The effect of Vitamin D and Vitamin D-based therapies on hemorrhage risk in cerebral cavernous malformations: A systematic review.

Background: Cerebral cavernous malformations (CCMs) are vascular abnormalities with a risk of intracerebral hemorrhage. Surgical resection is the first-line treatment for many cases, but deeply located lesions may pose high operative risks, leading to growing interest in medical management. Among these options, Vitamin D may be a potential candidate, and this study aims to evaluate its association with hemorrhage risk in patients with CCM. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed/MEDLINE, Scopus, Embase, and Cochrane databases were screened. Included studies were radiologically confirmed CCMs that assessed Vitamin D status and hemorrhagic outcomes. Results: Three observational studies involving 477 patients were analyzed. Hemorrhagic presentation appeared to be associated with lower median Vitamin D levels (25.5 ng/mL vs. 31.0 ng/mL; Conclusion: Although the current literature is limited, observational evidence suggests that Vitamin D deficiency may be associated with increased hemorrhage risk and greater disease severity in patients with CCMs, whereas supplementation may help stabilize and reduce hemorrhage risk. However, the certainty of evidence remains limited by observational designs and small sample sizes. Further randomized controlled trials with larger sample sizes are needed to establish the optimal dose and duration of Vitamin D supplementation in CCM management.