Australian researchers have found that the more severe the vitamin D deficiency, the greater the risk of mortality, according to a study published in the Annals of Internal Medicine by the University of South Australia.
Vitamin D is an important nutrient that helps maintain good health and keep our bones and muscles strong and healthy.
First author and UniSA PhD candidate Josh Sutherland said while vitamin D has been connected with mortality, it has been challenging to establish causal effects.
“Although severe vitamin D deficiency is rarer in Australia than elsewhere in the world, it can still affect those who have health vulnerabilities, the elderly, and those who do not acquire enough vitamin D from healthy sun exposure and dietary sources,” he said.
“Our study provides strong evidence for the connection between low levels of vitamin D and mortality, and this is the first of its kind to also include respiratory disease related mortality as an outcome.
“We used a new genetic method to explore and affirm the non-linear relationships that we’ve seen in observational settings, and through this are able give strong evidence for the connection between low vitamin D status and premature death.
“Vitamin D deficiency has been connected with mortality, but as clinical trials have often failed to recruit people with low vitamin D levels – or have been prohibited from including vitamin deficient participants – it's been challenging to establish causal relationships."
The Mendelian randomisation study evaluated 307 601 records from the UK Biobank. Low levels of vitamin D were noted as less than <25 nmol/L with the average concentration found to be 45.2 nmol/L. Over a 14-year follow-up period, researchers found that the risk for death significantly decreased with increased vitamin D concentrations, with the strongest effects seen among those with severe deficiencies.
Senior investigator and director of UniSA’s Australian Centre for Precision Health Professor Elina Hyppönen said more research was now needed to establish effective public health strategies that could help achieve national guidelines and reduce the risk of premature death associated with low vitamin D levels.
“The take-home message here is simple: the key is in the prevention. It is not good enough to think about vitamin D deficiency when already facing life-challenging situations, when early action could make all the difference,” she said. “It is very important to continue public health efforts to ensure the vulnerable and elderly maintain sufficient vitamin D levels throughout the year.”
Study details
Vitamin D Deficiency Increases Mortality Risk in the UK Biobank
Joshua P. Sutherland, Ang Zhou, Elina Hyppönen.
Published in the Annals of Internal Medicine on 25 October 2022.
Background
Low vitamin D status is associated with increased mortality, but randomised trials on severely deficient participants are lacking.
Objective
To assess genetic evidence for the causal role of low vitamin D status in mortality.
Design
Nonlinear Mendelian randomisation analyses.
Setting
UK Biobank, a large-scale, prospective cohort from England, Scotland, and Wales with participants recruited between March 2006 and July 2010.
Participants
307 601 unrelated UK Biobank participants of white European ancestry (aged 37 to 73 years at recruitment) with available measurements of 25-hydroxyvitamin D (25-(OH)D) and genetic data.
Measurements
Genetically predicted 25-(OH)D was estimated using 35 confirmed variants of 25-(OH)D. All-cause and cause-specific mortality (cardiovascular disease [CVD], cancer, and respiratory) were recorded up to June 2020.
Results
There were 18 700 deaths during the 14 years of follow-up. The association of genetically predicted 25-(OH)D with all-cause mortality was L-shaped (P for nonlinearity < 0.001), and risk for death decreased steeply with increasing concentrations until 50 nmol/L. Evidence for an association was also seen in analyses of mortality from cancer, CVD, and respiratory diseases (P ≤ 0.033 for all outcomes). Odds of all-cause mortality in the genetic analysis were estimated to increase by 25% (odds ratio, 1.25 [95% CI, 1.16 to 1.35]) for participants with a measured 25-(OH)D concentration of 25 nmol/L compared with 50 nmol/L.
Limitations
Analyses were restricted to a white European population. A genetic approach is best suited to providing proof of principle on causality, whereas the strength of the association is approximate.
Conclusion
Our study supports a causal relationship between vitamin D deficiency and mortality. Additional research needs to identify strategies that meet the National Academy of Medicine's guideline of greater than 50 nmol/L and that reduce the premature risk for death associated with low vitamin D levels.
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