Effects of Branched-Chain Amino Acids on Parameters Evaluating Sarcopenia in Liver Cirrhosis: Systematic Review and Meta-Analysis

Abstract

IntroductionSarcopenia is a major element of malnutrition in liver cirrhosis (LC) and is present in 30–70% of this population, being associated with a poor overall prognosis due to related complications such as hepatic encephalopathy, ascites, and portal hypertension. This systematic review and meta-analysis aimed to evaluate the effects of branched-chain amino acids (BCAA) supplementation on several parameters used to assess sarcopenia in LC.Materials and MethodsA comprehensive systematic electronic search was performed in PubMed, EMBASE, Scopus, Cochrane Library, and ClinicalTrials.gov databases using predefined keywords. We included full articles that satisfied the inclusion and exclusion criteria. Quality assessment of included studies was conducted using Cochrane Collaboration's tool and NHLBI quality assessment tools for interventional and observational studies, respectively. The principal summary outcome was the mean difference (MD) in the evaluated parameters. We performed a pre- and post-intervention analysis and comparison between two intervention groups (BCAA vs. controls) of the evaluated parameters when applicable.ResultsA total of 12 studies involving 1,225 subjects were included in our qualitative synthesis and five in our quantitative synthesis. At baseline vs. post-intervention assessment, subjects receiving BCAA supplementation were found to have a significant improvement in skeletal muscle index (SMI) (−0.347 [95% CI −0.628–0.067; p-value 0.015]) and mid-arm muscle circumference (MAMC) (−1.273 [95% CI (−2.251–0.294; p-value 0.011]). However, no improvements were reported in handgrip (-0.616 [95% CI −2.818–1.586; p-value 0.584]) and triceps subcutaneous fat (1.10 [95% CI −0.814–3.014; p-value 0.263]).ConclusionFollowing BCAA supplementation, several parameters used to evaluate sarcopenia in LC patients were found to be improved, including SMI and MAMC. Nevertheless, no improvements were seen in handgrip and triceps subcutaneous fat. Results should be interpreted with caution due to the limited methodological quality of the included studies.

Nutritional Support in Acute Liver Failure

“…Almost 40% of the amino acids needed by mammals are BCAAs. Moreover, these BCAAs altogether or leucine alone can sustain protein synthesis and can inhibit protein breakdown [ 28 ].…”

Association of lithocholic acid with skeletal muscle hypertrophy through TGR5-IGF-1 and skeletal muscle mass in chronic liver disease rats and humans

“…BCAA supplementation is approved for use in CLD patients within the clinical setting as a means to provide compensatory albumin thus maintaining liver function (European Association for the Study of the Liver. Electronic address and European Association for the Study of the, 2019), as well as increased muscle mass associated with an acceleration of the TCA cycle (Ismaiel et al, 2022). In our previous study, we reported that hepatocellular damage was attenuated using BCAA supplementation as a result of improved lipid metabolism and mitochondrial damage repair in CLD rats (Tamai et al, 2021).…”

“…A variety of factors are altered in hepatic sarcopenia, including decreased serum branched-chain amino acid (BCAA) levels (Tajiri and Shimizu, 2018), increased bile acids (BAs) (Kobayashi et al, 2017), abnormal insulin growth factor-1 (IGF-1) and mammalian target of rapamycin (mTOR) signaling pathways (Allen et al, 2021), increased reactive oxygen species and increased inflammatory cytokines and myostatin expression (Ebadi et al, 2019, Allen et al, 2021). BCAA supplementation has been shown to significantly improve skeletal muscle index measurements (Ismaiel et al, 2022). In contrast, anti-myostatin monoclonal neutralizing antibodies developed by several companies failed in clinical trials targeted to treat Duchenne muscular dystrophy (Wagner, 2020).…”

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases

“…such as sleep disturbance (change in Epworth Sleepiness Scale: BCAA group, -5.5 vs. control group, 1.2; P <0.05) [ 145 ]. and nutritional status or sarcopenia [ 139 , 146 , 147 ]. As for the method of BCAA administration, both taking BCAAs as drugs and eating BCAA-rich foods during late-night meals were effective [ 139 , 148 , 149 ].…”

“…145 and nutritional status or sarcopenia. 139,146,147 As for the method of BCAA administration, both taking BCAAs as drugs and eating BCAA-rich foods during late-night meals were effective. 139,148,149 On the other hand, BCAA administration did not lead to improvements in measures of liver function itself, such as Model for End-stage Liver Disease (MELD) or Child-Turcotte-Pugh (CTP) scores, in many studies.…”