What effect do ketones have on Alzheimer’s disease?

Alzheimer’s disease commonly features a reduced ability to generate energy from glucose, and this deficit may largely affect cognitive function. So how might this be remedied? Enter ketones. Some evidence suggests that although glucose metabolism may be impaired, the brain’s ability to utilize ketone bodies for energy is relatively unaffected, at least in the early stages of Alzheimer’s disease.^[1] Given this, a ketogenic diet or ketogenic supplements may improve neuronal energy production and produce clinical benefits.

One RCT looked at the effect of a ketogenic supplement called AC-1202 (which consists mostly of caprylic acid) on cognitive function among 152 people with mild to moderate Alzheimer’s disease.^[2] For 90 days participants took either AC-1202 or a placebo, with cognitive function assessed using two tests: the ADAS-Cog and MMSE. ADAS-Cog scores had improved at day 45, but not at day 90, and there was no difference in MMSE scores between groups at any point. Interestingly, a subgroup analysis found that ADAS-Cog scores were improved at days 45 and 90 in non-carriers of APOE4 but not improved at either time point in carriers of the gene.

A crossover RCT published in 2021 examined the effect of a ketogenic diet on 26 people with Alzheimer’s disease.^[3] Participants were assigned to follow either a ketogenic diet (with a target of 6% of calories from carbohydrates) or low-fat diet for 12 weeks, later switching to the other diet after a 10-week washout period. Compared with the low-fat diet, the ketogenic diet improved both the ability to perform daily activities and quality of life. The ketogenic diet did not improve cognitive function in the overall analysis, but an improvement was seen when compliance was factored in (including only assessing participants who achieved a beta-hydroxybutyrate (a ketone body) level of at least 0.6 millimoles per liter).