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Genetic evidence suggests a causal relationship between levels of vitamin D and mortality in people with low vitamin D levels, according to researchers.

In a study published in The Lancet Diabetes & Endocrinology, a team led by the University of Cambridge aimed to determine whether genetic predisposition to high vitamin D levels plays a role in one's overall health.

Using data from 33 prospective studies – including UK Biobank, the European Prospective Investigation into Cancer and Nutrition Cardiovascular Disease study (EPIC-CVD) and 31 studies from the Vitamin D Studies Collaboration (VitDSC) – the group conducted both observational and genetic analyses. 

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They analyzed data from 386,406 middle-aged individuals with European ancestry.

Participants were followed for an average of 9.5 years, did not have cardiovascular disease at baseline and underwent valid 25(OH)D measurements.

The major circulating form of vitamin D, 25(OH)D, is measured using a blood test.

Of the 386,406 patients, 33,546 people developed coronary heart disease, 18,166 people had a stroke and 27,885 people died.

To better comprehend the role of vitamin D levels in these cases, the researchers used Mendelian randomization – a process that uses genetic variants specifically related to a particular exposure to compare genetically defined population subgroups with different average levels of the exposure.

Analyzing 25(OH)D measurements, the authors did not find an association between genetic predisposition to higher vitamin D levels and coronary heart disease, stroke or death.

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However, for participants with vitamin D deficiency – lower than 25 nanomoles per liter – the group said genetic analyses provided strong evidence for an inverse link between a lower mortality risk and genetic predisposition to higher levels of vitamin D.

There was also a link between genetic predisposition to 10 nanomoles per liter higher levels 25(OH)D and a 30% lower all-cause mortality risk, though effects were only evident in individuals with levels of vitamin D below 40 nanomoles per liter.

"Stratified Mendelian randomization analyses suggest a causal relationship between 25(OH)D concentrations and mortality for individuals with low vitamin D status," they wrote. 

There were some limitations noted, including that the analysis was comprised of solely middle-aged participants of European ancestries. 

Nevertheless, these conclusions, the authors assert, have implications for the design of vitamin D supplementation trials and potential disease prevention strategies.

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Vitamin D is both a nutrient and a hormone that our bodies produce, and is produced endogenously when ultraviolet (UV) rays from sunlight strike the skin and trigger vitamin D synthesis, according to the National Institutes of Health Office of Dietary Supplements. 

While vitamin D – or calciferol – has been known to help the body absorb and retain calcium and phosphorous, Harvard University's T.H. Chan School of Public Health notes that laboratory studies show it can reduce cancer cell growth, help control infections and reduce inflammation.