Research & Education

Predictors of Progression to Chronic Migraine

If you or someone you know experiences migraines, then you know these debilitating attacks are far more than mere headaches. The Migraine Research Foundation calls migraine “a neurological disease with extremely incapacitating neurological symptoms.” Attacks typically last between 4 and 72 hours, and in 15-20% of cases the head pain is preceded by neurological symptoms, such as visual disturbances, dizziness, extreme sensitivity to sound, light, touch and smell, and tingling or numbness in the extremities or face. An occasional migraine is bad enough, but what about chronic migraine? Recent research has identified factors that may predict the progression from episodic to chronic migraine. 


Chronic migraine (CM) is a subtype of chronic daily headache in which an individual experiences 15 or more migraine days per month. These severe attacks may leave those afflicted functionally disabled, unable to work, and with a poor quality of life. The research, published in Cephalalgia, the journal of the International Headache Society, was a systematic review and meta-analysis of observational cohort studies that reported risk factors for CM among people with episodic migraine. Eleven studies were eligible for inclusion. Researchers found “strong evidence” that having 10 or more migraine days per month was a predictor of progression to CM. Moderate evidence indicated that depression or 5 or more headache days increased risk, while having an annual household income greater than $50,000 was protective against progression to CM. Medication overuse and allodynia were also predictive of progression to CM but the evidence was deemed “very low quality.” 


On the surface, this information may not seem immediately helpful for healthcare professionals. After all, increasing a chronic migraine patient’s household income is not exactly within the scope of practice of doctors and nutritionists. However, being aware of the other risk factors for progression of episodic migraine to CM may help practitioners find effective interventions, and this can also help patients take a more active role in their own care.


Numerous nutritional and dietary interventions have been shown to reduce the frequency and severity of migraine. The herb feverfew has an impressive body of literature supporting its efficacy for this purpose. Riboflavin (vitamin B2) has also been studied for migraine prophylaxis. A systematic review found a consistent positive therapeutic effect in adults, but a mixed effect among pediatric and adolescent patients. A high dose—as much as 400 mg/day—may be needed to elicit a clinical effect. (This is the dose employed in several studies looking at riboflavin for migraine.)


Magnesium may also be a key player in migraine prophylaxis. It’s not much of an exaggeration to call magnesium a “miracle worker” nutrient. Adequate magnesium is critical for maintaining the electrolyte balance that contributes to proper polarization of neuronal membranes. (Overlapping pathophysiologic mechanisms have been noted between migraine and epilepsy, with seizures also being associated with abnormalities in neuronal polarization.) Researchers note that routine blood tests for magnesium status may not accurately reflect true body stores, since only about 2% is measurable in the extracellular space. (Bones store 67% of the body’s magnesium, with another 31% located intracellularly.) With this in mind, and noting that as many as half of all migraine sufferers may be magnesium deficient, researchers have gone so far as to say that “oral magnesium is warranted in all migraine sufferers.” 


Magnesium repletion may be especially important for women who experience migraines associated with their menstrual cycle. A small study of women with menstrual migraine found that 45% of participants had deficient levels of serum ionized magnesium during menstrual attacks, compared to 15% during non-menstrual attacks, 14% during menstruation without a migraine, and 15% between menstruations and between migraine attacks.


Beyond specific nutrients, a wholesale dietary change may offer relief for some chronic migraineurs. A previous article explored the beneficial role of ketogenic diets in reducing frequency and severity of migraine. Having originally been developed as a dietary therapy for medication-resistant epilepsy, it’s not a far stretch to see how “keto” could be helpful for those with chronic migraine considering the commonalities between the two conditions. A case report details twin sisters with high-frequency migraine (5-6 attacks per month) who started a ketogenic diet for the purpose of weight loss and experienced the unexpected “side-effect” of complete remission of migraines while they were in dietary ketosis. (They took several nutritional supplements as well, but at levels much lower than would be considered to have a pharmacological effect.)


Fluctuations in blood glucose and insulin may trigger migraines in susceptible people, so it’s not surprising that migraineurs have a high prevalence of insulin resistance and metabolic syndrome. In one study, out of 210 patients with metabolic syndrome, migraine prevalence was estimated at almost 12 percent in men and over 22 percent in women—higher than in the general population. A different survey showed that among 135 migraine patients, more than 30 percent had metabolic syndrome. Ketogenic diets are known to have a powerful lowering effect on blood glucose and insulin, so to the extent that either chronic or episodic migraine may be driven by elevations or rapid fluctuations in these, ketogenic diets may be helpful for stabilizing these contributors. 


The paper in Cephalalgia noted moderate evidence for depression as a risk factor for progression to CM. Emerging clinical evidence and mechanistic research suggests ketogenic diets may be useful for addressing depression and other mood disorders, so that may be another factor in favor of a migraineur trialing this very low-carb way of eating.