BHBs and Healthy Aging of The Brain
In a previous article, I dissected the physical characteristics of beta hydroxybutyrate, known in short as BHBs. These are exogenous (meaning external) sources of the fuel source in the body known as ketones which are water-soluble compounds produced as a by-product substrate when the body burns fat for energy. They are almost always present in small quantities, but when fat is being used as a primary fuel source ketone production amplifies and they are carried from the liver though the blood to vital organs including the brain, heart, and additionally skeletal muscle for energy. In today’s article, let us focus in specifically on the research for BHBs and their possible benefits on cognition as we age!
BHBs — A Brain Boost
Now to discuss how exogenous BHBs can affect cognitive aging, we must first briefly cover exactly what ketones do regarding the brain. Under ‘normal’ circumstances, the brain’s preferred fuel source is glucose for the generation of adenosine triphosphate (ATP). It has been shown that the 1.5 kg human brain utilizes 100 to 150 g glucose per day and 20% of the total body oxygen consumption. When glucose is sparse such as during times of fasting or a ketogenic diet, ketones become the preferred fuel source of the brain and has been shown in research that in longstanding starvation, ketones can provide 60 to 70% of the energy needs of the brain1.
It is important to note that while a lot of the proposed benefits of BHBs are in theory and based on the rationale that they serve as an alternative fuel source for the brain when glucose is absent, there isn’t a lot of data (just yet) on ‘healthy’ populations, however when it comes to improving the cognition in those with Alzheimer’s and other degenerative brain conditions, the research is starting to compile at a nice pace, hence the focus of today’s article2.
Before BHBs had emerged onto the scene, the ketogenic diet had been used therapeutically with promising effects for those suffering from Alzheimer’s and Parkinson’s disease and that it is well documented that Alzheimer’s as well as some forms of epilepsy can be treated effectively with ketogenic diet. It was further found that for epilepsy, it appears advantageous to administer the highest possible fraction of the patients’ calorie need in the form of ketone bodies, which may reduce glucose metabolism sufficiently to impair glutamate production in neurons. Much lower doses of ketone bodies can have therapeutic effect in Alzheimer’s disease by different mechanisms and enabling ketone bodies to supply a fraction of needed ATP may partly compensate for the deficiency in glucose metabolism in Alzheimer’s patients3. So, with this in mind, the ketone bodies by way of ketogenic dieting or supplementation of BHBs not only solves the issue of an energy source but can even ameliorate neurodegenerative diseases of the brain when glucose metabolism is inhibited, and ketones use can be more prevalent.
Taking a look at the data, there are multiple research studies that have been conducted in humans, specifically on Alzheimer’s patients. In one study, it was shown that in 152 subjects diagnosed with mild to moderate Alzheimer’s when ingesting a ketogenic supplement had rapidly elevated serum ketone bodies and resulted in significant differences in ADAS-Cog scores compared to the placebo4.
What are a few of the factors that contribute to the neuroprotective effects of BHBs? It has been shown that BHBs are more energy efficient than glucose and can stimulate mitochondrial biogenesis via the upregulation of genes encoding energy metabolism and mitochondrial enzymes5. There is a marked increase in the free energy of ATP hydrolysis, as demonstrated by a 25% increase in hydrolytic work of isolated rat perfused heart preparations when exposed to ketone bodies (KB)6 There is also noted pathways of neuroprotection via attenuation of the formation of reactive oxygen species, enhanced cerebral blood flow via ketone uptake by up to 39% and reduced overall cerebral cell death7–9.
Now with this data in hand, you, or someone you know may be interested in giving BHB supplementation a go. With the emergence of the keto diet popularity and the supplementation that coincides, one can imagine how many different types of products have flooded the market. However not all are created equal and some various issues that have arose is lack of purity, less than optimal potency due to mixed isomers (DL) and some production methods use formaldehyde as a component. One that I have used in formulations is KetoVantage® as it is consistent in quality with HPLC purity verified, is the active isomer D and does not have the formaldehyde issue. There are other quality BHB suppliers, but speaking from an experience perspective, that is what I recommend for consistency and quality.
With this information in hand, I hope you learned something new and can apply it to live a long and healthy life while maintaining sharp cognitive function. Until next time, stay sharp, stay curious and as always, stay informed on your research!
References
1. Owen O. Brain Metabolism during Fasting. J Clin Invest. 1967;46(10):1589–1595. doi:10.1172/JCI105650
2. Jensen N. Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases. Int J Mol Sci. 2020;21(22). doi:10.3390/ijms21228767
3. Hertz L. Effects of ketone bodies in Alzheimer’s disease in relation to neural hypometabolism, β‐amyloid toxicity, and astrocyte function. J Neurochem. 2015;134(1). doi:10.1111/jnc.13107
4. Henderson S. Study of the Ketogenic Agent AC-1202 in Mild to Moderate Alzheimer’s Disease: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Nur Metab. 2009;6(31). doi:10.1186/1743–7075–6–31
5. Veech R. Ketone bodies, potential therapeutic uses. IUBMB Life. 2001;51(4):241–247. doi:10.1080/152165401753311780
6. Kashiwaya Y. Control of glucose utilization in working perfused rat heart. J Biol Chem. 1994;269(41):25502–25514.
7. Krebs H. Equilibrium relations between pyridine nucleotides and adenine nucleotides and their roles in the regulation of metabolic processes. Adv Enzyme Regul. 1969;7:397–413. doi:10.1016/0065–2571(69)90030–2
8. Hasselbalch S. Changes in cerebral blood flow and carbohydrate metabolism during acute hyperketonemia. Am J Physiol. 1996;270(Pt. I):E746–51. doi:10.1152/ajpendo.1996.270.5.E746
9. Gasior M. Neuroprotective and disease-modifying effects of the ketogenic diet. Behav Pharmacol. 2006;17(5–6):431–439. doi:10.1097/00008877–200609000–00009
