Evaluation of the effects of combination therapy with branched‐chain amino acid and zinc supplements on nitrogen metabolism in liver cirrhosis

Hayashi, Miho; Ikezawa, Kenji; Ono, Akiko; Okabayashi, Sachiyo; Hayashi, Yoshito; Shimizu, Satoshi; Mizuno, Tokuo; Murakami, Kosaku; Akasaka, Tomofumi; Naito, Masafumi; Michida, Tomoki; Ueshima, Dan; Nada, Takayuki; Kawaguchi, Keizaburo; Nakamura, T; Katayama, Kazuhiro

doi:10.1111/j.1872-034x.2007.00095.x

Cited by 42 publications

(32 citation statements)

References 18 publications

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“…The number of patients who received oral zinc supplementation ranged from 20 to 90. A total of 233 patients from three countries, Belgium [10], Italy [11], and Japan [1,16], were included. All studies involved patients with cirrhosis and different stages of encephalopathy.…”

Section: Resultsmentioning

confidence: 99%

“…All studies involved patients with cirrhosis and different stages of encephalopathy. The doses used were zinc sulfate 600 mg/d [16], zinc acetate 600 mg/d [10,11], or polaprezinc 225 mg/d [1] (containing 51 mg of zinc and 174 mg of l -carnosine). All studies were randomized, double-blind, placebo-controlled trials (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Hayashi et al [16] reported improved nitrogen metabolism in patients with liver cirrhosis after administration of branched-chain amino acids and zinc. Forty patients with liver cirrhosis, low serum albumin, and low zinc levels were randomized to receive either branched-chain amino acids alone or a combination of branched-chain amino acids and zinc supplements.…”

Section: Resultsmentioning

confidence: 99%

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A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy

Chavez-Tapia

Cesar-Arce

Barrientos‐Gutiérrez

et al. 2013

Nutr J

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Background and aimBecause low serum zinc levels precipitate hepatic encephalopathy, zinc supplementation is considered a potential therapeutic option. The aim of this study was to assess the effects of oral zinc supplementation in the treatment of hepatic encephalopathy.MethodsFor this systematic review and meta-analysis, data sources included electronic databases (CENTRAL, MEDLINE, EMBASE) and manual searching. Randomized clinical trials of adult patients diagnosed with liver cirrhosis and hepatic encephalopathy were included. The types of interventions considered were any oral zinc supplementation versus no intervention, placebo, or other interventions for the management of hepatic encephalopathy. The data were analyzed by calculating the RR for each trial and expressing the uncertainty as 95% CI. Continuous data were analyzed by calculating the standard mean differences (SMD) between groups within each trial and their 95% CI. Statistical heterogeneity was defined as a P-value > 0.10 (χ2) or I2 > 25%.ResultsFour trials with a total of 233 patients were included. Oral zinc supplementation was associated with a significant improvement in performance on the number connection test (SMD –0.62; 95% CI –1.12 to –0.11) reported in three trials (n = 189), but not with encephalopathy recurrence reduction (RR 0.64; 95% CI 0.26 to 1.59) reported in two trials (n = 169). Other clinically significant outcomes (mortality, liver related morbidity, quality of life) were not reported.ConclusionOral zinc supplementation improved performance on the number connection test, but no evidence about other clinical or biochemical outcomes was available.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy

Chavez-Tapia

Cesar-Arce

Barrientos‐Gutiérrez

et al. 2013

Nutr J

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“…In cirrhotic rats, oral zinc supplementation increased hepatic OTC activity, leading to a decrease in blood ammonia levels 80 , 81 . In cirrhotic patients, BCAAs in combination with zinc administration significantly decreased blood ammonia levels and improved HE compared to BCAA supplementation alone 82 , 83 …”

Section: Additive Effects Of Zinc and Amino Acids To Oral Bcaa Supplementioning

confidence: 99%

Effects of Oral Branched‐Chain Amino Acids on Hepatic Encephalopathy and Outcome in Patients With Liver Cirrhosis

2013

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Branched-chain amino acids (BCAAs) constituting of valine, leucine, and isoleucine act as both substrates of proteins and as key regulators for various nutrient metabolisms. Patients with liver cirrhosis frequently lack sufficient BCAAs and therefore suffer from various metabolic disorders. Hepatic encephalopathy (HE) is a severe metabolic disorder with neurologic manifestations such as flapping tremors and coma in patients with liver cirrhosis. In addition, a mild form of HE known as minimal HE (MHE) is an important social issue because it occurs in up to 80% of patients with chronic liver disease and affects prognosis and activities of daily living, possibly resulting in falls and motor vehicle accidents. Although HE/MHE can be caused by various pathological conditions, including in an accumulation of mercaptans, short-chain fatty acids, and alterations in the gut flora, hyperammonemia has also been implicated in an important pathogenesis of HE/MHE. Besides urea cycle of liver, ammonia can be detoxified in the skeletal muscles by the amidation process for glutamine synthesis using BCAAs. Thus, BCAA supplementation may enhance detoxification of ammonia in skeletal muscle and may be a possible therapeutic strategy for HE/MHE. In this review, we summarize the clinical impacts of BCAA supplementation on HE/MHE and discuss possible mechanisms for a BCAA-induced improvement of HE/MHE. Furthermore, we present some modifications of oral BCAA therapy for improvement of efficacy in HE treatment. We also briefly describe pleiotropic benefits of BCAAs on life-threatening events and overall prognosis in patients with liver cirrhosis.

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“…Accordingly, 70%-75% of patients with decompensated liver cirrhosis exhibit a more or less pronounced zinc deficiency. In various studies, an improvement of liver function, nutritional status and hepatic encephalopathy, as well as a decrease of ascites and an improvement of immunological parameters have been demonstrated in these patients following controlled zinc substitution [20,96,[98][99][100][101].…”

Section: Substitution Of Zinc Deficiency In Vivomentioning

confidence: 99%

The influence of the trace element zinc on the immune system

Schubert

Guttek

Reinhold

et al. 2015

LaboratoriumsMedizin

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Clinical and experimental examinations showed a close relationship between zinc as an essential trace element and the immune system. Thus, cellular and humoral components from both the innate and the adaptive immune system are affected by zinc. Human zinc deficiencies are frequently connected with disturbed immune functions. Controlled zinc substitution results in a normalization of zinc serum levels, zinc homeostasis, and the immunological parameters. As shown in in vitro experiments, low zinc concentrations stimulate functional parameters of immune cells, but high zinc concentrations are suppressive or cytotoxic for these cells. Recently, the immunosuppressive effect of zinc was demonstrated in animal models of T-cell-dependent autoimmune diseases, like experimental autoimmune encephalomyelitis. Moreover, decreased serum/plasma zinc concentrations have been detected in patients with different autoimmune diseases. Prospective studies should verify the possibility of controlled immunosuppressive zinc therapies for these diseases.

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Evaluation of the effects of combination therapy with branched‐chain amino acid and zinc supplements on nitrogen metabolism in liver cirrhosis

Abstract: More improvement in disorders of nitrogen metabolism in liver cirrhosis occurred after administration of BCAA with zinc than after BCAA alone over 5-6 months of treatment. Further investigation is necessary to determine mechanisms of the action and longer-term clinical efficacy.

Cited by 42 publications

References 18 publications

A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy

A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy

Effects of Oral Branched‐Chain Amino Acids on Hepatic Encephalopathy and Outcome in Patients With Liver Cirrhosis

The influence of the trace element zinc on the immune system

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