Glutathion & Biotransformation

This page contains educational material about glutathione used as a biotransformation product in the body. This information is for educational purposes only. Nothing in this text is intended to serve as medical advice. All medical decisions should be made only with the guidance of your own personal medical authority. I am doing my best to get this data up quickly and correctly. If you find errors in this data, please let me know.

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Glutathione: The Special amino acid complex that so much depends on!

This section will explain what glutathione is and how to support it in the body. If you want to learn about glutathione conjugation, go to this link.

Glutathione (γ-glutamyl-cysteinyl-glycine) is a tripeptide found in all cells where it is the major intracellular antioxidant. It is synthesized particularly in the liver and red blood cells. It is the most abundant thiol (sulfhydryl) containing substance in the body. It is an amazing friend to us all. It is there to protect us from inflammatory responses. With glutathione around it keeps all inflammation down through its super hero antioxidant abilities. When it is depleted inflammation can take over our body. Glutathione is found in nearly every compartment of our cells, including the nucleus. Glutathione is the main antioxidant for mitochondria, the little power-house factories inside each cell that convert nutrients into energy. Without our mitochondria we would have no energy.

Glutathione as an Antioxidant and Redox Potential

Glutathione exists in two forms. The oxidized form called glutathione disulfide (GSSG) and the reduced form called glutathione (GSH). Only GSH has the antioxidant activity. GSH is used by the body to neutralize reactive oxygen species which leads to the formation of GSSG from GSH. The GSH uses the enzyme glutathione peroxidase to reduce free radicals. Glutathione is oxidized to GSSG in this process. GSSG can be recycled to GSH. This recycling back to GSH needs the enzyme glutathione reductase to facilitate the reduction of GSSG to GSH. It requires NADPH and forms two GSH molecules from the one GSSG molecule.

You may have heard about reduced glutathione(GSH) and oxidized glutathione(GSSG). The ratio of GSH to GSSG controls the "redox potential" in the cells. It is the reduced glutathione that is guarding our body. GSH is a part of our antioxidant system and protects us from "free radicals". Free radicals are molecules that are unstable because they have unpaired electrons and are looking for another electron to steal in order to become stable They steal electrons from the mitochondria, thereby damaging the mitochondria, causing inflammation and degeneration.

Here is another way to examine this process: GSH will sacrifice themselves by giving an electron to a free radical. This happens with the help of an enzyme called glutathione peroxidase. This turns the glutathione (GSH) into glutathione disulfide (GSSG). The GSSG is now a free radical itself, but it can be turned back into its reduced state via an enzyme called glutathione reductase (GSR) using NADPH as an electron donor. This reinstates it back into its old GSH self again. Redox status (measure of reduced glutathione to oxidized glutathione) within the cells is reflected by the ratio of reduced GSH to oxidized GSSG (GSH/GSSG).This is used as a measure of cell toxicity. In healthy cells, more than 90% of the total glutathione pool is in the reduced form (GSH) and less than 10% in the disulfide form (GSSG).

You can see that these enzymes are a really important part of the process of glutathione's super hero abilities. We need enough glutathione and we also need glutathione peroxidase and glutathione reductase for this system to work effectively and for us to stay healthy. Without this recycling process going smoothly we are in deep doo doo.

De Novo synthesis of Glutathione:

New GSH can be made from scratch. This is called de novo synthesis. To make glutathione we need L-glutamine, L-cysteine, and glycine. L-glutatmate and L-cysteine are added together with the help of the rate limiting enzyme Glutamate-cysteine ligase (AKA γ-glutamylcysteine synthetase or glutamylcysteine ligase) and is dependant on ATP. You get L-γ-Glutamyl-L cysteine. This is the rate limiting step of making glutathione and the rate limiting amino acid is cysteine. Next, glycine is added to the the newly created L-γ-Glutamyl-L-cysteine with the enzymatic help of glutathione synthase and powered by ATP. This produces reduced glutathione (GSH).

Glutathione can be recycled back to its constitutive amino acids by γ-glutamyl-n-transferase and dipeptidase.

A primary phase II transformation route is conjugation with glutathione. Reduced glutathione, in conjugation with glutathione reductase, glutathione peroxidase, and glutathione-S-transferase are involved in conjugation. Through direct conjugation, it detoxifies many xenobiotics (foreign compounds) and carcinogens, both organic and inorganic. The elimination of heavy metals such as mercury, lead, and arsenic is dependent upon adequate levels of glutathione, which in turn is dependent upon adequate levels of methionine and cysteine. When increased levels of toxic compounds are present, more methionine is utilized for cysteine and glutathione synthesis. Glutathione conjugation is probably the most important detoxification pathway for industrial toxins and carcinogens and 60% of toxins excreted in the bile are excreted in this way. Glutathione conjugation also produces water-soluble mercaptates which are excreted via the kidneys.

It is synthesized in the body but toxins, poor diet and pollution as well as stress, aging, trauma, infections and radiation all deplete glutathione levels. The sulfhydryl group (SH) of cysteine serves as a proton donor and is responsible for the biological activity of glutathione. Cysteine is the rate-limiting factor in cellular glutathione synthesis, since this amino acid is relatively rare in foodstuffs. Normally glutathione is recycled in the body, except when the toxic load becomes too great. 33%-50% of people are missing normal GSTM1 (a gene) function. This gene is necessary to make enough glutathione.

Since glutathione is the master detoxifier in our body, a deficiency creates a serious lack of anitoxidant status and promotes liver dysfunction as well as liver damage. Exposure to high levels of toxins depletes glutathione faster than it can be produced or absorbed from the diet. This results in increased susceptibility to toxin-induced diseases, such as cancer, especially if phase I detoxification system is highly active. Disease states due to glutathione deficiency are not uncommon. Health conditions like mold susceptibility (CFIDS), Parkinson's and Alzheimer's have been linked to glutathione deficiency. Autoimmune diseases are linked to low glutathione levels. Glutathione is needed to protect us from damage due to cigarette smoke, radiation exposure, and alcohol to name a few environmental toxins it protects us from.

Glutathione is necessary for both phase 1 and phase 2 of our detoxification pathways. There is evidence that glutathione may be necessary to keep some types of toxic metabolites from being created from mycotoxins. The aflatoxin AFB1 can be metabolized by the Cytochrome P450 system to AFB1-8,9-epoxide (AFBO) which can become quite hazardous or can be excreted via the urine with the use of glutathione. Glutathione S-transferase is needed to conjugate AFBO and excrete it in the urine. If AFBO is not conjugated and excreted it can cause toxicity including cancer.(Brammler and others 2000)

Transforming Growth Factor - Beta (TGF-Beta)
It has been shown that decreased levels of GSH will stimulate production of TGF-β and that when GSH is replenished, the production of TGF-β will be decreased

Gene Control of Glutathione by Nrf2
Glutathione biosynthesis, glutathione peroxidases, glutathione S-transferases and glutathione S-conjugate efflux pumps function in a coordinated fashion to facilitate a coordinated response to oxidative stress. Regulation of this response is facilitated by the antioxidant responsive element (ARE) which is located in the promoters of many of the genes that are induced by oxidative and chemical stress.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor that is release when there is an increase in oxidative stress. It translocates to the nucleus where it binds and activates ARE and upregulates several genes associated with glutathione synthesis. Nrf2 is found in most types of cells. Nrf2 induces the rate-limiting enzyme for (GSH) synthesis, γ-glutamyl-cysteine synthetase, as well as glutathione synthase needed to make glutathione from scratch.

Even if Nrf2 is upregulated, research has shown that Nrf2 may be damaged after its production by excess oxidative stress. Without functioning Nrf2 the genes which make γ-glutamyl-cysteine synthetase, as well as glutathione synthase can not be formed and new GSH is not made.

If the genes needed to produce glutathione are not functioning, supplying the building block of glutathione production, N-acetyl-cysteine (NAC) is much less efficient than supplying the whole molecule of glutathione using a liposomal encapsulation of glutathione or other absorbable form.

Nrf2 also controls the formation of the glutathione s-transferases (GSTs). These are necessary for glutathione conjugation which is a Phase II biotransformational process that detoxifies toxins.

What Specifically is Glutathione Involved With?

It is the major endogenous antioxidant produced by the cells, participating directly in the neutralization of free radicals and reactive oxygen compounds, as well as maintaining exogenous antioxidants such as vitamins C and E in their reduced (active) forms.

The organs that are highest in glutathione levels are the eye, the ears, the lung, the liver, the kidneys, and the skin. These organs have the highest concentrations of glutathione, for good reason, because these organs are subject to all of the toxins in the environment.

It regulates the nitric oxide cycle, which is critical for life but can be problematic if unregulated.

Regarding muscles, research has shown that raising glutathione levels decrease muscle damage, reduce recovery time, increase strength and endurance and shift metabolism from fat production to muscle development.

It is a necessary to support the immune system in its job of fighting infections and preventing cancer. e.g., (1) modulating antigen presentation to lymphocytes, thereby influencing cytokine production and type of response (cellular or humoral) that develops, (2) enhancing proliferation of lymphocytes, thereby increasing magnitude of response, (3) enhancing killing activity of cytotoxic T cells and NK cells, and (4) regulating apoptosis, thereby maintaining control of the immune response. Low glutathione is seen in autoimmune disease. GSH depletion in antigen presenting cells inhibits Th1-associated cytokine production and/or favors Th-2-associated responses. Multiple chemical sensitivities seen are associated with decreased Th-1, increased Th-2 response.

It is involved in numerous metabolic and biochemical reactions such as DNA synthesis and repair, protein synthesis, prostaglandin synthesis, amino acid transport, and enzyme activation. Every system in the body can be affected by the state of the glutathione system, especially the immune system, the nervous system, the gastrointestinal system and the lungs.

A deficiency can be induced either by diseases that increase the need for glutathione, deficiencies of the nutrients needed for synthesis or for synthesis of glutathione reductase or glutathione peroxidase, or diseases that inhibit its formation.

Cellular consequences of decreased glutathione antioxidant potential are:
Reduced ability to detoxify environmental toxins and heavy metals, resulting in neurotoxicity
Oxidation of cysteine thiol (SH) groups in proteins, resulting in altered function of proteins
Decreased liver GSH synthesis, resulting in reduced glutathione conjugation in the liver
Degeneration of the lining of the intestinal tract, resulting increased gut permeability and autoimmunity
Increased Th2, altered thymic T cell subsets, resulting in autoimmune issues
Reduced S-adenosylmethionine synthesis and increased SAH accumulation, resulting inhibition of methyltransferase and reduced ability to methylate and excrete toxins from the body.

Glutathione is also the most critical and integral part of your detoxification system. Many toxins are conjugated in the liver by glutathione, which then carries them into the bile and the stool and hopefully out of your body unless they get picked back up into the body via the enterohepatic circulation. (This is where a bile sequestrant such as cholestyramine comes in.)

When we are overwhelmed with too many toxins or excessive oxidative stress, glutathione becomes depleted and we can't get rid of toxins. Soon we are in the downward spiral of chronic illness.

Interesting Factoids
Low levels of glutathione peroxidase are seen in vitiligo (H. Zedan, 2015), relapsing-remitting multiple sclerosis (k. Socha, 2014), and type 2 diabetes (O. Sedighi, 2014) and thought to be a contributing factor in these diseases.

Glutathione peroxidase genetic polymorphisms may also be associated with development of celiac disease. (M. Katar, 2014)

The hepatotoxic effects of acetaminophen, a drug responsible for considerable drug-induced liver injury are brought on with xcessive doses of this common analgesic/antipyretic drug. This causes rapidly depleted intracellular GSH reserves.


How to Optimize Glutathione Levels


Glutathione is available through two routes: diet and synthesis. Dietary glutathione (found in fresh fruits and vegetables, cooked fish, and meat) is absorbed well by the intestines and does not appear to be affected by the digestive processes. Dietary glutathione in foods appears to be efficiently absorbed into the blood. However, the same does not appear to be true for glutathione supplements usually. There are more recently glutathione supplements that appear to be helping clinically.

Fresh fruits and vegetables will raise levels of glutathione, but cooked foods contained far less.

Sulfur-rich foods: onions, garlic, all cruciferous vegetables such a broccoli, collards, cabbage, kale, cauliflower, kohlrabi, watercress, etc.

Whey from making cheese or whey products: The whey protein needs to be bioactive and made from non-denatured proteins ("denaturing" refers to the breakdown of the normal protein structure). Use non-pasteurized, organic produced milk.

Other foods known to support glutathione production: Asparagus, avocado, raw eggs, turmeric, spinach, unprocessed meats and walnuts.


Exercise will enhance glutathione levels.

Relaxation Techniques

Relaxation Techniques will also enhance glutathione levels. According to a study by Mahagita, meditation diminishes oxidative stress and therefore raises glutathione. The same results are seen in this yoga study. These studies are about meditation and yoga, however, I believe any technique such as controlled breathing, prayer, and biofeedback can reduce oxidative stress and increase glutathione.

Relaxation Techniques will change gene expression and enhance glutathione levels. This includes mediation, prayer, yoga and biofeedback. Research by Herbert Benson showed that genes that triggered inflammation and cell death were turned off in the research group that regularly practiced relaxation techniques. However, this deactivation did not appear to be permanent. The daily practice of relaxation techniques was necessary to sustain benefits.

When the control group was taught techniques to evoke the relaxation response, about 1,500 genes changed their expression within 8 weeks. These were many of the same genes seen in the group that have been practicing these relaxation techniques for years.



Clinicians have found in the past that most glutathione supplements have not been useful. However, I am using acetyl-Glutathione by Allergy Research that does appear to be clinically useful. Acetyl-Glutathione is a form of oral glutathione that is stable in the stomach and gastrointestinal tract, and well absorbed.

Liposomal glutathione is a form that people use with success also.

A research article studying the increase of glutathione in the body after consumption came up with the following data:

A 2015 published 6 month randomized, placebo-controlled trail with oral glutathione (250 or 1,000 mg/day) in healthy adults showed an increase of glutathione in blood after 1,3 and 6 months vs control. At 6 months there was a 30-35% increase in red blood cell levels,plasma and white blood cells. There was a 260% increase in buccal cell level in the high dose group and in the low dose group an increase of 17-29% in blood and red blood cells respectively. The results were time and dose dependent. They returned to baseline after a 1 month period of abstinance from glutatione. A reduced oxidative stress level was shown in both groups by the decrease in oxidized to reduced glutathione ratio in whole blood after 6 months. There was a two-fold increase in natural killer cell activity vs. the controls at 3 months.

Nebulized (inhaled) glutathione is also used but should only be used under the care of a trained practitioner. Bronchoconstriction has occured among patients who are thought to be sulfite-sensitive. Inhalation of GSH results in a mechanism of action that is thought to be confined to the upper airways and lungs and will not influence plasma levels to a significant degree. This is what most research has shown. However, there are people who claim to get cognitive effects from taking inhaled glutathione, so I am not sure research has the full picture yet. At least we do know GSH inhalation exerts its effects upon the lower respiratory tract and the upper respiratory tract. It may exert other yet unknown effects.

Research shows inhaled GSH is potentially indicated for the following clinical conditions: cystic fibrosis, chronic otitis media with effusion, HIV seropositive individuals, idiopathic pulmonary fibrosis and chronic rhinitis. These are just the conditions with good research. Of course inhalation of glutathione could be useful in many more conditions. Asthma is a condition where inhaled GSH cannot be recommended since this treatment caused notable side effects (e.g. breathlessness, bronchoconstriction and cough) in one study. These side effects were linked primarily to the production of sulfites that occurred when GSH was in solution. Anyone who has a sulfite sensitivity should not use nebulized/inhaled gluathione. More data on nebulilzed glutathione can be found in this research article.

Enhancing our production of glutathione is another way to go and what I have mostly done in the past due to poor clinical efficacy of glutathione products. Here are some methods used to increase glutathione.

Methylation nutrients: Active folate (a large segment of people need active folate-L-5-methyltetrahydrofolate), vitamins B6(as Pyridoxal 5'-phosphate sodium) and B12(in the active form of methylcobalamin), and Betain Anhydrous (trimethylglycine). These are very critical to keep the body producing glutathione. Methylation and the production and recycling of glutathione are some of the most important biochemical functions in your body. I use a product called Methyl-Guard Plus by Thorne.

Interruption of the remethylation of the methionine cycle leads to decreased production of glutathione. The decreased availability of methylcobalamin is part of this defect and injections of methylcobalamin (b12) have been shown to restore the methionine cycle in situations where there is a deficiency of methylcobalamin. In a twist of biochemical irony, glutathione appears to be needed to maintain the production of methylcobalamin and the function of the methionine cycle.

Need following cofactors/substrates to metabolize glutathione: methionine, cysteine, glycine, Selenium, B1, B2, B6 Vit C Vit E, zinc, magnesium, vitamin D

Magnesium - Much of our United States populace is deficient in magnesium. Glutathione requires magnesium for synthesis.

Selenium - Glutathione peroxidase is necessary for glutathione to act as an antioxidant. Glutathione peroxidase is a seleium-dependent enzyme. Selenium deficiency is common in malabsorption and gastrointestinal disease. Some people live in areas were there is no selenium in the soil and other people live in areas where the soil contains toxic levels of selenium.

Zinc - the rate limiting enzyme γ-glutamylcysteine synthetase that is necessary to make glutathione, depends on zinc for its activity.

Riboflavin (B2) - Glutathione reductase is necessary to change glutathione disulfide (Oixdized glutathione) back into the reduced state. Glutathione reductase is a riboflavin -dependent enzyme.

Amino Acids: Cysteine,Glutamine and Glycine are all necessary to make glutathione. The rate limiting aminio acid is usually cysteien. However, there are conditions which could deplete one of the other amino acids. For instance a stressful surgery has been shown to deplete glutatmine.

NADPH - Necessary for recycling of glultathione from glutathione disulfide to glutathione.

Vit C and E help the body recycle glutathione

In healthy individuals, a daily dosage of 500 mg of vitamin C may be sufficient to elevate and maintain good tissue glutathione levels. In one double-blind study, the average red blood cell glutathione concentration rose nearly 50% with 500 mg/day of vitamin C. Increasing the dosage to 2,000 mg only raised red blood cell (RBC) glutathione levels by another 5%. Vitamin C raises glutathione by increasing its rate of synthesis.

Milk thistle: 1 Tablespoon BID Milk thistle contains a mixture of several related polyphenolic compounds called silymarin. Silymarin is an antioxidant which lowers the liver's oxidative stress associated with toxin metabolism, particularly lipid peroxidation, which has the effect of conserving cellular glutathione levels. Like NAC, silymarin can protect against acetaminophen toxicity (possibly by the similar mechanism of preserving glutathione levels). Silymarin, however, may be a more effective antidote than NAC for acetaminophen toxicity if the treatment is delayed (in an animal model, it was effective when administered up to 24 hours after overdose).

Turmeric - Curcuma longa

Cordyseps sinensis Research shows it increases the powerful antioxidant glutathione peroxidase. Glutathione peroxidase helps the productivity of glutathione and vice versa.

alpha lipoic acid - time released (I use alamax CR  600 mg alpha lipoic acid and Biotin 450 mcg per capsule) Start with one cap BID and increase to 2 cap BID taken on an empty stomach.
Side effects: little data, but skin rash possible. It will chelate heavy metals, so if you have a heavy metal issue, you might notice some detox activity from it. The most common is nausea.

Whey – Needs to be non-pasteurized and organic. Want precursors from whey as follows:
Serum albumin, alfa lactoalbumin, lactoferin, beta lactoglobulin
These globular proteins are high in cysteine and cysteine residues and can be manufactured into glutathione easily.


N-acetylcysteine: Contains sulfur amino acids including a dimer of cysteine. N-acetyl cysteine is a precursor to cysteine, and thus can be used for glutathione production. It is a free radical scavenger on its own, effective at reducing oxidative stress, particularly due to heavy metal toxicity. Because it can directly replenish glutathione stores, NAC is more effective than methionine or SAMe at preventing liver damage, and is the current treatment for acetaminophen toxicity. It is an effective treatment for acute liver failure due to non-acetaminophen drug toxicity as well. It is readily absorbed and boosts glutathione levels. It readily crosses the cell membrane and increases intracellular gluthatione levels. This has been used for years to help treat asthma and lung disease and to treat people with life-threatening liver failure from Tylenol overdose. It is given to prevent kidney damage from dyes used during x-ray studies. It can be toxic at doses over 1.5 grams and some people do not do well with this supplement.

Methionine: Cysteine is generated from methionine catabolism via the transsulfuration pathway, so dietary methionine can replace cysteine to support glutathione synthesis. Check out the methylation and transulfuration pathways to understand how cysteine is made from this precursor.

SAMe - AKA S-adenosylmethionine: Cysteine is generated from S-Adenosyl Methionine, so SAMe can replace cysteine to support glutathione synthesis. Methionine is turned into SAMe with the help of the enzyme methionine adenosyl-transferase. It is simply one step closer to making glutathione than methionine is. Check out the methylation and transulfuration pathways to understand how cysteine is made from these precursors.

Active vitamin D - 1,25-dihydroxyvitamin D3 has been shown to increase glutathione levels in the brain and may be a catalyst for glutathione production.

Vitamin B 6 - cystathionine B-synthase (CBS) and cystathionine lyase are both B6 dependent enzymes that are involved in transulfuration of homocysteine on its pathway to make glutathione.

Nrf2 - Nrf2 induces the rate-limiting enzyme for (GSH) synthesis, γ-glutamyl-cysteine synthetase, thereby elevating tissue GSH levels. So upregulation of Nrf2 is upregulation of de novo glutathione sythesis.

Things that use up glutathione or down-regulate it

Environmental Toxins: smoking, mercury

Smoking increases the rate of utilization of glutathione, both in the detoxification of nicotine and in the neutralization of free radicals produced by the toxins in the smoke.

Mercury has a high affinity for thiol (sulfhydryl (-SH)) groups. Glutathione (GSH), provides the major intracellular defense against mercury-induced neurotoxicity. High levels of mercury will use up glutathione.

Health Conditions: protein malnutrition, herpes, Cancer, HIV/AIDS, Type 2 diabetes, hepatitis, Parkinson's disease are all associated with lower levels of glutathione.

Acetaminophen (tylenol) toxicity depletes glutathione: Acetaminophen is conjugated wtih gluguronate(80%) and sulfate (10%). The remaining acetaminophen is oxidized by CYP450 to the toxic metabolite, N-acetyl-p-benzoquinone imine. This undergoes glutathione conjugation. However, in an overdose, the glucuronidation and sulfation pathways become saturated and acetaminophen is metabolized into more N-acetyl-p-benzoquinone imine than the glutathione (GSH) can keep up with. The GSH is depelted. This leads to cellular toxicity and liver necrosis.

The rate limiting enzyme for making gluatathione, γ-glutamylcysteine synthetase is down-regulated by Transforming Growth Factor - beta and by prolonged oxidant exposure in in vitro studies.


Oxidant stress, nitrosative stress, inflammatory cytokines, cancer, cancer chemotherapy, ionizing radiation, heat shock, inhibition of GCS activity, GSH depletion, GSH conjugation, prostaglandin A2, heavy metals, antioxidants, and insulin increase GCS transcription or activity in a variety of cells (2,8). In contrast, dietary protein deficiency, dexamethasone, erythropoietin, tumor growth factor β, hyperglycemia, and GCS phosphorylation decrease GCS transcription or activity. Nuclear factor κB mediates the upregulation of GCS expression in response to oxidant stress, inflammatory cytokines, and buthionine sulfoximine-induced GSH depletion (2,8). S-nitrosation of GCS protein by NO donors (e.g., S-nitroso-L-cysteine and S-nitroso-L-cysteinylglycine) reduces enzyme activity (8), suggesting a link between NO (a metabolite of L-arginine) and GSH metabolism. Indeed, an increase in NO production by inducible NO synthase causes GCS inhibition and GSH depletion in cytokine-activated macrophages and neurons (12). In this regard, glucosamine, taurine, n-3 PUFAs, phytoestrogens, polyphenols, carotenoids, and zinc, which inhibit the expression of inducible NO synthase and NO production (13), may prevent or attenuate GSH depletion in cells. Conversely, high-fat diet, saturated long-chain fatty acids, low-density lipoproteins, linoleic acid, and iron, which enhance the expression of inducible NO synthase and NO production (13), may exacerbate the loss of GSH from cells.

The Immune System and Glutathione

The central role of glutathione in a variety of cell functions related to immune defense has been demonstrated in previous studies.

A decrease in glutathione in antigen-presenting cells correlates with increased Th2 response.

Decreased glutathione found in macrophage cells from children with chronic asthma has been shown to be related to decreased bacterial phagocytosis.

Children with chronic asthma, had decreased glutathione related to post-translational modification of Nrf2.

Decreased glutathione and decreased macrophage defense against intracellular infection with Mycobacterium tuberculosis occurs in the macrophages of individuals with HIV. The decrease in glutathione in the macrophage of HIV+ individuals was shown to be due to a decrease in the gene expression of the enzymes of glutathione production .

Restoration of glutathione levels in the mycotoxin exposed mouse dendritic cells using NAC or glutathione ethyl ester restored IL-12 secretion and prevented the mycotoxin-induced increase of airway inflammation and airway hyperreactivity.

Restoration of glutathione using NAC in the macrophages of children with asthma restored phagocytosis in the ex vivo model.


An increase in urinary excretion of 5-oxoproline, an intermediate of the γ-glutamyl cycle, is a useful indicator of reduced availability of cysteine and/or glycine for GSH synthesis in vivo


It appears that mycotoxins can decrease the formation of glutathione due to decreased gene expression of the enzymes needed to form glutathione. In humans this chronic depletion of glutathione has been shown to lead to chronic health conditions, including chronic asthma. A decrease in glutathione due to mycotoxin-related depletion may contribute to the range of conditions associated with mycotoxin accumulation. Since the mycotoxins destory the action of the enzymes necessary for glutathione production, glutathione may need to be supplemented rather than supplementing the rate limiting amino acid as n-acetyl-cysteine. Glutathione has been beneficially used in animal research of aflatoxin-related hepatocellular carcinoma. Anecdotal reports from clinicians and individuals with CIRS due to water-damaged buildings, suggest that studies using liposomal glutathione in the management of mycotoxin-related conditions may be warranted. Acetyl-glutathione is being used with good results also now. Nebulized glutathione is also used but should only be used under the care of a trained practitioner. Bronchoconstriction has occured among patients who are thought to be sulfite-sensitive.

Glutathione depletion in antigen presenting cells inhibits Th1-associated cytokine production and/or favors Th-2-associated responses. Multiple chemical sensitivities in individuals are thought to be associated with decreased Th-1, increased Th-2 response. Mycotoxins (as well as other toxins) can deplete the body of glutathione and could add to the problems with an improper antigen presenting cells activity that has already be theorized to be an issue for people with sensitive HLA-DR haplotypes.

Research is proving that oxidative stress is a significant factor in the pathophysiology of mycotoxin-related illness. Oxidative stress appears to be directly related to suppression of glutamate-cysteine ligase catalytic subunit (GCLC), gene function, post-translational modification of Nrf2 or the presence of excess tranforming growth factor-beta (TGF-β). This suggests that the lack of glutathione may be due to the inability of mycotoxin-affected cells to adequately form glutathione.

The demonstration that the oxidative stress associated with mycotoxins can be related to direct suppression of enzymes for glutathione synthesis, post-translational modification of Nrf2 or the presence of excess TGF-β suggests that the lack of glutathione may be due to the inability of mycotoxin-affected cells to adequately form glutathione. Decreased function of the enzymes of glutathione production results in a microenvironment depleted of glutathione on a chronic basis. In humans, deficiency of glutathione can lead to chronic conditions. Mycotoxin-related depletion of glutathione may contribute to the range of conditions associated with mycotoxin accumulation. The lack of function of the enzymes of glutathione production in these conditions suggests that more efficient resolution of the effects of glutathione depletion may require the administration of the complete glutathione molecule. These observations echo an early report regarding the benefit of glutathione in the management of aflatoxin-related hepatocellular carcinoma in an animal model, which proposed that administration of the intact glutathione molecule was needed for benefit of the use of glutathione.

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