INSERM U1144 Optimisation Thérapeutique en Neuropsychopharmacologie, Université de Paris, Paris, France.
Centre de Neurologie Cognitive/CMRR Paris Nord Ile de France, APHP Nord Université de Paris, Lariboisière Hospital 200, rue du Faubourg Saint Denis, 75010, Paris, France.
Alzheimers Res Ther. 2020 Apr 14;12(1):42. doi: 10.1186/s13195-020-00615-4.
Brain amyloid deposition and neurofibrillary tangles in Alzheimer's disease (AD) are associated with complex neuroinflammatory reactions such as microglial activation and cytokine production. Glucose metabolism is closely related to neuroinflammation. Ketogenic diets (KDs) include a high amount of fat, low carbohydrate and medium-chain triglyceride (MCT) intake. KDs lead to the production of ketone bodies to fuel the brain, in the absence of glucose. These nutritional interventions are validated treatments of pharmacoresistant epilepsy, consequently leading to a better intellectual development in epileptic children. In neurodegenerative diseases and cognitive decline, potential benefits of KD were previously pointed out, but the published evidence remains scarce. The main objective of this review was to critically examine the evidence regarding KD or MCT intake effects both in AD and ageing animal models and in humans.
We conducted a review based on a systematic search of interventional trials published from January 2000 to March 2019 found on MEDLINE and Cochrane databases. Overall, 11 animal and 11 human studies were included in the present review. In preclinical studies, this review revealed an improvement of cognition and motor function in AD mouse model and ageing animals. However, the KD and ketone supplementation were also associated with significant weight loss. In human studies, most of the published articles showed a significant improvement of cognitive outcomes (global cognition, memory and executive functions) with ketone supplementation or KD, regardless of the severity of cognitive impairments previously detected. Both interventions seemed acceptable and efficient to achieve ketosis.
The KD or MCT intake might be promising ways to alter cognitive symptoms in AD, especially at the prodromal stage of the disease. The need for efficient disease-modifying strategies suggests to pursue further KD interventional studies to assess the efficacy, the adherence to this diet and the potential adverse effects of these nutritional approaches.
阿尔茨海默病（AD）中的脑淀粉样蛋白沉积和神经原纤维缠结与复杂的神经炎症反应有关，如小胶质细胞激活和细胞因子产生。葡萄糖代谢与神经炎症密切相关。生酮饮食（KDs）包括高脂肪、低碳水化合物和中链甘油三酯（MCT）的摄入。KD 导致酮体的产生以在没有葡萄糖的情况下为大脑提供燃料。这些营养干预措施是治疗耐药性癫痫的有效方法，因此导致癫痫儿童的智力发育更好。在神经退行性疾病和认知能力下降中，以前曾指出 KD 的潜在益处，但发表的证据仍然很少。本综述的主要目的是批判性地检查 KD 或 MCT 摄入对 AD 和衰老动物模型以及人类的影响的证据。
我们进行了一项综述，基于对从 2000 年 1 月至 2019 年 3 月发表的 MEDLINE 和 Cochrane 数据库中的干预性试验进行了系统搜索。总的来说，本综述包括 11 项动物研究和 11 项人类研究。在临床前研究中，本综述显示 KD 或 MCT 摄入可改善 AD 小鼠模型和衰老动物的认知和运动功能。然而，KD 和酮补充剂也与显著的体重减轻有关。在人类研究中，大多数已发表的文章表明，酮补充或 KD 与认知结果的显著改善相关，无论以前检测到的认知障碍的严重程度如何。这两种干预措施似乎都可以接受且有效地达到酮症状态。
KD 或 MCT 的摄入可能是改变 AD 认知症状的有前途的方法，特别是在疾病的前驱期。需要有效的疾病修饰策略，建议进一步进行 KD 干预研究，以评估这些营养方法的疗效、对这种饮食的依从性和潜在的不良反应。
