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.