β-Hydroxybutyrate – Are BHB salts all created equal?
Estimated reading time: 7 minutes
There are three ketone bodies created on a ketogenic diet. These ketone bodies are acetoacetate (AcAc), beta-hydroxybutyrate (BHB), and acetone. Acetoacetate is the first ketone body produced from the breakdown of fats in the liver. A portion of acetoacetate is then converted into beta-hydroxybutyrate, the most abundant and stable ketone body in circulation.
Although three ketone bodies are produced on a ketogenic diet, this blog post is about BHB. There is a lot of interest in producing one’s own BHB through a ketogenic diet and supplementation. Lots of people use different forms of exogenous ketones to help their brain health.
These signaling functions of BHB broadly link the outside environment to epigenetic gene regulation and cellular function, and their actions may be relevant to a variety of human diseases as well as human aging.Newman, J. C., & Verdin, E. (2017). β-Hydroxybutyrate: a signaling metabolite. Annual review of nutrition, 37, 51-76. https://www.annualreviews.org/doi/10.1146/annurev-nutr-071816-064916
But I want you to understand that there are some differences in BHB forms available.
D-BHB (D-beta-hydroxybutyrate) and L-BHB (L-beta-hydroxybutyrate) are two forms of the ketone body beta-hydroxybutyrate, and they’re actually stereoisomers. In simpler terms, they are molecules that share the same chemical formula and structure but have different arrangements of atoms in space, making them mirror images of each other.
The real difference between these two lies in their biological roles and activity in the body. D-BHB is the biologically active form, meaning it’s the one that plays a significant part in energy production and metabolism.
When you’re following a ketogenic diet or fasting, your liver produces D-BHB as the main ketone body. It acts as an alternative energy source for your brain, heart, and muscles when glucose is scarce. D-BHB is the form that has been shown to have various positive effects on cellular processes, such as boosting mitochondrial function, autophagy, and mitochondrial biogenesis.
All of these are important for brain health! You can learn more about these mitochondrial processes here in this blog post I wrote:
In contrast, L-BHB is the biologically inactive form of beta-hydroxybutyrate. It’s produced in smaller amounts in the body and has limited metabolic functions. However, it’s worth noting that recent research is starting to uncover potential roles for L-BHB in different cellular processes.
How does L-BHB turn into D-BHB?
In the human body, the conversion of L-BHB to D-BHB occurs through a process called stereoisomerization. In the molecular world, stereoisomerization is the process where a molecule changes its three-dimensional arrangement of atoms, converting one stereoisomer into another without altering the overall molecular structure. This change in the spatial arrangement can lead to differences in the properties and functions of the resulting isomers. (If you are having a hard time visualizing this explanation, this blog post is a must-read, as it has some great graphics created by super smart people).
In the world of BHB, conversion is facilitated by an enzyme called beta-hydroxybutyrate dehydrogenase (BDH1), which is present in the mitochondria of cells, primarily in the liver.
The enzyme BDH1 catalyzes the reversible interconversion between the two stereoisomers, L-BHB and D-BHB. The reaction also involves the coenzyme NAD+/NADH. In the presence of BDH1 and NAD+, L-BHB is oxidized to form acetoacetate while reducing NAD+ to NADH. Subsequently, acetoacetate can be reduced back to D-BHB, with NADH being oxidized back to NAD+ in the process.
It’s worth noting that this process of interconversion is not highly efficient, as L-BHB is present in the body in much smaller quantities compared to D-BHB, and the enzyme BDH1 has a higher affinity for D-BHB. As a result, the majority of ketone bodies utilized for energy are D-BHB, which is the biologically active form responsible for most of the health benefits associated with ketosis
A deeper knowledge of the endogenous actions of BHB, and improved tools for delivering BHB or replicating its effects, offers promise for the improvement of human health span and longevity.Newman, John C., and Eric Verdin. “β-Hydroxybutyrate: a signaling metabolite.” Annual review of nutrition 37 (2017): 51-76. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640868/
What kind of BHB am I taking?
Most ketone salts on the market are a mixture of D-BHB and L-BHB. This is because the production process of ketone salts often results in a racemic mixture, which contains equal amounts of the two stereoisomers, D-BHB and L-BHB. These products are sometimes referred to as “racemic BHB salts” or simply “BHB salts.”
D-BHB is significantly more ketogenic and provides fewer calories than a racemic mixture of BHB or medium chain triglyceride.Cuenoud, B., Hartweg, M., Godin, J. P., Croteau, E., Maltais, M., Castellano, C. A., … & Cunnane, S. C. (2020). Metabolism of exogenous D-beta-hydroxybutyrate, an energy substrate avidly consumed by the heart and kidney. Frontiers in Nutrition, 13. https://doi.org/10.3389/fnut.2020.00013
It’s important to note that the D-BHB is the biologically active form, which has been associated with most of the health benefits attributed to ketone bodies, such as improved energy metabolism, cognitive function, and cellular processes. L-BHB, being less biologically active, doesn’t contribute as much to these benefits.
When you test your blood ketones on your Keto-Mojo (affiliate link), or any other blood ketone monitoring device, you should know that they only measure D-BHB. So when you consume a racemic (D/L-BHB) electrolyte salt, the increased plasma L-BHB levels go undetected by your blood ketone meter.
While racemic BHB salts are the most common, some companies have started to produce and market ketone supplements containing only the D-BHB form, often referred to as “D-BHB salts” or “D-BHB esters.” These products aim to provide the benefits of ketone bodies more efficiently by exclusively delivering the biologically active D-BHB isomer. However, D-BHB supplements tend to be more expensive compared to the racemic BHB salts due to the more complex production process involved in isolating the D-BHB isomer.
Why would I use a racemic BHB salt when I can have the D-BHB form?
When it comes to L-BHB, it only makes up a small portion—around 2-3%—of our total BHB production during fasting. This has led to an assumption that L-BHB may not have significant functions in the body. But research has started to show that L-BHB is doing more than just hanging around waiting to be turned into D-BHB. It’s found to be involved in metabolism and could have roles beyond simply being an intermediate in the beta-oxidation of fats.
For example, a recent study used a technique to analyze and measure the distribution of the L-BHB and D-BHB isomers in different tissues of the rats, both before and after administration of a racemic ketone supplement containing both isomers. They found that a single high dose of a racemic ketone supplement containing both L-BHB and D-BHB caused a significant increase in L-BHB in all tissues, particularly in the brain.
Cell cultures provide clues that L-BHB has benefits in reducing inflammation. And it appears that having both L-BHB and D-BHB together in circulation at the same time may help upregulate immune function.
I would not completely disparage L-BHB as an inferior exogenous ketone supplement yet.
Research is still being done.
If you can get your hands on some D-BHB, go ahead and see if you find it works better for you than L-BHB. But if you can’t, or you can’t afford the more bio-identical form, don’t freak out. I use L-BHB in what I suspect is a racemic mixture, and I find it really helpful for my brain. I also recommend it to people I work with. And I am excited to follow the research literature that comes out to learn more.
I hope you found this blog post helpful in learning all the ways you can feel better!
Cuenoud, B., Hartweg, M., Godin, J. P., Croteau, E., Maltais, M., Castellano, C. A., … & Cunnane, S. C. (2020). Metabolism of exogenous D-beta-hydroxybutyrate, an energy substrate avidly consumed by the heart and kidney. Frontiers in Nutrition, 13. https://doi.org/10.3389/fnut.2020.00013
Han, Y. M., Ramprasath, T., & Zou, M. H. (2020). β-hydroxybutyrate and its metabolic effects on age-associated pathology. Experimental & Molecular Medicine, 52(4), 548-555. https://doi.org/10.1038/s12276-020-0415-z
Newman, J. C., & Verdin, E. (2017). β-Hydroxybutyrate: a signaling metabolite. Annual review of nutrition, 37, 51-76. https://www.annualreviews.org/doi/10.1146/annurev-nutr-071816-064916
Storoschuk, K., & Ari D’Agostino, C. “Why do we need both D-BHB and L-BHB?” Keto Nutrition: Science to Application. (Aug 14, 2022). https://ketonutrition.org/why-do-we-need-both-d-bhb-and-l-bhb/
Youm, Y. H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., … & Dixit, V. D. (2015). The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nature medicine, 21(3), 263-269. https://www.nature.com/articles/nm.3804