{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T09:42:49Z","timestamp":1775122969234,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T00:00:00Z","timestamp":1587081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zeria Pharmaceutical Co., Ltd.","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Zinc intake is recommended for zinc deficiency. In clinical practice, polaprezinc has been used as a zinc replacement therapy for zinc deficiency. However, the efficacy of polaprezinc has not been established. To confirm the efficacy on zinc deficiency of polaprezinc and provide additional information on an appropriate regimen, we conducted a systematic review using individual patient data (IPD). We searched PubMed, the Japanese database Ichushi, and the database owned by the marketing authorization holder of polaprezinc. Randomized placebo-controlled trials that reported the serum zinc concentration were eligible. The mean difference of the change from baseline in serum zinc concentration was estimated using a fixed-effects model. The linear dose\u2013response relationship and the subgroup effects were also assessed. Out of 54 unique randomized clinical trials (RCTs), four studies met the eligibility criteria, and we could access IPD for all of them. All three doses of polaprezinc (75 mg, 150 mg, and 300 mg) and the placebo group were examined. The dose-combined overall polaprezinc increased the change from baseline by a mean of 9.08 \u00b5g\/dL (95% confidence interval: 5.46, 12.70; heterogeneity:      I 2      = 0.61%) compared to the placebo. A significant dose\u2013response relationship was confirmed (p &lt; 0.001). Baseline serum zinc concentration was considered an effect modifier in polaprezinc 300 mg. All doses of polaprezinc were tolerable, but a dose\u2013response relationship with adverse events (AEs) was observed in gastrointestinal disorders. The dose of 300 mg may be useful among patients with baseline serum zinc concentration of less than 70 \u00b5g\/dL, and 150 mg for 70 \u00b5g\/dL or more.<\/jats:p>","DOI":"10.3390\/nu12041128","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T04:49:38Z","timestamp":1587444578000},"page":"1128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy and Safety of Polaprezinc (Zinc Compound) on Zinc Deficiency: A Systematic Review and Dose\u2013Response Meta-Analysis of Randomized Clinical Trials Using Individual Patient Data"],"prefix":"10.3390","volume":"12","author":[{"given":"Kei","family":"Furihata","sequence":"first","affiliation":[{"name":"Biostatistics, Data Science, Clinical Administration, Zeria Pharmaceutical Co., Ltd., 10-11, Nihonbashi Kobuna-cho, Chuo-ku, Tokyo 103-8351, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Tsuchikawa","sequence":"additional","affiliation":[{"name":"Biostatistics, Data Science, Clinical Administration, Zeria Pharmaceutical Co., Ltd., 10-11, Nihonbashi Kobuna-cho, Chuo-ku, Tokyo 103-8351, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaki","family":"Miwa","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5443-788X","authenticated-orcid":false,"given":"Yuji","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-chi, Kawaramachi-Hirokoji Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5468-8988","authenticated-orcid":false,"given":"Koji","family":"Oba","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Sakagami","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, Hyogo 663-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1152\/physrev.1993.73.1.79","article-title":"The Biochemical Basis of Zinc Physiology","volume":"73","author":"Vallee","year":"1993","journal-title":"Physiol. 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