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

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