Vitamin D3's Effects on Inflammatory and Oxidative Biomarkers in MS

Multiple sclerosis (MS) is marked by intertwined inflammatory and oxidative pathways that contribute to tissue injury and disease progression. In this context, vitamin D has long attracted interest as a modifiable factor with immunomodulatory and antioxidant potential.

A recent study by Asadpour and colleagues offers a focused look at how short-term, high-dose vitamin D3 supplementation may influence circulating biomarkers tied to these processes, particularly chitinase-3-like protein 1 (CHI3L1, also known as YKL-40) and measures of oxidative stress.

CHI3L1 is a secreted glycoprotein produced largely by activated astrocytes and microglia. While it lacks enzymatic chitinase activity, it functions as a signaling molecule involved in inflammation, tissue remodeling, and neurodegeneration. In MS, elevated serum and cerebrospinal fluid CHI3L1 levels have been associated with disease activity and progression, making it a biomarker of growing interest. Oxidative stress markers, including lipid peroxidation products and antioxidant enzyme activity, provide complementary insight into the cellular environment driving neural injury.

Study Design

This investigation was conducted in Iran as a single-arm, open-label, pre-post clinical trial. The study enrolled 35 adults with multiple sclerosis, all of whom were female and between 30 and 56 years of age. Participants received oral vitamin D3 at a dose of 50,000 IU once weekly for a total of eight weeks. The trial did not include randomization, blinding, or a placebo control group. Throughout the intervention period, patients continued their existing disease-modifying therapies without changes.

Outcomes were evaluated by measuring serum 25-hydroxyvitamin D levels, CHI3L1, total oxidant status, malondialdehyde, total antioxidant capacity, and the activities of key antioxidant enzymes. All biomarkers were assessed before and after supplementation using established ELISA-based and colorimetric laboratory assays.

Results After Eight Weeks

Vitamin D3 supplementation produced a robust rise in serum 25-hydroxyvitamin D, increasing from 20.80 ± 8.6 ng/mL at baseline to 39.11 ± 12.26 ng/mL (p < 0.001). This biochemical correction was accompanied by notable shifts in inflammatory and oxidative markers.

Serum CHI3L1 levels declined by approximately 21.7%, falling from 33.28 ± 8.9 ng/mL to 26.05 ± 9.1 ng/mL (p < 0.001). The strong inverse correlation between 25-hydroxyvitamin D and CHI3L1 (r = −0.999, p < 0.001) suggests a close relationship between vitamin D status and this neuroinflammatory biomarker.

Markers of oxidative stress moved in a consistent direction. Total oxidant status dropped markedly (p < 0.001), as did malondialdehyde, a lipid peroxidation marker (p < 0.001). In parallel, antioxidant defenses improved, total antioxidant capacity increased (p < 0.001), and activities of superoxide dismutase, catalase, and glutathione peroxidase rose significantly.

Interpreting the Signal With Appropriate Caution

Taken together, these findings suggest that vitamin D3 supplementation may simultaneously dampen inflammatory signaling, reflected by lower CHI3L1, and rebalance redox homeostasis in MS. Mechanistically, this aligns with known vitamin D receptor-mediated effects on cytokine profiles and antioxidant gene expression. However, the study’s design limits causal inference. Without a control group, placebo effects, regression to the mean, or interactions with ongoing therapies cannot be excluded.

Importantly, this work focuses exclusively on biomarkers. Clinical outcomes such as relapse rate, disability progression, or MRI activity were not assessed. As such, the results are best viewed as hypothesis-generating rather than practice-changing.

Why This Study Matters

By linking vitamin D3 supplementation to concurrent reductions in CHI3L1 and oxidative stress markers, this study highlights a potential biological pathway through which vitamin D could influence MS pathophysiology. For clinicians and researchers, it underscores the value of biomarker-driven studies in refining therapeutic hypotheses, and the need for larger, randomized trials to determine whether these molecular shifts translate into meaningful clinical benefit.

Reference

Asadpour S, Mazdeh M, Karimi J, Khodadadi I, Shafiee G. Vitamin D3 Supplementation Modulates Inflammatory Protein CHI3L1/YKL-40 and Oxidative Stress Status in Multiple Sclerosis. Neuropsychopharmacol Rep. 2025;45(4):e70076. doi:10.1002/npr2.70076