Branched-Chain Amino Acid Supplementation in Sports. A Literature Review on Its Role in Mitigating Muscle Soreness and Enhancing Training Efficacy

Delayed onset muscle soreness (DOMS) is a symptom of exercise-induced muscle damage that occurs following exercise. Previous research has indicated that branched-chain amino acid (BCAA) supplementation may attenuate exercise-induced muscle damage that causes delayed onset muscle soreness, however the results are inconsistent. The primary aim of this study was to examine the previous literature assessing the effect of BCAA supplementation on DOMS following an acute bout of exercise in adults. This review was conducted in accordance with PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses), and identified peer-reviewed articles comparing a BCAA supplement to a placebo non-BCAA supplement following an acute bout of exercise. An electronic search of three databases (EbscoHost, Web of Science, and SPORTDiscus) yielded 42 articles after duplicates were removed. All studies included in the current analyis were: 1) peer-reviewed publications; 2) available in English; 3) utilized a random control design that compared a BCAA group to a placebo control group following exercise; 4) and assessed soreness of muscle tissue during recovery. DOMS was assessed in 61 participants following ingestion of a BCAA supplement over the course of these interventions. The cumulative results of 37 effects gathered from 8 studies published between 2007 and 2017 indicated that BCAA supplementation reduced DOMS following exercise training (ES=0.7286, 95% CI: 0.5017 to 0.9555, p<0.001). A large decrease in DOMS occurs following BCAA supplementation after exercise compared to a placebo supplement.

Effect of a 40-weeks multicomponent exercise program and branched chain amino acids supplementation on functional fitness and mental health in frail older persons.

Branched-chain amino acids (BCAA) and nitrate have become increasingly popular mainly for their potential effect on individuals' health and secondary as ergogenic aids. The purpose of this narrative review was to incorporate the current scientific evidence of BCAA and nitrate supplementation on athletic performance and health. The current recommendations of BCAA and nitrate supplementation are discussed, as well as possible health complications associated with its intake. Pubmed, Scopus, and Web of Science were searched for articles on the effects of BCAA and nitrate supplementation in humans. The positive effect of BCAAs supplementation on athletic performance does not appear to be fully established. BCAAs supplementation seems to be recommended for all athletes who exercise vigorously daily, as it enhances their recovery after causing exercise-induced muscle damage. BCAAs supplementation reduces the feeling of delayed muscle pain, which follows because of muscle damage. Limited scientific data suggest a potentially beneficial effect of BCAAs on reducing central fatigue. Several clinical conditions could benefit from BCAAs' consumption. However, there are no reliable markers to evaluate or quantify their requirements. There are no exact consumption protocols and absolute recommendations, mainly because BCAAs are also obtained through the consumption of animal protein. Dietary nitrates lower blood pressure, reduce the cost of exercise oxygen, and, at least sometimes, enhance exercise capacity. Taking supplements for 2-6 days (or up to 15 days) can increase athletic performance during high-intensity exercise. The duration of continuous maximum exercise for which nitrates appear to be ergogenic is between 5-30 min. There is limited evidence that nitrates are beneficial in prolonged exercise performance (40 min), at least when administered short term. Supplementation of approximately 5-9 mmol of nitrate/day for 1-15 days may have beneficial effects on normal exercise responses, although the exact dose-response relationship has not yet been established. Five to 9 mmol of nitrates can be easily consumed in the normal diet and there is currently no evidence to adequately document that taking additional nitrates produces greater benefits. The effectiveness of acute nitrate supplementation is likely to depend on many factors, such as sex, health, hypoxia, diet, and level of fitness/training experience of the subjects. Nitrate needs are most likely met by ingesting approximately 250-500 g of leafy and root vegetables per day; however, dietary supplements might represent a more convenient and accurate way of covering an athlete's nitrate needs.

In previous work, dietary branched-chain amino acid (BCAA) supplementation, precursors to de novo glutamate and γ-aminobutyric acid (GABA) synthesis, restored impaired sleep-wake regulation and orexin neuronal activity following traumatic brain injury (TBI) in mice. TBI was speculated to reduce orexin neuronal activity through decreased regional excitatory (glutamate) and/or increased inhibitory (GABA) input. Therefore, we hypothesized that TBI would decrease synaptic glutamate and/or increase synaptic GABA in nerve terminals contacting orexin neurons, and BCAA supplementation would restore TBI-induced changes in synaptic glutamate and/or GABA. Brain tissue was processed for orexin pre-embed diaminobenzidine labeling and glutamate or GABA postembed immunogold labeling. The density of glutamate and GABA immunogold within presynaptic nerve terminals contacting orexin-positive lateral hypothalamic neurons was quantified using electron microscopy in three groups of mice (n = 8 per group): Sham/noninjured controls, TBI without BCAA supplementation, and TBI with BCAA supplementation (given for 5 days, 48 hr post-TBI). Glutamate and GABA were also quantified within the cortical penumbral region (layer VIb) adjacent to the TBI lesion. In the hypothalamus and cortex, TBI decreased relative glutamate density in presynaptic terminals making axodendritic contacts. However, BCAA supplementation only restored relative glutamate density within presynaptic terminals contacting orexin-positive hypothalamic neurons. BCAA supplementation did not change relative glutamate density in presynaptic terminals making axosomatic contacts, or relative GABA density in presynaptic terminals making axosomatic or axodendritic contacts, within either the hypothalamus or cortex. These results suggest TBI compromises orexin neuron function via decreased glutamate density and highlight BCAA supplementation as a potential therapy to restore glutamate density to orexin neurons.

It has been reported that branched-chain amino acids (BCAA) supplementation can improve nutritional status and reduce liver-related complications in patients with decompensated cirrhosis. BCAA supplementation reportedly reduces the incidence of hepatocellular carcinoma (HCC) in obese cirrhotic patients infected with hepatitis C virus (HCV). We investigated the effects of oral supplementation with BCAA granules on hepatocarcinogenesis in patients with HCV-related cirrhosis using propensity score matching. A total of 60 patients with HCV-related cirrhosis and without history of HCC who were selected by one-to-one matching of propensity scores: 30 patients receiving 12 g/day of BCAA granules for 3 months or more (BCAA group) and 30 being observed without BCAA supplementation (control group). The impact of BCAA supplementation was analyzed on the incidence of HCC. The 3- and 5-year rates of HCC development were 13.7% and 13.7% in the BCAA group and 35.1% and 44.5% in the control group, respectively. The BCAA group had a significantly lower rate of HCC than the control group (P = 0.032). Multivariate analysis for factors that were associated with hepatocarcinogenesis indicated that BCAA supplementation was independently associated with a reduced incidence of HCC (hazard ratio 0.131; 95% confidence interval, 0.032-0.530; P = 0.004) along with sex and serum α-fetoprotein. Obesity (body mass index, ≥25 kg/m(2) ) was not significantly associated with an increased incidence of HCC. Oral supplementation with BCAA granules is associated with a reduced incidence of HCC in patients with HCV-related cirrhosis regardless of the presence of obesity based on the propensity score analysis.

Previous studies have reported the positive effects of branched-chain amino acids (BCAAs) supplementation on lowering plasma markers of muscle damage and subjective soreness after resistance exercise. However, a variety of factors can potentially moderate its efficacy. This meta-analysis aimed to summarize the evidence regarding the effect of BCAAs supplementation on plasma muscle damage markers and soreness after resistance exercise in only trained males, by considering the plasma lactate dehydrogenase (LDH) and creatine kinase (CK). Randomized controlled trials were identified through a computerized literature search for the period 2010–2020. The pooled data were analyzed with the random-effects model and heterogeneity using I2. Cochrane Collaboration tools was used for the assessment of risk of bias. Nine studies met the inclusion criteria. A positive effect was found for CK at <24, 24, and 48 h after exercise and for muscle soreness at <24 h only. However, the positive effect was not evident for plasma LDH at any follow-up time. Different outcomes for post-exercise responses may suggest that BCAAs supplementation can attenuate muscle damage and ameliorate muscle soreness after resistance exercise in trained males.

A considerable number of studies have reported that maternal protein restriction may disturb fetal growth and organ development due to a lower availability of amino acids. Leucine, one of branched-chain amino acid (BCAA) promotes protein synthesis through mechanistic target of rapamycin signaling. Here, we investigated the effects of BCAA supplementation in the dams fed a low-protein diet on serum and hepatic biochemical parameters of protein metabolism of dams and their offspring. Female ICR mice were fed a control (20% casein), a low-protein (10% casein), a low-protein with 2% BCAAs or a low-protein with 2% alanine diet for 2 weeks before mating and then throughout pregnancy and lactation. Alanine was used as an amino nitrogen control for the BCAA. Dams and their male offspring were sacrificed at postnatal day 21. There were no changes in body weight and fat mass in low-protein fed dams; however, BCAA supplementation significantly increased fat mass and serum leptin levels. Low-protein diet consumption reduced maternal protein synthesis based on biochemical analysis of serum albumin and hepatic protein levels and immunoblotting of S6 protein, which were increased by BCAA and alanine supplementation. Offspring from dams fed a low-protein diet exhibited lower body and organ weights. Body weight and hepatic protein levels of the offspring were increased by alanine supplementation. However, the decreased serum biochemical parameters, including glucose, triglyceride, total protein and albumin levels in the low-protein offspring group were not changed in response to BCAA or alanine supplementation. A reduced density of the hepatic vessel system in the offspring from dams fed a low-protein diet was restored in the offspring from dams fed either BCAA and alanine-supplemented diet. These results suggest that supplementation of amino nitrogen per se may be responsible for inducing hepatic protein synthesis in the dams fed a low-protein diet and alleviating the distorted growth and liver development of their offspring.

Sarcopenia is highly prevalent and associated with poor outcomes in cirrhotic patients. We aimed to evaluate the efficacy of exercise, protein supplementation, and branched-chain amino acid (BCAA) supplementation in treating cirrhotic sarcopenia. PubMed, Embase, Scopus and the Cochrane Library were searched for randomized controlled trials of exercise, protein supplementation, and/or BCAA supplementation on improving at least one of the sarcopenia features: muscle mass, muscle strength and physical performance. Differences in post- and pre-intervention changes between intervention and control arms were calculated as a standardized mean difference (SMD), with 95% confidence interval (CI). A network meta-analysis (NMA), component NMA, pairwise meta-analysis (PW-MA) of 23 trials comprising 1525 participants were performed. By NMA, combined exercise with protein and BCAA supplementations had the greatest effect on increasing muscle mass (SMD 2.12; 95%CI: 0.59-3.65). Exercise alone or with BCAA/protein supplementation also significantly increased muscle mass, but protein or BCAA supplementation alone did not increase muscle mass. By PW-MA, exercise significantly improved physical performance versus control (SMD 1.43; 95%CI: 0.63-2.17; p < 0.01; I² = 59%) and exercise plus protein supplementation was superior to protein alone (SMD 0.66; 95%CI: 0.26-1.06; p = 0.001; I² = 0%). In the systematic review of effects of BCAA supplementation on muscle strength, its impact was inconclusive. Exercise is the mainstay of sarcopenia treatment in cirrhosis and is most effective at improving muscle mass when combined with protein and BCAA supplementation. Nutritional supplementation alone does not enhance muscle mass. Further well-designed studies are needed to identify the most effective type of exercise.

The aim of this study was to evaluate the effect of strenuous exercise on the functions of peritoneal macrophages in rats and to test the hypothesis that branched-chain amino acid (BCAA) supplementation will be beneficial to the macrophages of rats from strenuous exercise. Forty male Wistar rats were randomly divided into five groups: (C) Control, E) Exercise, (E1) Exercise with one week to recover, (ES) Exercise + Supplementation and (ES1) Exercise + Supplementation with 1 week to recover. All rats except those of the sedentary control were subjected to four weeks of strenuous exercise. Blood hemoglobin, serum testosterone and BCAA levels were tested. Peritoneal macrophages functions were also determined at the same time. The data showed that hemoglobin, testosterone, BCAA levels, and body weight in group E decreased significantly as compared with that of group C. Meanwhile, phagocytosis capacity (decreased by 17.07%, p = 0.031), reactive oxygen species (ROS) production (decreased by 26%, p = 0.003) and MHC II mRNA (decreased by 22%, p = 0.041) of macrophages decreased in the strenuous exercise group as compared with group C. However, the chemotaxis of macrophages did not change significantly. In addition, BCAA supplementation could slightly increase the serum BCAA levels of rats from strenuous exercise (increased by 6.70%, p > 0.05). Moreover, the body weight, the blood hemoglobin, the serum testosterone and the function of peritoneal macrophages in group ES did not change significantly as compared with group E. These results suggest that long-term intensive exercise impairs the function of macrophages, which is essential for microbicidal capability. This may represent a novel mechanism of immunosuppression induced by strenuous exercise. Moreover, the impaired function of macrophage induced by strenuous exercise could not be ameliorated by BCAA supplementation in the dosing and timing used for this study.

Branched-Chain Amino Acid (BCAA) supplementation has shown benefits in reducing liver cirrhosis complications, improving survival, and potentially lowering hepatocellular carcinoma risk, but evidence on long-term outcomes remains limited. This real-world study evaluates clinical outcomes of liver cirrhosis patients receiving BCAA supplementation. This retrospective cohort study used the TriNetX US Collaborative Network to identify liver cirrhosis patients aged ≥ 18 years, stratified by BCAA supplementation after diagnosis. Propensity score matching (PSM) balanced cohorts by demographics, body mass index, Model for End-Stage Liver Disease (MELD) score components, and baseline history of cirrhosis complications, including hepatic encephalopathy (HE), sarcopenia, spontaneous bacterial peritonitis (SBP), acute kidney injury (AKI), and falls. Composite and individual outcomes within 5 years were assessed using odds ratios (OR) with 95% confidence intervals (CI). Among 2,176 matched patients per group, BCAA supplementation was associated with lower rates of the composite outcome (OR 0.81, 95% CI: 0.71-0.92), HE (OR 0.63, 95% CI: 0.49-0.79), SBP (OR 0.77, 95% CI: 0.60-0.99), falls (OR 0.64, 95% CI: 0.53-0.78), all-cause emergency room visits (OR 0.56, 95% CI: 0.50-0.64), and hospitalizations (OR 0.68, 95% CI: 0.60-0.76). Liver transplantation occurred more frequently in the BCAA group (OR 1.49, 95% CI: 1.08-2.06). Sarcopenia rates were similar (OR 1.00, 95% CI: 0.42-2.41), while AKI was slightly more frequent (OR 1.13, 95% CI: 1.00-1.28). Subgroup analysis showed greater benefit in viral hepatitis-associated (OR 0.69, 95% CI: 0.53-0.90) and alcohol-associated cirrhosis (OR 0.73, 95% CI: 0.60-0.89), compared to MASLD (OR 0.81, 95% CI: 0.60-1.08). BCAA supplementation was associated with significant reductions in several cirrhosis-related complications, with most benefits observed in viral hepatitis-associated and alcohol-associated cirrhosis.

Sarcopenia impairs prognosis of patients with liver cirrhosis

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.

The excessive production of pro-inflammatory mediators, characteristic of obesity, leads to neuroinflammation. Zinc (Zn) and the branched-chain amino acids (BCAA) are supplements known for their immunomodulatory properties. Our goal was to evaluate if Zn or BCAA supplementation can affect long-term recognition memory and neuroinflammatory parameters of obese rats after a high-fat diet (HFD). Three-month-old Wistar rats were divided into six groups: Standard diet (SD) + vehicle; SD + Zn; SD + BCAA; High-fat diet (HFD) + vehicle; HFD + Zn; and HFD + BCAA. Diets were administrated for 19weeks, Zn (1,2mg/kg/day) or BCAA (750mg/kg/day) supplementation was conducted in the last 4weeks. Long-term recognition memory was evaluated by the novel object recognition test. IL-1β immunoreactivity in the cortex and hippocampus, and IL-6 levels in the cortex tissue were assessed. Astrogliosis were evaluated through GFAP + cell count and morphological analysis (Sholl Method). Zn supplementation improved object recognition memory in HFD-fed rats, which was not observed following BCAA supplementation. The levels of IL-6 in the cerebralcortex were higher after HFD, which was not diminished after neither supplementation. Obesity also led to increased IL-1β immunoreactivity in the cerebral cortex and hippocampus, which was reduced by Zn. BCAA supplementation also diminished IL-1β immunoreactivity, but only in the hippocampus. We also showed that astrocyte reactivity caused by HFD is area-dependent, being the cerebral cortex more susceptible to the diet. Even though BCAA and Zn can affect IL-1β immunoreactivity and astrocyte morphology, only Zn improved memory. Future studies are needed to clarify the pathways by which Zn improves cognition in obesity.

Branched-chain amino acids (BCAA) supplementation has been considered an interesting nutritional strategy to improve skeletal muscle protein turnover in several conditions. In this context, there is evidence that resistance exercise (RE)-derived biochemical markers of muscle soreness (creatine kinase (CK), aldolase, myoglobin), soreness, and functional strength may be modulated by BCAA supplementation in order to favor of muscle adaptation. However, few studies have investigated such effects in well-controlled conditions in humans. Therefore, the aim of this short report is to describe the potential therapeutic effects of BCAA supplementation on RE-based muscle damage in humans. The main point is that BCAA supplementation may decrease some biochemical markers related with muscle soreness but this does not necessarily reflect on muscle functionality.

Branched-Chain Amino Acid Supplementation Does Not Preserve Lean Mass or Affect Metabolic Profile in Adults with Overweight or Obesity in a Randomized Controlled Weight Loss Intervention