title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka, Japan. Electronic address: katayama-ka@mc.pref.osaka.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katayama
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Saito
authors.affiliation: Division of Gastroenterology, Department of Medicine and Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Ryujin
authors.initials: R
authors.lastname: Endo
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sawara
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.affiliation: Department of Internal Medicine, Morioka Municipal Hospital, Morioka, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Kato
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kohgo
authors.affiliation: Department of Gastroenterology and Hepatology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.affiliation: Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Department of Nutritional Medicine, Osaka City University Graduate School of Human Life Science, Osaka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Habu
authors.affiliation: Department of Internal Medicine, Osaka Koseinenkin Hospital, Osaka, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.affiliation: Department of Nutritional Science, Morioka University, Morioka, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000641:Ammonia / Q000097:blood*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014131:Trace Elements / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D015032:Zinc / Q000097:blood / Q000172:deficiency / Q000494:pharmacology / Q000627:therapeutic use*; D019345:Zinc Acetate / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D014131:Trace Elements; D000641:Ammonia; D019345:Zinc Acetate; D015032:Zinc
keywords: Ammonia metabolism; Hepatic encephalopathy; Nutritional intervention; Trace element; Zinc acetate