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.