Glutathione or its building blocks: which raises glutathione?
Both routes have raised glutathione in people, measured in blood. Taking glutathione daily for months raised blood levels (Richie 2015), and supplying its building blocks, cysteine and glycine, raised red-cell glutathione in older adults (Sekhar 2011; Kumar 2023). The building-block route works with the cell's own machinery. None of the studies in our library compared the two head to head.
Why the building-block idea exists
Glutathione is made inside cells, and its synthesis is controlled by the supply of cysteine and by glutamate cysteine ligase (Lu 2013). Older adults had lower red-cell cysteine and glycine and made glutathione more slowly than younger adults, which points to a supply problem (Sekhar 2011).
What the precursor trials found
Two weeks of cysteine and glycine raised red-cell glutathione by about 95% in eight older adults (Sekhar 2011). In a 16-week placebo-controlled trial in 24 older adults, glycine plus N-acetylcysteine (GlyNAC) corrected glutathione deficiency and improved oxidative stress, inflammation, gait speed and strength (Kumar 2023). A larger two-week trial in 114 healthy older adults found no rise across the whole group, but a rise in those with high oxidative stress and low starting glutathione (Lizzo 2022).
What the direct glutathione trials found
A single large dose did not raise plasma glutathione (Witschi 1992). Daily doses for six months did (Richie 2015).
Inside the cartilage cell
The cartilage evidence is about supply. Removing cystine from the culture medium drained human chondrocytes of glutathione (Del Carlo 2003); NAC protected cartilage cells only while they could still make glutathione (Nakagawa 2010); and alpha-lipoic acid raised cells' glutathione by improving cysteine uptake (Han 1997). That is the logic behind Gluthanol™.
Other questions people ask
Who seems to benefit most from building blocks?
In the largest trial, people who started with high oxidative stress and low glutathione (Lizzo 2022).
Sources
- Richie JP Jr, Nichenametla S, Neidig W et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr 2015.
- Sekhar RV, Patel SG, Guthikonda AP et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr 2011.
- Kumar P, Liu C, Suliburk J et al. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci 2023.
- Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013.
- Lizzo G, Migliavacca E, Lamers D et al. A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. Front Aging 2022.
- Witschi A, Reddy S, Stofer B et al. The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992.
- Carlo MD Jr, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 2003.
- Nakagawa S, Arai Y, Mazda O et al. N-acetylcysteine prevents nitric oxide-induced chondrocyte apoptosis and cartilage degeneration in an experimental model of osteoarthritis. J Orthop Res 2010.
- Han D, Handelman G, Marcocci L et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 1997.
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What is GlyNAC?
GlyNAC is a combination of glycine and N-acetylcysteine (NAC), two of glutathione's building blocks, studied as a way to correct glutathione deficiency in older adults....
What is Gluthanol™?
Gluthanol™ is a proprietary blend of N-acetylcysteine, L-glycine, L-glutamine and alpha-lipoic acid, built to supply the raw materials cartilage cells make glutathione...
How do cartilage cells make glutathione?
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