Cavestro Cinzia
Headache Centre, Department of Neurology, ASL CN2, Community Health Center-Former San Lazzaro Hospital, 12051 Alba, Italy.
Brain Sci. 2025 Apr 29;15(5):474. doi: 10.3390/brainsci15050474.
Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, it has been known that certain foods can trigger migraine attacks, which led for many years to the recommendation of elimination diets-now understood to primarily target histamine-rich foods. Over the past two decades, attention has shifted toward underlying metabolic disturbances, leading to the development of dietary approaches specifically aimed at addressing these dysfunctions.
A scoping literature review was conducted using PubMed and Embase to evaluate the relationships among migraine, insulin-related mechanisms, neurogenic inflammation, and dietary interventions. Initial searches focused on "MIGRAINE AND (neurogenic inflammation)" (2019-15 April 2025), followed by expanded searches from 1950 onward using terms such as "MIGRAINE AND (insulin, insulin resistance, hyperinsulinism)", and "MIGRAINE AND (diet, dietary, nutrition, nutritional)". A specific search also targeted "(INSULIN OR insulin resistance OR hyperinsulinism) AND (neurogenic inflammation)". Abstracts were screened, full texts were retrieved, and duplicates or irrelevant publications were excluded. No filters were applied by article type or language. Systematic reviews and meta-analyses were prioritized when available.
Migraine pathogenesis involves trigeminovascular system activation, neurogenic inflammation mediated by CGRP and PACAP, immune dysregulation, mast cell activation, and cortical spreading depression (CSD). Emerging evidence highlights significant associations between migraine, insulin resistance, and hyperinsulinism. Hyperinsulinism contributes to migraine through TRPV1 sensitization, increased CGRP release, oxidative stress, mitochondrial dysfunction, and systemic inflammation. Metabolic dysfunction, including obesity and insulin resistance, exacerbates migraine severity and frequency. Dietary interventions, particularly anti-inflammatory, Mediterranean, and ketogenic diets, show promise in reducing migraine frequency and severity through mechanisms involving reduced inflammation, oxidative stress, improved mitochondrial function, and glucose metabolism stabilization.
The interplay between insulin resistance, metabolic dysfunction, and neuroinflammation is crucial in migraine pathophysiology. Targeted dietary interventions, including ketogenic and Mediterranean diets, demonstrate significant potential in managing migraines, emphasizing the need for personalized nutritional strategies to optimize therapeutic outcomes.
偏头痛是一种常见的神经系统疾病，其特征为反复出现的头痛，并伴有自主神经和神经症状，在全球范围内对生活质量产生重大影响。其发病机制涉及遗传、神经、炎症和代谢因素，胰岛素抵抗和代谢功能障碍越来越被认为是重要的促成因素。从历史上看，人们就知道某些食物会引发偏头痛发作，这导致多年来一直推荐采用排除饮食法——现在认为主要针对富含组胺的食物。在过去二十年中，注意力已转向潜在的代谢紊乱，从而产生了专门旨在解决这些功能障碍的饮食方法。
使用PubMed和Embase进行了一项范围综述，以评估偏头痛、胰岛素相关机制、神经源性炎症和饮食干预之间的关系。最初的搜索聚焦于“偏头痛与（神经源性炎症）”（2019年4月15日至2025年），随后从1950年起使用“偏头痛与（胰岛素、胰岛素抵抗、高胰岛素血症）”以及“偏头痛与（饮食、膳食、营养、营养的）”等术语进行扩展搜索。还进行了一项特定搜索，目标是“（胰岛素或胰岛素抵抗或高胰岛素血症）与（神经源性炎症）”。对摘要进行筛选，检索全文，并排除重复或不相关的出版物。未按文章类型或语言应用筛选条件。如有系统评价和荟萃分析，则优先选用。
偏头痛的发病机制涉及三叉神经血管系统激活、由降钙素基因相关肽（CGRP）和垂体腺苷酸环化酶激活肽（PACAP）介导的神经源性炎症、免疫失调、肥大细胞激活和皮层扩散性抑制（CSD）。新出现的证据突出了偏头痛、胰岛素抵抗和高胰岛素血症之间的显著关联。高胰岛素血症通过瞬时受体电位香草酸亚型1（TRPV1）致敏、CGRP释放增加、氧化应激、线粒体功能障碍和全身炎症导致偏头痛。包括肥胖和胰岛素抵抗在内的代谢功能障碍会加剧偏头痛的严重程度和发作频率。饮食干预，特别是抗炎饮食、地中海饮食和生酮饮食，通过减少炎症、氧化应激、改善线粒体功能和稳定葡萄糖代谢等机制，在降低偏头痛频率和严重程度方面显示出前景。
胰岛素抵抗、代谢功能障碍和神经炎症之间的相互作用在偏头痛病理生理学中至关重要。包括生酮饮食和地中海饮食在内的针对性饮食干预在偏头痛管理中显示出巨大潜力，强调了制定个性化营养策略以优化治疗效果的必要性。
