As a side note, another supplement may be of interest for GSH build up: Whey Protein Concentrate (WPC).
You see, Whey and Creatine (another interesting topic) aren’t just aimed for athletic performances
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by VRP Editorial Staff
Whey Protein Concentrate (WPC) is a new nutritional supplement that is rich in protein (up to 95%), lactalbumin, minerals, and vitamins. Unlike whey protein isolates (WPI) that process and filter out vital nutrients, Whey Protein Concentrate (WPC) retains the highest amount of immune-enhancing proteins, including:
Lactoferrin, an iron-binding, iron-modulating protein that possesses anti-viral, anti-bacterial and anti-inflammatory properties.
Immunoglobulins (IgG) that support the immune system.
Bovine Serum Albumin, along with Lactoferrin and IgG, provides generous amounts of Cysteine and Glutamine, precursors to Glutathione (GSH).
Unique Nutritional Value
Whey protein concentrate first became popular with weightlifters and bodybuilders, ever watchful for a superior, high-protein, low-fat supplement to incorporate in their training programs. WPC also quickly gained the interest of medical researchers who were impressed with its ability to improve metabolism, speed repair of injuries and strengthen the immune response, implying that WPC could aid in the treatment of chronic wounds, especially ulcerations from diabetes and hypertension. (1)
WPC contains high levels of essential and non-essential amino acids known to support wound healing. These include arginine, glycine, and particularly the branched-chain amino acids (BCAA), leucine, isoleucine and valine, which are essential to promote healing of bones, skin, and muscle tissues. Another amino acid, proline, aids in the production of collagen, heals cartilage, and strengthens joints, tendons and cardiac muscle.
Most important of all the reported benefits of WPC is its unique ability to increase intracellular production of glutathione (GSH), a protein that provides protection for a number of organ systems, including the crystalline lens of the eye, the retina, prostate gland, and the immune system.
Glutathione (GSH)
Glutathione, an intracellular thiol (sulfur-containing compound), participates in numerous intracellular reactions, including the production of coenzymes, the transport of amino acids, and the recycling and maintenance of tissue ascorbate (Vitamin C) and alpha-tocopherol (vitamin E) levels. (2)
Glutathione is also the body's principal antioxidant, providing intracellular defense against oxidative stresses caused by free radicals, reactive oxygen intermediates, and certain toxic chemicals. The two primary antioxidant mechanisms of glutathione are its ability to detoxify hydrogen peroxide (H2O2) and other organoperoxidases (free radicals), and to defend against oxidation within cells via the Glutathione Redux Cycle. (3,4) This role as a free radical scavenger is primarily accomplished through glutathione peroxidase (GSH px). GSH px interacts with the H2O2 to reduce it to harmless water, thus limiting its electron-stealing capacity.
Free-radicals are known to damage cells, DNA, and contribute to cancer transformation and loss of cell immunity to viral or bacterial infection. Many theories of aging and disease are based upon the formation of free radicals and the subsequent reduction in glutathione levels that allows for an accumulation of free radicals to remain within a cell and organ or organ system. GSH levels have been shown to decrease in situations of insufficient protein intake, or by depletion when the body is placed in a state of high oxidative stress, such as occurs during illness, infection, trauma, medication or surgery. GSH deficiency is also associated with diabetes, liver disease, cataracts, HIV infection, respiratory distress syndrome, cancer, and idiopathic pulmonary fibrosis.
Whey and Glutathione
Glutathione is a low molecular weight tripeptide synthesized in the body from the amino acids cysteine, glutamine, and glycine. Cysteine is found in the lowest concentration of all protein-forming amino acids in the blood and is therefore the rate-limiting factor for GSH production. WPC has been shown to act as a cysteine donor to augment intracellular GSH production.
In one study of 20 healthy young adults, those receiving WPC showed significant increases in lymphocyte GSH levels versus placebo. Researchers hypothesized that the increases in peripheral blood lymphocyte GSH concentrations resulted from the upregulation of GSH production in response to oxidative stress, and that WPC was effective in acting as an intracellular cysteine donor. (5)
In a second instance, whole blood GSH levels increased significantly (94%) following regular intake of WPC by a patient being treated for obstructive airway disease related to smoking, asthma and lung cancer. In the case study, the researchers reported that the patient showed symptomatic improvement in pulmonary function that coincided with taking WPC. Conversely her condition worsened when WPC was withdrawn, and improved following re-introduction, leading the researchers to state that, 'Her final respiratory status is objectively and subjectively better than at any time in the previous four years.' (6)
Immune Support
Both cysteine and glutamine are principle players in the coordinated T-cell response of macrophages and lymphocytes. (2) Intracellular glutathione has also been shown to influence how well T- and B-lymphocyte cells function. (7,8) In addition, intracellular glutathione availability affects the production of phagocytes (macrophages, monocytes and neutrophils).
Wound Healing
Researchers have found that WPC spurs cells to grow and promotes the body's normal repair of injuries. WPC was also found to encourage rapid wound healing in rats and pigs. (9)
Cataracts
Cataract formation occurs when an oxidative (free radical) insult to the epithelial cells of the lens is unopposed, leading to the unfolding of lens protein structures, increased cellular oxidation, and a decrease in glutathione peroxidase, which protects and repairs cellular damage. (10-12)
Lenticular glutathione levels have been shown to decrease in an age-dependent manner, (13-15) dropping from a concentration of 3.5 umol/g at age 20 to 1.8 umol/g at age 65. Researchers have also documented a lack of GSH in cataractous lenses, indicating that is a precipitating factor in age-related cataract formation. (13)
Glutathione and its enzyme, glutathione peroxidase, act as potent antioxidants to protect lens clarity by halting and/or correcting cellular damage caused by free-radicals. Experimental data have shown that taking WPC, which contains high levels of cysteine/cystine, may supply the lens with additional glutathione and delay cataract development, and even prevent cataract development. (16)
Macular degeneration
Lipid peroxidation plays a major role in retinal macular degeneration. (17) The retina is known to contain relatively high levels of antioxidants and antioxidant enzymes, (18) including three members of the glutathione system: glutathione peroxidase, reductase, and transferase. As levels of these antioxidants decrease with increasing age, (19) retinal changes associated with macular degeneration begin to develop. (19) Dietary supplementation with WPC is theorized to replenish the antioxidant activity of the retina by glutathione to halt the progressive lipid peroxidation occurring during age-related macular degeneration (ARMD). (1)
Immunity
The process of enhancing the immune response is accomplished through the replenishment of glutathione (GSH). It has been theorized that the ability of lymphocytes (CD4 cells) to correct oxidative damage is determined by their capacity to regenerate intracellular stores of glutathione, which allows them to respond vigorously to a wide variety of antigens. (20)
In 1981, researchers discovered that mice fed a non-denatured whey protein concentrate exhibited a marked increase in antibody production in response to T-cell dependent antigens. (21) Numerous experiments in subsequent years have confirmed this early observation. (22-29) Thus, enhanced immunity against colds and hepatitis, and most dramatically, pneumococcal infection, (27) could be accomplished through dietary supplementation with whey protein concentrates (WPCs).
An interesting finding was that the immunosustaining effect of the WPC not only increased intercellular levels of GSH or GSH precursors at the time of ingestion, but also built up stores of these substances within the cells which lasts for a substantial post-ingestion time interval. (20)
Cancer
The role of free radicals is thought to be a major factor in tumor formation. Evidence supporting the anti-tumor forming capacity of whey protein is illustrated by a University of Wisconsin study in which androgens are shown to be responsible for depleting GSH levels in the prostate. This relatively GSH-free environment is thought to promote prostate carcinogenesis in men. (30) This condition was reversed in vitro by increasing colonial levels of GSH via continuous whey protein supplementation.
HIV and AIDS
The mechanism by which whey protein concentrate yields an enhanced immune response indicates a potential role for support of HIV-infected individuals. Animal studies are yielding promising reports regarding prolonged life spans of infected animals in the laboratory, while theoretical data (31) and initial clinical observations in humans have produced evidence that dietary supplementation with WPCs can provide definite benefits to the HIV-infected individual.
Researches have reported that HIV-infected individuals have lower GSH concentrations in their blood lymphocytes, (32) and that the more glutathione patients carry in their CD4 helper T-cells, the cells primarily targeted by the HIV virus, the greater the chance of increased longevity. (33)
Supplementation with whey protein concentrates is also being investigated as a method of treatment for AIDS. WPCs may help AIDS patients maintain body weight and limit wasting syndrome. In one study, WPCs were given to fourteen AIDS-infected children (ages 8 months to 15 years) in an attempt to determine the efficacy of daily oral dietary ingestion of whey proteins. Researchers found no toxic side effects and an average weight gain of 3.2 lbs, up to 18% from their entrance weight. (34)
Researchers have also reported that a modified version of protein extracted from whey blocked the AIDS virus from infecting cells in vitro. (35) In a National Institutes of Health sponsored study, the scientists modified beta-lactoglobulin to produce a substance referred to as B69. They reported that B69 latched onto a protein structure called CD4 on the surface of cells, which kept the AIDS virus from using this site as an entryway into the cell.
References:
1. David Marshall, OD, PhD. Current Concepts on Whey Protein Usage, Prepared for The Cleveland Eye Clinic
2. Mortenssson, J., and Meister, A. Glutathione Deficiency Decreases Tissue Ascorbate Levels in Newborn Rats: Ascorbate Spares Glutathione and Protects. Proc. Natl. Acad. Sci. USA 88:4656-46460, 1991.
3. Rathburn, WB. Glutathione Metabolism in the Mammalian Ocular Lens. 194-206.
4. Reddy, VN. Glutathione and its Function in the Lens - An Overview. Exp Eye Res.50:771-778, 1990.
5. Lands, LC., Grey, V, Smountas, AA, Kramer, VG, McKenna, D. Lymphocyte Glutathione Levels in Children With Cystic Fibrosis. Chest. 1999;116:201-205.
6. Lothian, B, Grey, V, Kimoff, J, Lands, LC. Treatment of Obstructive Airway Disease With a Cysteine Donor Protein, Chest 2000 117:914-916
7. Spector, A.. The Search for a Solution to Senile Cataracts Proctor Lecture. Invest Oph. and Vis Sci. 25: 130-146, 1984.
8. Li, WC., and Spector, A.. Lens Epithelial Cell Apoptosis is an Early Event in the Development of UVB-induced Cataract. Free Radical Biology and Medicine 20:3: 310-311, 1996.
9. Daily InSight. A Better Whey to Heal? Academic Press, 1997.
10. Spector, A. Oxidation and Cataract. Symposium Paper. 1984 Human Cataract Formation. Ciba Foundation Symposium 106, 48-64, 1984.
11. Spector, A., Wang, GM., Wang, RR., Li, WC., and Kuszak, JR.. A Brief Photochemically Induced Oxidative Insult Causes Irreversible Lens Damage and Cataract I. Transparency and Epithelial Cell Layer. Exp Eye Res. 60: 471-481, 1995.
12. Spector, A., Wang, GW., Wang, RR., Li, WC., and Kleiman, NJ.. A Brief Photochemically Induced Oxidative Insult Causes Irreversible Lens Damage and Cataract II. Mechanism of Action. Exp Eye Res. 60: 483- 493, 1995.
13. Rathburn, WB. Glutathione in Ocular Tissues. 469-510.
14. Rathburn, WB. Glutathione Metabolism in the Mammalian Ocular Lens. 194-206.
15. Reddy, VN. Glutathione and its Function in the Lens: An Overview. Exp Eye Res.50:771-778, 1990.
16. Spector, A., Wang, GM., Wang, RR., Garner, WH., Moll, H.. The Prevention of Cataract Caused by Oxidative Stress in Cultured Rat Lenses. I H2O2 and Photochemically Induced Cataract. Curr Eye Res. 12:2: 163-179, 1993.
17. Taylor, A., Jaques, PF.. Oxidation and Aging: Impact on Vision. In: Sies, H., Erdman, J., Williams, G. (Eds.) Proceedings International Conference on Antioxidants. Princeton, New Jersey, Univ. Press, 1992.
18. Newsome, DA., Miceli, MV., Liles, MR.. Antioxidants in the Retinal Pigment Epithelium. In: Prog Retinal Eye Res. 13: 101-123, 1994.
19. Dovrat, A., and Gershon, D.. Rat Lens Superoxide Dismutase and Glucose-6-phosphate dehydrogenase: Studies on the Catalytic Activity and the Fate of Enzyme Antigen as a Function of Age. Exp Eye Res. 33: 651-655, 1981.
20. Fidelus, RK., Tsan, MF.. Glutathione and Lymphocyte Activation: A Function of Aging and Auto-immune Disease. Immunology 61: 503-508, 1987.
21. Bounous, G., Stevenson, MM., Konshavn, PAL.. Influence of Dietary Lactalbumin Hydrosolate on the Immune System of Mice and Resistance to Salmonellosis. J. Infect. Dis. 144: 282, 1981.
22. Bounous, G., Kongshavn, PAL. Influence of Dietary Proteins on the Immune System of Mice. J. Nutr. 112: 1747-1755, 1982.
23. Bounous, G., Letourneau, L., Kongshavn, PAL.. Influence of Dietary Protein Type on the Immune System of Mice. J. Nutr. 113: 1415-1421, 1983.
24. Bounous, G., Kongshavn, PAL. Differential effect of Dietary Protein Type on the B-cell and T-cell Immune Response in Mice. J. Nutr. 115: 1403-1408, 1985.
25. Bounous, G., Shenouda, N., Kongshavn, PAL., Osmond, DG.. Mechanism of Altered B-cell Response induced by Changes in Dietary Protein Type in Mice. J. Nutr. 115: 1409-1417, 1985.
26. Bounous, G., Kongshavn, PAL., Gold, P.. The Immunoenhancing Property of Dietary whey Protein Concentrate. Clin. Invest. Med. 11: 271-278, 1988.
27. Bounous, G., Kongshavn, PAL. Influence of Protein Type in Nutritionally Adequate Diets on the Development of Immunity. In: Friedman, M. ed. Absorption and Utilization of Amino Acids. CRC Press. 2: 219-223, 1989.
28. Parker, N., Goodrum, KJ. A Comparison of Casein, Lactalbumin, and Soy Protein Effect on the Immune Response to a T-dependent antigen. Nutrit. Res. 10: 781-792, 1990.
29. Hirai, R., Nakai, S., Kikuishi, H, Kawai, K.. Evaluation of the Immunological Enhancement Activities of Immunocal. Otsuka Pharmaceutical Co. Cellular Technology Institute, 1990.
30. Waterfall, JF., Sims, P.. Epoxy Derivatives of Aromatic Polycyclic Hydrocarbons. The Properties and Metabolism of Epoxides Related to Benzo(a)pyrene and to 7-8 and 9-dihydrobenzo(a)pyrene. Biochem J. 128: 265-277, 1972.
31. Noelle, RJ., Lawrence, DA.. Determination of Glutathione in Lymphocytes and Possible Association of Redox state and Proliferative Capacity of Lymphocytes. Biochem J. 198: 571-579, 1981.
32. Staal, FJT., Roederer, M., Israelski, DM., Bubp, J.. Intracellular Glutathione levels in T cell Subsets Decreases in HIV-infected individuals. AIDS Res and Hum Retroviruses 8: 305-311, 1992.
33. Herzenberg, L., De Rosa, S., Dubs, G., Roederer, M.. Glutathione Deficiency is Associated with Impaired survival in HIV Disease. Proc Natl Acad Sci USA 94: 1967-1972, 1997.
34. CTN Trial Results. Whey protein Supplementation. Whey Protein Supplementation in HIV-infected Children: A Pilot Study. 1997
35. The Associated Press News Release. Whey Eyed as AIDS Blocker. The Associated Press, New York, New York, 1995.
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The information in this article is not intended to provide personal medical advice, which should be obtained from a medical professional, and has not been approved by the U.S. FDA.