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

**Authors:** Sevda Asadpour, Mehrdokht Mazdeh, Jamshid Karimi, Iraj Khodadadi, Gholamreza Shafiee

PMC · DOI: 10.1002/npr2.70076 · Neuropsychopharmacology Reports · 2025-11-23

## TL;DR

An 8-week vitamin D3 supplement reduced inflammation and oxidative stress in multiple sclerosis patients.

## Contribution

The study shows vitamin D3 lowers CHI3L1/YKL-40 and oxidative stress in MS patients.

## Key findings

- Vitamin D3 supplementation significantly increased serum 25(OH)D levels.
- CHI3L1 concentration decreased by 21.7% after supplementation.
- Oxidative stress markers like TOS and MDA were significantly reduced.

## Abstract

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.

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.

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 H2O2 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 Fe2+/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).

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.

In multiple sclerosis (MS) as a chronic autoimmune neurodegenerative disorder, 8‐week vitamin D3 supplementation was associated with reductions in the neuroinflammatory biomarker Chitinase‐3‐like protein 1 (CHI3L1) and oxidative stress markers, while suggesting enhancement of antioxidant capacity. Nevertheless, the observed biomarker changes support vitamin D3 as a potential adjunct therapy targeting interconnected pathological pathways in MS.

## Linked entities

- **Proteins:** CHI3L1 (chitinase 3 like 1), SOD1 (superoxide dismutase 1), CAT (catalase), GPX (probable phospholipid hydroperoxide glutathione peroxidase)
- **Chemicals:** vitamin D3 (PubChem CID 5280795), MDA (PubChem CID 1614), Fe2+ (PubChem CID 23925)
- **Diseases:** multiple sclerosis (MONDO:0005301)

## Full-text entities

- **Genes:** CAT (catalase) [NCBI Gene 847], SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, CHI3L1 (chitinase 3 like 1) [NCBI Gene 1116] {aka ASRT7, CGP-39, GP-39, GP39, HC-gp39, HCGP-3P}
- **Diseases:** neuroinflammation (MESH:D000090862), Inflammatory (MESH:D007249), MS (MESH:D009103)
- **Chemicals:** Vitamin D (MESH:D014807), 25(OH)D (-), MDA (MESH:D015104), H2O2 (MESH:D006861), Vitamin D3 (MESH:D002762)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12641099/full.md

## References

83 references — full list in the complete paper: https://tomesphere.com/paper/PMC12641099/full.md

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Source: https://tomesphere.com/paper/PMC12641099