Priming effects of ketone monoester supplementation on theta-burst stimulation-induced plasticity in the primary motor cortex: a randomized placebo-controlled crossover study
- 1University Putra Malaysia
Abstract
Neurological and cardiovascular disorders frequently coexist, yet targeted dual-system interventions remain underinvestigated. Transcranial magnetic stimulation (TMS), including intermittent and continuous theta-burst stimulation (iTBS/cTBS), non-invasively modulates primary motor cortex (M1) excitability. Concurrently, ketone monoesters (KME) show neuroprotective potential and alter cardiovascular hemodynamics. In a randomized, double-blind, placebo-controlled crossover study, 44 healthy young adults were stratified to receive iTBS or cTBS (n = 22/group). Participants completed two sessions separated by 1 week, consuming either a KME or placebo beverage, followed by TBS 1-hour post-ingestion. Motor evoked potentials (MEPs) from the right first dorsal interosseous muscle were tracked for 30 minutes post-stimulation. Blood pressure was measured every 3-5 minutes, heart rate was monitored continuously, and venous blood was sampled for glucose, {beta}-hydroxybutyrate (BHB), pro-BDNF, mature BDNF (mBDNF), and the BDNF rs6265 polymorphism. We found that KME significantly elevated blood BHB and heart rate while decreasing blood glucose and diastolic blood pressure. KME did not alter resting motor threshold, baseline MEP amplitude, or MEP latency. Factorial analysis showed no significant modification of post-TBS MEP time courses by KME. In exploratory within-condition analyses, placebo-cTBS induced significant late increases in MEP amplitude, whereas KME-cTBS showed a blunted post-stimulation response. Serum mBDNF and pro-BDNF concentrations remained unchanged. In conclusion, combining KME and TBS is feasible, well-tolerated, and may exert concurrent neurological and cardiovascular effects. This work opens the door to a novel metabolic-neuromodulatory avenue that merits confirmation in larger cohorts and establishment of clinical relevance in patients with comorbid neurological and cardiovascular disorders.
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BibTeX
@misc{tomeh2026priming,
title = {{Priming effects of ketone monoester supplementation on theta-burst stimulation-induced plasticity in the primary motor cortex: a randomized placebo-controlled crossover study}},
author = {A. Tomeh and A. H. K. Yusof Khan and Z. Abu Zaid and K.-H. Ling and L. N. Inche Mat and H. Basri and M. H. Abu Bakar and N. I. Sofea Suhaimi and W. A. Wan Sulaiman},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.26362322},
url = {https://www.medrxiv.org/content/10.64898/2026.09.09.26362322v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Priming effects of ketone monoester supplementation on theta-burst stimulation-induced plasticity in the primary motor cortex: a randomized placebo-controlled crossover study
AU - A. Tomeh
AU - A. H. K. Yusof Khan
AU - Z. Abu Zaid
AU - K.-H. Ling
AU - L. N. Inche Mat
AU - H. Basri
AU - M. H. Abu Bakar
AU - N. I. Sofea Suhaimi
AU - W. A. Wan Sulaiman
PY - 2026
DA - 2026/09/09
PB - medRxiv
DO - 10.64898/2026.09.09.26362322
UR - https://www.medrxiv.org/content/10.64898/2026.09.09.26362322v1
AB - Neurological and cardiovascular disorders frequently coexist, yet targeted dual-system interventions remain underinvestigated. Transcranial magnetic stimulation (TMS), including intermittent and continuous theta-burst stimulation (iTBS/cTBS), non-invasively modulates primary motor cortex (M1) excitability. Concurrently, ketone monoesters (KME) show neuroprotective potential and alter cardiovascular hemodynamics. In a randomized, double-blind, placebo-controlled crossover study, 44 healthy young adults were stratified to receive iTBS or cTBS (n = 22/group). Participants completed two sessions separated by 1 week, consuming either a KME or placebo beverage, followed by TBS 1-hour post-ingestion. Motor evoked potentials (MEPs) from the right first dorsal interosseous muscle were tracked for 30 minutes post-stimulation. Blood pressure was measured every 3-5 minutes, heart rate was monitored continuously, and venous blood was sampled for glucose, {beta}-hydroxybutyrate (BHB), pro-BDNF, mature BDNF (mBDNF), and the BDNF rs6265 polymorphism. We found that KME significantly elevated blood BHB and heart rate while decreasing blood glucose and diastolic blood pressure. KME did not alter resting motor threshold, baseline MEP amplitude, or MEP latency. Factorial analysis showed no significant modification of post-TBS MEP time courses by KME. In exploratory within-condition analyses, placebo-cTBS induced significant late increases in MEP amplitude, whereas KME-cTBS showed a blunted post-stimulation response. Serum mBDNF and pro-BDNF concentrations remained unchanged. In conclusion, combining KME and TBS is feasible, well-tolerated, and may exert concurrent neurological and cardiovascular effects. This work opens the door to a novel metabolic-neuromodulatory avenue that merits confirmation in larger cohorts and establishment of clinical relevance in patients with comorbid neurological and cardiovascular disorders.
ER -