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

Journal article


Lizzo, Giulia, Migliavacca, Eugenia, Lamers, Daniela, Frézal, Adrien, Corthesy, John, Vinyes-Parès, Gerard, Bosco, Nabil, Karagounis, Leonidas, Hövelmann, Ulrike, Heise, Tim, Von Eynatten, Maximilian and Gut, Philipp. (2022). 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. Frontiers in Aging. 3, p. Article 852569. https://doi.org/10.3389/fragi.2022.852569
AuthorsLizzo, Giulia, Migliavacca, Eugenia, Lamers, Daniela, Frézal, Adrien, Corthesy, John, Vinyes-Parès, Gerard, Bosco, Nabil, Karagounis, Leonidas, Hövelmann, Ulrike, Heise, Tim, Von Eynatten, Maximilian and Gut, Philipp
Abstract

Glycine and cysteine are non-essential amino acids that are required to generate glutathione, an intracellular tripeptide that neutralizes reactive oxygen species and prevents tissue damage. During aging glutathione demand is thought to increase, but whether additional dietary intake of glycine and cysteine contributes towards the generation of glutathione in healthy older adults is not well understood. We investigated supplementation with glycine and n-acetylcysteine (GlyNAC) at three different daily doses for 2 weeks (low dose: 2.4 g, medium dose: 4.8 g, or high dose: 7.2 g/day, 1:1 ratio) in a randomized, controlled clinical trial in 114 healthy volunteers. Despite representing a cohort of healthy older adults (age mean = 65 years), we found significantly higher baseline levels of markers of oxidative stress, including that of malondialdehyde (MDA, 0.158 vs. 0.136 µmol/L, p < 0.0001), total cysteine (Cysteine-T, 314.8 vs. 276 µM, p < 0.0001), oxidized glutathione (GSSG, 174.5 vs. 132.3 µmol/L, p < 0.0001), and a lower ratio of reduced to oxidized glutathione (GSH-F:GSSG) (11.78 vs. 15.26, p = 0.0018) compared to a young reference group (age mean = 31.7 years, n = 20). GlyNAC supplementation was safe and well tolerated by the subjects, but did not increase levels of GSH-F:GSSG (end of study, placebo = 12.49 vs. 7.2 g = 12.65, p-value = 0.739) or that of total glutathione (GSH-T) (end of study, placebo = 903.5 vs. 7.2 g = 959.6 mg/L, p-value = 0.278), the primary endpoint of the study. Post-hoc analyses revealed that a subset of subjects characterized by high oxidative stress (above the median for MDA) and low baseline GSH-T status (below the median), who received the medium and high doses of GlyNAC, presented increased glutathione generation (end of study, placebo = 819.7 vs. 4.8g/7.2 g = 905.4 mg/L, p-value = 0.016). In summary GlyNAC supplementation is safe, well tolerated, and may increase glutathione levels in older adults with high glutathione demand.

Keywordsglycine; n-acetylcysteine; glutathione; total cysteine; cardiometabolic diseases; healthy aging; oxidative stress; nutrition
Year2022
JournalFrontiers in Aging
Journal citation3, p. Article 852569
PublisherFrontiers Media S.A.
ISSN2673-6217
Digital Object Identifier (DOI)https://doi.org/10.3389/fragi.2022.852569
PubMed ID35821844
Scopus EID2-s2.0-85137625288
PubMed Central IDPMC9261343
Open accessPublished as ‘gold’ (paid) open access
Page range1-14
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online07 Mar 2022
Publication process dates
Accepted08 Feb 2022
Deposited28 Nov 2023
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