Effect of exogenous β-hydroxybutyrate on BDNF signaling, cognition, and amyloid precursor protein processing in humans with T2D and insulin-resistant rodents.
Level 2 - randomized trial
Randomized controlled trials in humans with parallel animal models
PubMed 39804761 · doi:10.1152/ajpcell.00867.2024
What was done
Parallel human randomized trials and mouse models evaluated the effects of exogenous beta-hydroxybutyrate supplementation on brain health markers. In adults with type 2 diabetes, the effect of acute and short-term ketone monoester supplementation on circulating BDNF and cognition was evaluated. In C57BL/6J mice with and without insulin resistance, acute and chronic beta-hydroxybutyrate supplementation was tested for effects on cortical BDNF content, recognition memory, and amyloid precursor protein processing.
What was found
The abstract reports no numerical values or statistical metrics. In humans with type 2 diabetes, ketone supplementation showed no effect on plasma BDNF levels or cognition. In mice, neither acute nor chronic beta-hydroxybutyrate altered recognition memory or cortical BDNF content, though supplementation positively modulated beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) activity.
Why it matters
These findings challenge the assumption that exogenous ketones enhance BDNF expression to support cognitive function in type 2 diabetes. They redirect mechanistic focus toward alternative neuroprotective targets, such as APP processing pathways.
Limits
The abstract omits human and animal sample sizes, exact dosages, treatment durations, and quantitative statistical estimates. Human data are restricted to acute and short-term outcomes in type 2 diabetes, leaving long-term cognitive and neurodegenerative endpoints unassessed.
Cited by
- contradicts Beta-hydroxybutyrate increases brain GABA levels, elevates BDNF, and reduces cellular oxidation.