N-acetylcysteine prevents glutathione decrease and does not interfere with paracetamol antinociceptive effect at therapeutic dosage: a randomized double-blind controlled trial in healthy subjects.
Level 2 - randomized trial
Randomized double-blind crossover controlled trial
PubMed 30471141 · doi:10.1111/fcp.12437
What was done
A double-blind, randomized crossover trial in 24 healthy volunteers evaluated whether N-acetylcysteine (NAC) alters the analgesic effect of paracetamol (APAP) or prevents APAP-induced glutathione (GSH) depletion. Participants received oral APAP (1 g four times daily for 4 days) combined with either NAC or placebo. The primary endpoint was the area under the curve (AUC 0–240 min) of pain intensity following experimental thermal pain stimulation. Whole blood GSH and liver enzymes (ASAT, ALAT) were assessed at baseline (Day 0) and Day 4.
What was found
The antinociceptive effect of APAP was similar between the APAP/NAC and APAP/placebo arms. Blood GSH remained at baseline levels in the APAP/NAC group but significantly declined in the APAP/placebo group (P = 0.033). Specific numerical values for pain AUC, GSH levels, and liver enzyme concentrations were not reported in the abstract.
Why it matters
These findings suggest that NAC can mitigate the reduction in glutathione caused by standard therapeutic doses of paracetamol without compromising pain relief, supporting potential protective co-administration strategies.
Limits
The sample size was small (n = 24) and limited to healthy volunteers exposed to short-term experimental thermal pain rather than clinical pain. The exposure lasted only 4 days, and exact numerical effect sizes for pain ratings and biomarker changes were omitted from the abstract.
Cited by
- supports Supplementing with N-acetylcysteine (NAC) supports glutathione production and detoxification in the body.