How are VDR and fatigue related?

The vitamin D receptor (VDR) is frequently linked to fatigue, especially in chronic conditions like multiple sclerosis, fibromyalgia, and chronic fatigue syndrome. Polymorphisms such as FokI (rs2228570) and BsmI (rs1544410) can alter VDR signaling, potentially affecting immune regulation, mitochondrial function, and muscle recovery. Some studies report associations between certain VDR variants and higher fatigue levels, while others find no significant link. The evidence is mixed and largely mechanistic or observational; causal conclusions cannot be drawn. Consumer DNA tests often include VDR SNPs, but their predictive value for fatigue is low. Vitamin D status, lifestyle, and comorbidities are far more influential. Interpreting a VDR genotype in isolation without clinical context is misleading. Persistent fatigue should prompt a medical evaluation of vitamin D levels, regardless of VDR genotype.