Clin Nutr ESPEN. 2026 Jul 17:103599. doi: 10.1016/j.clnesp.2026.103599. Online ahead of print.
ABSTRACT
The role of vitamin D supplementation in health outcomes remains a subject of debate. While severe deficiency has been linked to conditions such as rickets, osteomalacia, and secondary hyperparathyroidism, large-scale randomized controlled trials have not consistently shown the expected benefits of universal supplementation in general populations with adequate serum levels. Observational studies suggest that there is an association between serum 25-hydroxyvitamin D levels and all-cause mortality, falls, and cardiovascular events. The optimal range for these levels is around 20-30 ng/mL (50-75 nmol/L). One perspective advocates maintaining higher targets and continued universal supplementation based on widespread deficiency and observational data. The opposing viewpoint advocates for the cessation of universal supplementation, the implementation of individualized treatment plans, and the reduction of target levels. This position is supported by unfavorable trial results and Mendelian randomization studies that challenge the established causality. In this review, we propose a novel, evidence-based middle-path framework that explicitly distinguishes deficiency treatment from universal prevention, defines a safe and effective target range of 20-30 ng/mL (50-75 nmol/L), and advocates tailored strategies for high-risk subgroups (e.g., nursing home residents, malabsorption, glucocorticoid users, chronic kidney disease, and pregnancy). This stratified framework is distinct from previous dichotomous approaches in that it systematically integrates therapeutic and preventive indications, safety considerations at the upper end of the U-shaped curve, and disease-specific metabolic alterations into a single, actionable clinical algorithm. This conceptual shift from indiscriminate supplementation to precision intervention offers a practical resolution to the ongoing clinical debate. Future research should prioritize the design of trials with deficient populations, ensuring adequate follow-up and systematic safety monitoring. The transition from universal supplementation to precision intervention signifies a shift in modern medicine's approach, moving from addressing deficiencies to managing complex systems.
PMID:42468847 | DOI:10.1016/j.clnesp.2026.103599