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 In chemistry, a mixture is a material made up of two or more different chemical substances which are not chemically bonded. A mixture is the physical combination of two or more substances in which the identities are retained and are mixed in the ...

of zinc and L-carnosine. It is an

approved drug An approved drug is a medicinal preparation that has been validated for a therapeutic use by a ruling authority of a government. This process is usually specific by country, unless specified otherwise. Process by country United States In the ...

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. Historica ...

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...

and

South Korea South Korea, officially the Republic of Korea (ROK), is a country in East Asia, constituting the southern part of the Korea, Korean Peninsula and sharing a Korean Demilitarized Zone, land border with North Korea. Its western border is formed ...

where it is clinically used to treat

gastric ulcers Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines i ...

. Clinical studies have also shown its efficacy for oral mucositis, esophagitis, proctitis, taste alteration and dermatitis during and after

radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...

. In the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

, zinc carnosine is regulated as a New Dietary Ingredient, where notification with the US-FDA is required. In

Australia Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...

, it is regulated as a

complementary medicine Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability, or evidence from clinical trials. Complementary medicine (CM), complementary and alt ...

. In

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...

, it is regulated as a

Natural Health Product The term natural health product (NHP) is used in Canada to describe substances such as vitamins and minerals, herbal medicines, homeopathic preparations, energy drinks, probiotics, and many alternative and traditional medicines. A 2010 survey showe ...

Mechanisms of action

Gastrointestinal

Its mechanism of action is oxygen radical scavenging, anti-oxidation, and acceleration of gastrointestinal wound healing. It exhibits 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 Cytoprotection is a process by which chemical compounds provide protection to cells against harmful agents. Gastric cytoprotectant A gastric cytoprotectant is any medication that combats ulcers not by reducing gastric acid but by increasing mucosa ...

through regulating

heat shock protein Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including expo ...

s and

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...

s, and by stabilizing

mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...

s. It does so without affecting the secretion of gastric acid. It has a potential to stimulate

Hsp70 The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an importa ...

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 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

p21 p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated ...

and Bax expression and

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

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 ''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 Zinc sulfide (or zinc sulphide) is an inorganic compound with the chemical formula of ZnS. This is the main form of zinc found in nature, where it mainly occurs as the mineral sphalerite. Although this mineral is usually black because of various i ...

for

mucositis Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy and radiotherapy treatment for cancer. Mucositis can occur anywhere along the gastrointestinal ( ...

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 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%

sodium alginate Alginic acid, also called algin, is a naturally occurring, edible polysaccharide found in brown algae. It is hydrophilic and forms a viscous gum when hydrated. With metals such as sodium and calcium, its salts are known as alginates. Its colou ...

has been used. Alternatively, it has been used as a

lozenge Lozenge or losange may refer to: * Lozenge (shape), a type of rhombus *Throat lozenge, a tablet intended to be dissolved slowly in the mouth to suppress throat ailments *Lozenge (heraldry), a diamond-shaped object that can be placed on the field of ...

containing 18.75 mg, four times a day. It has also been used as a

suppository A suppository is a dosage form used to deliver medications by insertion into a body orifice where it dissolves or melts to exert local or systemic effects. There are three types of suppositories, each to insert into a different sections: rectal su ...

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 Copper deficiency, or hypocupremia, is defined either as insufficient copper to meet the needs of the body, or as a serum copper level below the normal range. Symptoms may include fatigue, decreased red blood cells, early greying of the hair, a ...

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

deteriorated. As a mitigative, supplementation of 2 mg/day copper as glycinate chelate safely increases Cu-Zn

superoxide dismutase Superoxide dismutase (SOD, ) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide () radical into ordinary molecular oxygen (O2) and hydrogen peroxide (). Superoxide is produced as a by-product of oxygen me ...

activity. There is no evidence of a reduced tumor response to

References

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