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

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

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.

Keywords: Ammonia metabolism; Hepatic encephalopathy; Nutritional intervention; Trace element; Zinc acetate.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Ammonia / blood*
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Hyperammonemia / blood
  • Hyperammonemia / drug therapy*
  • Hyperammonemia / etiology
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy*
  • Male
  • Middle Aged
  • Trace Elements / blood
  • Trace Elements / pharmacology
  • Trace Elements / therapeutic use*
  • Treatment Outcome
  • Zinc / blood
  • Zinc / deficiency
  • Zinc / pharmacology
  • Zinc / therapeutic use*
  • Zinc Acetate / pharmacology
  • Zinc Acetate / therapeutic use

Substances

  • Trace Elements
  • Ammonia
  • Zinc Acetate
  • Zinc