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

Abstract

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; P = .006; number of RCTs, k = 6; total sample size, N = 389; I2 = 0%). BCAAs were also found to be beneficial for ascites (RR = 0.55; 95% CI = 0.35 to 0.86; P = .008; k = 4; N = 296; I2 = 0%), body weight (MD = 3.24 kg; 95% CI = 0.44 to 6.04; P = .02; k = 3; N = 196; I2 = 24%), and hospitalization length (MD = −2.07 days; 95% CI = −3.97 to −0.17; P = .03; k = 5; N = 362; I2 = 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.

Soy Protein Alleviates Malnutrition in Weaning Rats by Regulating Gut Microbiota Composition and Serum Metabolites

“…Therefore, the restoration of this metabolism and the content in the colon were critical in malnutrition improvement. At the same time, phenylalanine, isoleucine, and valine were also decreased in LPG which coincided with our previous results ( 31 ). Vitamin B 6 metabolism in the colon showed significant influence among LPG and other groups because the deficiency of tryptophan decreased the tryptophan-nicotinamide conversion rate, while subsequently influenced the vitamin B 6 metabolism ( 32 ).…”

Probiotics Evaluation in Oncological Surgery: A Systematic Review of 36 Randomized Controlled Trials Assessing 21 Diverse Formulations

“…The complete methodology has been described in detail elsewhere [ 23 ]. Briefly, the protocol was registered a priori on PROSPERO (CRD42018086168), and followed guidance of the Cochrane Handbook [ 24 ], CIOMS Working Group X report [ 25 ], and PRISMA reporting criteria [ 26 ].…”

“…This publication is part of a larger endeavor to prepare multiple systematic reviews based on a prioritization exercise [ 27 ], to refine our research agenda and considering 10 natural health products. A detailed report covering the perioperative use of branched-chain amino acids stream was recently published [ 23 ]. Study inclusion criteria: studies evaluating synbiotics (i.e., probiotics with prebiotics) or probiotics in patients undergoing cancer-related surgery, any route of administration, duration, dose, and formulation (i.e., used alone or in combinations), compared to active control, placebo, or no added treatment (e.g., standard care).…”

Amino acids and cancer: potential for therapies?

“…In general, some questions remain unanswered regarding metabolism function and the extent to which amino acid intake may benefit patients with cancer-induced cachexia. Among the nutritional strategies of cancer patients, increased protein intake can be effective in providing amino acids, especially those with a supposed anticatabolic action [3,4 ▪▪ ,14–18].…”