Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease

Abstract

Background Brain energy metabolism is impaired in Alzheimer’s disease (AD), which may be mitigated by a ketogenic diet. We conducted a randomized crossover trial to determine whether a 12-week modified ketogenic diet improved cognition, daily function, or quality of life in a hospital clinic of AD patients. Methods We randomly assigned patients with clinically confirmed diagnoses of AD to a modified ketogenic diet or usual diet supplemented with low-fat healthy-eating guidelines and enrolled them in a single-phase, assessor-blinded, two-period crossover trial (two 12-week treatment periods, separated by a 10-week washout period). Primary outcomes were mean within-individual changes in the Addenbrookes Cognitive Examination - III (ACE-III) scale, AD Cooperative Study - Activities of Daily Living (ADCS-ADL) inventory, and Quality of Life in AD (QOL-AD) questionnaire over 12 weeks. Secondary outcomes considered changes in cardiovascular risk factors and adverse effects. Results We randomized 26 patients, of whom 21 (81%) completed the ketogenic diet; only one withdrawal was attributed to the ketogenic diet. While on the ketogenic diet, patients achieved sustained physiological ketosis (12-week mean beta-hydroxybutyrate level: 0.95 ± 0.34 mmol/L). Compared with usual diet, patients on the ketogenic diet increased their mean within-individual ADCS-ADL (+ 3.13 ± 5.01 points, P = 0.0067) and QOL-AD (+ 3.37 ± 6.86 points, P = 0.023) scores; the ACE-III also increased, but not significantly (+ 2.12 ± 8.70 points, P = 0.24). Changes in cardiovascular risk factors were mostly favourable, and adverse effects were mild. Conclusions This is the first randomized trial to investigate the impact of a ketogenic diet in patients with uniform diagnoses of AD. High rates of retention, adherence, and safety appear to be achievable in applying a 12-week modified ketogenic diet to AD patients. Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily function and quality of life, two factors of great importance to people living with dementia. Trial registration This trial is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12618001450202. The trial was registered on August 28, 2018.

Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers

“…Although this particular manuscript aims to focus on disease prevention, it is worth noting that dietary interventions that increase βhB have shown to be effective at improving symptoms in individuals with AD, in part, by supplying an alternative source of fuel, as opposed to glucose, to the brain [77][78][79]. For example, a recent randomized controlled crossover trial comparing a 12-week ketogenic diet to a 12-week low-fat diet found that the former caused significant improvements in daily functioning and overall quality of life as compared to the latter [80]. We choose to comment briefly on these symptom data both to further the rationale for providing a ketogenic option to at-risk patients and to acknowledge that there is a lack of consensus over whether ApoE4 carriers constitute a less responsive group to ketogenic therapy.…”

Food for thought: the emerging role of a ketogenic diet in Alzheimer’s disease management

“…In the modified Mediterranean-ketogenic diet (Med-KD), carbohydrates, fat, and protein provide less than 10%, 60-65%, and 30-35% of energy, respectively [8]. Researchers from New Zealand have used another KD plan, which provides an average macronutrient ratio of 58% fat (26% saturated, 32% non-saturated), 29% protein, 7% fiber, and 6% net carbohydrates by weight [9]. The main fat sources in these ketogenic diets are long-chain fatty acids.…”

“…In a recently published randomized crossover trial, Phillips et al [9] determine whether a 12-week modified KD improved cognition, daily function, or quality of life in a hospital clinic of AD patients. Patients achieved sustained physiological ketosis.…”

“…Although the above-cited studies reported good KD or MCT supplementation tolerance and no severe side effects, the long-term safety must be assessed. The reported short-term mild side effects included increased irritability, increased fatigue, sugar cravings, insomnia, muscle cramps, constipation, excessive hunger, nausea, headache, and diarrhea [9]. Particular attention should be paid to the influence of these dietary interventions on patients' nutritional status.…”

Case Report: Ketogenic Diet Is Associated With Improvements in Chronic Obstructive Pulmonary Disease

“…Ketogenic diets (KD) have a near century long history of being used to treat pediatric epilepsy ( 7 ), and newer research is beginning to explore their therapeutic potential in other chronic disease, such as type II diabetes ( 8 , 9 ), polycystic ovarian syndrome ( 10 ), Alzheimer's disease ( 11 ), Parkinson's disease ( 12 ), cardiovascular risk ( 13 ), metabolic syndrome ( 14 ), and various mental illnesses ( 15 ). Many of these disease have an inflammatory component and, correspondingly, well-formulated ketogenic diets have been shown to improve a broad spectrum of inflammatory markers ( 16 ).…”