Zinc carnosine (polaprezinc) is a chelate compound of zinc and L-carnosine indicated for healing damaged mucosal tissue. Its antioxidant and anti-inflammatory properties,¹ combined with zinc’s ability to modify epithelial tight junction permeability² and support specialised epithelial cells (i.e. Paneth cells),³ make it an ideal cytoprotective agent for enhancing intestinal barrier function, protection, and repair.

Zinc and carnosine both have beneficial effects on mucosal tissue but low local adherence. Taken together as zinc carnosine, it has a slow dissociation rate in the stomach due to being dissolvable in acid and polymeric in nature. This prolongs its local therapeutic effects without affecting gastric emptying. Furthermore, zinc carnosine displays a high affinity for ulcerous sites where it can exert its effects. Underlying its restorative effects on the gastric and intestinal mucosa are the following abilities. Zinc carnosine can:¹

- Suppress nuclear factor-kappa B (NFκB) with subsequent effects on
  inflammatory cytokine production

- Scavenge free radicals

- Increase the local expression of antioxidant enzymes

- Stimulate heat shock protein 72 (Hsp72), which combats protein-damaging
  cellular stress

- Increase gene expression of insulin-like growth factor (IGF)-1

Figure 1. Proposed Cytoprotective, Anti-inflammatory and Healing Mechanisms of Zinc Carnosine¹ 

An abundance of preclinical evidence demonstrates zinc carnosine’s effects in gastric ulceration^4-11 and colitis,^12,13 with effect seemingly equal to that of sulfasalazine, a disease-modifying antirheumatic drug (DMARD) used to treat ulcerative colitis and Crohn’s disease.¹³

Dosages Based on Human Studies

Zinc carnosine has been used effectively to treat conditions of the gastrointestinal tract (GIT) at the following doses and durations, based on human trials:¹

- Gastric ulcers: 100 to 200 mg/day for 8 weeks¹

- Gastritis: 150 mg/day for 2 weeks¹

- Helicobacter pylori eradication: 150 to 300 mg/day for 1 to 2 weeks with triple
  therapy^14-18

- Prevention of chemoradiotherapy-induced oral mucositis: 75 mg/day rinsed and
 swallowed,^1,19-24 75 mg/day as lozenges²⁵ or 150 mg/day not swallowed²⁶

- Aspirin-induced small intestinal injury: 150 mg/day for 4 weeks²⁷

- Gut permeability: 75 mg/day for 1 to 2 weeks^28,29

- Postendoscopic submucosal dissection: 150 mg/day for 4 to 8 weeks^1,30,31

Other studies have used zinc carnosine as an enema for ulcerative colitis (UC)³² and as a rectal ointment for haemorrhoids.³³ Oral use is expected to achieve positive effects, though an exact dosage range cannot be provided for lower GIT diseases.

Evidence-Based Prescribing of Zinc Carnosine

Use zinc carnosine to treat conditions characterised by mucosal damage, especially gastric wound repair. Beneficial effects resulting from the support of tissue healing can be expected from a dose of 75 to 300 mg of zinc carnosine daily, typically taken in divided doses, for anywhere from 1 to 8 weeks.¹

References

1. Efthymakis K, Neri M. The role of zinc L-carnosine in the prevention and treatment of gastrointestinal mucosal disease in humans: a review. Clin Res Hepatol Gastroenterol. 2022;46(7):101954. DOI: 10.1016/j.clinre.2022.101954

2. Wang X, Valenzano MC, Mercado JM, Zurbach EP, Mullin JM. Zinc supplementation modifies tight junctions and alters barrier function of Caco-2 human intestinal epithelial layers. Dig Dis Sci. 2013 Jan;58(1):77-87. DOI: 10.1007/s10620-012-2328-8

3. Podany AB, Wright J, Lamendella R, Soybel DI, Kelleher SL. ZnT2-mediated zinc import into Paneth cell granules is necessary for coordinated secretion and Paneth cell function in mice. Cell Mol Gastroenterol Hepatol. 2016 May;2(3):369-383. DOI: 10.1016/j.jcmgh.2015.12.006

4. Ito M, Shii D, Segami T, Kojima R, Suzuki Y. Preventive actions of N-(3-aminopropionyl)-L-histidinato zinc (Z-103) through increases in the activities of oxygen-derived free radical scavenging enzymes in the gastric mucosa on ethanol-induced gastric mucosal damage in rats. Jpn J Pharmacol. 1992 Jul;59(3):267-274. DOI: 10.1254/jjp.59.267

5. Cho CH. Protective effects of zinc L-carnosine (Z-103) on reserpine-induced gastric ulceration in rats. Drug Dev Res. 1992;27:61-65. DOI: 10.1002/ddr.430270107

6. Cho CH, Luk CT, Ogle CW. The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats. Life Sci. 1991;49(23):PL189-94. DOI: 10.1016/0024-3205(91)90321-2

7. Yoshikawa T, Naito Y, Tanigawa T, Yoneta T, Yasuda M, Ueda S, et al. Effect of zinc-carnosine chelate compound (Z-103), a novel antioxidant, on acute gastric mucosal injury induced by ischemia-reperfusion in rats. Free Radic Res Commun. 1991;14(4):289-296. DOI: 10.3109/10715769109088958

8. Matsukura T, Takahashi T, Nishimura Y, Ohtani T, Sawada M, Shibata K. Characterization of crystalline L-carnosine Zn(II) complex (Z-103), a novel anti-gastric ulcer agent: tautomeric change of imidazole moiety upon complexation. Chem Pharm Bull (Tokyo). 1990 Nov;38(11):3140-3146. DOI: 10.1248/cpb.38.3140

9. Arakawa T, Satoh H, Nakamura A, Nebiki H, Fukuda T, Sakuma H, et al. Effects of zinc L-carnosine on gastric mucosal and cell damage caused by ethanol in rats. Correlation with endogenous prostaglandin E2. Dig Dis Sci. 1990 May;35(5):559-566. DOI: 10.1007/BF01540402

10. Ito M, Tanaka T, Suzuki Y. Effect of N-(3-aminopropionyl)-L-histidinato zinc (Z-103) on healing and hydrocortisone-induced relapse of acetic acid ulcers in rats with limited food-intake-time. Jpn J Pharmacol. 1990 Apr;52(4):513-521. DOI: 10.1254/jjp.52.513

11. Ueki S, Seiki M, Yoneta T, Omata T, Hori Y, Ishikawa M, et al. Effect of Z-103 on compound 48/80-induced gastric lesions in rats. Scand J Gastroenterol Suppl. 1989;162:202-205. DOI: 10.3109/00365528909091161

12. Ohkawara T, Takeda H, Kato K, Miyashita K, Kato M, Iwanaga T, et al. Polaprezinc (N-(3-aminopropionyl)-L-histidinato zinc) ameliorates dextran sulfate sodium-induced colitis in mice. Scand J Gastroenterol. 2005 Nov;40(11):1321-1327. DOI: 10.1080/00365520510023530

13. Yoshikawa T, Yamaguchi T, Yoshida N, Yamamoto H, Kitazumi S, Takahashi S, et al. Effect of Z-103 on TNB-induced colitis in rats. Digestion. 1997;58(5):464-468. DOI: 10.1159/000201484

14. Ibrahim N, El Said H, Choukair A. Zinc carnosine-based modified bismuth quadruple therapy vs standard triple therapy for Helicobacter pylori eradication: a randomized controlled study. World J Clin Cases. 2022 Jan;10(1):227-235. DOI: 10.12998/wjcc.v10.i1.227

15. Wu D, Sun Z, Li T, Tan Q, Sun Y, Chen T, et al. Efficacy of quadruple regimen with polaprezinc for gastric Helicobacter pylori infection eradication: protocol for a single-centre, single-blind, non-inferiority, randomised clinical trial. BMJ Open. 2020 Nov;10(11):e037182. DOI: 10.1136/bmjopen-2020-037182

16. Tan B, Luo HQ, Xu H, Lv NH, Shi RH, Luo HS, et al. Polaprezinc combined with clarithromycin-based triple therapy for Helicobacter pylori-associated gastritis: a prospective, multicenter, randomized clinical trial. PLoS One. 2017;12(4):e0175625. DOI: 10.1371/journal.pone.0175625

17. Isomoto H, Furusu H, Ohnita K, Wen CY, Inoue K, Kohno S. Sofalcone, a mucoprotective agent, increases the cure rate of Helicobacter pylori infection when combined with rabeprazole, amoxicillin and clarithromycin. World J Gastroenterol. 2005 Mar;11(11):1629-1633. DOI: 10.3748/wjg.v11.i11.1629

18. Kashimura H, Suzuki K, Hassan M, Ikezawa K, Sawahata T, Watanabe T, et al. Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxycillin and clarithromycin increases the cure rate of Helicobacter pylori infection. Aliment Pharmacol Ther. 1999 Apr;13(4):483-487. DOI: 10.1046/j.1365-2036.1999.00510.x

19. Funato M, Ozeki M, Suzuki A, Ishihara M, Kobayashi R, Nozawa A, et al. Prophylactic effect of polaprezinc, a zinc-L-carnosine, against chemotherapy-induced oral mucositis in pediatric patients undergoing autologous stem cell transplantation. Anticancer Res. 2018 Aug;38(8):4691-4697. DOI: 10.21873/anticanres.12775

20. Hayashi H, Kobayashi R, Suzuki A, Yamada Y, Ishida M, Shakui T, et al. Preparation and clinical evaluation of a novel lozenge containing polaprezinc, a zinc-L-carnosine, for prevention of oral mucositis in patients with hematological cancer who received high-dose chemotherapy. Med Oncol. 2016 Aug;33(8):91. DOI: 10.1007/s12032-016-0795-z

21. Hayashi H, Kobayashi R, Suzuki A, Ishihara M, Nakamura N, Kitagawa J, Kanemura N, Kasahara S, Kitaichi K, Hara T, Tsurumi H, Moriwaki H, Itoh Y. Polaprezinc prevents oral mucositis in patients treated with high-dose chemotherapy followed by hematopoietic stem cell transplantation. Anticancer Res 2014;34(12):7271-7277.

22. Suzuki A, Kobayashi R, Shakui T, Kubota Y, Fukita M, Kuze B, et al. Effect of polaprezinc on oral mucositis, irradiation period, and time to discharge in patients with head and neck cancer. Head Neck. 2016 Sep;38(9):1387-1392. DOI: 10.1002/hed.24446

23. Hayashi H, Kobayashi R, Suzuki A, Ishihara M, Nakamura N, Kitagawa J, et al. Polaprezinc prevents oral mucositis in patients treated with high-dose chemotherapy followed by hematopoietic stem cell transplantation. Anticancer Res 2014;34(12):7271-7277.

24. Watanabe T, Ishihara M, Matsuura K, Mizuta K, Itoh Y. Polaprezinc prevents oral mucositis associated with radiochemotherapy in patients with head and neck cancer. Int J Cancer. 2010 Oct;127(8):1984-1990. DOI: 10.1002/ijc.25200

25. Kitagawa J, Kobayashi R, Nagata Y, Kasahara S, Ono T, Sawada M, et al. Polaprezinc for prevention of oral mucositis in patients receiving chemotherapy followed by hematopoietic stem cell transplantation: a multi-institutional randomized controlled trial. Int J Cancer. 2021 Mar;148(6):1462-1469. DOI: 10.1002/ijc.33316

26. Doi H, Fujiwara M, Suzuki H, Niwa Y, Nakayama M, Shikata T, et al. Polaprezinc reduces the severity of radiation-induced mucositis in head and neck cancer patients. Mol Clin Oncol. 2015 Mar;3(2):381-386. DOI: 10.3892/mco.2014.479

27. Watari I, Oka S, Tanaka S, Aoyama T, Imagawa H, Shishido T, et al. Effectiveness of polaprezinc for low-dose aspirin-induced small-bowel mucosal injuries as evaluated by capsule endoscopy: a pilot randomized controlled study. BMC Gastroenterol. 2013 Jul;13:108. DOI: 10.1186/1471-230X-13-108

28. Davison G, Marchbank T, March DS, Thatcher R, Playford RJ. Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers. Am J Clin Nutr. 2016 Aug;104(2):526-536. DOI: 10.3945/ajcn.116.134403

29. Mahmood A, FitzGerald AJ, Marchbank T, Ntatsaki E, Murray D, Ghosh S, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007 Feb;56(2):168-175. DOI: 10.1136/gut.2006.099929

30. Jung DH, Park JC, Lee YC, Lee SK, Shin SK, Chung H, et al. Comparison of the efficacy of polaprezinc plus proton pump inhibitor and rebamipide plus proton pump inhibitor treatments for endoscopic submucosal dissection-induced ulcers. J Clin Gastroenterol 2021;55(3):233-238. DOI: 10.1097/MCG.0000000000001357

31. Inaba T, Ishikawa S, Toyokawa T, Ishikawa H, Miyahara K, Wato M, et al. Basal protrusion of ulcers induced by endoscopic submucosal dissection (ESD) during treatment with proton pump inhibitors, and the suppressive effects of polaprezinc. Hepatogastroenterology. 2010;57(99-100):678-684.

32. Itagaki M, Saruta M, Saijo H, Mitobe J, Arihiro S, Matsuoka M, et al. Efficacy of zinc-carnosine chelate compound, polaprezinc, enemas in patients with ulcerative colitis. Scand J Gastroenterol. 2014 Feb;49(2):164-172. DOI: 10.3109/00365521.2013.863963

33. Pietroletti R, Giuliani A, Buonanno A, Mattei A, Fiasca F, Gallo G. Efficacy and tolerability of a new formulation in rectal ointment based on Zn-L-carnosine (Proctilor®) in the treatment of haemorrhoidal disease. Front Surg. 2022;9:818887. DOI: 10.3389/fsurg.2022.818887