Zinc Carnosine (Stomach)

OBJECTIVE: To investigate the clinical efficacy and safety of polaprezinc compared with rebamipide in the treatment of gastric ulcers (GU). METHODS: GU patients (n = 224) from 10 clinical centers were prospectively enrolled and randomly divided into a control (n = 113) or test (n = 111) group. The control group was treated with rebamipide tablets, while the test group was treated with polaprezinc. The primary endpoint was the effective treatment rate, which was confirmed by gastroscopy after 8 weeks of treatment. The secondary efficacy endpoint was the improvement rate of gastrointestinal symptoms after 4 and 8 weeks of treatment. RESULTS: The basic characteristics of the two groups were well balanced. For the primary efficacy endpoint, the effective rates confirmed by gastroscopy, after treatment for the test and control groups were 81.48% and 74.31% (P = 0.1557), respectively. After 4 and 8 weeks of treatments, both treatment groups had comparable improvements rates in gastrointestinal symptoms (test vs. control: 44.44% vs. 39.45% [P = 0.4559] and 81.48% vs. 77.06% [P = 0.4223]). Further, the two groups had similar adverse events and reactions to the study drugs. CONCLUSION: These findings suggest that the efficacy and safety of polaprezinc were similar to those of rebamipide in the treatment of GU.

Polaprezinc [N-(3-aminopropionyl)-L-histidinato zinc] (PZ), an anti-ulcer drug, is a chelate compound consisting of zinc and L-carnosine. PZ has been shown to prevent gastric mucosal injury. In the present study, we investigated the inhibitory effect of PZ on indomethacin (IND)-induced apoptosis in a rat gastric mucosal cell line, RGM1. Pretreatment with PZ suppressed caspase-3 activation and subsequent apoptosis in the cells exposed to 500 microM IND in a dose-dependent manner, and 50 microM PZ exhibited the maximum inhibitory effect. Among PZ subcomponents, zinc but not L-carnosine played a pivotal role in this antiapoptotic function. PZ did not affect mitochondrial cytochrome c release upstream of caspase-3 activation in the IND-induced apoptotic signal pathway. Treatment with 500 microM IND evidently produced reactive oxygen species (ROS) in RGM1 cells. However, PZ did not scavenge ROS in IND-treated cells. Moreover, N-acetylL-cysteine, a potent antioxidant, inhibited ROS generation but did not suppress apoptosis in RGM1 cells exposed to IND. These observations demonstrate a novel pharmacological action of PZ; i.e., that PZ, and in particular its zinc subcomponent, inhibits apoptosis via inhibition of caspase-3 activation but not antioxidant activity.

Effects of a novel zinc compound polaprezinc [N-(3-aminopropionyl)-L-histidinatozinc] and sucralfate on the mucosal ulcerogenic responses induced by monochloramine (NH2Cl) were examined in rat stomachs. Oral administration of NH2Cl (>60 mM) produced severe lesions in unanesthetized rat stomachs, with concomitant increase of lipid peroxidation. These lesions were aggravated by sensory deafferentation but not affected by pretreatment with indomethacin or L-NAME. The mucosal ulcerogenic response to NH2Cl was significantly inhibited by oral pretreatment with either dmPGE2 (10 microg/kg), capsaicin (30 mg/kg), or NOR-3 (3 mg/kg), the NO donor. Gastric lesions induced by NH2Cl were also inhibited by prior oral administration of polaprezinc (3-30 mg/kg) as well as sucralfate (30 and 100 mg/kg). The protective effect of polaprezinc was not affected by any pretreatments such as indomethacin, L-NAME, or sensory deafferentation, while that of sucralfate was significantly mitigated in the presence of either indomethacin or L-NAME. On the other hand, mucosal exposure to NH4OH (60 mM) caused a marked PD reduction in ex vivo stomachs made ischemic by bleeding from the carotid artery, followed by severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischemia were also attenuated by prior application of polaprezinc, while dmPGE2 and sucralfate prevented such lesions without affecting the reduced PD response. These results suggest that: (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa, (2) both polaprezinc and sucralfate protect the stomach against injury caused by NH2Cl, and (3) the mechanisms underlying the protective action of sucralfate may be partly mediated by both endogenous PGs and NO but may be different from those of polaprezinc.

INTRODUCTION: Proton-pump inhibitor (PPI) monotherapy is standard for artificial ulcer healing after gastric endoscopic submucosal dissection, but evidence on the efficacy of PPI combined with gastric mucosal protectants remains inconclusive. This network meta-analysis aimed to compare the efficacy of 10 mucosal protectants combined with PPIs. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and <ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> until January 2025. Included were 20 randomized controlled trials (n = 2,000) comparing PPI monotherapy versus PPI combined with protectants (e.g., rebamipide, ecabet, polaprezinc) or active controls. Primary outcomes included ulcer area reduction, healing rates (4/8 weeks), longest ulcer diameter, and bleeding risk. Frequentist random-effects models synthesized risk ratios (RRs) and MDs with 95% CIs. Consistency was evaluated using design-by-treatment interaction and node splitting. Risk of bias (RoB 2.0) was assessed at the outcome level. Certainty of evidence was graded with GRADE. RESULTS: Bismuth subcitrate-magnesium granules (BMG) + PPI most effectively reduced 4-week ulcer area (MD: -62.50 mm2, 95% CI: -87.25 to -37.75 vs. PPI; SUCRA = 94%). Ecabet sodium (EB) + PPI achieved the highest 8-week healing rate (RR: 7.71, 95% CI: 5.52-9.91). Hydrotalcite (HT) + PPI best reduced ulcer diameter (MD: -1.87 mm), while teprenone (TN) + PPI optimally prevented bleeding (RR: -3.41, 95% CI: -5.43 to -1.38). Rebamipide + PPI showed efficacy heterogeneity, particularly in large ulcers (>40 mm). CONCLUSIONS: PPI-based combinations likely accelerate healing versus PPI alone, but conclusions are hypothesis generating given indirect evidence and regional concentration of trials. Combination therapy outperforms PPI monotherapy. BMG + PPI is optimal for early ulcer healing, EB + PPI for long-term healing, HT + PPI for diameter reduction, and TN + PPI for bleeding prevention. Stratified regimens by ulcer characteristics are recommended. © 2025 S. Karger AG, Basel.

Fracture healing is a complex biological process that can be delayed by systemic or local factors. Polaprezinc, a zinc-L-carnosine complex with antioxidant, anti-inflammatory, and regenerative properties, has shown promise in tissue repair, but its role in bone regeneration remains underexplored. To evaluate the effectiveness and safety of polaprezinc as an adjuvant therapy in enhancing fracture healing among adults with closed fractures. A prospective, single-center, controlled, non-randomized interventional study was conducted over a 3 months period at a tertiary care hospital in Hyderabad. A total of 100 adults (18-85 years) with radiologically confirmed closed fractures were assigned to two groups: an intervention group receiving standard orthopedic care plus oral polaprezinc (75 mg twice daily) and a control group receiving standard care alone. Clinical outcomes were assessed using the Visual Analogue Scale (VAS) for pain and weight-bearing ability, while radiological outcomes were measured using the Radiographic Healing Scale (RHS) and REBORNE Scale at 4, 8, and 12 weeks. Safety was monitored through laboratory tests and adverse event reporting. The polaprezinc group demonstrated significantly faster radiological union and stronger callus formation compared with controls (RHS and REBORNE scores, p < 0.05). Pain reduction was greater in the intervention group (VAS improvement: t = 5.696, p < 0.05). Mean fracture healing time was shortened by approximately one week. No serious adverse events were reported, and compliance was high. Polaprezinc as an adjunct to standard fracture care significantly improved radiological and clinical healing outcomes, reduced pain, and maintained an excellent safety profile. These findings support its potential as a safe and effective adjuvant in fracture management, warranting confirmation in larger multicenter trials. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Zinc supplementation may ameliorate zinc deficiency in maintenance hemodialysis patients; however, no standard protocol has been established. This study aimed to investigate the effects of zinc acetate hydrate (ZAH) and polaprezinc (PPZ) as zinc supplements in hemodialysis patients. We enrolled 75 hemodialysis patients with serum zinc levels <60 μg/dL for this study and randomly assigned Zinc supplementation to these 75 patients: 37 received ZAH (50 mg/day), and 38 received PPZ (34 mg/day). Serum zinc levels of both groups were compared every 4 weeks for 1 year. In both groups, serum zinc levels significantly increased at 4-52 weeks. Serum zinc levels were significantly higher in the ZAH group at 4-12 weeks; however, no significant differences were observed between the groups at 16-52 weeks. Adverse events requiring a reduction in the zinc dose, including copper deficiency, occurred significantly more frequently in the ZAH group. In conclusion, PPZ can safely maintain serum zinc levels for 1 year. ZAH provides rapid zinc supplementation but can cause adverse events.

BACKGROUND: Zinc plays an important role in appetite regulation. L-Carnosine, an endogenous dipeptide, may also regulate eating behavior via its histaminergic and antiglutamatergic properties. Polaprezinc (zinc-L-carnosine complex) is a medication for gastric ulcers. A small case series reported successful treatment of binge eating with add-on polaprezinc. METHODS: This was an open trial of add-on polaprezinc in patients with binge eating disorder (BED; n = 22) or bulimia nervosa (BN; n = 7) receiving antidepressants. A 4-week baseline period was followed by a 16-week polaprezinc treatment at 150 mg/d (containing 34 mg zinc and 116 mg L-carnosine) in addition to ongoing psychotropic medications. We also assessed their zinc status via a laboratory index and zinc deficiency-related symptoms. RESULTS: At the study end, both conditions showed a significant reduction in the 4-week frequency of combined objective and subjective binge eating episodes, the 4-week frequency of days when at least 1 such episode occurred (only in BED), several aspects of eating disorder psychopathology (rated by the Eating Disorder Examination-Questionnaire), and comorbid depressive symptoms (rated by the 16-item Quick Inventory of Depressive Symptomatology [Self-Report]). Serum copper/zinc ratio decreased from 1.4 to 1.1 on average in both conditions. All patients had multiple zinc deficiency-related symptoms at baseline that substantially improved after polaprezinc treatment. Overall, the effectiveness of polaprezinc was greater in BED patients than in BN patients, with minor adverse effects. CONCLUSIONS: These findings offer preliminary evidence for the effectiveness of polaprezinc in treating BED and BN and suggest the involvement of zinc deficiency in these conditions.

BACKGROUND: To investigate whether pre-dialysis level of serum creatinine (SCre) could indicate the responsiveness to zinc supplementation of patients on maintenance hemodialysis (MHD). METHODS: We retrospectively reviewed the results of our previous randomized study of 91 patients who had been on MHD and received zinc supplementation with either zinc acetate hydrate (ZAH; zinc, 50 mg/day) or polaprezinc (PPZ; zinc, 34 mg/day). A late response to zinc supplementation was defined as a serum zinc level of < 80 μg/dL three months after the study began. Patients were divided into two groups: late response (serum zinc level < 80 μg/dL) and early response (serum zinc level ≥ 80 μg/dL). Factors independently associated with a late response to zinc supplementation were determined using inverse probability of treatment weighting (IPTW) multivariate logistic analysis. RESULTS: Of 91 patients, 86 continued to receive zinc supplementation after three months. The mean pre-dialysis SCre level was 10.0 mg/dL. The number of patients with a late response and response to zinc supplementation was 32 and 54, respectively. There was a significant negative correlation between the pre-dialysis SCre and the Δserum zinc change for 3 months. (r = - 0.284, P = 0.008). IPTW multivariate analysis showed that a pre-dialysis SCre level ≥ 10.0 mg/dL (odds ratio, 3.71; 95% confidence interval; 1.24-11.1, P = 0.022) was an independent factor associated with a late response to zinc supplementation. CONCLUSIONS: Pre-dialysis SCre level was independently associated with responsiveness to zinc supplementation after three months in patients on MHD.

BACKGROUND: Heavy exercise causes gut symptoms and, in extreme cases, heat stroke that is due to the increased intestinal permeability of luminal toxins. OBJECTIVE: We examined whether zinc carnosine (ZnC), a health-food product taken alone or in combination with bovine colostrum (a natural source of growth factors), would moderate such effects. DESIGN: Eight volunteers completed a 4-arm, double-blind, placebo-controlled crossover protocol (14 d of placebo, ZnC, colostrum, or ZnC plus colostrum) before undertaking standardized exercise 2 and 14 d after the start of treatment. Changes in epithelial resistance, apoptosis signaling molecules, and tight junction (TJ) protein phosphorylation in response to a 2°C rise in body temperature were determined with the use of Caco-2 and HT29 intestinal cells. RESULTS: Body temperature increased 2°C, and gut permeability (5-h urinary lactulose:rhamnose ratios) increased 3-fold after exercise (from 0.32 ± 0.016 baseline to 1.0 ± 0.017 at 14 d; P < 0.01). ZnC or colostrum truncated the rise by 70% after 14 d of treatment. The combination treatment gave an additional benefit, and truncated exercise induced increase at 2 d (30% reduction; P < 0.01). A 2°C temperature rise in in vitro studies caused the doubling of apoptosis and reduced epithelial resistance 3-4-fold. ZnC or colostrum truncated these effects (35-50%) with the greatest response seen with the combination treatment (all P < 0.01). Mechanisms of action included increasing heat shock protein 70 and truncating temperature-induced changes in B cell leukemia/lymphoma-2 associated X protein α and B cell lymphoma 2. ZnC also increased total occludin and reduced phosphorylated tyrosine claudin, phosphorylated tyrosine occludin, and phosphorylated serine occludin, thereby enhancing the TJ formation and stabilization. CONCLUSION: ZnC, taken alone or with colostrum, increased epithelial resistance and the TJ structure and may have value for athletes and in the prevention of heat stroke in military personnel. This trial was registered at www.isrctn.com as ISRCTN51159138. © 2016 American Society for Nutrition.

BACKGROUND: In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI). METHODS: Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL). RESULTS: There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI. CONCLUSIONS: Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.

SCOPE: An increased intake of Zinc (Zn) may reduce the risk of degenerative diseases but may prove to be toxic if taken in excess. This study aimed to investigate whether zinc carnosine supplement can improve Zn status, genome stability events, and Zn transporter gene expression in an elderly (65-85 years) South Australian cohort with low plasma Zn levels. METHODS AND RESULTS: A 12-week placebo-controlled intervention trial was performed with 84 volunteers completing the study, (placebo, n = 42) and (Zn group, n = 42). Plasma Zn was significantly increased (p < 0.05) by 5.69% in the Zn supplemented group after 12 weeks. A significant (p < 0.05) decrease in the micronucleus frequency (-24.18%) was observed for the Zn supplemented cohort relative to baseline compared to the placebo group. Reductions of -7.09% for tail moment and -8.76% for tail intensity were observed for the Zn group (relative to baseline) (p < 0.05). Telomere base damage was found to be also significantly decreased in the Zn group (p < 0.05). Both MT1A and ZIP1 expression showed a significant increase in the Zn supplemented group (p < 0.05). CONCLUSION: Zn supplementation may have a beneficial effect in an elderly population with low Zn levels by improving Zn status, antioxidant profile, and lowering DNA damage. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Zinc (Zn) is an essential trace element, which has been shown to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption in vitro. In thalassemia, major patients Zn supplementation was reported to increase whole-body bone mineral content and areal bone mineral density. Therefore, we investigated the effect of Zn supplementation on bone formation in hemodialysis (HD) patients. Nine male patients with age of 66 (35-78) years indicated by median (range), HD vintage of 57 (4-97) months and serum intact parathyroid hormone (PTH) of 113 (6-310) pg/mL were supplemented with polaprezinc containing 34 mg Zn/day for 18 months. Doses of vitamin D were not changed during supplementation. Blood was collected at baseline, 3, 6, 12 and 18 months. Serum Zn increased significantly from 58 (52-65) μg/dL to 71 (57-93) μg/dL at three months and remained unchanged until 18 months. No changes were observed in serum intact PTH during supplementation. Although we found no changes in serum bone alkaline phosphatase (BAP) during Zn supplementation analyzed by Friedman test and Scheffe post hoc test, a significant trend of increase in serum BAP was verified by Jonckheere-Terpstra test (p = 0.0409). On the contrary, there was no trend in serum TRACP5b by Jonckheere-Terpstra test. Therefore, we suggested the effect of Zn supplementation on promoting bone formation, not affected by the status of PTH and vitamin D, in HD patients with normal or low turnover bone.

Chelated zinc-carnosine and vitamin E [GastriCalm(®) (GCM); Teva Animal Health] is marketed as an anti-emetic supplement for dogs to assist the repair of damaged stomach and intestinal mucosa. The purpose of this prospective, double-blinded, placebo-controlled trial was to determine whether GCM reduced the frequency of vomiting, diarrhoea and appetite changes during initiation of ciclosporin (Atopica(®); Novartis Animal Health) therapy for the treatment of canine atopic dermatitis. Sixty privately owned dogs diagnosed with atopic dermatitis were randomly assigned to GCM (n=30) or placebo (n=30) groups. All dogs received ∼ 5 mg/kg ciclosporin (range, 3.5-5.8 mg/kg) once daily. Dogs <13.6 kg received half a tablet of GCM or placebo; dogs ≥ 13.6 kg received one tablet once daily. GastriCalm(®) or placebo was administered 30 min prior to eating, and the ciclosporin was administered 2 h after feeding. Owners recorded episodes of vomiting, diarrhoea and appetite changes. Dogs were examined on days 0 and 14. Forty-one of 60 dogs (68.3%) had at least one episode of vomiting, diarrhoea or appetite change, leaving nine placebo dogs (30%) and ten GCM dogs (33.3%) free of adverse events (AE). Twenty-seven of 60 dogs (45%) vomited, and 15 of 60 (25%) had diarrhoea. There was no significant difference in episodes of individual AEs, but the placebo group had a significantly lower total AE score (summation of episodes of appetite change, vomiting and diarrhoea; P=0.022). Small dogs (<6.82 kg) had significantly fewer total AEs in both treatment groups and tolerated ciclosporin better than larger dogs (P<0.05). © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.

We investigated the effects of zinc supplementation on clinical observations in chronic hepatitis C patients receiving pegylated interferon (PEG-IFN) alpha-2b plus ribavirin combination therapy. Patients were randomly allocated to receive 150 mg polaprezinc (zinc group, n=11) or no supplement (control group, n=12) daily in addition to PEG-IFN alpha-2b plus ribavirin therapy and 300 mg vitamin E and 600 mg vitamin C supplementation daily for 48 wk. Among the patients who continued treatment, the serum alanine aminotransferase (ALT) level at 12 wk in the zinc group was significantly lower than that in the control group. All patients in the zinc group (9/9) and 67% (8/12) of the control patients at 24 wk, and all patients in the zinc group (7/7) and 60% (6/10) of the control patients at 48 wk showed a decrease in serum ALT levels to within the normal range (7-44 U/L). HCV RNA disappeared in all patients (7/7) in the zinc group and in 8 of 10 control patients at 48 wk. Polaprezinc supplementation decreased plasma thiobarbituric acid reactive substances and prevented the decrease of polyunsaturated fatty acids of erythrocyte membrane phospholipids. No significant differences were observed in the dosage of medicines or other clinical data during the treatment. These observations indicate that polaprezinc supplementation may have induced some antioxidative functions in the liver which resulted in reduced hepatocyte injury during PEG-IFN alpha-2b plus ribavirin therapy.

BACKGROUND: Zinc carnosine (ZnC) is a health food product claimed to possess health-promoting and gastrointestinal supportive activity. Scientific evidence underlying these claims is, however, limited. AIM: To examine the effect of ZnC on various models of gut injury and repair, and in a clinical trial. METHODS: In vitro studies used pro-migratory (wounded monolayer) and proliferation ([(3)H]-thymidine incorporation) assays of human colonic (HT29), rat intestinal epithelial (RIE) and canine kidney (MDCK) epithelial cells. In vivo studies used a rat model of gastric damage (indomethacin/restraint) and a mouse model of small-intestinal (indomethacin) damage. Healthy volunteers (n = 10) undertook a randomised crossover trial comparing changes in gut permeability (lactulose:rhamnose ratios) before and after 5 days of indomethacin treatment (50 mg three times a day) with ZnC (37.5 mg twice daily) or placebo coadministration. RESULTS: ZnC stimulated migration and proliferation of cells in a dose-dependent manner (maximum effects in both assays at 100 micromol/l using HT29 cells), causing an approximate threefold increase in migration and proliferation (both p<0.01). Oral ZnC decreased gastric (75% reduction at 5 mg/ml) and small-intestinal injury (50% reduction in villus shortening at 40 mg/ml; both p<0.01). In volunteers, indomethacin caused a threefold increase in gut permeability in the control arm; lactulose:rhamnose ratios were (mean (standard error of mean)) 0.35 (0.035) before indomethacin treatment and 0.88 (0.11) after 5 days of indomethacin treatment (p<0.01), whereas no significant increase in permeability was seen when ZnC was coadministered. CONCLUSION: ZnC, at concentrations likely to be found in the gut lumen, stabilises gut mucosa. Further studies are warranted.

AIM: To study the therapeutic effect of interferon (IFN) and ribavirin with zinc supplement on patients with chronic hepatitis C viral (HCV) infection. METHODS: A total of 102 patients confirmed histologically to have chronic HCV infection with genotype 1b and more than 100 KIU/mL of HCV were randomly assigned to each arm of the study and each received 10 million units of pegylated interferon (IFN-alpha-2b) daily for 4 wk followed by the same dose every other day for 20 wk plus ribavirin (600 or 800 mg/d depending on body weight), with or without polaprezinc (150 mg/d) orally for 24 wk. The primary endpoint was sustained virological response (SVR) defined as negative HCV-RNA in the serum 6 mo after treatment. RESULTS: There were no differences in the clinical background between the two groups except for more females in the dual therapy group than in the other group (P<0.05). SVR was observed in 33.3% of the triple therapy group and 33.3% of the dual therapy group. The side effects were almost the same in both groups except for gastrointestinal symptoms, which were less in the triple therapy group (P=0.019). CONCLUSION: Considered together, triple therapy of zinc plus IFN and ribavirin for HCV infection patients with genotype 1b and high viral load is not better than dual therapy except for lower incidence of gastrointestinal side effects.