A recent study published in the journal Atherosclerosis confirms previous research that higher vitamin D levels are significantly associated with reduced risk of mortality.
Research continues to prove that maintaining higher vitamin D levels reduces one’s risk of mortality. However, the research that illustrates this relationship is largely of observational design. Why, you might ask? Randomized controlled trials (RCTs), the gold standard of research, requires a lot of money and time. For a randomized controlled trial to prove that vitamin D supplementation reduces the risk of mortality, researchers would need enough people to be affected by the outcome (i.e. mortality) for them to properly assess how vitamin D supplementation affects the incidence of mortality.
Since RCTs allow researchers to prove causation, and observational studies only prove association, vitamin D skeptics believe that observational studies are merely showing that health conscious people are vitamin D sufficient. In other words, they argue that someone who supplements with vitamin D is also more likely to exercise frequently, eat more nutritiously, etc. Thus, vitamin D sufficient people have reduced mortality rates. To address this, researchers must adjust for confounding factors, variables that affect both the outcome (mortality) and the exposure (vitamin D).
Researchers recently tested their hypothesis that low vitamin D status is associated with all-cause mortality, independent of confounding factors. They analyzed 10,517 adults over the age of 35 in NHANES III data (1988-1994) with a 20-year mortality follow-up. The researchers adjusted the results for a wide variety of potential confounding factors, including the following:
Sex, race, diabetes, blood pressure meds, income, taking vitamin D supplements, physical activity, alcohol, age, BMI, blood pressure, CRP, estimated glomerular filtration rate, albumin:creatinine urinary secretion ratio, serum lipoprotein(a), serum thyroxine, season, region, total serum carotenoids, serum iron, RBC folate, serum vitamin C, serum vitamin A, serum vitamin E, serum homocysteine and serum total calcium
The analysis revealed these results:
- There was a significant inverse relationship between coronary heart disease mortality and vitamin D status in the unadjusted model.
- After adjusting for confounding factors, only the highest quartile, vitamin D levels above 32 ng/ml, was inversely associated with coronary heart disease mortality (p < 0.05).
- A significant inverse relationship existed between vitamin D levels and all-cause mortality (p < 0.05).
The researchers concluded,
“Our analysis showed that even when adjusting for dietary effects, the risk of low vitamin D persisted for all-cause mortality. However, for coronary heart disease mortality a strong inverse association was not found, but comparing the highest quartile to the lowest quartile of vitamin D levels was associated with an inverse association with [coronary heart disease] mortality.”
The study possessed multiple unique strengths. First, it adjusted for a very large range of confounders, which allowed the researchers to better isolate the relationship between vitamin D status and mortality. Second, it included a sample size of greater than 10,000, making the results more reliable. Lastly, the study included a 20-year follow up.
While reviewing the study’s results, it’s important to note that these findings have been replicated in other studies. Furthermore, a Mendelian randomization study, a design capable of proving causality, determined that genetically low vitamin D status was associated with higher all-cause mortality and cancer mortality, but not cardiovascular mortality.
Tovey, A. & Cannell, JJ. New study suggests higher vitamin D levels associated with reduced risk of mortality. The Vitamin D Council Blog & Newsletter, 2016.