Abstract
- Background
Impaired cerebral glucose metabolism represents a critical potential pathophysiological hallmark and early driver of mild cognitive impairment (MCI). Because vulnerable neurons exhibit compromised glucose uptake and bioenergetic deficits over time, this pilot study examined the therapeutic potential of artificially increasing circulating ketone bodies through medium-chain triglyceride (MCT) supplementation as an alternative metabolic substrate to beneficially modulate brain homeostasis and support cognitive function in subjects with MCI.
- Methods
A pilot randomized, placebo-controlled clinical trial was conducted enrolling six participants diagnosed with mild cognitive impairment. Participants were randomly assigned to receive a daily oral supplementation of 56 g/day of either medium-chain triglycerides (MCTs) or an identical placebo over a 24-week intervention period. Comprehensive physiological and neuropsychological evaluations were systematically performed:
Metabolic Monitoring: Fasting serum concentrations of the primary ketone body β-hydroxybutyrate were quantified.
Genetic Profiling: Apolipoprotein-E4 (APOE-ε4) status was assessed.
Cognitive Assessment: Standardized cognitive and memory performance tests were administered. Given the small pilot sample size, analyses focused primarily on the examination of raw score trajectories.
- Results
Daily dietary supplementation with MCT oil demonstrated clear metabolic shifts and preliminary cognitive benefits:
Ketogenic Response: Intake of 56 g/day of MCT oil successfully elevated circulating serum ketone body (β-hydroxybutyrate) concentrations compared to baseline and placebo conditions.
Cognitive & Memory Enhancement: Participants receiving the MCT intervention exhibited improvements in memory test scores, whereas individuals in the placebo control group showed no measurable cognitive improvements across any tested measures.
Trial Feasibility & Safety: The 24-week intervention protocol was successfully completed, confirming practical study feasibility and laying the groundwork for larger trials.
- Conclusions
Consumption of 56 g/day of medium-chain triglycerides for 24 weeks successfully increases serum ketone concentrations and enhances memory performance in subjects with mild cognitive impairment. These pilot findings establish MCT supplementation as a highly promising, metabolically targeted candidate strategy for larger, definitive randomized controlled trials investigating ketone precursors as disease-modifying interventions for cognitive decline.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4669977/