What role does BDNF play in fatigue?

BDNF (Brain-Derived Neurotrophic Factor) is a protein primarily known for supporting neuronal survival and plasticity. Regarding fatigue, BDNF is thought to influence mitochondrial function and energy homeostasis in the brain. Some studies report lower BDNF levels in chronic fatigue syndrome (ME/CFS) or cancer-related fatigue. However, the evidence is largely mechanistic and correlational; no strong human intervention trials confirm a causal role. BDNF levels are also modulated by exercise, diet, and stress, complicating interpretation. Direct clinical utility of BDNF measurement or supplementation for fatigue is not established. Genetic testing for BDNF variants (e.g., Val66Met) has limited predictive value. In summary, BDNF is a promising but unproven biomarker for fatigue, with evidence best described as mechanistic or mixed.