From the Vitamin D Paradox to Precision Nutrition: Targeted Supplementation, Assay Pitfalls, and Clinical Decision-Making
Abstract
Purpose of review: Vitamin D is a pleiotropic secosteroid with established skeletal functions and proposed extraskeletal effects; however, its clinical application remains contentious. Despite extensive observational evidence linking low 25(OH)D concentrations to chronic diseases, randomized controlled trials (RCTs) have largely failed to confirm many of these associations. This review focuses on the practical clinical management of vitamin D, integrating determinants of vitamin D status, assay-related limitations, targeted testing, evidence-based supplementation, and decision-making within a precision-nutrition context.
Recent findings: The discordance between observational and interventional evidence is partly explained by the inclusion of vitamin D-replete populations in major trials, background supplementation, non-linear dose-response relationships, and assay variability. For skeletal outcomes, clinically meaningful effects are mainly observed in deficiency, whereas selected benefits have been reported in specific populations, including mortality reduction in adults aged ≥ 75 years, a modest reduction in cancer mortality, and reduced progression to diabetes in adults with high-risk prediabetes. The 2024 Endocrine Society guideline recommends empiric supplementation for selected groups and discourages routine screening in healthy adults. Daily or weekly dosing is preferred to intermittent high-dose regimens, which may increase falls and fractures. Standardization…
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