Branched-chain amino acids supplements in the late evening decrease the frequency of muscle cramps with advanced hepatic cirrhosis

Sako, Katsumi; Imamura, Yasushi; Nishimata, Hiroto; Tahara, Kenji; Kubozono, Osamu; Tsubouchi, Hirohito

doi:10.1016/s1386-6346(03)00152-9

Cited by 33 publications

(39 citation statements)

References 5 publications

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“…We also demonstrated that no subjective symptoms were significantly improved by the BCAA and zinc-enriched supplementation. BCAAs and zinc have been previously reported to improve muscle cramps and taste disorders (16,29,30), respectively. However, these symptoms were mild in the study subjects at baseline.…”

Section: Discussionmentioning

confidence: 99%

Effects of branched-chain amino acids and zinc-enriched nutrients on prognosticators in HCV-infected patients: A multicenter randomized controlled trial

Kawaguchi

Nagao

Abe

et al. 2014

Molecular Medicine Reports

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Abstract. Branched-chain amino acids (BCAAs) and trace element deficiencies are associated with poor prognosis in hepatitis C virus (HCV)-infected patients. The aim of this study was to investigate the effects of BCAA and zinc-enriched supplementation on prognostic factors in HCV-infected patients. Fifty-three HCV-infected patients were enrolled in this multicenter randomized controlled trial. The patients were assigned to either the placebo (n=27) or supplement group (n=26; 6,400 mg/day BCAAs and 10 mg/day zinc) and were followed up for 60 days. Primary outcomes were prognostic factors for chronic liver disease, including the serum BCAA-to-tyrosine ratio (BTR), zinc levels and α-fetoprotein (AFP) levels. There were no significant differences in any of the prognostic factors between the placebo and supplement groups at baseline. In the supplement group, the BTR and zinc levels were significantly increased compared with the placebo group (BTR: 5.14±1.59 vs. 4.23±1.14, P= 0.0290; zinc: 76±11 vs. 68±11 µg/dl, P=0.0497). No significant differences were observed in AFP levels between the groups in the whole analysis. However, a stratification analysis showed a significant reduction in ΔAFP levels in the supplement group, with elevated AFP levels compared with the other groups (-2.72±3.45 ng/ml, P= 0.0079). It was demonstrated that BCAA and zinc-enriched supplementation increased the BTR and zinc levels in the HCV-infected patients. Furthermore, the supplementation reduced the serum AFP levels in patients who had elevated serum AFP levels at baseline. Thus, BCAA and zinc-enriched supplementation may prolong the survival of HCV-infected patients by improving amino acid imbalance and zinc deficiency, and by partly downregulating AFP.

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Section: Discussionmentioning

confidence: 99%

Effects of branched-chain amino acids and zinc-enriched nutrients on prognosticators in HCV-infected patients: A multicenter randomized controlled trial

Kawaguchi

Nagao

Abe

et al. 2014

Molecular Medicine Reports

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“…It has been demonstrated that BCAA supplementation ameliorates plasma albumin levels in patients (7). Moreover, it is noteworthy that this treatment dramatically decreased the frequency of muscle cramp in patients (8), suggesting that BCAA supplementation may also improve muscle protein metabolism.…”

Section: Regulation Of Protein Metabolism By Leucinementioning

confidence: 97%

Novel Physiological Functions of Branched-Chain Amino Acids

Shimomura

Kitaura

Kadota

et al. 2015

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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Branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) are nutritionally indispensable (essential) amino acids for humans. We acquire these amino acids mainly as food proteins, in which the BCAAs account for ~20% of the amino acids. The ingested BCAAs are used for protein synthesis in the body. The daily requirement for BCAAs in adults is estimated to be 85 mg/kg body weight (BW) (39, 20, and 26 mg/ kg BW for Leu, Ile, and Val, respectively) using methods such as indicator amino acid oxidation and 24-hour balance studies (1). The primary physiological function of BCAAs is as the building blocks of proteins; however, recent studies have contributed to the mounting evidence for other physiological functions. In this review, we summarize the current findings on the physiological functions of BCAAs, including those from our own studies. Regulation of BCAA CatabolismThe main BCAA catabolic pathway occurs within mitochondria. The first 2 steps of the pathway are common to the 3 BCAAs and are especially important for the regulation of BCAA catabolism (2) (Fig. 1). The first step of the pathway is the reversible transamination of BCAAs catalyzed by branched-chain aminotransferase (BCAT) to produce corresponding branched-chain a-ketoacids (BCKAs). The second step involves the oxidative decarboxylation of BCKAs catalyzed by the BCKA dehydrogenase (BCKDH) complex to produce corresponding CoA esters. Since this reaction is irreversible, it is a rate-limiting step in BCAA catabolism. Furthermore, the BCKDH complex is subject to covalent modification; BCKDH kinase (BDK) is responsible for inactivation of the complex by phosphorylation and BCKDH phosphatase reactivates the complex by dephosphorylation (2). Therefore, the enzyme activity of the BCKDH complex can be quickly changed in response to alterations in physiological conditions. Aberrations of the enzymes involved in the first two steps of BCAA catabolism have a great impact on the circulating concentrations of BCAAs; a defect in the mitochondrial BCAT (BCAT2) gene of mice resulted in a markedly high level of plasma BCAAs (3), and BDK-knockout (KO) mice, in which the BCKDH complex in all tissues was almost fully activated, showed significantly low concentrations of plasma BCAAs (4). Regulation of Protein Metabolism by LeucineThe mammalian target of rapamycin complex 1 (mTORC1) is a serine-threonine protein kinase that controls translation initiation and is responsive to cellular levels of free amino acids (5). mTORC1 phosphorylates and activates the protein kinase p70S6K1, which subsequently phosphorylates eukaryotic initiation factor 4B (eIF4B) and programmed cell death 4 (PDCD4), and phosphorylates eIF4E-binding protein 1 (eIF4E-BP1), thereby permitting eIF4E to associate with eIF4G to form eIF4F. Thus, mTORC1 stimulates the joining of mRNA to the 43S preinitiation complex and has a global effect on protein synthesis. Furthermore, mTORC1 regulates cellular proteolysis by inhibiting the formation of autophagosomes (6). It is also known that leucine strongly...

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“…Table 3 provides a summary of all studies completed that examined BCAA supplementation in older adults (average age >60) with liver cirrhosis. Of the 9 studies completed to date, 7 showed improvements in nitrogen balance, ratio of branched chain to aromatic amino acids, serum albumin, fuel metabolism, quality of life scores, liver function, muscle mass, and survival, as well as decreases in serum ketone bodies and muscle cramps [72][73][74][75][83][84][85] . Two of the studies showed no significant differences between the treatment group and the control group [38,82] ; however, they both included very small sample sizes.…”

Section: Branched Chain Amino Acid Supplementation In Older Adults Wimentioning

confidence: 99%

“…A summary of studies providing late evening or overnight supplementation to older adults (average age >60) with cirrhosis can be found in table 2. Of the 7 studies completed to date, all showed various positive benefits including improvements in nitrogen balance, ratio of branched chain to aromatic amino acids, serum albumin, fuel metabolism, and quality of life scores and decreases in serum ketone bodies and muscle cramps [57,68,[72][73][74][75][76] . The majority of the studies lasted 3 months or less, with one being 12 months.…”

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confidence: 99%

Protein Recommendations for Older Adults with Cirrhosis: A Review

Iiames

Logomarsino

2015

Journal of Gastroenterology and Hepatology Research

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Protein intake has a key role in liver cirrhosis in older adults. However, types and amounts of protein intake in cirrhosis have been controversial. The aim of this paper is to investigate the optimal protein intake for management of cirrhosis and prevention of hepatic encephalopathy in older adults. Protein restriction of 0.6 g/kg/d has traditionally been used as medical nutrition therapy in liver cirrhosis. However, recent evidence has shown that protein restrictions have many negative consequences for older adults with cirrhosis. Current research indicates protein intakes of 1.2-1.5 g/ kg/d in liver cirrhosis; however, many older adults do not consume this amount. Strategies to help increase protein intake and manage cirrhosis include ensuring adequate protein at every meal through either regular intake or supplementation, protein supplementation prior to bedtime or overnight, and supplementation with branchedchain amino acids. An emphasis on vegetable protein versus animal protein is probably not an advantageous treatment option because of lack of conclusive evidence regarding benefits and potential negative side effects. and progression of chronic liver disease and cirrhosis.There are several different factors that naturally occur in older adulthood that help contribute to the development of chronic liver disease and cirrhosis. After reaching maximum size in early adulthood, the liver steadily decreases in both size and the amount of blood flow it receives, leading to decreased function and efficiency over time [10] . Also, increased ammonia production and bacterial overgrowth are common in older adulthood, both of which are thought to play a key role in development of hepatic encephalopathy [11] . Older adults tend to have chronic constipation, intestinal dysmotility, and increased colonic transit time, which predisposes them to increased ammonia production [12] . Finally, older adulthood is associated with a higher incidence of diabetes, which is strongly correlated to progression of liver cirrhosis [13] . Pathogenesis of malnutrition in older adults with cirrhosisIt is estimated that 20% of patients with compensated cirrhosis and 60% of patients with decompensated cirrhosis have malnutrition [14] . In older adults, protein energy malnutrition is associated with high health care costs, increased frequency of infection and bedsores, increased morbidity and mortality, and poor physical functioning [4,5] . In canine trials, poor nutritional status has been shown to encourage the development of hepatic encephalopathy [15] . In addition, malnutrition in cirrhosis is positively associated with old age [14] . Multiple factors help contribute to the development of malnutrition in older adults with cirrhosis, including inadequate intake, altered absorption, sarcopenia, and altered metabolism. All causes must be explored and taken into consideration when developing treatment and prevention strategies.In older adults, food intake naturally decreases over time [16] , which promotes the development of malnutri...

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Branched-chain amino acids supplements in the late evening decrease the frequency of muscle cramps with advanced hepatic cirrhosis

Cited by 33 publications

References 5 publications

Effects of branched-chain amino acids and zinc-enriched nutrients on prognosticators in HCV-infected patients: A multicenter randomized controlled trial

Effects of branched-chain amino acids and zinc-enriched nutrients on prognosticators in HCV-infected patients: A multicenter randomized controlled trial

Novel Physiological Functions of Branched-Chain Amino Acids

Protein Recommendations for Older Adults with Cirrhosis: A Review

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