You’ve heard of zinc, maybe you’ve heard of carnosine, but probably have never heard of zinc carnosine.
For anyone dealing with gut issues, zinc carnosine holds some promise. Whether it’s an H pylori infection, ulcers, gastritis or intestinal inflammation, the unique structure of this supplement has been shown to help.
This article breaks it all down for you with a review of the gut health issues zinc carnosine can support, dosages and more.
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What is zinc carnosine?
Zinc carnosine is a novel compound that’s shown interesting results in relieving symptoms of dyspepsia and improving Helicobacter pylori infection among other benefits.
It’s been clinically researched for over 20 years with over 20 published studies.
Zinc carnosine goes by many names: Polaprezinc, Promac, L-CAZ, and Z-103 and is a chelate of a zinc ion plus carnosine (a dipeptide of beta-alanine and l-histidine) in a 1:1 ratio.
This unique combination of l-carnosine and zinc has been well studied in both controlled human trials and animal studies.
Its unique structure is estimated to be three times more effective when it comes to healing than the individual ingredients it’s made up of; zinc and carnosine (1, 2, 3).
For this reason, zinc carnosine has been shown to have greater ulcer healing effects than cimetidine; a first-generation anti-ulcer drug with significant drug-drug interactions (4, 5, 6).
It’s actually been used in Japan as a treatment for a variety of gastric-related issues since 1994.
Why zinc?
Zinc is an essential mineral that naturally occurs in some foods, added to others via fortification, and is available as a nutritional supplement.
Zinc is a cofactor, meaning it facilitates biochemical and physiological reactions involved in a variety of activities such as maintaining a sense of smell and taste, wound healing, playing a role in your immune function, supporting cell division, DNA repair and more (7).
As a cofactor, zinc is a true multitasker. It helps out with over 300 different, yet interdependent enzymatic reactions, not the least of which is immunity, DNA repair, and wound healing which is why it’s so beneficial when it comes to gut and digestive wellness.
Zinc’s role in gut health has long been established and a zinc deficiency is one of the leading risk factors for gastrointestinal diseases and disorders, given that 70% of the immune system is found in your digestive tract (8).
Zinc has been used to treat infections (viral, bacterial and parasitic), increased gut permeability [a.k.a. leaky gut] and intestinal inflammation, and supports wound healing (ulcers) (9, 10).
Why carnosine?
I’ve written about the many potential health benefits of carnosine before such as antiglycation, protecting the brain and memory, and possibly reducing the risk and progression of cataracts.
Carnosine has been investigated for its ability to improve wound healing in models of tissue damage but the amounts used in those studies were much higher than what’s present in zinc carnosine, or even standalone carnosine supplements (11, 12, 13).
In terms of ulcer healing, l-carnosine doesn’t seem to help on its own, possibly because it’s not retained at the site of inflammation long enough for it to work (5).
The advantage of zinc carnosine is that it allows for a slower dissociation in the stomach and along the digestive tract as it makes its way down.
Normally zinc is liberated from food quickly within the stomach and then is absorbed along the first part of the small intestine. For normal requirements, this is a good thing. You want the zinc to be liberated from food so it can be absorbed.
But for gut and intestinal healing, quick release and absorption aren’t good. That doesn’t allow for a more localized concentration of zinc where it’s needed most, at the site of tissue injury.
It’s thought that zinc carnosine adheres nicely to the inflamed mucosal tissue and/or stomach/intestinal lining longer. The polymetric complex of mineral and amino acid has been shown to ‘hang out’ in the stomach twice as long as taking zinc on its own does (6).
This helps to deliver both zinc and carnosine to the site of inflammation where they can promote healing directly to the gastrointestinal tissue (5, 6, 14).
Zinc carnosine benefits
Besides having a good track record for healing gastric and duodenal tissue injury such as ulcers, zinc carnosine has also been successfully used and studied for other gastrointestinal disorders.
Leaky gut repair
After the treatment of ulcers and H pylori infection, leaky gut, or increased intestinal permeability is the next most common use of zinc carnosine.
The physical barrier between the contents of your digestive tract and your circulation (bloodstream and lymphatic system) is only one cell thick. Digestive tract cells (epithelial) are connected to each other by a network of proteins called tight junctions.
Tight junctions usually prevent the passage of toxins from the gut lumen (the inside of the gut) into the blood.
Many things can cause these tight junctions to relax; increasing the space in-between the cells. In this sense, the gut/intestinal tract becomes more porous, or “leaky”. When that happens, bacteria, bacterial toxins, food antigens, etc can enter the circulation leading to inflammation and more.
Leaky gut, a.k.a. gut barrier dysfunction can be caused by many different things:
- Uncontrolled Celiac disease & IBD (Crohn’s and Ulcerative Colitis)
- Chronic alcohol use
- Alcohol-induced liver damage
- Gut infections and parasites
- Salmonella and other enteric bacteria infections
- SIBO (Small Intestinal Bacterial Overgrowth)
- Medications
- Antibiotics
- NSAIDs (ibuprofen, naproxen, ASA, etc)
Current data indicate that zinc carnosine may improve the health of the epithelium and the tight junction structure.
For example, zinc carnosine has been shown, for example, to improve NSAID-induced small intestinal injury. In one study, when given with the anti-inflammatory drug indomethacin, zinc carnosine was able to prevent small intestinal increased permeability that can occur with this category of drugs (14).
The zinc carnosine leaky gut connection has solid evidence behind it; enough to consider using if you’re dealing with gut barrier dysfunction (confirmed) or even if suspected.
Helicobacter pylori (H. pylori)
H. pylori is a type of bacteria. These germs can enter your body and live in your digestive tract. After many years, they can cause sores, called ulcers, in the lining of your stomach or the upper part of your small intestine. For some people, an infection can lead to stomach cancer.
Zinc has antiseptic properties. Zinc lozenges can help to reduce the duration of colds and sore throats due to its antimicrobial actions (15, 16, 17).
FUN FACT: low stomach acid increases the risk for H pylori and other bacterial infections in both the stomach and digestive tract. Stomach acid naturally declines with age
So it’s not surprising that zinc carnosine would have antibacterial properties of interests in the digestive tract. Zinc carnosine interferes an enzyme (urease) used by the H pylori bacteria needed to proliferate within an acidic environment (H pylori raises the pH of the stomach, e.g. makes it less acidic) allowing it to survive
Decreases gut inflammation
A consequence of digestive disorders and diseases, as well as, certain foods (wheat intolerance), beverages (alcohol) and medications (medications, NSAIDs), is inflammation; irritation to the smooth and vulnerable lining of the gastrointestinal tract, from mouth to anus.
Zinc carnosine has been shown to prevent and treat inflammation caused by the concerns mentioned above including alcohol in a rat model (R). In one study, zinc carnosine was able to reduce lesions in an experimental model using ASA (18).
This holds promise as long-term use of NSAIDs causes intestinal inflammation, lesions, and damage.
It’s been shown to reduce the inflammatory response by the stomach to H pylori (19). In response to this type of infection, the cells of the stomach secrete large amounts of interleukin 8 (IL-8) which recruits and activates the immune system (20).
Zinc carnosine suppresses inflammation-promoting cytokines (pro-inflammatory proteins) production and secretion in stomach cell cultures and ‘turn down’ stomach cells inflammatory response (21).
Improves exercise-induced gut damage
Heavy exercise has long been known to tax the body in different ways. Marathoners, triathletes and long-distance runners have a greater risk for, and incidence of, acute respiratory illnesses for example (22, 23).
Likewise, heavy exercise causes gut symptoms and in some cases, heat stroke or even elevated body temperatures which can increase intestinal permeability (leaky gut) with translocation of luminal toxins into the general circulation (24, 25). The use of NSAIDs, as mentioned, is known to disrupt the gut barrier; medications that are routinely used by athletes and serious exercisers alike (26).
The aforementioned movement of intestinal toxins, bacteria, and food antigens into the bloodstream leads to an inflammatory cascade which, in turn, worsens the loss of the intestinal barrier. This can lead to systemic effects such as exertional heat stroke, hyperthermia, and endotoxemia (27).
Gastrointestinal symptoms commonly reported in high-intensity, high-stress and high-volume training athletes such as cramps, diarrhea, nausea, and bleeding are likely due, in part, to a combination of reduced splanchnic blood flow, hormonal changes, increased body temperature AND altered gut permeability (28, 29, 30).
A study examined whether zinc carnosine, taken alone or in combination with bovine colostrum (a natural source of growth factors), would moderate any of these exercise-related effects. It looked at the role of this supplement on post-recovery; a crucial part of the training process. (31, 32). The results of the 14 day, double-blind, placebo-controlled study showed the use of zinc-carnosine to be beneficial in supporting epithelial resistance post-exercise.
Maintains a healthy gut lining
Maintaining a healthy gut lining is central to optimal gut barrier function.
Luckily, this is where zinc carnosine can play a role. On its own, zinc has been shown to support the intestinal barrier given zinc’s role in DNA maintenance, wound healing and immunity (33).
Zinc carnosine has been shown in animal models to protect the stomach mucosa (the mucous lining that protects the stomach) against experimentally induced tissue damage and ulcerations (34, 35, 36, 37, 38).
A study looking at villi health, the small, finger-like structures in the small intestine that help to absorb digested food found that zinc carnosine administration helped to prevent problematic villus shortening in an animal model by 50% (14).
FUN FACT: villi can be damaged and shortened in uncontrolled celiac disease, over-use of NASAID medications, Benicar (blood pressure medication), antibiotics, SIBO, Crohn’s disease, lymphoma, parasitic infections, chronic alcohol and other substance use,
This is important because villi and their smaller structures, microvilli, increase the absorptive surface area of the small intestines ensuring maximal absorption of nutrients (vitamins, minerals, protein, fats, etc).
You want your villi and microvilli to be as long as they’re meant to be. Shorter villi equal poorer nutrient absorption so anything that can prevent or reverse villus shorting is good and zinc carnosine does just that.
A double-blind, randomized controlled crossover trial found similar protective effects by zinc carnosine in a group of healthy volunteers who took 37.5 mg twice daily (75 mg total) compared to placebo underscoring zinc carnosine’s beneficial role on the gut lining (14).
Prevent radiation-related mucositis
Oral mucositis (painful inflammation and ulceration of the mucous membranes lining the digestive tract0, is one of the most distressing side-effects during cancer therapy, particularly in patients with head-and-neck cancer receiving chemotherapy and/or radiotherapy or those who receive high-dose chemotherapy and radiotherapy followed by bone marrow transplantation.
Mucositis makes if difficult to eat and the risk of overt protein, energy, and micronutrient malnutrition is a real concern.
A zinc carnosine mouth rinse has been shown to reduce the incidence rates of mucositis along with improvements in pain, xerostomia and taste disturbance. The treatment group also required fewer painkillers and the amount of food patients were able to eat was significantly higher (39, 40).
Protects gastric cells
Free radicals and oxidation might be difficult to conceptualize. In simple terms, free radicals are unstable molecules because they have atoms that are looking to regain balance.
They steal electrons from other molecules resulting in oxidation of those molecules. You’ve seen oxidation whenever an apple core is left on the counter. Oxygen steals electrons from the sugars and proteins in the expose apple flesh and the core turns brown.
Oxidation can occur in your stomach too and your stomach cells are vulnerable just like that apple core. Luckily, zinc carnosine prevents this (antioxidant) and has been shown to be protective in various oxidative pathologies including gastritis (41).
Ulcerative colitis
Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the colon (large intestine). The disease causes small sores in the lining of the colon resulting in pain and large amounts of discharge (pus and mucus).
It’s managed mostly with medications but also diet and supplements. Zinc carnosine has been shown to be a stand out for UC.
A randomized, double-blind placebo-controlled study in patients with active UC was given either 150 mg of zinc carnosine or a placebo per day via an enema.
Both groups had induction therapy (treat with anti-inflammatory steroids) prior to the start of the study.
The group who got the 150mg of zinc carnosine showed improvement of their inflammation and discomfort levels compared to the placebo group who had no improvement (41).
Improves ulcers
A rat studied showed that zinc carnosine accelerated the healing of experimentally-induced gastric ulcers using hydrocortisone and acetic acid (43).
Numerous human studies have shown benefit for gastritis, gastric and/or duodenal ulcers. In one randomized, multi-center, placebo-controlled trial subjects with confirmed gastric ulcers were randomly assigned to one of four groups:
- 150 mg of zinc carnosine and its placebo, or
- 800 mg of cetraxate hydrochloride (a mucosal protective agent) or its placebo
Medications, supplement, and placebos were started within 1 week of endoscopy-diagnosed gastric ulcer and were continued for 8 weeks.
The results for zinc carnosine were impressive.
For “marked improvement”, symptoms were comparable between zinc carnosine and cetraxate at both 4 weeks and 8 weeks: 61% better in the zinc-carnosine group and 61.5% in the cetraxate group, and 75% markedly improved compared to 72% for the cetraxate group respectively.
Zinc carnosine is a unique nutritional supplement that supports stomach mucosal defenses and helps to heal gastric ulcers
Zinc carnosine faired better with the endoscopic cure rates: 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 (A, B).
Similar findings were found in several other studies looking at the impact of zinc carnosine of gastric ulcers with up to 80% improvements by week 8 in classic ulcer-related symptoms:
- Epigastric pain
- Heartburn
- Nausea and vomiting
- Abdominal distension
- Diarrhea and constipation
- Hematemesis
- Melena and epigastric tenderness
There were also significant improvements in endoscopic healing rates in the zinc carnosine group (C, D, E, F, G, H, I).
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How much should you take?
Whether as a standalone or part of a gut-healing supplement, the usual dosage for zinc carnosine is 75 mg per day. For reference:
- 75 mg zinc carnosine = about 17 mg of zinc & 59 mg carnosine
- 150 mg therefore = about 34 mg zinc & 158 mg carnosine
In Japan, where zinc carnosine is an approved anti-ulcer drug, the typical dose is 75-150 mg per day. This provides a daily dose of 34 mg of zinc and 158 mg of carnosine. Some practitioners may use 150 mg twice a day; this would provide a large 68 mg dose of elemental zinc which, if taken longer than 8 weeks, will need copper balancing (see below).
From a therapeutic point of view, most studies have found benefit within 2 weeks of taking 75-150 mg per day with up to 75% improvement in digestive symptoms.
To allow better healing, 8 weeks is typically the minimum duration of treatment. Many who try this supplement, often stop after a month or so and don’t achieve the healing they’re hoping for.
The amount of zinc from this supplement is under the Tolerable Upper Intake Level (UL) of 40 mg per day which is defined as the highest average daily intake level likely to pose no risk of adverse health effects (44, 39).
Keep in mind that you would still be getting zinc from food so the total amount of zinc from all sources would take you over the UL of 40 mg when using zinc carnosine for gut healing.
But, the UL IS NOT an upper limit or cut-off; there’s little to no risk for toxicity when taking zinc carnosine for 8 to 12 weeks for therapeutic purposes.
Zinc and copper
The potential concern of getting too much zinc, from food, supplements, or both is that over the long term, a very high intake of zinc (60 to 100 mg or more per day) for several months can lead to a copper deficiency (39).
To balance an intake of this much zinc, additional copper would be needed for a short period of time. Typically the ratio of total zinc: copper is 2:1. This however really should be done under the guidance of a regulated health practitioner.
Safety, uses, and contraindications
There are few zinc carnosine side effects if any to worry about provided you follow safe dosages. Both of its ‘building blocks’, zinc and carnosine, are safe.
It’s best not to take more than 150 mg (75 mg x 2) of zinc carnosine per day unless otherwise instructed by a qualified health practitioner.
If higher dosages of zinc are indicated (more than 60 mg for longer than 8 to 12 weeks), whether that’s zinc carnosine or a regular zinc supplement, then you have to consider balancing it with some extra copper.
The standard treatment for H pylori infection is the so-called “Triple Therapy” consisting of amoxicillin, clarithromycin, and a proton pump inhibitor (PPI) such as pantoprazole (Pantoloc), etc.
Zinc carnosine can be safely used as an adjunctive treatment to the triple therapy.
Zinc carnosine shows no detrimental effects on chemotherapy or radiotherapy when used to prevent mucositis (39, 40). This is beneficial as mucositis is a common reason to stop those therapies.
Bottom line
Zinc-carnosine is a unique nutritional supplement that’s been studied for over 20 with a decent amount of published studies supporting its use.
It’s been approved as a treatment for ulcers in Japan since the mid-90s.
It has a unique structure that enables both zinc and carnosine to be delivered and retained at the site of tissue damage longer than traditional zinc supplements. Zinc carnosine’s polymeric structure enables zinc to be more therapeutic than either zinc or carnosine are on their own.
Zinc carnosine has its best evidence for the treatment of both gastric and duodenal ulcers and it also appears to enhance the stomach’s mucosal defenses providing protection against gastritis, as well as, oxidative damage to stomach cells.
It helps to prevent gut barrier dysfunction and maintains small intestinal mucosal integrity thereby reducing the incidence of leaky gut that’s often seen with parasitic infections, SIBO, NSAID overuse, chronic alcohol use, and exercise-related gut damage.
Typical doses are in the 75 to 150 mg range, one to two times per day, for at least 8 to 12 weeks. At these doses and duration, up to 80% improvement in symptoms is typically seen.
Zinc carnosine is safe when taken at typical doses, for the typical treatment duration of 2 to 3 months. If you plan to take it longer, speak with a licensed health practitioner about balancing your intake of total zinc with copper.
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Additional References
A. Wollschlaeger B. Zinc-carnosine for the management of gastric ulcers: clinical application and literature review. JANA. 2003;6(2):33.
B. 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.
C. 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.
D. Hayakawa A, Inoue M, Kunizaki M, et al. Clinical evaluation of Z-103 on gastric ulcer. Jpn Pharmacol Ther. 1992;20(1).
E. 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.
F. 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).
G. 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.
H. 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.
I. 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.
J. 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.
Doug Cook RDN is a Toronto based integrative and functional nutritionist and dietitian with a focus on digestive, gut, and mental health. Follow me on Facebook, Instagram and Twitter.