A wave of recent research has begun to explore theories involving metabolic causes for migraine that promise new therapeutic directions and plausible strategies to prevent future migraines.
Migraine has been a known medical entity for centuries, and yet there is still little understanding of the underlying mechanisms. New research indicates that may be because efforts have focused largely on pathologies of the brain, when the origins of migraine may be initiated at a much broader cellular level in the endocrine system. Neurovascular mechanisms of migraine have long been studied, but new evidence suggests that migraine is very likely a type of energy-deficit syndrome with mitochondrial dysfunction that leads to a cascade of neurologic events.1
The advent of magnetic resonance spectroscopy (MRS) has allowed measurement of many substances involved in energy metabolism, including lactate, magnesium, and adenosine triphosphate, which have implications in the expression of migraine symptoms.1,2 Studies using MRS have identified pathophysiology in the hypothalamus, thalamus, and brain-stem that support an endocrine etiology for migraine.2
A 2019 review by Gross et al1 published in Nature Reviews explored this theory further, stating that recent clinical evidence “suggests that migraine is a response to cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity and that the attack itself helps to restore brain energy homeostasis and reduces harmful oxidative stress levels.” The review described peripheral abnormalities of mitochondrial enzyme function and glucose metabolism and oxidative stress as specific responses to external triggers that can result in migraine in individuals who exhibit cerebral hyperresponsiveness and abnormalities of central sensory processing.1-3
“Several metabolic pathways are likely to be involved depending on the genetic profile of the patient,” coauthor Jean Schoenen, MD, PhD, a clinician at the Headache Research Unit at Citadelle Hospital and Professor of Functional Neuroanatomy and Clinical Professor of Neurology at the University of Liege in Belgium told Neurology Advisor.