{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T23:58:06Z","timestamp":1781308686146,"version":"3.54.1"},"reference-count":150,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brain Research UK","award":["PhD Studentship"],"award-info":[{"award-number":["PhD Studentship"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Senior Fellowship (104612\/Z\/14\/Z)"],"award-info":[{"award-number":["Senior Fellowship (104612\/Z\/14\/Z)"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Sir Jules Thorn Charitable Trust","award":["Sir Jules Thorn Award for Biomedical Science"],"award-info":[{"award-number":["Sir Jules Thorn Award for Biomedical Science"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>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\u2019s deficiencies may provide an approach to ameliorate migraine.<\/jats:p>","DOI":"10.3390\/life11050415","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T21:35:39Z","timestamp":1619904939000},"page":"415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The Role of Metabolism in Migraine Pathophysiology and Susceptibility"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5560-802X","authenticated-orcid":false,"given":"Olivia","family":"Grech","sequence":"first","affiliation":[{"name":"Metabolic Neurology, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6314-4437","authenticated-orcid":false,"given":"Susan P.","family":"Mollan","sequence":"additional","affiliation":[{"name":"Birmingham Neuro-Ophthalmology Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin R.","family":"Wakerley","sequence":"additional","affiliation":[{"name":"Metabolic Neurology, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Department of Neurology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Trust, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5712-2776","authenticated-orcid":false,"given":"Daniel","family":"Fulton","sequence":"additional","affiliation":[{"name":"Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth G.","family":"Lavery","sequence":"additional","affiliation":[{"name":"Metabolic Neurology, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra J.","family":"Sinclair","sequence":"additional","affiliation":[{"name":"Metabolic Neurology, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham B15 2TH, UK"},{"name":"Department of Neurology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Trust, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"James","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/S1474-4422(18)30322-3","article-title":"Global, regional, and national burden of migraine and tension-type headache, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"17","author":"Stovner","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1129-2377-14-1","article-title":"Migraine: The seventh disabler","volume":"14","author":"Steiner","year":"2013","journal-title":"J. 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