Creatine Supplementation to Improve Sarcopenia in Chronic Liver Disease: Facts and Perspectives

Abstract

Creatine supplementation has been one of the most studied and useful ergogenic nutritional support for athletes to improve performance, strength, and muscular mass. Over time creatine has shown beneficial effects in several human disease conditions. This review aims to summarise the current evidence for creatine supplementation in advanced chronic liver disease and its complications, primarily in sarcopenic cirrhotic patients, because this condition is known to be associated with poor prognosis and outcomes. Although creatine supplementation in chronic liver disease seems to be barely investigated and not studied in human patients, its potential efficacy on chronic liver disease is indirectly highlighted in animal models of non-alcoholic fatty liver disease, bringing beneficial effects in the fatty liver. Similarly, encephalopathy and fatigue seem to have beneficial effects. Creatine supplementation has demonstrated effects in sarcopenia in the elderly with and without resistance training suggesting a potential role in improving this condition in patients with advanced chronic liver disease. Creatine supplementation could address several critical points of chronic liver disease and its complications. Further studies are needed to support the clinical burden of this hypothesis.

Keywords: ACLD; advanced liver diseases; chronic liver disease; cirrhosis; creatine; fatigue; muscle; nutrition; portal hypertension; sarcopenia; supplementation.

Figure 1

Creatine biosynthesis: GAA is synthesised in the kidney from arginine and glycine in a reaction catalysed by AGAT. Then GAA is released into the blood circulation and transported to the liver, transforming it into creatine with the contribution of GAMT and SAM. Finally, creatine is distributed via the bloodstream mainly to muscles and the brain.

Figure 2

Factors and pathways are influencing sarcopenia in advanced chronic liver disease. Physical inactivity, elevated hepatic gluconeogenesis, impaired insulin/IGF-1 signalling, alcoholic cirrhosis, portal hypertension complications, pro-inflammatory cytokines, hyperammonemia, loop diuretics and hypotestosteronemia are all factors associated with sarcopenia in advanced chronic liver disease. Several signalling pathways, in particular, myostatin activation and ubiquitin–proteasome degradation, influence and alter mitochondrial function; mTOR inhibition, NFkB signalling, apoptosis and elevated eIF2 phosphorylation are involved in sarcopenia in advanced chronic liver disease. BCAA branched-chain amino acids, eIF2 eukaryotic initiation factor 2, IGF-1 insulin-like growth factor 1, NFkB nuclear factor-kB. Modified by [72].