Benefits
Prescription use in Japan and a 224-patient comparison trial
In Japan, polaprezinc has been a prescription drug for gastric ulcer since 1994 (Promac). In a trial of 224 ulcer patients at 10 hospitals in China, 8 weeks of polaprezinc gave endoscopy-confirmed response rates similar to rebamipide, another ulcer drug (81% vs 74%, not a significant difference). There was no placebo group. This is research on treating a diagnosed ulcer, not on gut health in healthy people.
Gut permeability under an NSAID or exercise challenge
Gut permeability can be measured with a sugar-absorption test (the lactulose:rhamnose ratio); "leaky gut" is not an established diagnosis. In 10 healthy volunteers given the NSAID indomethacin for 5 days, permeability roughly tripled on placebo but did not rise significantly with zinc carnosine (37.5 mg twice daily). In 8 volunteers, 14 days of zinc carnosine cut the exercise-induced rise by about 70%. Both were tiny lab-marker studies.
Use alongside prescribed triple antibiotic therapy
In a 2017 open-label trial in China sponsored by a polaprezinc maker (303 patients completed), adding polaprezinc to 14 days of triple antibiotic therapy for H. pylori raised eradication from 59% to about 76 to 77%. A 2022 meta-analysis of that trial and two smaller ones (396 patients) found higher eradication but rated the evidence very low certainty. This is a drug given with prescribed antibiotics, not a self-treatment.
Small-bowel lining in long-term low-dose aspirin users
In a Japanese pilot study, 20 patients aged 62 to 86 on long-term low-dose aspirin with small-bowel injury on capsule endoscopy took polaprezinc 150 mg a day or no treatment for 4 weeks. Lesion counts fell within the polaprezinc group but not the untreated group, yet the overall capsule-endoscopy score did not differ between groups, and there was no placebo. It does not show protection for healthy painkiller users.
Mechanism of action
Sticks to the gut lining for local action
The chelate has a high affinity for the mucous glycoproteins that coat the stomach and intestine, so it adheres to damaged tissue and releases zinc and carnosine locally instead of being quickly absorbed and cleared.
Zinc supports tissue repair
In cell-culture work, zinc carnosine increased the growth and migration of gut-lining cells and raised levels of the tight-junction protein occludin. These effects come from cell and animal studies.
Carnosine calms oxidative and inflammatory stress
In cell and animal studies, carnosine mops up reactive oxygen species, binds metal ions and dampens NF-kB inflammatory signaling. These effects have not been shown as clinical outcomes in people.
Clinical trials
Multicenter (10 hospitals in China), randomized, double-blind, double-dummy trial comparing polaprezinc (zinc-L-carnosine) with the ulcer drug rebamipide for gastric ulcer healing. (Shen et al. 2022, Med Eng Phys)
224 patients with gastric ulcer at 10 hospitals 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), which is no significant difference; the abstract reports no non-inferiority margin. Symptom improvement and adverse events were similar. With no placebo arm, the trial shows the two ulcer drugs performed alike, not how much either beats no treatment.
Combined human and experimental study of oral zinc carnosine on gut integrity and repair. (Mahmood et al. 2007, Gut)
10 healthy volunteers in a randomized crossover (zinc carnosine 37.5 mg twice daily or placebo, each with indomethacin 50 mg three times daily for 5 days). The rest of the paper is cell-line work and rat and mouse injury models.
On placebo, indomethacin raised the lactulose:rhamnose permeability ratio about threefold (0.35 to 0.88); with zinc carnosine there was no significant rise. This is a lab marker in 10 people over 5 days, not a measure of symptoms. The effects on cell repair and on stomach and intestinal injury were shown only in cell lines, rats and mice. The senior author disclosed giving evidence to the US FDA on health claims for zinc carnosine.
Prospective, multicenter, randomized, open-label (no placebo) trial in 11 Chinese cities, sponsored by polaprezinc maker Broadwell Pharmaceutical, of polaprezinc added to clarithromycin-based triple therapy for H. pylori-associated gastritis. (Tan et al. 2017, PLoS One)
Treatment-naive patients with Helicobacter pylori gastritis in 11 Chinese cities; 303 completed (polaprezinc 150 mg/day, polaprezinc 300 mg/day, or antibiotics alone, for 14 days).
Intention-to-treat eradication was 77.0% (150 mg/day) and 75.9% (300 mg/day) with polaprezinc versus 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. This tested a drug given alongside prescribed antibiotics.