Targeting low-grade inflammation in multiple sclerosis through the Wim Hof method or lifestyle intervention: a pilot comparative study

Abstract Background Disease-modifying therapies (DMTs) in multiple sclerosis (MS) effectively reduce relapse activity but have limited impact on chronic progression and neurodegeneration. Non-pharmacological interventions such as structured exercise or the Wim Hof Method (WHM- which includes breathing exercises, cold exposure, and meditation), may offer complementary immunomodulatory and neuroprotective benefits. Objectives To compare the effects of WHM and a lifestyle intervention (LIFE; structured physical activity and nutritional counseling) on systemic inflammation and neurodegeneration biomarkers in patients with MS. Methods In this randomized, prospective pilot trial, 60 MS patients (2017 McDonald criteria, EDSS 1.0–5.5) were allocated to WHM, LIFE, or control (CTRL) for 12 weeks. Serum cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed at baseline and after 12 weeks. Mixed repeated-measures ANOVA with Bonferroni correction was applied. Results Complete datasets were obtained and analyzed for 43 participants (12 WHM, 17 LIFE, 14 CTRL; power= 0.81). Both interventions significantly reduced IL-17A and IL-18 (p<0.001), indicating attenuation of Th17-related inflammation. WHM further decreased IFN-γ, while LIFE lowered IL-8. No significant changes were observed for IL-1β, IL-6, IL-12p70, NfL, or GFAP. Both interventions were well tolerated, with no treatment-related adverse events. Conclusions Both WHM and lifestyle modification demonstrated comparable short-term anti-inflammatory effects in MS, supporting their safety and feasibility as adjunctive strategies to DMT. Although neurodegeneration biomarkers remained unchanged, the consistent reduction of IL-17A and IL-18 highlights their potential to modulate smoldering inflammation. Larger, longer-term trials are warranted to determine their sustained effects on disease progression.