Glutathione is a substance, the levels of which in our cells are predictive of how long we will live. There are very few other factors which are as predictive of our life expectancy as is our level of cellular glutathione. Glutathione has been called the "master antioxidant", and regulates the actions of lesser antioxidants such as vitamin C, and vitamin E within the body. "We literally cannot survive without this
antioxidant," Earl Mindell, R.Ph., Ph.D. "What You Should Know
about the Super Antioxidant Miracle"
"Without glutathione, other important antioxidants such as vitamins C
and E cannot do their job adequately to protect your body against
disease." Breakthrough in Cell Defense, Allan Somersall,
Ph.D., M.D., and Gustavo Bounous, M.D. FRCS(C)
"No other antioxidant is as important to overall health as
glutathione. It is the regulator and regenerator of immune cells and the most valuable
detoxifying agent in the human body. Low levels are associated with hepatic dysfunction, immune dysfunction, cardiac disease, premature aging, and
death." The Immune System Cure, Lorna R. Vanderhaeghe
& Patrick J.D. Bouic, Ph.D.
Glutathione (L-gammaglutamyl-L-cysteinylglycine) is a tri-peptide of the amino acids cysteine, glycine, and glutamic acid. Glutathione is an antioxidant compound found in living animal and plant tissue. It takes up and gives off hydrogen and is important in cellular respiration. A deficiency of glutathione can cause hemolysis (destruction of red blood cells, leading to anemia) and oxidative stress. Glutathione is essential in intermediary metabolism as a donor of sulfhydryl groups which are essential for the detoxification of acetaminophen. [PDR Medical Dictionary. Spraycar. 1999] Selenium is a structural component of, and a co-factor for the antioxidant enzyme glutathione peroxidase.
Glutathione is the major endogenous antioxidant produced by the cell. Glutathione participates directly in the neutralization of free radicals, reactive oxygen compounds, and maintains exogenous antioxidants such as vitamins C and E in their reduced (active) forms. In addition, through direct conjugation, glutathione plays a role in the detoxification of many xenobiotics (foreign compounds) both organic and inorganic. Glutathione is an essential component of the human immune response. Proposed mechanisms of immune enhancement include:
optimizing macrophage functions,
offsetting oxidative damage associated with lymphocyte monoclonal expansion, and
stabilizing the mitochondrial membrane thereby, reducing apoptosis in lymphocytes
Cysteine is a sulfur-containing (sulfhydryl) amino acid which is present in many proteins, and is in the same class as methionine. Because it is a sulfur-based amino acid, cysteine acts as an antioxidant in the body. Cysteine is an important source of sulfur in human metabolism, and although it is classified as a non-essential amino acid, cysteine may be essential for infants, and may at some point be recognized as an essential or conditionally essential amino acid. The systemic availability of oral glutathione is negligible; the vast majority of it must be manufactured intracellularly. Glutathione (GSH) is a tripeptide made up of the three amino acids cysteine, glycine and glutamate. Glutamate and glycine are readily available in most North American diets, but the availability of cysteine makes it be the rate-limiting substrate for the synthesis of glutathione within the cell. It is the sulfhydryl (thiol) group (SH) of cysteine that serves as proton-donor and is responsible for the biological activity of glutathione.
The free amino acid cysteine does not represent an ideal delivery system to the cell. It is potentially toxic and is spontaneously catabolized in the gastrointestinal tract and blood plasma. Conversely, cysteine absorbed during digestion as cystine (two cysteine molecules linked by a disulfide bond) in the gastrointestinal tract is more stable than the free amino acid cysteine. The disulfide bond is pepsin and trypsin-resistant, but may be split by heat, low pH, and mechanical stress. Cystine travels safely through the GI tract and blood plasma and is promptly reduced to the two cysteine molecules upon cell entry.
Cystine is the preferred form of cysteine for the synthesis of glutathione in macrophages and astrocytes. Lymphocytes and neurons prefer cysteine for glutathione production optimizing glutathione levels in macrophages and astrocytes with cystine allows these cells to provide cysteine to lymphocytes and neurons directly upon demand.
Immunocal Bioactive Whey Protein is a specially prepared whey protein isolate which contains the thermolabile proteins serum albumin, alpha lactalbumin and lactoferrin. These proteins contain high levels of cystine residues that could be denatured by heat, low pH, or mechanical stress (inherent to most extraction processes). It is therefore recommended that high-speed mechanical blending or heating (above 118 degrees F) be avoided in the preparation of whey protein isolates such as Bioactive Whey Protein. In serum albumin there are 17 cystine residues and 6 glutamylcystine (Glu-Cys) dipeptides; in lactoferrin, 17 cystine residues and 4 GluCys dipeptides; and in alpha-lactalbumin, 4 cystine residues. In particular, the Glu-Cys dipeptides very readily enter the cell to be synthesized into GSH. Of interest, the Glu-Cys dipeptide is an exclusive feature of the only obligatory foods in the early life of mammals and oviparous species, those being milk and egg white respectively. When subject to heat or shearing forces, the fragile disulfide bonds within these peptides are broken and the bioavailability of the glutathione precursors is greatly diminished. As an antioxidant, glutathione is essential for allowing lymphocytes to express their full potential, without being hampered by oxyradical accumulation during the oxygen requiring development of the immune response. In a similar fashion, GSH delays the muscular fatigue induced by oxyradicals during the aerobic phase of strenuous muscular contraction. As a detoxification agent, glutathione has been demonstrated to be effective against a number of xenobiotics, including chemical pollutants, various carcinogens and ultraviolet radiation.
Glutathione is a tightly regulated intracellular constituent and is limited in its production by negative feedback inhibition of its own synthesis through the enzyme gamma-glutamylcysteine synthetase, thus greatly minimizing any possibility of overdosage. [source: Physician's Desk Reference for Prescription Drugs (PDR) 2001, p. 1563].
Oral glutathione supplements as discussed previously, are virtually ineffective, since glutathione is a protein and is digested in the stomach before reaching the blood stream or tissues of the body. Researchers found that 3 grams of glutathione taken orally were ineffective in increasing circulating glutathione (glutathione in the bloodstream) in a clinical study evaluating the benefits of oral glutathione. Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. (source: Eur J Clin Pharmacol 1992;43(6):667-9) IV Glutathione is effective but expensive, uncomfortable, and somewhat impractical requiring infusions 2 times per week using an Intravenous (IV) line. Glutathione precursors are a better solution (except in acute cases of acetominophen overdose toxicity, where speed of administration is critical for hepatic preservation).
N-acetyl-L-cysteine (NAC) is an amine protected version of cysteine that is rapidly hydrolyzed in the body to the amino acid cysteine. (Cysteine is the monomer amino acid).
NAC supplements are moderately effective, but dosing is limited due to toxic side effects (such as headache, dizziness, blurred vision) associated with cysteine supplementation.
Cystine is a disulfide linked dimer of cysteine, and a rich nutritional source of cystine in the diet is undenatured whey proteins. The link is a disulfide bond which is readily reduced to the corresponding thiol (-SH).
Scientifically, the best way to increase glutathione levels is to take a supplement rich in cystine (a disulfide-bonded form of cysteine). Immunocal undenatured whey protein provides on of the richest sources of cystine known to science, and because cystine contains two weakly bonded molecules of cysteine, Immunocal is a unique "cysteine delivery vehicle".
This form is virtually free of the toxic side effects associated with the single molecule (NAC). Two molecules of cysteine are connected by a weak disulfide bond to form a molecule of cystine. The disulfide-bonded cysteine is not digested, but is transported by the blood stream to the tissues of the body. Here, within the cells of the body, the weak disulfide bond between the two cysteine molecules is cleaved, and the cell has 2 molecules of cysteine from which glutathione can be manufactured. The greatest dietary source of cystine is bio-active, undenatured whey protein, and the only whey protein which has been studied in clinical trials at major Universities and Medical Schools and which is clinically proven to enhance or normalize glutathione levels is called "Immunocal". Bioactive Whey Protein is the only bioactive whey protein listed in the PDR (Physicians Desk Reference for Prescription Drugs), even though it is available without a prescription.
"A review article published in the Annals of Pharmacology
stated that glutathione is important in DNA synthesis and repair, protein and
prostaglandin synthesis, amino acid transport, detoxification of toxins and
carcinogens, enhancement of the immune system, and protection from oxidation
and enzyme activations." The Immune System Cure, Lorna R.
Vanderhaeghe & Patrick J.D. Bouic, Ph.D.
"Glutathione has potent anti-viral properties - if
tissue and serum glutathione levels are significantly increased, the replication of most pathogens are slowed or stopped. Conversely, glutathione deficiency produces a pro-viral
effect." Paul Cheney, M.D., Ph.D. and expert in the treatment of Chronic Fatigue Syndrome. Transcribed from a workshop presentation on
the clinical management of Chronic Fatigue Syndrome
Lymphocytes, cells vital for effective immune function, depend on GSH for their
proper function and replication. IMMUNOLOGY 61: 503-508 1987
As we age, there is a precipitous drop in GSH levels.
Lower glutathione levels have been implicated in many diseases associated with
aging. Journal of Clinical Epidemiology 47: 1021-28 1994
Antioxidants are well documented to play vital roles in health maintenance
and disease prevention. GSH is your cells' own major antioxidant. Biochemical Pharmacology 47: 2113-2123 1994
GSH plays a role in eliminating many carcinogens as well as maintaining
immune function. Cancer Letters 57: 91-94 1991
Strong muscular activity, such as that experienced by athletes, generates
oxyradicals [free radicals] leading to muscle fatigue and poorer performance.
GSH neutralizes these radicals. Sport Medicine 21: 213-238, 1996
GSH detoxifies many pollutants, carcinogens, and poisons, including many
in fuel exhaust and cigarette smoke. It retards damage from radiation such as
seen with loss of the ozone. Annual Reviews of Biochemistry 52: 711-780 1983
Glutathione, or GSH, is a naturally occurring protein that protects
every cell, tissue, and organ from toxic free radicals and disease. It is a
tripeptide of three amino acids - glycine, glutamate (glutamic acid), and
cysteine. These precursors are necessary for the manufacture of glutathione
within the cells.
Find Out More
PubMed is the U.S.
National Library of Medicine's search
service to access the 10 million citations in Medline and other related
databases, with links to participating online journals published since 1966. When you access the
PubMed site, enter your search word(s) into the form and click on the
"Search" button. A list of abstracts will appear. Click on the
author's name to read the abstract.
Clinical Management of Chronic Fatigue Syndrome (CFS, CFIDS) -
transcript of a workshop by Paul Cheney, M.D., one of the leading authorities
on Chronic Fatigue Syndrome and Fibromyalgia in the U.S., and founder/director
of the Cheney Clinic, Feb. 1999. This study emphasized the central role of
glutathione deficiency in the symptomology of Chronic Fatigue Syndrome.
CFS Radio Program -
Feb. 28, 1999, Roger G. Mazlen M.D., Host, with Dr. Paul Cheney, discussing Dr.
Cheney's CFS research.
The famous Louis Pasteur Institute for Research issues a book every
year which goes to all the major medical schools in Europe, Canada, and the
U.S.A. This book is entitled Oxidative Stress in Cancer, Aids and
Neurodegenerative Diseases, co-authored by Luc Montagnier,
co-discoverer of the AIDS virus. Chapter 42 of this book is entirely devoted to
a discussion of Immune Enhancing Whey protein®. It reads, "Nutriceutical Modulation
of Glutathione with a Humanized Native Milk Serum Protein Isolate, Bioactive Whey Protein:
Application in Cancer and AIDS".
Montreal Children's Hospital: Dr. Larry Lands just presented results
from a double-blind study in the area of Cystic Fibrosis and muscle performance
in healthy young adults. He presented his findings at the American Lung
Association's Symposium in San Diego, April 26th, 1999. Dr. Lands showed that
Immune Enhancing Whey Protein® raised the
cellular levels of glutathione in young athletes on the product by 35%, and
improved muscle performance by up to 13%.
proteins in cancer prevention.", Bounous G, Batist G, Gold P
Montreal General Hospital, McGill University, Quebec, Canada. "We and
others have demonstrated that whey protein diets result in increased
glutathione (GSH) concentration in a number of tissues, and that some of the
beneficial effects of whey protein intake are abrogated by inhibition of GSH
synthesis. Whey protein is particularly rich in substrates for GSH synthesis.
We suggest that whey protein may be exerting its effect on carcinogenesis by
enhancing GSH concentration."
The Effect of Bioactive Whey Protein, Commercial Whey Protein, and Casein on Immune Response Bounous G, Batist G. Immunoenhancing property of dietary whey protein in mice: Role of glutathione. Clin Invest Med 12:154-61, 1989. Graph showing Optimization of the immune response in animals fed the Patented Whey Protein Concentrate (WPC)--Bioactive Whey Protein occured because of significantly greater glutathione production (>120%) in their lymphocytes (immune cells or white blood cells) than those animals fed Commercial WPC or Casein. This increased glutathione production following Bioactive Whey Protein supplementation was attributed to the abundance of known glutathione dietary precursors including serum albumin, alpha lactalbumin, and lactoferrin. Commercial whey protein contains significantly less of these precursors of glutathione. Additionally, the immunosustaining effect of Bioactive Whey Protein® Patented WPC was significantly greater than that of soy protein isolate in a study conducted by Bounous et al in Canada.
Graph showing results of Bioactive Whey Protein supplementation in mice and rats previously exposed to potent carcinogens (cancer-causing agents) resulted in a remarkably lower tumor mass than in those animals supplemented with casein, standard feed, or meat. Bounous G., et al. Clin Invest Med 11:213, 1988. This study was conducted with mice and rats exposed to (by feeding) potent carcinogens (cancer-causing agents). These animals were subsequently placed on protein diets of similar nutritional efficiency (Protein Efficiency Ratios, or PER), but from the three different protein sources. The COLON TUMOR MASS in animals fed the patented Whey Protein Concentrate (WPC) Bioactive Whey Protein was LOWER than the tumor mass in animals fed casein protein, standard feed, or meat, suggesting a protective effect associated with Bioactive Whey Protein supplementation. The immune stimulating effect of Bioactive Whey Protein Patented WPC was significantly greater than that of commercial Whey Protein Concentrate and Casein Protein in a separate study conducted by Bounous et al in Canada. Additionally, the immunosustaining effect of Bioactive Whey Protein Patented WPC was significantly greater than that of soy protein isolate in a study conducted by Bounous et al in Canada.
proteins as a food supplement in HIV-seropositive individuals.",
Bounous G, Baruchel S, Falutz J, Gold P Department of Surgery, Montreal General
Hospital, Quebec. "In conclusion, these preliminary data indicate that, in
patients who maintain an adequate total caloric intake, the addition of
"bioactive" whey protein concentrate as a significant portion of
total protein intake increases body weight and shows elevation of glutathione
(GSH) content of mononuclear cells toward normal levels."
biological activity of undenatured dietary whey proteins: role of
glutathione." , Bounous G, Gold P Department of Surgery, Montreal
General Hospital Research Institute, Quebec. "The presence in the serum
albumin fraction of glutamylcysteine groups (rare in food protein) and the
specific intramolecular bond as related to the undenatured conformation of the
molecule are considered to be key factors in the glutathione-promoting activity
of the protein mixture."
immunoenhancing property of dietary whey protein concentrate.",
Bounous G, Kongshavn PA, Gold P Montreal General Hospital Research Institute,
Quebec, Canada."Mixing lactalbumin with either casein or soy protein in a 20 g protein/100 g diet formula significantly enhanced the immune response in
comparison to that of mice fed diets containing 20% soy protein or
Graph showing Superior Immunosustaining effect of Bioactive Whey Protein Patented WPC versus Casein and Isolated Soy Protein Bounous G. et al. J Nutr. 113:1415, 1983 The immune response in animals fed the patented Whey Protein Concentrate (WPC) Bioactive Whey Protein was up to 400% greater than the immune response in animals fed casein or isolated soy proteins. Peak antibody production by speen lymphocytes (number of plaque forming cells) was measured after antigen challenge in mice fed protein diets of similar nutritional efficiency (Protein Efficiency Ratios, or PER), but from the three different protein sources. Similarly, the immune stimulating effect of Bioactive Whey Protein Patented WPC was significantly greater than that of commercial Whey Protein Concentrate in a separate study conducted by Bounous et al in Canada.
of supplementation with a cysteine donor on muscular performance."
Lands LC, Grey VL, Smountas AA Division of Respiratory Medicine, McGill
University Health Centre-Montreal Children's Hospital, Montreal, Quebec,
Canada. "This is the first study to demonstrate that prolonged
supplementation with a product designed to augment antioxidant defenses
resulted in improved volitional performance. "
Longevity: A significant body of data is beginning to emerge suggesting a benefit of glutathione enhancement in longevity. Several animal studies have demonstrated a 35% to 50% increase in longevity as compared to matched controls. In addition to living longer, these animals were healthier and had fewer degenerative conditions.