Discussion
obesity, hypometabolic, ketosis, hyperexcitable, migraine, Migraine, weight loss
OBESITY, KETOSIS, PATHOPHYSIOLOGY, MIGRAINE, MIGRAINE
This randomized controlled study brings new evidence of the efficacy of VLCKD in the management of high frequency episodic migraine in patients with overweight and obesity [Importantly, monthly migraine days (MMD) were significantly reduced by VLCKD, as compared with the control diet, at all time points during the study. At week 8, a significant difference in MMDs emerged between the two dietary groups (VLCKD − 6.4 ± 4.8 vs HBD − 2.2 ± 5.0, p = 0.008). A further increased mean reduction in MMD was observed in the VLCKD group at week 12, well beyond the end of ketosis phase, as well as at week 24, when all patients were on same dietary regimen (HBD). These results are even more interesting when considering that patients allocated to VLCKD had a more complex migraine picture compared to those allocated to HBD, documented by significantly higher baseline MMDs. Notably, weight loss and visceral fat reduction were also greater in VLCKD than HBD and persisted after ketosis cessation.Concomitantly, VLCKD induced a significantly higher weight loss and visceral fat reduction (Fig. The therapeutic effect of ketone bodies in migraine relies on multiple mechanisms. Migraine brain is hyperexcitable and hypometabolic. Hence, ketone bodies represent a strategic and more efficacious metabolic fuel source, able to counteract defective neuronal glucose metabolism and to restore brain energy production in patients with migraine [Also quality of life was improved during VLCKD treatment, particularly in several aspects of daily life, as general health (5.7 ± 11.7, p = 0.023), physical activity (10.6 ± 18.5, p = 0.009) and social relationship (12.2 ± 22.7, p = 0.013). When compared with HBD group, adherence to diet was higher in VLCKD group until week 8 (Fig. A hallmark of VLCKD is represented by a prolonged mild ketosis state, which allows an acceptable tolerance to the nutritional regimen due to its anorexigenic actions, and to its favourable effects on general well-being, and only transient mild side effects, [The present study documents anti-inflammatory effects in patients treated with VLCKD but not in those receiving HBD. In the former, we observed a reduction in white blood cells count and neutrophils at all study time points, in keeping with previous reports [Lymphocytes subpopulations levels were not significantly altered by VLCKD, confirming the preservation of specific immune responses after this dietary regimen. However, Treg/Th17 ratio was increased in VLCKD group, and reduced in HBD group, even if these effects did not reach statistical significance (Fig. We then wanted to explore the impact of both dietary regimens on plasma aldosterone, renin and salt balance, given the strong implication of RAAS in the pathophysiology of both migraine and obesity. Interestingly, VLCKD significantly increased aldosterone plasma level at week 8 (p = 0.003, Fig. A strenght of this study is represented by the multidisciplinary team (including neurologists, nutritionists, psychologists and endocrinologists) who followed patients during the clinical trial, which increased adherence to the study. Importantly, the study was characterised by a long term follow up, since patients were followed for at least 24 weeks, well beyond the end of the ketosis phase, and included a special population of patients, presenting a high risk of chronicization. Finally, we evaluated the impact of nutritional treatments on the response of the immune system (with particular regard to inflammatory and regulatory T cells), and RAAS adaptation to dietary regimens and weight loss.This study has several limitations: first of all the number of subjects enrolled is small, with several treatement discontinuations, mostly due to COVID pandemic. Moreover, our patients’ population included a small proportion of male patients (5.1%), in line with migraine epidemiology [