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Increased mortality linked to genetically low vitamin D

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Recent study findings suggest an association between low 25-hydroxyvitamin D concentrations and all-cause mortality, cancer mortality and other mortality, but not cardiovascular mortality.

Børge G. Nordestgaard, MD, DMSc, professor at Copenhagen University Hospital in Denmark, and colleagues evaluated 95,766 white participants from three cohorts in Copenhagen to determine whether genetically low 25-(OH)D concentrations are linked to increased mortality. Plasma 25-(OH)D measurements were available for 35,334 participants.

Børge G. Nordestgaard

Participants were evaluated for genetic variants in DHCR7 and CYP2R1. From the study entry until its end in 2013, 10,349 participants died.

All-cause and cause-specific mortality were associated with a 20 nmol/L lower plasma 25-(OH)D concentration; specifically, the adjusted HRs were 1.19 (95% CI, 1.14-1.25) for all-cause mortality, 1.18 (95% CI, 1.09-1.28) for CV mortality, 1.12 (95% CI, 1.03-1.22) for cancer mortality and 1.27 (95% CI, 1.15-1.4) for other mortality.

There was a 1.9-nmol/L decrease in plasma 25-(OH)D concentration associated with each increase in DHCR7/CYP2R1 allele score. For each one DHCR7/CYP2R1 allele score increase, the HRs were 1.02 (95% CI, 1-1.03) for all-cause mortality, 0.98 (95% CI, 0.96-1.01) for CV mortality, and 1.03 (95% CI, 1-1.06) for cancer mortality and other mortality.

For all-cause mortality, the OR was 1.3 (95% CI, 1.05-1.61) for a genetically determined 20 nmol/L lower plasma 25-(OH)D concentration.

“Our data suggest that low vitamin D is a direct cause of increased mortality,” Nordestgarrd told Endocrine Today. “The best advice to patients is to get enough sunshine (up to half an hour on arms, face and neck a couple of times a week) and to get fatty fish. Whether vitamin D supplements are advisable for healthy people await publication of large randomized trials in 2017.”

In an accompanying editorial, Paul Welsh, PhD, and Naveed Sattar, MD, PhD, of the University of Glasgow, wrote that the study findings provide optimism for upcoming results of new trials, “more so if they are rapidly confirmed by additional Mendelian randomization studies with greater power.”

“Mendelian randomization is an important emerging research tool, is here to stay, and is beginning to be recognized by guideline committees,” Welsh and Sattar wrote. “Of course, in research where randomized trials are possible (or indeed ongoing), mendelian randomization studies should not displace them as the gold standard evidence in clinical guidelines or in the minds of health care professionals. In the meantime, there may well be yet more ‘groundhog days’ for vitamin D.” – by Amber Cox

For more information:

Afzal S. BMJ. 2014;349:g6330.

Welsh P. BMJ. 2014;349:g6599.

Disclosure: The study was funded in part by the Copenhagen County Foundation, Copenhagen University Hospital, Danish Heart Foundation, Danish Medical Research Council and Herlev Hospital.