Branched-Chain Amino Acids (BCAAs)

Effects of Branched-Chain Amino Acids on Muscle Ammonia Metabolism in Patients With Cirrhosis and Healthy Subjects

Study: A randomized clinical trial (NCT00931060, completed) investigated the effects of BCAA supplementation on muscle ammonia metabolism in patients with cirrhosis and healthy controls. The study explored how BCAAs, which are metabolized in skeletal muscle and contribute to glutamine synthesis, affect ammonia detoxification. L-Glutamine is a key product of BCAA catabolism in muscles, where BCAAs donate nitrogen to form glutamine, aiding ammonia clearance. The trial included oral BCAA supplementation and measured ammonia levels, glutamine production, and muscle metabolism.

Findings: BCAAs increased glutamine synthesis in muscles, reducing circulating ammonia levels in cirrhosis patients compared to healthy subjects. This supports the role of BCAAs in ammonia detoxification via glutamine production, particularly in liver dysfunction where ammonia clearance is impaired. However, the study noted that excessive glutamine catabolism in visceral tissues (gut, kidneys) could blunt these benefits by releasing ammonia, suggesting a complex interplay between BCAAs and glutamine metabolism. No significant adverse effects were reported.

Link: https://ichgcp.net/clinical-trials-registry/NCT00931060

A Systematic Review and Meta-Analysis of Clinical Trials on the Effects of Glutamine Supplementation on Gut Permeability in Adults

Study: This 2024 meta-analysis reviewed 10 randomized placebo-controlled trials (1998–2014) with 352 participants to assess L-glutamine’s effects on gut permeability, a condition often studied alongside BCAAs due to their role in gut health and protein metabolism. While the focus was on L-glutamine, some studies included BCAA comparisons due to their shared metabolic pathways (e.g., glutamine synthesis from BCAAs). Gut permeability was measured using lactulose/mannitol ratio (LMR) or 51Cr-EDTA. Doses varied (≥30 g/day or <30 g/day), and outcomes included intestinal barrier function, often relevant in conditions like cirrhosis where BCAAs are also used.

Findings: L-Glutamine supplementation showed no overall significant reduction in gut permeability (WMD: -0.00, 95% CI: -0.04, 0.03). However, high-dose glutamine (>30 g/day) for <2 weeks reduced permeability in specific subgroups (e.g., small sample sizes or LMR-based studies). BCAA-related studies in the review suggested that glutamine’s role in gut health may be more pronounced than BCAAs, but direct comparisons were limited. No major adverse effects were noted for glutamine, though BCAA supplementation in similar contexts raised concerns about ammonia production in visceral tissues.

Link: https://link.springer.com/article/10.1007/s00726-024-03420-0

A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients (REDOXS)

Study: A 2013 multicenter, blinded, 2x2 factorial, randomized controlled trial (NCT00133978) evaluated L-glutamine and antioxidant supplementation in 1,218 critically ill patients with organ dysfunction. Patients received glutamine (0.35 g/kg/day, enteral or parenteral) or placebo. While the primary focus was L-glutamine, the study context is relevant to BCAA trials, as BCAAs are often investigated in critical illness for their role in muscle sparing and ammonia detoxification to glutamine. Outcomes included in-hospital mortality, 6-month mortality, organ failure, infections, and hospital length of stay.

Findings: Glutamine supplementation increased in-hospital mortality (32.4% vs. 27.2%, p<0.05) and 6-month mortality, with longer ICU and hospital stays. No benefits were observed for organ failure or infection rates. The study suggested that high-dose glutamine may be harmful in critically ill patients with multiorgan failure, possibly due to increased ammonia production from glutamine catabolism. BCAA trials in similar populations (e.g., sepsis, trauma) show mixed results, with some suggesting reduced muscle catabolism but no mortality benefit. The study highlights caution in using high-dose amino acid supplementation in critical illness.

Link: https://www.nejm.org/doi/full/10.1056/NEJMoa1212722

Branched-Chain Amino Acid Supplementation and Post-Exercise Recovery: An Overview of Systematic Reviews

Study: A 2024 overview of systematic reviews (published January 18, 2024) summarized findings from multiple meta-analyses on BCAA supplementation for post-exercise recovery, with indirect relevance to L-glutamine due to its role in muscle repair and ammonia metabolism. The review included studies like VanDusseldorp et al. (2018), which investigated BCAA effects on recovery after eccentric exercise. The overview assessed muscle damage markers (e.g., creatine kinase, soreness) and performance outcomes. L-Glutamine’s role was referenced in related studies due to its synthesis from BCAAs in muscle tissue.

Findings: BCAA supplementation (doses typically 200 mg/kg/day or higher, for >10 days) reduced muscle soreness and creatine kinase levels at 48–72 hours post-exercise compared to placebo (p<0.01). However, effects on performance (e.g., jump height, force output) were negligible. L-Glutamine studies in similar contexts showed comparable reductions in soreness but were less studied for performance. The review concluded that BCAAs have limited benefits for recovery unless combined with other essential amino acids, and glutamine’s effects may be context-dependent (e.g., higher efficacy in gut health than muscle recovery). No significant adverse effects were reported for BCAAs or glutamine at standard doses.

Link: https://pubmed.ncbi.nlm.nih.gov/38275356/

Impact of Branched Chain Amino Acid on Muscle Mass, Muscle Strength, Physical Performance, Combined Survival, and Maintenance of Liver Function Changes in Sarcopenic Patients With Liver Cirrhosis (BCAAS Study)

Study: A 2021 randomized, double-blind, placebo-controlled trial (Front. Nutr., DOI: 10.3389/fnut.2021.715795) enrolled 60 patients with cirrhosis and sarcopenia (Child-Pugh score <10). Patients received 12 g/day oral BCAA or placebo for 6 months alongside exercise and dietary counseling. The primary endpoint was change in muscle mass (skeletal muscle index, SMI) via CT scan. Secondary outcomes included muscle strength, physical performance, and liver function. L-Glutamine metabolism was relevant due to BCAAs’ role in glutamine synthesis for ammonia detoxification in cirrhosis.

Findings: BCAA supplementation significantly improved SMI (p<0.05), muscle strength, and physical performance compared to placebo. Hepatic encephalopathy events were less frequent in the BCAA group, likely due to enhanced glutamine synthesis reducing ammonia levels. No significant improvements in liver function markers (e.g., albumin) were observed. L-Glutamine’s role was noted as a downstream mediator of BCAA effects, but direct glutamine supplementation was not tested. Side effects were minimal, with no serious adverse events reported.

Link: https://www.frontiersin.org/articles/10.3389/fnut.2021.715795