Lactate Infusion Increases Circulating pro-Brain-Derived Neurotrophic Factor Levels in Humans

Exercise has been shown to improve brain health by stimulating mature brain-derived neurotrophic factor (mBDNF) production. Murine model data and correlational studies in humans suggest that lactate may play a role in increasing mBDNF levels. Less is known about the effect on the pro-BDNF isoform and if lactate can exert an effect on mBDNF levels in humans without a simultaneous exercise stimulus. We aimed to investigate how increased systemic lactate levels in humans at rest alter plasma- and muscle levels of the two BDNF isoforms. Eighteen young, healthy volunteers (50% female) were recruited and received either a venous infusion of sodium lactate or a volume-matched infusion of isotonic saline. Twelve of the participants were assigned to an experimental group using a crossover design for blood sampling while donating muscle biopsies during lactate infusion, and six participants were assigned to act as a control group for muscle biopsy sampling. Blood was collected before, during, and for two hours of recovery, while muscle was collected before and after the infusion. Samples were analyzed for pro- and mBDNF using enzyme-linked immunosorbent assay and immunoblotting. Lactate infusion elevated plasma lactate levels tenfold (p < 0.0001), and muscle lactate by 29%, p = 0.004. Plasma mBDNF levels were unaffected by the intervention, while pro-BDNF increased by 32% in plasma (p = 0.0179) but remained unaltered in muscle. Our results indicate that lactate alone can alter levels of circulating pro-BDNF, however, for additional effects on mBDNF, exercise may need to be added.