Branched-chain amino acid enriched supplements as therapy for liver disease

Altered amino acid metabolism is a hallmark of liver disease, characterized by low levels of circulating BCAAs and elevated levels of circulating aromatic amino acids, and methionine. Although overwhelming evidence indicates that the incidence of complications of liver disease increases with malnutrition, the reported impact of nutritional therapy, specifically BCAA supplementation, on outcomes in patients with liver disease has varied with the indication. Multiple small studies report the beneficial effects of BCAA supplementation, including improved metabolic profiles, as measured by protein sparing and/or normalization of respiratory quotients and clinical improvement of hepatic encephalopathy. Other studies have failed to show a clinical benefit of BCAA supplementation. The data concerning the impact of BCAA supplementation in prophylaxis of long-term morbidity and mortality in patients with cirrhosis is more promising and has been the subject of 2, large randomized controlled trials. In a study of 174 patients with advanced cirrhosis, who were randomized to either BCAA or 1 of 2 control arms, the combined event rates were seen to be significantly reduced in the BCAA supplementation arm, although this was not true for individual complications. In a more recent, larger, randomized controlled trial (n = 646) using a more palatable formulation, investigators demonstrated that long-term BCAA supplementation is associated with decreased frequency of hepatic failure and overall complication frequency. Both studies found improved nutritional status associated with BCAA supplementation. On balance, BCAA supplementation appears to be associated with decreased frequency of complications of cirrhosis and improved nutritional status when prescribed as maintenance therapy. Cost and palatability may limit the potential applicability of this treatment modality.