Benefits
Gut permeability under an NSAID or exercise challenge
Gut permeability can be measured with a sugar test (the lactulose:rhamnose ratio). In 10 healthy volunteers taking the NSAID indomethacin, the ratio roughly tripled on placebo but did not rise significantly with zinc carnosine. In 8 healthy volunteers it cut an exercise-induced rise by about 70%. Both studies were tiny, measured a lab marker rather than symptoms, and did not name the PepZinGI brand.
Studied as a prescription ulcer drug in patients
The same compound is a Japanese prescription drug for gastric ulcer (polaprezinc). In a trial of 224 ulcer patients at 10 hospitals in China, 8 weeks of polaprezinc gave endoscopic healing rates similar to the ulcer drug rebamipide (81% vs 74%, not a significant difference), with no placebo group. This is about a diagnosed ulcer under a doctor's care, not gut health in healthy people.
Studied as an add-on to H. pylori antibiotic therapy
In an open-label trial sponsored by a polaprezinc maker (303 patients completed), adding polaprezinc to 14 days of triple antibiotic therapy raised the eradication rate from 59% to about 76 to 77%. A meta-analysis of 3 such trials rated the certainty of this evidence very low. Heartburn and other symptoms improved in every arm, antibiotics alone included. H. pylori needs medical treatment.
Small-bowel findings in long-term aspirin users
In a pilot study of 20 patients aged 62 to 86 on long-term low-dose aspirin with small-bowel injury on capsule endoscopy, polaprezinc 150 mg/day for 4 weeks reduced lesion counts within its own group, while the untreated group did not change. The change in overall capsule score did not differ between groups, and there was no placebo.
Mechanism of action
Acts at the stomach lining (lab and animal data)
An independent review summarizes animal and laboratory work attributing the compound's effects in ulcer models to binding at the ulcer site, local healing, lower inflammatory cytokines including TNF-alpha, and higher heat shock proteins. These are not human outcomes.
Cell repair and tight-junction effects in cell lines
In human gut cell lines, zinc carnosine increased cell migration and growth about threefold, and in heat-stressed gut cells it raised total occludin and reduced claudin and occludin phosphorylation, changes linked with tighter junctions. Tight-junction proteins were not measured in people.
Clinical trials
Randomized, double-blind, placebo-controlled 4-arm crossover (placebo, zinc carnosine, bovine colostrum, or both, 14 days each) with added cell-line experiments; zinc carnosine 37.5 mg twice daily per the trial registration; brand not named (Davison et al. 2016, Am J Clin Nutr).
8 healthy volunteers (recreationally active men per the registration) doing 20 minutes of hard treadmill running.
Exercise raised body temperature 2°C and tripled the 5-hour urinary lactulose:rhamnose ratio. After 14 days, zinc carnosine or colostrum cut that rise by about 70%, and the combination worked faster. A lab marker in 8 people, not symptoms or performance; tight-junction protein changes were seen only in cell lines.
Multicenter, randomized, double-blind, double-dummy trial comparing polaprezinc (zinc-L-carnosine, brand not named) with the ulcer drug rebamipide (Shen et al. 2022, Med Eng Phys).
224 patients with gastric ulcer at 10 clinical centers in China (111 polaprezinc, 113 rebamipide).
After 8 weeks, endoscopy-confirmed effective rates were 81.5% with polaprezinc and 74.3% with rebamipide (P = 0.16), no significant difference. Symptom improvement and adverse events were similar. With no placebo arm, the trial shows the two drugs performed alike, not how either compares with no treatment.
Randomized crossover in healthy volunteers plus cell-line, rat and mouse experiments; the paper does not name the PepZinGI brand (Mahmood et al. 2007, Gut).
10 healthy volunteers taking indomethacin 50 mg three times daily for 5 days with zinc carnosine 37.5 mg twice daily or placebo.
On placebo, indomethacin raised the lactulose:rhamnose ratio about threefold (0.35 to 0.88); with zinc carnosine there was no significant rise. A lab marker in 10 people over 5 days, not symptoms. The senior author disclosed giving evidence to the US FDA on zinc carnosine health claims.
Prospective, multicenter, randomized, open-label trial of polaprezinc (Ruilaisheng, Broadwell Pharmaceutical, the sponsor) added to clarithromycin-based triple therapy (Tan et al. 2017, PLoS One).
Treatment-naive patients with H. pylori gastritis in 11 Chinese cities; 303 completed (polaprezinc 75 mg or 150 mg twice daily plus antibiotics, or antibiotics alone, for 14 days).
Intention-to-treat eradication was 77.0% and 75.9% with polaprezinc vs 58.6% with antibiotics alone (P < 0.01). The higher dose added no benefit and had more adverse events (5.1% vs 2.8%). Symptoms improved from baseline in all three arms.