What role does Vitamin D 25-OH play in fatigue?

Vitamin D (25-OH) is a biomarker for vitamin D status and has been linked to fatigue, particularly in cases of deficiency. The evidence is largely observational, showing an inverse association between serum 25-OH levels and fatigue symptoms, especially in risk groups such as older adults, individuals with chronic diseases, or those with darker skin. Mechanistic plausibility includes vitamin D's role in muscle function (deficiency can cause myopathy), immune regulation (chronic inflammation as a driver of fatigue), and mitochondrial energy metabolism. However, randomized controlled trials (RCTs) on supplementation yield mixed results: correction of deficiency may reduce fatigue, but supplementation in replete individuals shows no consistent benefit. Thus, the evidence is moderate – a causal link is not firmly established. Testing 25-OH can be useful in unexplained fatigue, but it should not be used in isolation. Caveat: high-dose supplementation without deficiency can be toxic. Clinical interpretation is essential.