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Study breakdown

Vitamin D Injections for Warts Work by Boosting the Antimicrobial Peptide LL-37

Interventional ClinicalLow Moderate evidence
The takeaway

Injecting vitamin D directly into warts cleared 40% of them completely and significantly boosted the antimicrobial peptide LL-37, revealing how the treatment activates the skin's natural viral defense.

40% complete wart clearance

Vitamin D injections significantly increased LL-37 expression in wart tissue (p=0.003), with the highest LL-37 levels in patients whose warts cleared completely.

What the researchers found

Injecting vitamin D directly into common warts (verruca vulgaris) significantly increased expression of the antimicrobial peptide LL-37 (cathelicidin) in the skin (p=0.003). Of 20 patients treated, 40% showed complete wart clearance and 35% showed partial response. Warts that cleared completely had the highest LL-37 expression (p=0.022).

After treatment, the skin also showed decreased epidermal thickness and reduced inflammatory cell density, indicating the immune response was shifting from chronic inflammation toward effective viral clearance driven by LL-37.

Why it matters

LL-37 is the body's primary antimicrobial peptide and plays a key role in fighting viral infections in the skin. This study provides a mechanistic explanation for why vitamin D injections work against warts — they boost the skin's natural LL-37 production, helping the immune system recognize and clear the HPV virus. This connects two major research areas: vitamin D's role in immunity and cathelicidin's antiviral properties.

The numbers in context

n=20 patients · 10 healthy controls · 40% complete response · 35% partial response · 25% no response · LL-37 increase p=0.003 · Complete responders p=0.022 · Max 4 sessions every 2 weeks

How the study worked

Twenty patients with multiple common warts received intralesional vitamin D3 injections every 2 weeks for up to 4 sessions or until warts cleared. Skin biopsies were taken before and after treatment and compared to samples from 10 healthy controls. LL-37 expression was assessed by immunohistochemistry. Histopathological changes in the epidermis and dermis were also evaluated.

Who was studied

20 patients with multiple common warts (verruca vulgaris) and 10 healthy age/sex-matched controls

What this study cannot tell us

Small sample size (20 patients) limits generalizability. No placebo or sham injection control group — response could partly be due to the injection itself triggering local immunity. The study was not blinded. No long-term follow-up to assess recurrence rates.

How to read the evidence

This is a small interventional study with 20 patients and no control group receiving sham injections. While the immunohistochemical evidence linking vitamin D to LL-37 upregulation is compelling, the lack of blinding and small sample limit the strength of the clinical efficacy findings.

When this study was published

Published in 2022. The connection between vitamin D and cathelicidin expression remains an active research area, and intralesional vitamin D for warts continues to be studied.

The bigger picture

LL-37 is increasingly recognized as a frontline defender in skin immunity, with roles in fighting bacteria, viruses, and fungi. This study adds wart clearance to LL-37's growing resume and demonstrates that its expression can be deliberately upregulated through vitamin D — a finding with implications for other skin infections and conditions where cathelicidin deficiency plays a role.

Questions still open

  • Could topical or oral vitamin D supplementation boost LL-37 enough to prevent wart recurrence?
  • Would patients with low baseline vitamin D levels show even greater responses to intralesional injection?
  • Could this LL-37-boosting mechanism be exploited for other HPV-driven conditions like genital warts or cervical dysplasia?

Common questions

How does vitamin D help clear warts?
When injected directly into warts, vitamin D boosts production of LL-37, an antimicrobial peptide that helps your immune system fight the HPV virus causing the wart. In this study, patients whose warts cleared completely had the highest LL-37 levels, showing a direct link between the peptide and treatment success.
What is LL-37 and why does it matter for skin infections?
LL-37 (cathelicidin) is your body's main antimicrobial peptide in the skin. It kills bacteria, viruses, and fungi by disrupting their membranes. This study showed that vitamin D can boost LL-37 production in wart tissue, suggesting the peptide plays a key role in helping the immune system recognize and clear HPV-infected skin cells.

Read the original research

Intralesional injection of vitamin D in verruca vulgaris increases cathelicidin (LL37) expression; therapeutic and immunohistochemical study.

The Journal of dermatological treatment, 33(1), 291-296

Citation

Sorour, Neveen E; Elesawy, Fatma M; Abdou, Asmaa G; Abdelazeem, Sara E; Akl, Essam M. (2022). Intralesional injection of vitamin D in verruca vulgaris increases cathelicidin (LL37) expression; therapeutic and immunohistochemical study.. The Journal of dermatological treatment, 33(1), 291-296. https://doi.org/10.1080/09546634.2020.1750554