2213-8587(13)70212-2).
Many of the same authors argued against routine vitamin D blood tests in 2012.
In the current study, like all meta-analyses, Bolland et al weighted their conclusions based on the number of subjects in each of the studies reviewed. For example, the Women’s Health Initiative (WHI) study – a study of 400 IU/day of vitamin D and 1,000 mg/day of calcium, and the placebo group was free to take vitamin D – was given 84% of the weight in the authors’ analysis of stroke prevention. That is, their meta-analysis of stroke prevention was basically a rehashing of the WHI data.
Another RCT that Bolland et al gave great weight was Trivedi et al’s 5 year study of 100,000 IU every four months, which was given 71% of the weight in the prevention of heart attack.
Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003 Mar 1;326(7387):469.
I found it interesting that Trivedi et al did not look at cancer as an end point back in 2003.
A recent Cochrane meta-analysis concluded that even low dose vitamin D appears to reduce cancer mortality by almost 15%.
Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014 Jan 10;1:CD007470.
Furthermore Bolland et al excluded 12 randomized controlled trials, the majority of which were positive, for various reasons.
At Bolland’s defense, on the other hand, if vitamin D had an effect on these endpoints, one would think low doses would show some effect. In this Bolland et al study, if the effect size was less than 15%, the analysis was considered negative. Maybe the dose was so low, or the vitamin D given in un-physiological ways (monthly doses) was ineffective, that the effect size was only 10%. I could not tell from how they presented their data.
The authors argued that more trials of vitamin D are a waste of money and resources and will be negative.
Luckily researchers at Harvard do not agree, as we all wait for their VITAL study results expected around 2017. It is a study of 20,000 healthy Americans, half of which will take an extra 2,000 IU/day compared to a group of 10,000 subjects getting a vitamin D placebo. The study will measure vitamin D blood levels in all subjects, so we will know if any of the placebo group started taking vitamin D. It will give us specific results for those subjects who obtained blood levels of > 40 ng/ml. The VITAL study will measure dozens of clinical endpoints with cancer and cardiovascular disease being the primary end points.
I will be shocked if 2,000 IU/day has no effect on any clinical endpoint.