A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain

Abstract

During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O 2 /(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio-venous differences (AV) for O 2 , glucose (glc) and lactate (lac) were evaluated in nine healthy subjects at rest and during and after exercise to exhaustion. The cerebrospinal fluid (CSF) was drained through a lumbar puncture immediately after exercise, while control values were obtained from six other healthy young subjects. In a second experiment magnetic resonance spectroscopy ( 1 H-MRS) was performed after exhaustive exercise to assess lactate levels in the brain (n = 5). Exercise increased the AV O2 from 3.2 ± 0.1 at rest to 3.5 ± 0.2 mM (mean ± S.E.M.; P < 0.05) and the AV glc from 0.6 ± 0.0 to 0.9 ± 0.1 mM (P < 0.01). Notably, the AV lac increased from 0.0 ± 0.0 to 1.3 ± 0.2 mM at the point of exhaustion (P < 0.01). Thus, maximal exercise reduced the cerebral metabolic ratio from 6.0 ± 0.3 to 2.8 ± 0.2 (P < 0.05) and it remained low during the early recovery. Despite this, the CSF concentration of lactate postexercise (1.2 ± 0.1 mM; n = 7) was not different from baseline (1.4 ± 0.1 mM; n = 6). Also, the 1 H-MRS signal from lactate obtained after exercise was smaller than the estimated detection limit of ∼1.5 mM. The finding that an increase in lactate could not be detected in the CSF or within the brain rules out accumulation in a distribution volume and indicates that the lactate taken up by the brain is metabolized.

Lactate: The Ultimate Cerebral Oxidative Energy Substrate?

“…This evidence should at least raise some doubt regarding the notion that lactate is a dead-end product. Moreover, a recent human study by Dalsgaard et al (2004) has indicated that lactate, produced during exercise, is taken up and metabolized by the brain. Nevertheless, the widely accepted dogma that, aerobically, pyruvate, not lactate, is the final product of glycolysis (reaction II) is both chemically and thermodynamically flawed.…”

Fuelling Cerebral Activity in Exercising Man

“…Lactate is cotransported with one H + (Becker et al, 2004;Juel, 2001) and, at any given lactate concentration, the H + (or pH) gradient between blood and brain influences lactate transport, as illustrated by an increased lactate uptake when pH becomes low (Oldendorf et al, 1979). Often even maximal exercise elicits, but a small decrease in pH (Dalsgaard et al, 2002(Dalsgaard et al, , 2004c). Yet, in a competitive setting such as elite rowing blood pH may decrease to as low as B6.8, with blood lactate increasing up to B30 mmol/L (Nielsen, 1999).…”

“…(reviewed in Gladden, 2004;Hertz and Dienel, 2005;Pierre and Pellerin, 2005). As transport is down the concentration gradient, a significant lactate uptake requires that the arterial level exceeds that within the brain of B1.5 mmol/L (Abi-Saab et al, 2002;Dalsgaard et al, 2004c) ( Table 1). Thus, from an arterial lactate concentration < 1 mmol/L in a physically inactive subject, a several fold increase in the arterial concentration, as during strenuous exercise, is required to accelerate transport.…”

Increase brain lactate in hepatic encephalopathy: Cause or consequence?

“…It has previously been demonstrated lactate cannot easily cross the bloodbrain barrier (Hertz andDienel, 2002 andAuer, 1986), infusing lactate intravenously does not increase CSF lactate (Alexander et al, 1962) and levels of blood and CSF lactate are regulated independently (Posner and Plum, 1967). However, others have documented that the blood-brain barrier is permeable to lactate (Dalsgaard et al, 2004, Smith et al, 2003and Oldendorf, 1973 and the lactate transporter MCT1 is expressed on endothelial cells (Gerhart et al, 1997). Furthermore, Tofteng and Larsen (2002) in a case report describing a patient with severe ALF and brain edema found microdialysate (extracellular) lactate was influenced by alterations in arterial concentrations of lactate.…”