Lactate fuels the human brain during exercise

Abstract

The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up lactate in proportion to the arterial concentration. Cerebral lactate uptake, together with glucose uptake, is larger than the uptake accounted for by the concomitant O(2) uptake, as reflected by the decrease in cerebral metabolic ratio (CMR) [the cerebral molar uptake ratio O(2)/(glucose+(1/2) lactate)] from a resting value of 6 to <2. The CMR also decreases when plasma lactate is not increased, as during prolonged exercise, cerebral activation associated with mental activity, or exposure to a stressful situation. The CMR decrease is prevented with combined beta(1)- and beta(2)-adrenergic receptor blockade but not with beta(1)-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a beta(2)-adrenergic receptor mechanism enhances glucose and perhaps lactate transport across the blood-brain barrier. The pattern of CMR decrease under various forms of brain activation suggests that lactate may partially replace glucose as a substrate for oxidation. Thus, the notion of the human brain as an obligatory glucose consumer is not without exceptions.

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).…”

“…The quantity of lactate that accumulates in the brain during an activation episode is < 5% of the pyruvate formed from glucose (Dienel et al, 2007a). The lactate level in a normal resting brain is linearly related to that of pyruvate (Dienel and Cruz, 2008), and its increase (Quistorff et al, 2008). Large increases in brain lactate level are abnormal (Siesjö , 1978), and metabolic assays using high, flooding doses of lactate (greater than B3 mmol/L) mimic brain pathology or physically active subjects.…”

“…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). …”

“…Acidification, ATP, and citrate can inhibit phosphofructokinase in a very complex, concentration-dependent manner that is influenced by other modulators of this enzyme and can reduce CMR glc . Notably, some studies have shown that glucose uptake and utilization does increase (Table 9) during strenuous exercise in rats (Vissing et al, 1996) and in humans who also have increased lactate uptake and oxidation (Quistorff et al, 2008). High lactate levels that arise during strenuous exercise or hypoxic episodes may be 'biologically intended' to be glucose-sparing, similar to ketone bodies during starvation.…”

Brain Nonoxidative Carbohydrate Consumption is Not Explained by Export of an Unknown Carbon Source: Evaluation of the Arterial and Jugular Venous Metabolome

“…During maximal exercise, the brain may take up B3.5 times more carbohydrate than can be accounted for by its oxygen uptake. Thus, during maximal exercise, this unaccounted-for uptake can reach B1 mmol/100 g of carbohydrate for the whole brain (10 to 15 mmol) or up to 40 to 50% of the total carbohydrate uptake (Quistorff et al, 2008). As brain activation takes place repeatedly during the day, we considered that cerebral nonoxidative carbohydrate consumption could be reversed in the recovery from cerebral activation, including exercise.…”