Preferential lactate metabolism in the human brain during exogenous and endogenous hyperlactataemia.
Level 3 - non-randomized controlled study
Controlled within-subject crossover physiological study in healthy humans without explicit mention of randomization.
PubMed 41037311 · doi:10.1113/JP289216
What was done
Thirteen healthy adults (6 females) underwent two matched hyperlactataemia protocols (~4 and ~8 mmol/L arterial lactate): passive intravenous sodium lactate infusion (exogenous) and cycling exercise (endogenous). Researchers combined radial arterial and internal jugular venous blood sampling with cerebral blood flow (CBF) measurements to determine cerebral metabolic rates of oxygen (CMRO2), glucose (CMR_Glc), and lactate (CMR_iLac).
What was found
Cerebral blood flow was higher during exogenous infusion than during exercise (P < 0.001), despite infusion causing systemic alkalosis (P < 0.001). Total CMRO2 remained unchanged across both conditions and lactate levels (P = 0.610). CMR_Glc decreased significantly with increasing lactate (P = 0.009) with no difference between exercise and infusion conditions (P = 0.373). CMR_iLac increased in a dose-dependent manner (P < 0.001) similarly across conditions (P = 0.972). At 8 mmol/L arterial lactate, circulating lactate accounted for 24% of total cerebral oxidative metabolism.
Why it matters
This study demonstrates that the healthy human brain readily shifts from glucose to lactate oxidation based strictly on circulating substrate concentration, regardless of whether hyperlactataemia is generated by physical exertion or passive infusion.
Limits
The study had a small sample size (n = 13) restricted to healthy adults, precluding generalization to clinical populations with impaired cerebral metabolism or older adults. The abstract does not specify whether protocol order was randomized, and only acute, short-term metabolic responses were evaluated.
Cited by
- supports Human studies show that lactate generated from vigorous exercise crosses into the brain.