Effects of Ketone Ester Supplementation on Cognition and Appetite in Individuals with and Without Metabolic syndrome: A Randomized Trial

There are currently no non-pharmacological solutions to combat the appetite and cognitive dysfunctions associated with metabolic syndrome (MetS). Ketosis may be a potential solution, though the restrictive nature of dietary ketosis limits its long-term utility. Oral administration of exogenous ketone esters (KE) independently induces ketosis, eliciting hyperketonemia without the need for prolonged dietary restrictions. However, the acute effects of oral KEs on appetite and cognition have not been evaluated in individuals with MetS. For this randomized, single-blind, placebo-controlled, matched-pairs crossover study, 10 individuals with MetS and 10 without (non-MetS) matched for age, sex, and race/ethnicity completed a cardiometabolic screening/familiarization visit and two experimental trials. During the experimental trials, cognitive function, subjective appetite, and respiratory gases were measured at baseline and for 2h following the ingestion of a randomly assigned KE or placebo drink. Post-trial food intake was also collected. Independent of MetS group, indices of working memory significantly improved (<i>p</i> ≤ .035), and blood glucose significantly decreased (<i>p</i> < .001), following KE ingestion. However, after the KE condition, markers of subjective appetite (<i>p</i> ≤ .048) only decreased in the non-MetS group. Post-trial relative fat intake was higher in the MetS group than the non-MetS group following the KE (<i>p</i> = .002), and lower after the KE than the placebo for the non-MetS group (<i>p</i> = .028). Our findings indicate that while cognitive function may increase following KE ingestion independent of MetS, appetite may only decrease in those without MetS; providing further insight to our understanding of the behavioral and metabolic responses to exogenous ketosis.