Glutathione the mother of antioxidants, but how helpful can it really be as a supplement?

Introduction to Glutathione


Glutathione the mother of antioxidants, but how helpful can it really be as a supplement?

Formula: C10H17N3O6S

Also known as: 
Gamma-Glutamylcysteinylglycine, Gamma-L-Glutamyl-L-Cysteinylglycine, Gamma-L-Glutamyl-L-Cystéinylglycine, Glutathion, Glutatión, L-Gamma-Glutamyl-L-Cysteinyl-Glycine, L-Gamma-Glutamyl-L-Cystéinyl-Glycine, L-Glutathion, L-Glutathione

“Reports of how antioxidants protect us against cancer, heart disease, and nearly eighty other diseases appear regularly in the media. Vitamin C is the major antioxidant in the blood; vitamin E is the vital antioxidant in cell membranes and lipoproteins. However, in the cell interior – where the real toxin war is being waged – the most important antioxidant is glutathione.” Alan H. Pressman, D.C., Ph.D., C.C.N.

Glutathione is a substance produced naturally in our body and by the liver. It can be found in fruits, vegetables, and meats, plants, animals, fungi, and some bacteria and archaea. Glutathione (γ-L-Glutamyl-L-cysteinylglycine) is an amino acid containing molecule (peptide) comprised of one molecule of L-glutamic acid, L-cysteine, and Glycine each. Although oral glutathione supplementation does not efficiently increase glutathione inside cells   for the two following reasons, it can be absorbed into the blood stream. 

Glutathione the mother of antioxidants, but how helpful can it really be as a supplement?

Supplementation of glutathione is thought to support this pool of glutathione in a cell and thus maintain the efficacy of the entire glutathione system. It currently has a limited role in nutritional supplementation due to the following pharmacokinetic properties:

  1. There may be some absorption of glutathione, but it cannot enter cells intact. It must be metabolized to form L-cystine before being taken up.
  2. Provision of L-cysteine within the cell is all that is needed to increase glutathione synthesis, and N-Acetylcysteine does this efficiently cheaper in cost.

In effect, glutathione is an indirect and expensive way to provide dietary L-cysteine. Dietary protein itself, including L-cysteine rich sources such as Whey Protein, are effective but inefficient ways to increase L-cysteine intake in the diet and N-Acetylcysteine is both more efficient and cheaper than glutathione.

Little more about the N-Acetylcysteine

N-acetyl cysteine is also used for preventing alcoholic liver damage also for chest pain (unstable angina), bile duct blockage in infants, amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease), Alzheimer’s disease. Nitroglycerin and Activated charcoal interacts with N-ACETYL CYSTEINE.

Glutathione is Known for

It is usually known for Treating or preventing alcoholism, asthma, cancer, heart disease (atherosclerosis and high cholesterol), hepatitis, liver disease, diseases that weaken the body’s defense system (including AIDS and chronic fatigue syndrome), memory loss, Alzheimer’s disease, osteoarthritis, and Parkinson’s disease. But as mentioned above the effects of Glutathione in oral intake is not as expected. It just does not work that way. 

Yes it is strong and the mother of all antioxidants, Yes it can be found in liver and improves liver conditions but, and this is important. But it does not work orally. as mentioned for two main reasons if you try to get it directly by food or supplement you should not really expect much antioxidant effects out of it. Again the main reason for that is that There may be some absorption of glutathione in blood stream, but it cannot enter cells intact. It must be metabolized to form L-cystine before being taken up. So maybe it is not a good idea to eat it Glutathione to get it. 

But how should we get Glutathione?

Glutathione the mother of antioxidants, but how helpful can it really be as a supplement?

As a matter of fact glutathione is an indirect and expensive way to provide dietary L-cysteine which is the main reason we want to get Glutathione into our system. Dietary protein itself, including L-cysteine rich sources such as Whey Protein, are effective but inefficient ways to increase L-cysteine intake in the diet but N-Acetylcysteine is both more efficient and cheaper than glutathione. 

So if you want to increase Glutathione in your body try geting some N-Acetylcysteine, not glutathione. N-acetyl cysteine or NAC is the best source of cysteine we know. NAC is readily absorbed by the body to yield cysteine, which in turn, is used to manufacture glutathione. Next to NAC, you should check if your glutathione supplement has Vit. CVitamin C is a potent antioxidant in itself. Vitamin C is not manufactured by the body. So, we must take it in our diet and through oral supplementation. 

Why must Vitamin C be taken with NAC?

Vitamin C helps recycle glutathione once it has been used up by the body in quenching free radicals and toxins. The quenching of free radicals or the reduction-oxidation (redox) processes always occur in the body. Therefore, glutathione is constantly used up by the body. In the presence of Vitamin C, oxidized glutathione is recycled and converted to its reduced state once again.

And also try these:

1. Try bioactive whey protein.
2. Exercise boosts your glutathione levels
3. N-acetyl-cysteine.
4. Selenium. This important mineral helps the body recycle and produce more glutathione.
5. Milk thistle

Get it Glutathione for

Online website sources and some useful articles to read on Glutathione:

Online website sources and some useful articles to read on Glutathione:

Online website sources and some useful articles to read on Glutathione:

seful articles to read on Glutathione:

Wu G1, et al Glutathione metabolism and its implications for health . J Nutr. (2004)

Filomeni G1, Rotilio G, Ciriolo MR Cell signalling and the glutathione redox system . Biochem Pharmacol. (2002)

Dickinson DA1, Forman HJ Cellular glutathione and thiols metabolism . Biochem Pharmacol. (2002)

Flagg EW1, et al Dietary glutathione intake in humans and the relationship between intake and plasma total glutathione level . Nutr Cancer. (1994)

Griffith OW1, Mulcahy RT The enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase . Adv Enzymol Relat Areas Mol Biol. (1999)

Reliene R1, Schiestl RH Glutathione depletion by buthionine sulfoximine induces DNA deletions in mice . Carcinogenesis. (2006)

Das GC1, et al Enhanced gamma-glutamylcysteine synthetase activity decreases drug-induced oxidative stress levels and cytotoxicity . Mol Carcinog. (2006)

Beutler E, Gelbart T, Pegelow C Erythrocyte glutathione synthetase deficiency leads not only to glutathione but also to glutathione-S-transferase deficiency . J Clin Invest. (1986)

Richman PG, Meister A Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione . J Biol Chem. (1975)

Huang CS1, Moore WR, Meister A On the active site thiol of gamma-glutamylcysteine synthetase: relationships to catalysis, inhibition, and regulation . Proc Natl Acad Sci U S A. (1988)

Gipp JJ1, Chang C, Mulcahy RT Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase . Biochem Biophys Res Commun. (1992)

Anderson ME Glutathione: an overview of biosynthesis and modulation . Chem Biol Interact. (1998)

Mutoh N1, et al Cloning and sequencing of the gene encoding the large subunit of glutathione synthetase of Schizosaccharomyces pombe . Biochem Biophys Res Commun. (1991)

Yamaguchi H1, et al Three-dimensional structure of the glutathione synthetase from Escherichia coli B at 2.0 A resolution . J Mol Biol. (1993)

Gali RR1, Board PG Sequencing and expression of a cDNA for human glutathione synthetase . Biochem J. (1995)

Gali RR1, Board PG Identification of an essential cysteine residue in human glutathione synthase . Biochem J. (1997)

Griffith OW, Meister A Differential inhibition of glutamine and gamma-glutamylcysteine synthetases by alpha-alkyl analogs of methionine sulfoximine that induce convulsions . J Biol Chem. (1978)

Meister A Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy . Pharmacol Ther. (1991)

Owen JB, Butterfield DA Measurement of oxidized/reduced glutathione ratio . Methods Mol Biol. (2010)

Chung PM1, Cappel RE, Gilbert HF Inhibition of glutathione disulfide reductase by glutathione . Arch Biochem Biophys. (1991)

Hayes JD1, Flanagan JU, Jowsey IR Glutathione transferases . Annu Rev Pharmacol Toxicol. (2005)

Eichholzer M1, et al Effects of selenium status, dietary glucosinolate intake and serum glutathione S-transferase α activity on the risk of benign prostatic hyperplasia . BJU Int. (2012)

Huenchuguala S1, et al Glutathione transferase mu 2 protects glioblastoma cells against aminochrome toxicity by preventing autophagy and lysosome dysfunction . Autophagy. (2014)

Lee WH1, Joshi P, Wen R Glutathione S-Transferase Pi Isoform (GSTP1) Expression in Murine Retina Increases with Developmental Maturity . Adv Exp Med Biol. (2014)

Landi S Mammalian class theta GST and differential susceptibility to carcinogens: a review . Mutat Res. (2000)

Board PG1, et al Zeta, a novel class of glutathione transferases in a range of species from plants to humans . Biochem J. (1997)

Hayes JD1, Strange RC Glutathione S-transferase polymorphisms and their biological consequences . Pharmacology. (2000)

Pemble SE1, Wardle AF, Taylor JB Glutathione S-transferase class Kappa: characterization by the cloning of rat mitochondrial GST and identification of a human homologue . Biochem J. (1996)

Robinson A1, et al Modelling and bioinformatics studies of the human Kappa-class glutathione transferase predict a novel third glutathione transferase family with similarity to prokaryotic 2-hydroxychromene-2-carboxylate isomerases . Biochem J. (2004)

Jakobsson PJ1, et al Common structural features of MAPEG — a widespread superfamily of membrane associated proteins with highly divergent functions in eicosanoid and glutathione metabolism . Protein Sci. (1999)

Brigelius-Flohé R1, Maiorino M Glutathione peroxidases . Biochim Biophys Acta. (2013)
Brigelius-Flohé R Glutathione peroxidases and redox-regulated transcription factors . Biol Chem. (2006)

Klatt P1, Lamas S Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress . Eur J Biochem. (2000)

Hill BG1, Bhatnagar A Role of glutathiolation in preservation, restoration and regulation of protein function . IUBMB Life. (2007)

Irihimovitch V1, Shapira M Glutathione redox potential modulated by reactive oxygen species regulates translation of Rubisco large subunit in the chloroplast . J Biol Chem. (2000)

Lockwood TD Redox control of protein degradation . Antioxid Redox Signal. (2000)

Hagen TM1, et al Fate of dietary glutathione: disposition in the gastrointestinal tract . Am J Physiol. (1990)

Garvey TQ 3rd, Hyman PE, Isselbacher KJ gamma-glutamyl transpeptidase of rat intestine: localization and possible role in amino acid transport . Gastroenterology. (1976)

Fukagawa NK1, Ajami AM, Young VR Plasma methionine and cysteine kinetics in response to an intravenous glutathione infusion in adult humans . Am J Physiol. (1996)

Iantomasi T1, et al Glutathione transport system in human small intestine epithelial cells . Biochim Biophys Acta. (1997)

Hagen TM1, et al Bioavailability of dietary glutathione: effect on plasma concentration . Am J Physiol. (1990)

Aw TY1, Wierzbicka G, Jones DP Oral glutathione increases tissue glutathione in vivo . Chem Biol Interact. (1991)

Witschi A1, et al The systemic availability of oral glutathione . Eur J Clin Pharmacol. (1992)

Aebi S1, Assereto R, Lauterburg BH High-dose intravenous glutathione in man. Pharmacokinetics and effects on cyst(e)ine in plasma and urine . Eur J Clin Invest. (1991)

Allen J1, Bradley RD Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers . J Altern Complement Med. (2011)

Richie JP Jr1, et al Randomized controlled trial of oral glutathione supplementation on body stores of glutathione . Eur J Nutr. (2014)

Thompson GA, Meister A Hydrolysis and transfer reactions catalyzed by gamma-glutamyl transpeptidase; evidence for separate substrate sites and for high affinity of L-cystine . Biochem Biophys Res Commun. (1976)

Orlowski M, Meister A The gamma-glutamyl cycle: a possible transport system for amino acids . Proc Natl Acad Sci U S A. (1970)

Kern JK1, et al A clinical trial of glutathione supplementation in autism spectrum disorders . Med Sci Monit. (2011)

Sze G1, et al Bidirectional membrane transport of intact glutathione in Hep G2 cells . Am J Physiol. (1993)

Benard O1, Balasubramanian KA Effect of oxidant exposure on thiol status in the intestinal mucosa . Biochem Pharmacol. (1993)

Lu SC1, et al Bidirectional glutathione transport by cultured human retinal pigment epithelial cells . Invest Ophthalmol Vis Sci. (1995)

Kannan R1, et al Identification of a novel, sodium-dependent, reduced glutathione transporter in the rat lens epithelium . Invest Ophthalmol Vis Sci. (1996)

Pastore A1, et al Analysis of glutathione: implication in redox and detoxification . Clin Chim Acta. (2003)

van Bladeren PJ Glutathione conjugation as a bioactivation reaction . Chem Biol Interact. (2000)
Barycki JJ1, Colman RF Identification of the nonsubstrate steroid binding site of rat liver glutathione S-transferase, isozyme 1-1, by the steroid affinity label, 3beta-(iodoacetoxy)dehydroisoandrosterone . Arch Biochem Biophys. (1997)