Across two large longitudinal cohorts totaling more than 468,000 adults in Israel and a matched US network, serum 25-hydroxyvitamin D below 10 ng/mL was associated with substantially higher all-cause mortality (adjusted HR 2.57 and 1.59) and elevated risk across metabolic, cardiovascular, renal, neurodegenerative, and microvascular outcomes. Pharmacy-dispensed supplementation modeled longitudinally showed dose-dependent risk reduction, with a mortality hazard ratio of 0.72 for exposure equivalent to raising serum levels by more than 10 ng/mL. Marginal structural Cox models with inverse-probability weighting produced results consistent with conventional adjustment, strengthening the case for a modifiable contribution.
Key Points
- Severe deficiency below 10 ng/mL doubled adjusted all-cause mortality risk
- Supplementation showed dose-dependent mortality reduction, hazard ratio 0.72
- Risk elevation spanned cardiovascular, renal, neurodegenerative, and microvascular outcomes
Longevity Analysis
Severe deficiency behaves less like an isolated nutrient gap and more like a systemic vulnerability marker, tracking simultaneously with vascular integrity, renal filtration capacity, cognitive decline, and metabolic regulation — consistent with vitamin D's role as a steroid hormone with receptors distributed across nearly every tissue. The absence of any association with skin malignancy functions as an internal negative control, arguing against pure confounding by sun exposure or general health-seeking behavior. The practical implication is narrow and measurable: identify the deficiency through serum testing rather than assumption, correct it to sufficiency, and sustain that correction, since the benefit observed here scaled with the magnitude and duration of repletion rather than with supplementation alone.
Original published by Wiley Aging Cell, by Ariel Israel, Abraham Weizman, Sarah Israel, Shai Ashkenazi, Eytan Ruppin, Eli Magen, Eugene Merzon, Shlomo Vinker .