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Nutrition. 2014 Nov-Dec;30(11-12):1409-14. doi: 10.1016/j.nut.2014.04.018. Epub 2014 May 10.

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

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Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka, Japan. Electronic address:
Division of Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, Nishinomiya, Japan.
Division of Gastroenterology, Department of Medicine and Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Department of Internal Medicine, Morioka Municipal Hospital, Morioka, Japan.
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
Department of Gastroenterology and Hepatology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.
Department of Nutritional Medicine, Osaka City University Graduate School of Human Life Science, Osaka, Japan.
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.



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.


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.


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.


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.


Ammonia metabolism; Hepatic encephalopathy; Nutritional intervention; Trace element; Zinc acetate

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