Branched-chain amino acids in liver disease: new aspects of long known phenomena

To provide an overview of findings on the role of branched-chain amino acids (BCAAs) in the pathophysiology, pathobiochemistry, and treatment of liver cirrhosis and its complications that have been published since or were not included in the last review on this topic in 2007 in this journal.

There has been continued interest in the potential of oral BCAA supplements in improving energy metabolism, nitrogen metabolism, carbohydrate metabolism, insulin resistance, severity of liver disease, serum albumin levels, quality of serum albumin, or postoperative complication rates. Unfortunately, many trials suffer from lacking or inadequate controls or small sample size. In a fine example of scientific perseverance, Dutch researchers uncovered the long-known phenomenon of ingested blood being highly comagenic in patients with cirrhosis to be due to the low biologic value of blood protein. The absence of isoleucine and the abundance of leucine in the hemoglobin molecule by way of BCAA antagonism leads to impaired protein synthesis and azotemia paving the way for hepatic encephalopathy.

Recognizing hypoisoleucinemia and BCAA antagonism following gastrointestinal bleeding, and its successful treatment by isoleucine infusion has advanced our understanding of the role of BCAA in liver cirrhosis.