Effects of Zinc Acetate on Serum Zinc Concentrations in Chronic Liver Diseases: a Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial and a Dose Adjustment Trial

Kazuhiro Katayama, Atsushi Hosui, Yoshiyuki Sakai, Minoru Itou, Yasushi Matsuzaki, Yoriyuki Takamori, Keiko Hosho, Tomomi Tsuru, Yasuhiro Takikawa, Kojiro Michitaka, Eishin Ogawa, Yoko Miyoshi, Toshifumi Ito, Shinobu Ida, Izumi Hamada, Katsunori Miyoshi, Hiroko Kodama, Tetsuo Takehara, Kazuhiro Katayama, Atsushi Hosui, Yoshiyuki Sakai, Minoru Itou, Yasushi Matsuzaki, Yoriyuki Takamori, Keiko Hosho, Tomomi Tsuru, Yasuhiro Takikawa, Kojiro Michitaka, Eishin Ogawa, Yoko Miyoshi, Toshifumi Ito, Shinobu Ida, Izumi Hamada, Katsunori Miyoshi, Hiroko Kodama, Tetsuo Takehara

Abstract

The essential trace element zinc maintains liver functions. Liver diseases can alter overall zinc concentrations, and hypozincemia is associated with various hepatic pathologies. Modulating systemic zinc through dietary supplementation is potentially useful for liver diseases. We evaluated the usefulness of zinc (NPC-02; acetate formulation) supplementation. We conducted two NPC-02 studies on zinc-deficient patients (serum zinc < 70 μg/dL). Study 1: double-blind, randomized, placebo-controlled trial on 57 subjects with chronic liver diseases comparing serum zinc in patients given NPC-02 (NPC-02 group) versus placebo (Placebo group). Study 2: dose adjustment study on 43 subjects with/without liver diseases to determine proportions maintaining serum zinc target (≥ 80 μg/dL but < 200 μg/dL). In study 1, NPC-02 subjects had higher serum zinc concentrations at week 8 than Placebo subjects (83.2 ± 20.2 and 61.3 ± 12.0, respectively; P < 0.0001), and more NPC-02 than Placebo subjects achieved the serum zinc target (15/27 vs. 1/26). In study 2, the NPC-02-induced serum zinc increase was dose-dependent in subjects both with and without liver diseases (r = 0.5143, P = 0.0022 and r = 0.5753, P = 0.0005, respectively). Interestingly, there was a marginally positive correlation between serum zinc and albumin levels in subjects with but not in those without liver diseases (r = 0.4028, P = 0.0631 and r = 0.1360, P = 0.5567, respectively). NPC-02 dose-dependently increases serum zinc in hypozincemic patients, regardless of liver disease. NPC-02 is a potentially effective therapy for liver cirrhosis, in which zinc deficiency is common. Clinical trial registry number: NCT02337569, NCT02321865.

Keywords: Chronic liver disease; Dose adjustment; Hypozincemia; NPC-02; Serum zinc concentration; Zinc deficiency.

Conflict of interest statement

KK received a payment from Nobelpharma Co., Ltd. for lectures. HK received payments from Nobelpharma Co., Ltd. for medical advisory and lectures. IH is an employee, and KMiyoshi is a former employee of Nobelpharma Co., Ltd., which provided financial support for this study. The remaining authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow diagram of subjects in Study 1
Fig. 2
Fig. 2
Changes in serum zinc concentrations in the NPC-02 and Placebo groups at weeks 4 and 8. The serum zinc concentration increment was larger in the NPC-02 group than in the Placebo group at weeks 4 and 8. NPC-02 group, NPC-02-treated group; Placebo group, placebo-treated group
Fig. 3
Fig. 3
Increase in serum zinc concentration by amount of zinc from baseline in subjects with (a) and without (b) chronic liver diseases. Since this was a dose adjustment study, multiple data were available for one subject who had received increasing NPC-02 doses, and all of these data were included in the analysis. The serum zinc concentration was dose-dependently increased in subjects both with and without liver diseases
Fig. 4
Fig. 4
Correlation between baseline serum zinc and albumin concentrations in patients with (a) and without (b) chronic liver diseases. There was a correlation between baseline serum zinc and albumin concentrations, which did not reach statistical significance but was marginally positive (P = 0.063), in subjects with but not in those without liver diseases

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Source: PubMed

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