Kinetic Analysis of the Human Blood-Brain Barrier Transport of Lactate and Its Influence by Hypercapnia
Authors: Gitte Moos Knudsen, Olaf B. Paulson, Marianne M. Hertz
DOI / Source: https://doi.org/10.1038/jcbfm.1991.107
Date: 1991
Reading level: Advanced
Why This Matters for Freedivers
Freediving often involves rising CO₂ (hypercapnia) and a drop in blood pH—especially in long statics, hard dynamics, or repetitive dives. This paper shows that when CO₂ is high, the brain may take up lactate from the blood more easily. That’s interesting because lactate isn’t just a “muscle waste product” — it’s also a brain fuel and a signaling molecule, so CO₂-heavy sessions might shift brain chemistry in ways that could affect how the end of a breath-hold feels.
Synopsis
This study looked at how easily lactate crosses the blood-brain barrier (BBB) in humans, and whether high CO₂ changes that transport. Lactate is central in situations where oxygen is limited (like intense effort or low-oxygen states), and the brain can both produce lactate and use it as fuel. But in the early 1990s, the actual human BBB transport kinetics for lactate hadn’t been properly described.
The researchers studied 18 hospital patients who were already undergoing carotid angiography procedures (so arterial and jugular venous access were available). They used a “double indicator” tracer technique: a small bolus containing labeled lactate plus reference tracers was injected into the carotid artery, and then rapid blood sampling from the jugular vein tracked how the tracers came out over time. With a kinetic model that accounts for backflux and differences in capillary transit times, they estimated how strongly lactate moves from blood into brain and from brain back into blood (permeability-surface area products).
The key baseline finding is that lactate can cross the BBB fairly easily: average unidirectional extraction was about 15%, and transport into the brain (PS1) was around 0.08 ml/g/min, with transport back out (PS2) of similar size—consistent with a mostly equilibrative, carrier-mediated system rather than one-way “pumping.”
Then they induced hypercapnia in 9 of the patients by having them breathe CO₂. As expected, CO₂ rose and blood pH fell. Under these conditions, cerebral blood flow nearly doubled—and importantly, the BBB transport into the brain (PS1) for lactate increased markedly (about a doubling). The authors argue the most likely driver is the pH change affecting the carrier system, rather than simply “more capillaries opening up.”
For freediving, the takeaway isn’t “CO₂ makes lactate go into the brain and that’s good/bad.” It’s more subtle: high CO₂ and lower pH can change what crosses into the brain and how fast. Since hard breath-holds push CO₂ up and pH down, this is a neat piece of evidence that the brain’s fuel/chemistry environment during or after apnea could be shifting in ways we rarely think about.
Abstract
Blood-brain barrier permeability to L-lactate was studied in 18 patients using a double indicator technique. Venous outflow curves were obtained during normocapnia and hypercapnia and analyzed with a model that accounts for tracer backflux and heterogeneity of capillary transit times. The average unidirectional extraction of L-lactate was 15%. Transport from blood to brain (PS1) was approximately 0.081 ml g⁻¹ min⁻¹, and transport from brain to blood (PS2) was of similar magnitude, consistent with an equilibrative transport mechanism. In hypercapnia, arterial pH decreased from 7.39 to 7.26 and PS1 for L-lactate increased significantly (about 110%). PS2 and intracellular uptake estimates also increased, though not all changes reached statistical significance. The results indicate that L-lactate is readily taken up by the human brain and that brain permeability to lactate is enhanced during hypercapnia, likely through a pH-related effect on transport.