Changes in Glutathione Metabolites and Reactive Oxygen Species from Baseline to Post-Treatment in Breast Cancer Survivors with Psychoneurological Symptoms Receiving Acupuncture

Objectives: To investigate acupuncture-induced changes in targeted glutathione metabolites in breast cancer survivors with psychoneurological symptoms (PNS) and to examine associations between these metabolic changes and PNS improvements. Methods: This exploratory phase II single-arm study (N = 42) evaluated a 10-session, 5-week acupuncture intervention for PNS management in breast cancer survivors. Targeted glutathione metabolites (ie, reduced glutathione (GSH), oxidized glutathione (GSSG), cysteine-glutathione disulfide (CySSG), GSH/GSSG ratio) and reactive oxygen species (ROS) were measured pre- and post-treatment. Paired t -test and Wilcoxon signed-rank tests assessed changes in these biomarkers. The PNS were assessed using Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Results: ROS levels significantly increased post-treatment (2.34 ± 1.02-2.83 ± 1.23 μmol/L, P = .017), while GSSG levels significantly decreased (0.19 ± 0.23-0.12 ± 0.23 µmol/L, P < .001). GSH/GSSG ratio significantly increased (2.73 ± 1.21-5.38 ± 1.99, P < .001), indicating a shift toward reduced oxidative stress. GSH and CySSG levels showed non-significant increases after acupuncture (GSH: 0.38 ± 0.14-0.42 ± 0.16 µmol/L, P = .07; CySSG: 0.00503 ± 0.00082-0.00532 ± 0.00076 µmol/L, P = .06). No significant correlations were found between changes in GSH metabolites and PNS composite scores or individual symptom scores. Conclusion: Acupuncture may modulate GSH metabolism, improve redox balance, and enhance antioxidant capacity in breast cancer survivors with PNS. However, these biochemical changes were not correlated with PNS improvement, suggesting that alternative pathways may mediate acupuncture’s therapeutic effects. Trial registry information: The study was registered in ClinicalTrials.gov (Identifier: NCT05417451).