The role of metabolism in migraine pathophysiology and susceptibility

Migraine is a highly prevalent and disabling primary headache disorder, however its pathophysiology remains unclear, hindering successful treatment. A number of key secondary headache disorders have headaches that mimic migraine. Evidence has suggested a role of mitochondrial dysfunction and an imbalance between energetic supply and demand that may contribute towards migraine susceptibility. Targeting these deficits with nutraceutical supplementation may provide an additional adjunctive therapy. Neuroimaging techniques have demonstrated a metabolic phenotype in migraine similar to mitochondrial cytopathies, featuring reduced free energy availability and increased metabolic rate. This is reciprocated in vivo when modelling a fundamental mechanism of migraine aura, cortical spreading depression. Trials assessing nutraceuticals successful in the treatment of mitochondrial cytopathies including magnesium, coenzyme q10 and riboflavin have also been conducted in migraine. Although promising results have emerged from nutraceutical trials in patients with levels of minerals or vitamins below a critical threshold, they are confounded by lacking control groups or cohorts that are not large enough to be representative. Energetic imbalance in migraine may be relevant in driving the tissue towards maximum metabolic capacity, leaving the brain lacking in free energy. Personalised medicine considering an individual’s deficiencies may provide an approach to ameliorate migraine.