Branched-chain amino acid supplementation in treatment of liver cirrhosis: Updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation
Language English Country United States Media print-electronic
Document type Journal Article, Review
PubMed
28760433
DOI
10.1016/j.nut.2017.04.003
PII: S0899-9007(17)30079-5
Knihovny.cz E-resources
- Keywords
- Glutamine, Hepatic encephalopathy, Nutrition, Phenylbutyrate, α-ketoglutarate,
- MeSH
- Ammonia metabolism MeSH
- Liver Cirrhosis drug therapy metabolism MeSH
- Ketoglutaric Acids metabolism MeSH
- Humans MeSH
- Dietary Supplements * MeSH
- Amino Acids, Branched-Chain adverse effects metabolism therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Ammonia MeSH
- Ketoglutaric Acids MeSH
- Amino Acids, Branched-Chain MeSH
Branched-chain amino acid (BCAA; valine, leucine, and isoleucine) supplementation is common for patients with liver cirrhosis due to decreased levels of BCAA in the blood plasma of these patients, which plays a role in pathogenesis of hepatic encephalopathy and cachexia. The unique pharmacologic properties of BCAA also are a factor for use as supplementation in this population. In the present article, BCAA is shown to provide nitrogen to alpha-ketoglutarate (α-KG) for synthesis of glutamate, which is a substrate for ammonia detoxification to glutamine (GLN) in the brain and muscles. The article also demonstrates that the favorable effects of BCAA supplementation might be associated with three adverse effects: draining of α-KG from tricarboxylic acid cycle (cataplerosis), increased GLN content and altered glutamatergic neurotransmission in the brain, and activated GLN catabolism to ammonia in the gut and kidneys. Cataplerosis of α-KG can be attenuated by dimethyl-α-ketoglutarate, l-ornithine-l-aspartate, and ornithine salt of α-KG. The pros and cons of GLN elimination from the body using phenylbutyrate (phenylacetate), which may impair liver regeneration and decrease BCAA levels, should be examined. The therapeutic potential of BCAA might be enhanced also by optimizing its supplementation protocol. It is concluded that the search for strategies attenuating adverse and increasing positive effects of the BCAA is needed to include the BCAA among standard medications for patients with cirrhosis of the liver.
References provided by Crossref.org
Side effects of amino acid supplements
Effects of branched-chain amino acids on muscles under hyperammonemic conditions
