Personalized nutritional ketosis through a whole‐food low‐carb diet, medium chain triglycerides, and other ketogenic strategies for people with mild cognitive impairment and Alzheimer’s disease

Abstract

AbstractInsulin resistance with abnormal brain glucose uptake, a brain‐energy gap, and neuroinflammation are common in the aging brain and are exaggerated in people with Alzheimer’s disease (AD) and in some people with MCI (Cunnane Nature Reviews Drug Discovery 2020). Ketones are an alternative fuel for the brain and ketone uptake is normal in brain regions affected by abnormal glucose uptake in AD (Castellano J Alzheim Dis 2015). Ketones are anti‐inflammatory (Kim Frontiers Immunol 2022) and lessen beta amyloid plaques, tau tangles, and anxiety in animal models (Kashiwaya PNAS 2000; Wu FASEB 2020). Increased brain energy from ketones has been demonstrated using PET imaging in clinical trials of MCT oil (Fortier Alz Dementia 2021), ketogenic diet (KD) (Neth Neurobiol Aging 2020), and exercise (Vandenberghe Appl Physiol Nutr Metab 2019). Recent studies report cognitive and/or other clinical improvements in MCI and/or AD with KD (Brandt J Alzheimers Dis 2019), modified Mediterranean KD (Neth Neurobiol Aging 2020), KD with MCT oil (Taylor Alzheimers Dement 2017), KD with coconut oil in keto study diet recipes (Phillips Alz Research & Therapy 2021), MCT oil with habitual diet (Reger Neurobio Ageing 2004; Constantini Nutri Metab 2009; Maynard Neuropsych Disease Treat 2013; Abe J Nutr Sci Vitaminol 2017; Abe J Nutr 2016; Xu et al. Clin Nutr 2020; Fortier Alz & Dementia 2021), and coconut oil with habitual diet (De la Rubia Orti Nutr Hosp 2017). Case reports of people with AD consuming KD, MCTs, and/or ketone ester also report cognitive improvement (Maynard Neuropsych Disease Treat 2013; Newport Alz Dementia 2015; Stoykovich Alz Dementia 2019; Morrill Diab Metab Syndr:Clin Res & Rev 2019). Ketone esters can rapidly and substantially increase blood ketone levels. Given the lack of any FDA‐approved drug that results in meaningful improvement for people with AD, accumulating evidence suggests that adopting a personalized program for people with AD, aiming for mild to moderate ketosis (blood betahydroxybutyrate levels 0.5‐2 mmol/L), could provide a safe and reasonable therapeutic approach to improve cognitive impairment and other symptoms and could offer a strategy to delay or prevent AD in persons at risk.