Deakin University, IMPACT Strategic Research Centre, Barwon Health, School of Medicine, Geelong, Victoria, Australia.
Department of Psychiatry, Chulalongkorn University, Faculty of Medicine, Bangkok, Thailand.
Eur Psychiatry. 2020 Jan 31;63(1):e8. doi: 10.1192/j.eurpsy.2019.13.
Nutritional ketosis, induced via either the classical ketogenic diet or the use of emulsified medium-chain triglycerides, is an established treatment for pharmaceutical resistant epilepsy in children and more recently in adults. In addition, the use of oral ketogenic compounds, fractionated coconut oil, very low carbohydrate intake, or ketone monoester supplementation has been reported to be potentially helpful in mild cognitive impairment, Parkinson's disease, schizophrenia, bipolar disorder, and autistic spectrum disorder. In these and other neurodegenerative and neuroprogressive disorders, there are detrimental effects of oxidative stress, mitochondrial dysfunction, and neuroinflammation on neuronal function. However, they also adversely impact on neurone-glia interactions, disrupting the role of microglia and astrocytes in central nervous system (CNS) homeostasis. Astrocytes are the main site of CNS fatty acid oxidation; the resulting ketone bodies constitute an important source of oxidative fuel for neurones in an environment of glucose restriction. Importantly, the lactate shuttle between astrocytes and neurones is dependent on glycogenolysis and glycolysis, resulting from the fact that the astrocytic filopodia responsible for lactate release are too narrow to accommodate mitochondria. The entry into the CNS of ketone bodies and fatty acids, as a result of nutritional ketosis, has effects on the astrocytic glutamate-glutamine cycle, glutamate synthase activity, and on the function of vesicular glutamate transporters, EAAT, Na+, K+-ATPase, Kir4.1, aquaporin-4, Cx34 and KATP channels, as well as on astrogliosis. These mechanisms are detailed and it is suggested that they would tend to mitigate the changes seen in many neurodegenerative and neuroprogressive disorders. Hence, it is hypothesized that nutritional ketosis may have therapeutic applications in such disorders.
营养性酮症，通过经典生酮饮食或使用乳化中链甘油三酯诱导，是一种已被确立的治疗儿童药物难治性癫痫的方法，最近也被用于治疗成人癫痫。此外，口服生酮化合物、分馏椰子油、极低碳水化合物摄入或酮单酯补充，已被报道在轻度认知障碍、帕金森病、精神分裂症、双相情感障碍和自闭症谱系障碍中可能有帮助。在这些和其他神经退行性和神经进行性疾病中，氧化应激、线粒体功能障碍和神经炎症对神经元功能有不利影响。然而，它们也对神经元-胶质细胞相互作用产生不利影响，破坏小胶质细胞和星形胶质细胞在中枢神经系统（CNS）稳态中的作用。星形胶质细胞是中枢神经系统脂肪酸氧化的主要部位；由此产生的酮体构成了在葡萄糖限制环境中神经元氧化燃料的重要来源。重要的是，星形胶质细胞和神经元之间的乳酸穿梭依赖于糖原分解和糖酵解，这是由于负责乳酸释放的星形胶质细胞丝状伪足太窄而无法容纳线粒体。由于营养性酮症，酮体和脂肪酸进入中枢神经系统，对星形胶质细胞谷氨酸-谷氨酰胺循环、谷氨酸合酶活性以及囊泡谷氨酸转运体、EAAT、Na+、K+-ATP 酶、Kir4.1、水通道蛋白-4、Cx34 和 KATP 通道的功能有影响，以及对星形胶质细胞增生的影响。这些机制被详细阐述，并且认为它们可能有助于减轻许多神经退行性和神经进行性疾病中观察到的变化。因此，有人假设营养性酮症可能在这些疾病中有治疗应用。
