INTRODUCTION
Vasovagal syncope (VVS) is a common and potentially debilitating condition with limited treatment strategies, particularly for frequent VVS.1, 2 VVS, the most common type of syncope,1, 2 accounts for 0.8-3.0% of emergency room visits and 1% of hospital admissions.3-6 VVS can be a life disturbing condition,7 and the quality of life of patients with recurrent VVS can be as impaired as the quality of life of patients with chronic diseases like rheumatoid arthritis8, 9 and chronic low back pain9. Furthermore, 33% of patients with VVS incur injuries due to their episodes, with more fragility among older patients.10 In addition to the lost productivity and other indirect costs, VVS directly imposes 2.4 billion dollars on the United States health system for hospitalization of patients with VVS annually.8, 11 Despite this enormous psychosocial and financial burden of VVS, there are scarce treatment options, especially for patients with frequent VVS.
The current guidelines suggest that improving our knowledge about the pathophysiology of VVS is critical in developing novel preventive and therapeutic strategies to reduce its burden.1, 2Therefore, it is encouraged to investigate the possible mechanisms as the basis of possible future interventions for treating VVS or at least a subgroup of these patients.12, 13 Increased serum levels of catecholamines might play a role in the pathophysiology of VVS,14-19 and vitamin B12 deficiency may cause increased catecholamines through biochemically plausible mechanisms.20, 21 Moreover, there is some evidence on the association of vitamin B12 deficiency and VVS in pediatric patients;22, 23 however, no methodologically rigorous study has ever investigated this possible association in adult or elderly patients with VVS.24 Furthermore, concurrent evaluation of vitamin B12 and folate, as two vitamins with interwoven biochemical pathways, is encouraged.22
In this case-control study, we aimed to investigate the possible association of vitamin B12 and folate deficiency with VVS in adults from the syncope unit of a tertiary referral hospital and a population-based cohort.