Investigation of Serum Nuclear Factor Erythroid 2–Related Factor 2 Levels, Oxidative Stress Parameters, and Thiol-Disulfide Homeostasis in Patients with Fibromyalgia

Background/Aims: In order to delineate the involvement of oxidative stress in fibromyalgia syndrome (FMS), this investigation analyzed systemic biomarkers - including nuclear factor erythroid 2 (Nrf2), total antioxidant status (TAS), total oxidant status (TOS) and thiol-disulfide equilibrium—in female patients with FMS and a reference group of healthy subjects. It was investigated how the patient group’s clinical characteristics, oxidative stress metrics, and Nrf2 levels related to one another. To date, no published studies have assessed serum Nrf2 levels in patients with FMS.

Materials and Methods: The study enrolled 50 healthy female participants and 60 FMS patients. Participants were evaluated using the Visual Analog Scale (VAS), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Scale (BDS), Beck Anxiety Scale (BAS), Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), the DN4 Neuropathic Pain Questionnaire, and the count of tender points (TP). Nrf2 level was measured by Enzyme-linked immunosorbent assay method, TAS, TOS, native thiol (NT), total thiol (TT), and disulfide levels were measured by spectrophotometric method.

Results: In comparison with the reference group of healthy subjects, patients with FMS displayed significantly elevated values in TP count, FIQ, BDS, BAS, PSQI, FSS, VAS, DN4, TAS, and TOS (P < .001). Conversely, levels of serum Nrf2 were markedly reduced in the FMS group (P < .001). The DN4 scores were negatively and significantly correlated with Nrf2 concentrations (P = .049).

Conclusion: The results point to a possible role for Nrf2 in the pathophysiology of FMS and may help identify and treat the condition, especially in individuals with neuropathic pain complaints. These findings are promising, as they indicate that the use of Nrf2 activators may be considered in patients with low Nrf2 levels. The potential utility of Nrf2-activating agents in such subgroups warrants further investigation.

Cite this article as: Aşık M, Gur A, Altindag O, Akaltun MS, Balbal E. Investigation of serum nuclear factor erythroid 2–related factor 2 levels, oxidative stress parameters, and thiol-disulfide homeostasis in patients with fibromyalgia. ArchRheumatol. Published online June 3, 2026. doi: 10.5152/ArchRheumatol.2026.25024.