_Glutathione_in_Cell_Defense | _Glutathione_Monograph | _Glutathione_NAC | _Glutathione_Cysteine | _Glutathione_Whey_Protein | _Glutathione_Wiki | _Glutathione_Disease | _Glutathione_ThioDoxGlutathione | _Glutathione_N-Acetyl-L-Cysteine |


_Glutathione_in_Cell_Defense

The Role of Glutathione in Cell Defense, with References to Clinical Deficiencies and Treatment

    Thomas A. Kwyer, M.D.

Glutathione Precursors: Amino Acids

  • L-Glutamate

  • L-Cysteine

    • the rate-limiting substrate
    • cystine (cysteine=cysteine) is an ideal form of cysteine for glutathione synthesis
  • Glycine

Glutathione: L-glutamylcysteinylglycine

  • DNA synthesis and repair

  • Protein synthesis

  • Prostaglandin synthesis

  • Amino acid transport

  • Metabolism of toxins and carcinogens

  • Immune system enhancement

  • Prevention of oxidative cell damage

  • Enzyme activation

    • Lomaestro, B. Ann Pharmacother, 1995 Dec;(12):1263 -73.

Immunonutrition in the Critically Ill: a Systematic Review of Clinical Outcomes (12 studies with 1,557 subjects, 1,482 of whom were analyzed)

  • “Objective: To perform a meta-analysis addressing whether enteral nutrition with immune-enhancing feeds benefit critically ill patients after trauma, sepsis, or major surgery.”

  • “Main outcome measures were mortality, infection,ventilator days, intensive care unit stay, hospital stay, diarrhea days, calorie intake and nitrogen intake.”

    • Beale, R., Crit. Care Med. 1999, Dec.;27(12):2799-805.

Immunonutrition in the Critically Ill: a Systematic Review of Clinical Outcomes (Summary)

  • BENEFITS:

    • Infection: a significant reduction in the relative risk of acquiring infection.
    • Ventilator Days: a significant reduction overall.
    • Hospital Length of Stay: the reduction in hospital LOS was significant.
  • SAFETY:

    • No increase in side effects of feeding was reported in patients receiving immunonutrition.

Effect of Immune Enhancement on Length of Therapeutic Intervention in Severe Abdominal Trauma

Effect of Immune Enhancement on Total Hospitalization Cost in Severe Abdominal Trauma

Effect of Immune Enhancement on Total Hospital Days in Severe Abdominal Trauma

Pathogenesis of Glutathione Deficiency: Cytokine Selection (Slide 1)

  • “Glutathione Levels in Antigen-presenting Cells Modulate Th1 Versus Th2 Response Patterns.” (Title of Article)

    • “...the Th1 pattern is characterized by interleukin 12 (IL-12) and interferon ? (IFN-?) production and the up-regulation cell-mediated, e.g.,delayed hypersensitvity, (DTH) responses.”
    • “The Th2 response pattern is characterized by IL-4 and IL-10 production and up-regulation of a variety of antibody responses.”
  • Peterson, J., Proc. Natl. Acad. Sci. U S A 1998, Mar. 17;95(6): 3071-3076.

Pathogenesis of Glutathione Deficiency: Cytokine Selection (Slide 2)

  • “Antigen-presenting cells (APC) -- macrophages, dendritic cells, and B cells -- are central to the development of either Th1 or Th2 immunity because antigen presentation and recognition are required to initiate responses.”

  • “...GSH depletion inhibits Th1-associated cytokine production and/or favors Th2-associated responses.”

    • Peterson, J., Proc. Natl. Acad. Sci. U S A 1998, Mar. 17;95(6): 3071-3076.

“Defective Antigen Processing Correlates with a Low Level of Intracellular Glutathione”

  • “Therefore, low intracellular glutathione levels in antigen-presenting cells correlate with defective processing of antigen with disulfide bonds, indicating that this thiol may be a critical factor in regulating productive antigen processing.”

    • Short, S., Eur. J. Immunol. 1996, Dec;26(12):3015-3020.
  • Most antigens are proteins with disulfide bonds. GSH reduces disulfide bonds. Low GSH prevents disulfide bond reduction.

  • 1. RSSR’ + GSH ? RSH + GSSR’

  • 2. GSSR’ + GSH ? GSSG + R’SH

“Lymphocyte Proliferation in Glutathione-depleted Lymphocytes: Direct Relationship Between Glutathione Availability and the Proliferative Response”

  • “Lymphocyte proliferation in response to mitogenic lectins is directly dependent upon glutathione (GSH) availability.”

  • “...the restoration of lymphocyte proliferation by exogenous GSH is more closely linked to effects on intracellular rather than extracellular GSH.”

  • “These studies confirm the importance of intracellular GSH in lymphocyte proliferation.”

    • Hamilos, D., Immunopharmacology, 1989, 18;223-235.

Pathogenesis of Glutathione Deficiency in the Immune Response: Summary

  • Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns.

  • Antigen presentation and recognition are required to initiate immune responses.

  • Key events that determine whether IFN-? is produced occur almost immediately.

  • IFN-? production predominates when GSH levels are high.

  • GSH depletion may play a key role in exacerbating HIV and other infectious diseases in which Th2 predominance is an important aspect of the disease pathology.

Pathogenesis of Glutathione Deficiency and Apoptosis: AIDS (Slide 1)

  • “Glutathione Deficiency is Associated with Impaired Survival in HIV Disease.” (Title of Article from Stanford)

  • “The crucial connection revealed here between GSH deficiency and survival in HIV disease was foreshadowed by several studies.”

  • Survival in all HIV+: GSB? 0.91 = 90%, GSB? 0.91 = 32%.

  • Survival in CD4 ? 200: GSB? 1.05 = 87%, GSB? 1.05 = 17%.

    • Herzenberg, L, Proc. Natl. Acad. Sci. U S A 1997, Mar. 4;94(5): 1967-1972.

Pathogenesis of Glutathione Deficiency and Apoptosis: AIDS (Slide 2)

  • “Type 1 and Type 2 Cytokines in HIV Infection -- a Possible Role in Apoptosis and Disease Progression.” (Title of Article)

  • “...a strong type 1/weak type 2 cytokine production profile was observed in HIV-seropositive patients with delayed or absent disease progression, whereas progression of HIV infection was characterized by a weak type 1/strong type 2 cytokine production profile.”

    • Clerici, M., Ann. Med. 1997, Jun.;29(3):185-188.

Pathogenesis of Glutathione Deficiency and Apoptosis: AIDS (Summary)

  • Glutathione Deficiency is Associated with Impaired Survival in HIV Disease.

  • Survival in all HIV+: GSB? 0.91 = 90%, GSB? 0.91 = 32%.

  • Survival in CD4? 200: GSB? 1.05 = 87%, GSB? 1.05 = 17%.

  • Antiretroviral therapies will not successfully eradicate HIV and HIV-seropositive patients will not be ultimately cured unless therapies aimed at restoring the immune system are associated with the antiretroviral drugs currently employed.

Benefits of Glutathione Enhancement in Disease or Stress: Pulmonary Disease

  • “We describe a case of a patient who had obstructive lung disease responsive to corticosteroids, and low whole blood GSH levels.”

  • “After 1 month of supplementation with a whey-based oral supplement designed to provide GSH precursors, whole blood GSH levels and pulmonary function increased significantly and dramatically.”

    • Lands, L., J. Appl. Physio. 1999, Oct.;87(4):1381-5.

Benefits of Glutathione Enhancement in Disease or Stress: Pulmonary Disease

  • Relationship to Immunocal® intake:

    • Time 6 on Immunocal® 1 month.
    • Time 7 off Immunocal®.
    • Time 8 back on Immunocal®.
  • Immunocal® significantly and dramatically increased pulmonary function.

Method of Intracellular GSH Enhancement: Undenatured Whey Protein Concentration

  • Contains highly concentrated amounts of cystine (cysteine = cysteine) because of a new Pasteurization technique which preserves the disulfide bond between the two cysteines.

  • The naturally occurring constituent heat labile proteins found in “Mother’s Milk” that imparts immune enhancement.

  • Dose: 10 - 40 grams per day for adults and ½ gram/Kg for infants and young children up to 40 Kg.

  • High dose to reverse cachexia: up to 120 grams has been reported (anecdotal) to increase total body weight 15% in two weeks in a near death AIDS patient with cachexia.

Cystine: the Preferred Substrate for Optimal Glutathione Synthesis and Immune Enhancement

  • Hepatic Nitrogen Metabolism: Cysteine from muscle catabolism arrives in the liver in the form of cystine. Enteral feeding of cystine takes advantage of this well-developed metabolic pathway that is also utilized when digesting breast milk which has well documented and indisputable immune enhancing properties.

  • Antigen Presenting Cells: Prefer cystine for GSH synthesis which is required to initiate the immune response then feed lymphocytes cysteine as an immunoregulatory signal.

  • Astrocytes: Prefer cystine for GSH synthesis and feed cysteine to neurons to protect against neurodegenerative diseases.

Proton Donation is the Basis for Preservation of the Amino Acid Pool (Positive Nitrogen Balance) (Dröge, W, FASEB J., 1997 Nov.;11(13):1077-89)

Proton Donation: the Sulfur of Glutathione can give up a Proton (H+)

    GSH + GSH ? GSSG + 2H+

Pathogenesis of Cystine Deficiency: Wasting Syndromes (Slide 1)

  • “Role of Cysteine and Glutathione in HIV Infection and Other Diseases Associated with Muscle Wasting and Immunological Dysfunction.” (Title of Article)

  • “Evidence suggests that 1) the cystine level is regulated primarily by the normal postabsorptive skeletal muscle protein catabolism, 2) the cystine level itself is a physiological regulator of nitrogen balance and body cell mass...”

    • Dröge, W., FASEB J. 1997, Nov;11(13):1077-89.

    Pathogenesis of Cystine Deficiency: Wasting Syndromes (Slide 2)

    • AIDS, sepsis, major injury, trauma, cancer, chronic fatigue syndrome, Crohn’s disease, ulcerative colitis, and athletic over-training are associated with:

      • low cystine,
      • low glutamine,
      • elevated glutamate,
      • increased urea production, and
      • reduced natural killer (NK) cell activity.

    Pathogenesis of Cystine Deficiency: Wasting Syndromes (Slide 3)

    • This diagram demonstrates the relationship between cystine and nitrogen balance to be as follows:

      • ? Cystine.
      • ? Protons (H+).
      • ? Bicarbonate (HCO2-).
      • ? Carbamoylphosphate.
      • Ammonium ion (NH4+) is saved.
    • This results in positive nitrogen balance with maintenance or increase in weight.

    Pathogenesis of Cystine Deficiency: Wasting Syndromes (Slide 4)

    • This diagram demonstrates the relationship between cystine and nitrogen balance to be as follows:

      • ? Cystine.
      • ? Protons (H+).
      • ? Bicarbonate (HCO2-) .
      • ? Carbamoylphosphate.
      • Ammonium ion (NH4+) is saved.
    • This results in negative nitrogen balance with decrease in weight and possible cachexia.

    Glutathione Precursor Transport: Cystine is Preferred form of Cysteine for GSH Synthesis

    • Cystine (cysteine=cysteine) is the preferred form of cysteine for macrophages and astrocytes.

      • “Macrophages consume cystine...” Gmunder, H., Macrophages Regulate Intracellular Glutathione Levels of Lymphocytes. Cell. Immunol., 1990, Aug.; 129(1): 32-46.
      • “These results demonstrate that astroglial cells prefer cystine...” Kranich, O., Glia, 1998, Jan.;22(1): 11-8.

    Pathogenesis of Cystine Deficiency: Wasting Syndromes (Slide 4)

    • This diagram demonstrates the relationship between cystine and nitrogen balance to be as follows:

      • ? Cystine.
      • ? Protons (H+).
      • ? Bicarbonate (HCO2-) .
      • ? Carbamoylphosphate.
      • Ammonium ion (NH4+) is saved.
    • This results in negative nitrogen balance with decrease in weight and possible cachexia.

    Glutathione Precursor Transport: Cystine is Preferred form of Cysteine for GSH Synthesis

    • Cystine (cysteine=cysteine) is the preferred form of cysteine for macrophages and astrocytes.

      • “Macrophages consume cystine...” Gmunder, H., Macrophages Regulate Intracellular Glutathione Levels of Lymphocytes. Cell. Immunol., 1990, Aug.; 129(1): 32-46.
      • “These results demonstrate that astroglial cells prefer cystine...” Kranich, O., Glia, 1998, Jan.;22(1): 11-8.

    Glutathione Depleting Agents

      Smoking.

      Alcohol.

      Caffeine.

      Acetaminophen.

      Drugs.

      Vigorous exercise.

      x-, ?- and UV radiation

      Xenobiotics.

    Total Parenteral Nutrition: the Road to Enteral Atrophy, Leaky Gut Syndrome and Pneumonitis

    • Enterocyte nutrient transport is one way: from the gut to the cell to the capillary.

    • Enterocytes cannot transport nutrients from the blood vessel.

    • Enterocytes starve as the rest of the body is fed by way of the vasculature.

    • Enterocytes pull away from each other as a consequence of gut atrophy.

    Total Parenteral Nutrition: the Road to Enteral Atrophy, Leaky Gut Syndrome and Pneumonitis

    • Bacteria slip between the atrophying enterocytes.

    • Bacteria enter lymph nodes and then gain access to thoracic duct.

    • The thoracic duct emtpies into the blood flowing toward the right heart and into the pulmonary circulation.

    • Atrophic gut cannot generate sufficient amounts of secretory IgA.

    • The lungs are also compromised and pneumonitis frequently occurs due to constant seeding and lack of IgA.


_Glutathione_Monograph

Glutathione

    Glutathione is a sulfur-containing amino acid that is an important part of the body's antioxidant defense system. Glutathione is composed of three different amino acids: cysteine, glutamic acid, and glycine. Vitamins B6 and riboflavin are critical for maintaining adequate levels of glutathione within the body.

   The term glutathione is typically used as a collective term to refer to the tripeptide L-gamma-glutamyl-L-cysteinylglycine in both its reduced and dimeric forms. Monomeric glutathione is also known as reduced glutathione and its dimer is also known as oxidized glutathione, glutathione disulfide and diglutathione. In this monograph, reduced glutathione will be called glutathione— this is its common usage by biochemists—and the glutathione dimer will be referred to as glutathione disulfide.

   Glutathione is widely found in all forms of life and plays an essential role in the health of organisms, particularly aerobic organisms. In animals, including humans, and in plants, glutathione is the predominant non-protein thiol and functions as a redox buffer, keeping with its own SH groups those of proteins in a reduced condition, among other antioxidant activities.

    Glutathione is involved in detoxification—it binds to toxins, such as heavy metals, solvents, and pesticides, and transforms them into a form that can be excreted in urine or bile. Glutathione is an important antioxidant. In preliminary research, dietary glutathione intake from fruit and raw vegetables has been associated with protection against some forms of cancer. Glutathione has inhibited cancer in test tube and animal studies. In preliminary research, higher glutathione levels have been associated with good health in older adults.

   Glutathione supplements appear to be efficiently absorbed in rats. However, the same may not be true for glutathione supplements in humans. For example, when seven healthy people were given a single application of up to 3,000 mg of glutathione, there was no increase in blood glutathione levels. The authors of the study concluded "it is not feasible to increase circulating glutathione to a clinically beneficial extent by the oral administrating of a single application of 3,000 mg of glutathione." Absorption of glutathione may be better in rats because unlike the gastrointestinal tract of rats, the human gastrointestinal tract contains significant amounts of an enzyme (gamma-glutamyltranspeptidase) that breaks down glutathione. Preliminary evidence has suggested that absorption of glutathione can occur in the mouth when glutathione tablets are placed between the teeth and the inner cheek.

   Glutathione is present in tissues in concentrations as high as one millimolar. Cysteine, the business residue of glutathione, neither has the solubility nor activity of glutathione at physiological pH. It appears that nature has built the cysteine molecule into the glutathione tripeptide to make the amino acid more soluble and allow it to have redox buffering activity in a living tissue environment. Glutathione plays roles in catalysis, metabolism, signal transduction, gene expression and apoptosis. It is a cofactor for glutathione S-transferases, enzymes which are involved in the detoxification of xenobiotics, including carcinogenic genotoxicants, and for the glutathione peroxidases, crucial selenium-containing antioxidant enzymes (see Selenium). It is involved in the regeneration of ascorbate from its oxidized form, dehydroascorbate. There are undoubtedly roles of glutathione that are still to be discovered.

    Glutathione (reduced) is known chemically as N-(N-L-gamma-glutamyl-L-cysteinyl)glycine and is abbreviated as GSH. Its molecular formula is C10H17N3O6S and its molecular weight is 307.33 daltons. Glutathione disulfide is also known as L-gamma-glutamyl-L-cysteinyl-glycine disulfide and is abbreviated as GSSG. Its molecular formula is C20H32N6O12S2.

_Glutathione_NAC

Glutathione N-Acetyl-L-Cysteine (NAC)

Glutathione, NAC, and Lipoic Acid

Health Defense Formula

See also:   N-Acetyl-L-Cysteine Abstracts
Lipoic Acid Abstracts

 

 


GLU-NAC PLUS™
60 caps
$26.95


PRODUCT DESCRIPTION: GLU-NAC PLUS™ contains 250 mg of reduced glutathione, 250 mg of n-acetyl-l-cysteine (NAC), and 5 mg of alpha lipoic acid per capsule. Glutathione and NAC (a major precursor of glutathione) both provide important protection against free radicals and toxins, as well as strengthen the immune system. Lipoic acid is a potent fat-soluble and water-soluble antioxidant with important metabolic and detoxification properties. Glu-Nac Plus™ is designed to be hypoallergenic, contains no magnesium stearate, and is suitable for hypersensitive individuals.

 

NUTRITIONAL CONSIDERATIONS & APPLICATIONS: Glutathione is considered the most powerful and versatile of the body's self-generated antioxidants. Glutathione plays a key role or is involved in: 1) Neutralizing free radicals and prevention of their formation both enzymatically and non-enzymatically, 2) Reducing oxidized Vitamin C and Vitamin E to their unoxidized states, 3) Phase I and II detoxification reactions, 4) Nucleic acid synthesis, 5) DNA repair, 6) Maintaining cellular redox potential, 7) Cellular differentiation and retarding the aging process, and 8) Maintaining normal brain function. In addition, Glutathione both is one of the strongest anti-cancer agents manufactured in the body and one of the most potent known antiviral agents. N-acetyl-l-cysteine (NAC) is the rate-limiting amino acid for the production of glutathione within the cells of the body; it has mucolytic properties, and is a powerful antioxidant and detoxifier. Some research indicates that NAC is more readily absorbed into certain cells of the body than glutathione and therefore is an excellent synergist with glutathione. Lipoic acid operates as an antioxidant in both its oxidized and reduced states, and has been shown to enhance glutathione levels.

The nutrients in Glu-Nac Plus™ provide powerful effects, especially relating to free radical protection, detoxification, immune system enhancement, reduced inflammation, and normal cellular functioning. This product provides outstanding nutritional support in a wide variety of conditions of poor health, and helps support and maintain a state of health and well-being.

COMPOSITION: 1 preservative-free capsule provides the following percentages of the Daily Value:

NUTRIENT

AMOUNT

% Daily Value

Glutathione (reduced)

250 mg

*

N-Acetyl-L-Cysteine

250 mg

*

Alpha Lipoic Acid

5 mg

*

* No established Daily Value

DIRECTIONS: As a dietary supplement take 1-2 capsules daily away from food, or as directed by a health care professional.

INGREDIENTS: Glu-Nac Plus™ only contains the highest quality glutathione (reduced), n-acetyl-l-cysteine, alpha lipoic acid, microcrystalline cellulose, gelatin (capsule), and the smallest amounts of silica and magnesium trisilicate.

Glu-Nac Plus™ does not contain wheat, rye, oats, corn, barley, gluten, soy, egg, dairy, yeast, sugar, sulfates, phosphates, chlorides, fats, wax, preservatives, colorings, or artificial flavorings.

These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.
GLU-NAC PLUS™ contains 250 mg of reduced glutathione, 250 mg of n-acetyl-l-cysteine (NAC), and 5 mg of alpha lipoic acid per capsule.
  • Glutathione and NAC (a major precursor of glutathione) provide important protection against toxins and free radicals, and strengthen the immune system.
  • Lipoic acid is a potent fat-soluble and water-soluble antioxidant with important metabolic and detoxification properties.
  • Glu-Nac Plus™ is designed to be hypoallergenic, contains no magnesium stearate, and is suitable for hypersensitive individuals.
  • When the plasma glutathione concentration is low, such as in patients with HIV infection, alcoholics, and patients with cirrhosis, increasing the availability of circulating glutathione by oral administration might be of therapeutic benefit. To assess the feasibility of supplementing oral glutathione we have determined the systemic availability of glutathione in 7 healthy volunteers. The basal concentrations of glutathione, cysteine, and glutamate in plasma were 6.2, 8.3, and 54 mumol.l-1 respectively. During the 270 min after the administration of glutathione in a dose of 0.15 mmol.kg-1 the concentrations of glutathione, cysteine, and glutamate in plasma did not increase significantly, suggesting that the systemic availability of glutathione is negligible in man. Because of hydrolysis of glutathione by intestinal and hepatic gamma-glutamyltransferase, dietary glutathione is not a major determinant of circulating glutathione, and it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione.
    Eur J Clin Pharmacol. 1992;43(6):667-9. The systemic availability of oral glutathione.
    The glutamate-glutamine cycle is a sequence of events by which an adequate supply of the neurotransmitter glutamate is maintained in the central nervous system.
    Initially, glial cells release glutamine, which is then taken up into presynaptic terminals and metabolized into glutamate by glutaminase (a mitochondrial enzyme). Glutamate can also be produced by transamination of 2-oxoglutarate, an intermediate in the Citric acid cycle.
    The glutamate that is synthesized in the presynaptic terminal is packaged into synaptic vesicles by the transporter VGLUT. Once the vesicle is released, glutamate is removed from the synaptic cleft by excitatory amino acid transporters (EAATs), of which there are five types. Glutamate taken up by glial cells is then converted into glutamine by glutamine synthetase, and transported out of the cells into the nerve terminal. This allows synaptic terminals and glial cells to work together in order to maintain a proper supply of glutamate.

    _Glutathione_Cysteine

    Glutathione (GSH) synthesis, precursors|Cystine, Cysteine 1 Whey 2 Health

    Glutathione (GSH)
    Cystine is the preferred precursor for glutathione synthesis

    Glutathione (GSH) is a tripeptide - a chain of three amino acids - cysteine, glycine, and glutamic acid - found in human cell tissue.

    Cysteine is potentially toxic and catabolized in the bodyGlutathione exists in the reduced form (GSH), and maintains a balance with its oxidized form (GSSG) - a disulfide. GSH is our body's Master Antioxidant.

    Cysteine - as a free amino acid - is potentially toxic and is spontaneously catabolized or destroyed in the gastrointestinal tract and blood plasma.

    Hence it does not represent an ideal delivery system to the cell.

    However, when it is present as a cysteine=cysteine dipeptide - called cystine - (two cysteine molecules linked by a disulfide bond) it is more stable than the free amino acid cysteine.


    Cystine is the preferred precursor for glutathione


    The di-peptide, cystine, travels safely through the digestive tract and blood and is promptly broken up or reduced to the two cysteine molecules when it enters the cell.

    How is Glutathione manufactured?

    Intracellular synthesis of glutathione with cysteine and glutamateGlutathione is synthesized inside your cells from the three amino acid precursors, L-glutamate, L-cysteine, and L- glycine.

    Glutathione synthesis is a two-step process involving the enzymes gamma-glutamylcysteine synthetase and GSH synthetase.

    The first reaction is the rate-limiting step and is effectively inhibited by GSH feedback.

    This means the reaction is controlled by its own end-product and slows down once enough glutathione is synthesised. The second reaction is not subject to negative feedback by GSH.

    When GSH is consumed or used up in the neutralisation of harmful oxyradicals, this feedback inhibition is lost.

    So now, the availability of L-cysteine as a precursor determines how much glutathione is synthesised by the cell.

    The amount of cysteine available can hence become the rate-limiting factor for the manufacture of glutathione.

    If cysteine levels drop, the body will convert methionine, another amino acid, to cysteine, but then other systems run out of methionine, which is needed for making protein.

    Macrophages (immune "scavenger" cells) and Astrocytes (a category of brain cells that influence the activity of neurons) prefer Cystine for manufacturing glutathione, while Lymphocytes and Neurons prefer cysteine.

    Optimizing glutathione levels in macrophages and astrocytes with cystine allows these cells to provide cysteine to lymphocytes and neurons directly upon demand.


    References:

    The systemic availability of oral glutathione
    Witschi A, Reddy S, Stofer B, Lauterburg BH. [Eur J Clin Pharmacol. 1992;43(6):667-9.]
    Because of hydrolysis of glutathione by intestinal and hepatic gamma-glutamyltransferase, dietary glutathione is not a major determinant of circulating glutathione, and it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of glutathione.



    Also see:

    From Cell to Super-Cell - with Glutathione

    Glutathione (GSH) - Master Antioxidant and Cellular Detoxifier

    Glutathione (GSH) & the Immune System - Your Lifeline to Health

    Un-denatured Whey Protein - The Best Way to Raise Glutathione Levels


    Diagram of Glutathione synthesis Courtesy of Michael W. King, Professor IU School of Medicine and IU Center for Regenerative Biology and Medicine, Terre Haute, IN. 47809

    Diagram of Glutathione disulfide Courtesy of Michael W. King, Professor IU School of Medicine and IU Center for Regenerative Biology and Medicine, Terre Haute, IN. 47809

    Diagrams of Cysteine and Cystine molecules courtesy of Cystinuria.org

     

    _Glutathione_Whey_Protein

    Discovery of the health benefits of A Whey Protein

    At the beginning of the 70’s, under the direction of Dr. Gustavo Bounous, MD, (FRCSC), a team of researchers from the Faculty of Medicine at McGill University (Canada), was studying proteins of animal and vegetable origins in order to feed the patients with an elemental diet that would allow them to reduce their stay in hospital. Since 1978, their studies had been focusing on whey proteins. This work led to the surprising discovery that a specific undenatured whey protein concentrate helped to sustain optimal Glutathione levels, high immunological reactivity and anticarcinogenic activity. Subsequent identification of the active ingredients present in this protein mixture led in 1993 to the production of a high-quality bioactive protein that was given the name A Whey Protein.

    This research was supported by the Medical Research Council of Canada and the National Institutes of Health in the United States. The observed effects of A Whey Protein which have been discovered at McGill University have been validated by numerous independent research centers worldwide, notable in Germany, Japan, Australia, France, United States and in Nova Scotia (Canada).

    Placebo-controlled clinical studies to prove the health benefits of A Whey Protein

    The gold standard for clinical evidence for efficacy is a placebo-controlled, double-blind clinical trial. present research activities therefore focus on controlled clinical trials in cooperation with various clinical partners in Montreal and other clinical centers in Canada and the U.S.A. The recently published study on the effects of a research formulation of A Whey Protein on lung cancer patients (Tozer et al. Antioxidants & Redox Signaling, 10:2, 395-402, 2008) is an example. This trial has shown quite impressive results with regard to the health benefits of this A Whey Protein formulation in the nutrition of seriously ill advanced lung cancer patients. Other clinical studies showing the efficacy of A Whey Protein have been performed and published by several clinical centers.

    Health benefits from regular consumption of A Whey Protein

    A Whey Protein contains several different proteins with special structural and functional properties which collectively provide a combination of important health benefits.

        The claim stating that A Whey Protein is effective in maintaining a strong immune system has been officially approved by Health Canada. Most people know that modern medicine is still relatively helpless in the face of viral epidemics such as HIV, SARS or the flu virus. In the time of globalization and increasing international travel activities it is only a question of time that a new epidemic will spread around the globe and eventually reach North America. Moreover, irrespective of these global threats, each of us is confronted with a constant barrage of colds and flus. The decisive question is whether the first encountered viruses will be eliminated by our immune system or stay and manifest themselves as a disease. This decisively depends on the strength of our immune system regardless of whether this moment is any time soon or in the more distant future. Someone who is taking A Whey Protein every day is best prepared for this moment.



        Cysteine is the limiting precursor for Glutathione, which plays a key role in the function of the immune system. Most notably it plays a critical role in the proliferation of lymphocytes, i.e. the cells that mediate specific immune responses. Cysteine and Glutathione concentrations show a strong and progressive age-related decline which starts at the age of 30. Older people are therefore more likely to feel the benefits of taking A Whey Protein. Healthy young adults have usually adequate levels of Cysteine and Glutathione for most of the time but occasionally experience episodes of low Glutathione levels. These episodes are possibly caused by unnoticed, symptomless viral infection and render even these otherwise strong persons vulnerable towards subsequent infections as their low Glutathione level compromises the immune system. Healthy young adults thus typically realize the benefits of taking A Whey Protein only after longer periods of time.

    By supporting Glutathione biosynthesis A Whey Protein enhances also the detoxifying function in the body. Without noticing it we are constantly exposed to environmental toxins such as heavy metals in low quality foods, in the increasingly polluted air which we breathe or in the water that we drink. The body is therefore constantly engaged in the important task of eliminating such toxins. One of the most important detoxifying mechanisms involves Glutathione which binds to certain toxins and forms a water-soluble complex that is ultimately excreted in the urine or bile as waste. In extreme cases such as in the case of poisoning by excessive doses of certain medicals drugs this process severely depletes the Glutathione levels in the liver and can lead to life-threatening conditions. These patients are typically treated and rescued by a Glutathione-promoting drug to replenish the Glutathione pool and to detoxify the victim.

    Glutathione is best known for its antioxidant function which indirectly is also enhanced by A Whey Protein. At all times living organisms are internally generating oxygen radicals and hydrogen peroxide, both of which cause massive oxidative tissue damage and other forms of oxidative stress unless neutralized by Glutathione. By scavenging oxygen radicals and hydrogen peroxide, Glutathione normally controls the oxidative stress and protects the structural constituents of the cells against the damaging effects of these molecules. Without Glutathione the cells would rapidly be destroyed. Other antioxidants, such as vitamin A, vitamin C or vitamin E have also a protecting function but Glutathione is by far the most abundant antioxidant in cells and tissues. Insufficient amounts of Glutathione can therefore not be compensated by these antioxidant vitamins.

    The age-related decrease in Glutathione plays, therefore, an important role in aging and oxidative stress-related disease conditions such as cardiovascular diseases and obesity. Several independent studies in animals have shown that Cysteine supplementation causes a decrease in protein oxidation and reverses the age-related decline in various biochemical functions. As the cognitive decline is one of the most devastating consequences of aging, it was particularly interesting to see that Cysteine supplementation reduces the rate of oxidative structural damage in the brain and ameliorates the decline of memory functions in animals.

    Glutathione is clearly the most important antioxidant in the body and has been the object of intense research during the last 30 years. Presently, more than 80,000 scientific articles on Glutathione are listed on Pub Med (www.pubmed.gov) and this number is increased by approximately 3-5,000 new articles every year. Glutathione consists of the three amino acids, glutamate, Cysteine and glycine and is synthesized from these precursors within the cells and tissues. The production of Glutathione is typically limited by the availability of Cysteine. The sulfidryl (thiol) group of Cysteine serves as an electron donor and is responsible for the biological activity of Glutathione. However, taking supplements of the free amino acid Cysteine is not advisable because Cysteine is oxidized on the shelf and in the digestive tract. In order to raise the cellular Glutathione level, it is far better to use a supplement with “stabilized” Cysteine residues such as A Whey Protein.

    The effect on muscle functions is another important health benefit from regular consumption of A Whey Protein. Due to its special composition and structural properties, A Whey Protein can help to ameliorate the loss of skeletal muscle mass and muscle function which is one of the hallmarks of aging. This process is called sarcopenia which starts in the fourth decade of life and accelerates as we age. As the loss of muscle mass is associated with the loss of muscle function, it increases the risk of falls and fractures, compromises the ability to visit friends or to maintain other social functions, and ultimately contributes to the loss of quality of life in old age. As skeletal muscle tissues represent about half of the protein mass in the human body, the loss of muscle mass means above all a net loss of protein. Physical exercise, notably resistance training, is the best investigated method shown to increase muscle mass and muscle function even in elderly persons. This effect of physical exercise can be strongly enhanced by A Whey Protein. The undenatured Cysteine- and leucine-rich whey protein was found to be more effective than casein or soy protein, and is therefore the ideal dietary protein source to support the maintenance of skeletal muscle mass and muscle function. A Whey Protein consists of a combination of several proteins which are rapidly digested and therefore lead to a rapid increase of its constituent amino acids in the blood plasma with a peak at about two hours after protein consumption. The most important amino acids for the enhancement of muscle functions in the elderly are leucine and Cysteine which are contained in A Whey Protein in relatively high amounts. Ideally, A Whey Protein should therefore be consumed immediately after physical exercise because the maximum availability of the amino acids in the blood coincides in this case with the time window of maximum exercise induced skeletal muscle protein synthesis. Ideally, a person of 80 kg body weight should consume about 10g-30g A Whey Protein after exercise. An additional small amount of A Whey Protein (e.g. 10g) may be consumed in the morning to account for the relatively low plasma Cysteine and intracellular Glutathione levels at the end of the night. The rest of the daily protein intake may be distributed over the day.

    Most of the clinical studies and complementary animal studies on the effects of Cysteine supplementation on oxidative stress, muscle functions, and immunological functions have been performed with another Cysteine derivative, N-acetylCysteine, because this agent allows the investigator to identify Cysteine as the causative agent. However, if an amount of 10-30g leucine- and Cysteine-rich A Whey Protein per 80 kg body weight per day is regularly used to improve muscle protein synthesis and muscle function, this is also sufficient to meet the increased need for Cysteine to ameliorate the age-related oxidative stress and to maintain a strong immune system. Any additional consumption of N-acetylCysteine or Alpha-lipoic acid as complementary supplements may not only be unnecessary, but also disadvantageous. N-acetylCysteine, for example, can cause certain adverse effects. Moreover, oral consumption of N-acetylCysteine typically leads to a relatively high temporary increase in Cysteine/N-acetylCysteine concentrations in the blood, a large proportion of which is converted within the oxidative environment of the blood into the corresponding disulfide which is essentially useless for cells and tissues, and a substantial proportion is simply catabolized and converted into metabolic acids. Alpha-lipoic acid has the unique property of travelling through lipid membranes and is therefore capable of shuttling oxidative and reducing equivalents across membranes. It is contained in moderate amounts in most cells and tissues and plays an important physiological role in this context. If present at relatively higher concentrations, it shuttles oxidative equivalents from the oxidative environment of the blood into the cells and tissues and thereby effectively acts as an oxidant for cells rather than an antioxidant.

    Taken together, A Whey Protein helps the body to defend itself against several common health hazards which are becoming increasingly important as one gets older. A Whey Protein does this by strengthening four key functions which may be easily remembered by the four letters:

    A – FOR ANTIOXIDANT DEFENSE

    I – FOR IMMUNE FUNCTIONS

    D – FOR DETOXIFICATION

    Plus

    M – FOR MUSCLE FUNCTION


    Raising Glutathione Using Cysteine

    In Search of the Best Strategy for Cysteine Supplementation

    by Dr. Wulf Dröge, Ph.D, Senior Vice-President, Research & Development

    Enhancement of Glutathione levels through Cysteine supplementation has proven and important health benefits. But consumers have questions about the best available source of Cysteine. Immunotec provides the answer.

    A series of clinical studies and complementary laboratory experiments has shown that aging is associated with a progressive decrease in plasma Cysteine and intracellular Glutathione concentrations.

    This decrease leads to (and can be viewed as a manifestation of) age-related oxidative stress. Cysteine and Glutathione concentrations are particularly low during the night and early morning hours, i.e. during periods of starvation.

    Click here to read the complete article


    Cysteine, N-AcetylCysteine (NAC), and A Whey Protein®

     

    by Dr. Jimmy Gutman, Medical Consultant

    Research over the past quarter century has shown that the limiting factor for our body’s ability to make Glutathione, is the availability of Cysteine in our diet. There are several options, let’s look at Cysteine itself, N-acetylCysteine (NAC) and A Whey Protein.

    The amino acid Cysteine can be found in supplement form in pills and powders. Unfortunately just eating Cysteine has not proved to be an effective way to raise Glutathione. Cysteine alone is quickly oxidized in the digestive system and does not make it to the cells in an appreciable quantity. Cysteine must be in a form that can survive the trip through the gut, into the bloodstream and across the cell membrane.

    Click here to read the complete article


    Changing the Aging Paradigm

    by Dr. Wulf Dröge, Ph.D, Senior Vice-President, Research & Development

    Most people consider the process of aging and death as an integral part of their life, but two key scientific findings have changed our concept of aging dramatically... Most people consider the process of aging and death as an integral part of their life, but two key scientific findings have changed our concept of aging dramatically...

    The first important finding dates back to 1954 when “free radicals”, i.e. a highly aggressive type of small chemical molecules, were first discovered in living tissues. In view of the chemically aggressive nature of free radicals, Dr. Denham Harman proposed in 1954 that aging may be — at least to a large extent — the consequence of free-radical-inflicted tissue damage.


    A Whey Protein Platinum

    The Next Generation of Scientific Support

    by Jimmy Gutman MD, FACEP

    Anti-aging Medicine...what a term!

    Believe it or not, there are physicians who believe this is a term that represents a questionable area of practice with equally questionable outcomes!

    To these individuals, I pose the questions - “What was the average age span of an American at the turn of the twentieth century?” (ANSWER: 46 years old) “What was the average longevity for an American male in 1967?” (ANSWER: 68 years of age) “What is it today?” (ANSWER: Pushing 80!)

    Click here to read the complete article


    Glutathione in Health and Disease

     

    by Patricia Kongshavn, MSc, Ph.D.

    Glutathione (g-glutamylcysteinylglycine, GSH) is a water-soluble tripeptide composed of the amino acids glutamate, Cysteine, and glycine.

    Present in all mammalian cells, it is widely distributed throughout the animal and plant kingdoms, underscoring its fundamental biological significance.

    GSH is an endogenous antioxidant of great importance, as well as being a detoxicant of exogenous and endogenous toxic compounds. In addition, it plays a vital role in....

    Historic Firsts in Whey Protein, Glutathione, and the Immune System

    SCIENCE IS A BIT LIKE SPORTS: THE CREDIT GOES TO THE ONES WHO WERE FIRST

    (To view the publications, go to www.pubmed.com, search for "pubmed" and enter the 7 digit numbers given below.

    1981/1988: Gustavo Bounous and colleagues were the first to discover the effect of a whey protein on the immune system.

    J. Infect Dis. 1981 Sept;144:281. Pubmed PMID:7024433
    Influence of dietary lactalbumin hydrolysate on the immune system of mice and resistance to salmonellosis.
    Bounous G, Stevenson MM, Kongshavn PA.

    Clin Invest Med. 1988 Aug;11:271-8. Pubmed PMID:3168349
    The immunoenhancing property of dietary whey protein concentrate.
    Bounous G, Kongshavn PA, Gold P.
    “The plaque-forming cell response to sheep red blood cells was found to be enhanced in mice fed a formula diet containing 20g lactalbumin/100 g diet”. (The humoral immune response eliminates bacteria in the body).


    1986: Wulf Dröge and colleagues were the first to discover the effect of Glutathione on the immune system in a living organism.

    Immunobiology. 1986 Aug;172:151-6. Pubmed PMID:3490430
    Glutathione augments the activation of cytotoxic T lymphocytes in vivo.
    Dröge W, Pottmeyer-Gerber C, Schmidt H, Nick S.
    “The activation of T lymphocytes in vivo was found to be augmented by Glutathione”. (Cytotoxic T cells eliminate virus-infected cells in the body, and T cells help B cells to produce a humoral immune response).


    1989: Wulf Dröge and colleagues were the first to discover that HIV-infected patients have abnormally low Cysteine and Glutathione levels.

    Biol Chem Hoppe Seyler. 1989 Feb;370:101-8. Pubmed PMID: 2784973
    Low concentrations of acid-soluble thiol (Cysteine) in the blood plasma of HIV-1 infected patients.
    Eck HP, Gmünder H, Hartmann M, Petzoldt D, Daniel V, Dröge W.
    “Blood plasma from HIV-1-infected persons contains decreased Cysteine concentrations. The intracellular Glutathione concentration in peripheral blood-mononuclear cells (PBMC) and monocytes from HIV positive persons are also significantly decreased”.


    1989: Gustavo Bounous and colleagues were the first to discover that Glutathione plays a role in the effect of whey protein on the immune system.

    Clin Invest Med. 1989 June;12:154-61. Pubmed PMID:2743633
    Immunoenhancing property of dietary whey protein in mice: role of Glutathione.
    Bounous G, Batist G, Gold P.
    “Enhancement of host humoral immune response is associated with sustained production of splenic Glutathione in whey protein fed mice”.


    1998: Wulf Dröge and colleagues were the first to discover the age-related decrease in the plasma concentration of Cysteine, the limiting precursor of Glutathione.

    Blood. 1998 July; 92:59-67. Pubmed PMID: 9639500
    The Redox State as a Correlate of Senescence and Wasting and as a Target for Therapeutic Intervention
    Hack V, Breitkreutz R, Kinscherf R, Rörer H, Bartsch P, Taut F, Benner A and Dröge W.
    “Our study showed a decrease in the plasma thiol level indicative of an age-dependent shift to a more oxidized condition”.


    2008: Gustavo Bounous & Wulf Dröge and colleagues were the first to show in a placebo controlled clinical trial the health benefits of an undenatured whey protein isolate in cancer patients.

    Antiox. & Redox Signaling. 2008. Feb;10:395-402. PMID:18158761.
    Cysteine-Rich Protein Reverses Weight Loss in Lung Cancer Patients Receiving Chemotherapy or Radiotherapy
    Tozer RG, Tai P, Falconer W, Ducruet T, Karabadjian A, Bounous G, Molson JH, Dröge W.
    “The patients treated with the Cysteine-rich protein had a mean increase of 2.5% body weight, whereas casein-treated patients lost 2.6%”.


    _Glutathione_Wiki

    Glutathione

    Glutathione (GSH) is a tripeptide. Glutathione contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side chain. Glutathione is an antioxidant that helps protect cells from reactive oxygen species such as free radicals and peroxides.

        Thiol groups are kept in a reduced state at a concentration of approximately ~5 mM in animal cells. In effect, glutathione reduces any disulfide bond formed within cytoplasmic proteins to cysteines by acting as an electron donor. In the process, glutathione is converted to its oxidized form glutathione disulfide (GSSG). Glutathione is found almost exclusively in its reduced form, since the enzyme that reverts it from its oxidized form, glutathione reductase, is constitutively active and inducible upon oxidative stress. In fact, the ratio of reduced glutathione to oxidized glutathione within cells is often used scientifically as a measure of cellular toxicity.

    Biosynthesis
    Glutathione is not an essential nutrient since it can be synthesized from the amino acids L-cysteine, L-glutamic acid and glycine.

        It is synthesized in two adenosine triphosphate-dependent steps:
  • First, gamma-glutamylcysteine is synthesized from L-glutamate and cysteine via the enzyme gamma-glutamylcysteine synthetase (a.k.a. glutamate cysteine ligase, GCL). This reaction is the rate-limiting step in glutathione synthesis.
  • Second, glycine is added to the C-terminal of gamma-glutamylcysteine via the enzyme glutathione synthetase.

        Animal glutamate cysteine ligase (GCL) is a heterodimeric enzyme composed of a catalytic (GCLC) and modulatory (GCLM) subunit. GCLC constitutes all the enzymatic activity, whereas GCLM increases the catalytic efficiency of GCLC.
  • Function

    Glutathione exists in reduced (GSH) and oxidized (GSSG) states. In the reduced state, the thiol group of cysteine is able to donate a reducing equivalent (H++ e-) to other unstable molecules, such as reactive oxygen species. In donating an electron, glutathione itself becomes reactive, but readily reacts with another reactive glutathione to form glutathione disulfide (GSSG). Such a reaction is possible due to the relatively high concentration of glutathione in cells (up to 5 mM in the liver). GSH can be regenerated from GSSG by the enzyme glutathione reductase.

        In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH) and less than 10% exists in the disulfide form (GSSG). An increased GSSG-to-GSH ratio is considered indicative of oxidative stress.

        GSH is known as a substrate in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is also capable of participating in non-enzymatic conjugation with some chemicals, as in the case of N-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450-reactive metabolite formed by paracetamol (or acetaminophen as it is known in the US), that becomes toxic when GSH is depleted by an overdose of acetaminophen.

        Glutathione conjugates to NAPQI and helps to detoxify it, in this capacity protects cellular protein thiol groups, which would otherwise become covalently modified; when all GSH has been spent, NAPQI begins to react with the cellular proteins, killing the cells in the process. The preferred treatment for an overdose of this painkiller is the administration (usually in atomized form) of N-acetyl-L-cysteine, which is processed by cells to L-cysteine and used in the de novo synthesis of GSH.

        Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism.

        This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-lactoyl-glutathione. Glyoxalase II (EC 3.1.2.6) catalyzes the hydrolysis of S-D-lactoyl-glutathione to glutathione and D-lactic acid.

        Glutathione has been used as an inhibitor of melanin in the cosmetics industry. In countries like the Philippines, this product is sold as a whitening soap. Glutathione competitively inhibits melanin synthesis in the reaction of tyrosinase and L-DOPA by interrupting L-DOPA's ability to bind to tyrosinase during melanin synthesis. The inhibition of melanin synthesis was reversed by increasing the concentration of L-DOPA, but not by increasing tyrosinase. Although the synthesized melanin was aggregated within 1 h, the aggregation was inhibited by the addition of glutathione. These results indicate that glutathione inhibits the synthesis and agglutination of melanin by interrupting the function of L-DOPA. "

    Supplementation

    Supplementing has been difficult, as research suggests that glutathione taken orally is not well absorbed across the GI tract. In a study of acute oral administration of a very large dose (3 grams) of oral glutathione, Witschi and coworkers found that "it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione."[20][21]

        However, tissue and sperm glutathione concentrations can be raised by increased intake of the precursor cysteine, or in chronic conditions, by S-adenosylmethionine (SAMe).[22][23] Glutathione precursors rich in cysteine include N-acetylcysteine (NAC)[24][25] and undenatured whey protein,[26][27][28][29][30][31][32][33] and these supplements have been shown to increase glutathione content within the cell. N-Acetylcysteine is available both as a drug and as a generic supplement.

        Glutathione has shown positive preliminary results in several studies of glutathione's ability to affect levels of reactive oxygen species,[34] [35] which may have implications in the reduction of cancer rates.[36]

    Pathology     Excess glutamate at synapses, which may be released in conditions such as traumatic brain injury, can prevent the uptake of cysteine, a necessary building block of glutathione. Without the protection from oxidative injury afforded by glutathione, cells may be damaged or killed.

    Glutathione-ascorbate cycle

    The glutathione-ascorbate cycle is a metabolic pathway that detoxifies hydrogen peroxide (H2O2), which is a reactive oxygen species that is produced as a waste product in metabolism. The cycle involves the antioxidant metabolites: ascorbate, glutathione and NADPH and the enzymes linking these metabolites.[1] In the first step of this pathway, H2O2 is reduced to water by ascorbate peroxidase (APX) using ascorbate as the electron donor. The oxidized ascorbate (monodehydroascorbate) is regenerated by monodehydroascorbate reductase (MDAR).[2] However, monodehydroascorbate is a radical and if not rapidly reduced it disproportionates into ascorbate and dehydroascorbate. Dehydroascorbate is reduced to ascorbate by dehydroascorbate reductase at the expense of GSH, yielding oxidized glutathione (GSSG). Finally GSSG is reduced by glutathione reductase (GR) using NADPH as electon donor. Thus ascorbate and glutathione are not consumed; the net electron flow is from NADPH to H2O2. The reduction of dehydroascorbate may be non-enzymatic or catalysed by proteins with dehydroascorbate reductase (DHAR) activity, such as glutathione S-transferase omega 1 or glutaredoxins

    _Glutathione_Disease

    Glutathione Therapy in Parkinson`s Disease
    Glutathione Therapy in Disease
        Glutathione is the brain's master antioxidant. Intravenous glutathione therapy and taking glutathione precursors have both been shown to be effective alleviating the symptoms of Parkinson`s Disease.

        Parkinson`s Disease (PD), a devastating illness, occurs in one of every 100 people over 65.

    It is a slowly progressing disease of the nervous system that results in progressive destruction of brain cells (neurons) in an area of the brain called the substantia nigra. Death occurs usually as a result of secondary complications such as infection.

        One of the mechanisms known to destroy neurons is damage by free radicals or reactive oxygen species - destructive molecules produced by oxidation of the neurotransmitter dopamine.

    The Role of Dopamine
    The cells of the substantia nigra use dopamine - a chemical messenger between brain or nerve cells - to communicate with cells in another region of the brain called the striatum.

    When nigral cells are lost, nigral dopamine levels fall, resulting in a decrease in striatal dopamine.

    The typical symptoms of PD - motor function deficiencies characterized by muscle rigidity, jerky movements, rhythmic resting tremors - are the result of low levels of striatal dopamine.

    Most dopaminergic drugs used to treat PD, are aimed at temporarily replenishing or mimicking dopamine. They improve some symptoms, but do not restore normal brain function nor halt brain cell destruction.

    Dopaminergic drugs are generally effective at first in reducing many PD symptoms, but over time they lose their effect.

    They also cause severe side effects because they overstimulate nerve cells elsewhere in the body and cause confusion, hallucinations, nausea and fluctuations in the movement of limbs.

    The Role of Antioxidants
    When dopaminergic neurons are lost in the course of Parkinson`s disease, the metabolism of dopamine is increased - which in turn increases the formation of highly neurotoxic hydroxyl radicals.

    The most important free radical scavenger in the cells of the substantia nigra is the powerful brain antioxidant, glutathione. Glutathione levels in PD patients are low.

    And as we age, levels of glutathione in the dopaminergic neurons of the substantia nigra decreases. This appears to hasten cell death and advance the progression of PD.

    At least 80 percent of the substantia nigra cells are lost before symptoms of Parkinson`s disease become apparent. This is why it becomes essential to protect or maintain these cells under oxidative stress.

    How does Glutathione help in Parkinson`s Disease?
    Several factors explain why glutathione is so beneficial in Parkinson`s disease.

    1. Glutathione increases the sensitivity of the brain to dopamine. So although glutathione doesn't raise dopamine levels, it allows the dopamine in the brain to be more effective.

    2. Glutathione's powerful antioxidant activity protects the brain from free radical damage.

    3. An even more intriguing benefit of glutathione lies in its powerful detoxification ability.

    Its a well known fact that most Parkinson`s patients are deficient in their ability to detoxify chemicals to which they are exposed.

    The unfortunate few who harbor an inherited flaw in their detoxification pathways are at far greater risk to the brain damaging effects of a wide variety of toxins.

    Glutathione is one of the most important components of the liver`s detoxification system. Glutathione therapy is one of the most effective techniques for enhancing liver and brain detoxification.

    Glutathione treatments considerably improve some of the symptoms of Parkinson`s disease including difficulties with rigidity, walking, movement, coordination and speech. A marked reduction of tremor has been observed as well as a decrease in depression.

    Glutathione and N-acetyl-L-cysteine (a glutathione precursor) have been shown to be very effective in protecting the nerves in the substantia nigra from being destroyed by oxidative stress.

    Glutathione Therapy in Parkinson`s Disease

    The practical problem in increasing glutathione levels is that taking glutathione itself as a supplement does not boost cellular glutathione levels, since glutathione breaks down in the digestive tract before it reaches the cells.

    However, intravenous glutathione therapy and taking glutathione precursors are both effective in boosting intracellular levels of glutathione.

    Intravenous Glutathione Therapy:

    Intravenous glutathione injections have been shown to have amazing and quick results.

    Dr. David Perlmutter, a pioneer in this therapy, has developed a protocol utilized at the Perlmutter Health Center for administering intravenous glutathione to Parkinson`s patients.

    Following even a single dosage of intravenous glutathione - often in as little as 15 minutes - the ability to walk, turn around and move their arms is almost completely restored.

    Glutathione Precursors:
    Dietary antioxidants and supplements that increase cellular glutathione, such as alpha lipoic acid, NAC, pycnogenol, the herb silymarin (milk thistle), are effective in restoring normal function.

    N-acetyl-cysteine (NAC) and un-denatured whey protein, like Immunocal, both supply glutathione precursors intracellularly, enhance the body`s production of glutathione and aid the detoxification process.

    Other nutritional supplements which aid the detoxification process include selenium, vitamins E and C.
        Glutathione is an orphan drug for the treatment of AIDS-associated cachexia. It is thought that this disorder is due, in part, to oxidatively-stressed and damaged enterocytes. There is some evidence that although orally administered glutathione may not be absorbed into the blood from the small intestine to any significant extent, that it may be absorbed into the enterocytes where it may help repair damaged cells. Glutathione in one form or another is the subject of some medicinal chemistry research and some clinical trials. For example, an aerosolized form of glutathione is being studied in AIDS and cystic fibrosis patients. Glutathione, the principal antioxidant of the deep lung, appears to be diminished in those with AIDS. Prodrugs of gamma-L-glutamyl-L-cysteine are being evaluated as anticataract agents.

    _Glutathione_ThioDoxGlutathione

    N.E.E.D.S., Inc. Product Fact Sheet
    Vitamins & Supplements - Professional-Grade
    Glutathione
    ThioDox Glutathione Complex
    Allergy Research Group

    ITEM NUMBER:

    ARG-6008-090
    SIZE:

    90 Tablets
    POTENCY:
    ADDITIONAL SIZES AVAILABLE:
    PRODUCT DESCRIPTION:
    Formulated to enhance and protect liver, brain and eye function. Provides antioxidant activity, enhances effectiveness of other antioxidants, supports detoxification, immune system function and glutathione levels, and helps regulate blood sugar and homocysteine levels. These nutrients are of the highest quality and purity obtainable. Hypoallergenic.

    WARNINGS:



    ADDITIONAL INFO:
    Variations in product color may occur. Keep in a cool, dry place, tightly capped.

    PACKAGING:
    White Plastic

    Supplement Facts
    Serving Size: 1 Tablet
    Servings per container: 90

    Amount Per Serving
    Vitamin C (as Ascorbic Acid)
    10 mg

    Thiamin (as Thiamin Tetrahydrofurfuryl Disulfide)
    5 mg

    Riboflavin (as Riboflavin-5-Phosphate)
    10 mg

    Selenium (as L-Selenomethionine)
    20 mcg

    N-Acetyl-L-Cysteine
    250 mg

    L-Glutathione (Reduced)
    200 mg

    Lipoic Acid
    150 mg



    INGREDIENTS:


    OTHER INGREDIENTS:
    Dicalcium Phosphate, Cellulose, Magnesium Stearate, Silicon Dioxide and Stearic Acid.

    DOES NOT CONTAIN:
    Common Allergens (Antigens), Preservatives, Diluents or Artificial Additives.

    SUGGESTED USE:
    As a dietary supplement, 1 to 4 tablets daily with meals, or as directed by a healthcare practitioner.





    _Glutathione_N-Acetyl-L-Cysteine

    Glutathione N-Acetyl-L-Cysteine (NAC)

    Glutathione, NAC, and Lipoic Acid

    Health Defense Formula

    See also:   N-Acetyl-L-Cysteine Abstracts
    Lipoic Acid Abstracts

     

     


    GLU-NAC PLUS™
    60 caps
    $26.95


    PRODUCT DESCRIPTION: GLU-NAC PLUS™ contains 250 mg of reduced glutathione, 250 mg of n-acetyl-l-cysteine (NAC), and 5 mg of alpha lipoic acid per capsule. Glutathione and NAC (a major precursor of glutathione) both provide important protection against free radicals and toxins, as well as strengthen the immune system. Lipoic acid is a potent fat-soluble and water-soluble antioxidant with important metabolic and detoxification properties. Glu-Nac Plus™ is designed to be hypoallergenic, contains no magnesium stearate, and is suitable for hypersensitive individuals.

     

    NUTRITIONAL CONSIDERATIONS & APPLICATIONS: Glutathione is considered the most powerful and versatile of the body's self-generated antioxidants. Glutathione plays a key role or is involved in: 1) Neutralizing free radicals and prevention of their formation both enzymatically and non-enzymatically, 2) Reducing oxidized Vitamin C and Vitamin E to their unoxidized states, 3) Phase I and II detoxification reactions, 4) Nucleic acid synthesis, 5) DNA repair, 6) Maintaining cellular redox potential, 7) Cellular differentiation and retarding the aging process, and 8) Maintaining normal brain function. In addition, Glutathione both is one of the strongest anti-cancer agents manufactured in the body and one of the most potent known antiviral agents. N-acetyl-l-cysteine (NAC) is the rate-limiting amino acid for the production of glutathione within the cells of the body; it has mucolytic properties, and is a powerful antioxidant and detoxifier. Some research indicates that NAC is more readily absorbed into certain cells of the body than glutathione and therefore is an excellent synergist with glutathione. Lipoic acid operates as an antioxidant in both its oxidized and reduced states, and has been shown to enhance glutathione levels.

    The nutrients in Glu-Nac Plus™ provide powerful effects, especially relating to free radical protection, detoxification, immune system enhancement, reduced inflammation, and normal cellular functioning. This product provides outstanding nutritional support in a wide variety of conditions of poor health, and helps support and maintain a state of health and well-being.

    COMPOSITION: 1 preservative-free capsule provides the following percentages of the Daily Value:

    NUTRIENT

    AMOUNT

    % Daily Value

    Glutathione (reduced)

    250 mg

    *

    N-Acetyl-L-Cysteine

    250 mg

    *

    Alpha Lipoic Acid

    5 mg

    *

    * No established Daily Value

    DIRECTIONS: As a dietary supplement take 1-2 capsules daily away from food, or as directed by a health care professional.

    INGREDIENTS: Glu-Nac Plus™ only contains the highest quality glutathione (reduced), n-acetyl-l-cysteine, alpha lipoic acid, microcrystalline cellulose, gelatin (capsule), and the smallest amounts of silica and magnesium trisilicate.

    Glu-Nac Plus™ does not contain wheat, rye, oats, corn, barley, gluten, soy, egg, dairy, yeast, sugar, sulfates, phosphates, chlorides, fats, wax, preservatives, colorings, or artificial flavorings.

    These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.