Polaprezinc
Zinc chelated with the dipeptide L-carnosine: a prescription ulcer drug in Japan, tested in trials for mucositis, taste loss and zinc deficiency
Polaprezinc is a complex of zinc and L-carnosine, the beta-alanine and histidine dipeptide found in muscle. It was developed in Japan as a drug that protects the stomach lining and has been prescribed there for gastric ulcer since 1994. Randomised trials have tested it for ulcers left by endoscopic surgery, mouth sores during cancer treatment, taste disorders and low zinc. In the United States zinc-carnosine is sold as a dietary supplement, which means no regulator checked it for safety or effect before sale.
Manufacturer's recommended dosing (Japanese label): 75 mg, Twice a day, after breakfast and at bedtime, Oral Details ↓
Recommended Dosing
Manufacturer's recommended dosing (Japanese label)
From the prescribing information. Other doses studied, if any, are in the full dosing data below.
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Polaprezinc is what you get when zinc is bound to L-carnosine, a dipeptide of beta-alanine and histidine that the body makes in muscle and brain. The result is a white or yellowish crystalline powder that hardly dissolves in water but does dissolve in dilute acid. Two Japanese companies developed it, and it was first approved in Japan in 1994 as an anti-ulcer drug. The current Japanese label for the 75 mg tablet lists gastric ulcer as its use, at 75 mg twice a day after breakfast and at bedtime.
Its ulcer evidence is mostly head-to-head against rebamipide, another Japanese mucosal protectant. In a double-blind, double-dummy trial in 224 people with gastric ulcer, healing on endoscopy after eight weeks was 81% with polaprezinc and 74% with rebamipide, a difference that was not significant, and side effects were similar. In 210 people with the large artificial ulcers that endoscopic submucosal dissection leaves behind, polaprezinc 150 mg a day plus pantoprazole healed about 90% of ulcers in four weeks, no worse than rebamipide plus pantoprazole. A 2026 network meta-analysis of 20 trials of protectants after dissection found that adding a protectant to the acid blocker probably speeds healing, but it did not single out polaprezinc as best.
Because it puts zinc in contact with the gut lining, polaprezinc has been tried wherever the lining breaks down. In a pilot trial of people taking low-dose aspirin, four weeks of 150 mg a day reduced small-bowel erosions seen by capsule camera. In volunteers taking indomethacin, zinc-carnosine stopped the rise in gut permeability the painkiller caused, and in volunteers whose heavy exercise raised body temperature by 2°C it blunted a three-fold rise in permeability. Used as an enema in active ulcerative colitis it improved endoscopic and clinical scores within a week in a small trial.
The mouth is another target. In head and neck cancer, a polaprezinc rinse cut the rate of mouth sores, pain and taste change during radiochemotherapy compared with an azulene rinse, without lowering tumour response. In stem cell transplant patients a polaprezinc lozenge started before chemotherapy halved grade 2 or worse mouth sores in one multicentre trial, but an Australian trial of a polaprezinc mouthwash found no effect on severe mouth sores. Results have differed with the form in which it was given.
Polaprezinc is also a way of giving zinc. A dose-response meta-analysis of individual patient data from four placebo-controlled trials found that 75, 150 and 300 mg raised serum zinc in proportion to dose, with more stomach complaints at higher doses. In idiopathic taste disorder, the highest dose tested, containing 68 mg of zinc a day, improved taste sensitivity over placebo. In people on dialysis, zinc acetate raised zinc faster but caused more copper deficiency than polaprezinc, which kept zinc up over a year.
Outside Japan its status differs. It has no US or EU drug approval. In the United States zinc-carnosine is sold as a dietary supplement, and under US law the companies that sell supplements, not the FDA, are responsible for checking safety and labelling before sale; the products are not reviewed as drugs. In the EU, the food safety authority twice declined to confirm the safety of zinc L-carnosine as a novel food for supplements, in 2022 and 2026, because the particle size and how much zinc it delivers were not adequately characterised. The Japanese label warns of liver injury and copper deficiency.
Mechanism of Action
Polaprezinc protects and repairs the lining of the gut and mouth; most of the mechanism work comes from animals and cells, and points to zinc-driven protective enzymes and stress proteins.
Antioxidant enzymes
In rat stomach it switched on heme oxygenase-1 in surface cells; blocking that enzyme worsened acid injury and removed part of polaprezinc's protection.
Gut barrier
In volunteers it prevented the rise in gut permeability caused by indomethacin and by heavy exercise, and in gut cells it raised heat shock protein 70 and the tight-junction protein occludin.
Zinc supply
Taken by mouth it raises blood and serum zinc in a dose-related way, which is why it is used for zinc deficiency and taste disorders in Japan.
Published Research
These are studies of polaprezinc (zinc L-carnosine) itself, read from their PubMed abstracts: randomised trials in ulcers, mucositis, taste disorder, zinc deficiency and other conditions, a bioequivalence study, safety opinions from the EU food safety authority, one animal mechanism study and reviews. Studies of carnosine alone or of other zinc salts are not carded here.
Gastric ulcer: as good as rebamipide
In a multicentre, double-blind, double-dummy trial, 224 people with gastric ulcer took polaprezinc or rebamipide for eight weeks. Endoscopic healing rates were 81.5% and 74.3%, a difference that was not significant, symptom relief was similar at four and eight weeks, and adverse events did not differ.
Ulcers after endoscopic dissection
Two hundred and ten patients with ulcers left by endoscopic submucosal dissection took polaprezinc 150 mg a day or rebamipide 300 mg a day, each with pantoprazole 40 mg. At four weeks 90.3% and 91.4% had healed by intention to treat, meeting the test for non-inferiority; shorter procedures predicted better healing.
Dose-response for zinc deficiency
An individual-patient meta-analysis of four placebo-controlled trials found that polaprezinc 75, 150 and 300 mg raised serum zinc by 9.1 µg/dL more than placebo overall, rising with dose. Stomach and bowel complaints also rose with dose. The authors suggested 300 mg when baseline zinc is under 70 µg/dL and 150 mg above it.
Taste disorders: the highest dose helped
In a double-blind trial, 109 people with idiopathic taste disorder took placebo or polaprezinc containing 17, 34 or 68 mg of zinc a day for 12 weeks. Only the 68 mg zinc group improved taste sensitivity significantly over placebo. Side effects, including raised triglycerides and alkaline phosphatase and lower serum iron, were not serious.
Fewer mouth sores during head and neck radiochemotherapy
Thirty-one patients receiving radiochemotherapy for head and neck cancer were randomised to a polaprezinc rinse or an azulene rinse. Mouth sores, pain, dry mouth and taste change were all much less common with polaprezinc, patients used fewer painkillers and ate more, and tumour response was 88% against 92%.
Lozenges before transplant chemotherapy
In a multicentre trial of 88 evaluable patients having high-dose chemotherapy and stem cell transplant, starting polaprezinc lozenges before chemotherapy cut grade 2 or worse mouth sores from 44.7% to 22.0% compared with starting them only once sores appeared. Grade 3 sores, engraftment and other adverse events did not differ.
A mouthwash did not prevent severe mouth sores
An open-label trial randomised 108 adults undergoing stem cell transplant to a polaprezinc or a sodium bicarbonate mouthwash. Severe (grade 3 to 4) mouth sores occurred in 35% and 36%, and duration, pain and function did not differ. Throat pain outweighed mouth pain in both groups.
Gargle-and-swallow during transplant
In a retrospective comparison of 120 transplant patients, those who gargled and swallowed a polaprezinc suspension had milder mouth sores, mouth pain and taste change, and less severe acute graft-versus-host disease, with no difference in infections or survival.
Aspirin injury in the small bowel
Twenty long-term low-dose aspirin users with small-bowel injury on capsule endoscopy were randomised to polaprezinc 150 mg a day for four weeks or no treatment. The number of red spots and erosions fell significantly on repeat capsule study in the polaprezinc group and not in controls.
Blocked the gut leak caused by indomethacin
In a crossover trial in ten healthy volunteers, five days of indomethacin tripled gut permeability with placebo, but not when zinc-carnosine 37.5 mg twice daily was taken alongside. In cells it sped wound closure and growth, and in rodents it reduced stomach and small-bowel injury.
Gut permeability after heavy exercise
Eight volunteers took placebo, zinc-carnosine, bovine colostrum or both for 14 days in a double-blind crossover before standardised exercise that raised body temperature 2°C. Exercise tripled gut permeability; zinc-carnosine or colostrum cut the rise by 70%, and the pair worked earlier, at two days.
Meta-analysis: added to H. pylori triple therapy
Three randomised trials with 396 patients compared triple therapy with and without polaprezinc. Adding polaprezinc roughly doubled the odds of eradicating H. pylori (odds ratio 2.0 by intention to treat) without more adverse events, though the authors called the evidence scarce.
Bioequivalence: blood zinc after single doses
In two crossover studies in 48 healthy Chinese adults, a generic and the original polaprezinc granules gave equivalent blood zinc exposure after 75 mg fasting and 300 mg with food. Peak blood zinc was about 1.3 and 0.9 µg/mL, and both products were well tolerated.
Dialysis patients: slower than zinc acetate
Ninety-one people on haemodialysis with low zinc were randomised to zinc acetate (50 mg zinc a day) or polaprezinc (34 mg zinc a day). Zinc acetate raised serum zinc faster over three months and lowered serum copper, which polaprezinc did not; anaemia control did not differ.
Dialysis patients over a year
In 75 haemodialysis patients with serum zinc under 60 µg/dL, zinc acetate raised zinc faster in the first 12 weeks, but from week 16 to 52 levels were the same with polaprezinc. Adverse events needing a dose cut, including copper deficiency, were more frequent with zinc acetate.
Enemas in active ulcerative colitis
In an investigator-blinded trial, 28 patients with active ulcerative colitis received usual induction therapy with or without a 150 mg polaprezinc enema. After a week, endoscopic scores improved in more bowel segments and the Mayo score fell further with polaprezinc; response or remission was 71% against 10%.
Pressure ulcers in an open trial
Fourteen patients with stage II to IV pressure ulcers took polaprezinc 150 mg a day, carrying 116 mg carnosine and 34 mg zinc, for up to eight weeks. The healing score improved from week one and 11 healed. Serum zinc rose while serum copper fell, and one patient's existing copper deficiency got worse.
After a heart attack
Fifty patients with a first heart attack were randomised to polaprezinc or none after coronary stenting. Blood and urine zinc were higher with polaprezinc at day eight, an inflammation ratio was lower, and ejection fraction rose significantly by nine months, though the abstract does not compare the change between groups.
EU food safety review, 2022: safety not established
Asked whether zinc L-carnosine could be a novel food and a zinc source in supplements, the EFSA panel found it is absorbed and supplies zinc, but because its particles, possibly including nanoparticles, were not characterised, it could not establish safety or how much zinc becomes available.
EU food safety review, 2026: still not established
A second EFSA opinion on zinc L-carnosine for supplements concluded it remained insufficiently characterised: small particles could not be excluded, quick dissolution in the stomach was not supported, and neither its zinc bioavailability nor its safety could be established.
A review of the drug
A review describes polaprezinc's chemistry (an off-white crystalline powder almost insoluble in water, soluble in dilute acids and alkalis), its joint development by two Japanese companies and first approval in Japan in 1994, and its patents, preparations, pharmacokinetics and clinical research.
Switches on heme oxygenase-1 in the stomach
In rats, polaprezinc given into the stomach raised heme oxygenase-1 messenger RNA four-fold at 200 mg/kg within three hours, mainly in surface mucosal cells. Blocking the enzyme worsened acid-induced lesions and offset polaprezinc's protection, pointing to it as one mechanism.
Dosing Data
Polaprezinc is a prescription drug in Japan. The first row is the dose on the current Japanese label for gastric ulcer; the rest are amounts given in published human trials, as their abstracts state them.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Polaprezinc is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: we hold no copy of the preparation section of the label behind Polaprezinc's dose. Its label, named in Recommended Dosing above, is the source; the reconstitution calculator does the arithmetic for any vial.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Polaprezinc, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Polaprezinc stays intact once mixed.
How it is taken
As the approved label gives it: Oral (Twice a day, after breakfast and at bedtime; Promac D Tablets 75 (Japan): gastric ulcer, adults).
Source: Manufacturer's recommended dosing (Japanese label): the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Promac D Tablets 75 (Japan): gastric ulcer, adults: As prescribed; adjusted for age and symptoms.
When effects appear: unknown; no source on this page gives a time to effect for Polaprezinc. Results reported in the studies are under Published Research.
Source: Manufacturer's recommended dosing (Japanese label), the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Liver injury and jaundice, listed as a serious reaction on the Japanese label (Promac D label, 2023); Copper deficiency, with anaemia or low blood counts in malnourished patients, because zinc blocks copper absorption (Promac D label, 2023; PMID 24691900); Stomach and bowel complaints, more frequent at higher doses (PMID 32316581); Raised triglycerides and alkaline phosphatase and lower serum iron in a taste-disorder trial (PMID 19037756); Adverse events similar to rebamipide in an ulcer trial (PMID 35999163). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Polaprezinc. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the Japanese label and the trials above”).
Interactions
Unknown: a PubMed search for human interaction studies of Polaprezinc (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Polaprezinc products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Polaprezinc's expected mass, 289.6 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Not FDA Approved (Approved in Japan as an anti-ulcer drug since 1994 (PMID 34721687)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the Japanese label and the trials above.
Contraindications & Cautions
Cautions from the label and the evidence.
Legal Status
Polaprezinc is a prescription anti-ulcer drug in Japan and a dietary supplement ingredient in the United States.
Frequently Asked Questions
?What is polaprezinc?
A complex of zinc and L-carnosine, the dipeptide of beta-alanine and histidine. It is a prescription anti-ulcer drug in Japan, first approved there in 1994.
?Is polaprezinc the same as zinc carnosine supplements?
Zinc L-carnosine is the same compound. In Japan it is a regulated prescription drug; in the US it is sold as a dietary supplement, so no regulator checks what each product contains or whether it works before it is sold.
?What dose is used in Japan?
The current Japanese label for gastric ulcer gives 75 mg twice a day for adults, after breakfast and at bedtime, adjusted for age and symptoms.
?Does it work for ulcers?
In randomised trials it healed gastric ulcers and ulcers left by endoscopic surgery about as well as rebamipide, another Japanese mucosal protectant. It has not been compared with placebo for ulcer healing in the trials read here.
?Can polaprezinc cause copper deficiency?
Yes. Zinc competes with copper for absorption; the Japanese label lists copper deficiency as a serious reaction, and serum copper fell in an eight-week pressure-ulcer trial.
?Is it approved in Europe?
No. It has no EU medicine authorisation, and EFSA could not confirm its safety as a supplement ingredient in 2022 or 2026.
References
- [clinical-trial] Shen W, et al. "Efficacy and safety of polaprezinc in the treatment of gastric ulcer: A multicenter, randomized, double-blind, double-dummy, positive-controlled clinical trial." Med Eng Phys, 2022;110:103860. PMID: 35999163.
- [clinical-trial] Jung DH, 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. PMID: 32341237.
- [review] Chen Z, et al. "A Network Meta-Analysis of Pharmacological Treatments for Gastric Mucosal Protection in Artificial Ulcers following Endoscopic Submucosal Dissection of the Stomach." Pharmacology, 2026;111(2):59-73. PMID: 41442424.
- [review] Furihata K, et al. "Efficacy and Safety of Polaprezinc (Zinc Compound) on Zinc Deficiency: A Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials Using Individual Patient Data." Nutrients, 2020;12(4). PMID: 32316581.
- [clinical-trial] Sakagami M, et al. "A zinc-containing compound, Polaprezinc, is effective for patients with taste disorders: randomized, double-blind, placebo-controlled, multi-center study." Acta Otolaryngol, 2009;129(10):1115-20. PMID: 19037756.
- [clinical-trial] Watanabe T, et al. "Polaprezinc prevents oral mucositis associated with radiochemotherapy in patients with head and neck cancer." Int J Cancer, 2010;127(8):1984-90. PMID: 20104529.
- [clinical-trial] Kitagawa J, 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;148(6):1462-1469. PMID: 32984946.
- [clinical-trial] Nakagaki M, et al. "A randomised trial of topical polaprezinc to prevent oral mucositis in patients undergoing haematopoietic stem cell transplantation (ToPaZ study)." Support Care Cancer, 2023;32(1):44. PMID: 38112867.
- [pubmed] Tsubura-Okubo M, et al. "Oral management with polaprezinc solution reduces adverse events in haematopoietic stem cell transplantation patients." Int J Oral Maxillofac Surg, 2021;50(7):906-914. PMID: 33144049.
- [clinical-trial] Watari I, 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;13:108. PMID: 23826914.
- [clinical-trial] Mahmood A, et al. "Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes." Gut, 2007;56(2):168-75. PMID: 16777920.
- [clinical-trial] Davison G, et al. "Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers." Am J Clin Nutr, 2016;104(2):526-36. PMID: 27357095.
- [review] Mahmoud A, et al. "Efficacy and Safety of Polaprezinc-Based Therapy versus the Standard Triple Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Nutrients, 2022;14(19). PMID: 36235778.
- [clinical-trial] Xiao M, et al. "Pharmacokinetics and Safety of Polaprezinc Granules Oral Administration in Healthy Chinese Volunteers Under Fasting and Fed Conditions." Clin Transl Sci, 2025;18(7):e70278. PMID: 40663018.
- [clinical-trial] Okamoto T, et al. "Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: A single-center, open-label, prospective randomized study." Ther Apher Dial, 2020;24(5):568-577. PMID: 31794152.
- [pubmed] Kumagai E, et al. "Zinc Acetate Hydrate Supplementation versus Polaprezinc Supplementation for Improving Hypozincemia in Hemodialysis Patients: A Randomized Clinical Trial." Int J Nephrol, 2023;2023:2403755. PMID: 37840640.
- [clinical-trial] Itagaki M, et al. "Efficacy of zinc-carnosine chelate compound, Polaprezinc, enemas in patients with ulcerative colitis." Scand J Gastroenterol, 2014;49(2):164-72. PMID: 24286534.
- [clinical-trial] Sakae K, et al. "Oral treatment of pressure ulcers with polaprezinc (zinc L-carnosine complex): 8-week open-label trial." Biol Trace Elem Res, 2014;158(3):280-8. PMID: 24691900.
- [clinical-trial] Yoshikawa F, et al. "Beneficial effect of polaprezinc on cardiac function post-myocardial infarction: A prospective and randomized clinical trial." Medicine (Baltimore), 2019;98(10):e14637. PMID: 30855449.
- [pubmed] EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), et al. "Safety of zinc l-carnosine as a Novel food pursuant to Regulation (EU) 2015/2283 and the bioavailability of zinc from this source in the context of Directive 2002/46/EC on food supplements." EFSA J, 2022;20(6):e07332. PMID: 35706682.
- [pubmed] EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), et al. "Safety of zinc l-carnosine as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of zinc from this source in the context of Directive 2002/46/EC." EFSA J, 2026;24(6):e10144. PMID: 42317619.
- [review] Li M, et al. "Recent advances on polaprezinc for medical use (Review)." Exp Ther Med, 2021;22(6):1445. PMID: 34721687.
- [pubmed] Ueda K, et al. "Polaprezinc (Zinc L-carnosine) is a potent inducer of anti-oxidative stress enzyme, heme oxygenase (HO)-1 - a new mechanism of gastric mucosal protection." J Pharmacol Sci, 2009;110(3):285-94. PMID: 19542683.
- [other] PubChem CID 9817450, Polaprezinc: formula C9H12N4O3Zn, molecular weight 289.6. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/9817450
- [other] Zeria Pharmaceutical. Promac D Tablets 75 (polaprezinc) package insert, 1st edition, revised July 2023 (PMDA; read October 29, 2026). https://www.pmda.go.jp/PmdaSearch/iyakuDetail/380077_2329027F1029_1_09
- [other] US FDA. Dietary Supplements (content current as of October 1, 2024): supplement firms are responsible for evaluating the safety and labeling of their products before marketing. Read October 29, 2026. https://www.fda.gov/food/dietary-supplements
- [other] NIH Office of Dietary Supplements, Dietary Supplement Label Database: US supplement labels listing zinc-carnosine as an ingredient. Searched October 29, 2026. https://dsld.od.nih.gov/
Sources & Citations
Every study on this page was read from its PubMed record on October 28 or 29, 2026. The Japanese label was read on PMDA's site on October 29, 2026; US status comes from Drugs@FDA (openFDA), the NIH Dietary Supplement Label Database and FDA's dietary supplement page, and EU status from the EMA list. Searches recorded on October 28, 2026: PubMed trials with polaprezinc in the title 20; ClinicalTrials.gov 3 (ulcer, reflux and prostate cancer studies); Drugs@FDA and the EMA list 0. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.