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Quick Summary tl;dr
This randomized controlled crossover trial was a strong research study because each participant served as her/his own control, the dietary interventions were conducted for a long period of time, and the assessors were blinded to the intervention.
A ketogenic diet improves symptoms of Alzheimer’s disease, including daily functioning and quality of life, as compared to a low-fat diet.
At the that I’m writing this, it’s been less than four hours since an exciting research paper went live in the journal Alzheimer’s Research & Therapy entitled, “Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease.” ( Matthew C. L. Phillips, 2021) This research has several strengths that have been absent in prior human studies and shows convincingly that a ketogenic diet improves symptoms of Alzheimer’s disease.
Background
A decrease in brain’s ability to use glucose as a fuel is thought to be one of the early steps in the development of cognitive decline and Alzheimer’s disease. Therefore, it makes sense that providing ketone bodies, an alternate source of fuel for the brain that also boosts mitochondrial biogenesis and protects against amyloid toxicity, would improve cognition in those with Alzheimer’s disease.
Ketone bodies are a fuel for the brain that boost mitochondrial biogenesis and protect against Alzheimer’s amyloid toxicity.
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Study Design and Strengths
This study was a two-period randomized controlled crossover trial comparing a ketogenic diet with a low-fat diet. This jargon means that each of the participants underwent both dietary protocols in a random order so that each person could serve as her/his own control, eliminating between-person variability. Such randomized crossover trials are the gold standard for clinical research.
The diets themselves both appeared relatively healthy, with the low-fat diet being based on the New Zealand healthy eating guidelines. The ketogenic diet was 58% calories from fat, which was sufficient to help participants achieve nutritional ketosis, and the low-fat diet was 11% calories from fat. Each dietary intervention was conducted for 12 weeks with a 10-week washout period between the diets. This is presumably enough time for adaptation to occur.
Not only did each participant undergo each diet, but both diets were presented to participants as healthy options and the assessors who examined participants’ symptoms before and after the intervention were blinded to the participants’ groups. This suggests that any differences observed between the diets were a result of the diet and not participant or assessor bias.
Symptoms were measured before and after the interventions using three assessments.
- Activities of Daily Living (ADCS-ADL) inventory was used to assess individuals’ abilities to function in daily life.
- Quality of Life in AD (QOL-AD) questionnaire was used to determine quality of life.
- Addenbrookes Cognitive Examination — III (ACE-III) scale was used to assess cognition (attention, memory, fluency, language, and visuospatial ability).
On all tests, higher scores represent better performance.
Results and Conclusions
Average blood 𝛽-hydroxybutyrate levels in the ketogenic diet group were 0.95 mM, confirming that the patients did adhere to the diet overall. Only one of the twenty-six participants abandoned the ketogenic diet because of an adverse outcome, which was diarrhea as the result of consuming more coconut oil than instructed. Whoops! In a word, the diet was “sustainable,” even for those with dementia.
Ketogenic diets are sustainable, even if you have dementia.
Most importantly, symptoms significantly improved in individuals who sustained even mild nutritional ketosis, as compared to the low-fat group. On the ADCS-ADL inventory for daily functioning, scores improved +2.95 points in the ketogenic group as compared to low-fat (p = 0.04). On the QOL-AD questionnaire for quality of life, scores improved +4.28 points in the ketogenic group as compared to low-fat (p = 0.03). On the ACE-III scale for cognition, scores were trending towards an improvement, +2.56 (p = 0.12). Thus, as compared to the low-fat diet, daily functioning and quality of life improved significantly on the ketogenic diet, and cognition appeared to improve, although the difference was just shy of significance likely because of the small sample size and relatively light degree of ketosis.
Ketogenic diets are better than low-fat diets for improvement Alzheimer’s disease symptoms.
Cardiovascular risk also improved on the ketogenic diet as compared to the low-fat diet, as measured by improvements in weight, BMI, HDL, HbA1c and a trend towards improved triglycerides. LDL also increased, but given the improvements in other metrics (in particular HDL and trending triglycerides), this was unlikely to constitue a meaningful increase in risk. An LDL subfractionation would likely have revealed an increase in big, fluffy healthy LDL, not small dense LDL.
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