# Study, Research & Technical Information About Glutathione > Welcome to Glutathionereporter.com. Glutathione GSH, master antioxidant, most studied molecule; a tripeptide made using precursor gamma-glutamylcysteine GGC is important for Heath & Wellness. --- ## Pages - [Contribute](https://www.glutathionereporter.com/contribute/) - [Welcome to glutathionereporter.com](https://www.glutathionereporter.com/about/): Glutathione is one of the most studied molecules in healthcare. More than 80,000 papers on glutathione published in peer reviewed... - [Home](https://www.glutathionereporter.com/): Welcome to Glutathionereporter. com Glutathione is one of the most studied molecules in healthcare. More than 80,000 papers on glutathione... --- ## Posts - [Glutathione Depletion in Mitochondrial Diseases](https://www.glutathionereporter.com/glutathione-depletion-in-mitochondrial-diseases/): Author: Ishika Jaitly Mitochondria are cellular substructures that function as energy powerhouses for almost all eukaryotic cells, including those of... - [Glutathione and Sunburn / Skin Damage](https://www.glutathionereporter.com/glutathione-and-sunburn-skin-damage/): Author: Sophie Van Der Helder A biological antioxidant is defined as “any substance that, when present at low concentrations, significantly... - [Glutathione Depletion and Osteoporosis](https://www.glutathionereporter.com/glutathione-depletion-and-osteoporosis/): Author: Emma Beukers Osteoporosis is a debilitating skeletal condition characterized by low bone density, causing bone fragility and increased risk... - [Glutathione and Long Covid/Chronic Fatigue Syndrome](https://www.glutathionereporter.com/glutathione-and-long-covid-or-chronic-fatigue-syndrome/): COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which has been at the forefront of people’s minds since... - [Glutathione and Cystic Fibrosis](https://www.glutathionereporter.com/glutathione-and-cystic-fibrosis/): Systemic glutathione deficiency, inflammation, and oxidative stress are hallmarks of cystic fibrosis, an inherited disease that causes persistent lung infections... - [Glutathione and Eye Disease](https://www.glutathionereporter.com/glutathione-and-eye-disease/): Glutathione Depletion and Diseases of the Eye: Cataract and Macular Degeneration Author:- Ishika Jaitly Cataract A cataract is an opacification... - [Glutathione and Osteoarthritis](https://www.glutathionereporter.com/glutathione-and-osteoarthritis/): Osteoarthritis is a chronic inflammatory disease which results in the protective tissue (cartilage) at the joints of bones to break... - [Glutathione and kidney disease](https://www.glutathionereporter.com/glutathione-and-kidney-disease/): Oxidative stress is considered a main player in kidney disease and associated mortality rates. This sustained production of free radicals... - [Glutathione and cardiovascular diseases](https://www.glutathionereporter.com/glutathione-and-cardiovascular-diseases/): Cardiovascular disease (CDV) is the number 1 cause of death globally, taking an estimated 18 million lives each year. Whilst... - [Glutathione and infertility](https://www.glutathionereporter.com/glutathione-and-infertility/): Globally, infertility is a major health problem and can cause significant financial and psychological stress. In many cases, the cause... - [Glutathione and diabetes](https://www.glutathionereporter.com/glutathione-and-diabetes/): Diabetes has become one of the most prominent chronic diseases in many of the world’s populations. Whilst type 1 is... - [Glutathione and its many (dis)guises](https://www.glutathionereporter.com/glutathione-and-its-many-disguises/): There is an on-going proliferation of alternative delivery systems for Glutathione (GSH) in the misguided attempt that one may be... - [Glutathione and other diseases](https://www.glutathionereporter.com/glutathione-and-other-diseases/): Glutathione and diabetes Diabetes has become one of the most prominent chronic diseases in many of the world’s populations. Whilst... - [How a physician explains antioxidants to patients](https://www.glutathionereporter.com/how-a-physician-explains-antioxidants-to-patients/): By William Sears, MD After more than 50 years of practice, by far two of the most difficult concepts to... - [Gamma-Glutamylcysteine increases cellular glutathione](https://www.glutathionereporter.com/gamma-glutamylcysteine-increases-cellular-glutathione/): Gamma-glutamylcysteine, (GGC) is a naturally occurring dipeptide found in all mammalian life and is a key intermediate in the gamma... - [Glutathione and Covid-19 Infection](https://www.glutathionereporter.com/glutathione-and-covid-19-infection/): Given that a vaccine for COVID-19 is quite possibly a long way off, it is more important than ever to... - [N-Acetylcysteine (NAC) cannot increase cellular Glutathione levels](https://www.glutathionereporter.com/n-acetylcysteine-nac-cannot-increase-cellular-glutathione-levels/): Over the years, there have been countless papers written on the importance of glutathione (GSH) and the myriad of ways... - [Raising cellular Glutathione levels with Gamma-Glutamylcysteine](https://www.glutathionereporter.com/raising-cellular-glutathione-levels-with-gamma-glutamylcysteine/): A human clinical trial demonstrated that oral Gamma-glutamylcysteine (GGC) is directly taken up by cells and increases glutathione (GSH) within... - [Glutathione supplementation cannot increase cellular Glutathione levels](https://www.glutathionereporter.com/glutathione-supplementation-cannot-increase-cellular-glutathione-levels/): Glutathione is exclusively made inside cells and is produced in two steps: The first makes gamma-glutamylcysteine (GGC) from the amino... - [Glutathione’s importance in maintaining health](https://www.glutathionereporter.com/glutathiones-importance-in-maintaining-health/): Glutathione (GSH) is the body’s powerful weapon in the fight against both acute and chronic inflammation. Researchers generally agree that... - [Glutathione and Viral Infection](https://www.glutathionereporter.com/glutathione-and-viral-infection/): There is a growing body of scientific and medical literature that suggests glutathione (GSH) may play a key role in... - [Glutathione and Toxicology and Liver Disease](https://www.glutathionereporter.com/glutathione-and-toxicology-and-liver-disease/): Glutathione (GSH) plays an essential part in neutralizing reactive oxygen (ROS) species such as peroxide and superoxide ion. It is... - [Glutathione and sports nutrition](https://www.glutathionereporter.com/glutathione-and-sports-nutrition/): Exercise plays an important part in keeping us healthy. But it is not without its pitfalls. As exercise intensity increases,... - [Glutathione and Neurodegenerative Disease](https://www.glutathionereporter.com/glutathione-and-neurodegenerative-disease/): It’s well known that our risk of developing chronic diseases increases as we age. The reasons behind this are incredibly... - [Glutathione and Lung Disease](https://www.glutathionereporter.com/glutathione-and-lung-disease/): The extensive surface area and blood supply in our lungs enables them to provide our bodies with sufficient oxygen for... - [Glutathione and the Immune system](https://www.glutathionereporter.com/glutathione-and-the-immune-system/): A growing body of research has demonstrated that glutathione (GSH) is a key player in the immune system and the... - [Glutathione and Gastrointestinal Disease](https://www.glutathionereporter.com/glutathione-and-gastrointestinal-disease/): The extensive surface area of our digestive system enables us to extract all of the essential nutrients from our diet.... - [Glutathione and Cancer](https://www.glutathionereporter.com/glutathione-and-cancer/): Cancer is an incredibly complex disease. Almost any type of cell in the body has the potential to become cancerous... - [Glutathione and the aging process](https://www.glutathionereporter.com/glutathione-and-the-aging-process/): The body’s mechanism for dealing with oxidative stress becomes less efficient as we get older. This decline in function is... - [Glutathione and the human body](https://www.glutathionereporter.com/glutathione-and-the-human-body/): Glutathione’s (GSH’s) main role as an antioxidant is the use of its thiol (-SH) group as a nucleophilic scavenger and... - [Glutathione and Homeostasis](https://www.glutathionereporter.com/glutathione-and-homeostasis/): Homeostasis refers to any process that living things use to actively maintain fairly stable conditions necessary for survival. Unlike your... - [Glutathione and Inflammation](https://www.glutathionereporter.com/glutathione-and-inflammation/): Over many decades of extensive research, glutathione (GSH) has emerged as the crucial player in regulating inflammation . It does... - [Inflammation](https://www.glutathionereporter.com/inflammation/): Our immune system is an incredible achievement of evolution without which we would succumb to even the slightest infection. It... - [What is Gamma-Glutamylcysteine (GGC)](https://www.glutathionereporter.com/what-is-gamma-glutamylcysteine-ggc/): Gamma-glutamylcysteine (GGC) is a dipeptide and is the immediate precursor to the tripeptide glutathione (GSH). The intracellular concentration of gamma-glutamylcysteine... - [Measuring cellular Glutathione concentration](https://www.glutathionereporter.com/measuring-cellular-glutathione-concentration/): One of the impediments to knowing one’s glutathione (GSH) status is the lack of standardized analytical methods for determining glutathione... - [How do cells produce Glutathione?](https://www.glutathionereporter.com/how-do-cells-produce-glutathione/): Glutathione (GSH) is synthesized in the cytoplasm in virtually all cells from its constituent amino acids by two sequential ATP-requiring... - [Glutathione and it’s importance to Life](https://www.glutathionereporter.com/glutathione-and-its-importance-to-life/): Glutathione, often referred to as the “Master Antioxidant”, is the most biologically abundant antioxidant that protects almost all aerobic (air... - [What is Glutathione](https://www.glutathionereporter.com/what-is-glutathione/): Glutathione (GSH) is often termed the “master antioxidant”. This tripeptide is ubiquitous in nature and is produced by every organism... --- # # Detailed Content ## Pages Name Email Mobile Article Description Upload Article (PDF only) All Fields are mandatory --- Glutathione is one of the most studied molecules in healthcare. More than 80,000 papers on glutathione published in peer reviewed scientific journals attest to the importance of this peptide in health and wellness. The content on this website has been selected to educate healthcare practitioners and others with a deep interest in maintaining good health. By it’s very nature, the subject is highly technical and though an attempt has been made to simplify the content matter, it does need a higher than common level of comprehension from the general public. Healthcare professionals and persons engaged in related fields of scientific research will have no difficulty in understanding the material presented. This website provides extensive information, together with references to published scientific literature, on all aspects of glutathione including on the relationships between glutathione and chronic diseases. Whereas the large number of published studies demonstrates correlation between depleted cellular glutathione and chronic diseases there do not appear to have been any studies to demonstrate the effect of increasing cellular glutathione on these diseases. This is probably because, until very recently, there was no confirmed way to increase cellular glutathione. One of the objectives of this website is to provide healthcare professionals the technical information they would need to determine whether their patients could benefit from increasing cellular glutathione and to advise them accordingly. Another objective is to provide references to researchers in related fields thereby encouraging them to study the therapeutic effects of increasing cellular glutathione. To members of the general... --- Welcome to Glutathionereporter. com Glutathione is one of the most studied molecules in healthcare. More than 80,000 papers on glutathione published in peer reviewed scientific journals attest to the importance of this peptide in health and wellness. The content on this website has been selected to educate healthcare practitioners and others with a deep interest in maintaining good health. By its very nature, the subject is highly technical and though an attempt has been made to simplify the content matter... 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push(block_tdi_12_600); GlutathioneWhat is GlutathioneGlutathione Reporter - May 7, 2020 edit Glutathione (GSH) is often termed the “master antioxidant”. This tripeptide is ubiquitous in nature and is produced by every organism from bacteria, to plants to animals that derives energy from oxidative phosphorylation and respiration. Glutathione is synthesized in the cytosol of each cell by the action of two enzymes in an elegantly regulated system that allows it to be maintained at different homeostatic levels in different tissue types, with... Continue reading GlutathioneGlutathione and it’s importance to LifeGlutathione Reporter - May 11, 2020 edit Glutathione, often referred to as... --- --- ## Posts Author: Ishika Jaitly Mitochondria are cellular substructures that function as energy powerhouses for almost all eukaryotic cells, including those of humans . The number of mitochondria in a cell can vary widely . Red blood cells, for example, have none, whereas liver cells can contain up to two thousand . Mitochondria are integral to our survival due to the variety of roles they play in our biochemistry, the most important of which is the production of adenosine triphosphate (ATP) by aerobic respiration . This process involves oxidative phosphorylation, which utilizes oxygen to release the energy contained in the foods we eat. The energy is initially stored in ATP, which subsequently releases this energy to power the body’s metabolic reactions. During this process, ATP is broken down into adenosine diphosphate (ADP) and inorganic phosphate (Pi). Since mitochondria are essential to our very existence, it is unsurprising that the effects of mitochondrial diseases can be severe, and sometimes lethal, spanning a wide-ranging spectrum of physiological and biochemical symptoms (see Table 1 for examples). Mitochondrial diseases in humans can arise from a myriad of mutations in mitochondrial and nuclear (cellular) DNA . Collectively, mitochondrial diseases are reported to affect 1 in every 5,000 adults, making them quite prevalent in comparison to other hereditary metabolic disorders . Primary Mitochondrial Disease SubtypeClassic SymptomsLeigh Syndrome (subacute necrotizing encephalomyelopathy)Muscle spasms, fatigue . Alpers–Huttenlocher syndromeEpilepsy, liver deterioration . Leber hereditary optic neuropathyProgressive loss of vision in both eyes, most commonly seen in young males . Mitochondrial encephalopathy lactic... --- Author: Sophie Van Der Helder A biological antioxidant is defined as “any substance that, when present at low concentrations, significantly delays or prevents the oxidation of oxidizable substrates” . Oxidizable substrates in the body, such as DNA and proteins, can incur damage by accepting electrons from unstable reactive oxygen species (ROS), which are generated by exogenous and endogenous means. Ultra-violet radiation (UVR) is a type of ionizing radiation that significantly increases ROS formation as its short wavelength and high frequency possesses enough energy to knock electrons out of oxygen molecules. This makes them highly unstable. Everyday UVR exposure often leads to sunburn, and long-term repeated exposure can additionally result in substantial skin and DNA damage that may lead to the development of melanoma and other skin cancers . When the body’s antioxidant defence system becomes overwhelmed due to an influx of ROS, a cascade of oxidative damage can occur. If the DNA or membrane of a cell is irreversibly damaged, it will be marked for programmed cell death (apoptosis). This process releases inflammatory markers such as prostaglandins, which are responsible for inducing the symptoms of sunburn: Vasodilation, swelling and pain . Oxidative damage can accumulate over time if UVR exposure is frequent, accelerating photoaging and consequently increasing the appearance of wrinkles, pigmentation and blotchiness. The Skin Cancer Foundation states that photoaging is responsible for 90% of visible changes to the skin . The symptoms of photoaging occur due to the oxidation of dermal collagen fibre bundles, which are proteins responsible... --- Author: Emma Beukers Osteoporosis is a debilitating skeletal condition characterized by low bone density, causing bone fragility and increased risk of bone fractures . The body constantly renews bone tissue by absorbing old tissue and regenerating new tissue. As we get older, these two processes become unbalanced, resulting in increased bone resorption and decreased bone formation . This is a contributing factor for the gradual loss in bone density and strength as we age. Other factors impacting bone health may include cellular changes, genetic damage due to complex age-related changes as well as nutritional deficiencies of calcium and vitamin D. Oxidative stress can also negatively affect bone health . Oxidative stress occurs due to excessive reactive oxygen species (ROS) paired with inadequate levels of antioxidants, in particular glutathione . The level of ROS in the body increases with age and as a result of negative lifestyle factors such as smoking and obesity . This progressively weakens the maintenance of functional tissues and further negatively impacts the balance of bone formation and bone resorption . The body has a finely tuned antioxidant system which neutralizes ROS. This includes the group of antioxidant vitamins such as C & E, but in particular glutathione, which is the most powerful antioxidant in its own right. Glutathione also recycles Vitamins C & E and is therefore the cornerstone of our complex antioxidant response . The importance of glutathione is well recognized in the medical community . We also know that the body’s production of glutathione... --- COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which has been at the forefront of people’s minds since its emergence in late 2019. It is fair to say that the pandemic it unleashed throughout the world will resonate with us for many years. The arrival of successful vaccines has tilted the pandemic in our favour, but there is a sinister side to this story. Not long after COVID-19 became synonymous with the collapse of tourism, businesses and overburdened health systems, reports of people surfaced who suffered from a condition that became known as Long Covid. In essence, Long Covid is a lingering illness in people who have contracted COVID-19 and then presumably recovered because the virus was no longer detectable. Regardless of how severe the initial onset of COVID-19 manifested itself, a significant proportion of patients report debilitating symptoms long after the virus has been eliminated from their body . An Irish study found that over 50% of patients with COVID-19 reported persistent fatigue more than 10 weeks after initial symptoms . Likewise, researchers in Italy confirmed troublesome symptoms sixty days after initial onset . The US Centers for Disease Control and Prevention similarly concluded ongoing symptoms such as fatigue and cough. They found this to be more prevalent in older people or those suffering from chronic diseases. But is this a hallmark of SARS-CoV-2 and entirely unexpected? The short answer is no, because there is a range of viruses that cause post-infectious fatigue syndrome. Similar conditions have... --- Systemic glutathione deficiency, inflammation, and oxidative stress are hallmarks of cystic fibrosis, an inherited disease that causes persistent lung infections and severe damage to the respiratory system and many of the body organs. Improvements to current antioxidant therapeutic strategies are needed. The dietary supplement, gamma-glutamylcysteine (GGC), which is the immediate precursor to glutathione, rapidly boosts cellular glutathione levels following a single dose in healthy individuals.   GGC was recently used in a study by a group of scientists at the University of New South Wales on cell lines from individuals with cystic fibrosis in a series of revealing in vitro studies . The efficacy of GGC against oxidative stress induced by Pseudomonas aeruginosa, which is a common and chronic pathogen infecting lungs of cystic fibrosis patients was evaluated. When assessed as both a prophylactic and as a treatment GGC effectively attenuated some forms of oxidative stress, while significantly increasing total intracellular glutathione levels, metabolic viability and improving epithelial cell barrier integrity. Together, these findings indicate that GGC has therapeutic potential for treatment and prevention of oxidative stress-related damage to airways in cystic fibrosis. For more information see:- https://encyclopedia. pub/4014 Reference 1. Hewson, C. K. C. , A. ; Wong, S. L. ; Pandzic, E. ; Zhong, L. ; Fernando, B. S. M. ; Awatade, N. T. ; Hart-Smith, G. ; Whan, R. M. ; Thomas, S. R. ; Jaffe, A. ; Bridge, W. J. ; Waters, S. A. , Novel Antioxidant Therapy with the Immediate Precursor to Glutathione, γ-Glutamylcysteine (GGC),... --- Glutathione Depletion and Diseases of the Eye: Cataract and Macular Degeneration Author:- Ishika Jaitly Cataract A cataract is an opacification of the lens and is the leading cause of blindness worldwide. The WHO estimates around 20 million people have bilateral blindness from cataracts. As longevity increases, the impact of cataracts on society is also expected to increase . The three major risk factors in the development of cataracts are ageing, diabetes and exposure to sunlight , with ageing considered to be the most prominent . While little can be done to modify the risk that advanced age poses, limiting exposure to sunlight is associated with a lower incidence of cataracts. Although not yet fully understood, the likely cause is the ionizing UV radiation spectrum of sunlight. This ionizing radiation promotes oxidative stress in the lens by producing damaging reactive oxygen species (ROS) . Commonly known as free radicals, ROS are primarily quenched by the two principal components of the antioxidant defence system of the lens: Glutathione (GSH) and ascorbic acid . Both are crucial in preventing the gradual loss of transparency of the lens , which is the classic symptom of cataracts. During childhood, the lens possesses the highest levels of GSH of all tissues in the body . However, with increasing age, GSH homeostasis becomes progressively dysfunctional in the centre of the lens . Eventually, this results in chronically insufficient GSH levels to neutralize the ROS, leading to oxidative stress that damages lens proteins. The consequence is the formation... --- Osteoarthritis is a chronic inflammatory disease which results in the protective tissue (cartilage) at the joints of bones to break down. It is a painful disease that worsens with both age and obesity and cannot be cured. It is caused by several factors, but its progression is significantly related to oxidative stress and the generation of free radicals in the joint fluid . A recent review on the role of glutathione in osteoarthritis has revealed a that depleted glutathione exacerbated oxidative stress as seen in chronic inflammatory disorders such as osteoarthritis . In addition, some studies showed that the current treatments for increasing glutathione including supplementation with n-acetylcysteine were showing some minor improvements in symptoms.   With its ability to be efficiently transported into cells and rapidly increase cellular glutathione, orally administered gamma-glutamylcysteine is expected to show an even greater effect by reducing cartilage degradation and inflammation markers as well as significant improvements in pain and functional outcomes. References 1. Daghestani, H. N. and V. B. Kraus, Inflammatory biomarkers in osteoarthritis. Osteoarthritis and cartilage, 2015. 23(11): p. 1890-1896. https://pubmed. ncbi. nlm. nih. gov/26521734 2. Zhu, S. , et al. , Glutathione as a mediator of cartilage oxidative stress resistance and resilience during aging and osteoarthritis. Connective Tissue Research, 2020. 61(1): p. 34-47. https://doi. org/10. 1080/03008207. 2019. 1665035 3. Setti, T. , et al. , The protective role of glutathione in osteoarthritis. Journal of Clinical Orthopaedics and Trauma, 2020. https://www. journal-cot. com/article/S0976-5662(20)30440-9/fulltext --- Oxidative stress is considered a main player in kidney disease and associated mortality rates. This sustained production of free radicals is in part caused by the frequent and regular dialysis required to treat patients. Glutathione demand in these patients is therefore much higher in order to cope with the increased oxidative stress. Low levels of glutathione are a hallmark in kidney disease and this is thought to be caused by diminished levels of an enzyme called GCL which is the first step in the production of cellular glutathione. This enzyme is responsible for the production of gamma-glutamylcysteine, the direct precursor to glutathione. Since cysteine is removed from the blood in dialysis patients, supplementing with cysteine has a positive effect on glutathione levels, however it only addresses a small part of the problem. The diminished levels of GCL are of much greater concern. To address this problematic enzyme in dialysis patients, supplementation with gamma-glutamylcysteine has been shown to bypass GCL altogether by providing cells with the first building block of glutathione. Not only does gamma-glutamylcysteine readily enter cells, once inside it is quickly and easily converted to glutathione. References Alhamdani, M. S. , Impairment of glutathione biosynthetic pathway in uraemia and dialysis. Nephrol Dial Transplant, 2005. 20(1): p. 124-8. Santangelo, F. , et al. , Restoring glutathione as a therapeutic strategy in chronic kidney disease. Nephrology Dialysis Transplantation, 2004. 19(8): p. 1951-5. Ashworth, A. and S. T. Webb, Does the prophylactic administration of N-acetylcysteine prevent acute kidney injury following cardiac surgery?... --- Cardiovascular disease (CDV) is the number 1 cause of death globally, taking an estimated 18 million lives each year. Whilst an increased risk of CDV is often genetic in origin, the effect of negative lifestyle choices such as excessive alcohol consumption, smoking and poor diet play a well documented role in the development of CVD. Complications in the cardiovascular system arise from elevated levels of free radicals which cause tissue damage and interrupt cellular signalling mechanisms . Apart from lifestyle choices, there is a wide range of medical conditions that, by their nature, produce excessive free radicals, including diabetes, hypertension, stroke, and obesity. Whilst small bouts of increased levels of free radicals is normal, indeed required for signalling purposes and immune responses, it is the oxidative stress caused by sustained and excessive free radical production that leads to deleterious health outcomes . Means to prevent this sustained damage caused by oxidative stress have been studies extensively and are of major therapeutic interest . Whilst there is an abundance of pharmacological means to control chronic diseases such as diabetes or hypertension, reducing excessive production of free radicals from all possible sources presents a major challenge. As the principal intracellular antioxidant, Glutathione has been extensively researched. This interest stems from numerous studies into chronic diseases in which elevated levels of free radicals cause sustained oxidative stress. Glutathione acts directly by scavenging free radicals and several studies have reported that patients with heart disease have lower levels of glutathione. Furthermore, a reduction of... --- Globally, infertility is a major health problem and can cause significant financial and psychological stress. In many cases, the cause of infertility cannot be established, but oxidative stress is believed to be a major contributor due to its influence on the reproductive lifespan of both men and women. Treatments that focus on enhancing the cellular antioxidant defense mechanism therefore play an important role in combating infertility and complications during pregnancy. Glutathione has shown to be the most effective antioxidant in the body due to its ability to not only boost the antioxidant defense, but also recycle other key antioxidant such as Vitamin C. References Agarwal, A. and L. H. Sekhon, The role of antioxidant therapy in the treatment of male infertility. Human Fertility, 2010. 13(4): p. 217-225. Adeoye, O. , et al. , Review on the role of glutathione on oxidative stress and infertility. JBRA Assist Reprod, 2018. 22(1): p. 61-66. Ross, C. , et al. , A systematic review of the effect of oral antioxidants on male infertility. Reproductive biomedicine online, 2010. 20(6): p. 711-723. Lanzafame, F. M. , et al. , Oxidative stress and medical antioxidant treatment in male infertility. Reproductive biomedicine online, 2009. 19(5): p. 638-659. --- Diabetes has become one of the most prominent chronic diseases in many of the world’s populations. Whilst type 1 is genetic in origin, type 2 is primarily a lifestyle disease. Diabetes and the associated hyperglycaemia (high blood glucose) is related to an increase in the production of free radicals by a process called glycation. In essence, it is a process whereby the elevated blood glucose binds to proteins, in turn creating free radicals. The free radicals produced by glycation can be up to 50 times higher than normal and are implicated in ageing and tissue damage. Additionally, both type 1 and 2 diabetes are associated with low glutathione. The resulting oxidative stress and depletion of the cellular antioxidant defense system contributes to the progress of coronary artery disease. This plays a major role in the development of diabetes and its ongoing complications. Glutathione in its role as a free radical scavenger has been shown to drastically reduce the occurrence and duration of oxidative stress. Enhancing cellular glutathione is therefore of paramount importance in managing diabetes and reducing negative medical outcomes. References Whillier, S. , P. W. Kuchel, and J. E. Raftos, Oxidative Stress in Type II Diabetes Mellitus and the Role of the Endogenous Antioxidant Glutathione, in Role of the Adipocyte in Development of Type 2 Diabetes, C. Croniger, Editor. 2011. Robertson, R. P. , et al. , Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes, 2003. 52(3): p. 581-7. Ballatori, N.... --- There is an on-going proliferation of alternative delivery systems for Glutathione (GSH) in the misguided attempt that one may be effective. This rather extended list includes oral, sublingual, liposomal, intranasal, inhalation, transdermal and intravenous applications; all of which have demonstrated the inadequacy of Glutathione (GSH) to increase cellular Glutathione (GSH). Most importantly, all these delivery systems ignore one fundamental fact: The concentration of Glutathione (GSH) inside the cell is much higher than outside the cell, no matter how much Glutathione (GSH) is consumed. In fact, it is about one thousand-fold higher, making diffusion across that kind of concentration gradient thermodynamically impossible . So why keep trying when the laws of nature are firmly against you? Before 2014, trialling the use of Glutathione (GSH) as a supplement was uncommon. Clinicians then were well aware of its limited use. However, several companies started manufacturing and marketing Glutathione (GSH) as a supplement shortly after that, even though there was very little evidence at best to show that it had potential to increase cellular Glutathione (GSH). Nonetheless, this led to researchers testing Glutathione's (GSH's) potential, and today, the U. S. Clinical Trial Register has a long list of over 30 completed trials, none of which have published any positive results. One type of delivery system that keeps appearing in the literature is liposomal Glutathione (GSH). This is simply Glutathione (GSH) encapsulated in a lipid (fatty) membrane. This approach is also doomed to fail for the same reason mentioned above, but one wonders if it... --- Glutathione and diabetes Diabetes has become one of the most prominent chronic diseases in many of the world’s populations. Whilst type 1 is genetic in origin, type 2 is primarily a lifestyle disease. Diabetes and the associated hyperglycaemia (high blood glucose) is related to an increase in the production of free radicals by a process called glycation. In essence, it is a process whereby the elevated blood glucose binds to proteins, in turn creating free radicals. The free radicals produced by glycation can be up to 50 times higher than normal and are implicated in ageing and tissue damage. Additionally, both type 1 and 2 diabetes are associated with low glutathione. The resulting oxidative stress and depletion of the cellular antioxidant defense system contributes to the progress of coronary artery disease. This plays a major role in the development of diabetes and its ongoing complications. Glutathione in its role as a free radical scavenger has been shown to drastically reduce the occurrence and duration of oxidative stress. Enhancing cellular glutathione is therefore of paramount importance in managing diabetes and reducing negative medical outcomes. Glutathione and infertility Globally, infertility is a major health problem and can cause significant financial and psychological stress. In many cases, the cause of infertility cannot be established, but oxidative stress is believed to be a major contributor due to its influence on the reproductive lifespan of both men and women. Treatments that focus on enhancing the cellular antioxidant defense mechanism therefore play an important role in... --- By William Sears, MD After more than 50 years of practice, by far two of the most difficult concepts to explain to patients are antioxidants and their nemeses, free radicals. Yet balancing these two powerful forces is essential to achieving a long healthspan, which is the amount of time you spend on this earth in good health. As physicians, we can and should do more than just tell patients to eat their blueberries and green, leafy vegetables. I’ve found that people are much more inclined to follow my advice when they understand why I’m telling them to do something. The human body is the most marvelous machine ever made. Patients may not completely understand how it works; they just know they depend on it to function properly 24/7. That’s similar to something else most of us depend on daily: our cars. Here’s how I often introduce people to antioxidants In my book “The Inflammation Solution,” I explain that your car engine produces exhaust from burning fuel. Your body’s engine is its metabolism. It produces “exhaust,” or by-products, called oxidants. If produced in just the right amount, these microscopic oxidants (also known as free radicals) act like antibiotics to attack germs that get into our cells. But if we have an excessive amount of exhaust (called oxidative stress), the free radicals damage our cells and tissues. Enter antioxidants. These are molecules you make and eat to mute the damaging effects of oxidative stress. The antioxidants that your body makes and the... --- Gamma-glutamylcysteine, (GGC) is a naturally occurring dipeptide found in all mammalian life and is a key intermediate in the gamma (γ) -glutamyl cycle first described by Meister in the 1970s . It is the most immediate precursor to the essential antioxidant glutathione (GSH) . Supplementation with glutathione (GSH) is incapable of increasing cellular glutathione (GSH) since the glutathione (GSH) concentration found in the extracellular environment is much lower than that found intracellularly by about a thousand-fold. This large difference means that there is an insurmountable concentration gradient that prohibits extracellular glutathione entering cells and it is only inside the cell where glutathione performs its essential functions. Gamma-Glutamylcysteine (GGC) is not subject to such a concentration gradient as it occurs in human plasma in the range of 1 – 5 µM and intracellularly at 5 – 10 µM . The intracellular concentration of gamma-glutamylcysteine (GGC) is generally low allowing it (GGC) to diffuse into the cell. Once inside the cell it (GGC) rapidly bonds to glycine to form glutathione (GSH). This second and final reaction step in glutathione (GSH) biosynthesis is catalyzed by the activity of the ATP dependent glutathione synthase (GS) enzyme. Although currently unproven, gamma-glutamylcysteine (GGC) may be the pathway intermediate of glutathione transportation in multicellular organisms . A human clinical study in healthy, non-fasting adults demonstrated that orally administered gamma-glutamylcysteine (GGC) can significantly increase lymphocyte glutathione (GSH) levels indicating systemic bioavailability, validating the therapeutic potential of gamma-glutamylcysteine (GGC) . Gamma-glutamylcysteine (GGC) is also capable of being a powerful... --- Given that a vaccine for COVID-19 is quite possibly a long way off, it is more important than ever to explore other avenues of protecting your health. Even if a successful vaccine becomes available, it will be many years before entire populations can be immunized. Strong scientific evidence is now implicating oxidative stress in individual’s susceptibility to detrimental health outcomes with COVID-19 . Some recent studies have shown that profoundly serious infections with COVID-19, and its associated high risk of death, are due to glutathione deficiency . Additionally, a preliminary pilot trial with two COVID-19 patients found some improvement in respiratory symptoms after dosing with glutathione . This has led to several researches advocating the use of either glutathione itself or N-acetylcysteine as a treatment for COVID-19 patients. Although the intention to increase cellular glutathione is likely to be of benefit for the reasons outlined below. The newly available precursor to glutathione called gamma-glutamylcysteine is more likely to be a more effective and rapid way of increasing cellular glutathione . COVID-19, like the common influenza virus, belong to the family of RNA viruses. Much evidence has accumulated over the past decade suggesting that patients infected with such RNA viruses are under chronic oxidative stress associated with glutathione depletion because oxidative stress, and the associated overproduction of reactive oxygen species, is a hallmark of RNA viruses. More importantly, an oxidative state promotes protein glutathionylation (S-S disulphide binding of glutathione to a cysteine residue). This provides a mechanism for RNA viruses to... --- Over the years, there have been countless papers written on the importance of glutathione (GSH) and the myriad of ways to supplement this free radical scavenger. By now, we are all aware of its significance in keeping us healthy, but, unfortunately, there are many myths on how to enhance cellular glutathione (GSH) effectively. We have already discounted the most apparent strategy in one of our articles in which we discuss why taking glutathione itself will not increase its concentration inside the cell. So, let’s move on to the most often quoted myth that the amino acid cysteine is in limited supply in the body. We are aware that cysteine is one of the three building blocks that make up glutathione, but is there any evidence to suggest that we may be low on cysteine? And, regardless, would taking cysteine be effective in increasing cellular glutathione (GSH)? On initial observation, the principle behind the theory of cysteine deficiency being a cause of low glutathione (GSH) appears reasonably sound, but it is not that simple. The first question is relatively easy to answer. The fact is that our diet usually contains plenty of cysteine and the other sulphur containing amino acid called methionine which can be easily converted into cysteine in the liver . For example, the typical American diet supplies much more than the recommended required quantity of cysteine . We can, therefore, rule out a cysteine deficiency. But would taking a cysteine supplement such as N-acetylcysteine (NAC) increase our cellular... --- A human clinical trial demonstrated that oral Gamma-glutamylcysteine (GGC) is directly taken up by cells and increases glutathione (GSH) within several hours. This ability to rapidly increase cellular glutathione (GSH), even in healthy subjects, is unlike any other supplement on the market, including glutathione itself. Gamma-glutamylcysteine (GGC) has the advantage of being able to diffuse into cells where it is effectively converted to glutathione (GSH) by an enzymatic reaction which simply adds the amino acid glycine. Unlike cysteine prodrugs, such as NAC, which only increase cellular glutathione (GSH) following severe depletion such as in acetaminophen (paracetamol) overdose, gamma-glutamylcysteine (GGC) does so without limitations. This ability to increase glutathione (GSH) regardless of the current state of cellular glutathione (GSH) makes gamma-glutamylcysteine (GGC) unique in the vast supplement market touting effective ways to do so. The body’s biochemistry clearly indicates and research confirms that consuming gamma-glutamylcysteine (GGC) is the only way to ensure healthy glutathione (GSH) levels for all individuals including those suffering from chronic disease and inflammation. Reference Zarka, M. H. and W. J. Bridge, Oral administration of γ-glutamylcysteine increases intracellular glutathione levels above homeostasis in a randomised human trial pilot study. Redox Biology, 2017. 11: p. 631-636. --- Glutathione is exclusively made inside cells and is produced in two steps: The first makes gamma-glutamylcysteine (GGC) from the amino acids glutamate and cysteine, and the second adds a glycine to the gamma-glutamylcysteine (GGC) to make the GSH tripeptide. During aging and in many chronic illnesses, our cells lose the capacity to make enough gamma-glutamylcysteine (GGC), which means cells do not produce sufficient glutathione (GSH) to protect against oxidative stress . Supplementation with glutathione will not increase cellular glutathione (GSH) for one simple reason. In the tissues of your body there are two very different environments. One is the fluid inside your cells (intracellular, about 70% of the total fluids) and the other is the fluid outside your cells (extracellular, about 30% of total fluids). The intracellular environment, which is bound by your cellular membranes, is where most of the essential reactions such as protein synthesis and energy production occur. Many of these reactions generate free radicals that can, if not controlled (neutralized), cause damage inside your body (oxidative stress). To counter this, your cellular glutathione (GSH) levels must be maintained at an optimal concentration (homeostasis) and in a tightly controlled (regulated) manner. The extracellular environment, such as the plasma of your blood, allows the transportation of nutrients to the cells and removal of waste products which in turn are processed in the liver and kidneys. The glutathione (GSH) concentration found in this environment (micromolar) is much lower than that found intracellularly (millimolar) by about a thousand-fold. This large concentration... --- Glutathione (GSH) is the body’s powerful weapon in the fight against both acute and chronic inflammation. Researchers generally agree that chronic inflammation can progress slowly, even from a younger age, but is nevertheless the cause of most chronic diseases and threatens people’s ongoing health and longevity. Chronic inflammation fundamentally means a constant excess of free radicals or reactive oxygen species (ROS) inside the cells. While these ROS continue to exist inside cells, the damage continues resulting in chronic disease. Maintenance of healthy levels of antioxidants is essential to reduce the risk of being exposed to excess free radicals. By far, the most abundant antioxidant produced by cells is glutathione (GSH). Apart from the aging process and chronic disease, glutathione (GSH) also plays an important role in the health of the body’s immune system, resistance to cancer and infectious diseases as well as in sports recovery. --- There is a growing body of scientific and medical literature that suggests glutathione (GSH) may play a key role in immune health. The elderly, and those affected by chronic disease, especially the respiratory and immuno- compromised, seem to be most vulnerable to viral infections and complications. These people are well known to have lower than normal glutathione (GSH) levels leading to their cells and tissue is suffering from chronic oxidative stress . Until the availability of gamma-glutamylcysteine (GGC) there was no effective way to significantly increase cellular glutathione (GSH) within hours . Traditionally, supplements had to be taken daily for many months before even a slight increase in glutathione (GSH) could be seen. Therefore, it has been almost impossible to determine the effectiveness of glutathione (GSH) augmentation as an antiviral strategy. Studies with NAC and glutathione have only had limited success . Much evidence has accumulated over the past decade suggesting that patients infected with viruses such as influenza are under chronic oxidative stress . This is particularly concerning if you already have low glutathione (GSH). A viral infection could lower your glutathione (GSH) below a critical point where oxidative stress progressively leads to tissue damage and organ failure. There is also evidence to support that increasing your glutathione (GSH) may act as a prophylactic to viral infection. A study published in 2003 demonstrated that glutathione has anti-influenza properties. Many viruses, just like influenza, affect the oral, nasal, and upper airway and therefore lead to oxidative stress, or other conditions... --- Glutathione (GSH) plays an essential part in neutralizing reactive oxygen (ROS) species such as peroxide and superoxide ion. It is therefore, justifiably, referred to as the “Master Antioxidant”. Glutathione (GSH) also plays an important role in the detoxification of several other categories of potentially toxic compounds our bodies must deal with constantly. These include: Endogenous reactive metabolites such as products arising from oxidative metabolism of lipids, nucleic acids and catecholaminesXenobiotics which are not normally found in the body and can include naturally occurring compounds or they can be man made in origin such as drugs or environmental pollutantsHeavy metals such as mercury, lead, cadmium and arsenic The chemical reactivity of many of these compounds cause interference with the normal biological processes and hence they are toxic. If left unchecked, these toxins can result in tissue damage or even be carcinogenic. Glutathione’s (GSH’s) role is to deactivate these reactive species through the activity of an enzyme called glutathione-S-transferase . The “S” refers to the unique and highly reactive sulfur on the glutathione molecule which chemically combines with the toxin to form a glutathione conjugate. This resulting conjugate is generally much more water soluble and is easily removed through excretion in the urine or further metabolized in the liver to other less toxic compounds. The liver is the main detoxification organ and has evolved a complex biochemistry to counter most adverse conditions. Glutathione (GSH) is the secret weapon in this defense mechanism and therefore is in much higher concentrations in the liver... --- Exercise plays an important part in keeping us healthy. But it is not without its pitfalls. As exercise intensity increases, our rate of respiration also increases and, in turn, so does the production of free radicals or reactive oxygen species (ROS). This can lead to what is commonly referred to as oxidative stress which can damage our cells and tissues. Ordinarily, the glutathione produced in our cells is a very effective ROS scavenger, neutralizing free radicals, such as the highly toxic superoxide and hydrogen peroxide before they can cause havoc. But during high intensity or endurance exercise, our cells may not have the capacity to keep up with the demand for glutathione. This results in a glutathione deficit where our body is unable to neutralize all of the ROS produced. We have all experienced this situation: Lack of energy, fatigue, listlessness and that 'run down' feeling, which is a common symptom of glutathione depletion following exercise. Sport scientists have long advocated the use of antioxidants to combat exercise related oxidative stress . Glutathione (GSH), being the 'Master Antioxidant' is the obvious choice. Not only does it have a profound effect on neutralizing ROS, but it also recycles Vitamin C which is also another important player in the recovery phase. Many sports supplements, however, only address the issue of protein/energy deficit and electrolyte loss during the recovery period, but this is only part of the problem. Whilst protein and electrolytes are easily and rapidly replenished, until now, restoring our glutathione (GSH)... --- It's well known that our risk of developing chronic diseases increases as we age. The reasons behind this are incredibly complex, but one of the most widely accepted explanations is called the “free radical theory of aging” . First conceived in 1956, it is one of the most thoroughly researched theories known and, although not fully proven, is the best theory so far. It provides conclusive evidence that oxidative stress is intimately involved in aging. As our lifespan increases, we become more susceptible to chronic disease. Especially those brought on by oxidative stress, like neurodegenerative diseases which insidiously affect our brain and cognition. A compromised glutathione (GSH) system in the brain has a strong correlation with oxidative stress and has been shown to be implicated in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, Huntington’s disease and multiple sclerosis . It is now possible to determine the concentration of glutathione (GSH) in living human brains using magnetic resonance spectroscopy (MRS), with multiple MRS studies showing depleted brain glutathione (GSH) levels in all the major neurodegenerative diseases . Strategies to increase neuronal or brain glutathione (GSH) as a potential treatment have been proposed by many researchers. However, none of the therapeutic candidates have been successful so far , with the major impediment for most being a failure to cross the blood-brain barrier. As yet, there is no available evidence to suggest that orally administered gamma-glutamylcysteine (GGC) can reach the human brain, but there are several... --- The extensive surface area and blood supply in our lungs enables them to provide our bodies with sufficient oxygen for us to generate the energy we need to survive. But this makes our lungs particularly susceptible to injury due to the relatively high concentration of reactive oxygen species (ROS) which are produced by our normal metabolism. Beyond this, environmental toxins in the air we breathe, including ozone, nitrogen oxides (from smog), mineral dusts (e. g. silica and asbestos), cigarette smoke and car exhaust, may cause further injury . Our lungs have evolved a complex biochemistry to counter these adverse conditions and glutathione (GSH) is a key player in our defense mechanisms. However, as we age, or with the progression of chronic disease, cellular glutathione (GSH) levels can fall below optimal for maintaining good health . Many lung diseases are associated with glutathione (GSH) deficiency. These include acute respiratory distress syndrome (ARDS), asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, idiopathic pulmonary fibrosis, chronic bronchitis and various viral and bacterial infections . An exaggerated inflammatory response is also implicated during the development of many lung diseases and this is further exacerbated by depleted glutathione (GSH) levels. In the case of cystic fibrosis, a common treatment, nebulized n-acetylcysteine (NAC), helps loosen the mucus that forms in the lungs. This has led some researchers to test NAC in various animal models of inflammatory lung disease. Some have shown partial success, and this is most likely due to NAC’s limited ability to increase glutathione... --- A growing body of research has demonstrated that glutathione (GSH) is a key player in the immune system and the pathology of infection, inflammation and immune-mediated disease . The role of reactive oxygen species (ROS) that are generated during the inflammatory response mediated by lymphocytes and the resulting oxidative stress has been revealed in more detail . The antioxidant defense systems in the aged and those suffering from chronic degenerative disease especially those associated with inflammatory or autoimmune disease has been demonstrated to be weakened . As the first line antioxidant, the maintenance of a healthy homeostatic level of cellular glutathione (GSH) is critical in keeping the immune system running optimally. The major reason as to why maintaining a healthy cellular glutathione (GSH) level is so critical for the immune system is related to the fact that lymphocytes perform their bacterial, viral and cancer cell killing functions by generating large amounts of ROS including superoxide and hydrogen peroxide. These free radicals are highly toxic and an exquisite fine control of how much and where in the cell they are generated is needed. Any overproduction of these ROS can be neutralised by glutathione(GSH). However, the pace of oxidant generation can often outstrip the cellular production of glutathione (GSH) which leads to a cascade of oxidative stress, inflammation and tissue damage. References Droge, W. and R. Breitkreutz, Glutathione and immune function. Proceedings of the Nutrition Society, 2000. 59(4): p. 595-600. Perricone, C. , C. De Carolis, and R. Perricone, Glutathione: A key... --- The extensive surface area of our digestive system enables us to extract all of the essential nutrients from our diet. The intestinal tract, with its extensive blood supply, has a remarkable ability to renew the epithelial cell lining every 4-5 days . This rapid turnover of cells makes our digestive system particularly susceptible to injury due to the relatively high concentration of reactive oxygen species (ROS) which are produced by our normal metabolism. Beyond this, toxins in the food we eat can cause further injury. Nitrosamines from processed meat and other heavy metals such as mercury are just a few examples of toxins we may ingest . Our digestive system has evolved a complex biochemistry to counter these adverse conditions and glutathione (GSH) is of major importance in this defense mechanism. The mucosal lining of the intestinal tract is rich in glutathione (GSH) and it has been suggested that it plays a vital role in gut barrier function. Inflammation and the associated oxidative damage induced by acute bacterial or viral infections may also be prevented . However, as we age, or with the progression of chronic disease, glutathione (GSH) levels may be less than optimal for maintaining good health. Many gastrointestinal (GI) diseases have been associated with glutathione (GSH) deficiency. These include inflammatory bowel disease , ulcerative colitis Crohn's disease and Celiac disease . An exaggerated inflammatory response is also implicated during the development of many gastrointestinal diseases and this is further exacerbated by depleted glutathione (GSH) levels. Many GI... --- Cancer is an incredibly complex disease. Almost any type of cell in the body has the potential to become cancerous and modern medicine has made great strides in treating cancer. However, like with any disease, prevention is better than a cure. Mutation in a cell's DNA, usually in multiple locations, is the primary cause of cells becoming cancerous. Commonly known as carcinogens, or mutagens in technical terms, they include reactive oxygen species (ROS), certain chemicals and radiation. Examples include ionizing radiation such as UV light or X-rays, and chemicals such as alkylating agents (e. g. nitrosamines and benzene, which becomes alkylating following its oxidation in the liver to form hydroxyquinone). Many mutagens occur naturally, but more and more, industrial pollution and the rise of ultra-processed foods, allow an ever-increasing amount of them to enter our daily lives through the food chain or just the environment we live in. Glutathione (GSH) has been shown to be the most important ally in your cells' defence against mutagens. Maintaining an optimal level of glutathione (GSH) in your cells is therefore critical for the prevention of cancer . Mechanistic information has been published on how glutathione deactivates mutagens through the activity of various glutathione dependent enzymes such as glutathione S-transferase and glutathione peroxidase . The nature of how impaired glutamate cysteine ligase, the enzyme that naturally produces gamma-glutamylcysteine (GGC), can make cells more susceptible to mutagens due to lower glutathione (GSH) has been well studied. The use of antioxidants such as glutathione (GSH) during... --- The body's mechanism for dealing with oxidative stress becomes less efficient as we get older. This decline in function is associated with the impairment of the first enzyme (glutamate cysteine ligase or GCL). As is to be expected with any such complex system, the likelihood of errors is increased. A dysfunctional GCL will result in insufficient γ-glutamylcysteine (GGC) being produced for the glutathione synthase enzyme to convert into glutathione (GSH). The resulting suboptimal homeostasis of glutathione (GSH) results in a decreased capacity to minimize oxidative stress, which is associated with poor outcomes during aging, inflammation and in multiple disease states. --- Glutathione's (GSH’s) main role as an antioxidant is the use of its thiol (-SH) group as a nucleophilic scavenger and electron donor. However, glutathione (GSH) has several other vital maintenance functions, including: A cofactor in the function of several antioxidant enzymes including, glutathione peroxidases, which are responsible for the degradation of peroxides and glutathione transferases which are responsible for the detoxification of xenobiotics. Maintenance of ascorbate (Vitamin C) in its reduced state so it can remain an effective antioxidant/reducing agent. It does this through the activity of the glutathione-dependent enzyme dehydroascorbate reductase. An essential component in an NADPH pathway that prevents cellular components from being oxidized. This function is essential for the maintenance of protein thiols, and the creation of deoxyribonucleotide precursors for DNA synthesis, through the reduction of ribonucleotides. Protein glutathionylation mediated through thiol disulfide exchange reactions which are involved in cellular signaling, cell-cycle regulation, proliferation and apoptosis. --- Homeostasis refers to any process that living things use to actively maintain fairly stable conditions necessary for survival. Unlike your body temperature, which is stable throughout your life, the homeostatic level of glutathione (GSH) progressively decreases as we get older or in chronic disease. This means that your cells will gradually produce a lower amount of glutathione (GSH) simply because the base line or homeostatic level decreases. This results in your glutathione (GSH) levels falling below the level necessary to neutralize free radicals and combat chronic inflammation. --- Over many decades of extensive research, glutathione (GSH) has emerged as the crucial player in regulating inflammation . It does so very effectively by destroying ROS, or free radicals, produced by our immune system in response to threats. In turn, this protects us from the insidious and often destructive effects of oxidative stress. But how is oxidative stress related to the immune system? The core mediators of the immune system, the lymphocytes, perform their bacterial, viral and cancer cell killing function by generating large amounts of ROS, including superoxide and hydrogen peroxide. These species are highly toxic, not only to the invaders, but also our very bodies. They effectively destroy foreign intruders by inducing large amounts of oxidative stress, but, if not kept in check, they can easily turn onto their host. Consequently, precise control of ROS production and elimination is needed . This is the reason why maintaining a healthy glutathione level is so essential. Glutathione (GSH) will efficiently neutralize an overproduction of ROS. The pace of free radical generation, however, can often surpass the cellular production of glutathione (GSH), leading to a cascade of oxidative stress, chronic inflammation and tissue damage. Combined with advancing age, poor lifestyle choices or environmental stressors, all of which reduce glutathione even further, poor health outcomes are likely. Even a temporary drop in optimal glutathione levels, as has been observed after extensive exercise for instance, may cause harm due to oxidative stress. As the first line of defense against oxidative stress, antioxidants are... --- Our immune system is an incredible achievement of evolution without which we would succumb to even the slightest infection. It performs its tasks quietly in the background most of the time, and only when we develop a fever, for instance, are we aware of its presence. There are occasions, however, when our immune system becomes too aggressive and persistent, and our very health suffers as a consequence. We generally distinguish between two types of inflammation: acute and chronic. Acute inflammation happens when our immune system responds to injury or infection. It serves to protect us from bacteria and viruses that could cause havoc with our health if left unchecked. Its intricate workings are well beyond the scope of this article, but, from experience, we are aware of some of the methods in the immune system’s defense arsenal. Pain, swelling, redness and heat are classic symptoms of our immune system’s attempt to control the damage. It does so by moving more blood through the affected area, effectively increasing our own ability to fight off invading pathogens or irritants. It also serves as the first steppingstone in the healing process. However, most of the critical functions take place in the background. The release of reactive oxygen species, known as ROS or free radicals, regulates our immune responses. It serves not only to destroy pathogens but is also part of a complex signaling system that stimulates the immune system. This elaborate mechanism, however, can also work against us. It may lead to conditions... --- Gamma-glutamylcysteine (GGC) is a dipeptide and is the immediate precursor to the tripeptide glutathione (GSH). The intracellular concentration of gamma-glutamylcysteine (GGC) is generally low because gamma-glutamylcysteine (GGC) reacts rapidly with glycine to form glutathione (GSH). This second and final reaction step in glutathione biosynthesis is catalyzed by the activity of the ATP dependent glutathione synthase (GS) enzyme. Gamma-glutamylcysteine (GGC) is essential to mammalian life. Mice that have had the glutamate-cysteine ligase (GCL) gene knocked out do not develop beyond the embryo stage and die before birth . This is because gamma-glutamylcysteine (GGC) is vital for the biosynthesis of glutathione (GSH). Since the production of cellular gamma-glutamylcysteine (GGC) in humans slows down with age, as well as during the progression of many chronic diseases, it has been postulated that supplementation with gamma-glutamylcysteine (GGC) could offer health benefits. Other benefits of gamma-glutamylcysteine (GGC) supplementation may extend to situations where glutathione (GSH) has been acutely lowered below optimum such as following strenuous exercise, and during trauma or episodes of poisoning. Several review articles have been published regarding the therapeutic potential of gamma-glutamylcysteine (GGC) to replenish glutathione in age-related and chronic disease states such as Alzheimer’s disease . Gamma-glutamylcysteine (GGC) is also capable of being a powerful antioxidant in its own right . A human clinical study in healthy, non-fasting adults demonstrated that orally administered gamma-glutamylcysteine (GGC) can significantly increase lymphocyte glutathione (GSH) levels indicating systemic bioavailability, validating the therapeutic potential of gamma-glutamylcysteine (GGC) . Animal model studies with gamma-glutamylcysteine (GGC) have supported it’s... --- One of the impediments to knowing one’s glutathione (GSH) status is the lack of standardized analytical methods for determining glutathione (GSH) in blood, plasma, tissue and cellular material. Unlike most other biochemical blood markers (e. g. cholesterol or glucose) glutathione (GSH) analysis is not part of the regular battery of tests performed when a blood sample is taken. This is due mostly to the labile nature of glutathione (GSH) in biological systems. Glutathione (GSH) is considered a high turnover dynamic molecule where it can both be readily oxidized to its disulphide form GSSG or also broken down to its constituent amino acids by the action of endogenous enzymes. This means that samples require immediate chilling and treatment. Sample pre-treatment usually begins with the addition of an acid which not only lyses the cells but also brings about the precipitation of many contaminating proteins. The resulting acidic sample pH also prevents glutathione (GSH) autoxidation to glutathione disulfide (GSSG) and inhibits most of the enzymes involved in glutathione (GSH) catabolism and oxidation. The resulting treated samples are usually then centrifuged to remove solids and the supernatant stored frozen prior to analysis. There are many methods available in the scientific literature for the analysis of glutathione (GSH) but none, however, are particularly reliable or simple. This is reflected in the literature values of blood glutathione (GSH) analysis which often vary greatly between laboratories using what seem to be similar methods . Methods include HPLC, HPLC-MS/MS and capillary electrophoresis . One of the most... --- Glutathione (GSH) is synthesized in the cytoplasm in virtually all cells from its constituent amino acids by two sequential ATP-requiring enzyme catalyzed reactions (see figure below) . The first reaction is the formation of the dipeptide γ-glutamylcysteine (GGC) from the amino acids L-glutamic acid and L-cysteine. The second reaction adds a glycine to the Gamma-glutamylcysteine to produce the tripeptide glutathione. The first reaction is rate limiting and is catalyzed by the enzyme glutamate-cysteine ligase (GCL, EC 6. 3. 2. 2; formerly γ-glutamylcysteine synthetase). GCL is composed of a heavy catalytic subunit (GCLC, MW ~ 73,000) and a light modifier (GCLM, MW ~ 30,000) subunit. GCL is the key control point for the homeostasis of cellular GSH and is regulated at multiple levels. Its regulation at a genetic level (both transcriptional and translational) and at a biochemical level (post-translational) are incredibly complex. The light modifier subunit GCLM is enzymatically inactive but plays an important regulatory function by lowering the Km of GCLC for glutamate and raising the Ki for glutathione (GSH) . The resulting holoenzyme dimer comprising the two subunits is catalytically more efficient and less subject to inhibition by glutathione (GSH) than GCLC alone. In rats, GCLC has a Km for glutamate that is about 10-fold higher than that of the GCL holoenzyme, which is higher than the cellular glutamate concentration in most tissues GCL is specific for the glutamyl moiety and is regulated physiologically by: (a) non-allosteric feedback competitive inhibition by glutathione (GSH) (Ki = 2. 3 mM) which... --- Glutathione, often referred to as the “Master Antioxidant”, is the most biologically abundant antioxidant that protects almost all aerobic (air breathing) organisms from bacteria to humans. It is found mainly intracellularly (inside cells) where its concentration is in the same order as that other vital nutrient, glucose. There is no doubt that glutathione is of utmost importance for the human body. In fact, it plays a vital role in living organisms by protecting cells from oxidative damage caused by a myriad of internal and external stressors. The importance of glutathione is highlighted by the fact that all cells produce their own glutathione. It comes as no surprise that glutathione has been the subject of more than 80,000 papers published in peer-reviewed scientific journals all over the world during the last two decades. No other molecule, other than possibly water and oxygen, has been studied more extensively by research scientists. Maintaining cellular glutathione levels is essential to good health. Unfortunately, for most diseases and disorders and during aging itself, our bodies lose the capacity to produce glutathione at homeostatic levels that are high enough to fight off the ravages of oxidative stress. --- Glutathione (GSH) is often termed the “master antioxidant”. This tripeptide is ubiquitous in nature and is produced by every organism from bacteria, to plants to animals that derives energy from oxidative phosphorylation and respiration. Glutathione is synthesized in the cytosol of each cell by the action of two enzymes in an elegantly regulated system that allows it to be maintained at different homeostatic levels in different tissue types, with the liver, given its detoxification role, having the highest amounts. Glutathione plays a pivotal role in most key physiological functions including but not limited to maintenance of cellular redox, neutralising free radicals, cell cycle regulation, proliferation, apoptosis, xenobiotic metabolism, and the recycling of other cellular antioxidants such as Vitamins C and E. Glutathione depletion and a corresponding increase in reactive oxygen species (ROS) during microbial infection is a key driver of the immune response and inflammation. Most chronic diseases are related to oxidative stress arising from the affected tissue losing the capacity to maintain glutathione at adequate healthy levels. The severity of many poisonings from drugs, alcohol, heavy metals and environmental toxins are related to an acute depletion of cellular glutathione. Progressive depletion of cellular glutathione is also used as a mechanism by many viruses to control their replication cycle during infection. --- ---