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Effect of zinc on liver cirrhosis with hyperammonemia: a preliminary randomized, placebo-controlled double-blind trial.

Abstract

OBJECTIVE

To our knowledge, no randomized study has shown whether zinc replacement therapy is effective for hyperammonemia in liver cirrhosis; therefore, we performed a double-blind, placebo-controlled trial to examine efficacy and safety of the zinc replacement therapy.

METHODS

Patients with liver cirrhosis and hyperammonemia (at or above the institutional reference value) and hypozincemia (≤65 μg/dL) were enrolled in the outpatient units of the participating institutions and were randomly divided to receive placebo (P group) or zinc acetate preparation at a dose of 3 capsules/d for a total zinc content of 150 mg/d (Z group) by the envelope method. Of the 18 enrolled patients, 6 dropped out; thus, the analyses included 12 patients (5 in the P group and 7 in the Z group). Variations in blood concentrations of zinc and ammonia as well as liver function test results were compared.

RESULTS

Blood zinc levels significantly increased in the Z group (P = 0.0037; Friedman test) but not the P group. Blood ammonia levels significantly decreased in the Z group (P = 0.0114; Friedman test) but not the P group. The percent change in blood ammonia level also revealed significant reduction at the eighth week in the Z group (P = 0.0188: Mann-Whitney test). No serious adverse events attributable to the zinc preparation were noted.

CONCLUSION

Although this study is preliminary and includes a small sample, it is, to our knowledge, the first randomized controlled trial to show that zinc supplementation for 3 mo seems effective and safe for treating hyperammonemia in liver cirrhosis. Studies with a larger sample size are needed to confirm our findings.

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  • Authors+Show Affiliations

    ,

    Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka, Japan. Electronic address: katayama-ka@mc.pref.osaka.jp.

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    Division of Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, Nishinomiya, Japan.

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    Division of Gastroenterology, Department of Medicine and Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan.

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    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.

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    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.

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    Division of Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, Nishinomiya, Japan.

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    Department of Internal Medicine, Morioka Municipal Hospital, Morioka, Japan.

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    Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.

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    Department of Gastroenterology and Hepatology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.

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    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.

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    Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.

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    Department of Nutritional Medicine, Osaka City University Graduate School of Human Life Science, Osaka, Japan.

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    Department of Internal Medicine, Osaka Koseinenkin Hospital, Osaka, Japan.

    ,

    Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.

    Department of Nutritional Science, Morioka University, Morioka, Japan.

    Source

    MeSH

    Aged
    Aged, 80 and over
    Ammonia
    Dietary Supplements
    Double-Blind Method
    Female
    Humans
    Hyperammonemia
    Liver Cirrhosis
    Male
    Middle Aged
    Trace Elements
    Treatment Outcome
    Zinc
    Zinc Acetate

    Pub Type(s)

    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25280421

    Citation

    Katayama, Kazuhiro, et al. "Effect of Zinc On Liver Cirrhosis With Hyperammonemia: a Preliminary Randomized, Placebo-controlled Double-blind Trial." Nutrition (Burbank, Los Angeles County, Calif.), vol. 30, no. 11-12, 2014, pp. 1409-14.
    Katayama K, Saito M, Kawaguchi T, et al. Effect of zinc on liver cirrhosis with hyperammonemia: a preliminary randomized, placebo-controlled double-blind trial. Nutrition. 2014;30(11-12):1409-14.
    Katayama, K., Saito, M., Kawaguchi, T., Endo, R., Sawara, K., Nishiguchi, S., ... Suzuki, K. (2014). Effect of zinc on liver cirrhosis with hyperammonemia: a preliminary randomized, placebo-controlled double-blind trial. Nutrition (Burbank, Los Angeles County, Calif.), 30(11-12), pp. 1409-14. doi:10.1016/j.nut.2014.04.018.
    Katayama K, et al. Effect of Zinc On Liver Cirrhosis With Hyperammonemia: a Preliminary Randomized, Placebo-controlled Double-blind Trial. Nutrition. 2014;30(11-12):1409-14. PubMed PMID: 25280421.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effect of zinc on liver cirrhosis with hyperammonemia: a preliminary randomized, placebo-controlled double-blind trial. AU - Katayama,Kazuhiro, AU - Saito,Masanori, AU - Kawaguchi,Takumi, AU - Endo,Ryujin, AU - Sawara,Kei, AU - Nishiguchi,Shuhei, AU - Kato,Akinobu, AU - Kohgo,Hiroshi, AU - Suzuki,Kazutomo, AU - Sakaida,Isao, AU - Ueno,Yoshiyuki, AU - Habu,Daiki, AU - Ito,Toshifumi, AU - Moriwaki,Hisataka, AU - Suzuki,Kazuyuki, Y1 - 2014/05/10/ PY - 2014/01/06/received PY - 2014/04/12/revised PY - 2014/04/17/accepted PY - 2014/10/5/entrez PY - 2014/10/5/pubmed PY - 2015/6/2/medline KW - Ammonia metabolism KW - Hepatic encephalopathy KW - Nutritional intervention KW - Trace element KW - Zinc acetate SP - 1409 EP - 14 JF - Nutrition (Burbank, Los Angeles County, Calif.) JO - Nutrition VL - 30 IS - 11-12 N2 - OBJECTIVE: To our knowledge, no randomized study has shown whether zinc replacement therapy is effective for hyperammonemia in liver cirrhosis; therefore, we performed a double-blind, placebo-controlled trial to examine efficacy and safety of the zinc replacement therapy. METHODS: Patients with liver cirrhosis and hyperammonemia (at or above the institutional reference value) and hypozincemia (≤65 μg/dL) were enrolled in the outpatient units of the participating institutions and were randomly divided to receive placebo (P group) or zinc acetate preparation at a dose of 3 capsules/d for a total zinc content of 150 mg/d (Z group) by the envelope method. Of the 18 enrolled patients, 6 dropped out; thus, the analyses included 12 patients (5 in the P group and 7 in the Z group). Variations in blood concentrations of zinc and ammonia as well as liver function test results were compared. RESULTS: Blood zinc levels significantly increased in the Z group (P = 0.0037; Friedman test) but not the P group. Blood ammonia levels significantly decreased in the Z group (P = 0.0114; Friedman test) but not the P group. The percent change in blood ammonia level also revealed significant reduction at the eighth week in the Z group (P = 0.0188: Mann-Whitney test). No serious adverse events attributable to the zinc preparation were noted. CONCLUSION: Although this study is preliminary and includes a small sample, it is, to our knowledge, the first randomized controlled trial to show that zinc supplementation for 3 mo seems effective and safe for treating hyperammonemia in liver cirrhosis. Studies with a larger sample size are needed to confirm our findings. SN - 1873-1244 UR - https://www.unboundmedicine.com/medline/citation/25280421/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0899-9007(14)00210-X DB - PRIME DP - Unbound Medicine ER -