Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease.
Level 2 - randomized trial
Individual randomized crossover trial
PubMed 33622392 · doi:10.1186/s13195-021-00783-x
What was done
In an assessor-blinded, two-period randomized crossover trial, 26 patients with clinically confirmed Alzheimer's disease were assigned to a 12-week modified ketogenic diet versus a usual diet supplemented with low-fat healthy-eating guidelines, separated by a 10-week washout period. Primary outcomes evaluated within-individual changes in cognition (Addenbrookes Cognitive Examination - III, ACE-III), daily function (AD Cooperative Study - Activities of Daily Living, ADCS-ADL), and quality of life (Quality of Life in AD, QOL-AD). Secondary outcomes assessed cardiovascular risk factors and adverse effects.
What was found
A total of 21 patients (81%) completed the ketogenic diet, maintaining sustained physiological ketosis (mean 12-week beta-hydroxybutyrate: 0.95 ± 0.34 mmol/L). Compared with the usual diet, the ketogenic diet resulted in statistically significant within-individual improvements in ADCS-ADL (+3.13 ± 5.01 points, P = 0.0067) and QOL-AD (+3.37 ± 6.86 points, P = 0.023). Cognition on the ACE-III increased non-significantly (+2.12 ± 8.70 points, P = 0.24). Only one withdrawal was attributed to the diet, adverse effects were mild, and cardiovascular risk changes were reported as mostly favourable.
Why it matters
This trial indicates that a modified ketogenic diet is feasible in Alzheimer's disease and can yield meaningful improvements in daily function and quality of life.
Limits
The trial had a small sample size (n = 26 randomized, 21 completed) and a short 12-week intervention duration. Cognitive improvement did not reach statistical significance, and participants could not be blinded to dietary allocation.
Cited by
- partial Psychiatric disorders and cognitive decline have significant metabolic underpinnings, and improving metabolic health through targeted dietary interventions can lead to substantial clinical improvements without notable side effects.