Immunocal is a Science!

GLUTATHIONE (GSH) You may or may not have heard of `glutathione.' However, researchers and scientists continue to discover the importance of this substance in health and disease and in the next few years its name will become as well known as terms like 'cholesterol' or 'vitamin.' Your life depends on glutathione. ..THE IMPORTANCE OF GLUTATHIONE Glutathione's importance to your health cannot be overstated. Your im­mune system is constantly.. (Dr Gutman's book).>>>>>>
GLUTATHIONE (GSH)You may or may not have heard of `glutathione.' However, researchers and scientists continue to discover the importance of this substance in health and disease and in the next few years its name will become as well known as terms like 'cholesterol' or 'vitamin.' Your life depends on glutathione. With­out it, your liver would shrivel up and die from the overwhelming accumu­lation of toxins, your cells would disintegrate from unrestrained oxidative stress and, as if you needed more problems, your body would have little resistance to bacteria, viruses or cancers. So many protective systems of the body, including its use of vitamins C and E, depend heavily upon this re­markable molecule.THE IMPORTANCE OF GLUTATHIONEGlutathione's importance to your health cannot be overstated. Your im­mune system is constantly on the prowl for pathogens—agents of cellular damage, toxicity and disease. To neutralize them the body needs a ready supply of glutathione. If it doesn't have enough, some of the invaders will get through, infecting the body and/or contributing to aging, long-term accumulative damage—even eventual cancer. We can't avoid illness and ag­ing altogether—though a few scientists are pursuing the age-old dream of immortality—but by keeping our intracellular glutathione levels up we also keep our immune system on the ball and fully armed. GSH is fundamental to the immune response.RESEARCH ON GLUTATHIONEIn the last twenty years the volume of research into GSH has grown im­mensely. A huge variety of theoretical papers, bench-top laboratory experi­ments, epidemiological studies, animal projects and—most importantly—clinical trials on humans, has linked glutathione to an extraordinary variety of illnesses. The list is long and would be hard to believe were it not for the strength and credibility of the research. However, it is now clear that glutathione's role in the immune response, detoxification and antioxidation is pivotal. Without it, many bodily processes would fail.All the information in this book is derived from the scientific reports listed at the end of each chapter. Hundreds of articles have described how elevated glutathione levels help combat the infirmities of aging, such as Parkinson's disease, Alzheimer's disease, cataract formation, macular degen­eration, and cancers of aging (e.g. prostate cancer). You will find references to all these subjects listed in the index.1-GLUTATHIONE (GSH) 11
GSH is also known to play a crucial role in the cardiovascular system, helping prevent heart disease, stroke, atherosclerosis and reperfusion injury. In an ideal situation where the patient is exercising, eating properly, avoid­ing tobacco and maintaining a good general lifestyle, raising glutathione levels can actually help reverse atherosclerosis (see chapter 9).In the digestive system glutathione helps the body fight inflammatory bowel disease, hepatitis, malnutrition, pancreatitis and peptic ulcer. Its antioxidant properties and its role in maintaining the immune response have led to inter­esting strategies against these all-too-common problems (see chapter 15).Overdosing of certain drugs has been treated for some time with a variety of GSH-enhancing drugs that have become mainstays in critical care medi­cine. However only recently has it been recognized that GSH is a powerful detoxifier of many other nasty substances—including those released from ciga­rette smoke and auto exhaust, such pollutants as heavy metals and pesticides, and many well-known carcinogens. Believe it or not, the evidence shows that GSH even helps prevent hearing loss from noise pollution (see chapter 17).In infectious disease and immunology, glutathione's anti-viral properties help the body fight AIDS, hepatitis, herpes and the common cold. Its role in com­bating bacterial infection has also been clearly described. Although raised GSH levels do not effect a "cure," they elevate and sustain our natural immune re­sponse, providing reinforcement to deal with the threats at hand and minimiz­ing damage. GSH also has potential applications against some autoimmune dysfunctions, chronic fatigue syndrome and states of immunosuppression.The immune system is on constant alert against the threat of cancer. Glu­tathione helps prevent carcinogenesis (the transformation of normal cells into cancer cells) by eliminating carcinogens and mutagens from the body and by slowing down oxidative damage to DNA and other sensitive structures within the cell. In cases of diagnosed cancer, glutathione has been shown to suppress tumor growth, prevent the wasting disease associated with advanced cancer and ease the side effects of chemotherapy and radiotherapy (see chapter 5).In pulmonary or respiratory medicine, raised glutathione levels have been used for many years in Europe and now increasingly in North America. Glu­tathione can break up mucus (especially in cystic fibrosis), reduce the danger of asthmatic attacks, aid in both acute and chronic bronchitis and fight emphy­sema and pulmonary fibrosis. All these mechanisms are described in chapter 14.We have also included chapters on glutathione's many metabolic func­tions, including its role in complications of diabetes, reduction of choles­terol and oxidation of bad cholesterol (LDL), and its support of red blood cell levels in patients suffering from kidney failure.Finally, we present research emphasizing the importance of glutathione in the healthy individual. For the physically active, GSH enhances athletic12 GLUTATHIONE
performance, decreases recovery time from physical stress and aids in im­mune function. For the average person, its role in health maintenance just can't be overestimated. Glutathione modulation is an essential part of staying young, active and healthy (see chapters 23 and 24).In his book on antioxidants (What You Should Know About the Super Antioxidant Miracle) Dr. Earl Mindell states "We literally cannot survive without this miraculous antioxidant." Dr. John T. Pinto of the Sloan Kettering Cancer Center in New York proclaims, "It is the master antioxi­dant." Jean Carper in her book Stop Aging Now! claims, "You must get your levels of glutathione up if you want to keep your youth and live longer. High levels of GSH predict good health and a long life. Low levels predict early disease and death."Closer to the raw science of glutathione, Dr. Gustavo Bounous, a re­searcher and leading authority on GSH and nutrition at McGill University in Montreal says, "In view of existing scientific data, all we can expect from the environment is continued pollution, ozone depletion, and the increased virulence of infections. I think that enhancing glutathione levels will allow for a better quality of life."You don't have to be a scientist to understand that as society 'progresses' we become increasingly dependent upon technology and have to live with its many unhealthy by-products. Not all of them are as tangible as toxic waste. There's the stress and hurry of modern life—few of us take the time to listen closely to our bodies' demands, to eat and exercise accordingly, nor even to rest as often as we might need. We are driven by forces that some­times leave us numb to our spiritual and physical needs. Our whole being is affected, but a strong immune system can help take the physiological brunt of it. What it needs is regular maintenance and the all-important raw mate­rials to make glutathione.GSH-THE MOLECULEGlutathione is the general term for glutathone sulfhydryl, abbreviated as GSH. The `SH' represents the critically active sulfur sulfhydryl group. GSH is a peptide (very small protein) that occurs naturally within the body, where it is assembled by individual cells from its three components—the amino-acids glycine, glutamate (glutamic acid), and the all-important cysteine. Because it contains three amino acids it is referred to as a tripeptide. Glutathione's molecular structure is represented in figure 2.Of these three amino acids, cysteine is the hardest to find. Cysteine is a sulfur-containing amino acid that contributes the sulfhydryl group to the molecule, making it also the most important of these raw ingredients. When cells have cysteine, they can efficiently manufacture GSH. However, this1-GLUTATHIONE (GSH) 13

amino-acid is absent or deficient in many diets. Also, it must be in an acces­sible form. Cysteine has trouble surviving the trip from your mouth to your cells unless it's part of a larger protein.


Without adequate cysteine, cells can't produce enough GSH and the body suffers on three fronts: cellular oxidation contributes to general decline and aging, toxins accumulate in the body causing further damage, and the immune system is compromised, leaving us vulnerable to disease.
On the other hand, there are many benefits for the body with elevated glutathione levels. Its metabolic functions include:
q Enhanced immune functionq Elimination of toxinsq Elimination of carcinogensq Antioxidant cell protectionq Protection against ionizing radiationq DNA synthesis and repairq Protein synthesisq Prostaglandin synthesisq Leukotriene synthesisq Amino acid transportq Enzyme activation and regulation
These functions can be summarized into three general categories:
1 ANTIOXIDANT - GSH is the most powerful antioxidant occurring natu­rally in your body. The effectiveness of other antioxidants like vitamins C and E depends on glutathione. This is described in the following pages.
2 DETOXIFIER - Dozens of toxins are eliminated by the GSH enzyme system, including drug metabolites, pollutants, carcinogens and radiation damage. It's no surprise that GSH concentrations are highest in the liver, the body's major detoxifying organ (see chapter a).
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3 IMMUNE SYSTEM ENHANCER - The immune system is dependent upon GSH for its proper functioning, in particular the creation and maintenance of T-cell lymphocytes, the body's frontline defense against infection. See chapter 3 for details.These three functions are not separate. As far as the immune system is con­cerned, it is just using GSH to do its job. A GSH molecule may neutralize a free radical, be recycled by the GSH system and then eliminate a stray toxin. The remainder of part 1 describes these functions in detail and how we can maintain them. Before we look at its antioxidant role we must de­scribe the processes of oxidation.OXIDATION AND ANTIOXIDATIONToday there is enormous growth in the markets for preventative and anti-aging medicine, and much time and money has been spent looking into the wear and tear of living, breathing and eating. This non-stop activity places continuous stress on every cell of the body, and every cell must respond or suffer damage. Terms like oxidation, free radical, oxyradical and antioxi­dant are used to describe these processes. What do they mean?Each and every cell in the body is a biological machine that is gradually worn down by the work of staying alive. It's an imperfect system. Like all machines, cells derive their energy from the consumption (oxidation) of fuel—nutrients and oxygen—but at a price. This process produces harmful waste products (free radicals or oxyradicals). One of our cells' most routine tasks is to neutralize and remove these wastes, and the key substance it uses is glutathione. Glutathione is the body's principal antioxidant. When it runs out, oxyradicals proliferate, slowly but surely wreaking havoc. In Part Two you will see that severe GSH deficiency is common to many diseases, especially in their advanced, chronic conditions.How do oxyradicals form? If you were to look inside a cell you'd see thousands of tiny chemical reactions that use oxygen to metabolize nutri­ents and release energy. This is the necessary process of oxidation. But oxi­dation produces harmful byproducts—oxyradicals, or unstable atoms.An atom is a nucleus orbited by electrons. By working in pairs like children on a seesaw electrons maintain a balanced and stable orbit. But sometimes during oxidation an electron is knocked off its orbit, leaving its partner un­balanced, as shown in figure 3. The remaining electron spontaneously cor­rects the imbalance by stealing a neighbor's electron, which then does the same again. Imagine a playground full of children jumping from seesaw to seesaw. The resulting chain reaction of disrupted molecules can cause untold damage to individual cells. Fortunately, our cells are equipped with natural antioxidants—agents that neutralize free radicals by giving them an electron,1—GLUTATHIONE (GSH) 15
rather as a playground monitor ensures that each child has a partner.
This process of oxidation and antioxidation occurs continuously. Oxida­tion isn't a bad thing—after all, it provides energy and is also a frontline defense against bacteria and viruses. But if our diet lacks certain nutrients or vitamins, or if our body experiences excessive oxidative stress and in­creased oxyradical production, individual cells inevitably suffer. This isn't surprising. After all, oxidation causes metal to rust, apples to rot and butter to turn rancid. It also causes natural aging in humans. But its effects don't end there. Free radicals can damage or destroy cell walls, cause cell death (apoptosis) and disrupt DNA patterns, potentially leading to cancer.Lipid peroxidation (a precipitous oxidative chain reaction) is responsible for the breakdown of fats, particularly 'bad' cholesterol (LDL-cholesterol) which damages arteries and leads to blocked blood vessels, heart disease and stroke (see chapter 9). The list of ailments caused by oxidation and free radical formation grows longer every day. In fact, a whole new field of medi­cine has developed, called 'Free Radical Biology.' It studies the diseases and potential damaging effects of oxidative stress. Today there is no doubt that antioxidants help diminish cell damage, lessen the threat of disease and slow the harmful effects of aging.Many factors contribute to oxidative stress. Some of them are poor diet, pollution, drugs, radiation, stress, trauma, injury, burns, aging and infection by bacteria or viruses. Each time your immune system confronts a threat, free radicals are released. Free radicals are also created in large numbers during exercise, when more energy is used and the rate of oxidation increases, and every time your body encounters fatigue, illness, inflammation, pollution, toxins and radiation. As you will see in the following paragraphs, glutathione is the body's key natural antioxidant. You can minimize oxidative damage by raising intracellular GSH levels and keeping them there.GLUTATHIONE-THE MASTER ANTIOXIDANT
How does GSH work with other antioxidants? They all have their advan­tages and disadvantages. You should never stop using established supple‑

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ments like vitamins C and E. These substances act synergistically with GSH—i.e., they enhance each other's effectiveness. We call GSH the mas­ter antioxidant because it replenishes the action of many other antioxi­dants. When vitamins C and E pick up an oxyradical they must hand it off to the GSH system so they are free to go back and get others. GSH simi­larly neutralizes peroxide and lipoic acid. In fact, all of these antioxidants help to neutralize each other, and glutathione is at the center of cellular antioxidation. It is GSH—not the vitamin—that ultimately neutralizes the radical. A GSH molecule encounters a destructive, positively-charged hydroxyl radical and gives it an electron, turning it into harmless water. The GSH molecule has not become a radical but pairs up with another radicalized GSH molecule to form neutral, non-toxic GSSG.
Another synergistic antioxidant is selenium. Studies show it to be clinically
similar to glutathione and it is an integral component of the important en‑
zyme GSH-peroxidase. For this reason selenium is considered a GSH-booster.
None of these important but lesser antioxidants occur naturally in the
cell—only glutathione. All others are obtained from the food we eat. GSH is
1-GLUTATHIONE (GSH) 17
a vital, natural component of your cells—an endogenous antioxidant. It is manufactured within from amino-acid precursors. If you want to boost your body's defenses against oxidation, your best bet is to give it the raw materials it needs to produce glutathione. GSH is at the heart of cellular antioxidation. It works in conjunction with the secondary (exogenous) antioxidants perox­ide, lipoic acid, vitamin C and vitamin E, relieving them of destructive charged ions and enabling them to return to the battle.
GSH—THE IMMUNE SYSTEM ENHANCER
A body well-stocked with intracellular glutathione fights illness more effectively than one that depends on exogenous (dietary) antioxidants. GSH helps prevent pathogens from gaining a foothold. And when they do get through they are confronted by an enhanced immune system. Glutathione therefore provides both preventive and therapeutic advantages. This is mainly because elevated glutathione levels enable the body to produce more white blood cells. These constitute the most important division of the immune system's ground-troops. Glutathione's overall role in the immune response is discussed in chapter 3.
GSH—THE DETOXIFIER
We inhale and ingest natural and synthetic toxins every day of our lives and can't possibly avoid them, especially in our technological times, our congested, polluted cities and with our engineered food supplies. As long as it has the health and nourishment it needs the body goes to great lengths to eliminate toxins and protect itself. Our main organ of detoxification is the liver—the largest organ in the body and also the depository of the body's highest con‑


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centrations of glutathione. Experimental studies have shown that low glu­tathione levels lead to poor liver function, and result in unnecessarily large quantities of toxins circulating through the body. There, they continuously damage individual cells and organs. Chapter 2 describes the role of glutathione in detoxification. The liver and its function is described in chapter
CONCLUSION
Glutathione carries out many crucial functions in our body, of which three stand out. GSH is 1) the most important naturally-occurring antioxidant in our cells, 2) a key enzyme system for the detoxification of countless noxious substances and 3) a critical element that sustains the functioning and well­being of our immune systems. These vital roles are now beyond doubt and considerable research is underway to uncover the full range of clinical appli­cations for the preventative and therapeutic roles of elevated GSH levels.
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REFERENCES TO CHAPTER IGLUTATHIONE (GSH)
BEUTLER E. Nutritional and metabolic as­pects of glutathione. Annual Review of Nutri­tion 9:287-302, 1989BRAVERMAN E, PFEIFFER C, BLUM K, SMAYDA R. The Healing Nutrients Within: Facts, Findings, and New Research on Amino Acids. [ISBN 0-87983-706-3] Keats Publish­ing, New Canaan, Connecticut, 1987BRAY T, TAYLOR C. Enhancement of tissue glutathione for antioxidant and immune func­tions in malnutrition. Biochemistry Pharma­cology 47:2113-23, 1994CARPER J. Stop Aging Now! [ISBN o-o6- 018355-1] Harper Collins Publishers, New York, NY 1995COMMANDEUR JNM, STIJNTJES GJ, VERMEULEN NPE. Enzymes and transport systems involved in the formation and dispo­sition of glutathione s-conjugates Pharmaco­logical Reviews 47: 271-330, 1995DENEKE SM, FANBURG BL. Regulation of cellular glutathione. American Physiological So­ciety 1,163-L173, 1989FAHEY, RC. Protection of DNA by Thiols. Pharmac. Therapeut. 39: 101-108, 5988
KIDD PM. Glutathione: Systemic protectant against oxidative and free radical damage. Al­ternative Medicine Review 2:155-176, 1997KIDD PM, Huber W. Natural antioxidants—First line of defense in Living with the AIDS virus: A strategy for long term survival. PMK Biomedical-Nutritional Consulting: 115-142, 1991LOMAESTRO B, MALONE M. Glutathione in health and disease: Pharmacotherapeutic Issues. Annals of Pharmacotherapy 29:1263-73, 1995MEISTER A. Glutathione metabolism. Meth­ods in Enzymology 252:3-7, 1995MEISTER A, ANDERSON ME. Glutathione. Ann Revue Biochemistry 52:711-60, 1983MINDELL E. What you should Know About the Super Antioxidant Miracle. [ISBN 0-87983-721-7] Keats Publishing, New Canaan, Connecticut, 1996PRESSMAN AH . The GSH Phenomenon. [ISBN 0-312-15135-7] St. Martin's Press, New York NY. First Edition, 1997
by Jimmy Gutman MD GLUTATHIONE

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