Data published in Frontiers in Nutrition indicated that the cognitive benefits were determined by the supplement type and dose, with ketone ester (KetE) and medium chain triglyceride (MCT) both associated with statistically significant cognitive improvement. <\/p>\n
\u201cThe present findings are promising and offer interesting perspective for future research and clinical translation,\u201d wrote scientists from the University of Hasselt (Belgium), the Buck Institute for Research on Aging (USA), and Component Health (Ireland). \u201cGiven the beneficial cognitive effects of EK [endogenous ketones] in both healthy and cognitively impaired individuals, no known safety concerns and acceptable tolerance profiles, EK are a candidate for further research and clinical translation. <\/p>\n
\u201cIt is likely that the greatest effect would be seen if EK were used in synergy with other interventions, such as diet and exercise; this should be addressed in future research.\u201d<\/p>\n
Ketones<\/p>\n
Early research into exogenous ketones attempted to replicate the benefits of the ketogenic diet without changing what people eat: When the body goes into starvation mode because it does not have enough carbohydrates (or glucose), it will then resort to burning its own fat reserves to make ketones, a process commonly understood as ketosis. This can occur during fasting or participating in lengthy periods of exercise.<\/p>\n
\u201cThe canonical primary role of ketone bodies (or ketones) including \u03b2-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone, is to act as a metabolic substrate for brain function during development, and in settings of low carbohydrate availability,\u201d explained the researchers behind the new meta-analysis. \u201cIndeed, classic experiments [\u2026] found that ketones entering the brain via select, widely expressed mono-carboxylate transporters can account for up to 60% of brain metabolic needs during prolonged starvation.\u201d<\/p>\n
Supplementing with exogenous ketones puts ketones directly into the bloodstream and bypasses the fat burning step that a ketogenic diet would require. Beyond supplying energy to brain, heart and skeletal muscle tissues, ketosis has been linked to non-energetic (signaling molecule) benefits including cognitive performance, reduced inflammation, weight loss, reversal of metabolic syndrome and improved immune function. <\/p>\n
Despite a number of studies being published in the literature, no systematic review or meta-analysis has previous been performed to consolidate the data around exogenous ketones and cognitive performance.<\/p>\n
Study details <\/p>\n
The researchers pooled data from 29 randomized controlled trials including a total of 1,117 participants for their meta-analysis. <\/p>\n
Exogenous ketone supplementation was associated with a statistically significant improvement in cognitive performance, compared with placebo, said the researchers. <\/p>\n
Additional analysis revealed no differences between the type of supplementation, study duration, population type (healthy people or people with Alzheimer\u2019s), or the presence of acute cognitive stressors, they said. <\/p>\n
A positive association was detected between daily exogenous ketone dose and cognitive improvement, they added. <\/p>\n
\u201cGiven that KetE have a larger impact on circulating ketones concentrations than both MCT and ketone salts, their use in long duration studies of cognition represents a promising direction for future research,\u201d wrote the researchers. \u201cHowever, the most ketogenic and most widely studied ketone ester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is known to have a bitter taste which may limit long-term use, whereas MCTs and medium chain fatty acid esters such as bis-ocatnoyl (R),1-3-butanediol have a neutral taste, making them more translatable for long-term use, despite a lower ketone exposure. These trade-offs highlight the need to balance biological potency with translational practicality.\u201d<\/p>\n
The researchers called for well-powered, long-term trials to elucidate optimal dosing, formulation, and clinical applicability.<\/p>\n
Ketones and aging: Beyond the brain<\/p>\n
Another aspect of healthspan being linked to ketosis is related to frailty. The Buck Institute for Research on Aging launched the first-ever clinical trial on the effects of ketone supplementation on frailty in 2023 after receiving a $3.5 million grant from the National Institutes of Health.<\/p>\n