Ketogenic diets help anxiety disorders

How could a ketogenic diet help my anxiety? Or improve my symptoms of Generalized Anxiety Disorder (GAD), Panic Disorder (PD), Social Anxiety Disorder (SAD), Obsessive-Compulsive Disorder (OCD), and or Post-Traumatic Stress Disorder (PTSD)?

Ketogenic diets help anxiety disorders by mediating the underlying pathologies of mental illness that are primarily metabolic in nature. These include glucose hypometabolism, neurotransmitter imbalances, oxidative stress, and inflammation.

Introduction

In this post, I will go into what the biological mechanisms of symptom reduction are when using a ketogenic diet for mental illness. My goal is to do so in a way that is easy to understand. Few people benefit from overcomplicated biochemistry explanations using words and processes they do not understand. My goal is for you to be able to read this blog post and then be able to explain how a ketogenic diet helps treat mental illness, and anxiety disorders in particular, to friends and family.

This blog post is an introduction to ketogenic diets for anxiety disorders in general. In this post, we describe the mechanisms involved in mental illness in general, in which anxiety is obviously a category, and discuss the therapeutic effects of the ketogenic diet on those mechanisms.

You may also want to read the posts I have written applying the ketogenic diet to the underlying pathologies seen in specific populations. There are more in-depth blog posts about using the ketogenic diet as a treatment for anxiety disorders.

Post-Traumatic Stress Disorder(PTSD)

Generalized Anxiety Disorder (GAD)

Panic Disorder (PD)

Social Anxiety Disorder (SAD)

Obsessive-Compulsive Disorder (OCD)

This is a different way to evaluate the literature about whether or not a particular therapy can be helpful for a particular diagnosis. Usually, we wait (sometimes for decades or longer) for randomized-controlled trials looking at a very specific therapy paired with a very specific diagnosis and/or population. But that is not the only way to evaluate whether or not therapy might be useful.

It can make perfect sense to explore whether we can modify those mechanisms with substances or interventions that have an effect on those same pathways. And while I am always excited about RCTs, there are plenty of people suffering from anxiety disorders right now at this moment. Today. They may not be getting adequate symptom control from the standard of care or be looking for an actual cure as opposed to symptom reduction models. These individuals may want to better understand the ketogenic diet as a treatment for anxiety disorders.

It is my hope that by the end of this post you will have a better understanding of the current evidence base for its use in anxiety disorders and why it can have benefits beyond what is offered by current psychopharmacological treatments.

What is happening in my brain that is causing my mental illness?

In a review of biological mechanisms, this current (2020) review discussed the four key underlying pathologies that are seen in mental illnesses and discusses how a ketogenic diet can influence mental health symptoms.

• Glucose Hypometabolism
• Neurotransmitter Imbalances
• Oxidative Stress
• Inflammation

Let’s go over each of these in a little more detail.

Glucose Hypometabolism

Glucose Hypometabolism is a metabolic disorder in the brain. It basically means that your neurons are not using glucose well as fuel in certain parts of your brain. A brain that does not have adequate fuel, even if you are eating plenty of food, is a starving brain. A starving brain is stressed and it calls the alarm in many different ways. These ways can include the other factors of inflammation, neurotransmitter imbalance, and oxidative stress that we will be discussing. When brain cells do not get adequate fuel they die. If enough brain cells in a particular area die we see brain structures shrink. Memory and cognition begin to become impaired.

A ketogenic diet, by definition, generates an alternative brain fuel known as ketones. Ketones can get into neuronal cells in the brain easily and bypass the broken cell machinery not allowing other fuels like glucose to enter. The brain shifts from attempting to use a primarily glucose-based metabolism to a fat and ketone-based metabolism. As you can imagine, a brain that can access fuel is a better working brain.

But the role of ketones as a fuel source is just the beginning of what they can do for an ailing or distressed brain. The ketones themselves have some of their own very positive effects. It is not just that the brain is being fed energy. The ketones themselves do not just maintain metabolic functioning, but they act as something called a signaling molecule. And a signaling molecule is basically like a little messenger running around, giving your cells updates about what is happening in the body, so that your cell can then manage its machinery to do the best thing at that moment. The information that these signaling molecules give is powerful enough to turn your genes on and off even! Ketones as signaling molecules have the power to help your cells do things to help you burn more fat for fuel or other purposes, reduce oxidative stress and increase the protection of your brain.

β-HB (a kind of ketone) is currently considered not solely an energy substrate for maintaining metabolic homeostasis but also acts as a signaling molecule of modulating lipolysis, oxidative stress, and neuroprotection.

Wang, L., Chen, P., & Xiao, W. (2021)

It is easy to see that a ketogenic diet, which acts as a signaling molecule that tends to make more of those important things happen, could be very beneficial in treating those underlying pathological mechanisms of mental illness (which includes anxiety disorders) that were introduced at the beginning of this post.

Neurotransmitter Imbalances

Hyperglycemia is a term used to describe blood sugar levels getting too high for the body to manage. If your body cannot manage glucose levels it cannot stop it from causing damage to tissues. Even people without a diagnosis of diabetes struggle with hyperglycemia. Many without even knowing it. It has been long established in the literature that hyperglycemia or the body’s inability to handle the amount of glucose (sugar) in the blood, creates inflammation. Oxidative stress is what happens when you don’t have enough antioxidants to offset the damage trying to occur from all the inflammation happening.

But wait a minute you say, this section is about neurotransmitter imbalances. Inflammation and oxidative stress are supposed to come later. And I would agree with you. Except for inflammation and the resulting oxidative stress that occurs because inflammation sets the stage for neurotransmitter imbalances.

There are many different pathways that affect neurotransmitter creation, balance, how long they hang around in the synapses to be enjoyed and used, and how they get broken down. But the best example of neurotransmitter imbalance when inflammation is high has to do with something we call the tryptophan steal. Tryptophan is an amino acid that comes from the protein you eat. That part isn’t the important part of our example. What is important is for us to illustrate what happens to tryptophan when it is in an inflammatory environment. An inflammatory environment is often, and I would argue most commonly caused, by eating more dietary carbohydrates than your particular body can handle.

And what do we restrict in a ketogenic diet? Carbohydrates. And what does that do? Reduce inflammation. And what magical signaling properties do some ketones have? Reduction of inflammation. And a well-formulated ketogenic diet increases the pool of nutrients available to make the most powerful antioxidant ever, that your own body can make with the right metabolic environment and that will deal will oxidative stress? Ok, sorry. Now I am jumping ahead too far. I got a little excited.

But I know you are getting the idea!

So let’s say your brain wants to make neurotransmitters out of the tryptophan you ate. If your inflammation is high, your body will take that tryptophan and make MORE of a neurotransmitter called Glutamate. Up to 100x more than it normally would if that tryptophan had encountered a less inflamed and stressed internal environment. Glutamate is an excitatory neurotransmitter. And you obviously need some because it is part of a well-balanced brain. But the amount made while the body is inflamed or under oxidative stress creates a lot more than is needed. Glutamate at too high of levels CREATES ANXIETY.

In excess, glutamate is the neurotransmitter for being overwhelmed and freaked out. It is a particularly unpleasant neurotransmitter imbalance that too many people live with and think is just a part of their daily lives every single day. And it may just very likely be that their carbohydrate-dominant diet is perpetuating this unpleasant neurotransmitter imbalance. This same pathway that makes too much glutamate in a high inflammation and oxidative stress environment negatively affects the balance in other neurotransmitters like dopamine, serotonin, and GABA. It reduces the creation of something called Brain-Derived Neurotrophic Factor (BDNF), which is what your brain needs (and plenty of it!) to help you learn, remember, and heal the effects of all that inflammation and oxidative stress that is happening (for whatever reason).

This next piece is just my opinion and even possibly a hypothesis I picked up from people I have followed and learned from along the way. But if so, I agree with them. It seems to me that it is almost as if your brain knows it is being “attacked” or is in “danger” with all that high inflammation. It is trying to tell you it cannot handle what you are doing. It wants to tell you to be on alert! Anxious. It needs to sound the alarm that it is not ok! And it has no other way to tell you. But it is not a very efficient way, is it? Because you don’t make the connection. You think you are anxious because of traffic, or your kids, or your job, or that making dinner is just too overwhelming. We are human beings constantly trying to make sense of our experiences, so we make connections between things that seem the most obvious. We start to avoid anything that we think stresses us out. Never knowing that a possible source of the stress we feel is happening internally as a direct result of our lifestyle choices.

But what happens to tryptophan if you do not have excessive amounts of inflammation or are suffering from oxidative stress? Tryptophan can then be used to “upregulate” or make more of the neurotransmitter GABA. GABA also needs to be balanced in the brain, but a little too much of it does not create an environment of excitability. In fact, many people would like more GABA.

Ever heard of Gabapentin? Often used as a mood stabilizer in psychiatric disorders? You guessed it. It works to increase GABA. Except in its attempts to increase GABA, it often causes side effects for people. Like sleepiness and brain fog. Increasing GABA with a ketogenic diet does not produce the same side effects as medications trying to accomplish the same thing.

GABA is the neurotransmitter of feeling “chill” and “I got this” and of not feeling overwhelmed with the ups and downs of life or the idea of new challenges. Who couldn’t use more GABA? Particularly those suffering from Post-Traumatic Stress Disorder (PTSD), Generalized Anxiety Disorder (GAD), Panic Disorder, and Obsessive-Compulsive Disorder (OCD)?

Are there other neurotransmitter imbalances involved in anxiety disorders? Of course, there is! That was just one very important and easily illustrated example. Some happen just from nutrient imbalances alone, which can cause inflammation and oxidative stress in their own right. As I have said in other blog posts. You may not need a full ketogenic diet to improve symptoms of anxiety. But it is important to note that the majority of Americans are not metabolically healthy and are very likely eating a much larger amount of dietary carbohydrates than their body (and brain) can handle. And that this alone can cause and contribute to the development of anxiety symptoms. So in that respect, it is an important and relevant example for the majority of individuals reading this blog today, trying to discover how the ketogenic diet could work for them or those they love.

Doesn’t it make sense to treat a fundamentally metabolic set of pathologies, which mental illnesses are, with a complimentary metabolic approach?

Nicholas G. Norowitz, Department of Physiology, Anatomy and Genetics, Oxford University (link)

Oxidative Stress

As I explained above, oxidative stress is what happens when you do not have enough anti-oxidants to protect you from all the biological fallout of just being alive. The job of antioxidants is big and important. Most people believe that this means they need to consume foods that have been identified as antioxidant-rich and take supplements like Vitamin E and C in order to protect themselves from this particular type of biological damage. But the reality is that you could not take enough supplementation or eat enough antioxidant-rich food to match the power of an antioxidant you could be making yourself, from inside your body, known as glutathione. And your internal production of glutathione skyrockets on a ketogenic diet. Remember how ketones act as signaling molecules? They tell your body to make more glutathione. And as long as you are eating a well-formulated ketogenic diet that has an abundance of what you need to make more glutathione, your body will do just that!

You came equipped with your own antioxidant system. I am sure the supplement industry does not want you to know that but it’s true.

If you think about it, this makes sense. We did not have grocery stores or year-long access to a variety of fruits and vegetables full of antioxidants throughout our history. Were there some? Well yes of course! Regionally there were likely many different dietary sources of increased antioxidants. But also, you came with your own machinery and that machinery makes an antioxidant more powerful than anything else you can put in your mouth for that purpose. So what is happening that our own endogenous antioxidant powerhouse known as glutathione is not able to keep all that oxidative stress in check?

You guessed it. Diets that contain levels of carbohydrates our bodies cannot manage increase inflammation. To deal with that inflammation we have to use a LOT of nutrients as cofactors to try to keep the damage in check. And those cofactors are also needed to make our glutathione. And if we are using them up with a highly processed carbohydrate diet full of things industrial oils (that will likely be another blog post) we become depleted, and we are not available to make the glutathione levels we need. Also, if we don’t make sufficient amounts of ketones because our diets are too high in carbohydrates for us, how can those ketones signal to our cells to make some extra to help us out?

So what does Oxidative Stress mean in mental illness and in anxiety in particular? There is a very strong association between levels of oxidative stress and anxiety disorders, although the direct causal factors are still being teased out. It is a strong enough association that the use of antioxidants is discussed in the research literature as a treatment for anxiety disorders.

Well there you go, you may say to yourself. I don’t need a ketogenic diet. I can just take more antioxidants. And I suppose that is an option. But do tell me when you have determined just the right dose of antioxidants, in the perfect form and combination, that reduces the damage that comes from oxidative stress in the brain to such a degree that you can eat all the sugar, processed carbohydrates, and inflammatory seed oils you want and not suffer from anxiety symptoms. As you can see, theoretically, using the antioxidants you eat or take as supplements as a way to reduce anxiety sounds like a great treatment option. And it may certainly help your symptoms, especially if you stop some of the other major metabolic stressors of sugar, refined carbohydrates, and other highly inflammatory industrial food products.

As I said, we do not always have to attempt a ketogenic diet to treat anxiety disorders. But eliminating unnecessary metabolic stressors AND rocketing your internal glutathione levels up using a ketogenic diet sounds like a level of intervention that you not only should know about but deserve to know is an option. Anxiety symptoms are awful. And you deserve to feel well and be without those symptoms as soon as possible. I don’t want to see you experimenting constantly with vitamin C dosages, taking a bunch of expensive anti-oxidant supplements, and continuing to suffer over the years when you could feel the benefits of reduced oxidative stress with the ketogenic diet in as little as a few weeks or months.

In mental illness, and specifically in anxiety, there is increased oxidative stress. Ketogenic diets reduce that pathology by allowing the body to make more of the powerful antioxidant known as glutathione. The level of glutathione your body makes seems to be well-equipped to deal with much of the oxidative stress that comes with being alive. When you remove unnecessary internal metabolic stressors and improve the nutrition availability in your diet, this directly improves your internal antioxidant mechanisms and reduces oxidative stress in your brain, quite possibly leading to a reduction in anxiety symptoms.

Inflammation

Inflammatory cytokines are a cause of neuronal inflammation. These inflammatory cytokines are actually a part of the brain’s own immune system. The immune system in the body and the one in the brain stay physically separate but they are able to talk to one another. For example, when you are acutely ill your body’s immune system will communicate with your brain’s immune system. The inflammatory cytokines then make you want to lie down, stay still, and rest. I give this example because I need you to understand that these inflammatory substances in the brain are powerful. And can literally control your behavior.

Anxious and overwhelmed and can’t get off the couch? It could be that unloading the dishwasher is just too much. It could also be that neuronal inflammation is telling you to stay still and not move. Do you have high neuronal inflammation because you are stressed about the dishwasher? Likely not. It likely is due to something else. It could be coming from a huge variety of things. But one of the causes could be your diet.

But wait a minute, you say! How can my food choices influence my immune system? That makes no sense!

Remember the term hyperglycemia? Meaning too much blood sugar or a level of blood sugar that is higher than your body can handle is occurring? This state influences your immune system in a negative way. It has been shown that hyperglycemia promotes the creation of proinflammatory cytokines (aka inflammation) and it makes it harder for your immune system to deal with threats. An immune system that is impaired by high blood sugar cannot knock out a threat in a quick and decisive manner. And the entire time that your immune system is fighting off some low-grade infection or virus, those inflammatory cytokines are hanging out in your brain just that much longer. And we know from what we have learned before how brain inflammation will then affect our neurotransmitter balance and our levels of oxidative stress. For example, inflammatory cytokines trigger the activation of an enzyme that degrades serotonin and the amino acid precursor tryptophan. It is believed this is one of the many mechanisms involved between inflammation and the neurotransmitter imbalances seen in anxiety disorders.

Because you have made it this far into this blog post, you know what that means for your anxiety! And if we have cerebral hypo-metabolism as well, we know how that lack of fuel stresses the brain and perpetuates your symptom cycle. You have learned that it is all connected.

So fine you say, I will reduce my sugar and my refined carbohydrates and that should do the trick! I will have a better immune system. And you absolutely would! That may be all you need to do and if that is the case I am super happy for you! A whole foods diet is a powerful intervention for many people. So why would you still maybe want to try a ketogenic diet for your anxiety disorder?

Because ketones have special properties. Not only are they important signaling molecules as described above, but they are also powerful in reducing inflammation. We think that they reduce inflammation by blocking some of the inflammatory pathways. And while we have mostly been discussing metabolic stressors that increase inflammation, dietary influences are not the only source.

We are bombarded with chemicals. We have leaky guts causing autoimmune reactions (which also are mirrored in the brain). We have gut microbiomes that are not ideal and could be causing inflammation in our brains. We don’t prioritize sleep which can increase inflammation. We encounter normal and not-so-normal psychological stressors that induce inflammation. Heck, even just being under fluorescent lights has been shown to increase inflammation.

You can change your diet, which I absolutely think you should! That will definitely help. But there are so many places you will be potentially getting brain inflammation from that it makes sense to increase the production of ketones. Ketones can help you fight the neuronal inflammation that is just going to be a part of our modern environment.

And the less inflammation you have as a result of employing ketones to work for you, the fewer micronutrients you are going to use up fighting inflammation.

And the more micronutrients you have available, the more glutathione you can produce to help with oxidative stress.

And the lower your oxidative stress and neuronal inflammation, the better you will be able to balance your neurotransmitters.

And are you loving as much as I am how this is all connected?!! And how your knowledge of the underlying mechanisms involved in your anxiety symptoms are coming together?!

Sharing this with you in a way you can understand is an absolute joy for me!

If you are still a little confused about the difference between oxidative stress and neuroinflammation and how they are related, you may enjoy this article below!

If Your Brain Were a City: Understanding Oxidative Stress and Neuroinflammation

Conclusion

The ketogenic diet is a powerful intervention that has benefits and may correct one or more of the four pathological underlying mechanisms underlying mental illness and anxiety disorders.

You can choose to use it as first-line therapy for your anxiety disorder.

You can attempt to use it in place of medications.

You can use it as a powerful complementary therapy with mental health counseling (my personal favorite).

And if you decide to use it in conjunction with your medications that you are already on, do let your prescriber know. As the ketogenic diet modulates all of those pathways that have been influencing your anxiety disorder, it will change how you respond to your medications, both in what symptoms you might get, and their effectiveness. If you are on medications please work with a qualified mental health professional and prescriber that is knowledgeable regarding ketogenic and medication adjustment.

You may have anxiety and depression, and some other co-occurring disorders such as ADHD, Alcoholism, or PTSD and may find those posts helpful in making your decision about whether a ketogenic diet is something you want to try for symptom relief.

Ketogenic Diets for ADHD

Ketogenic Diet Treats Alcoholism

Post-Traumatic Stress Disorder(PTSD)

As always, please feel free to learn more about my online program designed to help people learn how to treat their own mood and cognitive issues using a combination of the ketogenic diet and functional nutrition.

Brain Fog Recovery Program

Like what you are reading on the blog? Consider signing up and receiving this free eBook so you can learn about ways to work with me on your wellness goals.

Free Brain Nutrition Guide

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References

Alessandra das Graças Fedoce, Frederico Ferreira, Robert G. Bota, Vicent Bonet-Costa, Patrick Y. Sun & Kelvin J. A. Davies (2018) The role of oxidative stress in anxiety disorder: cause or consequence?, Free Radical Research, 52:7, 737-750, DOI: 10.1080/10715762.2018.1475733

Ask the Scientists: What is Cell Signalling. https://askthescientists.com/qa/what-is-cell-signaling/

Betteridge D. J. (2000). What is oxidative stress?. Metabolism: clinical and experimental, 49(2 Suppl 1), 3–8. https://doi.org/10.1016/s0026-0495(00)80077-3

Bouayed, J., Rammal, H., & Soulimani, R. (2009). Oxidative stress and anxiety: relationship and cellular pathways. Oxidative medicine and cellular longevity, 2(2), 63–67. https://doi.org/10.4161/oxim.2.2.7944

Hu, R., Xia, C. Q., Butfiloski, E., & Clare-Salzler, M. (2018). Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection. Clinical immunology (Orlando, Fla.), 195, 139–148. https://doi.org/10.1016/j.clim.2018.06.003

Jeong EA, Jeon BT, Shin HJ, Kim N, Lee DH, Kim HJ, et al. Ketogenic diet-induced peroxisome proliferator-activated receptor-gamma activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures. Exp Neurol. 2011;232(2):195–202.

Maalouf, M., Sullivan, P.G., David, L., Kim D.Y. & Rho, J.M. (2007). Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience, 145(1), 256-264. https://doi.org/10.1016/j.neuroscience.2006.11.065.

Inflammation. National Institute of Environmental and Health Sciences. https://www.niehs.nih.gov/health/topics/conditions/inflammation/index.cfm

Paige Niepoetter and Chaya Gopalan. (2019). The Effects of Ketogenic Diets on Psychiatric Disorders Involving Mitochondrial Dysfunction: A Literature Review of the Influence of Dieting on Autism, Depression, Anxiety, and Schizophrenia. HAPS Educator, v23 n2 p426-431. https://files.eric.ed.gov/fulltext/EJ1233662.pdf

Paoli, A., Gorini, S. & Caprio, M. The dark side of the spoon – glucose, ketones and COVID-19: a possible role for ketogenic diet?. J Transl Med 18, 441 (2020). https://doi.org/10.1186/s12967-020-02600-9

Norwitz, N. G., Dalai, Sethi, & Palmer, C. M. (2020). Ketogenic diet as a metabolic treatment for mental illness. Current opinion in endocrinology, diabetes, and obesity, 27(5), 269–274. https://doi.org/10.1097/MED.0000000000000564

Samina, S., Gaurav, C., and Asghar, M. (2012). Advances in Protein Chemistry and Structural Biology – Chapter One – Inflammation in Anxiety.
https://doi.org/10.1016/B978-0-12-398314-5.00001-5.
(https://www.sciencedirect.com/science/article/pii/B9780123983145000015)

Vincent, A. M., McLean, L. L., Backus, C., & Feldman, E. L. (2005). Short-term hyperglycemia produces oxidative damage and apoptosis in neurons. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 19(6), 638–640. https://doi.org/10.1096/fj.04-2513fje

Volpe, C.M.O., Villar-Delfino, P.H., dos Anjos, P.M.F. et al. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis 9, 119 (2018). https://doi.org/10.1038/s41419-017-0135-z

Wang, L., Chen, P., & Xiao, W. (2021). β-hydroxybutyrate as an Anti-Aging Metabolite. Nutrients, 13(10), 3420. https://doi.org/10.3390/nu13103420

White, H., Venkatesh, B. Clinical review: Ketones and brain injury. Crit Care 15, 219 (2011). https://doi.org/10.1186/cc10020