Genetically low vitamin D levels linked to all-cause mortality

A new study published in the British Medical Journal (BMJ) may provide evidence of a causal association between vitamin D deficiency and increased risk of death, after finding a higher risk of all-cause mortality among people with genetically low concentrations of the vitamin.

Many people are regularly taking vitamin D supplements with the aim of living longer, so the researchers wanted to determine whether vitamin D deficiency is a cause of increased mortality.

This is not the first study to document a link between vitamin D deficiency and mortality. Earlier this year, a team of researchers reported on research linking low vitamin D levels to all-cause mortality and cancer prognosis, while another study from the University of California-San Diego associated vitamin D deficiency with premature death.

But the researchers of this latest study at the Department of Clinical Biochemistry at Copenhagen University Hospital in Denmark - note that one question remains unclear: are low vitamin D levels a cause of poor health or a result of it?

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

'Clinical implications of findings remain limited'

To address this question, the research team analyzed 95,766 individuals from Denmark who had been assessed for variants in the genes DHCR7 and CYP2R1, which are known to lower vitamin D levels in the body. Such an analysis is called mendelian randomization.

The participants were identified from three cohorts: the Copenhagen City Heart Study, the Copenhagen General Population Study and the Copenhagen Ischemic Heart Disease Study.

Vitamin D levels - as measured by 25-hydroxyvitamin D concentrations - were recorded among 35,334 participants, and other factors that may influence mortality - such as physical activity levels, alcohol consumption, body mass index (BMI), blood pressure, cholesterol levels and smoking status - were recorded.

Results of the analysis revealed that participants with genetically low vitamin D levels were at higher risk of all-cause mortality, including cancer, compared with those who did not have genetically low vitamin D levels.

The researchers note, however, that they did not find any association between genetically low vitamin D concentrations and increased risk of cardiovascular mortality.

Commenting on their findings, the researchers say:

"These findings are compatible with the notion that genetically low 25-hydroxyvitamin D concentrations may be causally associated with mortality due to cancer and other causes, but also suggest that the observational association with cardiovascular mortality could be the result of confounding.

The clinical implication of our findings remain limited, as widespread vitamin D supplementation can be recommended only after benefit is shown in randomized intervention trials."

In a editorial linked to the study, two scientists - both of the British Heart Foundation in the UK - say that in this study, "the epidemiological cliché that 'more data are required to confirm these findings' once again applies."

They add, however, that the findings "provide some cause for optimism" regarding the results of future large clinical trials assessing the link between vitamin D deficiency and mortality. They note that vitamin D supplementation trials - such as the VITamin D and OmegA-3 TriaL (VITAL) - are due to end in 2017, "so we do not have to wait too long to see whether mendelian randomization studies and large-scale trials are in agreement."

Another team of researchers recently reported on a study suggesting that adults with asthma who have vitamin D deficiency may be at much higher risk of asthma attacks.

References:

1. Genetically low vitamin D concentrations and increased mortality: mendelian randomisation analysis in three large cohorts, Borge Nordestgaard, et al., BMJ, doi: 10.1136/bmj.g6330, published online 18 November 2014.
2. Vitamin D genes and mortality: harnessing genetics to re-examine the case for vitamin D, Paul Welsh, Naveed Sattar, BMJ, doi: 10.1136/bmj.g6599, published online 18 November 2014, editorial.