Glutathione Information

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GLUTATHIONE (GSH), a naturally occurring protein, is called a peptide. It is composed of three amino acids: glycine, glutamine and cysteine. Cysteine contains sulfur and gives glutathione its sulfuric aroma. It also plays a major role in glutathione’s antioxidant and detoxification functions.

Glutathione functions to:
Protect cells against free radicals that cause oxidation damage
Neutralize/remove toxins
Enhance immune function
Regulate protein and DNA growth

Glutathione, with its anti-inflammatory properties, is considered a “key antioxidant” in the functioning of cells. Antioxidant means it helps prevent oxidative stress.

OXIDATIVE STRESS
Oxidation in the outside world is the chemical mechanism that causes rust. Inside the body oxidation damage, called oxidative stress, causes damage to the proteins that keep the cells and their membranes running. Oxidative stress refers to toxins produced inside the body, free radicals, and those from without, which are caused by the environment. Glutathione plays a critical role in defending cells again oxidative stress.

Glutathione deficiency contributes to oxidative stress, which plays a key role in aging and the pathogenesis of many diseases including kwashiorkor, seizure, Alzheimer’s disease, Parkinson’s disease, liver disease, cystic fibrosis, sickle cell anemia, HIV, AIDS, cancer, heart attack, stroke, and diabetes.(1)

ALZHEIMER'S DISEASE
In one study it was shown that the concentration of glutathione was decreased in red blood cells from male Alzheimer’s disease patients compared with age- and gender-matched controls. (7)

ASTHMA
A study of asthmatic children found an inverse correlation between the level of glutathione and the severity of asthma attack. Lowest levels of glutathione were found during acute asthmatic attacks. (8)

ATHEROSCLEROSIS
Regarding a study performed on atherosclerotic mice using ReadiSorb Liposomal Glutathione: "We thus conclude that liposomal glutathione possesses anti-oxidative and anti-atherogenic properties towards lipoproteins and macrophages, leading to attenuation of atherosclerosis development." (15)

AUTISM
This study looked at the metabolism of autistic children. Impairments in the methylation cycle, a very critical part of our body’s functioning, were found. Because of this problem in the methylation cycle, autistic children are predisposed to low glutathione which prevents them from detoxifying normally. It was also found that certain co-enzymes, all non-pharmaceutical, support that cycle. (10)

CHRONIC FATIGUE SYNDROME
The role of oxidative stress in CFS is an important area for current and future research as it suggests the use of antioxidants in the management of CFS. Specifically, the dietary supplements glutathione, N-acetylcysteine, alpha-lipoic acid... may be beneficial.(14)

CYSTIC FIBROSIS AND LUNG DISEASE
In cystic fibrosis, lung disease is typified by an inflammatory response. This leads to oxidative stress in the lungs. Glutathione is the primary intracellular antioxidant, and provides an important defense in the epithelial lining fluid. (2)

“… GSH system dysfunction may be the trigger for initial depletion of other antioxidants and may also play a role in initiating the over-inflammation characteristic of cystic fibrosis. Proper GSH system functioning also affects immune system competence and mucus viscosity, both of relevance to cystic fibrosis pathophysiology. In a way, cystic fibrosis may be thought of as the first identified disease with GSH system dysfunction”. (3)

Glutathione is present in the epithelial lining fluid of the normal lower respiratory tract, where it is thought to play a major role in providing antioxidant protection to the epithelial cells. A study done on patients with IPF (idiopathic pulmonary fibrosis) showed the lower respiratory tracts to be chronically depleted of glutathione. (4)

Oxidant/antioxidant imbalance, a major cause of cell damage, is the hallmark for lung inflammation. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extra-cellular protective antioxidant against oxidative stress, which plays a key role in the control of signaling and pro-inflammatory processes in the lungs. (16)

Use of a daily GSH regimen appears to be associated in CF patients with significant improvement in lung function and weight, and a significant decline in bacteria cultured in this uncontrolled study. (20)

HEAVY METAL TOXICITY, MERCURY TOXICITY
Whilst iron (Fe), copper (Cu), chromium (Cr), vanadium (V) and cobalt (Co) undergo redox-cycling reactions, for a second group of metals, mercury (Hg), cadmium (Cd) and nickel (Ni), the primary route for their toxicity is depletion of glutathione... (13)

Cells exposed to methylmercury showed a decrease in glutathione peroxidase activity. Simultaneous administration of 10 mM glutathione with 2.5 and 5.0 microM methylmercury dramatically prevented cell injury. (17)

Glutathione-mercury complexes have been found in the liver, kidney, and brain, and appear to be the primary form in which mercury is transported and eliminated from the body. (18)

Glutathione depletion and glutathione supplementation have specific effects on mercury toxicity, both by altering antioxidant status in the body and by directly affecting excretion of mercury and other heavy metals in the bile. (19)

HIV
Glutathione is essential for the viability and function of virtually all cells. In vitro studies showing that low GSH levels both promote HIV expression and impair T cell function suggesting a link between GSH depletion and HIV disease progression. (9)

INFLUENZA
...the data suggest that the thiol antioxidant GSH has an anti-influenza activity in vitro and in vivo. Oxidative stress or other conditions that deplete GSH in the epithelium of the oral, nasal, and upper airway may, therefore, enhance susceptibility to influenza infection. (12)

PARKINSON'S DISEASE
Rational, integrative management of Parkinson’s disease requires, among other things, aggressive repletion of glutathione. (5)

There is a reduction in the levels of reduced glutathione in … Lewy body disease (presymptomatic Parkinson’s disease) of the same magnitude as occurs in advanced Parkinson's disease. This would suggest that alterations in glutathione function are an early marker of pathology in Parkinson's disease… (6)

Past studies have shown that depletion of the naturally occurring antioxidant in the affected area of the brain is one of the earliest signs of PD, but this study shows that glutathione depletion may be a causal factor in the disorder. (11)

(1) Guoyao, Wu et al Glutathione metabolism and its implications for health J Nutr. 2004 Mar; 134(3):489-92.
(2) Lands, L et al. Lymphocyte Glutathione Levels in Children With Cystic Fibrosis. Chest. 1999; 116:201-205.
(3) Hudson, VM New insights into the pathogenesis of cystic fibrosis: pivotal role of glutathione system dysfunction and implications for therapy. Treat Respir Med. 2004; 3(6):353-63.
(4) Cantin AM et al Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis. Am Rev Respir Dis. 1989 Feb; 139(2):370-2.
(5) Kidd PM Parkinson's disease as multifactorial oxidative neurodegeneration: implications for integrative management. Altern Med Rev. 2000 Dec; 5(6):502-29.
(6) Jenner P Altered mitochondrial function, iron metabolism and glutathione levels in Parkinson's disease. Acta Neurol Scand Suppl. 1993; 146:6-13.
(7) Liu H, et al Gender differences in glutathione metabolism in Alzheimer's disease J Neurosci Res. 2005 Mar 15;79(6):861-7.
(8) Bibi H et al. Erythrocyte glutathione peroxidase activity in asthmatic children. Ann Allergy. 1988 Nov; 61(5):339-40.
(9) Herzenberg, LA et al Glutathione deficiency is associated with impaired survival in HIV disease Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1967-72.
(10) James, SJ et al Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec; 80(6):1611-7.
(11) Shankar J et al Inducible Alterations of Glutathione Levels in Adult Dopaminergic Midbrain Neurons Result in Nigrostriatal Degeneration. J. Neurosci., Dec 2007; 27: 13997 - 14006.
(12) Cai, J et al Inhibition of influenza infection by glutathione. Free Radic Biol Med. 2003 Apr 1;34(7):928-36.
(13) Valko, M et al Metals, toxicity and oxidative stress.Curr Med Chem. 2005;12(10):1161-208.
(14) Logan, AC Chronic fatigue syndrome: oxidative stress and dietary modifications.Altern Med Rev. 2001 Oct;6(5):450-9.
(15) Rosenblat, M et al Anti-oxidant and anti-atherogenic properties of liposomal glutathione: studies in vitro, and in the atherosclerotic apolipoprotein E-deficient mice. Atherosclerosis. 2007 Dec;195(2):e61-8.
(16) Rahman I. Regulation of glutathione in inflammation and chronic lung diseases. Mutat Res. 2005 Nov 11;579(1-2):58-80.
(17) Kromidas L. The protective effects of glutathione against methylmercury cytotoxicity. Toxicol Lett 1990;51:67-80.
(18) Zalups RK. Molecular interactions with mercury in the kidney. Pharmacol Rev 2000;52:113-143.
(19) Patrick, L. Mercury toxicity and antioxidants: part I: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Alternative Medicine Review, Dec, 2002
(20) Visca, A. Improvement in clinical markers in CF patients using a reduced glutathione regimen: An uncontrolled, observational study. J Cyst Fibros 2008 May 20 (epub)