basierend auf
Bewertungen
What exactly is glutathione?
- Glutathione is a tripeptide made up of the 3 amino acids glutamic acid, cysteine and glycine
- It occurs in 2 states, which are converted into one another:
- Reduced glutathione (GSH)
- Oxidized glutathione disulfide (GSSG) (2 H+ removed)
- In terms of food law, it is a “functional food protein” (no amino acid, therefore no restrictions on use)
- Glutathione can be synthesized and recycled by humans, but different building blocks are essential
-
Prerequisite for glutathione synthesis and recycling
- Amino acids (L-glutamate, L-cysteine, L-glycine as well as precursors methionine and possibly. N-acetylcysteine) à high dependence on cysteine availability!
- Enzymes (Ɣ-glutamyl transpeptidase, peptidase, Ɣ-glutamyl cyclotransferase, Ɣ-glutamyl cysteine synthetase, GSH synthetase) à high dependence on activity of Ɣ-glutamyl cysteine synthetase
- Cofactors that support synthesis and recycling (α-lipoic acid, vitamin C, vitamin E, vitamin B2, vitamin B3, magnesium)
- Energy and functional mitochondria (incl. Cofactors such as coenzyme Q10, L-carnitine, vitamins B1, B2 and B3) à GSH synthesis is ATP-dependent
Bioavailability of oral glutathione
- The digestive tract absorbs GSH and other nutritionally useful peptides intact (e.g. Casomorphins, proteases)
- Active transport through intestinal membranes or Intestinal epithelial cells detected (with partial degradation to amino acids intracellularly)
- Probably also absorption as Glu-Cys dipeptide and resynthesis of the tripeptide (in the liver)
- GSH intake improves the GSH status more than corresponding amounts of the individual amino acids
- GSH takes on functions in the intestine as well as in the organism extracellularly and in various cell compartments
- Healthy intestinal mucosa important for absorption of di-/tripeptides
- Reasons why some authors were unable to detect an increase in GSH in plasma after oral GSH administration:
- Short GSH half-life
- With low GSH concentration and poor redox status, no GSH increase
(high GSH consumption for regeneration of other redox systems, such as Ascorbic acid)
Effects of glutathione
Antioxidant effects
-
Non-enzymatic antioxidant
- most important hydrophilic antioxidant of the cell (directly binds radicals and nitric oxide (NO) and reduces other antioxidants)
- is oxidized to GSSG (and reduced again with the help of the enzyme glutathione reductase)
-
Coenzyme for enzymatic glutathione peroxidases (metalloenzymes)
- reduce toxic peroxides such as hydrogen peroxide and lipid hydroperoxides by reacting with glutathione)
- Enzymes are proteins (require amino acids, zinc, vitamins B6 and B12)
- Enzymes require activators (selenium, zinc, manganese)
- reduce toxic peroxides such as hydrogen peroxide and lipid hydroperoxides by reacting with glutathione)
Regeneration of antioxidants
Inactivation of activated oxygen
Detoxifying effects of GSH
-
Glutathione in detoxification phase I
- Disposal of radical metabolites (part of the redox network)
-
Glutathione in detoxification phases II and III
- Coenzyme for glutathione S-transferases
-
Binding partner of pollutants
- catches via thiol/sulfhydryl/SH group toxins, polyvalent heavy metals such as mercury, cadmium, lead and other foreign substances
- forms pollutant glutathione complexes, which are excreted as mercapturic acid derivatives via the kidneys and bile
- reduced by complex formation with “good” trace elements pro-oxidative risk of high concentrations of these substances (e.g.b Fenton reaction of iron with vitamin C)
- Note: GSH is compatible with other chelating agents such as α-lipoic acid can be combined.
Glutathione and detoxification phase II
Causes of glutathione deficiency and possible consequences
-
Causes
- Low intake (e.g.b Nutrition, absorption disorders)
- High demand (e.g.b Radical exposure, pollution, illness, lifestyle errors, age, stress, sport)
- Disorders of glutathione synthesis and metabolism (e.g.b Deficiency of amino acids, glutathione reductase or glutathione peroxidase)
-
Consequences
- Oxidative and nitrosative (NO) stress
- Lack of energy
- Deficit of thiol groups (-SH)
- Detoxification disorders
- Immunosuppression and susceptibility to infections
- Reperfusion damage, increased hemolysis rates
- neurological, psychomotor, cardiovascular, ocular and hepatic disorders
Glutathione diagnostics
- Diet and lifestyle history
- Special symptoms
- Laboratory examination
- Total glutathione (erythrocytes): 1805-3600 μmol/l
- GSH reduced (leukocytes or erythrocytes): 962-3329 μmol/l
- GSH:GSSG ratio (serum): 99:1 to 90:10 (no information about the intracellular situation)
- Glutathione peroxidase: 4170-10880 U/l
- In the case of stress/illnesses, initially shift the quotient GSH / GSSG
- Long-term decrease in total glutathione
Glutathione requirement
- The exact glutathione requirement in addition to diet and self-synthesis is not exactly known and depends on many factors (intake, synthesis, individual situation)
- In the case of stress/illnesses, the quotient GSH / GSSG is initially shifted
- Long-term decrease in total glutathione
- Disturbances only become apparent when the GSH inventory is < 1 g (thus there is already a lack of approx. 7 g on “normal stock”)
- In addition, continued high GSH requirements due to continued stress
Typical glutathione dosage
|
Substance |
Dosage orally (per day) |
Dosage parenteral (per day) |
|
Glutathione prevention (if there are risks) |
0.2 – 1 g |
- |
|
Glutathione therapy initial |
1-5g |
400-600 mg |
|
Glutathione follow-up care (after therapy) |
0.6-1.2g |
- |
-
Oral bioavailability is assured!
(e.g.b Richie JP et al.; Randomized controlled trial of oral glutathione supplementation on
body stores of glutathione; European Journal of Nutrition 2014)
Glutathione content of foods (Source: Reuss F)
|
Food |
GSH mg/kg |
|
Brewer's yeast extract (fresh) |
10000 (Reiff, 1960) |