Refractory migraine is a particularly disabling form of chronic migraine, unresponsive to multiple prophylactic strategies. Ketogenic diet (KD) is useful to treat migraine but poorly tested for refractory migraine.

We started exploring the efficacy and safety of KD, as compared to a non-ketogenic dietary regimen similar in reduction of carbohydrate intake (low-carb diet, LCD), in refractory migraine. Secondary objective was to explore whether ketones have a role in the prophylaxis induced by KD on migraine.

In a first trial, 22 patients with refractory migraine were included and completed the study. Thirteen (mean age 36.8 ± 12.9 years, 11 females, 2 males) were assigned to the KD arm and eight (mean age 50.9 ± 10.8 years; all females), not eligible for KD, to LCD. Patients treated with KD showed a significant reduction in the frequency of migraine attacks, intensity of headache, and amount of drug intake. No significant benefit was seen in the LCD group. A relationship between ketone production and effect on headache was observed among patients with a good response to KD. In a second study, additional 31 refractory migraineurs were treated with these two dietary regimens, 26 with the same KD scheme and 5 with a LCD. Results were comparable with those of the first study.

KD might be a useful option in refractory migraine. Ketones seem to have a role in migraine modulation and their regular measurement might be useful to monitor KD in migraineurs. Larger, randomized, and controlled trials are needed to confirm these data.