Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines

Abstract

Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain NOT THE PUBLISHED VERSION; this is the author's final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page.Amino Acids, Vol. 45, No. 5 (November 2013): pg. 1133-1142. DOI. This article is © Springer and permission has been granted for this version to appear in e-Publications@Marquette. Springer does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from Springer.2 tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in hypothalamus. BCAA reduced hypothalamic tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on hypothalamic tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

Metformin Promotes Anxiolytic and Antidepressant-Like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids

“…Thus, we hypothesized that chronic exposure to an HFD could raise plasma BCAA concentrations sufficiently to limit the uptake of tryptophan into the brain as a result of the competition between amino acids, and thereby reduce neuronal 5-HT synthesis and release from nerve terminals. This is consistent with findings reporting that supplementation in BCAAs reduced brain 5-HT content in rats (Choi et al, 2013) and induced depressive-like symptoms in rodents such as anxiety (Coppola et al, 2013) or anhedonia (Scaini et al, 2014). By attenuating circulating BCAA levels, Met could favor tryptophan availability in the brain and thereby positively reverberate on central 5-HT tone.…”

Effects of supplementation with branched chain amino acids and ornithine aspartate on plasma ammonia and central fatigue during exercise in healthy men

“…The decrease in the fTRP/BCAA ratio would lead to decreased tryptophan transport across the blood-brain barrier because BCAA and tryptophan compete for entry by the same large neutral amino acid transporter [15][16][17]. This should lead to a lower level of 5-hydroxytryptamine responsible for central fatigue [15,23,50]. Thus, the ingestion of BCAA could reduce the exercise-induced increase in brain tryptophan uptake and delay fatigue.…”

“…In this regard, it seems worth mentioning that MCRT reflects not only one pathway of the selected neurotransmitter or the flow rate of neurophysiological and information processes, but also several cognitive modalities (attention, impulse control, processing speed, cognitive flexibility) that are created by the action of stimulus on the subject's sensory system [10,30]. During heavier but still submaximal workloads other involved pathways might dominate, for example BCAA also competitively inhibits tyrosine uptake into the brain, and thus catecholamine synthesis, which reduce physical performance [23].…”

Interactions in the Metabolism of Glutamate and the Branched-Chain Amino Acids and Ketoacids in the CNS

“…In recent years, however, considerable research has focused on the possibility that less onerous increases of branched-chain amino acids and ketoacids might prove beneficial in preventing brain injury, possibly by subtly modulating intra-cerebral levels of glutamate and/or glutamine. To this end, investigators have scrutinized the therapeutic potential of dietary branched-chain amino acid supplementation in diverse pathologic conditions, among them hepatic encephalopathy (Dam et al, 2013; Bak et al, 2013), fatigue (Newsholme and Blomstrand, 2006; Choi et al, 2013; Gluud et al, 2013), traumatic brain injury (Cole et al, 2010); appetite and energy sensing (Schwartz, 2013), obesity (Drgonova, 2013) and epilepsy (Evangeliou et al, 2009). It is probable that future investigation will broaden this repertoire still more.…”