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CONTENTS

WHAT IS GLUTATHIONE? 3Why Glutathione is Essentialto Health. . . . . . . . . . . .. 4The MasterAntioxidant. . . . . . . . . . . . . . . . . . . . . . . .. 4Food for the Immune System. . . . . . . . . . . . . . . . . . . .. 4NaturalDetoxification. . . . . . . . . . . . . . . . . . . . . . . . .. 4

Glutathione in Natural Medicine. . . . . . . . . . . . . . . . . . . 5Glutathione in Traditional Medicine. . . . . . . . . . . . . . . . 5DrugsThat RaiseGlutathione Levels. . . . . . . . . . . . . . . . 5Natural ProductsThat RaiseGlutathione Levels. . . . .. 6

GLUTATHIONEIN HEALTHAND DISEASE. . .. 8Puttingitalltogether. . . . . . . . . . . . . . . . . . . . . . . . . .. 8

SELECTED MEDICAL REFERENCES. . . . . . . . .. 10

Aging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Antioxidant Functions. . . . . . . . . . . . . . . . . . . . . . . . . . IO

NeurologicalDisease. . . . . . . . . . . . . . . . . . . . . . . . . . . . IO

Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Athletic performance. . . . . . . . . . . . . . . . . . . . . . . . . . . . IO

Toxins,Pollution, Radiation. . . . . . . . . . . . . . . . . . . . . . IO

AIDS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Heart disease, stroke and cholesterol. . . . . . . . . . . . . . . . IO

Diabetes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . II

Lung disease.. .. .. .. .. . .. .. .. .. .. .. .. .. . .. .. .. II

Digestivediseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . II

Hepatitis. . . . . . . . . . . . . ,. . . . . . . . . . . . . . . . . . . . . . . II

Kidney disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . II

Pregnancy, lactation and childbirth. . . . . . . . . . . . . . . . . II

BACK COVER: Inside each cell of the body the

gears of antioxidation ate driven by glutathione as

it recycles peroxide, lipoic acid, vitamin C and

vitamin E, putting them all back to work.

WHAT IS GLUTATHIONE?

. Glutathione (pronounced "gloota-thigh-own") is the body's essential health AID -

Antioxidant, Immune booster and Detoxifier. This small protein, produced natu-

rally in the body, maintains these three crucial protective functions. In fact, your

life depends on glutathione. Without it, your cells would disintegrate from unre-

strained oxidation, your body would have little resistance to bacteria, viruses and

cancer, and your liver would shrivel up from the eventual accumulation of toxins.

. Glutathione is not yet a household word. Even doctors who have heard the term

may have only a vague idea of it. However, everyone will soon b~ talking about thiscritical substance. There was a time when only scientists had heard of cholesterol

and vitamins, but today everyone knows about them. Now it's glutathione's turn.

In the last five years, over twenty-five thousand medical articles about this sub-

stance have been published, and this scientific understanding is gradually becom-

ing common knowledge.. Each and every cell in the body is responsible for its own supply of glutathione,and must have the necessary raw materials to make it. Glutathione is always in

great demand and is rapidly consumed when we experience any sort of pressure -

illness, stress, fatigue and even exercise. Some well-known causes of glutathione

depletion are shown in figure I. Glutathione levels also diminish as we age and many

diseases normally associated with aging have been linked to glutathione deficiency.

Figure 1 - Surviving in 4 hostile worldAdapted from KidJ & Huber, "N4tur4{ antioxidants -First lin~ of defens~, " 1991

"..., .

WHY GLUTATHIONE IS ESSENTIAL TO HEALTH

Glutathione's three major roles in the body are summarized by the letters A-I-D - Anti-

oxidant, Immune booster, and Detoxifier - three critical processes driven by glutathione.

THE MASTER ANTIOXIDANT (AID)

Over the past thirty years researchers have explored the value of antioxidants in good

health, as well as the treatment and prevention of diseases involving oxidative attack

by free radicals. This has produced a whole new branch of medicine - Free Radical

Biology. Free radicals have been implicated in all sorts of illness, including heart

disease, cancer, diabetes and aging itself

Well-known and widely used antioxidants such as vitamin C, vitamin E and sele-

nium neutralize free radicals. They occur naturally in nature, but not in the body -

they must be introduced as part of a balanced diet. Given the critical role of antioxidants

in good health, it is not surprising that the body itself manufactures its own natural

antioxidants. The most important of these is glutathione. Because all other antioxidants

depend upon the presence of glutathione to function properly, scientists call it "themaster antioxidant."

FOOD FOR THE IMMUNE SYSTEM (AID)

The immune system's function is to identify and attack germs and other invaders, including

cancer cells. A body with plenty of glutathione fights off these threats more easily by

denying most of them a foothold and by confronting the few that get through with an

enhanced immune system. Elevated glutathione levels enable the body to produce more

white blood cells - the most important front line defense of the immune system.

Glutathione plays a central role in the functions of these immune cells. Dr. Gustavo

Bounous, a leading glutathione expert says, "The limiting factor in the proper activity

of our lymphocytes (white blood cells) is the availability of glutathione." In other

words, healthy growth and activity of immune cells depend upon glutathione's availability.

Put simply, glutathione is 'food' for the immune system.

NATURAL DETOXIFICATION (AID)

Whether we know it or not, we are continually inhaling and ingesting natural and

synthetic toxins. They are unavoidable in these modern times, both in our polluted

cities and our engineered food supplies. When the body has its health and the nourish-

ment it needs it works tirelessly to eliminate toxins and protect itself, but increasing

levels of environmental pollution ~e. depleting its stores of glutathione more andmore rapidly. Our main organ of detoxification is the liver - the body's most concen-

trated source of glutathione. Studies show that low glutathione levels lead to poor

liver function, causing more and more toxins to circulate through the body and re-

sulting in damage to individual cells and organs. Doctors routinely use glutathione-

promoting drugs to detoxify victims of certain types of drug overdose.

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GLUTATHIONE IN NATURAL MEDICINE

Practitioners of complementary medicine have long advocated the use of milk thistle

for liver problems. It turns out that this herb works by modestly elevating glutathione

levels. The mineral selenium also produces subtle elevations in glutathione by be-

coming integrated into the enzyme glutathione peroxidase.

GLUTATHIONE IN TRADITIONAL MEDICINE

Emergency doctors, toxicologists and lung and liver specialists are well acquainted

with glutathione's therapeutic uses. American physicians seeking ways to raise a patient's

glutathione levels can open the standard Physician's Desk Reference (PDR) and find

two options - the pharmaceutical drug NAC (n-acetyl-cysteine), sold under brand-

names Parlodex and Mucomyst, and the natural dietary supplement lmmunocal (pat-

ented whey protein isolate).

DRUGS THAT RAISE GLUTATHIONE LEVELS

Pharmaceutical drugs like those shown in figure 2 have been used to raise glutathione

levels. However, they all produce side effects and are unsuitable for long-term use.

The drug NAC (n-acetyl-cysteine) is a potent glutathione precursor that has been

available for many years, and is also found on the shelves of health supplement stores.

This pharmaceutical chemical is used to break up mucus in lung diseases such as

cystic fibrosis, chronic bronchitis and asthma. It remains the standard treatment for

acetaminophen overdose. Most traditional glutathione studies on humans have beenconducted with NAC.

Figure 2 - Glutathione-promoting substances

PJ7!.Igs Niftturalprodu(U Clittatfiioheco..fadorsOral GlutathiQne SeleniumNAC

SAM Cysteine

Methionine

Melatonin

OTC

OTZ

Procysteine

Glutathione monoesters

Glutathione diesters

Glutamine

Lipoic Acid

Silymarin (milk thistle)

Whey Proteins

Bioactive wheyproteins (Immunocal")

Vitamin B1

Vitamin B2

Vitamin B6

Vitamin B12

Folate, Folic acid

. Vitamin C

Vitamin E

Other nutrients

NAC therapy has two common problems: firstly, it is a pharmaceutical drug andcarriesa certain toxicity itself;secondly,NAC-induced glutathione levelsreach a rapidpeak and decline within hours. The drug is thus described as having a short half-life.Rapid peaks are often followed by a sudden fall, often to below normal levels. Tomaintain constantly elevatedglutathione levels,NAC must be swallowed or injectedseveral times per day, and this is very hard on the body. Many people taking NACreport symptoms including rash, wheezing, nausea, vomiting, cramps and diarrhea.Others find the smell and taste unacceptable. Although rare, death has been reportedin association with NAC. However, it is still the most commonly used way to raise

glutathione levels in clinical settings.OTC (ornithine decarboxylase, procysteine), OTZ (oxothiazolidine carboxylate),

glutathione monoesters and glutathione diesters are all synthetic compounds withonly limited ability to raise glutathione levelsand have unproven safety records.

NATURAL PRODUCTS THAT RAISE GLUTATHIONE LEVELS

ORAL GLUTATHIONE

A variety of chemical companies package glutathione itself in pill or powder form,

but this is not particularly helpful to the body. A small amount of glutathione may

make it into the bloodstream, but most is lost during the digestive process and cannot

effectively raise intracellular glutathione levels. It may even lead to a possible decrease

in blood glutathione.

CYSTEINE (L-CYSTEINE)

Cysteine, availablethrough pharmacological suppliers and at health food stores, mayraise intracellular glutathione to a small extent but it is oxidized in the digestive tractand enters the bloodstream only with difficulty. Cysteine's toxicity is well describedin the medical literature.

METHIONINE (L-METHIONINE)

The essential amino acid methionine is present in many foods and has been identified

as a glutathione precursor. But it is also a precursor of homocysteine, recently recognized

as a high risk factor in the development of atherosclerosis (hardening of the arteries).

MELATONIN

Melatonin is known for its role in the regulation of sleep and 'waking cycles and is

popular for the treatment of jet lag, insomnia and other sleep disturbances. These

benefits may be explained by melatonin's ability to raise glutathione levels in the

brain, liver, muscle, blood serum and other tissues. However, the body's response to

melatonin varies greatly from one person to another, and its long-term safety has not

yet been established. This product should only be used under the guidance of an

appropriate health professional.

~

,

GLUTAMINE

Whether taken orally or intravenously, glutamine supplements raise glutathione con-

centrations, but completely healthy individuals shouldn't require supplemental

glutamine and it can lead to side effects such as gastrointestinal upset. Older people

as well as kidney and liver patients should be cautious. Any serious use of this supple-

ment must be monitored by a health professional.

LIpOIC ACID

Lipoic acid occurs naturally in the body but is also found on the shelves of health

food stores. It is known that as glutatathione molecules neutralize free redicals they

gradually become oxidized, but lipoic acid can replenish its antioxidant powers by

converting it back to a reduced form. It is still being investigated by scientists.

SILYMARIN(MILK THISTLE)

The milk thistle plant, (Silybum marianum, silymarin) has a long history in the

treatment of liver problems. It clearly prevents the oxidation of fats and maintains

glutathione levels, but possible toxic reactions include gas, cramps and diarrhea. Liver

disease should never be treated without the supervision of a health professional.

WHEY PROTEINS

Whey, a large group of proteins, is a constituent of milk from humans and other

mammals, and under ideal circumstances contains the building-blocks of glutathione.

Many whey products are marketed to health-conscious people but they vary greatly

in their protein content, their concentration, the forms of proteins present, and other

factors that affect the product's bioactivity (biological action). Perhaps the most

important criterion of all is the extent of the product's protein denaturation - a break-

down in the protein structure. This reduces its potential bioactivity in the body with-

out affecting its food value. In addition, many nutritionists point out that the fat or

lactose content of whey products may still b<';.high enough to cause concern. Others

have reservations about the milk industry and its liberal use of antibiotics and steroids

to boost production. Also, we cannot ignore the very real issue of fat-soluble and

water-soluble environmental toxins passing into the milk.

The whey content of truly fresh milk contains such potent glutathione building

blocks as lactoferrin, beta-lactalbumin and serum albumin - all easilydenaturedbyheat or mechanical agitation. Pasteurization and other industrial processes tend to

denature milk products and by the time they reach your table their bioactivity is lost.

To maintain the bioactivity of glutathione precursors whey proteins must be ex-

tracted from milk with special means, and careful monitoring is essential. Whey

products may contain anything from 20% to 90% protein. These proteins vary greatly

in their make-up as well as the extent to which their glutathione precursors are

denatured. So, although some whey proteins are bioactive, most are not.

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BIOACTIVE WHEY PROTEIN

Bioactive whey proteins contain high levels of non-denatured protein and this assures

their glutathione-promoting activity. Much of our knowledge of the glurathione-

sustaining effect of dietary whey proteins is the result of research initiated at Montreal's

McGill University in Canada during the early 1980'S. Dr. Gustavo Bounous was

studying protein supplementation in general when he discovered the bioactive potential

of whey protein in particular. He investigated its effect on the immune system and

published his ground-breaking results. They encouraged other scientific teams to

study the effects of glutathione-enhancement in tests on a wide variety of diseases.

Dr. Bounous and his team went on to develop Immunocal - a whey protein made

under pharmacological conditions to maximize the protein's bioactivity.Undenatured whey protein is a natural extract of milk - a safe, dependable and

effective way to sustain elevated glutathione levels.

GLUTATHIONE IN HEALTH AND DISEASE

It is believed that glutathione has an important role to play in the treatment and

prevention of hundreds of diseases. It may in the futUre be considered as importantto health as a well-rounded diet, exercise and good lifestyle. Clinical tests show that

raised glutathione levels may address some of the major health issues of our time -

heart disease, stroke, diabetes, high cholesterol, asthma, cigarette smoking, hepatitis,

AIDS and more. Glutathione provides the body with tools to fight off these threats

naturally.

Healthy people also benefit from elevated glutathione levels through an enhanced

ability to fight off toxins, infectious disease, pre-cancerous cells and the aging process

itself Diminished glutathione levels are a symptom of aging and are particularly evidentin such ailments as Parkinson's disease and Alzheimer's disease.

Glutathione is also important to physically active people. Many world-class ath-

letes are discovering that well-maintained glutathione levels give them the edge over

their competitors, bringing greater strength and endurance, decreased recovery time

from injury, less muscle pain and fatigue, and muscle-promoting activity.

PUTTING IT ALL TOGETHER

. Medical science is still ascertaining all the critical roles played by glutathione in

disease resistance and general good health. Clinical evidence links low glutathione

levels to the most common illnesses of our time as well as newly emerging diseases.

. As an essential AID to health, glutathione works as the master Antioxidant in our

body, optimizes the Immune system and Detoxifies a long list of pollutants and~~.~:~~~o~o UmnOHO. ~hQ h~..1H'C ~1"h~h;~"'Q ],"H,o10 "r,o "'AT r";o,orl h" ,o~T;no- 0-111-

Figure 3 - Raising glutathione levels: some possible clinical applications

Aging0 Parkinson'sdisease0 Alzheimer'sdisease0 Cataractformation0 Maculardegeneration0 Cancersof aging0 Prostate problems0 Osteoarthritis

Cardiovascular0 Prevents heart disease0 Prevents stroke0 Prevents atherosclerosis0 Reverses atherosclerosis

0 Prevents reperfusion injury

Digestive system0 Inflammatory bowel disease0 Hepatitis0 Malnutrition0 Pancreatitis

0 Peptic ulcer

Toxicology0 Detoxifies certain drug overdoses0 Detoxifies substances in cigarette

smoke, auto exhaust

0 Detoxifies pollutants includingheavy metals, pesticides

0 Preventshearing loss from noisepollution

0 Detoxifies many well-knowncarcinogens.

Infectious diseaseand immunology0 Anti-viral (AIDS,hepatitis, herpes,

common cold, etc.)0 Bacterial infection

0 Certain autoimmune dysfunctions0 Chronic fatigue syndrome0 ImmunosuppressionCancer

0 Cancer prevention0 Suppresses tumor growth0 Eliminates carcinogens, mutagens'0 Retards oxidative damage to DNA0 Prevents wasting disease0 Eases side effects of chemotherapy

and radiotherapy

Pulmonary0 Breaks up mucus0 Cystic fibrosis0 Asthma0 Chronic bronchitis

0 Emphysema0 Pulmonary fibrosisMetabolic0 Athletic enhancement

0 Decreases recovery time fromphysical stress

0 Decreases cholesterol LDLoxidation

Q Supports hemoglobin in kidneyfailure

0 Diabetes

tathione, since it is poorly absorbed through the digestive system. It must be manu-

factured within the cells of the body. Therefore, the best way to raise glutathione

levels is by providing the building blocks used by the cells to make it themselves.

. Pharmaceutical medicine has created drugs that do this very effectively, and they

have their uses in critical situations. But they also have side effects and repeated

use is clearly inadvisable. Recently, scientists have studied natural ways to raise

glutathione levels by safe, reliable dietary means. The emergence ofbioactive whey

proteins is an exciting step forward in nutritional supplementation.

SELECTED MEDICAL REFERENCES

AGING

It is well known that aging is accompanied by a precipitous fall in glutathione levels.

Lower glutathione levels are implicated in many diseases associated with aging in-

cluding cataracts, Alzheimer's disease, Parkinson's, atherosclerosis and others.

JOURNAL OF CLINICAL EPIDEMIOLOGY 47: 1021-26, 1994

ANTIOXIDANT FUNCTIONS

Antioxidants are well documented and known to possess vital roles in health mainte-

nance and disease prevention. Glutathione is your cell's own major antioxidant.

Maintaining elevated glutathione levels aids the body's natural antioxidant function.

BIOCHEMICAL PHARMACOLOGY47: 2113-2123, 1994

NEUROLOGICAL DISEASE

Low glutathione levels have been associated with neuro-degenerative diseases such as

MS (Multiple Sclerosis), ALS (Lou Gehrig's disease), Alzheimer's disease and

Parkinson's disease, among others.

THE LANCET 344: 796-798, 1994

CANCER

Glutathione plays a role in eliminating many carcinogens and also maintains an

optimized immune function, providing stronger anti-tumor defenses.

CANCER LETTERS 57: 91-94, 1991

ATHLETIC PERFORMANCE

Raised glutathione levels help increase strength and endurance. Those interested in

physical fitness can benefit from a definite atWetic edge.JOURNAL OF ApPLIED PHYSIOLOGY 87: 1381-1385, 1999

TOXINS, POLLUTION, RADIATION

Glutathione detoxifies a variety of pollutants, carcinogens and poisons, including many

found in fuel exhaust and cigarette smoke. It also retards damage from radiation

exposure due to the eroding ozone layer.

ANNUAL REVIEWS OF BIOCHEMISTRY 52: 711-760, 1983

AIDS

Lowglutathionelevelscorrespondto poor survivalin AIDS patients.Much docu-mentationdemonstratesthe roleof enhancedglutathionelevelsin AIDS.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCE, USA 94: 1967-72, 1997

10

HEART DISEASE, STROKE AND CHOLESTEROL

Raised glutathione levels fight the oxidation of circulating fats in the bloodstream,

including cholesterol, retarding the process of plaque formation in the arteries - theunderlying cause for most heart disease and stroke.

NUTRITION REVIEWS 54: 1-3°, 1996

DIABETES

Diabetics are more prone to infections and circulatory problems leading to heart

disease, kidney failure and blindness. Glutathione protects against the complicationsof diabetes.

CLINICAL SCIENCE 91:575-582, 1996

LUNG DISEASE

Doctors have used glutathione-promoting drugs to treat many lung diseases includ-

ing asthma, chronic bronchitis and emphysema. Newer potential therapeutic roles

can be found for cigarette smoke damage, pulmonary fibrosis and other illnesses.

AMERICAN JOURNAL OF MEDICAL SCIENCE 3°7:119-127, 1994

DIGESTIVE DISEASES

Glutathione protects the body from the inflammation of gastritis, stomach ulcers, pan-

creatitis and inflammatory bowel disease including ulcerative colitis and Crohn's disease.

GUT 42: 485-492, 1998

HEPATITIS

The liver is the major storehouse for glutathione. Glutathione is impaired in alco-

holic hepatitis as well as in viral hepatitis including hepatitis A, B, and C. Raised

glutathione levels restore liver fun~tion.AMERICAN JOURNAL OF GASTROENTEROLOGY 91: 2569-2573, 1996

KIDNEY DISEASE

People with kidney failure or dialysis suffer from higher levels of oxidative stress and

decreased glutathione levels. Raised glutathione levels help prevent anemia. .

NEPHRON 61: 404-408, 1992

PREGNANCY, LACTATION AND CHILDBIRTH

Glutathione's role in fetal and placental development is crucial. It also acts in the

placenta to detoxifY pollutants before they can reach the developing child. Many

complications of pregnancy have been linked with poor glutathione levels.EARLY HUMAN DEVELOPMENT 37: 167-174, 1994

Portions of this bookler adapted from Glutathione, Your Body's Most Powerfitl Protector, by DR. JIMMY

GUTMAN, @ 2°°4 Kudo.ca Communications Inc., Montreal, Canada.

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