Lactate as a Metabolite and a Regulator in the Central Nervous System
Authors: Patrizia Proia, Carlo Maria Di Liegro, Gabriella Schiera, Anna Fricano, Italia Di Liegro
DOI / Source: https://doi.org/10.3390/ijms17091450
Date: 01 September 2016
Reading level: Advanced
Why This Matters for Freedivers
Freediving is basically controlled hypoxia plus CO₂ buildup, and both of those push lactate biology into the spotlight. This review explains why lactate isn’t just “burn” or “waste”—it can fuel the brain and act like a signal molecule, meaning hard apnea sessions might influence the brain in ways that go beyond oxygen numbers.
Synopsis
Most people learn “lactate = fatigue.” This review explains why that idea is outdated, especially when you care about the brain.
First, lactate is a fuel, not just a byproduct. During intense effort (or low oxygen), the body produces lactate, releases it into the blood, and other organs can use it—including the brain. The paper explains how lactate can cross the blood–brain barrier using specific transport proteins called monocarboxylate transporters (MCTs). Different MCTs sit in different places: the barrier itself, astrocytes (support cells), and neurons. That layout matters because it sets up a “lactate traffic system” inside the brain.
Second, the review walks through the famous astrocyte–neuron lactate shuttle idea: when neurons are active, nearby astrocytes ramp up glycolysis and produce lactate, which neurons can then take up and burn as extra energy—especially when demand is high or glucose is limited. The authors also highlight that scientists still debate how big this effect is in everyday conditions, but it becomes especially relevant during stress, hypoxia, seizures, or heavy energy demand.
Third—and this is the coolest twist—lactate can behave like a signal, almost like a hormone. The paper describes a lactate receptor (often referred to as GPR81/HCAR1) found in brain regions involved in learning, and even on structures linked to blood flow regulation. That means lactate might help “tell the brain” about metabolic state and adjust activity, blood flow, and gene expression.
Finally, the review connects lactate to exercise benefits for the brain: exercise raises blood lactate, lactate can reach the brain, and there are links between lactate, plasticity-related genes, and factors associated with brain health and memory. In simple terms: lactate isn’t just something to avoid—it may be part of why hard physical work can leave the brain more resilient.
Abstract
More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even involved in processes as complex as memory formation and neuroprotection. As a matter of fact, exercise offers many benefits for our organisms, and seems to delay brain aging and neurodegeneration. Now, exercise induces the production and release of lactate into the blood which can reach the liver, the heart, and also the brain. Can lactate be a beneficial molecule produced during exercise, and offer neuroprotection? In this review, we summarize what we have known on lactate, discussing the roles that have been attributed to this molecule over time.