Generality
Glutathione or GSH is a natural tripeptide, which is a substance consisting of three amino acids, in the order glutamic acid, cysteine and glycine. This particular chemical composition gives glutathione a high capacity to oxidize or reduce, protecting proteins and other oxidizable compounds from the deleterious action of free radicals.
Many of these enzymes - whose activity is linked to the presence of selenium - catalyze the neutralization of hydrogen peroxide (a powerful free radical) and of other peroxides.
Reduced glutathione (2 G-SH) + Oss. (H 2 O 2 ) → Oxidized glutathione (GSSG) + 2 H 2 O
2 G-SH + ROOH → GSSG + ROH + H 2 O
As can be seen from the reactions reported above, reduced glutathione very willingly yields its hydrogen (H +), which acts as an acceptor of an electron (e-) coming from reactive oxygen molecules (free radicals).
At this point, having eliminated the danger of peroxide, oxidized glutathione, to regain its antioxidant activity, must return to its reduced form; this happens thanks to a NADPH-dependent enzyme, called glutathione reductase.
According to many scholars, this ability to regenerate continuously has contributed to considering glutathione as the most powerful antioxidant in the human body.
In healthy cells the ratio between reduced glutathione and oxidized glutathione is maintained around 9: 1; a decrease is considered an index of oxidative stress.
Chemical Structure of Glutathione (left) and Acetyl Cysteine (right).
Below, the chemical structure of the amino acids that lead to the synthesis of glutathione: in order (from left to right) glutamic acid, cysteine and glycine
In order for glutathione to carry out such actions, it is essential that it be supported by adequate amounts of selenium - a mineral that is abundant in foods of marine origin and offal - of riboflavin (Vit. B2) and niacin (Vit. PP).
Glutathione and Liver Health
Present in the body in a ubiquitous form, glutathione is particularly concentrated in the liver, where it protects hepatocytes from particularly toxic molecules of exogenous or endogenous origin (generated during the metabolism of some xenobiotics, such as certain drugs, for example paracetamol). In this case, glutathione, once conjugated to toxic metabolites in an enzymatic or non-enzymatic manner, cannot regenerate as easily (in part it is eliminated, mainly via the bile, and in part it undergoes further metabolizations).
An excessive concentration of toxic substances in the liver can therefore impoverish the tissue levels of glutathione, causing serious damage to the liver. Not surprisingly, in the clinic, reduced glutathione is administered intravenously as a direct and "fast" antidote to paracetamol poisoning.
Indications
Why is glutathione used? What is it for?
Glutathione is one of the main protagonists of the cellular antioxidant response.
Concentrated in the cytoplasmic environment, thanks to its particular chemical structure, glutathione intervenes in maintaining the correct state of intracellular oxidation-reduction, acting as a scavanger molecule against oxygen free radicals.
In addition to marked antioxidant activity, glutathione is also attributed to detoxifying, immunomodulating and cytoprotective activities.
For these reasons, from preliminary studies, integration with glutathione would seem useful in the event of:
- Diabetes and metabolic pathologies;
- Atherosclerosis;
- Respiratory disorders;
- Hearing loss;
- Male infertility;
- Heavy metal poisoning;
- AIDS.
From the commercial point of view, in virtue of the great importance attributed to free radicals in the appearance of various degenerative pathologies, glutathione supplements are painted as a sort of elixir of eternal youth, useful for delaying aging, to reinforce the immune defenses, to preserve the integrity of red blood cells and the lens of the eye, and to protect the body from ionizing radiation, heavy metals, alcohol, tobacco, drugs and neurodegenerative diseases such as Alzheimer's disease.
Property and Effectiveness
What benefits has glutathione shown during the studies?
The different biological functions of glutathione would seem to support its clinical utility.
From several clinical studies, and from numerous experimental studies, the administration of glutathione would seem useful in:
- Protect the liver from the transforming action of potential toxic substances;
- Protect the liver, kidneys and nervous system from the side effects of chemotherapy;
- Reduce the evolution of atherosclerosis by modulating platelet aggregation processes;
- Improve the clinical characteristics during oxidative pulmonary diseases;
- Improve insulin profile and activity in diabetes patients;
- Improve sperm motility and vitality in patients with fertility disorders.
limits of glutathione supplementation
Despite the encouraging clinical evidence, there are now several doubts, especially of a pharmacokinetic nature, relating to the real usefulness of glutathione supplementation.
All this could be traced back to the presence, in the intestine, of enzymes known as gamma glutamyl transferases, which would hydrolyse glutathione taken orally, drastically reducing its bioavailability.
To further compromise the bioavailability of this nutrient would contribute a marked first-pass metabolism and cellular sequestration exerted by enterocytes of the intestinal mucosa.
For these reasons, integration with glutathione precursors such as N-Acetyl-Cysteine would seem more effective.
The N-acetylcysteine, in addition to being proposed as an antioxidant and reinvigorating action supplement, is part of the composition of mucolytic drugs, which, taken by inhalation or oral treatment, facilitate the elimination of mucus from the airways. It is also administered intravenously in the treatment of acute paracetamol intoxication.
Doses and method of use
How to use glutathione
Glutathione is commercially available as a single ingredient or combined with other molecules with antioxidant activity.
Generally, the suggested glutathione dosage is included between 50 and 600 mg per day, depending on the patient's needs.
In order to enhance the antioxidant activity of glutathione, one could resort to the simultaneous use of other bioactive molecules such as selenium, B vitamins, vitamin A, C or E.
The suggested dosages for adequate supplementation with N-Acetylcysteine, replacing the direct one with glutathione, are generally 200-600 mg for 1-3 times a day.
Side effects
The use of glutathione, within the suggested dosages, is generally well tolerated and has no clinically relevant side effects.
The appearance of gastrointestinal adverse reactions has been observed very rarely.
Contraindications
When should glutathione not be used?
The use of glutathione is contraindicated in case of hypersensitivity to the active ingredient.
Pharmacological Interactions
Which drugs or foods can change the effect of glutathione?
Not known drug interactions are currently known.
However, the administration of glutathione could improve the tolerability of Cisplatin therapy, reducing its side effects.
Precautions for use
What do you need to know before taking glutathione?
The use of glutathione during pregnancy and in the subsequent period of breastfeeding should be carried out, if strictly necessary, only under strict medical supervision.
