Table 2.
Ketone studies investigating central nervous system outcomes.
| Year | Author (Ref) | Study | Population | No. participants | Formulation | Fasting | Intervention | Total average BHB dose | Insulin used | Findings overview | Concentration BHB | ADR |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1996 | Hasselbalch et al. (15) | Randomized crossover | Healthy | 8 | Racaemic BHB 55 mg/mL; pH 7.1 | 4-5 h post morning meal | 4-5 mg/kg/min for 3-3.5 h | No | Global increase in cerebral blood flow by 39%. Cerebral glucose metabolism reduced by 33% with a corresponding reduction in oxygen use for glucose metabolism from 97% to 74% during hyperketonaemia. | 0.31 ± 0.17 mM to 2.16 ± 0.42 mM post-infusion | Nil noted | |
| 2001 | Pan et al. (16) | Case-series | Healthy | 6 | Dextro-BHB 200 mM; pH 7.1 | Fasting | 80 μmol/kg/min followed by 20 μmol/kg/min for 75 min | No | Cerebral ketone uptake may be increased during a fasting state. | 0.20 ± 0.10 mM to 2.12 ± 0.30 mM post-infusion | Nil noted | |
| 2002 | Pan et al. (17) | Case-series | Healthy | 4 | Dextro-BHB 200 mM; pH 7.1 | Fasting | 16.7 mL/min for 20 min followed by 22 μmol/kg/min for 120 min | No | Rapid entry of BHB into the brain with a distribution similar to glucose. | Plasma post infusion: 2.25 ± 0.24 mM. Brain post infusion: 0.18 ± 0.06 mM. | Nil noted | |
| 2002 | Blomqvist et al. (18) | Placebo-controlled single-blinded | T1DM + Healthy controls | 6 T1DM/6 Controls | Racaemic BHB | Fasting | 6 mg/kg/min over 20 min followed by 3 mg/kg/min continuous infusion for up to 70 min | For T1DM patients only: maintain BGL between 6 and 12 mmol/L. | No difference in uptake rate was observed between T1DM and Healthy controls. Rate-limiting step for cerebral ketone metabolism is transfer from the blood to brain. | Post-infusion: T1DM 1.28 ± 0.31 μmol/mL; Healthy 0.98 ± 0.33 μmol/mL | Nil noted | |
| 2018 | Svart et al. (19) | Randomized placebo-controlled crossover | Healthy | 9 | Racaemic Na-3-OHB 75 g/L | Fasting | 0.22 g/kg/h 3-BHB for up to 4 h | No | Cerebral blood flow increased by 30% with a 14% reduction in cerebral glucose utilization. Oxygen consumption remained unchanged. | 0.2 ± 0.02 mM to 5.5 ± 0.4 mM post-infusion | Nil noted | |
| 2020 | Jensen et al. (20) | Randomized placebo-controlled double blinded crossover | T2DM | 18 | Racaemic Na-3-OHB 7.5% | Fasting | 0.22 g/kg/h for up to 3 h | 0.2 units/m2/min bolus over 3 min followed by 0.075 units/m2/min continuous infusion | Improved working memory performance in T2DM patients. No difference in global cognitive composite outcome was observed. | 0.1 ± 0.0 mM to 2.4 ± 0.6 mM post-infusion | Mild headache and light-headedness. |
ADR, adverse drug reaction; BHB, beta-hydroxybutyrate; CI, continuous infusion; CO, cardiac output; EG, euglycaemic clamp; FFA, free fatty acids; NEFA, non-esterified fatty acids; GFR, glomerular filtration rate; GH, growth hormone; HFrEF, heart failure with reduced ejection fraction; HR, heart rate; NYHA New York Heart Association; SVR, systemic vascular resistance; T1DM, type 1 or insulin-dependent Diabetes mellitus; T2DM, type 2 or non-insulin-dependent Diabetes mellitus; VT, ventricular tachycardia.
Data presented as mean ± standard error.