Randomised clinical trial: effect of adding branched chain amino acids to exercise and standard-of-care on muscle mass in cirrhotic patients with sarcopenia

Abstract

Background The role of branched-chain amino acids (BCAA) in improving muscle mass in cirrhosis is presently debatable. Aims To evaluate the role of BCAA in improving muscle mass in a double-blind randomized placebo-controlled trial in patients with cirrhosis having sarcopenia. Methods Consecutive patients with cirrhosis with Child–Pugh score < 10 and sarcopenia were randomized to receive either 12 g/day of BCAA orally or a placebo (1:1) for 6 months in addition to a home-based exercise program (30 min/day), dietary counselling and standard medical therapy. Sarcopenia was defined according to gender-specific axial skeletal muscle index (SMI) cut-offs. The primary endpoint was a change in muscle mass based on CT scan (SMI) after 6 months of supplementation. Results Sixty patients [mean age 41.6 ± 9.9 years; males (66.6%) of predominantly viral (40%) and alcohol-related (31.7%) cirrhosis] were randomized. Baseline clinical and demographic characters were similar except MELD score (10.2 ± 2.8 vs. 12.2 ± 3.5, p = 0.02) and calorie intake (1838.1 kcal ± 631.5 vs. 2217.5 kcal ± 707.3, p = 0.03), both being higher in the placebo arm. After adjusting for both baseline confounders, baseline SMI and protein intake, the change in SMI at 6 months was similar in both groups [mean adjusted difference (MAD) + 0.84, CI − 2.9; + 1.2, p = 0.42] by intention-to-treat analysis. The secondary outcomes including change in handgrip strength ( p = 0.65), 6-m gait speed ( p = 0.20), 6-min walk distance ( p = 0.39) were similar in both arms. Four patients had minor adverse events in each arm. Conclusion Addition of BCAA to exercise, dietary counselling and standard medical therapy did not improve muscle mass in patients with cirrhosis having sarcopenia. (CTRI/2019/05/019269). Trial registration number CTRI/2019/05/019269 (Clinical Trials Registry of India). Supplementary Information The online version contains supplementary material available at 10.1007/s12072-022-10334-7.

Insights into Pathogenesis, Nutritional and Drug Approach in Sarcopenia: A Systematic Review

“…The search performed in the databases resulted in the selection of studies related to the use of creatine, leucine, branched-chain amino acids, omega 3, and vitamin D. These studies showed that the supplementation with these substances can show benefits in the therapeutic approach of sarcopenic patients. Clinical trials were found only for the use of leucine [20,21], BCAA [22][23][24], omega-3 [25,26], and calcium [27][28][29][30]. These trials are summarized in Table 1.…”

“…Much discussion has been raised about the effects of the branched-chain amino acids (BCAA: include valine, leucine, and isoleucine) supplementation as a therapy for sarcopenia, as it encompasses some pathophysiological mechanisms that contribute to the maintenance of lean mass in various pathologies, such as liver cirrhosis, for which, even though there is no consensus on which patients can benefit from supplementation or the ideal amount for each patient, its use is supported [22,95]. In a randomized trial, sarcopenic patients with cirrhosis of the liver were chosen to receive 12 g/day of oral BCAA or placebo for six months, plus 30 min/day of exercise, diet, and standard medical therapy.…”

“…In a randomized trial, sarcopenic patients with cirrhosis of the liver were chosen to receive 12 g/day of oral BCAA or placebo for six months, plus 30 min/day of exercise, diet, and standard medical therapy. When analyzing the patients in the placebo group, it was concluded that adding BCAA associated with exercise did not significantly improve the functional measures of sarcopenia in patients with liver cirrhosis [22]. It is important to say that studies on the relationship between BCAA and aging-related syndrome, such as sarcopenia, generally present divergent conclusions about the benefits of BCAA supplementation.…”

Therapeutic Physical Exercise Programs in the Context of NASH Cirrhosis and Liver Transplantation: A Systematic Review

“…Malnutrition is frequent in patients with ESLD; it is observed in >50% of patients with decompensated liver disease and has long been recognized as a determinant prognostic and therapeutic factor [ 92 ]. In patients with cirrhosis and a Child–Pugh score <10 and sarcopenia, supplementation with amino acids for six months did not increase muscle mass relative to PA and dietary advice [ 93 ]. The combination of supplementation with branched-chain amino acids and a home-based exercise program at the anaerobic threshold for 12 months improved aerobic capacity but did not significantly change the body mass index or biochemical markers of liver function [ 94 ].…”

Nutritional Support in Acute Liver Failure

“…From a wider hepatologic perspective, in healthy people in general and in patients with liver cirrhosis specifically, BCAA supplementation promotes anabolic pathways and reduces cachexia, prevents and/or treats hepatic encephalopathy, alleviates fatigue during exercise, promotes wound repair, and stimulates insulin production [ 29 , 30 ]. Going in more detail, hydroxy-beta-methyl butyrate (HMB) is an active metabolite of leucine, with anti-catabolic properties, used in several randomized controlled trials (RCTs) in patients with liver cirrhosis against sarcopenia and fat accumulation in skeletal muscles [ 31 , 32 , 33 ].…”