Observational and randomised trial findings provide conflicting evidence over whether supplementing with vitamin D may benefit heart health in older adults. Do the findings of a recent randomised trial now offer patients a clearer picture? Rod Tucker takes a closer look, in the next topic examined in our Review series.

Research into the benefits of supplementary vitamin D has offered a wide range of findings to consider over the years.

For example, In 2019  a meta-analysis of 25 studies with over 10,000 participants concluded that vitamin D deficiency increases the rate of cardiovascular mortality. Does this mean that vitamin D supplementation is helpful for heart health? Potentially but the next part hopefully explains why these findings require a pinch of salt!

Although it had a positive finding, the analysis  - from various collaborative research teams based in Iran  - included only included prospective trials that convey association and not causation. In other words, it will never be possible to conclude from these trials whether vitamin D actually helps because the outcome (cardiovascular disease) might be related to another, unknown factor (referred to as a confounder). A recently adopted approach to overcome confounding in prospective or observational studies is Mendelian randomisation. One such study did conclude that vitamin D deficiency could increase the risk of cardiovascular disease, but (before we get too excited) another similar study failed to show that increased vitamin D levels benefited adverse cardiovascular outcomes.

As randomised, placebo-controlled trials  provide the highest quality evidence, have such trials provided evidence of a cardiovascular benefit from taking vitamin D? In short, no. The first which looked at both cancer and cardiovascular disease, concluded that vitamin D was no better than placebo. The second and which focused solely on cardiovascular disease came to a similar conclusion.

With the picture around vitamin D and cardiovascular health remaining unclear, you’d have thought that by now researchers simply wouldn’t bother with another, expensive randomised trial. But they did, and the results were not really surprising.

The D-Health trial

In a new trial, recently published in the BMJ, researchers set out to investigate whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events. The D-Health trial randomised participants to either 60,000 IU of vitamin D3 every month for five years or matching placebo. Although this trial focused solely on cardiovascular disease, the same authors had already previously published findings from the same trial that showed that high dose vitamin D in older adults had no effect on all-cause mortality.

But what about the impact on cardiovascular disease?

The D-Health trial included 21,302 people with 10,658 randomised to vitamin D. The serum vitamin D level increased to a mean of 115 mmol/L in those supplemented but was also quite high, at 77 mmol/L, in the placebo group. Compared to the placebo group, there was a 9% lower risk of a major cardiovascular event in those taking vitamin D (Hazard ratio, HR = 0.91, 95% CI 0.81 – 1.01). Since the upper confidence interval value was greater than one, the finding was not significant, i.e., it might have occurred by chance. The risk of a myocardial infarction was 19% lower (HR = 0.81, 95% CI 0.67 – 0.98) and which was just about significant. Although the researchers assessed other adverse cardiovascular events such as coronary revascularisation and strokes, the differences between vitamin D and placebo were all non-significant.

Not to be outdone by those pesky statistics, the authors wrote, ‘in this analysis of data from the D-Health trial we found some evidence that supplementation with 60,000 IU of vitamin D3 per month for up to five years reduce the incidence of major cardiovascular events.’ Interestingly, they also added that ‘the confidence intervals for total major cardiovascular events and coronary revascularisation were consistent with null findings. A translation of this might be: ‘We think that vitamin D helps, but, in reality, this effect might be no better than placebo.’

The findings from the D-Health trial are consistent with those of other randomised trials looking at vitamin D in cardiovascular disease, from which it is clear the supplement offers limited cardiovascular benefits.

Pharmacists should always look to the best available evidence to inform their practice. Consequently, we would better focus on lifestyle interventions such as smoking cessation, improving diet and increasing levels of physical activity to help reduce the risk of cardiovascular disease.

These interventions have a good evidence base and should be supported, as opposed to relying on a vitamin that offered much hope for a range of chronic conditions but that has failed to deliver tangible benefits.

Rod Tucker BPharm, PhD is a clinical writer