Genetically low vitamin D associated with increased mortality

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Genetically low vitamin D levels are associated with increased all cause mortality, (including cancer), but not with cardiovascular mortality, finds a large Danish study published in The BMJ this week.

Observational studies have suggested that lower levels of vitamin D are associated with increased mortality, but whether low vitamin D concentrations are a cause of increased mortality or simply a consequence of poor health is thus unclear.

This is an important question, say the authors, as millions of people worldwide are regularly taking vitamin D supplements, presumably with the aim of preventing diseases and hopefully living longer.

Genetic variants have been reliably associated with circulating concentrations of vitamin D, a marker of vitamin D status. So a research team based in Denmark set out to test the theory that genetically low vitamin D levels are associated with increased mortality, using a technique called mendelian randomisation.

The study involved 95,766 white participants of Danish descent from three cohorts in Copenhagen, who had genetic variants known to affect vitamin D levels.

Other common risk factors, such as smoking status, alcohol consumption, physical activity levels, blood pressure, cholesterol levels and body mass index were also recorded.

Participants were followed from study entry until 2013, during which time 10,349 died.

The results show that genetically low vitamin D levels were associated with increased all cause mortality, cancer mortality, and other mortality, but not with cardiovascular mortality.

These findings are compatible with the notion that genetically low vitamin D levels may be causally associated with mortality from cancer and other causes, say the authors, but also suggest that the association with cardiovascular mortality could be the result of other unmeasured (confounding) factors.

“The clinical implication of our findings remain limited, as widespread vitamin D supplementation can be recommended only after benefit is shown in randomised intervention trials,” they conclude.

The borderline significance of the findings means that we should be careful not to over-interpret, warn researchers at the British Heart Foundation Glasgow Cardiovascular Research Centre, in an accompanying editorial.

The epidemiological cliché that “more data are required to confirm these findings” once again applies, they write. Nevertheless, they agree that Mendelian randomisation is a useful tool in clinical research.

However, they point out that several trials of vitamin D supplementation will start reporting in 2017, “so we do not have to wait too long to see whether mendelian randomisation studies and large scale trials are in agreement.”