Zhang Y, Fang F, Tang J, et al. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. BMJ. 2019 Aug 12;366:l4673. doi: 10.1136/bmj.l4673.
Abstract

OBJECTIVE: To investigate whether vitamin D supplementation is associated with lower mortality in adults.

DESIGN: Systematic review and meta-analysis of randomised controlled trials.

DATA SOURCES: Medline, Embase, and the Cochrane Central Register from their inception to 26 December 2018.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group.

MAIN OUTCOME MEASURES: All cause mortality.

RESULTS: 52 trials with a total of 75 454 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I2=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.84, 0.74 to 0.95, 0%). 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.

STUDY REGISTRATION: PROSPERO registration number CRD42018117823.

Ratings by Clinicians (at least 3 per Specialty)
Specialty Score
Internal Medicine
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Public Health
Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

I think most providers are aware of the reduction in cancer mortality.

General Internal Medicine-Primary Care(US) rater

A lot of physicians still test and treat for Vitamin D deficiency, often using outdated high thresholds, while many others treat empirically. There is probably little harm from this, but probably also little benefit as demonstrated in this review.

General Internal Medicine-Primary Care(US) rater

Many individuals take vitamin supplements hoping to improve their health or prevent future adverse health outcomes. This research informs decision-making around the value of vitamin D supplementation.

Internal Medicine rater

I wonder whether we will ever get the message across that for average risk people, we really owe them an apology for spending so much time talking about vitamin D. I wonder which vitamin will be the next distraction? Sorry for the cynicism, but we have real health issues that go unaddressed.

Internal Medicine rater

I would be suspicious of bias in the cancer death data.

Public Health rater

Well done systematic review showing the `decline` of Vitamin D. As more research is done, the initial enthusiasm for Vitamin D supplementation has progressively declined. I am unimpressed by the subgroup analyses and doubt that large trials looking specifically at cancer or the difference between D2 and D3 will ever show much of a positive benefit.

Public Health rater

Very nicely done meta-analysis. The big findings were no overall reduction in mortality, but a significant decrease in cancer mortality. Also very interesting is the suggestion that D3 might have an effect vs D2.