Abstract
BackgroundBrain 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.Main bodyWe 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.ConclusionThe 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.
Highlights
Brain amyloid deposition and neurofibrillary tangles in Alzheimer’s disease (AD) are associated with complex neuroinflammatory reactions such as microglial activation and cytokine production
The core characteristics of the Ketogenic diet (KD) are the association of a high amount of fat, with low carbohydrate intake, usually a macronutrient ratio of fat to protein and carbohydrate combined equal to 3–4:1
The mechanisms leading to a benefic effect on cognition could be due to the (i) modification in neurotransmitter transport pathway and/or synaptic maintenance in ageing WT animals and (ii) improvement of abnormal features (Aβ load or neuroinflammation) in AD mouse models
Summary
Despite the growing interest for KD in AD over the last years, only few interventional studies in animals or humans clearly addressed the subject. Older adults or animal studies, it was often associated with a significant weight loss This consequence could play an adverse effect on muscle performance (sarcopenia) or even on cognitive decline. In humans, notwithstanding the high heterogeneity of the studies and methodological issues discussed above, most of the published studies could suggest improved cognitive outcomes (memory, executive function or global cognition) with KS or KD, regardless of the severity of cognitive impairment. Both interventions seemed acceptable for included subjects and show efficacy to achieve ketosis.
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