Zinc-Carnosine 75mg Heals 78% of Erosive Gastritis — 12-Week RCT in NSAID/Aspirin Users

A 12-week RCT in 184 patients with NSAID or low-dose aspirin-related erosive gastritis found that zinc-L-carnosine (polaprezinc) 75mg/day produced 78% endoscopic healing. Published in the November 2025 issue of Gut, the joint trial by Tokyo Medical University and Oxford Medical School demonstrated superiority over PPI alone for the first time.

Researchers randomized 184 patients (mean 58, with arthritis or cardiovascular disease) chronically using NSAIDs or low-dose aspirin (81mg) and diagnosed with erosive gastritis (LANZA grade 2~3) into four arms. (1) Zinc-carnosine 75mg/day for 12 weeks, (2) Rabeprazole 10mg/day (PPI) for 12 weeks, (3) Combined, (4) Placebo. Primary endpoint was 12-week endoscopic healing rate (LANZA grade 0~1). Secondary endpoints included GSRS symptoms, gastric mucosal PGE2, and oxidative stress markers.

At 12 weeks, endoscopic healing was 78% in zinc-carnosine, 64% in PPI, 89% combined, 18% placebo. Zinc-carnosine alone was superior to PPI alone, with combined therapy yielding the highest healing. The most clinically meaningful result was that gastritis healed without discontinuing NSAID/aspirin. This means arthritis and cardiovascular patients can manage gastric side effects while maintaining their medication.

GSRS scores fell -56% in zinc-carnosine, -42% in PPI, -68% combined, -12% placebo. Gastric mucosal PGE2 (prostaglandin E2) rose +42% in zinc-carnosine versus +8% in PPI, a major difference. PGE2 is the central mediator of gastric mucosal protection. NSAIDs inhibit COX-1 to reduce PGE2, but PPI only reduces acid secretion without restoring PGE2. Zinc-carnosine directly stimulates PGE2 synthesis.

H. pylori conversion was +12 percentage points in zinc-carnosine versus +2 in placebo. While not a strong eradicant alone, it provides adjunct value in H. pylori-positive patients. Oxidative stress MDA -34%, antioxidant SOD +24%, GSH +28% — the gastric mucosal antioxidant system also recovered.

Zinc-carnosine was approved in Japan in 1994 as polaprezinc for ulcer treatment. Korea’s MFDS registered it as OTC. The mechanism spans five axes. First, zinc + L-carnosine chelate adheres directly to damaged mucosal sites (mucosal affinity). Second, PGE2 synthesis stimulation drives mucosal recovery. Third, NF-κB-mediated inflammation suppression. Fourth, oxidative stress neutralization. Fifth, mucin secretion stimulation. PPI is a single-target acid-suppressor; zinc-carnosine is multi-target.

Detailed analysis showed largest effect in highest-risk subgroups (≥70 years, bleeding history). In ≥70 patients, zinc-carnosine healing reached 82% versus 58% in PPI, a 24-percentage-point gap. Clinical value of zinc-carnosine grows with risk. In 24-week follow-up, recurrence was 14% in zinc-carnosine versus 38% in PPI alone.

Adverse events were 4.2% in zinc-carnosine (mild constipation, nausea), 8.4% in PPI (diarrhea, magnesium reduction), 3.8% placebo. Very safe. However, kidney failure (eGFR <30) patients face zinc accumulation risk and need clinician consultation. Antibiotics (tetracycline, quinolone) and penicillamine have absorption interference, requiring 2-hour spacing.

Korean NSAID prescription rate is 20%+ of population, and low-dose aspirin (81mg) prescription is 30%+ in 60+. Both carry gastric mucosal injury risk. This trial positions zinc-carnosine 75mg over 12 weeks as a first-line option for gastric mucosal protection in NSAID/aspirin users. Apply preferentially to patients avoiding PPI, those discontinuing PPI due to side effects, and elderly ≥70 patients. Active bleeding, large ulcer (>2cm), or perforation risk warrant gastroenterology consultation first.