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Branched-chain amino acid supplementation in treatment of liver cirrhosis: Updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation

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 pro... Full description

Journal Title: Nutrition (Burbank Los Angeles County, Calif.), 2017-09, Vol.41, p.80-85
Main Author: Holecek, Milan
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: United States: Elsevier Inc
ID: ISSN: 0899-9007
Link: https://www.ncbi.nlm.nih.gov/pubmed/28760433
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title: Branched-chain amino acid supplementation in treatment of liver cirrhosis: Updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation
format: Article
creator:
  • Holecek, Milan
subjects:
  • Acids
  • Amino acids
  • Amino Acids, Branched-Chain - adverse effects
  • Amino Acids, Branched-Chain - metabolism
  • Amino Acids, Branched-Chain - therapeutic use
  • Ammonia
  • Ammonia - metabolism
  • Attenuation
  • Blood plasma
  • Brain
  • Branched chain amino acids
  • Cachexia
  • Care and treatment
  • Catabolism
  • Chain branching
  • Chains
  • Cirrhosis
  • Clinical trials
  • Detoxification
  • Dietary Supplements
  • Drainage
  • Encephalopathy
  • Exercise
  • Glutamatergic transmission
  • Glutamine
  • Hepatic encephalopathy
  • Hepatology
  • Humans
  • Isoleucine
  • Ketoglutaric acid
  • Ketoglutaric Acids - metabolism
  • Kidneys
  • Leucine
  • Liver
  • Liver cirrhosis
  • Liver Cirrhosis - drug therapy
  • Liver Cirrhosis - metabolism
  • Liver diseases
  • Maximum oxygen consumption
  • Metabolism
  • Muscles
  • Musculoskeletal system
  • Neurotransmission
  • Nitrogen
  • Nutrition
  • Ornithine
  • Pathogenesis
  • Patients
  • Pharmacology
  • Phenylbutyrate
  • Phenylbutyric acid
  • Physiological aspects
  • Proteins
  • Regeneration
  • Rodents
  • Salts
  • Side effects
  • Studies
  • Supplementation
  • Tricarboxylic acid cycle
  • Valine
  • α-ketoglutarate
ispartof: Nutrition (Burbank, Los Angeles County, Calif.), 2017-09, Vol.41, p.80-85
description: 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. •The branched-chain amino acids (BCAAs) enhance ammonia detoxification to glutamine (GLN).•Adverse side effects may be associated with use of BCAAs in the treatment of cirrhosis.•Adverse side effects are cataplerosis, altered neurotransmission, and GLN catabolism to ammonia.•Attenuation of adverse effects is needed to enhance therapeutic potential of the BCAA.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0899-9007
fulltext: fulltext
issn:
  • 0899-9007
  • 1873-1244
url: Link


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titleBranched-chain amino acid supplementation in treatment of liver cirrhosis: Updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation
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descriptionBranched-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. •The branched-chain amino acids (BCAAs) enhance ammonia detoxification to glutamine (GLN).•Adverse side effects may be associated with use of BCAAs in the treatment of cirrhosis.•Adverse side effects are cataplerosis, altered neurotransmission, and GLN catabolism to ammonia.•Attenuation of adverse effects is needed to enhance therapeutic potential of the BCAA.
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languageeng
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subjectAcids ; Amino acids ; Amino Acids, Branched-Chain - adverse effects ; Amino Acids, Branched-Chain - metabolism ; Amino Acids, Branched-Chain - therapeutic use ; Ammonia ; Ammonia - metabolism ; Attenuation ; Blood plasma ; Brain ; Branched chain amino acids ; Cachexia ; Care and treatment ; Catabolism ; Chain branching ; Chains ; Cirrhosis ; Clinical trials ; Detoxification ; Dietary Supplements ; Drainage ; Encephalopathy ; Exercise ; Glutamatergic transmission ; Glutamine ; Hepatic encephalopathy ; Hepatology ; Humans ; Isoleucine ; Ketoglutaric acid ; Ketoglutaric Acids - metabolism ; Kidneys ; Leucine ; Liver ; Liver cirrhosis ; Liver Cirrhosis - drug therapy ; Liver Cirrhosis - metabolism ; Liver diseases ; Maximum oxygen consumption ; Metabolism ; Muscles ; Musculoskeletal system ; Neurotransmission ; Nitrogen ; Nutrition ; Ornithine ; Pathogenesis ; Patients ; Pharmacology ; Phenylbutyrate ; Phenylbutyric acid ; Physiological aspects ; Proteins ; Regeneration ; Rodents ; Salts ; Side effects ; Studies ; Supplementation ; Tricarboxylic acid cycle ; Valine ; α-ketoglutarate
ispartofNutrition (Burbank, Los Angeles County, Calif.), 2017-09, Vol.41, p.80-85
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descriptionBranched-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. •The branched-chain amino acids (BCAAs) enhance ammonia detoxification to glutamine (GLN).•Adverse side effects may be associated with use of BCAAs in the treatment of cirrhosis.•Adverse side effects are cataplerosis, altered neurotransmission, and GLN catabolism to ammonia.•Attenuation of adverse effects is needed to enhance therapeutic potential of the BCAA.
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1Amino acids
2Amino Acids, Branched-Chain - adverse effects
3Amino Acids, Branched-Chain - metabolism
4Amino Acids, Branched-Chain - therapeutic use
5Ammonia
6Ammonia - metabolism
7Attenuation
8Blood plasma
9Brain
10Branched chain amino acids
11Cachexia
12Care and treatment
13Catabolism
14Chain branching
15Chains
16Cirrhosis
17Clinical trials
18Detoxification
19Dietary Supplements
20Drainage
21Encephalopathy
22Exercise
23Glutamatergic transmission
24Glutamine
25Hepatic encephalopathy
26Hepatology
27Humans
28Isoleucine
29Ketoglutaric acid
30Ketoglutaric Acids - metabolism
31Kidneys
32Leucine
33Liver
34Liver cirrhosis
35Liver Cirrhosis - drug therapy
36Liver Cirrhosis - metabolism
37Liver diseases
38Maximum oxygen consumption
39Metabolism
40Muscles
41Musculoskeletal system
42Neurotransmission
43Nitrogen
44Nutrition
45Ornithine
46Pathogenesis
47Patients
48Pharmacology
49Phenylbutyrate
50Phenylbutyric acid
51Physiological aspects
52Proteins
53Regeneration
54Rodents
55Salts
56Side effects
57Studies
58Supplementation
59Tricarboxylic acid cycle
60Valine
61α-ketoglutarate
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titleBranched-chain amino acid supplementation in treatment of liver cirrhosis: Updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation
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1Amino acids
2Amino Acids, Branched-Chain - adverse effects
3Amino Acids, Branched-Chain - metabolism
4Amino Acids, Branched-Chain - therapeutic use
5Ammonia
6Ammonia - metabolism
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9Brain
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11Cachexia
12Care and treatment
13Catabolism
14Chain branching
15Chains
16Cirrhosis
17Clinical trials
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19Dietary Supplements
20Drainage
21Encephalopathy
22Exercise
23Glutamatergic transmission
24Glutamine
25Hepatic encephalopathy
26Hepatology
27Humans
28Isoleucine
29Ketoglutaric acid
30Ketoglutaric Acids - metabolism
31Kidneys
32Leucine
33Liver
34Liver cirrhosis
35Liver Cirrhosis - drug therapy
36Liver Cirrhosis - metabolism
37Liver diseases
38Maximum oxygen consumption
39Metabolism
40Muscles
41Musculoskeletal system
42Neurotransmission
43Nitrogen
44Nutrition
45Ornithine
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47Patients
48Pharmacology
49Phenylbutyrate
50Phenylbutyric acid
51Physiological aspects
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atitleBranched-chain amino acid supplementation in treatment of liver cirrhosis: Updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation
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abstractBranched-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. •The branched-chain amino acids (BCAAs) enhance ammonia detoxification to glutamine (GLN).•Adverse side effects may be associated with use of BCAAs in the treatment of cirrhosis.•Adverse side effects are cataplerosis, altered neurotransmission, and GLN catabolism to ammonia.•Attenuation of adverse effects is needed to enhance therapeutic potential of the BCAA.
copUnited States
pubElsevier Inc
pmid28760433
doi10.1016/j.nut.2017.04.003