The Hypometabolic State of the Migraine Brain: Is a Ketogenic Diet the Answer?

Migraine pathophysiology involves a constellation of metabolic abnormalities. These interlinked contributory factors include mitochondrial dysfunction, an altered gut microbiome, neuroinflammation, oxidative stress, weight imbalance, and altered glucose metabolism. The ketogenic diet is an emerging therapy which may restore hypometabolism seen in chronic migraine. We describe contributions of metabolic dysfunction to chronic migraine pathophysiology and discuss the role of ketogenic diet therapy to improve cerebral metabolism.

A literature search of articles from OVID Medline, Embase, and Cochrane Library were reviewed until May 6, 2024. A total of 50 articles were included comprising case reports, case series, observational clinical trials, and narrative review articles.

Migraine pathophysiology involves significant hypometabolism, seen on functional imaging studies, so therapeutics which target these underlying deficiencies may ameliorate chronic migraine symptoms. The ketogenic diet reduces migraine days, pain intensity, and acute analgesic use. Current studies are limited by small sample sizes, inconsistent methodology precluding direct comparison between studies or pooling of results, and limited longitudinal follow-up.

While there is biological plausibility to reason that a ketogenic diet could correct metabolic mismatch in people with migraine, further randomized clinical trials with larger sample sizes are required to confirm the positive results of preliminary, uncontrolled studies.