Amino Acids and Indoleamines in the Brain after Infusion of Branched-Chain Amino Acids to Rats with Liver Ischemia

Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by decreased activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), which catalyzes the irreversible catabolism of branched-chain amino acids (BCAAs). Current management of this BCAA dyshomeostasis consists of dietary restriction of BCAAs and liver transplantation, which aims to partially restore functional BCKDC activity in the periphery. These treatments improve the circulating levels of BCAAs and significantly increase survival rates in MSUD patients. However, significant cognitive and psychiatric morbidities remain. Specifically, patients are at a higher lifetime risk for cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorder. Recent literature suggests that the neurological sequelae may be due to the brain-specific roles of BCAAs. This review will focus on the derangements of BCAAs observed in the brain of MSUD patients and will explore the potential mechanisms driving neurologic dysfunction. Finally, we will discuss recent evidence that implicates the relevance of BCAA metabolism in other neurological disorders. An understanding of the role of BCAAs in the central nervous system may facilitate future identification of novel therapeutic approaches in MSUD and a broad range of neurological disorders.

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Regional Analysis of Norepinephrine, Dopamine and Amino Acids in the Brain 18 Hours after Hepatectomy and Infusion of Branched-Chain Amino Acids

Hepatic Encephalopathy in Chronic Liver Failure ◽

10.1007/978-1-4684-4787-3_39 ◽

1984 ◽

pp. 375-380

Author(s):

M. Herlin ◽

J. H. James ◽

C. A. Nachbauer ◽

J. E. Fischer

Keyword(s):

Amino Acids ◽

Regional Analysis ◽

Branched Chain Amino Acids ◽

Branched Chain ◽

The Brain

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Serotonin Receptors in the Brain following Total Hepatectomy in Rats Treated with Branched-Chain Amino Acids

Journal of Parenteral and Enteral Nutrition ◽

10.1177/0148607189013003235 ◽

1989 ◽

Vol 13 (3) ◽

pp. 235-239 ◽

Cited By ~ 4

Author(s):

M. Bugge ◽

F. Bengtsson ◽

H. Hall ◽

I. Wedel ◽

A. Nobin ◽

...

Keyword(s):

Amino Acids ◽

Serotonin Receptors ◽

Branched Chain Amino Acids ◽

Branched Chain ◽

The Brain

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Branched-chain amino acids alter neurobehavioral function in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00373.2012 ◽

2013 ◽

Vol 304 (4) ◽

pp. E405-E413 ◽

Cited By ~ 23

Author(s):

Anna Coppola ◽

Brett R. Wenner ◽

Olga Ilkayeva ◽

Robert D. Stevens ◽

Mauro Maggioni ◽

...

Keyword(s):

Amino Acids ◽

Strong Association ◽

Aromatic Amino Acids ◽

High Energy ◽

Branched Chain Amino Acids ◽

Synaptic Function ◽

Behavioral Changes ◽

Neurobehavioral Function ◽

Branched Chain ◽

The Brain

Recently, we have described a strong association of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) with obesity and insulin resistance. In the current study, we have investigated the potential impact of BCAA on behavioral functions. We demonstrate that supplementation of either a high-sucrose or a high-fat diet with BCAA induces anxiety-like behavior in rats compared with control groups fed on unsupplemented diets. These behavioral changes are associated with a significant decrease in the concentration of tryptophan (Trp) in brain tissues and a consequent decrease in serotonin but no difference in indices of serotonin synaptic function. The anxiety-like behaviors and decreased levels of Trp in the brain of BCAA-fed rats were reversed by supplementation of Trp in the drinking water but not by administration of fluoxetine, a selective serotonin reuptake inhibitor, suggesting that the behavioral changes are independent of the serotonergic pathway of Trp metabolism. Instead, BCAA supplementation lowers the brain levels of another Trp-derived metabolite, kynurenic acid, and these levels are normalized by Trp supplementation. We conclude that supplementation of high-energy diets with BCAA causes neurobehavioral impairment. Since BCAA are elevated spontaneously in human obesity, our studies suggest a potential mechanism for explaining the strong association of obesity and mood disorders.

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Hepatic Encephalopathy: A Review

EMJ Hepatology ◽

10.33590/emjhepatol/21-00030 ◽

2021 ◽

pp. 89-97

Author(s):

Savan Kabaria ◽

Ishita Dalal ◽

Kapil Gupta ◽

Abhishek Bhurwal ◽

Minacapelli Carlos D. ◽

...

Keyword(s):

Amino Acids ◽

Liver Disease ◽

Hepatic Encephalopathy ◽

Hospital Costs ◽

Branched Chain Amino Acids ◽

Review Article ◽

Branched Chain ◽

New Research ◽

The Brain ◽

Recurrence Frequency

Hepatic encephalopathy (HE) is a reversible syndrome observed in patients with liver disease. The syndrome is characterised by a spectrum of neuropsychiatric abnormalities resulting from the accumulation of neurotoxic substances in the bloodstream and ultimately in the brain. HE is a huge burden to patients, caregivers, and the healthcare system. Common treatments for HE, including rifaximin and lactulose, have been shown to reduce the risk of recurrence, frequency of hospitalisations, hospital costs, and mortality. New research and therapeutics exist, including faecal transplants and small-molecule therapies such as branched-chain amino acids. This review article provides a general overview of the current understanding of HE.

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Only L-valine among branched-chain amino acids is effective in promoting the growth of the small intestinal mucosa

Gastroenterology ◽

10.1016/s0016-5085(01)83364-3 ◽

2001 ◽

Vol 120 (5) ◽

pp. A676-A676

Author(s):

T TAKAHASHI ◽

H DOI ◽

H KOMATSU ◽

K SATO ◽

O UEDA ◽

...

Keyword(s):

Amino Acids ◽

Intestinal Mucosa ◽

Branched Chain Amino Acids ◽

Small Intestinal Mucosa ◽

Small Intestinal ◽

Branched Chain

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The Weight Loss Effects of Branched Chain Amino Acids and Vitamin B6: A Randomized Controlled Trial on Obese and Overweight Women

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000511 ◽

2018 ◽

Vol 88 (1-2) ◽

pp. 80-89 ◽

Cited By ~ 3

Author(s):

Zahra Shakibay Novin ◽

Saeed Ghavamzadeh ◽

Alireza Mehdizadeh

Keyword(s):

Amino Acids ◽

Weight Loss ◽

Body Composition ◽

Vitamin B6 ◽

Controlled Trial ◽

Density Lipoprotein ◽

Branched Chain Amino Acids ◽

Model Assessment ◽

Waist To Hip Ratio ◽

Branched Chain

Abstract. Branched chain amino acids (BCAA), with vitamin B6 have been reported to improve fat metabolism and muscle synthesis. We hypothesized that supplementation with BCAA and vitamin B6 would result in more weight loss and improve body composition and blood markers related to cardiovascular diseases. Our aim was to determine whether the mentioned supplementation would affect weight loss, body composition, and cardiovascular risk factors during weight loss intervention. To this end, we performed a placebo-controlled randomized clinical trial in 42 overweight and obese women (BMI = 25–34.9 kg/m2). Taking a four-week moderate deficit calorie diet (–500 kcal/day), participants were randomized to receive BCAA (6 g/day) with vitamin B6 (40 mg/day) or placebo. Body composition variables measured with the use of bioelectrical impedance analysis, homeostatic model assessment, and plasma insulin, Low density lipoprotein, High density lipoprotein, Total Cholesterol, Triglyceride, and fasting blood sugar were measured. The result indicated that, weight loss was not significantly affected by BCAA and vitamin B6 supplementation (–2.43 ± 1.02 kg) or placebo (–1.64 ± 1.48 kg). However, significant time × treatment interactions in waist to hip ratio (P = 0.005), left leg lean (P = 0.004) and right leg lean (P = 0.023) were observed. Overall, supplementation with BCAA and vitamin B6 could preserve legs lean and also attenuated waist to hip ratio.

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