a woman doing an experiment

Will exogenous BHB supplements treat my mental illness?

I get it. You don’t want to change your diet. Totally understandable. And my answer to whether exogenous β-Hydroxybutyrate (also known as beta hydroxy-butyrate or BHB) supplements will treat your mental illness is that I don’t know. And even the experts on exogenous ketones don’t know. Although they strongly hypothesize that there could be a positive benefit,

… it is possible that exogenous ketone supplementation-induced ketosis may be an effective therapeutic tool against psychiatric diseases. Indeed, exogenous ketone supplements have a modulatory influence on behavior and anxiolytic effect in animal studies.

Kovács, Z., D’Agostino, D. P., Diamond, D., Kindy, M. S., Rogers, C., & Ari, C. (2019). Therapeutic potential of exogenous ketone supplement induced ketosis in the treatment of psychiatric disorders: review of current literature. Frontiers in psychiatry, 363. https://doi.org/10.3389/fpsyt.2019.00363

The Current State of Research on BHB Supplementation

But when that review was written in 2019 the research had not been done to answer the question of whether BHB supplementation could treat mental illness. And at the time of my writing this blog article you are reading, we still don’t know the answer. The research still hasn’t been done sufficiently to answer the question of whether BHB supplementation alone will treat your mental illness.

At present, there is a lack of comprehensive research on BHB supplementation as a standalone treatment for mental illnesses. Currently, published case studies, pilot trials, and Randomized Controlled Trials (RCTs) are primarily focused on the effectiveness of ketogenic diets in treating mental health conditions. I would imagine that in the future, research will broaden to investigate BHB supplementation on different mental illnesses specifically. I would expect (and hope) to see studies comparing the outcomes of patients on ketogenic diets to those using only BHB supplements. Additionally, research might explore the combined effects of ketogenic diets and supplementary ketone salts or other forms of BHB.

Ketogenic Diets and Their Relationship to BHB

Let’s look at that pretty cool research review that was done not that long ago, looking at the Therapeutic Potential of Exogenous Ketone Supplement Induced Ketosis in the Treatment of Psychiatric Disorders. They pulled a great deal from research on the ketogenic diet. Why? Because ketogenic diets produce three ketone bodies, one of which is BHB.

But nowhere in their review do they recommend that you attempt to use exogenous BHB supplementation as a treatment for your mental illness. They discuss the underlying mechanisms by which BHB, as a ketone body, helps treat neurological disorders and psychiatric illness, which is beyond impressive and hopeful. The authors are very respected researchers of ketone bodies and have clinical experience using exogenous ketones with a variety of neurological conditions. And even these authors call for further studies looking into the use of exogenous BHB supplementation in psychiatric populations.

Why? Because the current research best supports the use of ketogenic diets for neurological disorders and various mental illnesses. At least at this time.

Why Further Research is Crucial

But that’s not going to be the end of our discussion. Being a curious sort myself, I applaud your well-thought-out and reasonable question. It’s actually a really good question. And i want you to know that these things are also being thought about by researchers.

For example, there is really some exciting research promise and clinical applications for BHB infusions as a treatment in acute care situations.

As BHB can function as an alternative metabolic substrate to glucose during energetic stress, there is increasing interest in use of IV BHB in acute, in-patient conditions such as traumatic brain injury, or ischemic injury to the brain or heart

Storoschuk, K. L., Wood, T. R., & Stubbs, B. J. (2023). A systematic review and meta-regression of exogenous ketone infusion rates and resulting ketosis—A tool for clinicians and researchers. Frontiers in Physiology14. https://doi.org/10.3389/fphys.2023.1202186

What’s holding this up as an option in critical care units? Apparently, there isn’t a commercially available BHB in this form yet available. Somebody needs to get on that!

… the role of therapeutic ketosis in acute pathological states such as traumatic brain injury, stroke, heart failure and other diseases has been less extensively investigated due to the lack of a commercially available supply of intravenous BHB.

White, H., Heffernan, A. J., Worrall, S., Grunsfeld, A., & Thomas, M. (2021). A Systematic Review of Intravenous β-Hydroxybutyrate Use in Humans–A Promising Future Therapy?. Frontiers in Medicine, 1611. https://doi.org/10.3389/fmed.2021.740374

If there was IV BHB more readily available, I think it would still be a long time before we see it as a part of psychiatric treatment. Although I admit it would be really interesting to see research studies carefully designed for its use in acute psychiatric situations where treatment consent can still be given, and IRB approval of the study is even an option.

But no need to wait for IV methods of delivery! You should know that exogenous BHB supplementation can come in all kinds of forms but are typically made from a combination of BHB and mineral salts (i.e., potassium, calcium, sodium, or magnesium). Mixtures (racemic) of D and L-BHB forms, D-BHB alone, and some that are not bound to minerals (salts) are available.

There are ketone esters that have their own individual characteristics and considerations. Some have both D and L forms of BHB, some are monoesters and provide only D-BHB. There are practical considerations such as cost and some forms tasting pretty bad, but also in regards to their effects on metabolism. All are factors that need to be assessed with mental health populations looking to use them as either an adjunct to ketogenic diets or as a stand-alone treatment for mental health symptoms. All these variables would benefit from study.

BHB Supplementation Alone: A Clinical Perspective

Where do I stand on BHB supplementation alone?

I continue to be super excited about the emerging research on Beta-Hydroxybutyrate (BHB) and its role in neuropsychiatric health. It is super promising. However I want to be really clear with my current opinion on the use of BHB as a stand-alone treatment for mental illness and neurological disorders. As research comes out, my opinion may completely change. As always, I reserve the right to change my opinion based on what I learn in the future and the great research that will inevitably come out.

But here is the thing. I do not believe that simply supplementing with BHB or ketone salts will serve as an effective treatment for mental illness. In my clinical practice, I sometimes see improvements in mood and cognitive function using Ketone Salts (BHB Salts) as an adjunct on top of a well-formulated ketogenic diet that is optimized for the treatment of mental illness and neurological function. I have had many people try just the supplementation of BHB salts alone, without changing their diets.

While there is the occasional person who finds significant enough improvement and stops there, I have never seen this be the case for serious mental illnesses, such as schizophrenia, bipolar, treatment-resistant depression, or chronic anxiety. For most, any improvements seen in symptom reduction are described as insufficient or fleeting. Let’s talk about why that might be.

Mental illnesses are intricate conditions influenced by a myriad of factors, including genetics, environment, lifestyle, and brain chemistry, all of which are profoundly impacted by metabolic health. The benefits of BHB in the context of a ketogenic diet are part of a broader metabolic shift within the body and the brain, a shift that is not fully replicated by current supplementation with BHB alone.

Challenges and Realities of BHB Supplementation

While BHB can provide an alternative energy source for the brain, it does not correct the fundamental issue of impaired glucose uptake due to insulin resistance. Do you know exactly the dose of BHB you would have to ingest in order to fuel such a high-energy organ as the brain? Or to correct impaired immune function driving neuroinflammation? How much BHB supplementation is needed, and how often will it upregulate endogenous glutathione in the brain? Do you know what dose is needed to keep up with current levels of oxidative stress caused by eating a level of carbohydrates higher than one’s current metabolic health can handle? Do you know the dose amount and schedule needed to heal a brain despite an individual not making lifestyle changes needed to reduce these factors contributing to mental illness?

You don’t know?

Me neither. And neither do the researchers.

But beyond not knowing the perfect dosage for every brain, there are real practical considerations about relying solely on BHB supplements.

If you use BHB salts (also known as ketone salts), you will over-supply the mineral portion long before you get a sustainable energy source to fuel your brain.

But let’s say you find a D-BHB supplement that is not linked to salts (minerals), because they do exist on the market. Beyond the considerable cost of using such supplements throughout the day – a cost that is often prohibitive for many and not covered by insurance companies yet – there’s another challenge I really wonder about.

How will you fuel your brain while you sleep? When your higher carb intake occurs at dinner because you have not changed your diet, and your insulin resistance does not allow an adequate amount or duration of ketone production in order to stabilize neural networks, what does that mean for a brain trying to heal? I will tell you. High blood sugar levels continue to contribute to metabolic dysregulation, which BHB supplementation alone cannot fully rectify.

BHB has anti-inflammatory properties, but chronic high blood sugar and insulin resistance can perpetuate inflammatory pathways in the brain. BHB may alleviate some inflammation, acting as a molecular signaling body against chronic inflammation, but it doesn’t stop the ongoing inflammatory response caused by behaviors and environmental factors causing persistent metabolic imbalance.

BHB can reduce oxidative stress, but high blood sugar levels continuously generate reactive oxygen species, creating a cycle of oxidative damage. BHB supplementation can help, and yes, it can act as its own form of antioxidant, but it’s not a complete solution to the oxidative stress caused by chronic hyperglycemia.

I could go on about how untreated brain insulin resistance contributes to altered neurotransmitter function, reduced neuroplasticity, hormonal dysregulation, and compromised blood-brain barrier integrity, but you get the idea.

Also, let’s just throw out the fact that changing your diet changes your gut microbiome by modulating the fuels available to the microbiota. If you keep eating your usual diet, a BHB supplement is not going to change what your gut microbiome gets fed. As a result, you may not get the profound changes to the gut microbiome we see that improve epilepsy, which may very well be part of the effective treatment effects we see in using ketogenic diets for mental illness and neurological disorders.

The therapeutic potential of BHB in metabolic psychiatry is, in my current opinion, most effectively harnessed within the framework of a well-formulated ketogenic diet. This diet induces a comprehensive metabolic state that goes beyond the effects of BHB supplementation, impacting various aspects of brain health and function.

While BHB shows potential in influencing certain aspects of brain function, I don’t think it is going to pan out as a panacea. Relying solely on BHB supplements or ketone salts overlooks the critical importance of metabolic health on mental health, which may include diet, psychotherapy, and lifestyle changes that improve mitochondrial health and function.

Conclusion: Reflecting on BHB Supplementation and Mental Health

Let’s wrap this up with a story.

Once upon a time, there was a brain suffering from serious metabolic dysfunction. If this brain were a house, it would be engulfed in flames, or have lots of areas on fire. While exogenous BHB supplementation might help put the fire out, just as buckets of water would, we don’t know how much BHB would be needed to accomplish it. And if no diet or behavior changes were done to improve metabolic function in the brain, would BHB supplementation really be a treatment? Or would we just be using BHB supplementation as another form of symptom management, the way we currently attempt to do with medications?

So again, I get it. You don’t want to change your diet.

But I know for a fact that many of you really want to treat the root causes of your mental illness and get on with your life, enjoying your highest possible level of functioning. I know some of you are really fed up with symptom reduction models. They were never why you came seeking medical treatment, and you accepted medications only offering symptom reduction because it was all they had to offer at the time.

And I also know that some of you are happy to try something that just offers symptom reduction. And that is cool, too. Everyone has the right to know all the ways they can feel better. And BHB supplementation may do that for you. BHB supplementation might affect medications, so find a (hopefully ketogenic-trained) prescriber to talk through the pros and cons with you in the context of your current medications and diagnoses.

Regardless of which camp you are currently sitting in, I hope this article has been helpful in understanding the possible role of BHB supplementation in feeling better.


Cornuti, S., Chen, S., Lupori, L., Finamore, F., Carli, F., Samad, M., Fenizia, S., Caldarelli, M., Damiani, F., Raimondi, F., Mazziotti, R., Magnan, C., Rocchiccioli, S., Gastaldelli, A., Baldi, P., & Tognini, P. (2023). Brain histone beta-hydroxybutyrylation couples metabolism with gene expression. Cellular and Molecular Life Sciences, 80(1), 28. https://doi.org/10.1007/s00018-022-04673-9

He, Y., Cheng, X., Zhou, T., Li, D., Peng, J., Xu, Y., & Huang, W. (2023). β-Hydroxybutyrate as an epigenetic modifier: Underlying mechanisms and implications. Heliyon, 9(11). https://doi.org/10.1016/j.heliyon.2023.e21098

Kovács, Z., D’Agostino, D. P., Diamond, D., Kindy, M. S., Rogers, C., & Ari, C. (2019). Therapeutic Potential of Exogenous Ketone Supplement Induced Ketosis in the Treatment of Psychiatric Disorders: Review of Current Literature. Frontiers in Psychiatry, 10. https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00363

Soto-Mota, A., Norwitz, N. G., & Clarke, K. (2020). Why a d-β-hydroxybutyrate monoester? Biochemical Society Transactions, 48(1), 51–59. https://doi.org/10.1042/BST20190240

Storoschuk, K. L., Wood, T. R., & Stubbs, B. J. (2023). A systematic review and meta-regression of exogenous ketone infusion rates and resulting ketosis—A tool for clinicians and researchers. Frontiers in Physiology, 14, 1202186. https://doi.org/10.3389/fphys.2023.1202186

White, H., Heffernan, A. J., Worrall, S., Grunsfeld, A., & Thomas, M. (2021). A Systematic Review of Intravenous β-Hydroxybutyrate Use in Humans – A Promising Future Therapy? Frontiers in Medicine, 8. https://www.frontiersin.org/articles/10.3389/fmed.2021.740374


  1. Great post 🌹

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