Two weeks of GlyNAC did not raise glutathione in healthy older adults overall
This 2022 randomised, controlled trial gave 114 healthy older adults GlyNAC at one of three doses or a placebo for two weeks. GlyNAC did not raise glutathione across the group, which was the trial's main measure. A later analysis found a rise in the subgroup with high oxidative stress and low starting glutathione on the two higher doses.
What they did
Researchers randomly assigned 114 healthy volunteers, average age 65, to GlyNAC (glycine and N-acetylcysteine in equal amounts) at 2.4 g, 4.8 g or 7.2 g a day, or to placebo, for two weeks. They compared the older adults' starting values with a reference group of 20 younger adults, average age 31.7.
The main measures were total glutathione and the ratio of free reduced glutathione to oxidised glutathione (GSH:GSSG), along with markers of oxidative damage such as malondialdehyde (MDA).
What they found
At the start, the older adults had more signs of oxidative stress than the young reference group: higher MDA (0.158 versus 0.136 µmol/L), higher total cysteine, higher oxidised glutathione (174.5 versus 132.3 µmol/L) and a lower GSH:GSSG ratio (11.78 versus 15.26).
GlyNAC was safe and well tolerated, but it did not raise the GSH:GSSG ratio (12.65 on the highest dose versus 12.49 on placebo) or total glutathione (959.6 versus 903.5 mg/L), the trial's primary endpoint. Neither difference was statistically significant.
In an analysis done after the main results, people with above-median oxidative stress and below-median starting glutathione who took the medium or high dose had higher glutathione at the end than comparable people on placebo (905.4 versus 819.7 mg/L).
What it can't tell us
The main result was negative. The subgroup finding came from a post-hoc analysis, one chosen after the data were in, so it suggests a question for a future trial rather than settling one. Two weeks may be too short to show an effect in people who start healthy.
Glutathione was measured in blood, not cartilage, and joints were not assessed. Most of the authors were employed by the trial's commercial sponsor, which holds patents on and markets glycine and NAC products, as declared in the paper.
Why it matters
This is the largest GlyNAC trial in this library, and it did not reproduce the clear across-the-board rise seen in the smaller studies. Its subgroup result points to a possible reason: GlyNAC may matter most for people whose glutathione is low and whose oxidative stress is high, rather than for everyone. Read it alongside Kumar 2023, which studied older adults selected for glutathione deficiency over a longer period.
The paper
- 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.
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