In a 2020 review of randomized controlled studies, researchers found that ketone concentrations and cognitive performance differed between APOE4 carriers and APOE4 non-carriers (e2, e3), indicating a delayed response among the e4 carriers and an improved response among the non-e4 carriers.
In a 2022 review looking at the effects of the ketogenic diet on patients with Alzheimer’s disease, researchers commented that “there is an issue with assuming that all Alzheimer’s disease patients will react equally with the ketogenic diets. Patients with APOE4 alleles showed little statistical significance between cognitive improvements and ketone body levels.”
A study using a 40-gram dose of Caprylidene (MCT oil) “showed no changes in cerebral blood flow experienced by the subjects with Alzheimer’s disease and an APOE4 allele. As a result, the potential positive effects of a ketogenic diet on Alzheimer’s disease patients might be limited to those without the APOE4 allele.”
According to Dr. Angela Hanson, MD, geriatrician and researcher at UW Medicine, the efficacy of the treatment may depend on a person’s genetics. “Carefully controlled ketone studies have not benefited carriers of the APOE4 gene variant. In one case, APOE4 carriers got worse in the short-term and may have actually been harmed by ketosis.”
Dr. Hanson’s study also found that APOE4 non-carriers (e2 or e3) had improved measures of cognition and reduced inflammation on the low-fat diet compared to those on the high-fat diet, but the APOE4 carriers performed better on the high-fat diet (not ketogenic) than on the low-fat diet.
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