The Science of Glutathione

The Undiscovered "Natural Drug"

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A recent press release by CBS highlighted the need for a "universal or all-purpose drug" able to combat any germ or toxic chemical released by hostile forces. In general, the idea would be to bolster the defenses we already possess, in particular the immune system, to fight against infections and cancer. CBS made brief mention of two substances, cysteine and glutathione, that deserve much greater attention.

Glutathione is a key substance found in every cell in our body, and may be thought of as a "naturally occurring universal drug"? and one without adverse side effects! It is the cell's most important antioxidant, neutralizing "free radicals" that would otherwise damage or destroy the cells. The body produces free radicals during metabolism. Under any form of stress, such as chemical toxicity or bacterial infections, the body generates many more free radicals. If glutathione is in short supply, these free radicals can overwhelm the cell. Exposure to radiation from sunlight or other sources also results in increasing highly reactive free radicals that likewise our bodies need to neutralize.

Glutathione is also the main detoxifying agent in the body. It converts damaging chemical substances (toxins) into harmless products that the body eliminates. Such chemicals include cancer-producing substances, heavy metals, herbicides, pesticides, smoke and other pollutants. Thus, glutathione provides important protection against many environmental hazards. The liver is particularly rich in glutathione for this purpose.

The immune system is our main defense against infection. Once again, glutathione plays a vital role, enabling the immune system to function optimally, which it cannot do when glutathione is deficient. For example, the cells of the immune system (lymphocytes) cannot multiply as much, cannot produce as many antibodies, and cannot kill unwanted cells like cancer cells or those infected with a virus. Glutathione deficiency also adversely affects other systems and organs such as the lungs, the nervous system, and the intestinal tract.

It is on record that there are many medical disorders associated with glutathione deficiency. These include AIDS and cancer wasting, some intestinal disorders, lung diseases, over-trained athletes syndrome and trauma. Furthermore, as we age, glutathione levels decrease which no doubt explains, in part, an older person's lowered resistance to disease.

Glutathione is a very small protein made inside the cells from three amino acids obtained ultimately from our food or supplementation. One of these amino acids, cysteine, gives the glutathione its antioxidant and detoxifying properties. This amino acid is relatively rare in foodstuffs and this can lead to glutathione deficiency, even in healthy people. For example, one study demonstrated that, by feeding a cysteine enriched food product, namely Immunocal?, glutathione values increased by 35.5% in the lymphocytes of normal young adults. (see reference below)

It is well documented that glutathione sold as a dietary supplement is mostly destroyed during digestion and therefore is of little use. Cysteine itself is toxic and suffers the same fate unless chemically modified. Practitioners use N-acetyl cysteine as a supplement, but it has certain unpleasant side effects, even in moderate doses. Thus, the best source for cysteine supplementation is from cysteine-rich foodstuffs. It is normally present in food as the stable form, cystine (2 molecules of cysteine linked together). Our bodies digest, absorb, and carry cystine to the cells where they convert it into cysteine. Since heat or mechanical stress etc., easily split cystine into cysteine (where digestion destroys it), raw unprocessed foods or special food supplements high in bioactive cysteine (cystine) provide the best source of this vital amino acid.

Sixty years ago, Florey and Fleming revolutionized the medical treatment of infection with the discovery of antibiotics that act against a broad range of bacteria. Glutathione, a "natural drug", perhaps in the same way could provide a significant contribution towards defending ourselves against the growing number of diverse biological and chemical hazards facing our society today.

The Science of Glutathione

Patricia A.L. Kongshavn, Ph.D

Patricia Kongshavn received her Honors Degree in Natural Sciences as a Major Scholar at Cambridge University, and completed her doctorate in Immunology at McGill University after immigrating to Canada. She subsequently joined the Faculty of Medicine at McGill University and held appointments in the Departments of Physiology and Medicine, becoming Full Professor in 1986. Her research was funded by independent grants to her from the Medical Research Council of Canada, the National Cancer Institute of Canada and the National Institutes of Health in the United States.

Her main research was concerned with increasing basic knowledge of the immune system, with a focus on cellular immunology, host/parasite interactions and the genetics of natural resistance.

In the mid-1970's she began collaboration initiated by Dr Gustavo Bounous to research the influence of various dietary proteins on immune responsiveness. They published their first paper on this research in 1978 and continued their collaboration until 1989, during which period they co-authored 14 papers. This work led to the discovery of an undenatured whey protein concentrate that regulated glutathione levels and promoted immune enhancing and anti-carcinogenic activity. This led ultimately to the production of a high quality bioactive nutraceutical: Immunocal.

Glutathione

Glutathione is a small molecule found in almost every cell. It cannot enter most cells directly and therefore must be made inside the cell, from its three constituent amino acids: glycine, glutamate and cysteine. The rate at which glutathione can be made depends on the availability of cysteine, which is relatively scarce in foodstuffs. Furthermore, the cysteine molecule has a sulfur-containing portion which gives the whole glutathione molecule its "biochemical activity", i.e. its ability to carry out the following vitally important functions:

Firstly, glutathione is the major antioxidant produced by the cell, protecting it from "free radicals" ("oxygen radicals", "oxyradicals"). These highly reactive substances, if left unchecked, will damage or destroy key cell components (e.g. membranes, DNA) in microseconds. Oxyradicals are generated in the many thousand mitochondria located inside each cell, where nutrients like glucose are burnt using oxygen to make energy. (Mitochondria can be thought of as the batteries that provide the power for the cells to operate). Oxyradicals also come from pollutants, from UV radiation and other sources. In addition, glutathione recycles other well-known antioxidants such as vitamin C and vitamin E, keeping them in their active state.

Secondly, glutathione is a very important detoxifying agent, enabling the body to get rid of undesirable toxins and pollutants. It forms a soluble compound with the toxin that can then be excreted through the urine or the gut. The liver and kidneys contain high levels of glutathione as they have the greatest exposure to toxins. The lungs are also rich in glutathione partly for the same reason. Many cancer-producing chemicals, heavy metals, drug metabolites etc. are disposed of in this way.

Thirdly, glutathione plays a crucial role in maintaining a normal balance between oxidation and anti-oxidation. This, in turn, regulates many of the cell's vital functions, such as the synthesis and repair of DNA, the synthesis of proteins and the activation and regulation of enzymes.

Fourthly, glutathione is required in many of the intricate steps needed to carry out an immune response. For example, it is needed for the lymphocytes to multiply in order to develop a strong immune response, and for "killer" lymphocytes to be able to kill undesirable cells such as cancer cells or virally infected cells.

The importance of glutathione cannot be overstated. It has multiple roles as indicated and, indeed, as one examines each system or organ more closely, the necessity for glutathione becomes increasingly evident. Glutathione values decline with age and higher values in older people are seen to correlate with better health, underscoring the importance of this remarkable substance for maintaining a healthy, well-functioning body.

Reference: Lomaestro B, Malone M. Glutathione in health and disease: Pharmacotherapeutic Issues Ann Pharmacother 29: 1263-73,1995

Role of Cellular Glutathione

Most physicians are familiar with GSH in regards to its role in hepatic function, as a detoxifying substrate for acetaminophen overdoses, and more recently its importance in the maintenance of T-cell competence in HIV. However, the clinical application of GSH enhancement is just beginning to be elaborated and will have far-reaching effects.

Antioxidation

Glutathione is the major naturally-occurring antioxidant present in our cells. Other antioxidants introduced through our diet such as vitamins C and E depend on GSH for their function and recycling within the cell. The field of free-radical biology is burgeoning and the list of disease states linked to oxidative stress is growing rapidly.

Toxicology

Glutathione is a key substrate for the cytochrome P450 metabolic pathway, which is taxed daily, not only by a variety of prescription and non-prescription drugs, but also by a host of environmental toxins including heavy metals and many by-products of cigarette smoke and fuel exhaust.

Immune Modulation

Lymphocytes, in particular T-cell subsets, have a high demand for adequate GSH for their function and replication. GSH depletion in face of an acute or chronic inflammatory process, aging or infection, will lead to a blunted immune response.

Pharmacology of Glutathione

Glutathione is a tripeptide that must be manufactured within the cell. Oral glutathione ingestion is ineffective. The limiting substrate for GSH synthesis is the amino acid cysteine. Oral cysteine is rapidly catabolized in the GI-tract, carries a toxic potential, and is not recommended. GSH-promoting drugs have been used effectively for specific indications such as acetaminophen toxicity and cystic fibrosis. These "pro-drugs" such as NAC (N-acetyl-cysteine) have the disadvantage of having side effects and a short half-life.

The increasingly difficult journey to better health starts and ends with glutathione. This critical information is a must for anyone interested in prevention of disease or for those needing information on an existing condition, which may be a result of GSH depletion. You don't have to be a physician, scientist, or involved in the medical profession to grasp a clear understanding of the body's master antioxidant and it's critical role in cellular health, optimum immune response, and as a major detoxifier. Dr. Jimmy Gutman's book "Glutathione: Your Body's Most Powerful Healing Agent" is bringing this important information to the world. He obviously has spent mega time researching and writing of the benefits of GSH. He has taken the research and put it into language that the average person can understand and has kept the research documented so that the Medical Profession will respect his work as well. Being involved in the Health industry for 10yrs, I have learned the necessity for people increasing their Glutathione levels, there has been so much confusion on how to do this before this book! After reading this book you will be able to take control of a very important part of your health! Thanks again Dr. Gutman for your dedication and ability to teach those of us that are willing to learn.

Typical statement will suggest that cystine comes mostly from eggs, milk and cheese. Most of the albumin and lactalbumin, the primary cystine-containing proteins, are removed from the cheese and the kept in the whey (if the whey is cold-processed). Then cheese is cooked to sterilize it; this then breaks any cystine dipeptides left in it. For both of those reasons cheese is NOT a cystine source. The secret is to have the foods raw, cold-processed (and preferably concentrated). Only then they are cystine sources.

Glutathione and other antioxidants quench free radicals and glutathione is the organs' and tissues' main support in detoxification as well.

Inulin is required in order to correct bowel bacteria, at least until inulin-containing foods can do the job on their own.

Liver flushes are necessary in a lot of people as part of a cleansing program to reduce toxin load on the organs, especially the liver. But other facets of cleansing are also important, for example getting the toxin load out of the fatty tissues and such.

Nobel laureate Linus Pauling stated 'every disease and ailment is linked to a mineral deficiency'.

Look at your mineral intake; it's pretty hard to be healthy when you're malnourished. You'd think about pH (acidity) and its link to incorrect mineral levels, toxin load and poor diet. Consider balancing/improving HGH, DHEA, and other hormone levels to normal youthful values. Consider sources of pollution other than bad diet; environmental toxins include electromagnetic interference, which reduces immune system responses and actually has a cancer link on its own.

The list of considerations is much longer than that, and they all relate in some way to the overall level of disease you'll experience, including susceptibility to candida.

With all due respect the body produces L-glutathione from the amino acids cysteine 1, glutamic acid 2 and glycine 3. So why would one to spend money on supplementing when it is available in nutrient-dense foods?

With regard to your first statement, Bee, it's not free form cysteine, but cysteine peptides that enter the cells to make glutathione. Free-form cysteine is treated as a toxin and it dos not raise glutathione appreciably. Your statement is correct, but once the amino acids and selenium are within the cells.

Once inside the cells, cysteine is acknowledged as being the rate- limiting factor for glutathione production, but raw foods contain cysteine peptides in inadequate quantities to produce wellness in sick people, or for health maintenance as one ages even for the healthy because glutathione production falls with age. However, we get around this inadequacy by concentrating these peptides. It takes 500 gallons of whey for example to produce the cysteine-containing peptides in one 10-gram pouch of Immunocal. A lot of people are on two or even three pouches. You can see that in whey in a natural state the cysteine peptide concentration just isn't there and it would be impossible to get the 7 grams or more we might need.

So, to answer your question, this shows supplementation is valid. Centenarians have in common, unusually high levels of cellular glutathione. When glutathione levels fall, disease and oxidative damage occurs. Keeping those levels up beats back disease and infection, and quenches the oxidative stress that runs rampant in disease and aging. Obviously, it's a great idea to attend to this crucial antioxidant and detoxifier with ample amounts of a concentrated precursor nutrient.

Dr. Jimmy Gutman's book, "Glutathione: Your Body's Most Powerful Healing Agent" is well worth a read. It contains summaries and hundreds of references on how glutathione levels relate to both wellness and lack of it. It is an easy read but detailed enough to be suitable for the most avid health professional.

Duncan Crow

Glutathione

YOUR LIFE DEPENDS ON IT!

How is it that so many people succumb to so many common uncontrolled infections? The human immune system has the ability to fight degenerative and infectious diseases when the body has the necessary building blocks. Glutathione is one of the main ingredients needed in the body. Without it, cells would disintegrate, the body would have little resistance to bacteria, viruses and cancer, and the liver would shrivel up due to the accumulation of toxins.

• A heart attack is predictable based on glutathione levels.
• Many autoimmune diseases have a relationship to glutathione levels.
• When glutathione decreases to a certain level, death is predictable within 3 days.

Research shows most people having an illness with clinical symptoms are deficient in glutathione, and are low in natural killer cell activity. When glutathione is low there are problems with the transportation of amino acids, minerals, vitamins, glycoproteins (sugars), and nutrients.

Glutathione is a peptide, which is part of an amino acid, which is part of a protein, and it is manufactured in the cells. Glutathione is the master antioxidant, and as the body manufactures glutathione, the body's natural killer cells increase. As part of the immune system, natural killer cells are able to kill off unwanted virus, bacteria, and fungus.

Replenishing the body with the required amino acids gives the body the necessary building blocks to maintain necessary cell function. These building blocks come from un-denatured concentrated whole foods. Un-denatured means the sulfur bonds are not broken and the enzymes are still alive.

Clinical researchers have said that glutathione "super enhances" the immune system, rejuvenates the liver and lungs, and is the super antioxidant to the body to make other antioxidants work. Harper's BioChemistry also states that glutathione is a super antioxidant that protects blood cells from oxidative stress and damage.

Glutathione put simply is "food" for the immune system.

Thousands of people who have feelings of desperation and hopelessness can have hope again as they regain their health. The nagging question is: What is my glutathione level and would it be beneficial to increase it?

Whey

Un-denatured concentrated whole food whey provide precursors such as amino acids, peptides, enzymes and minerals. Precursors are amino acids, peptides, enzymes, vitamins and minerals that are commonly known as building blocks for the body to manufacture what it needs to function. The use of these products requires fewer supplements, versus individual supplementation that requires the use of dozens of products. Thor's Bioactive Whey is undenatured, making it more beneficial than ordinary whey products, as it has more active enzymes and amino acids.

Research shows that amino acids start losing their original structure above 40 degrees. The whey on the market today is microwaved at 30 degrees or heated to 88 degrees. Both processes change the amino acid structure to a form no longer beneficial to provide precursors so the body can manufacture glutathione. Heating proteins over 72 degrees destroys the disulfide bonds of the cysteine amino acid molecule and the protein bonds are broken, resulting in the enzymes and keratin to be unstabilized and the polypeptides not formed.

Experience shows that at least one packet of Bioactive Whey Protein is required daily to maintain the body's current level of glutathione. To raise the glutathione level, and if the body is not experiencing a life threatening disease or major trauma experience, then at least two packets per day are needed. If the body is in a compromised condition, then three to four packets are needed.

Whey is very volatile. Exposure to air, and the moisture in the air, changes the whey by activating the enzymes and denaturing it. When a Bioactive Whey packet is opened, it should be used within thirty minutes. The Bioactive Whey is so fragile, that if mixed in a blender, it heats up causing the benefits of the enzymes to be lost. It should be hand-mixed in a cup of water or juice, or folded into yogurt or applesauce.