Blood Lactate is an Important Energy Source for the Human Brain

Abstract

Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion (36 mumol per kg bw per min), and during 30 mins of cycling exercise at 75% of maximal oxygen uptake while the lactate infusion continued to establish arterial lactate concentrations of 0.89+/-0.08, 3.9+/-0.3, and 6.9+/-1.3 mmol/L, respectively. At rest, cerebral lactate utilization changed from a net lactate release of 0.06+/-0.01 to an uptake of 0.16+/-0.07 mmol/min during lactate infusion, with a concomitant decrease in the net glucose uptake. During exercise, the net cerebral lactate uptake was further increased to 0.28+/-0.16 mmol/min. Most (13)C-label from cerebral [1-(13)C]lactate uptake was released as (13)CO(2) with 100%+/-24%, 86%+/-15%, and 87%+/-30% at rest with and without lactate infusion and during exercise, respectively. The contribution of systemic lactate to cerebral energy expenditure was 8%+/-2%, 19%+/-4%, and 27%+/-4% for the respective conditions. In conclusion, systemic lactate is taken up and oxidized by the human brain and is an important substrate for the brain both under basal and hyperlactatemic conditions.

Prevention of Acute/Severe Hypoglycemia-Induced Neuron Death by Lactate Administration

“…Blood-brain barrier transport of lactate and other substrates occurs via both facilitated transport and diffusion. Therefore, increases in plasma concentration of these compounds should substantially increase their transport into the brain (Boumezbeur et al, 2011;van Hall et al, 2009). The dose of lactate used in the present studies is estimated to generate a lactate plasma concentration of B2 to 3 mM, which is about twofold to threefold higher than under physiological conditions, likely increasing brain lactate concentrations accordingly.…”

“…In their astrocyte-neuron lactate shuttle hypothesis, Pellerin and Magistretti (1994) proposed that lactate can be used by neurons (Magistretti et al, 1999;Pellerin et al, 2005). In addition to astrocyte-derived lactate, Boumezbeur et al (2011) and van Hall et al (2009) proposed that plasma-borne lactate may have an important role in supporting oxidative brain metabolism, suggesting that plasma-borne lactate fuels up to 60% of all cerebral metabolism and tricarboxylic acid (TCA) cycle activity even under normal physiological conditions. Consistent with this lactate-fuel hypothesis, several lines of study have also provided evidence that lactate can support energy metabolism during ischemia, which can rescue neuronal death after ischemia or under conditions of oxygen GD (Berthet et al, 2009).…”

Brain Lactate Metabolism: The Discoveries and the Controversies

“…Blood lactate is oxidized in the brain and more glucose is also consumed during exhaustive exercise, Brain lactate metabolism GA Dienel but there is also a decline in the oxygen/(glucose + 1 2 lactate) utilization ratio from B6 to as low as 1.7, and there is a large, unexplained excess carbohydrate taken up into brain that is not accounted for by oxidative metabolism or tissue metabolite accumulation or release (Dalsgaard, 2006;Quistorff et al, 2008;van Hall et al, 2009).…”

“…e Under 'resting' conditions, there is a slight efflux of lactate from the brain to blood as long as the blood lactate is relatively low (A, D; also see Madsen et al (1998); Linde et al (1999); Schmalbruch et al (2002)), in sharp contrast to the eye that releases large amounts of lactate under resting and activated conditions (C). When blood lactate increases above that in the brain during physical movement (D, rat) with moderate and strenuous exercise (E, human), lactate influx increases markedly and it becomes a significant brain fuel (Dalsgaard, 2006;Quistorff et al, 2008;van Hall et al, 2009). …”

Lactate flux during carotid endarterectomy under general anesthesia: correlation with various point-of-care monitors

“…9,[17][18][19] Our findings are controversial, but new work strongly suggests that lactate may well be the preferred substrate for cerebral metabolism both anerobically and aerobically. [20][21][22][23] Thus, in the face of diminished oxygen supply, as with carotid cross-clamping in patients at risk, influx of lactate may be critically important to serve as a fuel for cerebral metabolism. Our study suggests that such may be the case.…”