Evidence map›Paper›PMID 33622392›Full record

Trial reportAlzheimer's research & therapy2021

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

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 and 10 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06444568 (Efficacy of Modified Ketogenic Diet in Amnestic Mild Cognitive Impairments), which is not on this map. Cited by 147 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 5 pooled it
20.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06444568 naunknown statusnot on this mapstarted 2024, after this paper: background citation

Efficacy of Modified Ketogenic Diet in Amnestic Mild Cognitive Impairments

TypeinterventionalSponsorSaglik Bilimleri UniversitesiRan2024 to 2025Enrolled36ConditionsAmnestic Mild Cognitive Disorder, Amnestic Mild Cognitive ImpairmentArmsDietary Intervention
3 · Its place in the literature

Who cites it

147 citing papers in PubMed, 5 syntheses or guidelines pooled it, 233 citations in OpenAlex.

  1. Pooled it
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  16. Regulation of autophagy-mediated pathways by diet, physical activity, and sleep in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
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87 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 2 countries.

Matthew C L PhillipsDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand. Matthew.Phillips@waikatodhb.health.nz.ORCID 0000-0003-4183-7766
Laura M DeprezDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand.
Grace M N MortimerHealthy Kitchen Christchurch Ltd, Hamilton, New Zealand.
Deborah K J MurtaghHealthy Kitchen Christchurch Ltd, Hamilton, New Zealand.
Stacey McCoyDepartment of Dietetics Services, Waikato Hospital, Hamilton, New Zealand.
Ruth MylchreestDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand.
Linda J GilbertsonDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand.
Karen M ClarkDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand.
Patricia V SimpsonDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand.
Eileen J McManusDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand.
Jee-Eun OhDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand.
Satish YadavarajDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand.
Vanessa M KingLINC Mental Health Services, Tauranga Hospital, Tauranga, New Zealand.
Avinesh PillaiDepartment of Statistics, University of Auckland, Auckland, New Zealand.
Beatriz Romero-FerrandoDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand.
Martijn BrinkhuisMental Health Services for Older People, Waikato Hospital, Hamilton, New Zealand.
Bronwyn M CopelandMental Health Services for Older People, Tauranga Hospital, Tauranga, New Zealand.
Shah SamadOlder Persons and Rehabilitation Service, Waikato Hospital, Hamilton, New Zealand.
Shenyang LiaoOlder Persons and Rehabilitation Service, Waikato Hospital, Hamilton, New Zealand.
Jan A C SchepelDepartment of Neurology, Waikato Hospital, Hamilton, New Zealand.
Waikato Hospital · NZTauranga Hospital · NZUniversity of Auckland · NZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBrain 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.

methodsWe 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.

resultsWe 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.

conclusionsThis 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 registrationThis trial is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12618001450202 . The trial was registered on August 28, 2018.

Indexed as

Alzheimer DiseaseDiet, KetogenicActivities of Daily LivingCross-Over StudiesHumansQuality of LifeAlzheimer’s diseaseCognitionDaily functionKetogenic dietQuality of lifeRandomized crossover trial

Identifiers

PMID33622392
PMCPMC7901512
OpenAlexW3131138771

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.