In the present study, researchers explained that effects of 3-hydroxybutyrate (OHB) on cerebral blood flow (CBF) together with oxygen and glucose utilisation in humans using modern position emission tomography (PET) technique
Ketone bodies are neuroprotective in neurological disorders such as epilepsy. In evolutionary terms, the ability to generate ketone bodies 3-OHB and acetoacetate has been fundamental for mankind surviving times of dwindling food supplies and ketosis induced by fasting, exercise.
Most recently antidiabetic treatment with SGLT2-inhibitors may increase longevity in humans; it has also been reported that specific supplementation with 3-OHB increases lifespan in C. Elegans roundworms by 20%.
The brain relies on a constant rate of energy supply, and during metabolic stress, e.g. fasting, exercise, or severe disease, ketone bodies displace glucose as oxidative fuel.
In hyperketonemia states, 3-OHB is present in several fold higher concentration than acetoacetate, and there is evidence that 3-OHB promotes a more efficient ATP yield per oxygen molecule compared to lipid and carbohydrate fuels.
Furthermore, 3-OHB has been reported to lower reactive oxygen species (ROS) dependent oxidative stress in the central nervous system (CNS), to inhibit histone deacetylase(HDAC) induced oxidative stress, and to promote the expression of the brain-derived neurotrophic factor.
A ketogenic diet has proven beneficial in the treatment of epilepsy and may also have favourable effects in the treatment of neurodegenerative diseases, e.g. Alzheimer's and Parkinson's disease which are most prevalent in older adults.
In the study researchers randomly studied nine healthy human subjects twice—with and without a continuous infusion of 3-hydroxybutyrate–to define potential underlying mechanisms, assessed regionally (parietal, occipital, temporal, cortical grey, and frontal) by PET scan.
Researchers used a randomised, controlled crossover design with two arms separated by at least two weeks: i) saline infusion (0.9%) (CTR) and ii) ketone body infusion with 3-OHB (75g/ litre) (KET).
During 3-hydroxybutyrate infusions concentrations increased to 5.5±0.4 mmol/l and cerebral glucose utilisation decreased 14%, oxygen consumption remained unchanged, and cerebral blood flow increased 30%.
The study was designed to test whether an acute 4-h infusion with a high dose of 3-OHB affects CBF together with oxygen and glucose utilisation in humans using modern PET and MRI techniques. The studies found using these techniques are that CMRglu decreases 14% and CBF increases 30% under the influence of high 3-OHB concentrations. The 3-OHB levels in this study are equal to those seen after 4–8 weeks of fasting
Researchers conclude that acute 3-hydroxybutyrate infusion reduces cerebral glucose uptake and increases cerebral blood flow in all measured brain regions, without detectable effects on cerebral oxygen uptake though oxygen extraction decreased. Increased oxygen supply concomitant with unchanged oxygen utilisation may contribute to the neuroprotective effects of ketone bodies.