Vitamin D deficiency and risk of recurrent aphthous stomatitis: updated meta-analysis with trial sequential analysis

<jats:sec><jats:title>Background</jats:title><jats:p>Growing evidence suggests a significant association between vitamin D deficiency and RAS. Hence, the present meta-analysis and trial sequential analysis sought to investigate the potential association between low serum vitamin D levels and RAS.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>PubMed, Scopus, Embase, and Web of Science were comprehensively searched on December 1<jats:sup>st</jats:sup>, 2022 to retrieve all relevant studies. The grey literature was also searched via ProQuest. All case-control studies on the association between vitamin D and RAS were considered. The quality appraisal of the included studies was done using Newcastle-Ottawa scale. RevMan 5.0 and trial sequential analysis (TSA) programs were used for analyses.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 14 case-control studies with 1468 subjects (721 RAS patients and 747 controls) were included. The pooled data revealed a significant association between low serum levels of vitamin D and the risk of RAS (mean difference = – 8.73, 95% CI: – 12.02 to – 5.44, I<jats:sup>2</jats:sup> = 94%, P &amp;lt; 0.00001). Additionally, TSA findings indicated that the current studies surpassed the required information size, confirming that the differences were reliable.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The available evidence suggests that Vitamin D deficiency may have a role in the pathogenesis of RAS. Therefore, evaluation of vitamin D should be considered in RAS patients. Additionally, the results support the possibility of using vitamin D supplements in the management of RAS patients with inadequate serum levels of vitamin D. Future interventional studies are required to evaluate the benefits of vitamin D replacement in prevention and treatment of RAS.</jats:p></jats:sec>