Rethinking Clinical Vitamin D Research: Evidence, Methodology, and Future Directions

Despite decades of intensive research and thousands of published studies, fundamental questions regarding vitamin D requirements, thresholds, and clinical utility remain unresolved. This paradox reflects not a lack of interest or effort, but persistent methodological limitations in how clinical vitamin D research has been designed, conducted, interpreted, and translated into guidelines. Despite being a key regulator of mineral metabolism and systemic endocrine function, the evidence base guiding clinical practice surrounding vitamin D is often inconsistent or weak.This Research Topic aims to critically re-evaluate the foundations of clinical vitamin D research and to define how future studies should be designed to generate robust, actionable evidence. Rather than focusing on specific disease outcomes, this collection will emphasize study methodology, trial design, measurement standardization, and interpretive frameworks that underpin credible vitamin D research across skeletal and extra-skeletal settings, including careful evaluation of both benefits and potential risks of supplementation.We welcome contributions addressing, but not limited to, the following themes:• The scientific basis and limitations of current vitamin D intake recommendations, and what types of studies are required to establish evidence-based guidelines.• The concept of biochemical osteomalacia and its relevance for interpreting vitamin D deficiency and clinical endpoints.• Optimal design of future randomized controlled trials, including treat-to-target approaches, dosing strategies, and participant selection.• The respective roles of randomized trials versus observational studies in defining vitamin D thresholds and biological sufficiency.• The impact of ethnicity, genetics, and baseline vitamin D status on study design, interpretation, and generalizability.• Ethical considerations in vitamin D intervention studies, particularly in populations at risk of deficiency.• The plausibility and implications of context-specific vitamin D thresholds across different diseases or physiological states.• The need for standardized vitamin D assays, harmonized protocols, and coordinated research strategies to avoid fragmented, underpowered studies.• The potential long-term adverse effects of unrestricted or high-dose vitamin D supplementation, including implications for safety monitoring and risk–benefit assessment in clinical practice.• Lessons learned from recent pandemics, and how vitamin D research can be better prepared to address urgent public health questions in future global health crises.By bringing together experts in endocrinology, clinical trial design, epidemiology, and laboratory standardization, this Research Topic seeks to move the field beyond repetitive and inconclusive studies toward coherent, high-quality research frameworks capable of resolving long-standing uncertainties. The ultimate goal is to improve the reliability of vitamin D evidence and its translation into meaningful clinical practice. Topic editors: Rolf Jorde, Guri Grimnes, Lars Rejnmark Source: https://www.frontiersin.org/research-topics/77707/rethinking-clinical-vitamin-d-research-evidence-methodology-and-future-directions