Vitamin D Deficiency, Supplementation, and Risk of Mortality and Chronic Disease: Evidence from Matched Cohorts in Israel and the US

Vitamin D deficiency is widespread and has been linked to adverse health outcomes, but its causal role remains debated. We analyzed data from two large healthcare networks—Leumit Health Services in Israel and the US-based TriNetX network—using matched cohort designs to compare individuals with severe vitamin D deficiency (<10 ng/mL) to those with sufficient levels (>30 ng/mL). Vitamin D showed strong seasonal variation, and deficiency was associated with increased risks of mortality, cardiovascular events, dialysis, and leg/foot amputation in both cohorts. To assess causality, we modeled serum vitamin D levels based on monthly pharmacy-dispensed supplementation and performed time-dependent Cox regressions adjusting for baseline deficiency. We identified a dose-dependent reduction in risk with supplementation associated, independent of baseline levels, with substantial absolute risk reductions. These findings support vitamin D deficiency as a modifiable risk factor and provide a rationale for targeted clinical trials in severely deficient populations.