Migraine can be regarded as a conserved, adaptive response that occurs in genetically predisposed individuals with a mismatch between the brain’s energy reserve and workload. Given the high prevalence of migraine, genotypes associated with the condition seem likely to have conferred an evolutionary advantage. An increasing amount of 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 authors describe the evidence for abnormalities in energy metabolism and mitochondrial function in migraine, with a focus on clinical data, and consider the relationship of these abnormalities with the abnormal sensory processing and cerebral hyper-responsivity observed in migraine. The authors consider potential mechanisms by which metabolic abnormalities could generate attacks and highlight potential treatments that target cerebral metabolism, such as nutraceuticals, ketone bodies and dietary interventions.
- Prevalent triggers of migraine attacks can all be linked to unbalanced cerebral energy metabolism and/or oxidative stress.
- Magnetic resonance spectroscopy studies have shown that mitochondrial phosphorylation potential and ATP are decreased in the brains of people with migraine between attacks. Glucose (and lipid) metabolism and mitochondrial functions are abnormal in the peripheral blood.
- Among patients with migraine, various single nucleotide polymorphisms are present in non-coding mitochondrial DNA and nuclear-encoded mitochondrial proteins; common variants associated with migraine are functionally involved in mitochondrial metabolism.
- Metabolic enhancers, such as riboflavin and coenzyme Q10, and dietary or pharmacological ketogenesis improve migraine but novel, more efficient metabolic strategies are needed.
- Experimental studies indicate a link between cerebral energy disequilibrium and cortical spreading depression and/or trigeminovascular system activation; calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide could also help restore energy homeostasis.
- Migraine can be regarded as a conserved, adaptive response that occurs in individuals with a genetic predisposition and a mismatch between the brain’s energy reserve and workload.
Gross EC, Lisicki M, Fischer D, Sándor PS, Schoenen J: The metabolic face of migraine – from pathophysiology to treatment. Nature Rev. Neurol. [Epub ahead of print, Oct. 4, 2019; doi: 10.1038/s41582-019-0255-4].