Biochemical mechanism of VVS in vitamin B12/folate deficiency
The pathophysiology of VVS is poorly understood, and there are ongoing
efforts to address this gap in order to introduce novel treatment
strategies for this potentially debilitating
condition.30 According to a
hypothesis,31 VVS is characterized by an over
activation of the parasympathetic nervous system in response to an
exaggerated activation of the sympathetic nervous system, demonstrated
by increased serum levels of catecholamines.14-19Patients with VVS have normal resting serum
levels of catecholamines; nevertheless, their serum catecholamines start
to rise in response to head-up tilting, a similar situation to an actual
syncopal episode. 14-19Ineffective metabolism of
released catecholamines is suggested to play a key role in the increased
levels of these metabolites.21 There are two main
pathways for the metabolism of catecholamines,
catechol-O-methyltransferase (COMT)- and monoamine oxidase
(MAO)-dependent pathways. The COMT pathway requires S-adenosyl
methionine (SAM), of which normal levels necessitate sufficient serum
levels of vitamin B12 and folate.20 In fact, vitamin
B12 and folate are cofactors for the degradation of catecholamines.
Hence, vitamin B12 or folate deficiency can decrease SAM, decrease
COMT-dependent degradation of catecholamines, increase serum levels of
catecholamines in response to VVS triggers, and lead to syncope.