On the surface, it sounds dramatic. Low Vitamin D causes death. At least, that’s how the headlines would read if this were a criminal investigation. Hundreds of studies to date have published an inverse association between Vitamin D and the risk of death due to cardiovascular disease, cancer, and other causes: the lower the Vitamin D level, the higher the mortality risk.
However, there are many other studies that have shown the opposite: no relationship between Vitamin D and various cardiovascular, skeletal and metabolic outcomes. In fact, an umbrella review of a few hundred meta-analyses and systematic reviews (in other words, an overarching review of large datasets) found that “highly convincing evidence of a clear role of vitamin D does not exist for any outcome,” including skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases.
One possibility? It’s not a direct relationship. For example, a recent study showed yet again an association between low Vitamin D status and cardiovascular events (e.g., heart attacks) in patients with stable cardiovascular disease. This would suggest that low Vitamin D status exaggerates the risk of future cardiac events. However, authors of the study conducted further analyses and found that controlling for parathyroid hormone (PTH) levels abolished the association between Vitamin D deficiency and future cardiovascular risk. Since PTH increases Vitamin D conversion to the active form (1,25-dihydroxy Vitamin D) in the kidney as shown in the diagram, low Vitamin D levels may simply be a reflection of low PTH levels. No cause and effect, just an association. Similarly, since Vitamin D levels are influenced by physical activity, time spent outdoors, and diet, low Vitamin D may be a better indicator of poor health rather than a direct risk factor for various diseases.
Supplementation data are also very equivocal, with many large analyses showing no convincing effect of Vitamin D supplementation on fracture risk, heart disease, cancer, and overall mortality. As with all supplementation studies, there are major issues with metabolism, dosing, deficiency at baseline, and drug compliance that can make interpretation of the results quite difficult. Or, again these findings could reflect a lack of causal relationship between low Vitamin D, disease and mortality.
So what’s the take-home message? Is daily supplementation preventive or pointless, and how significant is a low Vitamin D level for current and future health? A recent article raised the excellent point that “short daily exposure to the sun at midday is presumably the best way to obtain robust levels of vitamin D,” yet our concerns about skin cancer often prevent us from obtaining adequate sun exposure. In essence, “both sun avoidance and excessive sun exposure are extreme behaviors that threaten our health.” So perhaps the best strategy is the moderate one: 15 minutes of walking or relaxing outside at lunchtime. Sounds quite D-lectable :)