Vitamin D Deficiency, Supplementation, and Aging-Related Morbidity and Mortality Across Two Longitudinal Population Cohorts.

Authors

Ariel Israel, Abraham Weizman, Sarah Israel, Shai Ashkenazi, Eytan Ruppin, Eli Magen, Eugene Merzon, Shlomo Vinker

Published in

Aging cell. Volume 25. Issue 10. Pages e70752.

Abstract

Vitamin D deficiency has been implicated in biological processes linked to aging and organismal resilience, yet its relationship to long-term systemic aging trajectories remains incompletely characterized. We analyzed longitudinal electronic health record data from two large healthcare systems: Leumit Health Services (LHS), a nationwide Israeli health organization, and TriNetX, a federated US research network. We examined more than 1.67 million serum 25-hydroxyvitamin D [25(OH)D] measurements from over 468,500 adults in LHS (2009-2020). Longitudinal matched analyses compared severe deficiency (< 10 ng/mL) with sufficiency (> 30 ng/mL) in LHS and were externally validated in 223,175 propensity score-matched TriNetX pairs; matched cohorts were approximately 54 years old, 65%-67% female, and followed for up to 10 years. In both populations, severe deficiency was associated with increased risks across multiple aging-related outcomes. All-cause mortality was higher in LHS (adjusted HR 2.57, 95% CI 2.38-2.79) and TriNetX (HR 1.59, 1.55-1.63). To assess modifiability, we modeled vitamin D supplementation longitudinally using pharmacy-dispensed purchases calibrated to predict serum 25(OH)D changes over time. Supplementation was independently associated with dose-dependent reductions across mortality and multiple aging-related outcomes; for > 10 ng/mL-equivalent supplementation, mortality HR was 0.72 (0.68-0.76), while showing no corresponding association for skin malignancy. To strengthen causal interpretation, we additionally implemented inverse-probability-of-treatment-weighted marginal structural Cox models for mortality, which yielded results consistent with conventional adjusted models. Together, these findings support severe vitamin D deficiency as an important and potentially modifiable determinant of systemic aging vulnerability and age-related multimorbidity in human populations.

PMID:
42850752
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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