Implications for practice and research
Our findings may support measuring serum vitamin B12 in adult patients with frequent VVS and treating existing deficiencies, particularly when other treatment strategies with a class I recommendation like increased salt and fluid intake are not effective.1, 2 The possible association of refractory and recurrent VVS with vitamin B12 deficiency, a potential clinical benefit of treating vitamin B12 deficiency,24, 32 and also the safety of its measurement and administration, encourage this approach in daily clinical practice; nonetheless, future research is warranted to define the role of vitamin B12 deficiency in VVS clearly. The current evidence and our findings call for future studies to investigate the association of vitamin B12 deficiency with VVS in adult patients with frequent VVS. Furthermore, future randomized controlled trials will determine the effectiveness of supplementation with vitamin B12 in these patients. The current evidence of this intervention lacks an appropriate control group,24, 32 which limits its authenticity and generalizability.