Vitamin D3 Supplementation Modulates Inflammatory Protein CHI3L1 / YKL ‐40 and Oxidative Stress Status in Multiple Sclerosis

Objective Multiple sclerosis ( MS ) is characterized by chronic neuroinflammation and oxidative stress. Vitamin D is believed to exert immunomodulatory and antioxidant effects, yet its impact on specific inflammatory proteins such as CHI3L1 ( YKL ‐40) in MS remains unclear. This study evaluated whether 8‐week vitamin D3 supplementation affects serum CHI3L1 levels, oxidative stress markers, and antioxidant enzyme activities in patients with MS . Methods In this single‐arm pre‐post clinical trial, 35 patients with MS (aged 30–56 years) received oral vitamin D3 supplementation (50 000 IU /week) for 8 weeks. Serum 25( OH )D and CHI3L1 levels were determined using commercial enzyme‐linked immunosorbent assay ( ELISA ) kits. oxidative stress markers were measured pre‐ and post‐intervention using commercial colorimetric kits. Statistical analysis was performed using paired t ‐tests or Wilcoxon signed‐rank tests. Results Vitamin D3 supplementation significantly increased serum 25( OH )D levels (20.80 ± 8.6 to 39.11 ± 12.26 ng/ mL ; p < 0.001). CHI3L1 concentration decreased by 21.7% (33.28 ± 8.9 to 26.05 ± 9.1 ng/ mL ; p < 0.001). oxidative stress was reduced, evidenced by lower TOS (1.55 ± 0.50 to 0.59 ± 0.23 mmol H 2 O 2 equiv./L; p < 0.001) and MDA (0.08 ± 0.03 to 0.05 ± 0.026 nmol/ mL ; p < 0.001). Antioxidant capacity improved, as demonstrated by elevated TAC (0.622 ± 0.138 to 0.797 ± 0.15 mmol Fe 2+ /L; p < 0.001) and increased activities of SOD (10.5%; p < 0.001), CAT (19.5%; p < 0.001), and GPx (35.6%; p < 0.05). Significant inverse correlations were observed between serum 25( OH )D and CHI3L1 ( r = −0.999, p < 0.001), TOS ( r = −0.456, p = 0.0058), and MDA ( r = −0.577, p < 0.001). Conclusion Vitamin D3 supplementation was associated with reductions in CHI3L1 and oxidative stress markers, while suggesting enhancement of antioxidant capacity. This observed biomarker changes support vitamin D3 as a potential adjunct therapy targeting interconnected pathological pathways in MS.