How are BDNF and fatigue related?

BDNF (Brain-Derived Neurotrophic Factor) is crucial for neuronal survival, growth, and synaptic plasticity. Some studies suggest a link between low BDNF levels and increased fatigue, particularly in conditions like chronic fatigue syndrome (ME/CFS) or depression. However, the evidence is mixed: other studies find no significant association, and effect sizes are generally small. BDNF is influenced by many lifestyle factors (exercise, stress, diet), so a single genetic variant (e.g., the common Val66Met polymorphism) from a consumer DNA test cannot reliably predict fatigue risk. Most reported variants have weak clinical significance. The proposed mechanism involves BDNF's role in mitochondrial biogenesis and neuroinflammation, but direct causality remains unproven. Fatigue is multifactorial, and genetic contributions are modest. Therefore, while BDNF is a biologically plausible player, consumer test results should be interpreted cautiously and not used for diagnosis or treatment decisions.