Study under review: Association between vitamin D supplementation and mortality: systematic review and meta-analysis
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 Study Deep Dives #37, vitamin D receptors are found in nearly all tissues in the body and are involved in several key biological processes, including calcium regulation, gene regulation, and cell differentiation. Deficiencies in vitamin D are often linked to negative outcomes, including rickets, osteomalacia, and inflammation. 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.
Study Deep Dives 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 Study Deep Dives 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 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 Study Deep Dives into account, it seems reasonable to think that vitamin D, although important and promising for many conditions, is no miracle substance.
Previous systematic reviews and meta-analyses 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 with an increased risk of cardiovascular disease events. 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 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 Study Deep Dives. 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.
Other Articles in Issue #60 (October 2019)
Vitamin D on the mind: can vitamin D help with Alzheimer's?
This randomized controlled trial suggests that supplementation has a surprisingly strong effect on aspects of cognition in people with mild Alzheimer's disease. But are the results a little too surprising?
Mini: Is vitamin D supplementation useful for pregnant women?
We've previously covered evidence suggesting that pregnant women supplementing with vitamin D have a lower risk of giving birth to babies with low birthweight. This Cochrane review suggests vitamin D may have other benefits as well.
The surprisingly satiating effects of fasted cardio
Skipping breakfast before morning cardio cuts out some calories early in the day, but are those calories just consumed later on?
Does plate size matter?
Previous research looking at whether shrinking one's plate actually shrinks one's food intake has been equivocal. This well-designed study sheds some stronger light on the issue.
Supplementing spirulina for metabolic maladies
This meta-analysis synthesizes the latest evidence concerning spirulina's ability to make a dent in the metabolic syndrome.
Red flags in study design cast doubt on soy supplementation study results
Want to know some reasons why we don't usually cover studies looking at proprietary supplement blends? Then read on.
Interview: Suzanne Robotti, Founder of MedShadow
In this interview we chat with the founder of MedShadow, a nonprofit whose mission is to provide the information needed to weigh the risks and benefits of healthcare treatments.