Zinc-L-Carnosine (Polaprezinc): Independent Evidence on Gastric Ulcer, H. pylori & Mucositis

Zinc-L-carnosine (polaprezinc, Promac) is a chelate designed to deliver zinc directly to damaged gastric tissue, and it has decades of use as an approved ulcer drug in Japan. In humans, the credible evidence clusters around three specific uses: healing gastric ulcers, boosting H. pylori eradication rates as an add-on to antibiotics, and reducing oral mucositis during cancer treatment. The popular supplement-marketing claim that it "seals" or "heals" a leaky gut in general, healthy populations is built on a single tiny, manufacturer-conflicted trial and otherwise-excluded animal and in-vitro data. This article covers what zinc-L-carnosine is, the forms sold, the claim-by-claim human evidence, safety and interactions, funding influences, and regulatory status.

Table of contents

• Evidence summary
• What zinc-L-carnosine is
• Forms and grades
• How it works
• Hype vs. evidence
• Benefits by claim
• What works and what does not
• Risks and side effects
• All interactions
• Who should avoid zinc-L-carnosine
• Dosage and how to take it
• Animal and in-vitro evidence (excluded from conclusions)
• Independent funding tracing
• Frequently asked questions
• Sources and funding notes

What zinc-L-carnosine is

Zinc-L-carnosine is a 1:1 chelate of zinc and L-carnosine (the dipeptide β-alanyl-L-histidine), with the pharmaceutical code name Z-103 and a molecular weight of approximately 289.6 g/mol (PubChem CID 6918055). Unlike a simple zinc salt, the chelate structure makes the compound muco-adherent: it binds preferentially to ulcerated or inflamed gastric mucosa, where zinc is released slowly and locally rather than being absorbed and distributed systemically all at once. This targeted, slow-release mechanism is the basis for combining zinc’s role in tissue repair and antioxidant defense with carnosine’s acid-buffering and free-radical-scavenging properties directly at the site of gastric injury (PubChem CID 6918055; Li et al., "Recent advances on polaprezinc," Experimental and Therapeutic Medicine, 2021).

The compound is best known under its pharmaceutical name polaprezinc and brand name Promac. It has been an approved prescription/OTC anti-ulcer drug in Japan since 1994, decades before it appeared as an unregulated dietary supplement in Western markets.

Forms and grades

This drug-versus-supplement split matters: in Japan, polaprezinc went through formal pharmaceutical approval trials. In Western markets, the same molecule is sold with none of that regulatory oversight, at doses derived from the Japanese drug literature rather than from independent Western trials.

How it works

The proposed mechanism is twofold: (1) the zinc-carnosine complex adheres to damaged mucosal tissue via affinity for exposed proteins in ulcerated areas, concentrating zinc delivery where healing is needed rather than diluting it throughout the body, and (2) zinc supports metallothionein induction, antioxidant enzyme activity, and epithelial repair, while carnosine contributes anti-inflammatory and radical-scavenging effects and buffers local pH (Li et al., Exp Ther Med 2021). Much of this mechanistic detail comes from cell and animal models rather than human mechanistic studies, so it should be read as a plausible explanation for the clinical trial results below — not as independent proof in its own right.

Hype vs. evidence

Supplement marketing for zinc-L-carnosine routinely blurs together its genuinely evidence-backed drug indications with much weaker or unsupported general "gut health" claims. This is the single most frequently cited "ZnC heals the gut" study behind most such marketing, and it deserves close scrutiny.

Mahmood et al. (Gut, 2007) ran a randomized crossover trial with only n=10 healthy volunteers. Five days of indomethacin (50 mg three times daily) roughly tripled small-bowel permeability (measured via the lactulose:rhamnose ratio), and ZnC 37.5 mg twice daily largely prevented this permeability increase compared with placebo (Mahmood et al., Gut 2007, full text; PMID 16777920).

A single n=10 crossover trial with manufacturer involvement is a thin foundation for the broad "protects your gut from NSAIDs" claims this study is routinely used to support in marketing materials. Outside this narrow crossover, broader claims that zinc-L-carnosine "heals" or "seals" leaky gut in general or healthy populations rest on in-vitro and animal wound-healing models, which are excluded from this article’s conclusions as they are not human evidence. There is insufficient independent human-trial evidence to support general leaky-gut repair claims for ZnC.

Benefits by claim

Gastric ulcer and gastritis

Polaprezinc is an established anti-ulcer drug in Japan, and the best modern evidence comes from a multicenter randomized controlled trial (n=224, 10 centers) in which polaprezinc was found non-inferior to rebamipide — a standard mucoprotective comparator drug — for endoscopically confirmed gastric-ulcer healing at 8 weeks: 81.5% healing with polaprezinc versus 74.3% with rebamipide (p=0.16), with comparable symptom improvement and safety profiles (multicenter non-inferiority RCT, PMID 35999163). A separate RCT examining ulcers induced by endoscopic submucosal dissection likewise found polaprezinc plus a proton-pump inhibitor performed comparably to rebamipide plus a PPI (ESD-induced ulcer RCT, PMC7960146).

Grade: Moderate. The effect is real and replicated across more than one trial, but the evidence base is concentrated in Japan and industry-linked sources, which tempers confidence relative to what an independently funded, multi-region trial program would provide.

H. pylori eradication (adjunct only)

The most independent and reassuring evidence for ZnC comes from this indication. A systematic review and meta-analysis of 3 RCTs (n=396) found that adding polaprezinc to standard triple therapy for H. pylori significantly improved eradication rates: pooled odds ratio 2.01 (95% CI 1.27–3.21, p=0.003) by intention-to-treat, and 2.65 (95% CI 1.55–4.54, p=0.0004) per-protocol, with no increase in adverse events (OR 1.06, 95% CI 0.55–2.06) (Abdelhamid et al., meta-analysis, PMC9573391). This meta-analysis was PROSPERO-registered (CRD42022349231) and states no commercial funding — making it the most independent anchor in the entire ZnC evidence base.

A separate Egyptian RCT (n=92) found that a zinc-carnosine-fortified bismuth quadruple therapy raised eradication rates to 93.5% versus 69.6% for standard triple therapy (p=0.003) — though because bismuth was added alongside ZnC, this trial cannot cleanly isolate ZnC’s individual contribution (Egyptian RCT, PMC8727261).

Grade: Moderate, specifically as an adjunct to standard antibiotic therapy — not as a standalone eradication treatment. This is the indication with the cleanest funding profile of the entire ZnC literature.

Oral mucositis in cancer treatment

Several concordant RCTs, largely conducted in Japan, show that polaprezinc/ZnC reduces the severity of oral mucositis caused by chemotherapy and head-and-neck radiotherapy:

• A head-and-neck radiotherapy RCT found ZnC oral rinse (37 mg/dL, four times daily, roughly 150 mg/day) reduced grade-3 mucosal mucositis from 40% to 29%, and symptomatic grade-3 mucositis from 60.7% to 39.3% (summarized in Hewlings & Kalman, Nutrients, 2020).
• A multi-institutional RCT of polaprezinc for preventing oral mucositis in patients undergoing chemotherapy plus hematopoietic stem-cell transplantation found a protective benefit (Kitagawa et al., International Journal of Cancer, 2021).
• A radiation-induced mucositis RCT in head-and-neck cancer patients reported reduced severity with polaprezinc treatment (Doi et al., Molecular and Clinical Oncology, 2014).

Grade: Moderate. This is arguably ZnC’s best-supported indication after gastric ulcer — several independent-enough RCTs point the same direction — though the trials are individually small, geographically concentrated in Japan, and some are industry-adjacent.

Functional dyspepsia and GERD

Polaprezinc is used clinically in Japan for gastritis-related dyspeptic symptoms, but robust, independent randomized trials specifically targeting functional dyspepsia or gastroesophageal reflux disease are lacking (Li et al. review, PMC8549086). Grade: Weak/Insufficient — this indication is extrapolated from the ulcer/gastritis literature rather than directly tested.

What works and what does not

Risks and side effects

The dominant long-term safety concern with zinc-L-carnosine is the zinc component itself, not the carnosine.

All interactions

Who should avoid zinc-L-carnosine

• Anyone taking quinolone or tetracycline antibiotics, or penicillamine should separate dosing from zinc-L-carnosine by at least 2 hours to avoid reduced drug absorption (NIH ODS Zinc).
• People using ZnC chronically at supplement doses should be aware of the cumulative zinc load, which approaches or exceeds the adult tolerable upper intake level, and the associated risk of copper depletion (NIH ODS Zinc; StatPearls NBK554548).
• Pregnant or breastfeeding individuals should avoid supraphysiologic dosing absent independent human safety data and medical guidance (NIH ODS Zinc).
• Anyone expecting general "leaky gut" repair or broad NSAID gut protection should not rely on zinc-L-carnosine, since the human evidence for these uses is a single small, manufacturer-conflicted trial and otherwise-excluded animal/in-vitro data (PMC1856764).
• Anyone with known copper deficiency or at elevated risk of it should use ZnC only under medical supervision, given the shared zinc-copper absorption pathway (NIH ODS Zinc).

Dosage and how to take it

Animal and in-vitro evidence (excluded from conclusions)

In keeping with a human-trial-only evidence standard, the following were identified during research and explicitly excluded from all efficacy and safety conclusions in this article:

• Animal studies — excluded: Rat gastric-damage (indomethacin/restraint) and mouse small-intestine models within Mahmood et al. (PMC1856764); rat indomethacin gastric-injury/hydrotalcite studies (PMC6487128).
• In-vitro (non-human) evidence: None was used to support any efficacy or safety conclusion in this article. The in-vitro portions of Mahmood et al. (human HT29 plus rat/canine cell lines) are mentioned only to characterize that study and are not relied upon for conclusions.
• Conflicted/downgraded sources used for context only: Polaprezinc reviews authored by pharmaceutical-company employees, such as contributors affiliated with Jilin Broadwell Pharmaceutical (PMC8549086).

Independent funding tracing

Understanding who funded the evidence behind zinc-L-carnosine is essential to interpreting it correctly:

• Zeria Pharmaceutical (Japan) is the originator of polaprezinc (Promac/Z-103). A large share of the foundational gastric-ulcer efficacy data is Zeria-sponsored or otherwise Japan-industry-linked (Li et al. review, PMC8549086).
• The pivotal small human NSAID-permeability study (Mahmood et al., 2007) had a Lonza co-author — Lonza manufactures zinc-L-carnosine commercially, representing a direct supplement-industry conflict on the one human data point in that paper (PMC1856764).
• The H. pylori adjunct meta-analysis and the 2022 multicenter non-inferiority ulcer RCT are comparatively more independent and represent the most trustworthy anchors in the ZnC literature (PMC9573391; PMID 35999163).
• Review articles used for background context, such as the Experimental and Therapeutic Medicine review, include pharmaceutical-industry-affiliated authors and are treated here as context rather than independent confirmation (Li et al., PMC8549086).

Regulatory status

• Japan and parts of Asia: Approved prescription/OTC drug (Promac) for gastric ulcer and gastritis since 1994 (PubChem CID 6918055).
• United States: Not an FDA-approved drug; sold as a dietary supplement (zinc-L-carnosine), meaning it has not gone through drug-level efficacy and safety review.
• European Union: Not an approved medicine EU-wide; regulatory status depends on the member state and may fall under food-supplement or novel-food categories, which EFSA governs (EFSA Novel Food).

Frequently asked questions

Does zinc-L-carnosine heal "leaky gut"?

Only very narrowly. The main human evidence relevant to gut permeability is a single n=10 crossover trial showing ZnC largely prevented NSAID-induced permeability increases — but that trial has a co-author affiliated with a commercial ZnC manufacturer (Mahmood et al., Gut 2007). For general "leaky gut" claims in healthy people or non-specific complaints, there is insufficient independent human-trial evidence, and most marketing relies on excluded animal and in-vitro data.

Does zinc-L-carnosine heal gastric ulcers?

Yes, with reasonable confidence. A multicenter RCT found it non-inferior to rebamipide, a standard mucoprotective drug, with 81.5% vs. 74.3% healing at 8 weeks (PMID 35999163). This is polaprezinc’s original, approved drug indication in Japan.

Does zinc-L-carnosine help eradicate H. pylori?

As an adjunct, yes. A meta-analysis of 3 RCTs found adding polaprezinc to standard triple therapy significantly improved eradication rates (pooled OR 2.01 by intention-to-treat), without increasing adverse events (PMC9573391). It is not a standalone treatment and should be combined with prescribed antibiotics.

Is zinc-L-carnosine safe to take long-term?

Short courses (up to about 8 weeks) at typical doses are generally well tolerated in trials. Long-term daily use approaches or exceeds the adult zinc tolerable upper intake level of 40 mg/day, raising the risk of copper depletion, which can cause anemia, neutropenia, and, in severe chronic cases, myeloneuropathy (NIH ODS Zinc; StatPearls NBK554548).

Is zinc-L-carnosine FDA-approved?

No. It is an approved prescription/OTC drug (Promac) in Japan and parts of Asia, but in the United States it is sold only as an unregulated dietary supplement, without FDA drug-level efficacy or safety review (PubChem CID 6918055).

Does zinc-L-carnosine protect against NSAID-induced gut damage?

The evidence is weak. The claim rests on a single n=10 crossover trial in which one co-author was affiliated with Lonza, a commercial manufacturer of zinc-L-carnosine — a direct conflict of interest on the only human data in that paper (PMC1856764). This is a thin foundation for the broad protective claims often made in marketing.

Sources and funding notes

• PubChem. Polaprezinc/Promac. CID 6918055
• Li Y, et al. Recent advances on polaprezinc. Experimental and Therapeutic Medicine. 2021. PMC8549086
• Hewlings S, Kalman D. A review of zinc-L-carnosine and its positive effects on gastrointestinal health. Nutrients. 2020. PMC7146259
• Multicenter randomized controlled non-inferiority trial of polaprezinc vs. rebamipide for gastric ulcer healing. PMID 35999163
• RCT of polaprezinc plus PPI vs. rebamipide plus PPI for endoscopic-submucosal-dissection-induced ulcers. PMC7960146
• Abdelhamid A, et al. Polaprezinc as an adjunct to Helicobacter pylori eradication therapy: systematic review and meta-analysis. PMC9573391
• Egyptian RCT of zinc-carnosine-fortified bismuth quadruple therapy for H. pylori eradication. PMC8727261
• Kitagawa Y, et al. Multi-institutional RCT of polaprezinc for prevention of oral mucositis in chemotherapy plus hematopoietic stem-cell transplantation. International Journal of Cancer. 2021
• Doi H, et al. Polaprezinc for radiation-induced oral mucositis in head-and-neck cancer. Molecular and Clinical Oncology. 2014. PMC4360858
• Mahmood A, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007. PMC1856764 (PMID 16777920)
• Nature Clinical Practice Gastroenterology & Hepatology commentary on Mahmood et al.
• Rat indomethacin gastric-injury/hydrotalcite study (animal; excluded from conclusions). PMC6487128
• NIH Office of Dietary Supplements. Zinc: Fact Sheet for Health Professionals
• Zinc Toxicity. StatPearls, NIH National Library of Medicine. NBK554548
• EFSA. Novel Food

Last reviewed: July 4, 2026.