Glutathione is a tri-peptide. It is the most important low molecular weight antioxidant synthesised in cells. It is capable of modulating the damage to important cellular components caused by free radicals, peroxides (reactive compounds that combine carbon and oxygen), lipid peroxides (free radical mediated chain of reactions, that once initiated results in oxidative deterioration of polyunsaturated lipids - they can compromise the integrity and function of the cell membrane in which the reside) and heavy metals. Essentially Glutathione (GSH) will guard cells against oxidative injury by reducing H2O2 and scavenging reactive oxygen and nitrogen species.
How is glutathione produced in the body?
The antioxidant is made up of 3 amino acids, which can be produced in the body determined by our exposure to such amino acids; glutamine, glycine and cysteine. The importance of a high protein diet along with cruciferous vegetables is essential, as I will come onto later.
Glutathione (GSH) is found in the cytosol of cells, where it is in the range of 1-10mM [1]. In most cells GSH concentration is 1-2 mM but in the tissues of the liver, where GSH is needed for detoxification, the hepatocytes concentration is more like 10mM.
Roles of glutathione:
As already discussed, glutathione plays a major role in reducing oxidative stress, neutralising free radicals, which can damage our body’s cells. Free radical scavenging is vital for the reduced risk of all diseases related to oxidative stress and inflammation, so basically all diseases… Cardiovascular Disease, Diabetes, Schizophrenia, Alzheimer’s and hundreds more.
Mitochondria:
GSH plays a role in regulating apoptosis versus necrosis. Cell death via apoptosis is orderly and controlled, but cell death via necrosis is quite simply inefficient blood flow to the tissue. You would have heard of the term ‘gangrene’, when large areas of tissue lose blood supply and die. Mitochondrial GSH depletion induces increased mitochondrial ROS exposure which impairs bioenergetics and promotes mitochondrial permeability transition pore opening which is critical for cell death [3]. Essentially low GSH levels trigger cell death. Elevated GSH levels provide protection against stress-induced apoptosis. [4]
Detoxification:
Before phase 2 detoxification, GSH will neutralise free radicals produced by phase 1 (metabolism of chemical toxins). If we are exposed to so many toxins that phase 1 essentially passes endless oxidised metabolites, made water soluble and passed onto phase 2, phase 2 gets overwhelmed. The oxidation process in phase 1 produces a lot of free radicals, and so GSH will be a huge player in modulating these effects. The elimination of many xenobiotic compounds can be accomplished through conjugation with GSH, via the Glutathione Conjugation pathway. So if we are deficient in GSH or we are unable to synthesise enough, one of our detox pathways is extremely impaired, and will not be able to expel foreign substances out of our body.
Glutathione can also recycle vitamins. So, vitamins that get oxidised can be reduced by GSH mechanisms that will see vitamin oxidant stress reversed. [5]
Glutathione and Alcohol Hangovers:
Glutathione (GSH) plays an important role in the detoxification of ethanol (EtOH) and acute EtOH administration leads to GSH depletion in the liver and other tissues [6]. The metabolic product of ethanol is blood acetaldehyde (a carcinogen), and it is the job of GSH to deal with this metabolite. If we get acetaldehyde toxicity, we will encounter such hangover symptoms like the headache. So, it would be a good idea to supplement glutathione to counteract the headache, or maybe not expose to ethanol metabolite build up in the first place… Who knows?
Cystic Fibrosis:
In cystic fibrosis patients, who secrete lower GSH than normal individuals into the lining fluid covering their alveoli, and in smokers, who have exposed their lungs to many oxidants including nitrogen dioxide and H2O2, there is both chronic inflammation and lower than normal GSH [7], and consequent organ damage and dysfunction. Secretion of GSH into the air space in cystic fibrosis is depressed because of a mutation of a protein called cystic fibrosis transport receptor (CFTR). Im not saying glutathione supplementation will help cystic fibrosis patients, i’m no doctor. But from this example we can see just how important the role of GSH in such diseases like CF.
Smokers:
In people who smoke, or inhale particles or other oxidants, there is potential inflammation that involves invasion of neutrophils from the blood through the endothelial and epithelial cells into the air spaces. As these neutrophils squeeze through the cells, they release HOCl (hypochlorous acid - a precursor to many free radicals and pro-oxidant) This will deplete GSH as its trying to protect and keep the integrity of the cells by reacting to and removing HOCl. [2]
How to naturally boost glutathione levels?
Consume sulphur-rich foods. Sulphur is required for the synthesis of glutathione. Dietary protein such as beef, fish and poultry, as well as cruciferous vegetables like broccoli, kale, brussel sprouts ets. Garlic and onions are also great.
Increase vitamin C consumption. It is theorised that vitamin C will attack a lot of free radicals first, sparing the need to deplete GSH to do the same job.
Selenium is a co-factor for glutathione, and we will get selenium in our diet through eating beef, chicken, fish and organ meats, cottage cheese, and some nuts.
Food naturally rich in glutathione are; spinach, avocados, asparagus.
As mentioned earlier, glutathione is a try-peptide, so it is dependant on amino acid availability to be synthesised. Having adequate protein intake with potential need to EAA or Whey protein supplementation to be included.
SLEEP! Long term sleep deprivation can up-regulate oxidative stress dramatically that will deplete GSH. [8]
Published by Luke French, Health Coach | 9th July 2020
[1] Meister A. Glutathione metabolism and its selective modification. J Biol Chem. 1988;263(33):17205-17208.
[2] Venglarik CJ, Giron-Calle J, Wigley AF, Malle E, Watanabe N, Forman HJ. Hypochlorous acid alters bronchial epithelial cell membrane properties and prevention by extracellular glutathione. J Appl Physiol (1985). 2003;95(6):2444-2452. doi:10.1152/japplphysiol.00002.2003
[3] Yuan L, Kaplowitz N. Glutathione in liver diseases and hepatotoxicity. Mol Aspects Med. 2009;30(1-2):29-41. doi:10.1016/j.mam.2008.08.003
[4] Circu ML, Aw TY. Glutathione and apoptosis. Free Radic Res. 2008;42(8):689-706. doi:10.1080/10715760802317663
[5] Recycling of vitamin C from its oxidized forms by human
James M.MayZhi-chaoQuDustin R.NeelXiaLi
[6] Vogt BL, Richie JP Jr. Glutathione depletion and recovery after acute ethanol administration in the aging mouse. Biochem Pharmacol. 2007;73(10):1613-1621. doi:10.1016/j.bcp.2007.01.033
[7] Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009;30(1-2):1-12. doi:10.1016/j.mam.2008.08.006
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