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Vitamin D as a Regulator of the Biological Clock-Implications for Circadian-Metabolic Dysregulation

Vesković M, Šutulović N, Djuric E, Hrnčić D, Marković AR, Stanojlović O, Mladenović D

International journal of molecular sciences, 2026

2 citations

Abstract

Circadian disruption represents a global health issue associated with cardiometabolic diseases, sleep disturbances, and mood disorders, driven by a pathophysiological network including clock gene dysregulation and impaired melatonin synthesis. Vitamin D exerts pleiotropic effects on metabolic regulation, immune function, neurotransmission, and possibly circadian synchronization. Emerging evidence suggests that vitamin D and its hydroxyderivatives modulate clock gene expression, influence transcriptional regulators such as retinoic acid receptor-related orphan receptors and REV-ERBs, and interact with melatonin synthesis and signaling. Vitamin D deficiency has been associated with metabolic syndrome, impaired sleep quality, and depression. Although interventional studies yield heterogeneous results, higher vitamin D status may confer protective metabolic and neurobehavioral effects. This review summarizes current evidence on the role of vitamin D in circadian disruption and evaluates its potential therapeutic relevance in circadian-metabolic dysregulation.

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