Effects of Exogenous Ketone Ester Supplementation on 3-hydroxybutyrate Concentrations in Human Cerebrospinal Fluid

It is well established that the brain is capable of consuming ketone bodies, especially during low glucose availability, e.g. fasting. Cerebral metabolism of ketone bodies depends on passage of the blood brain barrier and especially the global blood concentration of ketone bodies.

Ketone bodies can be administered exogenously, and the most commonly used in clinical trials is 3-hydroxybutyrate (3-OHB). 3-OHB is carried by simple diffusion and facilitated diffusion through several monocarboxylic acid transporters (MCTs) across the blood-brain barrier.

To our knowledge, no studies in human adults exist that concurrently measure 3-OHB concentrations in blood and cerebrospinal fluid (CSF) after ingestion or infusion of exogenous ketone supplementation, necessitating further study.

Aims:

* The 3-OHB CSF/blood ratio after oral ingestion of 30 g ketone ester - primary endpoint * The window of effect: Ketone supplementation 1 h or 2 h before CSF sampling * If concentration measurements by point-of-care testing are non-inferior to mass spectrometry * If acute 3-OHB ingestion increases plasma brain-derived neurotrophic factor (BDNF) levels