Zinc/Carnosine Complex: Informative Article

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INTRODUCTION

As a scientist, I am always astonished by the advancements medical

researchers are making in the development of life-saving drugs. As a

physician, I clearly understand the public’s growing interest in natural

remedies that enable the body to heal itself. And as a teacher, I can’t

help but tell people about a treatment that combines a natural approach to

healing and is grounded in actual scientific research. Zinc-Carnosine is

just such a breakthrough.

Having had a long-standing interest in the treatment of ulcers, as I

pointed out in the book’s Introduction, I was made aware of Zinc-Carnosine

several years ago. Because of my position as a visiting professor at the

University of Hong Kong’s medical school, I was fortunate enough to come

across a number of reports on Zinc-Carnosine. The scientific literature

seemed very credible. As it turns out, Zinc-Carnosine has had remarkable

success in Japan as a treatment for peptic ulcer disease, but the

supplement is hardly known in North America and Europe. Hopefully, this

book will change that.

Zinc-Carnosine deserves consideration as a first-line ulcer treatment in

this part of the world. Besides ulcers, Zinc-Carnosine is valuable for

treating gastritis and dyspepsia. The supplement represents a natural

healing approach to stomach ailments. Instead of obstructing an action of

the stomach—blocking acid production, neutralizing hydrochloric

acid—Zinc-Carnosine strengthens the stomach’s mucosal defenses. The

supplement harnesses the stomach’s natural ability to fight disease, battle

infection, and heal itself.

This chapter explains what Zinc-Carnosine is and examines whether it is

safe. I look at how the supplement heals ulcers and relieves ulcer pain. In

the second half of this chapter, I examine the science behind

Zinc-Carnosine. I will cite many studies that show how Zinc-Carnosine

achieves its healing power. However, let’s start at the beginning, and look

at zinc and L-carnosine—the two components of Zinc-Carnosine— separately.

WHAT IS ZINC?

Zinc, an essential mineral, is found in almost every body cell. Zinc is

important for the functioning of the immune system. It is a component of

many enzymes and necessary for DNA synthesis. Of interest to this

discussion, zinc plays a role in wound healing. It is involved in the

thymus gland’s production of T-lymphocytes, the white blood cells that

manage the response of the immune system to an injury or infection (the T

in T-lymphocyte stands for “thymus”). People with zinc deficiencies heal

poorly because their immune systems are impaired. As a measure of how

important zinc is to healing, a controlled study published in the ls of

Surgery found that the healing time of surgical wounds was reduced by 43

percent when patients took 220 mg of zinc sulfate three times daily.

Oysters are the best natural source of zinc. The mineral is also found in

beef, pork, seafood, beans, and nuts. Many breakfast cereals are fortified

with zinc.

WHAT IS L-CARNOSINE?

L-carnosine is a dipeptide bond composed of two essential amino acids,

L-histidine and beta-alanine. Amino acids are the material from which

protein is made. L-carnosine demonstrates antioxidant properties. It occurs

naturally in the cells of all mammals, so taking L-carnosine does not

introduce any foreign substances into your body. You can obtain L-carnosine

by including meat and beans in your regular diet.

The L-histidine part of the L-carnosine dipeptide is interesting because

histidine is the precursor of histamine, and, as Chapter 6 explains,

histamine plays a role in the production of hydrochloric acid in the

stomach. A precursor is a substance that precedes, and is necessary for,

the creation of another substance. It could be that the L-histidine creates

histamine that in some way controls or modulates the stomach’s production

of hydrochloric acid.

Zinc-Carnosine

When zinc and L-carnosine are chemically joined, a unique nutrient is

formed. It is called Zinc-Carnosine. It is insoluble in water and

heat-stable. Why is this important? First, because it doesn’t dissolve in

water, it doesn’t easily lose its potency, nor is it quickly flushed out of

the body. And second, being heat-stable, hot and cold temperatures will not

change its ability to work. The supplement’s heat-stability gives the pills

and tablets a long shelf-life.

The peptic-ulcer healing rate from Zinc-Carnosine, as observed by

endoscopy, is approximately 65 percent after the standard eight-week

treatment. The improvement, in terms of symptoms and other objective

criteria, is about 70 percent. Zinc-Carnosine is the first anti-ulcer drug

to include zinc, a substance known for its healing properties. How

Zinc-Carnosine works is explained throughout this chapter. Meanwhile, here

is what Zinc-Carnosine does in a nutshell.

This nutrient:

• Protects the membranes of epithelial cells in the stomach and brings the

cells back to their normal metabolism.

• Acts as an antioxidant.

• Has anti-inflammatory properties.

• Adheres to stomach ulcer sores and acts as a barrier between the sores

and caustic gastric juice.

• After adhering to sores, releases its zinc and L-carnosine for healing

purposes.

• Has an inhibitory effect on H. pylori bacteria.

• Is prostaglandin-independent and doesn’t interfere with the prostaglandin

production that is necessary for the stomach’s mucosal protection.

Patients taking Zinc-Carnosine have reported no significant adverse effects

or side effects. The supplement does not cause zinc toxicity or interfere

with the absorption of copper, which is a concern whenever zinc is ingested.

Zinc-Carnosine was developed in the late 1980s by Hamari Ltd. of Osaka in

Japan. Since 1994, it has been in widespread clinical use in Japan, where

it is known under the generic name polaprezinc. Based upon scientific data

supplied by the Japanese medical researchers, the inventors at Hamari took

out a complete line of patents in the United States, Canada, and Europe.

The first U.S. patent, 4,981,846, was issued in 1991 and covered the

composition of the Zinc-Carnosine molecule and its anti-ulcer activity.

Several more patents soon followed, but Zinc-Carnosine was not developed

commercially until it was submitted to the Food and Drug Administration as

a new dietary ingredient (NDI) in May 2002. After completing the review

process in late 2002, Zinc-Carnosine was made available as a supplement in

the United States.

Ingredients of Zinc-Carnosine

Zinc-Carnosine is a chelated—a chemically joined—compound that combines the

trace mineral zinc and L-carnosine. Chelated compounds are firmly attached,

which is an advantage in the digestive system where hydrochloric acid and

pepsin readily break down everything that comes their way. On their own,

zinc and L-carnosine soon disassociate in the stomach’s acidic environment,

but, owing to its chelated structure, the Zinc–L-carnosine compound doesn’t

disassociate as easily. This accounts for Zinc-Carnosine’s staying power in

the stomach. Both zinc and L-carnosine have healing properties in their own

right, but, as numerous experiments have demonstrated, the compounded

healing effect of the two ingredients is much greater than that of zinc or

L-carnosine on its own. As a compound, zinc and L-carnosine make for a

dynamic healing agent. Zinc-Carnosine is much greater than the sum of its

parts.

WHAT IS CHELATION?

Chelation is the chemical bonding or attaching together of two different

molecules. Chelation is quite different from physically mixing different

component parts. By chelating two components, you can slow their absorption

as nutrients. Chelation is often associated with essential minerals. We

need essential minerals for nutrition, but their consumption can have

uncomfortable side effects. The consumption of zinc by itself, for example,

can cause nausea. Chelation causes essential minerals to release their

molecules slowly, and, therefore, causes no uncomfortable side effects.

HOW ZINC CARNOSINE HEALS ULCERS

Zinc-Carnosine relieves stomach pain, heals ulcers, and perhaps prevents

them. How? The supplement works by strengthening the stomach mucosa,

sticking to the stomach wall and acting as a buffer to gastric acid,

serving as an antioxidant, controlling the inflammatory response to stomach

injury, and inhibiting the growth of H. pylori bacteria. You’ll learn more

about each of these important actions directly below, and will discover the

technical details of Zinc-Carnosine’s mode of action later in the chapter.

Strengthens the Stomach Mucosa

The lining of the stomach is protected from its own caustic gastric juice

by a thin gel-like layer of mucus. When this mucus layer erodes, the

stomach lining is exposed, and you can get an ulcer. Evidence suggests that

Zinc-Carnosine works primarily by strengthening the mucosal barrier between

the stomach lining and the harsh gastric juices of the stomach. The

supplement appears to adhere to the stomach wall to provide protection to

all areas of the stomach. These studies give a picture of Zinc-Carnosine’s

protective effect on the stomach lining:

• In an early study conducted at the Yokohama Red Cross Hospital in 1992,

twenty-five patients whose ulcers were confirmed by endoscopy were given 75

mg Zinc-Carnosine tablets twice daily (one after breakfast and one before

bed) for eight weeks. Drugs such as H2 blockers and proton pump inhibitors

that might affect the results of the study were prohibited. The

“disappearance rate” of epigastric pain symptoms in the patients was 53.3

percent after meals, 76.9 percent fasting, and 90.9 percent at night. Of

the twenty-five subjects who had a final assessment by endoscopy after the

eight weeks, 65 percent were healed of their gastric ulcers. This study is

interesting because the ulcers were healed without suppressing the

production of acid. Zinc-Carnosine was able to provide a genuine protective

effect to the stomach.

• In a double-blind study of three groups taking 50-mg, 75-mg, or 100-mg

Zinc-Carnosine tablets twice daily for eight weeks, the success rates of

the study as obtained by endoscopy were as follows: 50.8 percent for 100-mg

group, 58.6 percent for 150-mg group, and 53.6 percent for 200-mg group.

These studies show very clearly that Zinc-Carnosine has a protective effect

on the stomach, and that the supplement’s healing action is not based

solely on its role as a buffer of stomach acid.

Adheres to the Stomach Wall

Like bismuth and to a lesser degree sucralfate, Zinc-Carnosine coats the

stomach and acts as a barrier between ulcers and hydrochloric acid. In this

way, it protects ulcer sores from irritation by acid, relieves pain, and

permits the sores to heal. In a 1992 study called “The gastric mucosal

adhesiveness of Z-103 (Zinc-Carnosine) in rats with chronic ulcer,” M.

Seiki et al. concluded, “(Zinc-Carnosine) shows a long-term adhesive and

permeable action on the gastric mucosa in acetic acid ulcer rats, and it

has a comparable high affinity at the ulcerous site.” The scientists

attributed Zinc-Carnosine’s adhesiveness to its zinc content. They also

noted that the strength and duration of adhesiveness was dose-dependent,

which indicates that Zinc-Carnosine has a genuine adhesive effect in the

stomach.

Acts as an Antioxidant

More so than most other organs, the stomach is subject to oxidative stress

from alcohol, swallowed tobacco smoke or juice, and other harmful

substances. Zinc-Carnosine acts as an antioxidant to prevent these

substances from eroding the stomach lining. I describe experiments

involving Zinc-Carnosine and its antioxidant properties in the second half

of this chapter.

Tempers the Inflammatory Process

Inflammation is a natural response of the immune system to injury.

Nevertheless, too much inflammation in the stomach can cause ­gastritis and

painful ulcers. In experiments, the supplement Zinc-Carnosine retarded the

TNF-alpha secretion of interleukin-8, a ­molecule involved in the

inflammatory process. The supplement therefore appears to modulate the

immune-system response and keep inflammation in check.

Inhibits H. Pylori

H. pylori bacteria are responsible for seventy-five percent of stomach

ulcers worldwide. Zinc-Carnosine inhibits the growth of the bacteria,

probably by strengthening the stomach mucosa and making it less susceptible

to a bacterial infection.

OTHER INDICATIONS OF ZINC CARNOSINE

The digestive tract is a continuum. Although each organ plays a specific

role in absorption and digestion, the organs don’t begin and end abruptly.

If you were to take sequential tissue biopsies throughout the digestive

tract, you would see that there is a steady, gradual transition from one

organ to the next. Each organ has its epithelium and sublayer that supports

the epithelium. The mechanisms of cell survival and protection are the same

throughout. It stands to reason, therefore, that a drug or supplement that

is good for one part of the GI tract can also be good for another part.

Because Zinc-Carnosine heals ulcers in the stomach, scientists at Medical

School Hospital, Sendagi, Tokyo, decided to see if it could be used

effectively to treat mouth ulcers and stomatitis, the inflammation of the

lining of the mouth. For the experiment, rats’ cheek pouches were injected

with an acetic acid solution. After lesions formed, they were injected

daily with either Zinc-Carnosine or water. Beginning on the seventh day of

the experiment, lesions injected with Zinc-Carnosine healed significantly

better. The scientists also examined the mucous membrane in the rats’ cheek

pouches and found, in the Zinc-Carnosine group, that the thickening of the

mucous membrane was less severe.

This experiment shows that Zinc-Carnosine may be useful, for example, for

healing the stomatitis that often results from chemotherapy. Perhaps

scientists in the years to come will find other ways to put Zinc-Carnosine

to use. For instance, the supplement is now being investigated as a

sunscreen. Moreover, Zinc-Carnosine may be osteogenic, meaning that it

builds bones, and therefore could be a treatment option for osteoporosis.

Studies – Modes of Action

We know that Zinc-Carnosine works to relieve stomach pain, heal ulcers, and

perhaps prevent ulcers. For scientists, however, the major question is

never what, but how and why. How does Zinc-Carnosine relieve stomach pain

and heal ulcers? Since it was invented in the early 1990s, Zinc-Carnosine

has been the subject of several dozen studies, most of them conducted in

Japan, where ulcer patients have been taking the supplement for a decade.

In the remainder of this chapter, I look at studies that I believe reveal

the most about Zinc-Carnosine’s healing action. Of the numerous studies

conducted on Zinc-Carnosine, I selected those studies that were conducted

exceptionally well, or that examined a particular mode of healing action.

The studies reveal the how and the why of

Zinc-Carnosine.

The study of Zinc-Carnosine is still in its infancy. There is much that we

don’t know, but I believe that Zinc-Carnosine ranks with bismuth and proton

pump inhibitors as a therapy for treating ulcer disease. I predict that the

supplement will become a standard option for treating ulcers in the years

ahead. As the supplement gains in popularity, it will no doubt become the

subject of more studies, and the coming decade will probably bring to light

much that we don’t yet know about the healing action of Zinc-Carnosine.

Antioxidant Effect

Oxidation damages DNA, cell membranes, and tissue. It is caused by very

unstable, highly reactive molecules called free radicals that steal

electrons from other molecules. An antioxidant is a substance that reverses

this decay by deactivating unstable free radicals. In a study conducted at

the Zeria Pharmaceutical in Japan, researchers Y. Hori et al. looked at the

effect of Zinc-Carnosine as an antioxidant. In the test tube, the

researchers ­discovered that Zinc-Carnosine scavenged active-oxygen

free-radical species, including hydrogen peroxide. This free radical is

produced in the stomach and elsewhere in the body to kill pathogens. In the

stomach, however, it can also attack and erode the stomach lining. By

scavenging and destroying hydrogen-peroxide free radicals, Zinc-Carnosine

protected stomach cells in test-tube experiments. The scientists also

conducted experiments with Zinc-Carnosine on rats by inducing ischemia in

the rats’ stomachs and exposing the rats to 200-proof alcohol. Ischemia is

a condition in which blood flow to a part of the body is constricted. The

alcohol and lack of blood created massive oxidative stress in the rats’

stomachs, but the scientists discovered that free radical scavenging by

Zinc-Carnosine inhib­ited the damage created by ischemia and alcohol in a

dose-­dependent way. In other words, damage was reduced according to the

amount of Zinc-Carnosine fed to the rats. This is important because it

showed that Zinc-Carnosine had a genuine protective antioxidant effect on

the rats’ injured stomachs.

In a similar study conducted at Dokkyo University School of Medicine in

Japan, H. Hiraishi et al. looked at the antioxidant effect of

Zinc-Carnosine on stomach cells in the test tube. This study was

interesting because it involved cytochrome C, a protein found in cells.

Normally, cytochrome C figures in the creation of cellular energy, but when

a cell is damaged, it releases cytochrome C into its mitochondria, and this

triggers cell apoptosis, the programmed self-destruction, or death, of the

cell. Scientists can measure the release of cytochrome C from cells to get

a better understanding of how noxious agents such as alcohol affect cells.

If the cells release sufficient amounts of cytochrome C, it indicates that

they are being damaged. For the experiment, researchers cultured cells from

the fundus (the convex upper portion) of rats’ stomachs. Then, in the test

tube, they exposed the cells to hydrogen peroxide and 200-proof alcohol, as

well as various amounts of Zinc-Carnosine, and measured the cells’ release

of cytochrome C. The purpose of the experiment was to see if

Zinc-Carnosine, as measured by the release of cytochrome C, could prevent

cell damage. The scientists found that Zinc-Carnosine inhibited the release

of cytochrome C from the cells in a dose-dependent manner. In other words,

the more Zinc-Carnosine that was applied to a cell, the less likely it was

to be damaged by alcohol and hydrogen peroxide. This excellent experiment

clearly demonstrates that Zinc-Carnosine can protect stomach cells from

damage by alcohol and other noxious substances.

Inflammatory Response

Inflammation is a natural response on the part of the immune system to

injuries and infections. When you sprain your ankle, for example, redness,

warmth, and swelling occur at the site of the injury. In other words,

inflammation occurs. Swelling and redness are the result of blood vessels

dilating at the site of the injury so that more blood can arrive and bathe

the injury with white blood cells and other healing agents. Warmth is meant

to kill bacteria and toxins. The problem with inflammation of this kind is

that it can create problems in its own right. In the stomach, inflammation

can cause gastritis. Ulcers can appear where tissue is inflamed. And

inflammation, of course, is painful.

In the nucleus of certain kinds of cells are molecules that create

inflammation. These molecules include interleukin-8 (IL-8). Interleukins

are molecules that help white blood cells communicate with one another. In

gastric mucosal cells, IL-8 plays a major role in the inflammatory response

to an H. pylori infection. Because sustained inflammation is a risk for

gastric mucosal damage, agents that down-regulate the inflammatory

response—agents that retard the effect of IL-8 and decrease

inflammation—may be useful for treating H. pylori infections.

In a study conducted at Dokkyo University School of Medicine in Japan by T.

Shimada et al., scientists performed an experiment to see whether

Zinc-Carnosine down-regulates IL-8 and thereby controls the inflammatory

response of gastric mucosal cells to an H. pylori infection. Because a

molecule called NF-kappaB stimulates the production of IL-8, the scientists

also examined the effect of Zinc-Carnosine on NF-kappaB activity. The

experiment was undertaken with an enzyme-linked immunosorbent assay (ELISA)

and an electrophoretic mobility shift assay kit—two means of identifying

and quantifying proteins, in this case IL-8 and NF-kappaB.

The scientists found that Zinc-Carnosine suppressed the IL-8 secretion of

TNF-alpha (tumor necrosis factor-alpha), a powerful substance that creates

inflammation, in a dose-dependent manner. The more Zinc-Carnosine

administered, the less TNF-alpha produced. The supplement also suppressed

NF-kappaB. This experiment has implications for the treatment of H.

pylori-induced ulcers with Zinc-Carnosine. Zinc-Carnosine may be a good

candidate to serve along with antibiotics in triple and quadruple therapies

for the eradication of H. pylori. (These drug therapies are explained in

Chapter 6.) In any case, the supplement appears to retard the inflammatory

process, which helps in the prevention of ulcers and gastritis.

One point I’ve made in this book—and I’m sorry if I’ve been hammering at it

too obsessively—is that peptic ulcer disease caused by the use of NSAIDs is

on the rise, and that doctors need to find ways of treating ulcers in

patients who must keep taking NSAIDs for their osteoporosis or arthritis

pain. The following experiment is most interesting because it addressed

this problem head on. It examined the effect of Zinc-Carnosine on

aspirin-induced gastric mucosal injury. For the experiment, which was

conducted at the Kyoto Prefectural University of Medicine by Y Naito et

al., scientists pretreated rats with Zinc-Carnosine, and then, with a

catheter, poured acidified aspirin into the rats’ stomachs. This caused

acute inflammation and hemorrhaging ulcers, although the size of the

gastric erosions was significantly inhibited in a dose-dependent manner by

Zinc-Carnosine. Oxidative stress and the gastric concentration of tumor

necrosis factor-alpha (TNF-alpha) were also inhibited in a dose-dependent

manner. TNF-alpha, a cytokine, is involved in the inflammatory response.

This experiment suggests that Zinc-Carnosine, as well as being an

antioxidant, modulates the immune-system response to prevent inflammation

in the stomach caused by NSAIDs.

Human Insulin-Like Growth Factor 1 (IGF-1)

Human insulin-like growth factor 1 (IGF-1), a polypeptide, is involved in

the growth and development of muscle, fat, brain, and bone cells. It acts

as a stimulating hormone in protein synthesis. IGF-1 mimics some of the

metabolic actions of insulin. For example, it makes cells healthier by

stimulating the uptake of glucose and amino acids. Besides increasing the

production of mucus in the stomach and acting as an antioxidant,

Zinc-Carnosine may also heal gastric epithelial cells by stimulating the

production of IGF-1.

To test this theory, scientists at Kyoto Pharmaceutical University in

Kyoto, Japan led by S. Kato et al., performed an experiment on two groups

of rats. First, they injected an adjuvant in one group to induce arthritis.

Then they induced stomach ulcers in both groups. Rats in each group were

treated with either omeprazole, a proton pump inhibitor, or Zinc-Carnosine

for fourteen days. The scientists used arthritic rats for their experiment

because arthritis is known to decrease the production of IGF-1 in the

gastric mucosa. By comparing ulcer-healing rates in the arthritic and

nonarthritic rats, they could study how much of a role Zinc-Carnosine plays

in the production of IGF-1. In other words, they could discover if

Zinc-Carnosine heals ulcers in part by increasing IGF-1 production. This

experiment also served as a comparison between Zinc-Carnosine and the

proton pump inhibitor omeprazole.

Overall, ulcers in the arthritic rats healed more slowly than ulcers in the

nonarthritic rats. Both omeprazole and Zinc-Carnosine increased the healing

rates of arthritic rats, although, wrote the authors, the “omeprazole

action is mainly due to the inhibition of acid secretion, while the

polaprezinc (Zinc-Carnosine) effect, as shown in the study, may be ascribed

mainly to the stimulation of IGF-1.” The scientists judged the healing

effect of Zinc-Carnosine on arthritic rats “more pronounced” than that of

omeprazole. This experiment was especially interesting because it applies

to arthritic humans as well as arthritic rats. People with arthritis must

take NSAIDs to relieve the accompanying pain, and taking NSAIDs increases

their chances of getting an ulcer. This experiment shows that

Zinc-Carnosine may well be an excellent treatment for ulcer patients who

must continue taking NSAIDs for their arthritis, because the supplement

stimulates the production of IGF-1.

In a similar experiment conducted at Kyoto Pharmaceutical University,

scientists tested Zinc-Carnosine on diabetic rats. These rats, of course,

lack insulin. The object of the experiment was to determine if

Zinc-Carnosine could stimulate the production of insulin-like growth factor

1, and, in so doing, work to heal the rats’ ulcers. For the experiment,

rats were injected with streptozotocin, a substance that destroys the cells

in the pancreas that create insulin. Five weeks later, the newly diabetic

rats’ blood glucose levels (BGLs) were above 350 mg/100 ml, more than three

times higher than the normal level. They were given insulin to keep them

alive, hydrochloric acid to induce ulcers, and, twice daily for four days,

Zinc-Carnosine (3-30 mg/kg) or one of its components, zinc or L-carnosine.

Under the influence of Zinc-Carnosine, the rats’ ulcers healed within ten

days without affecting glucose levels or acid secretion. Zinc had a

similar, but not as pronounced effect, on healing rates, but L-carnosine

did not heal the rats’ ulcers. The scientists attributed Zinc-Carnosine’s

healing power to augmented IGF-1 synthesis in the rats’ stomach mucosa. It

appears that IGF-1 stimulation is indeed an important part of

Zinc-Carnosine’s mode of action in the stomach.

An interesting experiment conducted by K. Seto et al. of the Zeria

Pharmaceutical Company in Saitama, Japan, also attempted to clarify the

ulcer-healing properties of Zinc-Carnosine. For the experiment, the

scientists compared the effect of Zinc-Carnosine, as well as zinc by itself

and L-carnosine by itself, on fibroblast cells from humans, endothelial

cells from humans, and mucosal epithelial cells from guinea pigs’ stomachs.

The goal of the experiment was to find out how Zinc-Carnosine achieves its

healing power in tissue. The scientists were especially curious to compare

the effect of Zinc-Carnosine, zinc alone, and L-carnosine alone on cell

growth and proliferation. As part of the experiment, they also looked at

the effect of Zinc-Carnosine on the production of human insulin-like growth

factor 1 (IGF-1). As I explained earlier, this molecule is involved in the

growth and development of cells. Studies have shown that blood

concentrations of IGF-1 are low in zinc-deficient rats, and the scientists

wanted to discover if the zinc component of Zinc-Carnosine stimulates the

production of IGF-1.

Here are the results of the experiment:

• Zinc-Carnosine stimulated the growth and proliferation of human

endothelial and fibroblast cells, but had no effect on mucosal epithelial

cells from guinea pigs’ stomachs. Endothelial cells line the heart and

blood vessels. Fibroblast cells are found in collagen, the substance that

forms the structural mesh that shapes and nurtures skin, bones, muscles,

and tendons. This portion of the experiment indicates that Zinc-Carnosine

does not have a direct effect on the growth of mucosal cells in the lining

of the stomach.

• Zinc-Carnosine caused an increase in the gene expression of IGF-1 in

endothelial and fibroblast cells. This could provide a clue as to how

Zinc-Carnosine affects cells in the stomach lining. It could be that

Zinc-Carnosine makes stomach epithelial cells grow and develop by means of

a paracrine action. In other words, IGF-1 produced in endothelial cells may

be passed to epithelial cells on the stomach lining.

• Zinc-Carnosine dramatically increased the growth and development of

endothelial and fibroblast cells. By contrast, L-carnosine alone had no

effect on these cells, and zinc alone increased cell growth by a factor of

two, far below the growth rate of Zinc-Carnosine. This confirmed that zinc

is the essential healing component of Zinc-Carnosine, but that L-carnosine

plays a very important role in the compound, because it enhances the

healing power of the zinc.

Zinc-Carnosine and Prostaglandin E

In a rather ghastly but to-the-point experiment, H. Nishiwaki and his

colleagues at the Kyoto Pharmaceutical University in Japan pretreated rats

with 2 to 12 mg/ml of Zinc-Carnosine or 2 micrograms/ml of prostaglandin E

and then had the rats swallow 1 ml of ammonia or monochloramine (the

chloride of ammonia). Needless to say, these caustic substances soon caused

severe hemorrhagic ulcers. However, rats pretreated with Zinc-Carnosine had

smaller gastric lesions in a dose-dependent manner. Rats pretreated with

prostaglandin E also had smaller lesions. The scientists then anesthetized

the rats, opened their stomachs, and applied Zinc-Carnosine topically.

Again, the lesions receiving higher doses of Zinc-Carnosine showed more

improvement. However, this time the prostaglandin E had no effect.

This experiment is interesting because it addresses the supposition that

Zinc-Carnosine is prostaglandin-independent. In other words, the supplement

does not rely on prostaglandins to heal stomach tissue. As Chapter 3

explains, non-steroidal anti-inflammatory drugs (NSAIDs) interfere with

prostaglandin production and, in so doing, impair the stomach’s natural

mucosal defenses. If Zinc-Carnosine and prostaglandins have nothing to do

with each other as this experiment suggests, it is good news for ulcer

patients who must take NSAIDs for their joint pain. These patients can take

Zinc-Carnosine with the assurance that it will relieve pain because it

doesn’t rely on prostaglandins to do so.

ZINC-CARNOSINE'S INTERACTION WITH VARIOUS DRUGS

In an experiment conducted by S. Kato et al. involving Zinc-Carnosine and

the stomach’s mucosal layer, scientists in Kyoto Pharmaceutical University

performed another ghastly experiment on rats, this one involving

Zinc-Carnosine and sucralfate. As Chapter 6 explains, sucralfate (Sulcrate,

Antipepsin, Carafate) is a polymer that coats the stomach to form a barrier

between an ulcer and gastric acid. The drug can be purchased

over-the-counter. It is not a first-line treatment for ulcers, but it is

still used in treatments, especially in Japan. For the experiment,

scientists pretreated rats with Zinc-Carnosine (3 to 30 mg/kg), but this

time the rats were pretreated as well with significant amounts of

sucralfate (30 and 100 mg/kg) and indomethacin, an anti-inflammatory drug.

Then the rats were fed monochloramine (the chloride of ammonia). This

caused massive lipid peroxidation—free radicals “stealing” electrons from

cell membrane lipids to cause cell damage—and severe hemorrhaging.

The scientists reported that the protective effect of Zinc-Carnosine on the

stomach was not affected by indomethacin, but that the protective effect of

sucralfate was lessened. This experiment was interesting because much

higher doses of sucralfate than Zinc-Carnosine were needed to protect the

stomach, and, Zinc-Carnosine worked in spite of the presence of the

anti-inflammatory indomethacin, whereas sucralfate did not work. This

indicates that Zinc-Carnosine is worth considering as a treatment for

peptic ulcer disease in patients who are taking indomethacin for arthritis

pain and inflammation.

Apoptosis is the self-destruction, or death, of cells that normally occurs

when cells become abnormal. Cancer occurs when apoptosis fails and

malignant cells that normally die are permitted to keep living. On the

other hand, when you age, too much apoptosis occurs. Certain genes are

associated with apoptosis. When these genes are switched on, cells die.

Indomethacin, a drug that doctors prescribe to arthritis patients to lower

inflammation, causes apoptosis in certain types of cells.

To test the effectiveness of Zinc-Carnosine when it is used in combination

with indomethacin, Y. Fuji et al. at Tottori University in Yonago, Japan,

looked at the effect of Zinc-Carnosine on indomethacin-induced apoptosis in

mucosal cells from rats’ stomachs. The researchers discovered that

Zinc-Carnosine, in amounts as low as 5 microM, inhibited cell apoptosis,

and that 50 microM exhibited the maximum inhibitory effect. The scientists

determined that zinc, not L-carnosine, played the primary role in

inhibiting apoptosis. It appears the Zinc-Carnosine gives cells—that would

otherwise die by apoptosis at the hands of an anti-inflammatory drug—an

encouraging message to keep on living.

ZINC-CARNOSINE IN QUADRUPLE DRUG THERAPIES for H. PYLORI-CAUSED ULCERS

As Chapter 6 explains, the standard treatment for H. pylori-induced ulcers

is a triple or quadruple therapy consisting of two or three antibiotics and

one or two other drugs, usually a proton pump inhibitor or H2 blocker.

A very interesting study conducted at the Jutendo School of Medicine in

Tokyo threw Zinc-Carnosine into this mix. It attempted to discover if

Zinc-Carnosine could be useful along with other drugs in a

quadruple-therapy treatment for H. pylori-caused ulcers. The experiment

involved two antibiotics (amoxicillin and clarithromycin), the proton pump

inhibitor lansoprazole, and Zinc-Carnosine. Sixty-six ulcer patients with

H. pylori infections and dyspepsia took part in the seven-day study. The

subjects were divided into two groups. Group A, with thirty-one patients,

received lansoprazole (30 mg twice a day), amoxicillin (500 mg twice a

day), and clarithromycin (400 mg twice a day). Group B, with thirty-five

patients, received the same regimen plus Zinc-Carnosine (75 mg twice a

day). Five patients left the study due to severe diarrhea (a side effect of

antibiotic treatment). Of the patients who remained, twenty-four of

twenty-eight, or 86 percent, in Group A were rid of their H. pylori

infections. In Group B, thirty-three of thirty-three, or 100 percent, of

subjects were no longer infected with H. pylori. In this study,

Zinc-Carnosine significantly improved the cure rate of H. pylori-induced

ulcers in a seven-day quadruple-therapy regimen. By restoring the health of

the mucosa, Zinc-Carnosine may improve the stomach lining’s ability to

fight off an H. pylori infection.

DOSAGE

So how much Zinc-Carnosine should you take?

The standard adult dosage of Zinc-Carnosine is 75 mg a day—or, better

still, 37.5 mg twice daily—to be taken for eight weeks. Usually, the

supplement is taken in tablet form once in the morning and once before bed.

It is best taken with food. The cost of using the supplement is eighty

cents to one dollar per day.

Studies have shown that the optimal dose of Zinc-Carnosine is 150 mg per

day, not 75 mg. However, I recommend taking 75 mg daily because, first,

studies show that the effects of the optimal dose and recommended dose are

actually quite similar, and, second, taking 75 instead of 150 mg per day

enables patients to meet, but not exceed, the FDA’s recommended daily

intake (RDI) of zinc. Zinc-Carnosine has been studied on men and women in

the 16- to 75-age range, but as yet, no independent studies have been

conducted on children, pregnant women, or nursing mothers. Check with your

healthcare practitioner before you take Zinc-Carnosine if you are in one of

those groups. In any case, peptic ulcer disease is very uncommon in children.

IS IT SAFE?

Of course, the first question to ask about any drug or supplement is, “Is

it safe?” The answer where Zinc-Carnosine is concerned is a definitive

“yes.” Because the supplement contains zinc, toxicity is a concern. But, as

I will explain below, zinc is not really a problem. Moreover, the

supplement has shown a remarkable lack of side effects. This is good news

for people with peptic ulcer disease. The-majority of drugs used to treat

the disease—proton pump inhibitors and antibiotics—come with very

uncomfortable side effects. Remember, though, that no independent safety

studies have been conducted regarding the use of Zinc-Carnosine on

children, pregnant women, or nursing mothers.

TOXICITY CONCERNS

For adults, 15 mg is the recommended daily intake (RDI) of zinc. The zinc

content in Zinc-Carnosine is 22 percent. The recommended dose is 75 mg

daily, which means that a person taking Zinc-Carnosine gets roughly 15 mg

of zinc per day. This is the same amount of zinc found in multivitamins

such as One-A-Day. Moreover, this is well below the 40 mg tolerable upper

limit (TUI) established by the National Academy of Sciences for adults.

Even a person taking Zinc-Carnosine along with a daily multivitamin will

not exceed the TUI for zinc.

Copper deficiency is a concern to anyone taking zinc supplements because

high doses of zinc retard the body’s ability to absorb copper. Copper is

needed for producing red blood cells and manufacturing insulin. It also

plays a role in iron absorption. Still, someone would have to take an

enormous amount of Zinc-Carnosine to be deficient in copper. People taking

a multivitamin and Zinc-Carnosine are unlikely to acquire a copper

deficiency, because multivitamins contain copper.

For safety purposes, the Zeria Pharmaceutical Company in Japan conducted

two studies on zinc and copper as they pertain to the consumption of

Zinc-Carnosine:

• Scientists examined zinc and copper residues in the blood and organs of

rats that received repeated doses of Zinc-Carnosine. In animals that

received 75 mg/kg—more than 60 times the dosage in humans!—for fifty-two

weeks, no toxicity was observed. Tissue zinc and copper concentrations were

unaffected. At doses of 150 mg/kg for fifty-two weeks, the rats’ zinc

levels showed a slight increase in the blood, liver, and kidneys, but the

copper levels were not affected. Animals given 300 mg/kg—the equivalent of

a human being taking two hundred Zinc-Carnosine capsules a day—for a year

experienced decreased copper levels in their blood, liver, kidneys, testes,

lungs, and spleen. After five weeks of withdrawal from Zinc-Carnosine,

however, the rats’ zinc and copper levels returned to normal.

• Using radioactive tracers, scientists found that zinc levels in the blood

returned to their previous levels eleven hours after taking Zinc-Carnosine;

zinc concentrations in the liver, kidneys, testicles, prostate gland, and

brain remained constant. The zinc in Zinc-Carnosine did not cross the

blood-testis or blood-brain ­barrier.

A 75-mg daily dose of Zinc-Carnosine provides about 60 mg per day of

L-carnosine. This is nowhere near the 400 to 500 mg of L-carnosine found,

for example, in a quarter pound of pork. The L-carnosine in Zinc-Carnosine

is harmless.

Toxicity expert Dr. A. DiSilvestro—in a review of studies relevant

to the safety of Zinc-Carnosine submitted to the FDA as part of the

supplement’s new dietary ingredient review—had this to say about

Zinc-Carnosine’s safety: “At present, I can see no reason to expect

toxicity from a daily dose of 75 mg of Z-103 (Zinc-Carnosine). The two

individual constituents of Z-103 are already normal components of the human

body, the amounts administered are not large compared to other ways of

ingesting these constituents, and current research in vitro, in animals,

and in humans all give evidence of safety.”

SIDE EFFECTS AND ADVERSE EFFECTS

In a meta-analysis of studies done on Zinc-Carnosine, Dr. Bernd

Wollschlaeger found no adverse effects from the supplement. One

double-blind study reported a subject with nausea and one with numbness in

the lips, and another study reported a case of edema, but these side

effects could well have been caused by something besides Zinc-Carnosine.

None of the patients with side effects required further evaluation or

treatment.

DISADVANTAGES

I should pause a moment and explain the supplement’s disadvantages. As I

see it, there is only one drawback: As with most natural products,

Zinc-Carnosine does not stop ulcer pain right away, in the same manner as a

proton pump inhibitor. Pain relief is gradual, with most people feeling

some relief after two weeks, and substantial relief at the end of the

eight-week course of treatment. Needless to say, immediate relief from pain

is a powerful incentive to keep taking a drug or supplement. People who

take Zinc-Carnosine don’t have this incentive. However, Zinc-Carnosine

offers long-lasting relief from ulcer pain because it treats the disease’s

causes as well as its symptoms. Most drug treatments, by contrast, address

only symptoms. For example, they suppress acid production in the stomach,

but do nothing to address the ulcer sore that caused the pain to begin with.

CONCLUSION

Now that you know a little more about Zinc-Carnosine, make sure you don’t

use it as a substitute for medical advice. As excited as I am about this

supplement, I must urge you to seek evaluation by a healthcare

professional. If it is determined that your problem is a peptic ulcer, then

by all means, ask your physician about Zinc-Carnosine. If your doctor is

not familiar with the supplement, feel free to bring in this book. As my

father used to say, “You’re never too old to learn.”

I hope you found this book both informative and empowering. With the

“normal” stresses in our daily existence, our woefully inadequate

modern-day diets, and the less-than-friendly environment in which we

sometimes find ourselves, it’s no wonder so many of us suffer from a host

of stomach ailments. By writing this book, I have tried to provide the

individual looking for relief a balanced view of effective peptic ulcer

disease treatments—covering conventional, alternative, and breakthrough

therapies.

There are, however, a few things I’d like to mention in closing. One is the

overuse of antacids in this country. When we become accustomed to consuming

antacids like candies without any regard to their accumulative effects on

our body, we only add to our health problems. Antacid tablets are a

Catch-22, in that they relieve ulcer pain but also hide pain and permit

ulcers to remain—without being treated. H2-blocking drugs were originally

prescription drugs, but now they are sold over-the-counter, and, not

surprisingly, some people pop these inexpensive pills without any regard

for the long-term health consequences. H2 blockers, and proton pump

inhibitors as well, interfere with the metabolism of the stomach. They

lower stomach acidity, which relieves ulcer pain, but they also permit

germs and pathogens that would otherwise be killed by acid to survive.

Moreover, they interfere with the absorption of protein and vitamin B12.

Remember that the digestive tract is a continuum, and that disrupting it in

one area always has health consequences further down the line.

One final word: If, after reading this book, you do nothing to alleviate

your condition, then—in fact—you are a victim of your own choosing. This

book was designed to offer you a wide range of ways to treat and cure your

problem. If you are afraid of visiting your doctor because of what he or

she may find, remember that the odds are good that your condition is very

treatable. Waiting until the condition worsens can only complicate matters.

Forty years ago, it took an order from an Army doctor for me to go for

help. If that’s what it takes, consider this book your marching orders.