García-Gorrita Cayetano, San Onofre Nadia, Merino-Torres Juan F, Soriano Jose M
Food & Health Lab, Institute of Materials Science, University of Valencia, 46980 Paterna, Spain.
NUTRALiSS Research Group, Faculty of Health Sciences, Universitat Oberta de Catalunya, Rambla del Poblenou 156, 08018 Barcelona, Spain.
Nutrients. 2025 Aug 20;17(16):2699. doi: 10.3390/nu17162699.
Long-term obesity management consistently fails due to two major barriers: poor adherence, exacerbated by ultra-processed foods with addictive potential, and post-weight loss metabolic adaptation that reduces energy expenditure by approximately 500 kcal/day. Current paradigms-static diets and GLP-1 receptor agonists-address these barriers only partially. The objectives of this thesis-driven review are: (1) to conduct a focused evidence-mapping of Ketogenic-Mediterranean Diet (KMD) protocols; (2) to analyze why existing protocols have not explicitly countered metabolic adaptation; and (3) to present the Adaptive Ketogenic-Mediterranean Protocol (AKMP). Hybrid methodology-an argumentative narrative review anchored by a structured evidence-mapping search (PRISMA-style flow for transparency). We identified 29 studies implementing KMD protocols with significant weight loss and superior adherence. However, none of the published protocols explicitly implement anti-adaptive strategies, despite an estimated ketogenic metabolic advantage (≈100-300 kcal/day), context-dependent and more consistently observed in longer trials and during weight-maintenance settings. Unlike GLP-1 receptor agonists-which primarily suppress appetite, require ongoing pharmacotherapy, and do not directly mitigate the decline in energy expenditure-the AKMP couples a Mediterranean foundation for adherence with a ketogenic metabolic advantage and a biomarker-guided adjustment system explicitly designed to counter metabolic adaptation, aiming to improve the durability of weight loss and patient self-management. As a theoretical construct, the AKMP requires confirmation in prospective, controlled studies; accordingly, we outline a pragmatic 24-week pilot design in "Pragmatic Pilot Trial to Validate the AKMP-Incretin Sequencing".
长期肥胖管理一直未能成功,主要有两大障碍:一是依从性差,具有成瘾潜力的超加工食品加剧了这一问题;二是体重减轻后的代谢适应,使能量消耗每天减少约500千卡。当前的模式——静态饮食和胰高血糖素样肽-1受体激动剂——只能部分解决这些障碍。本论文驱动的综述的目的是:(1)对生酮-地中海饮食(KMD)方案进行有针对性的证据梳理;(2)分析现有方案为何未明确对抗代谢适应;(3)提出适应性生酮-地中海方案(AKMP)。采用混合方法——以结构化证据梳理搜索为基础的论证性叙述性综述(采用PRISMA式流程以确保透明度)。我们确定了29项实施KMD方案的研究,这些研究取得了显著的体重减轻和更高的依从性。然而,尽管估计生酮代谢优势约为每天100-300千卡,且在更长时间的试验和体重维持阶段更一致地观察到这种优势,但已发表的方案中没有一个明确实施抗适应策略。与主要抑制食欲、需要持续药物治疗且不能直接减轻能量消耗下降的胰高血糖素样肽-1受体激动剂不同,AKMP将基于地中海饮食的依从性基础与生酮代谢优势以及明确设计用于对抗代谢适应的生物标志物引导调整系统相结合,旨在提高体重减轻的持久性和患者自我管理能力。作为一种理论构想,AKMP需要在前瞻性对照研究中得到证实;因此,我们在“验证AKMP-肠促胰岛素序列的务实试点试验”中概述了一个务实的24周试点设计。