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.
But the researchers of this latest study - including Prof. Borge Nordestgaard of 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, Prof. Nordestgaard and colleagues 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, Naveed Sattar and Paul Welsh - 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."