Glutathione (GSH) is an organic compound that has been playing a very important role in nutritional supplements and so-called ‘superfoods’ for some time and is becoming a fundamental part of building a healthy lifestyle. The peculiarity of GSH is its high antioxidant potential.
Glutathione acts on reactive (oxidative) compounds in cells, which include:
- Reactive oxygen species (ROS, free radicals).
- lipid peroxides.
- Heavy metals.
GSH reduces these compounds, so biology and medicine consider that it has a dominant role in cell protection.
In the absence of glutathione in the cells, oxidative stress increases, with all the negative effects on cellular and organism health.
Glutathione is not only used as an antioxidant
The use of glutathione is also popular in the areas of:
- Increase fertility.
- Improve nervous health.
What is glutathione?
The organic compound known as glutathione is a so-called tripeptide, an oligopeptide, which consists of three amino acids:
- Glutamic acid (α-aminoglutaric acid)
- Cysteine (L-cysteine)
Because of the binding between individual amino acids, GSH is also called an atypical tripeptide.
Unlike many vitamins that the body cannot produce, glutathione is one of the nonessential nutritional supplements.
How can the level of glutathione be increased?
The tripeptide is synthesized with the help of enzymes so that the increase in glutathione level is possible in two ways.
On the one hand, the organic compound can be delivered directly to the body and on the other hand, it can be assumed that a higher supply of the amino acids leads to increased synthesis and, therefore, to a higher level of GSH.
What foods contain amino acids?
The concentrations of individual amino acids in different foods vary, so it’s important to keep a balanced diet.
For example, sunflower seeds, chicken eggs or whole-wheat flour contain higher concentrations of cysteine.
Glutamic acid is present in large quantities in cow’s milk or whole wheat flour and tomato puree.
All animal foods contain glycine.
It can also be found in plant foods, although there are fewer than contain it, among them are spinach, legumes, soy, cucumber or cabbage.
What benefits does glutathione have?
1. Glutathione improves type 2 diabetes
Type 2 diabetes leads to a detectable reduction in the concentration of GSH. The result is an increase in oxidative stress factors, which ultimately leads to greater tissue damage.
A study published by A Peer-Reviewed, consider that the cause of the decrease in GSH levels in patients is a lower synthesis rate since glutathione precursors are lacking.
The supply of precursors (amino acids) from the outside has proven to be a means to restart tripeptide synthesis.
Appropriate evidence arises from studies not only for diseases such as diabetes but also in the context of increased oxidative stress in elderly people.
2. A low glutathione synthesis can contribute to autism
A study conducted in the United States has shown that the activity of some enzymes involved in the synthesis of GSH is reduced in autistic diseases.
The activity of glutamate-cysteine ligase in the autistic subjects examined was almost two fifths below the activity in the control group.
Reduced enzyme activity was also demonstrated for glutathione reductase.
Imbalances in the availability of GSH between the autistic group and the control group are also mentioned in other publications, which show a relationship between GSH and the oxidized variant (GSSG) of up to 60 percent.
3. It can improve psoriasis
A study indicated that protein, when administered orally, improved psoriasis no matter whether there was or there was no additional treatment.
It had previously been shown that protein is good for increasing glutathione levels.
Although the researchers stated that more study is needed in this field.
4. Reduces cell damage in alcoholic and non-alcoholic fatty liver
Cellular death in the liver can be exacerbated by a deficiency of antioxidants, including glutathione.
This can lead to fatty liver disease, either for those who abuse alcohol or those who do not.
GSH has been shown to improve the levels of proteins, enzymes, and bilirubin in the blood of people with chronic, alcoholic and non-alcoholic liver disease.
A study found that glutathione is most effective when given intravenously and in high doses to people with fatty liver disease.
Participants in the study also showed reductions in malondialdehyde, a marker of cellular damage in the liver.
5. Glutathione protects blood vessels
A scientific team from the Medical Center of Ohio State University has shown that glutathione protects the blood vessels from cellular damage caused by reactive oxygen species (RSO).
Cellular damage increased significantly after treatment with buthionine sulfoximine ( a sulfoximine investigated as an adjunct with chemotherapy in the treatment of cancer), which the researchers attribute to the reduced availability of GSH in its cell structure.
Due to the fact that glutathione is the thiol (with low molecular weight) predominantly of the organism, changes are observed in the availability of GSH in relation to many diseases, such as:
- Tumor diseases
- Liver disease.
6. Glutathione counteracts cell aging
The glutathione tripeptide is associated with particularly extensive potential in relation to its antioxidant effect.
In the context of this property, medicine and biology address the question of how the compound plays a role in the aging of cells and organisms.
Free radicals / reactive oxygen species (ROS) are considered responsible for tissue damage or typical signs of aging. The main cause is oxidative stress induced by ROS.
According to several investigations, the intake of GSH or its precursors can counteract the aging process.
7. Increase the mobility of people with peripheral arterial disease.
Peripheral artery disease occurs when peripheral arteries become blocked by plaque. It usually occurs in the legs.
One study found that glutathione improves circulation, increasing the ability of study participants to walk painlessly for longer distances.
Participants who received GSH instead of a placebo saline solution received intravenous infusions twice a day for five days, and then were analyzed for mobility.
8. Reduces the symptoms of Parkinson’s disease
Parkinson’s disease affects the central nervous system and is defined by symptoms such as tremors, and currently, it has no cure.
One study documented the positive effects of intravenous glutathione on symptoms such as tremor and stiffness.
While more research is needed, this case report suggests that GSH can help reduce symptoms, improving the quality of life in people with this disease.
9. GSH deficiency favors rheumatoid arthritis
For elderly people, infectious diseases and autoimmune diseases become more common.
Some researchers suggest that this development is associated with a decrease in GSH levels in erythrocytes and serum.
As a possible consequence, the researchers explain the higher incidence of rheumatoid arthritis and forms of lupus erythematosus.
Animal studies show that the decrease in GSH is accompanied by a decrease in the activity of the synthesis enzyme with increasing age.
In mice, this effect was observed from the ninth month of life. By month 18, enzyme activity decreased by up to 56%.
10. Glutathione protects the beta cells of the pancreas
Type 2 diabetes is a disease that challenges modern health systems.
The development of the disease is influenced by the ability of beta cells (β cells) to deliver insulin in sufficient quantities.
Medicine is responsible for the reduction of insulin production due to the oxidative stress caused by ROS (which is associated with an increase in glucose levels).
An improvement in the availability of GSH leads, according to the results of several studies, to a positive effect on the protection of beta cells from oxidative damage and improves insulin sensitivity.
The cytoprotective effect of glutathione on the pancreas can also be observed in the consequences of the development of a GSH deficiency.
A research team in Poland has shown that patients with varying degrees of pancreatitis increase the level of oxidative lipid degeneration, reduce GSH levels and alter the activity of glutathione synthesis enzymes.
11. Glutathione relieves inflammation
Asthma, fibrosis or acute respiratory distress syndromes are often associated with inflammatory processes in the lung tissue.
Especially chronic forms of the disease are often associated with an imbalance of pro and anti-inflammatory factors.
Glutathione plays an important role here as the main antioxidant protection of cells.
Some consider that glutamate-cysteine ligase is a limiting factor in its synthesis, which may be influenced by inflammatory modulation factors.
The current research topic is the question of how glutathione can be activated and used as a therapeutic agent in the treatment of chronic inflammation of the lung tissue.
12. GSH protects against tumors of the gastrointestinal tract
Biology and medicine have identified GSH and glutathione synthesis enzymes, as an important cell-internal defense mechanism against reactive oxygen species.
A group study from Poland has shown significant differences between GSH levels before surgery and after surgery according to studies in patients with gastrointestinal tumors.
Parallel to the changes in glutathione concentration, an increase in lipid peroxidation (oxidative lipid degeneration) was observed.
13. GSH reduces the level of oxidative stress
For a long time, biology and medicine have suggested that stress is a cofactor for the development of several clinical conditions.
Researchers from India conducted experiments on animals, which were induced stress by immobilization.
After six hours, a reduction in glutathione was detected and at the same time, the concentration of degenerated fatty acids increased.
14. Protects nerve cells
Nerve cells mainly have the function of transmitting stimuli to the brain.
On the one hand, the stimulus may occur from the outside, for example, in relation to pain (such as burns), but the stimulation also works in the other direction.
If the nerve tissue cells are damaged, this has consequences. It is known that oxidative stress plays a role in the development of many degenerative diseases.
15. GSH derivatives protect cells against Amyotrophic Lateral Sclerosis (ALS)
Scientists have historically focused their research on glutathione because its antioxidant activity builds cellular protection against oxidative stress factors.
However, research shows that the synthesis and reduction of glutathione disulfide (GSSG) can be altered by several factors.
Recent work indicates an effect of GSH derivatives that elude these limiting factors and protect cells.
DNA binding protein is associated with the genesis of the ALS variants, which can be reconstructed.
16. Glutathione deficiency makes you susceptible to neurological damage
Neurological damage, which can subsequently lead to diseases such as Alzheimer’s or dementia, has been linked to oxidative stress for several years.
This is caused by a deficiency of GSH or alterations in the GSH: GSSG relationship.
Different studies in patients suggest a link between low levels of GSH and higher levels of degenerated protein (amyloidosis).
A reduced proportion of reduced and oxidized glutathione has led researchers to make DNA more susceptible to oxidative stress and its effects.
17. Glutathione protects against heavy metals
Heavy metal absorption is repeatedly associated with the development of various diseases, such as cancer. In addition, these metals are often considered toxic.
A representative is a chromium, to which carcinogenic properties are attributed.
In animal experiments, scientists have investigated how chromium affects oxidative stress and DNA damage, among others.
Part of the research studied how glutathione modulates and is able to effectively protect against chromium. It was shown that glutathione helps reduce the effect of heavy metals on the body.
Is the efficacy of glutathione enhanced by vitamins?
US researchers were able to demonstrate in a monocyte model that vitamin D intake leads to increased activity of glutamate-cysteine ligase and glutathione reductase, which results in increased synthesis of glutathione.
At the same time, vitamin D intake had a positive effect on ROS concentration and interleukin secretion.
The effect of increased enzyme activity cannot be observed only in relation to a vitamin D intake.
A positive effect can be tested for all vitamins, although the best support effect was achieved with vitamin E.
Possible consequences and symptoms of a lack of glutathione
Glutathione is an organic compound that the body produces naturally and is used in the context of cell defense, due to its antioxidant properties.
If this is not the case, sooner or later this condition becomes noticeable, especially since glutathione is a cysteine deposit for the body.
A glutathione deficiency may be the result of the lack of protein building blocks (amino acids), a reduced synthesis or a too-high conversion of GSH.
The latter has been observed by the researchers in relation to type I diabetes, unlike the case of type II diabetes, mere supplementation as a therapeutic complement is quite difficult.
The deficiency of glutathione can lead to different diseases
GSH deficiency or changes in enzyme activity are described in different publications and for various diseases, such as the fatty liver and liver cirrhosis.
The processes that lead to a decrease in glutathione concentration in clinical practice are partially confusing and are the subject of current research. However, previous work suggests that there is a direct relationship with the level of GSH for some clinical conditions.
How is glutathione formed?
A true peptide bond in organic chemistry develops between the COOH group (α-carboxy group) of one amino acid and the NH 2 group (amino group) of the second amino acid.
In glutathione, the link between glutamic acid and cysteine is produced through the γ-carboxy group.
This bond is produced by glutamate-cysteine ligase as the first step in glutathione biosynthesis.
The division of ATP (adenosine triphosphate) into ADP (adenosine diphosphate) produces γ-glutamylcysteine, which in turn is synthesized by another enzymatic process in glutathione.
What effects does glutathione have?
As for the effects and mechanisms behind the functions of glutathione, biochemistry and medicine have progressed significantly in recent years.
The chemical structure is responsible for the different modes of action of glutathione. For example, the thiol group of glutathione is responsible for reducing the properties.
In this context, glutathione acts as an electron donor, that is, it provides electrons, and therefore changes to the oxidized form. The reaction produces GSSG (glutathione disulfide).
The resulting disulfide bridge connects 2 glutathione to a dimer. Enzymatically, by glutathione disulfide reductase, the junction can be broken and glutathione disulfide (GSSG) can be reduced to glutathione.
This cycle is essential to maintain a beneficial environment within the cells.
What foods contain glutathione?
Possible suppliers include tomatoes, avocado or zucchini, and spinach.
As part of a balanced diet, it should generally not be necessary to administer additional glutathione from outside. However, several factors can influence glutathione levels.
A starting point is the synthesis of the compound in the organism/cells.
If the enzymes necessary for biosynthesis fail, glutathione is available in the long term in an insufficient quantity.
Deficiency symptoms are also conceivable in situations in which the GSH system is affected by the GSSG.
If there is no reduction in the oxidized form of glutathione, the cells lack the compound. This reaction is also enzymatically controlled by glutathione disulfide reductase (GR).
Quercetin and galangina
Quercetin and galangina are two examples of flavonoids that act in both directions in GSH.
Low doses of phytochemicals lead to an increase in the total concentration of GSH. At higher doses, plant substances inhibited reductase in leukemia cell lines.
Absorption and dosage of glutathione
Glutathione is marketed as a dietary supplement and ‘superfood’.
With regard to synthesis, scientists and doctors do not consider the tendency towards supplementation to be critical since glutathione can form in the body or cells.
The supply of additional glutathione from the outside is actually only necessary if a present defect is diagnosed.
Studies show that ingested GSH quickly converts to GSSG and accumulates in red blood cells or the liver.
Of considerable importance for the availability of glutathione are transport systems, with which glutathione exceeds the intestinal wall and enters the body’s own material cycle.
Researchers studying the influence of individual glutathione components have shown in several studies that an increase in their concentration also influences glutathione levels. Therefore, supplementation with L-cysteine has positive effects on the concentration of GSH.
This form of indirect supplementation is relevant to several clinical conditions.
The thiol group (-SH)
The body can produce the amino acid cysteine, however, for synthesis, two basic components are required: serine and methionine.
The amino acid serine provides the basic framework for the synthesis of cysteine in the synthesis process, while methionine contributes to the thiol group (-SH).
The formation of the amino acid for GSH takes place in the liver.
Because methionine (one of the two sulfur-containing amino acids), unlike cysteine, cannot be synthesized by humans, it requires an external supply.
A too low concentration of methionine, for example, due to deficiency and malnutrition, also influences glutathione formation through cysteine synthesis.
Therefore, the causative agents of a GSH deficiency are several triggers in which supplementation can be used.