Specialized formulas that are widely used for hepatic failure and hepatic encephalopathy are based on a high content of BCAAs to improve protein malnutrition and restore the amino acid and neuro-transmitter balance. Although BCAA-enriched formulas have been proven to improve neurological status in comatose liver patients it is not certain that this is achieved by the addition of BCAAs specifically, because of a lack of adequate control groups.

Since BCAAs compete with tryptophan for uptake by the brain, they have (in line with the ascribed benefits in hepatic encephalopathy) been applied as competitive antagonists for tryptophan transport, reducing tryptophan-induced cognitive impairment (see also section on tryptophan).

Isoleucine, which is absent in the hemoglobin molecule, can be supplemented to patients with upper gastrointestinal bleeding to restore the balance of amino acids that are taken up by the splanchnic organs. This has been demonstrated to improve mainly protein synthesis in liver and muscle in small observational studies. Prospective randomized clinical trials are, however, still lacking.

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