Metabolomic impacts of branched-chain amino acid supplementation during endurance exercise: a crossover study

2021 ◽  
Author(s):  
Jesse T. Peach ◽  
Dakota Funk ◽  
Lizzi Frothingham ◽  
Hunter Fausset ◽  
Isaac Rowland ◽  
...  
Keyword(s):  
Amino Acid ◽  
Perceived Exertion ◽  
Central Fatigue ◽  
Fold Increase ◽  
Amino Acid Supplementation ◽  
Serotonin Concentration ◽  
Serum Samples ◽  
Branched Chain ◽  
The Impact ◽  
Serum Serotonin

Abstract BackgroundSerotonin syntheses in the brain requires a steady supply of tryptophan. Branched chain amino acids (BCAA) and tryptophan are transported across the blood-brain barrier by the amino acid transporter LAT1. BCAA supplementation is predicted to decrease serotonin biosynthesis through LAT1 competition and reduce central fatigue during exercise. Despite a strong theoretical basis for BCAA to attenuate serotonin production and fatigue during exercise, a number of human clinical trials have failed to demonstrate these benefits. To shed light on this discrepancy, we measured the impact of BCAA supplementation on serotonin and associated metabolites during exercise.MethodsA cohort of endurance runners (n=10) participated in a randomized, placebo-controlled, crossover trial to determine impact of BCAA supplementation during a 60-minute run at 65% of VO2 max. Metabolomic analysis targeted for serotonin and untargeted analysis for biomarkers of BCAA supplementation using LCMS were performed on serum samples collected immediately before and after exercise.ResultsSerum BCAA levels were greater in the supplement group compared to placebo (p<0.05). Serum serotonin was lower immediately after BCAA supplementation and before exercise (p<0.05) but not after exercise. L-ornithine increased during exercise with BCAA treatment compared to placebo. Ratings of perceived exertion were no different in BCAA and placebo groups.ConclusionsBCAA supplementation led to a rapid decrease in serum serotonin concentration relative to placebo, which may be indicative of a central nervous system (CNS) mediated process. After exercise with BCAA supplementation, endurance athletes did not show lower serum serotonin concentration, but did present an almost three-fold increase in L-ornithine which has metabolic connections to cortisol and central fatigue.Trial Registration: ClinicalTrials.gov NCT04969536, retrospectively registered 20 July 2021, https://clinicaltrials.gov/ct2/show/NCT04969536

scholarly journals Branched-chain amino acid metabolism is regulated by ERRα in primary human myotubes and is further impaired by glucose loading in type 2 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Rasmus J. O. Sjögren ◽  
David Rizo-Roca ◽  
Alexander V. Chibalin ◽  
Elin Chorell ◽  
Regula Furrer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Amino Acid ◽  
Glucose Homeostasis ◽  
Gene Set ◽  
Branched Chain Amino Acid ◽  
Human Myotubes ◽  
Branched Chain ◽  
The Impact

Abstract Aims/hypothesis Increased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes pathogenesis. However, most metabolomic studies are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a metabolic challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism is partially unknown. This study aimed to identify differences in circulating and skeletal muscle BCAA levels in response to an OGTT in individuals with normal glucose tolerance (NGT) or type 2 diabetes. Additionally, transcription factors involved in the regulation of the BCAA gene set were identified. Methods Plasma and vastus lateralis muscle biopsies were obtained from individuals with NGT or type 2 diabetes before and after an OGTT. Plasma and quadriceps muscles were harvested from skeletal muscle-specific Ppargc1a knockout and transgenic mice. BCAA-related metabolites and genes were assessed by LC-MS/MS and quantitative RT-PCR, respectively. Small interfering RNA and adenovirus-mediated overexpression techniques were used in primary human skeletal muscle cells to study the role of PPARGC1A and ESRRA in the expression of the BCAA gene set. Radiolabelled leucine was used to analyse the impact of oestrogen-related receptor α (ERRα) knockdown on leucine oxidation. Results Impairments in BCAA catabolism in people with type 2 diabetes under fasting conditions were exacerbated after a glucose load. Branched-chain keto acids were reduced 37–56% after an OGTT in the NGT group, whereas no changes were detected in individuals with type 2 diabetes. These changes were concomitant with a stronger correlation with glucose homeostasis biomarkers and downregulated expression of branched-chain amino acid transaminase 2, branched-chain keto acid dehydrogenase complex subunits and 69% of downstream BCAA-related genes in skeletal muscle. In primary human myotubes overexpressing peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α, encoded by PPARGC1A), 61% of the analysed BCAA genes were upregulated, while 67% were downregulated in the quadriceps of skeletal muscle-specific Ppargc1a knockout mice. ESRRA (encoding ERRα) silencing completely abrogated the PGC-1α-induced upregulation of BCAA-related genes in primary human myotubes. Conclusions/interpretation Metabolic inflexibility in type 2 diabetes impacts BCAA homeostasis and attenuates the decrease in circulating and skeletal muscle BCAA-related metabolites after a glucose challenge. Transcriptional regulation of BCAA genes in primary human myotubes via PGC-1α is ERRα-dependent. Graphical abstract

Effects of branched-chain amino acid supplementation and/or aerobic exercise on mouse sperm quality and testosterone production

Andrologia ◽  
2018 ◽  
Vol 51 (2) ◽  
pp. e13183 ◽  
Author(s):  
Mehrnoosh Bahadorani ◽  
Marziyeh Tavalaee ◽  
Navid Abedpoor ◽  
Kamran Ghaedi ◽  
Mohammad N. Nazem ◽  
...  
Keyword(s):  
Amino Acid ◽  
Aerobic Exercise ◽  
Sperm Quality ◽  
Amino Acid Supplementation ◽  
Mouse Sperm ◽  
Acid Supplementation ◽  
Testosterone Production ◽  
Branched Chain Amino Acid ◽  
Branched Chain

Branched-chain amino acid supplementation augments plasma ammonia responses during exercise in humans

1993 ◽  
Vol 74 (6) ◽  
pp. 2711-2717 ◽  
Author(s):  
D. A. MacLean ◽  
T. E. Graham
Keyword(s):  
Fatty Acids ◽  
Amino Acid ◽  
Free Fatty Acids ◽  
Amino Acid Supplementation ◽  
Placebo Administration ◽  
Branched Chain Amino Acid ◽  
Placebo Trial ◽  
The Mean ◽  
Branched Chain ◽  
Exercise In Humans

This study examined the effects of branched-chain amino acid (BCAA) supplementation on amino acid and ammonia (NH3) responses during prolonged exercise in humans. Seven men cycled for 60 min at 75% of maximal O2 uptake after 45 min of either placebo (dextrose, 77 mg/kg) or BCAA (leucine + isoleucine + valine, 77 mg/kg) supplementation. Plasma samples (antecubital vein) were collected at rest and during exercise and analyzed for plasma NH3 and amino acids, whole blood glucose and lactate, and serum free fatty acids and glycerol. After BCAA administration, plasma BCAA levels increased from 375 +/- 22 to 760 +/- 80 microM (P < 0.05) by the onset of exercise and remained elevated throughout the experiment. Plasma NH3 concentrations increased continually during exercise for both trials and were higher (P < 0.05) after BCAA supplementation than after placebo administration. The mean plasma NH3 increase from rest to 60 min was 79 +/- 10 and 53 +/- 4 microM for BCAA and placebo trials, respectively. Plasma alanine and glutamine concentrations were elevated (P < 0.05) during exercise for both treatments. However, only glutamine concentrations were greater (P < 0.05) for BCAA trial than for placebo trial during exercise. There were no significant differences between treatments for glucose, lactate, free fatty acids, and glycerol or any other plasma amino acid. These data suggest that increased BCAA availability before exercise, when initial muscle glycogen is normal, results in significantly greater plasma NH3 responses during exercise than does placebo administration.

scholarly journals Branched Chain Amino Acid Supplementation Drives Metabolomic Shifts Downstream Of Serotonin In Endurance Runners

2021 ◽  
Vol 53 (8S) ◽  
pp. 283-283
Author(s):  
Jesse T. Peach ◽  
Dakota Funk ◽  
Lizzi Frothingham ◽  
McMilin R. Colleen ◽  
Brian Bothner ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Supplementation ◽  
Acid Supplementation ◽  
Branched Chain Amino Acid ◽  
Endurance Runners ◽  
Branched Chain
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