Are Supplemental Branched-Chain Amino Acids Beneficial During the Oncological Peri-Operative Period: A Systematic Review and Meta-Analysis.

BACKGROUND

Branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are essential amino acids involved in immune responses, and may have roles in protein malnutrition and sarcopenia. Furthermore, certain liver diseases have been associated with a decreased Fischer's ratio (BCAAs to aromatic amino acids; phenylalanine, tyrosine, and tryptophan). We aimed to evaluate the safety and efficacy of BCAAs use in patients with cancer undergoing surgery.

METHODS

MEDLINE, Embase, and CENTRAL were searched (inception to July 24, 2020) for randomized controlled trials (RCTs) and comparative observational studies in English evaluating BCAAs (alone or in combinations) during the oncological peri-operative period. Study selection, data extraction, and quality appraisal were done in duplicate. RCT risk-of-bias was appraised using Cochrane Risk-of-Bias tool, and observational studies' quality assessment was conducted with Newcastle-Ottawa Scale. Meta-analyses were conducted when appropriate.

RESULTS

20 articles were included comprising 13 RCTs and 6 observational cohort studies in 7 reports and 2019 total participants overall. Among 13 RCTs, 77% involved liver cancer. Methodological study quality scored substantial risk-of-bias across most RCTs. Meta-analysis of RCTs found a 38% decreased risk of post-operative infections in BCAAs group compared to controls (RR = 0.62; 95% CI = 0.44 to 0.87;  = .006; number of RCTs,  = 6; total sample size, N = 389;  = 0%). BCAAs were also found to be beneficial for ascites (RR = 0.55; 95% CI = 0.35 to 0.86;  = .008;  = 4; N = 296;  = 0%), body weight (MD = 3.24 kg; 95% CI = 0.44 to 6.04;  = .02;  = 3; N = 196;  = 24%), and hospitalization length (MD = -2.07 days; 95% CI = -3.97 to -0.17;  = .03;  = 5; N = 362;  = 59%). No differences were found between BCAAs and controls for mortality, recurrence, other post-operative complications (liver failure, edema, pleural effusion), blood loss, quality of life, ammonia level, and prothrombin time. No serious adverse events were related to BCAAs; however, serious adverse events were reported due to intravenous catheters. No safety concerns from observational studies were identified.

CONCLUSIONS

Branched-chain amino acids during the oncological surgical period demonstrated promise in reducing important post-operative morbidity from infections and ascites compared to controls. Blinded, placebo-controlled confirmatory trials of higher methodological quality are warranted, especially using oral, short-term BCAAs-enriched supplements within the context of recent ERAS programs.

PROSPERO REGISTRATION

CRD42018086168.