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Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease
Phillips MCL, Deprez LM, Mortimer GMN, Murtagh DKJ, McCoy S, Mylchreest R, Gilbertson LJ, Clark KM et al.. Alzheimer's research & therapy, 2021-02-23
Topic: Amyloid, tau and blood-test diagnosis
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.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Phillips, M. C. L., Deprez, L. M., Mortimer, G. M. N., Murtagh, D. K. J., McCoy, S., Mylchreest, R., et al. (2021). Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-021-00783-x
Vancouver
Phillips MCL, Deprez LM, Mortimer GMN, Murtagh DKJ, McCoy S, Mylchreest R, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease. Alzheimer's research & therapy. 2021. doi:10.1186/s13195-021-00783-x. PMID: 33622392.
BibTeX
@article{phillips2021-33622392,
author = {Phillips, M. C. L. and Deprez, L. M. and Mortimer, G. M. N. and Murtagh, D. K. J. and McCoy, S. and Mylchreest, R. and Gilbertson, L. J. and Clark, K. M. and others},
title = {{Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease}},
journal = {Alzheimer's research \& therapy},
year = {2021},
doi = {10.1186/s13195-021-00783-x},
pmid = {33622392},
url = {https://doi.org/10.1186/s13195-021-00783-x}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Results We randomized 26 patients, of whom 21 (81%) completed the ketogenic diet; only one withdrawal was attributed to the ketogenic diet.
- 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).
- 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.
Why it matters
In this small 12-week trial of 26 patients, a modified ketogenic diet improved daily function and quality of life scores, but the change in cognition was not significant. These are short-term results in a small sample and do not show that the diet treats, cures, or prevents Alzheimer's disease.
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Study details
- Study designrandomized controlled trial
- Participants26
- Evidence strengthHigh
How this study scored 70/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 26 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 251 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 35.9 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 5 / 6 | Cited 21.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 3 / 4 | Cited 133 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Jan Schepel: h-index 6 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Maastricht University: institution h-index 876 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33622392) |
| Free to read | 2 / 2 | Free to read |
| Total | 70 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13195-021-00783-x
- PubMed: 33622392
- Original source →
- Free full text: Alzheimer s Research & Therapy →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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