By Joseph E. Scherger, MD, MPH

Core Faculty, Eisenhower Health Family Medicine Residency Program, Eisenhower Health Center, La Quinta, CA; Clinical Professor, Keck School of Medicine, University of Southern California, Los Angeles

SYNOPSIS: In a randomized, crossover trial, patients with Alzheimer’s disease on a ketogenic diet for 12 weeks demonstrated improved cognition, daily function, and quality of life.

SOURCE: Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimers Res Ther 2021;13:51.

This randomized, crossover trial was conducted at a tertiary care hospital in New Zealand in 2019. The authors enrolled 26 patients (age 50 to 90 years) with Alzheimer’s disease (AD). A total of 21 completed the blinded crossover trial. All presented with clinically significant disease at various stages. For 12 weeks, patients ingested either a ketogenic diet or usual diet, supplemented with low-fat, healthy-eating guidelines for two weeks each. A 10-week wash out period separated the two dietary periods. Assessors were blinded as to which diet the patients were on, with measurements taken after each 12-week diet period. The primary outcomes were changes in the AD Cooperative Study – Activities of Daily Living (ADCS-ADL) inventory, the Addenbrooke’s Cognitive Examination III (ACE-III) scale, and Quality of Life in AD (QOL-AD) questionnaire. Secondary outcomes considered changes in cardiovascular risk factors and adverse events.

Compared with the usual diet, patients on the ketogenic diet increased their mean within-individual ADCS-ADL score by 3.13 points (P = 0.0067) and their QOL-AD by 3.37 points (P = 0.023). The ACE-III also increased by 2.12 points, but this did not reach statistical significance. Changes in cardiovascular risk factors were mostly favorable, with decreased body weight and BMI, lower HbA1c, and an increase in HDL cholesterol. LDL and total cholesterol also increased on the ketogenic diet, which, in the short term, was seen with burning fat. Adverse events were mild.

COMMENTARY

Ketones benefit the brain.1 Before phenytoin, clinicians prescribed a ketogenic diet to help treat epilepsy.2 Elevated blood sugar levels are harmful to the brain.3 Thus, it is not surprising that a ketogenic diet would improve function in patients with AD. What is remarkable is these benefits were seen after just two weeks. Although this study size was small and the period brief, this adds to the literature indicating diet may improve cognition in patients with AD.4 It is time we recognize and act on the data showing that high-sugar, high-carbohydrate diets are harmful, and that low-carbohydrate diets produce major health benefits. 

REFERENCES

  1. Hernandez AR, Hernandez CM, Campos K, et al. A ketogenic diet improves cognition and has biochemical effects in prefrontal cortex that are dissociable from hippocampus. Front Aging Neurosci 2018;10:391.
  2. D’Andrea Meira I, Romão TT, Pires do Prado HJ, et al. Ketogenic diet and epilepsy: What we know so far.
    Front Neurosci 2019;13:5.
  3. Harvard Medical School. Blood sugar on the brain. Harvard Heart Letter. March 2015.
  4. Bredesen DE, Amos EC, Canick J, et al. Reversal of cognitive decline in Alzheimer’s disease. Aging 2016;8:1250-1258.