Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Alzheimers Res Ther. 2021 02 23 ;13(1):51. Epub 2021 Feb 23. PMID: 33622392

Abstract Author(s):

Matthew C L Phillips, Laura M Deprez, Grace M N Mortimer, Deborah K J Murtagh, Stacey McCoy, Ruth Mylchreest, Linda J Gilbertson, Karen M Clark, Patricia V Simpson, Eileen J McManus, Jee-Eun Oh, Satish Yadavaraj, Vanessa M King, Avinesh Pillai, Beatriz Romero-Ferrando, Martijn Brinkhuis, Bronwyn M Copeland, Shah Samad, Shenyang Liao, Jan A C Schepel

Article Affiliation:

Matthew C L Phillips


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.

Study Type : Human Study

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