Zinc-Carnosine healing in the gut article

[Guest guest]

Here is an article I found about zinc-carnosine and how it can help

heal your gut. I know it's long and I probably shouldn't post the

whole thing but here it goes.

http://www.iherb.com/ulcers2.html

INTRODUCTION Back to Top

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? Back to Top

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? Back to Top

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? Back to Top

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 Back to Top

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 Back to Top

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 Back to Top

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 Back to Top

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 Back to Top

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? Back to Top

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 & #8209;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 Back to Top

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 Back to Top

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 Back to Top

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 Back to Top

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.