Glutathione is the body’s master detoxification molecule, able to detox free radicals, heavy metals, drugs, and other poisons. It’s so important to our health and wellbeing that cell levels are now becoming an important predictor of our lifespan.
Our cells make glutathione from 3 amino acids in a 2 part process. In phase 1, L-cysteine and L-glutamic acid are linked by an enzyme called glutamate cysteine ligase to form the molecule gamma-glutamylcysteine, or GGC. In the second phase, GGC is linked to glycine by the enzyme glutathione synthetase to form reduced glutathione, also known as GSH.
The popular and well-studied supplement NAC, or N-Acetyl Cysteine, provides the body with a readily available form of cysteine that can help the body increase GSH. However, certain research has shown that NAC increases cell glutathione primarily when the body is experiencing an acute GSH drop. This is the case with NAC used as an antidote for acetaminophen poisoning in hospitals worldwide since the 1960s. But it turns out that N-Acetyl Cysteine may not be sufficient to increase cell GSH levels beyond normal homeostasis.
So how do we increase long-term glutathione levels? The first thing to know is that GSH works with a number of nutrients that help increase its power and lifespan. For a few examples:
- Vitamin C is an antioxidant that can attack free radicals first, sparing GSH, and it can also help convert oxidized glutathione back into its original form. Taken by itself as a supplement, it has been shown to increase GSH levels in red blood cells.
- Levels of the antioxidant Vitamin E have similarly been shown to be significantly related to glutathione levels.
- The mineral selenium is really important, as it helps raise levels of the enzyme glutathione peroxidase, and is considered an essential cofactor for GSH activity.
- And Alpha Lipoic Acid is also considered a cofactor for GSH because it stimulates the essential enzyme GCL, and increases cell uptake of the amino acid cysteine.
The second thing to know is that ready-made gamma-glutamylcysteine, or GGC, has been shown to be better at increasing glutathione levels both in the short- and long-term. As far as I’m aware, two options currently exist to get GGC as a supplement, and the first is whey protein. Whey not only contains ample amounts of all 3 amino acids needed for GSH production; it also contains GGC in several forms such as lactoferrin and albumin. [“Serum albumin and lactoferrin are especially rich in disulfide-linked GGC bound to the cysteine residues contained in the proteins. For each serum albumin protein there are six bound molecules of GGC and for lactoferrin there are four.”] Several studies have shown whey’s ability to increase GSH levels for longer terms, making it perhaps THE top glutathione food out there. Quality is key though, so be sure to buy grass-fed, organic, cold-filtered whey; in a concentrate or isolate form. If you want a brand specifically researched to get good results, try Immunocal© Whey Protein, which research has shown markedly increases GSH in lymphocytes, or immune cells.
The second option is a supplement called Glyteine©, sold as the brand-name Continual G©. Glyteine(c) is simply GGC ready to be converted into reduced glutathione by the body. Studies have shown that GGC can rapidly increase cell GSH levels with a single dose. Being such an excellent supplement, it is a little pricey at about $3/dose; but with that being said, in emergency situations where extra GSH is needed and fast, it might seem pretty inexpensive.
If you spend the money to buy Continual G(c) though, be sure you’re also getting enough glycine, the third amino acid in the GSH equation. Glycine has the potential to be a rate-limiting nutrient for GSH production, and research has shown that GGC converts to a metabolite called 5-L-oxoproline that is excreted in the urine when there is not enough glycine available to complete the transition from GGC to GSH. This is mainly an issue for vegans and vegetarians, but most people can likely benefit from supplementing with glycine due to its numerous benefits.
Source Links:
1) Glutathione! [Joseph Pizzorno, ND, Editor in Chief] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/
2) Vitamin C augments lymphocyte glutathione in subjects with ascorbate deficiency: https://pubmed.ncbi.nlm.nih.gov/12499341/
3) Vitamin C elevates red blood cell glutathione in healthy adults
https://pubmed.ncbi.nlm.nih.gov/8317379/
4) Vitamin E supplementation restores glutathione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic children: https://pubmed.ncbi.nlm.nih.gov/10977039/
5) Role of selenium and glutathione peroxidase on development, growth, and oxidative balance in rat offspring: https://pubmed.ncbi.nlm.nih.gov/24080144/
6) Selenium regulation of glutathione peroxidase in human hepatoma cell line Hep3B: https://pubmed.ncbi.nlm.nih.gov/8391784/
7) α-Lipoic acid protects against the oxidative stress and cytotoxicity induced by cadmium in HepG2 cells through regenerating glutathione regulated by glutamate-cysteine ligase:
https://pubmed.ncbi.nlm.nih.gov/26365678/
8) Improved glutathione status in young adult patients with cystic fibrosis supplemented with whey protein: https://pubmed.ncbi.nlm.nih.gov/15463873/
9) Immuno-enhancing property of dietary whey protein in mice: role of glutathione: https://pubmed.ncbi.nlm.nih.gov/2743633/
10) The biological activity of undenatured dietary whey proteins: role of glutathione: https://pubmed.ncbi.nlm.nih.gov/1782728/
11) A Cysteine-Rich Whey Supplement (Immunocal®) Provides Neuroprotection from Diverse Oxidative Stress-Inducing Agents In Vitro by Preserving Cellular Glutathione:
https://pubmed.ncbi.nlm.nih.gov/28894506/
12) Effect of supplementation with a cysteine donor on muscular performance: https://pubmed.ncbi.nlm.nih.gov/10517767/
13) γ-Glutamylcysteine ameliorates oxidative injury in neurons and astrocytes in vitro and increases brain glutathione in vivo: https://www.sciencedirect.com/science/article/abs/pii/S0161813X10002299
14) Oral administration of γ-glutamylcysteine increases intracellular glutathione levels above homeostasis in a randomized human trial pilot study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5284489/
15) Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855430/