The Effects of Acute Ketone Monoester Ingestion on Resting Cerebral Blood Flow and Cognition in Young Adults

Abstract

Ketone monoester (KME) supplements are one exogenous ketone intervention which has demonstrated benefits to multiple facets of brain health, including cerebral blood flow (CBF) and cognition. However, it is unknown how KME impact CBF and cognition acutely, and whether the size of KME dose differentially impacts these outcomes. Higher KME doses lower blood pH and arterial CO2 (PaCO2), which are important regulators of CBF. We hypothesized that high-dose KME ingestion would lower CBF via acidosis-induced compensatory reductions in PaCO2, whereas low-dose KME ingestion would enhance CBF, mirroring past findings from other exogenous ketone interventions. Changes in cognitive function were also hypothesized to parallel CBF responses. Twenty young adults (age=23±3 years; BMI=23.4±2.2 kg/m2) participated. In a double-blinded, counterbalanced, crossover design, participants completed 3 separate conditions: 1) high-dose KME (0.6 g/kg); 2) low-dose KME (0.3 g/kg); or 3) placebo. Outcome measures were assessed at fasting baseline, 45-, and 120-min post-ingestion. CBF was assessed using Duplex ultrasound of the internal carotid and vertebral arteries. End-tidal CO2 (PETCO2) was measured using a gas analyzer, to approximate PaCO2. Hippocampal-dependent function was assessed using the lure discrimination index (LDI) and recognition memory score (REC) from the mnemonic similarity task. Over a 2-hour period post-ingestion, low- and high-dose KME lowered CBF to a different extent relative to baseline (45-min (low-dose, high-dose): ∆10.4%, ∆14.0%; 120-min (low-dose, high-dose): ∆6.2%, ∆18.6%; P < 0.001). These reductions were mirrored by dose-dependent reductions in PETCO2 and changes in CBF were positively correlated with changes in PETCO2 (P < 0.001, R2 = 0.219). Despite reductions in CBF, both LDI (P = 0.619) and REC (P = 0.651) were unchanged in the KME conditions. These findings provide a foundational characterization of the acute effects of KME dose on CBF and cognition, which will inform potential therapeutic recommendations on KME for brain health.