Seasonal and geographic variations in vitamin D levels among patients with familial Mediterranean fever: a systematic review and meta-analysis.

INTRODUCTION

Familial Mediterranean fever (FMF) is an autoinflammatory condition caused by a single-gene mutation, inherited in an autosomal recessive pattern, and characterized by recurrent episodes of self-limited inflammation. Studies suggest that vitamin D levels may be lower in FMF patients, but evidence remains unclear. This study aims to assess the relationship between FMF and serum vitamin D levels.

METHOD: We followed PRISMA guidelines and registered the protocol in PROSPERO (CRD420261299635). We searched PubMed, Scopus, and Web of Science up to December 2025 for observational studies comparing FMF patients with healthy controls. Our main outcomes were serum 25-hydroxyvitamin D, parathyroid hormone (PTH), and C-reactive protein (CRP). We combined the data as mean differences using a random-effects model.

RESULT: Ten studies (563 FMF patients) were included. The pooled analysis showed a significant drop in vitamin D levels in FMF patients compared to healthy controls. However, there was high heterogeneity between studies (I2 = 89%), with a wide 95% prediction interval (- 2.7 to 0.46). During the summer, we found no difference in vitamin D levels, though Egyptian patients had lower levels than Turkish patients. There were no significant differences in PTH or CRP.

CONCLUSION

Seasonal and regional factors play a significant role in determining vitamin D levels among FMF patients, with lower levels observed in winter and in Egyptian patients. Because of the high heterogeneity and low certainty, larger studies are needed to confirm the findings. Key Points • The first meta-analysis to compare vitamin D level between FMF patients and healthy individuals, findings show severe deficit in vitamin D level. • Many factors contribute to this decrease in vitamin D, starting from seasonal and geographical distribution and autoinflammatory state of FMF, making the fact of low vitamin D among FMF patients is highly individualized according to these prescribed factors. • Despite vitamin D deficit, there is no significant difference in PTH or CRP level.