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Background <p>The immunomodulatory role of vitamin D3 in autoimmune diseases is widely hypothesized, but its therapeutic efficacy remains contested. This meta-analysis quantifies the effect of vitamin D3 supplementation on biochemical, endocrine, and inflammatory parameters across various autoimmune conditions.</p> Methods <p>We systematically searched five databases for randomized controlled trials (RCTs) comparing vitamin D3 to placebo/control in autoimmune disease patients. Data from 27 RCTs (n = 1864) were pooled using a random-effects model. Subgroup analyses were conducted based on disease type, dosage, and duration.</p> Results <p>Vitamin D3 supplementation significantly increased serum 25(OH)D levels (WMD: 53.01 nmol/L, 95% CI: 36.29–69.73, <i>p</i> &lt; 0.001). It induced modest but significant increases in serum calcium (WMD: 0.18 mmol/L) and reductions in parathyroid hormone (WMD: − 8.37 pg/mL) and the inflammatory markers CRP (WMD: − 2.33 mg/L) and IL-6 (WMD: − 0.76 pg/mL). Benefits were more pronounced with longer duration (≥ 6 months) and in patients with multiple sclerosis. However, vitamin D3 showed no significant effect on key disease-specific outcomes, including neurofilament light chain in MS, hemoglobin A1c in type 1 diabetes, or pain scores in rheumatoid arthritis.</p> Conclusion <p>Vitamin D3 effectively corrects deficiency and exerts modest, systemic anti-inflammatory effects in autoimmune patients. Its impact is context-dependent, influenced by treatment duration and specific disease, supporting its role as a safe adjunctive therapy, though its effect on core disease activity markers is limited. There was significant heterogeneity (I<sup>2</sup> &gt; 90% for the majority of outcomes), which reflects actual clinical and methodological variation between trials. Although there is still some unexplained heterogeneity, subgroup analysis by disease type, duration, and dosage identified significant effect modifiers. Therefore, rather than being exact predictions for specific individuals, pooled estimates should be understood as average effects across various populations.</p>

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Effect of vitamin D3 supplementation on systemic inflammation and disease-specific markers in patients with autoimmune diseases: a comprehensive meta-analysis of randomized controlled trials

  • 期刊论文

  • 发表日期：

    2026年4月9日

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  • Amirreza Jabbari,
  • Hadi Esmaeili Gouvarchin Ghaleh,
  • Mina Alimohammadi,
  • Seyedeh Mahdieh Khoshnazar,
  • Mostafa Eslami Mahmoudabadi,
  • Amirhossein Heidari,
  • Kiavash Hushmandi

摘要

Background

The immunomodulatory role of vitamin D3 in autoimmune diseases is widely hypothesized, but its therapeutic efficacy remains contested. This meta-analysis quantifies the effect of vitamin D3 supplementation on biochemical, endocrine, and inflammatory parameters across various autoimmune conditions.

Methods

We systematically searched five databases for randomized controlled trials (RCTs) comparing vitamin D3 to placebo/control in autoimmune disease patients. Data from 27 RCTs (n = 1864) were pooled using a random-effects model. Subgroup analyses were conducted based on disease type, dosage, and duration.

Results

Vitamin D3 supplementation significantly increased serum 25(OH)D levels (WMD: 53.01 nmol/L, 95% CI: 36.29–69.73, p < 0.001). It induced modest but significant increases in serum calcium (WMD: 0.18 mmol/L) and reductions in parathyroid hormone (WMD: − 8.37 pg/mL) and the inflammatory markers CRP (WMD: − 2.33 mg/L) and IL-6 (WMD: − 0.76 pg/mL). Benefits were more pronounced with longer duration (≥ 6 months) and in patients with multiple sclerosis. However, vitamin D3 showed no significant effect on key disease-specific outcomes, including neurofilament light chain in MS, hemoglobin A1c in type 1 diabetes, or pain scores in rheumatoid arthritis.

Conclusion

Vitamin D3 effectively corrects deficiency and exerts modest, systemic anti-inflammatory effects in autoimmune patients. Its impact is context-dependent, influenced by treatment duration and specific disease, supporting its role as a safe adjunctive therapy, though its effect on core disease activity markers is limited. There was significant heterogeneity (I2 > 90% for the majority of outcomes), which reflects actual clinical and methodological variation between trials. Although there is still some unexplained heterogeneity, subgroup analysis by disease type, duration, and dosage identified significant effect modifiers. Therefore, rather than being exact predictions for specific individuals, pooled estimates should be understood as average effects across various populations.