Lack of effect: Massive meta-analysis reports no heart benefits for vitamin D supplements

The comprehensive meta-analysis of randomised clinical trials, published in JAMA Cardiology​, combined data from more than 83,000 people in 21 clinical trials to investigate whether supplementation with vitamin D is linked to a lower risk of cardiovascular disease events like heart attack or stroke.

Previous observational studies have suggested a link between low blood serum levels of vitamin D and an increased risk of these sort of cardiovascular disease events, however the observational nature of these studies means causation could not be shown and unmeasured confounding was a possibility, said the team led by Dr Mahmoud Barbarawi at Michigan State University, USA.

“Although previous randomized clinical trials assessing vitamin D supplementation and cardiovascular disease have been limited and inconclusive, several recent large-scale trials have added substantial data to the evidence base,”​ wrote Barbarawi and colleagues. “Therefore, we conducted a meta-analysis of all RCTs to date that evaluate the efficacy of vitamin D supplementation in the prevention of cardiovascular disease.”​

The team reviewed data from 21 clinical trials, including more than 83,000 people, in which participants were given vitamin D supplements or a placebo. However, this meta-analysis of data showed no difference in the incidences of cardiovascular events or all causes of death between the two groups.

“We thought it would show some benefit,”​ commented Barbarawi, a clinical instructor in the MSU College of Human Medicine and chief resident physician at Hurley Medical Center in Flint, Michigan. “It didn’t show even a small benefit. This was surprising.”​

The findings are consistent for both men and women and for people of different ages, the scientists said. However, a limitation of the study is that the definition of major adverse cardiovascular events varied between the different clinical trials.

Updated analysis​

The new findings provide an update to previous meta-analyses, which also reported that supplementation with vitamin D was not associated with reduced rates of CVD.

While the updated analysis extended the earlier findings to include several recent RCTs, it did not find any fresh link between vitamin D supplementation and heart conditions, said the authors – who noted that the inclusion criteria were randomised clinical trials that reported the effect of long-term (greater than one year) vitamin D supplementation on CVD events and all-cause mortality.

According to the findings of the new analysis vitamin D supplementation was not associated with reduced risks of major adverse cardiovascular events, myocardial infarction, stroke, cardiovascular disease mortality, or all-cause mortality compared with placebo.

“These results suggest that vitamin D supplementation may not confer cardiovascular protection and may not be indicated for this purpose,”​ said Barbarawi and his team, who noted that even though the findings showed no effect on heart health, some patients, such as those being treated for osteoporosis, still might benefit from the supplements.

Other factors at play?​

Since some studies have found a link between low levels of the vitamin and an increased risk of adverse cardiovascular events, Barbarawi suggests that other factors, such as outdoor physical activity and nutritional status, might explain the association.

“Observational studies are susceptible to uncontrolled confounding by outdoor physical activity, nutritional status, and prevalent chronic disease, which may influence serum 25 hydroxyvitamin D levels,”​ the team noted.

“In this updated meta-analysis, vitamin D supplementation was not associated with reduced major adverse cardiovascular events, individual CVD end points (myocardial infarction, stroke, CVD mortality), or all-cause mortality,”​ concluded the team. “The findings suggest that vitamin D supplementation does not confer cardiovascular protection.”​

However, the team added that additional trials of higher-dose vitamin D supplementation, perhaps targeting members of older age groups and with attention to other CVD end points such as heart failure, ‘are of interest.’

Source: JAMA Cardiology​
Published online ahead of print, doi: 10.1001/jamacardio.2019.1870​
“Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis”​
Authors: Mahmoud Barbarawi, et al​