A Randomized Double-Blind, Cross-Over Trial of very Low-Calorie Diet in Overweight Migraine Patients: A Possible Role for Ketones?

Cherubino Di Lorenzo,Gianluca Coppola,Vincenzo Parisi,Annarita Vestri,Jean Schoenen,Alessandro Pinto,Lorenzo M Donini,Giulio Sirianni,Mariano Serrao,Francesco Pierelli,Roberta Ienca,Alessandra Spagnoli,Giorgio Di Lorenzo

doi:10.3390/nu11081742

Abstract

Here we aimed at determining the therapeutic effect of a very low-calorie diet in overweight episodic migraine patients during a weight-loss intervention in which subjects alternated randomly between a very low-calorie ketogenic diet (VLCKD) and a very low-calorie non-ketogenic diet (VLCnKD) each for one month. In a nutritional program, 35 overweight obese migraine sufferers were allocated blindly to 1-month successive VLCKD or VLCnKD in random order (VLCKD-VLCnKD or VLCnKD-VLCD). The primary outcome measure was the reduction of migraine days each month compared to a 1-month pre-diet baseline. Secondary outcome measures were 50% responder rate for migraine days, reduction of monthly migraine attacks, abortive drug intake and body mass index (BMI) change. Only data from the intention-to-treat cohort (n = 35) will be presented. Patients who dropped out (n = 6) were considered as treatment failures. Regarding the primary outcome, during the VLCKD patients experienced −3.73 (95% CI: −5.31, −2.15) migraine days respect to VLCnKD (p < 0.0001). The 50% responder rate for migraine days was 74.28% (26/35 patients) during the VLCKD period, but only 8.57% (3/35 patients) during VLCnKD. Migraine attacks decreased by −3.02 (95% CI: −4.15, −1.88) during VLCKD respect to VLCnKD (p < 0.00001). There were no differences in the change of acute anti-migraine drug consumption (p = 0.112) and BMI (p = 0.354) between the 2 diets. A VLCKD has a preventive effect in overweight episodic migraine patients that appears within 1 month, suggesting that ketogenesis may be a useful therapeutic strategy for migraines.

Highlights

The ketogenic diet (KD) constitutes high-fat, adequate protein, and low-carbohydrate, and has been proven to be efficacious for the treatment of drug-resistant epilepsy [1]
During the very low-calorie ketogenic diet (VLCKD), patients experienced −3.02 migraine attacks in comparison to very low-calorie non-ketogenic diet (VLCnKD) treatment (Figure 2B)
The most striking result of our study is that a 4-week period VLCKD, despite inducing similar weight loss and glycemic profile, was significantly more effective than VLCnKD in preventing migraine attacks, as evidenced by a decrease in the frequency of migraine days and attacks, and a greater than

Summary

Introduction

The ketogenic diet (KD) constitutes high-fat, adequate protein, and low-carbohydrate, and has been proven to be efficacious for the treatment of drug-resistant epilepsy [1]. KD showed promising results for treating other neurological conditions (for example, glioblastomamultiforme, malignant glioma, and Alzheimer’s disease) [2]. Migraine is one of the many pathological conditions that has been reported to benefit from KD. In 1930, Barborka, one of the pioneers who popularized KD among adults, reported outstanding improvement of migraines following the initiation of KD in a study of 50 patients [4]. In 2006, a regimen of low-carbohydrate and low-fat diets based on food replacements for rapid weight loss in a cohort of patients with chronic migraine demonstrated concomitant improvement of their migraines. We demonstrated an analogous migraine-alleviating effect on a couple of overweight sisters who experienced migraines, and who followed a cyclic low-fat low-carbohydrate diet. The diet was followed in 3 repetitive phases, one phase every 3 months, during which the patients exhibited stable ketosis, as confirmed by urinary strips for the detection of ketosis, and reported improvements of their migraines [6]

Methods

Results

Conclusion