115: What Migraine Sufferers Need to Know About Metabolism & Insulin Resistance with Dr. Ben Bikman

Bikman emphasizes that migraines should be seen as a metabolic signal. Testing for insulin resistance is straightforward: a fasting insulin level and a HOMA-IR calculation (fasting glucose × fasting insulin / 405) provide a snapshot of insulin sensitivity. He mentions that many clinicians focus only on glucose or HbA1c, missing insulin resistance entirely. This protocol is a diagnostic gateway to the metabolic interventions he details later.

After presenting the strong dietary evidence, Bikman acknowledges that not everyone can go on a strict ketogenic diet immediately. He positions exogenous ketones as a quick, simple way to ‘test whether a metabolic intervention actually helps with your migraines because it's something you can do immediately.’ He strongly recommends choosing actual BHB, avoiding products that are only precursors, and mentions both ketone salts (electrolytes) and BHB acid forms. This practical step allows migraineurs to self-experiment with ketosis without dietary overhaul, potentially revealing whether energy instability is a major factor in their attacks.

Bikman mentions that very few drugs actually improve insulin sensitivity—most anti-diabetic medications simply lower glucose, sometimes worsening insulin resistance. Metformin is a rare exception. He points to a 2020 clinical trial showing that 500 mg twice daily reduced migraine frequency and severity on par with conventional migraine treatments. However, he quickly adds a caveat from previous episodes: metformin can blunt the positive adaptations to exercise, so it requires careful consideration in active individuals. This protocol is presented as a validated but not first-line metabolic tool, especially for those who cannot achieve sufficient diet-induced insulin sensitization.

Bikman explains that in insulin resistance, not only is biogenesis of new mitochondria impaired, but existing mitochondria become fragmented. His lab demonstrated that high insulin, through intermediate signaling, promotes mitochondrial fission, breaking the normally interconnected network into isolated chunks. These fragmented mitochondria produce less ATP per unit oxygen and generate more reactive oxygen species (ROS). This directly fuels the energy deficit that triggers cortical spreading depression, the wave of neuronal hyperactivity observed in migraine aura. The finding ties elevated insulin—common in insulin resistance—directly to the mitochondrial pathology seen in migraine brains.

Bikman traced the history to the early 1900s when the ketogenic diet was developed at Mayo Clinic for epilepsy. Physiologists noticed migraine improvement and published two key papers: a 1928 case series titled 'An experience with a ketogenic dietary in migraine' and a 1930 JAMA study of 50 adults with typical migraines. The 1928 report noted that about half the patients got relief, with a quarter achieving complete remission, especially those with metabolic irregularities like obesity. The 1930 study used 10–20 grams of carbs, 1 gram of protein per kilogram body weight, and the rest fat (often up to 200–300 grams daily), confirmed ketosis, and found attacks completely controlled in 14 patients and definitely improved in 25—about 80% responding. The authors at the time attributed success to stabilized blood sugar and reduced neuronal irritability, which Bikman notes is “shockingly predictive and accurate” given today’s understanding of insulin resistance, inflammation, and mitochondrial support by ketones. He laments that these findings were overlooked for decades, but now modern meta-analyses confirm similar ~80% reductions in attack frequency.