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Glutathione - its role as an antioxidant and in the body's detoxification

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)


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


Dosage orally (per day)

Dosage parenteral (per day)

Glutathione prevention (if there are risks)

0.2 – 1 g


Glutathione therapy initial


400-600 mg

Glutathione follow-up care (after therapy)



  • 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)


GSH mg/kg

Brewer's yeast extract (fresh)
Liver (fresh from the slaughter)
Liver (commercial product)
Beef muscle meat (fresh from the slaughter)
Asparagus (raw)
Ham ( Commercial goods)
Beef muscle meat (commercial goods)
Cauliflower (raw)
Potatoes (raw)

10000 (Reiff, 1960)
7370-10000 (Abuja, 2006)
310 (Bloem, 2003)
280 (Bloem, 2003)
280 (Bloem, 2003)



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