A unique combination of zinc and L-carnosine is used in the treatment of gastric ulcers. Clinical trials have demonstrated significant improvements in subjective and objective measures, including endoscopic findings within 4 to 8 weeks.
Zinc-carnosine is an artificially produced derivative of carnosine in which a zinc ion and carnosine are bound in a 1-to-1 ratio to create a chelate compound. It has been used in Japan since 1994 for gastritis, gastric ulcers, and dyspepsia symptoms. It appears that the combination chelate is 3 times more effective than each individual ingredient alone.1
Zinc is an essential trace element and a cofactor in more than 300 endogenous biochemical reactions. It plays a role in DNA and RNA synthesis, which is significant for tissue repair. Zinc also has antibacterial effects; deficiencies have been associated with microbial infections, intestinal inflammation, delayed wound healing, and impaired immune system function.2,3
L-carnosine is a dipeptide composed of beta-alanine and L-histidine. It is naturally present in muscle and nerve cells and is thought to have antioxidant properties.4 L-carnosine also appears to help transport the zinc-carnosine to the site of ulceration, where it adheres to gastric mucosa and provides its protective effects against damaging agents.5 Researchers theorize that the adherence of the molecule to the ulcerated tissue is a result of the formation of a bond between zinc and proteins that then form mixed ligand complexes. It is also thought that zinc-carnosine remains in the gastric juice without immediately being destroyed, thus allowing it time to provide its tissue-healing effects.
Zinc-carnosine is referred to in the literature under several names, including zinc-l-carnosine, Polaprezinc, Z-103, L-CAZ , and N(3 aminopropionyl)-L-histidine. Brand names vary, but the zinc-L-carnosine is the best-studied form of zinc-carnosine. Zinc-carnosine’s protective effects on gastric mucosa and ulcerations will be the focus of this nutrient profile.
Clinical Indications: A Focus on Gastric Ulcers
Zinc-carnosine has been shown in rat studies to protect the gastric mucosa against experimentally induced ulcerations6–11 and accelerate the healing of gastric ulcers.12 More importantly, numerous studies in humans have shown promise for gastric and/or duodenal ulcers and gastritis.
In a search and review of articles in which zinc-carnosine was used for the prevention and treatment of gastritis and gastric ulcers, 8 articles (with a total of 861 patients) were reviewed; however, only 1 met all the inclusion criteria.13 A total of 258 patients completed the study in the only randomized, multi-center, placebo-controlled, double-blind trial.14 Patients with confirmed gastric ulcers were randomly assigned to 1 of 4 groups receiving 150 mg daily of zinc-carnosine extract (Z-103) or its respective placebo, or 800 mg of cetraxate hydrochloride (a mucosal protective agent) or its respective placebo. Study medications were started within 1 week of endoscopy-diagnosed gastric ulcer and were continued for 8 weeks. Symptom improvements were classified as markedly improved, moderately improved, slightly improved, unchanged, or worsened for each of the symptoms: epigastric pain, heartburn, nausea/vomiting abdominal distension, diarrhea, constipation, hematemesis, melena, and epigastric tenderness. For marked improvement, symptoms were 61% better in the zinc-carnosine group and 61.5% in the cetraxate group at 4 weeks. At 8 weeks, the zinc-carnosine group increased to 75% markedly improved compared to 72% for the cetraxate group. The endoscopic cure rate was 26.3% in the zinc-carnosine group and 16.2% in the cetraxate group at 4 weeks and 60.4% in the zinc-carnosine group and 46.2% in the cetraxate group at 8 weeks.
Zinc-carnosine is a unique product that appears to enhance the stomach's mucosal defenses, providing significant improvements in gastric ulcer patients.
Another early study involved a double-blind multicenter comparison of 3 doses of zinc-carnosine: 50 mg, 75 mg, or 100 mg twice daily.15 All 3 treatment groups showed improvement in symptoms and endoscopic healing rates. Final objective and subjective improvement rates classified as “marked improvement” were 75.4% for the 100 mg group, 71.6% for the 150 mg group, and 78.5% for the 200 mg group. Lesser but still “moderate improvement” was 86.9%, 91.0%, and 87.7% respectively for each dose. Endoscopic final cure rates were 55% for the 100 mg group, 58.0% for the 150 mg group, and 54.4% for the 200 mg group. “Markedly improved or greater” by endoscopy was 80.0%, 79.7%, and 75.0% for each group respectively.
Another early study from 1992 was a double-blind clinical trial of individuals with gastric ulcer. Zinc-carnosine (75 mg) was given twice daily for 8 weeks.16 Significant improvement of 51.4% at 4 weeks and 60.7% at 8 weeks was seen. Endoscopic findings were normal or nearly normal in 37.8% at 4 weeks and 80.0% at 8 weeks. Similar positive results were seen in another with the same dose of 75 mg twice daily.17 "Significant improvement” was 69.8% in subjective and objective symptoms. Combined with “moderately improved,” the figure was 84.9%. Endoscopic healing was 31.6% after 4 weeks and 67.4% after 8 weeks.
Three other positive studies were published after 1992 using zinc-carnosine (75 mg) twice daily.18–20
In 1997, 2 studies showed impressive results. In 1 multicenter, double-blind study, individuals received zinc-carnosine (50 mg, 75 mg, or 100 mg) twice daily for 8 weeks.21 Final “markedly improved” rates for subjective and objective symptoms were 75.4% for the 100 mg group, 71.6% for the 150 mg group, and 78.5% for the 200 mg group. Final cure rates for endoscopic findings were 55.0% for the 100 mg group, 58% for the 150 mg group, and 54.4% for the 200 mg group.
The other 1997 study compared zinc-carnosine to sucralfate for gastric ulcer.22 Individuals with gastric ulcer were given either 50 mg of zinc-carnosine three times daily or 900 mg of sucralfate three times daily. Overall improvement was 81.2% in the zinc-carnosine group and 78.4% in the sucralfate group. Endoscopic improvement was also very similar in each group: 75.5% vs 71.3% respectively.
Other potential uses for zinc-carnosine include preventing nonsteroidal anti-inflammatory drug (NSAID)–induced gut permeability, suggesting a small intestinal protective effect23 and inhibiting the inflammatory response to Helicobacter pylori.24 In H. pylori infections, the epithelial cells of the gastric mucosa secrete large amounts of interleukin (IL)-8, which recruits and activates neutrophils as a response to the attachment of the H. pylori to the cell surface.25 Zinc-carnosine appears to suppress proinflammatory cytokine expression and secretion in gastric epithelial cell cultures and to down-regulate the gastric cells inflammatory response.26
Zinc-carnosine appears to inhibit the growth of H. pylori because of the interference of zinc with urease activity. H. pylori excretes urease to enhance its own proliferation in the acidic environment of the stomach. The urease catalyzes the hydrolysis of urea to ammonia and carbon dioxide. It is this presence of ammonia and its neutralizing effect on the gastric acids, raising the pH, that allows the H. pylori to survive in the gastric mucosal cells. The now achlorhydric and neutral pH state then allows the bacteria to penetrate through the mucus to the gastric epithelium where it can survive. The urease activity is essential for the initial gastric colonization of H. pylori. When the active nickel ion center of the urease is replaced with zinc, the urease is inactivated, leading to the inhibition of H. pylori.
The most common dosage of zinc-carnosine used in the published research is 75 mg twice daily.
Adverse Effects, Cautions, and Contraindications
I have only found cautionary statements for pregnancy, nursing, or when taking prescription drugs. While there is only 16 mg of zinc in one capsule of a 75 mg zinc-carnosine pill, it may be wise to increase copper intake due to zinc’s inhibition of copper absorption.
Zinc-carnosine is a unique product that appears to enhance the stomach’s mucosal defenses, providing significant improvements in gastric ulcer patients. It also supports small intestinal mucosal integrity and inhibits the inflammatory responses in H. pylori. Zinc-carnosine may be helpful in patients who do not have gastric ulcers, but have heartburn or other symptoms as a result of gastroesophageal reflux. Given the challenge of treating this condition successfully without over the counter and prescription medications, an alternative treatment would be very valuable.
The author is on the scientific advisory board of Integrative Therapeutics. She receives no direct compensation, but Integrative Therapeutics is a sponsor of the Institute of Women’s Health and Integrative Medicine (IWHIM) that Dr. Hudson owns and directs. They are also a sponsor of the Naturopathic Education and Research Consortium (NERC), a 501 c-3 non profit organization that Dr. Hudson founded and codirects.
- Korolkiewicz R, Fujita A, Seto K, et al. Polaprezinc exerts a salutary effect on impaired healing of acute gastric lesions in diabetic rats. Dig Dis Sci. 2000:45(6):1200-1209.
- Prasad A. Zinc: an overview. Nutrition. 1995;11:93-99.
- Soderberg TA, Sunzel B, Holm S, et al. Antibacterial effect of zinc oxide in vitro. Scand J Plast Reconstr Surg Hand Surg. 1990;24(3):193-107.
- Boldyrev A. Protection of proteins from oxidatives stress: a new illusion or a novel strategy? Ann NY Acad Sci. 2005;1057:193-205.
- Hiraishi H, Sasai T, Oinuma T, et al. Polaprezinc protects gastric mucosal cells from noxious agents through antioxidant properties in vitro. Aliment Pharmacol Ther. 1999;13:261-269.
- Ueki S, Seiki M, Yoneta T, et al. Effect of Z-103 on compound 48/80-induced gastric lesions in rats. Scand J Gastroenterol. 1989. 162:202-205.
- Matsukura T, Takahashi T, Nishimura Y, et al. Characterization of crystalline L-carnosine An (II) complex (Z-103), a novel anti-gastric ulcer agent: tautomeric change of imidazole moiety upon complexation. Chem Pharm Bull. 1990;38:3140-3146.
- Arakawa T, Satoh H, Nakamura A, et al. Effects of zinc L-carnosine on gastric mucosal and cell damage caused by ethanol in rats: correlation with endogenous prostaglandin E2. Dig Dis Sci. 1990;35:559-566.
- Cho C, Luk C, Ogle C. The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats. Life Sci. 1991;49:PL189-194.
- Yoshikawa T, Naito Y, Tanigawa T, et al. Effect of zinc-carnosine chelate compound (Z-103), a novel antioxidant, on acute gastric mucosal injury induced by ischemia-reperfusion in rats. Free Radic Res Commun. 1991;14:289-296.
- Ito M, Shii D, Segami T, et al. Preventive actions of N-(3-aminopropionyl)-L-histidinato zinc (Z-103) through increases in the activities of oxygen-derived free radical scavenging enzymes in the gastric mucosa on ethanol-induced gastric mucosal damage in rats. Jpn J Pharmacol. 1992;59:267-274.
- Ito M, Tanaka T, Suzuki Y. Effect of N-(3-aminopropionyl)-L-histidinato zinc (Z-103) on healing and hydrocortisone-induced relapse of acetic acid ulcers in rats with limited food-intake-time. Jpn J Pharmacol. 1990;52:513-521.
- Wollschlaeger B. Zinc-carnosine for the management of gastric ulcers: clinical application and literature review. JANA. 2003;6(2):33.
- Miyoshi A, Namiki A, Asagi S. Clinical evaluation of Z-103 on gastric ulcers: a multicenter double blind comparative study with cetraxate hydrochloride. Jpn Pharm Ther. 1992;20(1):199-223.
- Miyoshi A, Matsuo H, Miwa T, et al. Clinical evaluation of Z-103 in the treatment of gastric ulcer, a multicenter double-blind dose finding study. Jpn Pharmacol Ther. 1992;20(1):181-197.
- Hayakawa A, Inoue M, Kunizaki M, et al. Clinical evaluation of Z-103 on gastric ulcer. Jpn Pharmacol Ther. 1992;20(1).
- Morise K, Oka Y, Suzuki T, et al. Clinical evaluation of Z-103 in the treatment of gastric ulcer. Jpn Pharmacol. 1992;20(1):235-244.
- Suzuki Y, Kasanuki J, Yoshida H. Clinical evaluation of Z-103 on gastric ulcer Results of Phase II general clinical trial. Jpn Pharmacol Ther. 1992; 20(1).
- Misawa T, Chijiiwa Y, Nawada A, et al. Clinical study of Z-103 clinical effects on gastric ulcer and endocrine function. Jpn Pharmacol Ther. 1992;20(1):245-254.
- Amakawa T. Clinical evaluation of Z-103 on gastric ulcer- results of phase III general clinical trial. Jpn Pharmacol Ther. 1992;20(1):199-223.
- Miyoshi A, Namiki M, Iwasaki A, et al. Clinical evaluation of Z-103 in the treatment of gastritis. A multicenter double-blind dose finding study. Jpn Pharmacol Ther. 1997;25(5):1403-1442.
- Nakajima M. Clinical evaluation of Z-103 on gastritis. A double-blind controlled study using sucralfate as a comparator. Pharmacol Ther. 1997;25(4):325-366.
- Mahmood A, Fitzgerald A, Marchbank T, et al. Zinc carnosine, a health food supplement that stabilizes small bowel integrity and stimulates gut repair processes. Gut. 2007;56(2):168-175.
- Handa O, Yoshida N, Tanaka Y, et al. Can J Gastroenterol. 2002;16(11):785-789.
- Harada A, Mukaida N, Matsushima K. Interleukin 8 as a novel target for intervention therapy in acute inflammatory diseases. Mol Med Today. 1996;2(11):482-489.
- Shimada T, Watanabe N, Ohtsuka Y, et al. Polaprezinc down-regulates proinflammatory cytokine-induced nuclear factor- kappB activation and interleukin-8 expression in gastric epithelial cells. J Pharmacol Exp Ther. 1999;291(1):345-352.