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Can vitamin D impact mortality?

This meta-analysis suggests that if it does, the effect size on all-cause mortality is pretty darn small. However, supplementation may reduce the risk of dying from cancer.

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Study under review: Association between vitamin D supplementation and mortality: systematic review and meta-analysis

Introduction

Meta-analyzing vitamin D and the NERD

What can vitamin D do, or rather, what can it not do? In a short period of time, vitamin D, which is a group of fat-soluble steroid hormones, has skyrocketed to fame and is claimed by many to be a cure-all substance. However, beneath the hype is a group of compounds that play several important roles within the body.

As discussed in NERD #37, vitamin D receptors are found in nearly all tissues[1] in the body and are involved in several key biological processes, including calcium regulation[2], gene regulation[3], and cell differentiation[4]. Deficiencies in vitamin D are often linked to negative outcomes, including rickets[5], osteomalacia[6], and inflammation[7]. Luckily, food fortification and supplements are cheap and widely available, which also makes vitamin D supplementation a relatively easy intervention to study, not only for treating deficiencies, but for nearly every condition a researcher can think of.

NERD readers may have an idea of how vast this research area is. Previous issues covered studies investigating vitamin D supplementation as a means to prevent and/or treat bone fractures, cancer, sleep disorders, depression, common colds, multiple sclerosis, athletic performance, and several other conditions that are shown in Figure 1.

Context-dependently, many of these studies have shown supplements to be helpful, while a few have not. Vitamin D supplementation has certainly been studied for several other conditions that the NERD has not covered, and it is possible that, in these studies, supplementation may have shown little utility for the studied outcomes. Moreover, many of these studies may never even been published. After all, publication and citation bias[8] are real issues in the world of medical research, so many of these studies, which may have failed to show vitamin D in a positive light, will probably never have seen the light of day. Taking this and previous meta-analyses of vitamin D covered by the NERD into account, it seems reasonable to think that vitamin D, although important and promising for many conditions, is no miracle substance.

Vitamin D and Mortality

Previous systematic reviews[9][10] and meta-analyses[11] have suggested that vitamin D supplementation leads to a small reduction in the risk of mortality, but these studies are difficult to interpret. Many of them included trials where both vitamin D supplements and calcium supplements were administered together and then compared to placebo. This makes it challenging to single out the individual causal effect of vitamin D supplementation on mortality, and is compounded by the fact that calcium supplementation in certain populations has been associated[12] with an increased risk of cardiovascular disease events[13]. The existing reviews also lacked sufficient details about the individual studies they analyzed and the reviews may have lacked enough data to detect an effect that was clinically meaningful.

Thus, reviews to date may not have accurately estimated the effect of vitamin D supplementation on the risk of all-cause mortality. In the time that has passed since these papers have been published, several new clinical trials have come out, including trials[14] with large(r) sample sizes, and designs that address some of the limitations of previous trials. The study under review includes these new trials and attempts to address the limitations of past research syntheses to better estimate the effects of vitamin D on mortality.

Vitamin D is a group of important biological compounds that has been studied for several outcomes, many of which have been covered in previous issues of the NERD. Amongst the supplements’ many possible benefits, reducing the risk of mortality may be of most interest for the average reader. Previous studies have suggested that vitamin D supplementation shows promise for beneficial effects, but these studies suffered from methodological limitations that raise questions about their conclusions. The study under review attempts to address these limitations and includes newer trials.

Who and what was studied?

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Other Articles in Issue #60 (October 2019)