Normocapnic Breathing Mitigates Cerebral Blood Flow Reductions After Ketone Monoester Supplementation

Abstract

Infusion of ketone bodies, like beta-hydroxybutyrate (β-OHB), rapidly increases cerebral blood flow (CBF). However, pilot data suggests that acute ketone monoester (KME) ingestion disrupts blood pH and reduces arterial carbon dioxide (CO2), which may lower CBF and cerebrovascular reactivity (CVR). Whether preventing reductions in arterial CO2 mitigates reductions in CBF and CVR following KME ingestion is unknown. The purpose of this study was to test the hypothesis that global CBF (gCBF) and CVR would be higher when pressure of end-tidal CO2 (PETCO2) is maintained at baseline values following KME supplementation. Twenty-three young adults were recruited (age = 22 ± 2 yrs, BMI = 23.5 ± 3.6 kg/m2). In a single-blinded placebo-controlled randomized crossover design, participants completed two experimental conditions on separate days. Participants ingested 0.6 g KME /kg and rested for 60 min while breathing room air (poikilocapnia) or a gas mixture that clamped PETCO2 at baseline (normocapnia). gCBF was assessed using duplex ultrasound of the right internal carotid and vertebral arteries. CVR was induced by increasing PETCO2 to +3, +6, and +9 mmHg above baseline. Venous blood was drawn to measure β-OHB, pH, and bicarbonate (HCO3-). Outcomes were assessed at baseline, 45 min, and 60 min post-supplementation. gCBF was 16% higher during normocapnia compared to poikilocapnia at 45 min (P < 0.001) and 60 min (P = 0.019). Correspondingly, PETCO2 was higher during normocapnia at 45 min (+3.90 ± 4.15 mmHg; P = 0.002) and 60 min (+4.32 ± 5.34 mmHg; P = 0.007) compared to poikilocapnia. pH only reduced from baseline during normocapnia (∆ -0.05 ± 0.05; P = 0.005). HCO3- was significantly decreased in both conditions (P < 0.001). CVR was unchanged post-supplementation in either condition. Findings demonstrate that maintaining PETCO2 at normocapnia following KME supplementation mitigates gCBF reductions, and CVR is unchanged by KME supplementation.