Zinc L-carnosine (''beta''-alanyl-L-histidinato zinc) (''N''-(3-aminopropionyl)-L-histidinato zinc), often simply called zinc carnosine, and also known as polaprezinc, is a

mucosal A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...

protective chelate compound of

zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...

and L-carnosine invented by Hamari Chemicals, Ltd. It is a quadridentate 1:1 complex of a polymeric nature. Although it contains 23% zinc and 77% L-carnosine by mass, zinc carnosine is a molecule and not a mixture of zinc and L-carnosine. It is an approved drug requiring a

medical prescription A prescription, often abbreviated or Rx, is a formal communication from a physician or other registered health-care professional to a pharmacist, authorizing them to dispense a specific prescription drug for a specific patient. Historicall ...

in Japan and

South Korea South Korea, officially the Republic of Korea (ROK), is a country in East Asia, constituting the southern part of the Korean Peninsula and sharing a land border with North Korea. Its western border is formed by the Yellow Sea, while its eas ...

where it is clinically used to treat peptic ulcer, gastric ulcers. Clinical studies have also shown its efficacy for oral mucositis, esophagitis, proctitis, taste alteration and dermatitis during and after radiation therapy, radiotherapy. In the United States, zinc carnosine is regulated as a Dietary Supplement Health and Education Act of 1994, New Dietary Ingredient, where notification with the Food and Drug Administration, US-FDA is required. In Australia, it is regulated as a Regulation of alternative medicine#Australia, complementary medicine. In Canada, it is regulated as a Natural Health Product.

Mechanisms of action

Gastrointestinal

Its mechanism of action is oxygen radical scavenging, anti-oxidation, and acceleration of gastrointestinal wound healing. It exhibits reactive oxygen species, ROS-quenching activities. It can remain in the stomach without rapid dissociation and adhere specifically to ulcerous lesions, after which L-carnosine and zinc are released to heal the ulcer. It has been shown to stimulate mucus production and to maintain the integrity of the gastric mucosal barrier. It maintains homeostasis of the gastric mucosa by prostaglandin-independent cytoprotective effects due to anti-oxidative membrane stabilizing actions, and it promotes the repair of damaged tissues by wound healing action. It exerts cytoprotection through regulating heat shock proteins and chemokines, and by stabilizing mast cells. It does so without affecting the secretion of gastric acid. It has a potential to stimulate Hsp70 expression, with overexpression of Hsp70 being found to prevent the development of inflammatory process in the large intestinal mucosa provoked by various damaging factors. It decreases p53, p21 and Bcl-2-associated X protein, Bax expression and apoptosis in the intestine after irradiation. It possesses antioxidant, anti-inflammatory, and genomic stability enhancement effects, thereby having potential in preventing gastrointestinal cancer development. It exhibits an inhibitory effect on Helicobacter pylori, ''H. pylori''.

Comparisons

Its healing efficacy against ulceration is significantly greater than that of other zinc complexes, free L-carnosine, and zinc D-carnosine (which is not sold as a supplement to consumers). The pharmacological activity of zinc L-carnosine seems attributable mainly to zinc ion, presumably transported effectively into the ulcer by means of L-carnosine together with the action of L-carnosine itself. In contrast, a simple mixture of L-carnosine and zinc had a lesser effect, presumably due to rapid diffusion of L-carnosine and zinc ion in the entire stomach. Per preclinical data, zinc L-carnosine is superior to zinc sulfide for mucositis.

Other

It has a stimulatory effect on bone formation and a restorative effect on bone loss under various pathophysiologic conditions.

Usage

Zinc L-carnosine has been used orally or as an oral rinse, lozenge or suppository. The typical clinical oral dose is 150 mg/day, containing 34 mg zinc and 116 mg L-carnosine. (The Tolerable Upper Intake Level (UL) for total zinc intake from all sources in adults is 40 mg/day.) As an mouthwash, oral rinse, it has been used three to four times a day, with or without swallowing, providing a total amount of 150 mg/day. A solution of 5% alginic acid, sodium alginate has been used. Alternatively, it has been used as a throat lozenge, lozenge containing 18.75 mg, four times a day. It has also been used as a suppository of 75 mg with Witepsol as a base.

Safety

Good clinical compliance was observed at the typical clinical oral dose of 150 mg/day, with no symptomatic side effect reported. The adverse event rate was higher at high dose zinc L-carnosine (300 mg/day) without additional benefits, and therefore high dose is not recommended. Side-effects are associated with the amount of zinc intake. According to the Japanese product monograph, safety in children below the age of 12, pregnant women and lactating women are not established (no experience in use); and the level of use in the elderly population is suggested and recommended at 100 mg zinc L-carnosine per day because of reduced digestive system function in the general elderly population; and those with poor liver functions should be under medical supervision. Those with copper deficiency should also be under medical supervision. Although zinc L-carnosine caused an increase in serum zinc level, the serum copper level and copper:zinc ratio decreased, and a case of preexisting copper deficiency deteriorated. As a mitigative, supplementation of 2 mg/day copper as glycinate chelate safely increases Cu-Zn superoxide dismutase activity. There is no evidence of a reduced tumor response to radiotherapy.

References

{{Drugs for peptic ulcer and GORD Dietary supplements Dietary minerals Zinc compounds, L-carnosine