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how to increase glutathione on a ketogenic diet – supplements

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How do I increase glutathione on a ketogenic diet?

The amino acids glycine, cysteine, and glutamine are used in glutathione production. Eating foods that are good sources of complete amino acids or taking a balanced amino acid supplement will help you make more glutathione. Other important nutrients like B-vitamins, magnesium, selenium, zinc, iron, and alpha-lipoic acid can also help the body supercharge the already higher levels of glutathione possible on a ketogenic diet.

Introduction

This blog post will discuss how and why you may want to provide additional supplementation to increase your glutathione (GSH) production while on a ketogenic diet for mental illness or neurological disorders. 

This blog post contains multiple affiliate links. Please do not feel obligated to use them. They are here for your convenience.

If you are not on a ketogenic diet, you may still find this post to be very helpful in evaluating whether or not you are getting enough of what you need for improved glutathione production.

If you do not know what glutathione (also known as GSH) is or why you might need it to heal a mental illness or neurological disorder, I encourage you to read the following. 

If you are on a ketogenic diet, you are already doing a great thing to increase your glutathione. Lowering your carbohydrates and reducing the inflammation and oxidative stress that goes with that means more glutathione available to begin to heal your brain. If you are doing a well-formulated and nutrient-dense ketogenic diet, you are increasing your intake of what your body needs to make more glutathione. But it’s not just your reducing inflammation and oxidative stress with knowledgeable food choices or increased nutrient intake. 

The production of ketones you are making on your ketogenic diet improves your mitochondrial function. Because ketones are signaling molecules, they trigger adaptive transcriptions of genes that provide improved mitochondrial functioning. Mitochondria are the powerhouses of your cells, and this enhanced function and increase in energy will provide additional fuel for detoxification and healing processes in your neurons. 

This process may ultimately increase the levels of antioxidants (e.g., GSH) and detoxification enzymes, thereby improving brain function and alleviating neurodegeneration.

Shamshtein, D., & Liwinski, T. (2022). Ketogenic Therapy for Major Depressive Disorder: A Review of Neurobiological Evidence. Recent Progress in Nutrition2(1), 1-1. doi:10.21926/rpn.2201003

So the ketogenic diet all by itself is a huge glutathione boost! But let’s say you have a lot of healing to do. And you want more! Then what?!

Why don’t I just take a glutathione supplement?

You totally can! And that is a legitimate way to do it, now that we have liposomal glutathione, which we know is absorbed well by the body and used. It is not my preferred option with clients, and I will tell you why.

First of all, it can be expensive, depending on the brand. I would prefer my client’s budget for other supplements of important micronutrients, good quality food, and occasional testing. But there is a place in certain cases for supplementing directly with liposomal glutathione. 

Secondly, there have not been enough studies to show that pre-assembled glutathione gets into all cells without any issue. So if I supplement you with premade glutathione, I just don’t know how much you are absorbing for sure. Even the liposomal form, because we just don’t have all those studies yet. And if I hand you supplements for liposomal glutathione, I have no idea if it is getting to all the places that your brain and body need it to heal. It’s much better for me to make sure you have everything you need to make your own and trust your body knows how to deliver it where it needs to go. 

I know that my saying your body knows how to heal itself instead of saying that I, as the healthcare practitioner know best, might be a little shocking. 

It will be most shocking if you are reading it after being in the traditional medical model of being told that your doctors know what pill to give for what thing and that they know best. No. Your body often knows best. And if you have been sick for a long time and gone to a lot of doctors, you may have stopped trusting your body was on your side or that it knew what to do to help you feel better. 

That is not what went down. It’s time to change how you think about your body. What happened is that you didn’t know what or how to give your body what it needed to heal. And quite frankly, neither did your doctor. 

But I digress. 

The third reason I do not prefer supplementing glutathione directly is that your body already has wonderful mechanisms to determine how much needs to be made at any given time. I trust your body to be smarter than me. In fact, I know your body is smarter than me when it comes to knowing how much glutathione your body needs to make and at what rate to heal. As long as I help you get access to the rate-limiting precursors and make sure you are able to digest and absorb them, I know that your body is going to use those resources appropriately to help you heal. 

What if I give you a dose of supplemental liposomal glutathione each day that is not enough of what your body wants or needs? And you didn’t have enough of these other rate-limiting precursors or important nutrients to make more? I would slow down your healing.

What if I gave you a really big dose of supplemental liposomal glutathione each day, and you were doing just fine being able to make your own with the right precursors and nutrients? Well, then I just wasted a lot of your money.

So feel free to supplement liposomal glutathione if you feel like you just want that extra support to heal and you can afford it. And don’t prioritize its purchase over your well-formulated ketogenic diet grocery list. Don’t buy it and ignore the other important nutrients discussed in this blog post. You still need many of the amino acids and micronutrients we will discuss to make neurotransmitters and facilitate your healing!

If you want to take liposomal glutathione, you can find several good brands here (affiliate links):

I don’t recommend the liquid forms because they don’t taste good, and they don’t mix well in other things. But if you do need a liquid for whatever reason, you can find one here (affiliate link)

I would just simply take as directed on the back of the bottle. There does not appear to be any negative side effects of taking larger doses (up to 1000mg) for longer amounts of time. The range is between 250mg-1000mg, and it can take months to build up. You may want to take a mid-range to a higher dose if you are trying to recover from mental illness or a neurological disorder. You can discuss dosing with your healthcare provider. 

So let’s talk about all the things you might need to supercharge your ketogenic diet to treat your mental illness or neurological disorder and why.

Why you might need supplementation even though you are on a well-formulated, nutrient-rich ketogenic diet

You were or are ill – People with mental illnesses or neurological disorders can have genetic variances that require them to have particular forms of vitamins or more of certain vitamins or minerals. Until you get genetic testing and look at your nutrigenomics, you might not know what supplements and foods to increase to meet your needs. 

You may find getting genetic testing helpful through 23andme (affiliate link) and subscribe to geneticlifehacks.com (affiliate link) to learn more about yourself! 

Your prior diet depleted your nutrients like Thiamine (B1) and Magnesium and was probably insufficient in protein and vitamins, and minerals. Eating a well-formulated ketogenic diet will definitely help a great deal! But you may need to play a bit of catch-up through supplementation to feel better faster or to even recover from the deficit you are already in.  

Your prior diet produced a lot of inflammation that drained your nutrient stores to fight inflammation and oxidative stress.

Your prior diet was not nutrient-dense enough and included ultra-processed foods that crowded out your intake of what you needed for a well-functioning brain.

You were on medications that caused drug-induced nutritional deficiencies which left your stores of nutrients low that would be used to make more glutathione. If you do not know what drug-induced nutritional deficiencies are or what medications may cause them you may benefit from reading the following:

You were exposed to heavy metals, either acutely or chronically over your lifetime, and you need a lot of glutathione to help detox your system. Glutathione (and other specific supportive supplements) are particularly important if working with a functional medicine person during chelation therapies.

So what do you need to make sure you are making and recycling glutathione well to help heal your mental illness or neurological disorder?

Certain amino acids and micronutrient cofactors are needed to upregulate your glutathione production. Here is a good overview before we begin!

Graphic listing the glutathione cycle, precursor amino acids, and what nutrient cofactors are involved in glutathione production and maintenance. Created by http://www.mentalhealthketo.com

Amino Acids

You must get enough protein, and you must be able to break it down and absorb it properly. A good rule of thumb is a protein intake is between 0.8 g/kg and 1.8 g/kg (not lbs, kg) of body weight. 

Ketogenic diets for mental health and neurological disorders tend to be on the low side of protein traditionally. This level needs to take into consideration factors such as your age, activity level, how often you exercise, and how much healing you have to do. 

If you are vegan or vegetarian, know that you are only absorbing about half of the protein you think you are from plant-based sources and that you may need to supplement accordingly or be particularly careful in making sure your meals provide complete amino acid profiles. 

Ketogenic diets tend to be on the lower end of protein intake, but I don’t suggest that for all of my clients because of the factors I just mentioned. Also, different types of ketogenic diets use higher levels of protein intake and still successfully treat disorders, such as epilepsy. The modified-Atkins diet form of the ketogenic diet is a good example of this. 

Why do I want you to make sure you get enough protein if you are trying to upregulate your glutathione production on the ketogenic diet? 

Because glutathione production uses the amino-acids glycine, glutamine, and most importantly, cysteine. Cysteine is the rate-limiting factor. Meaning if you do not have enough cysteine, your body is limited in making as much glutathione as it wants and needs to heal. 

This does not mean I want you to run out and just supplement these three amino acids. People with mental illness should only supplement with individual amino acids if they work with a medical provider. Why? Because they are powerful enough to throw your neurotransmitters out of balance. I am infinitely more interested in you getting your amino acids from whole foods that come in balanced ratios.

To do that, you need to have sufficient stomach acid and the ability to break those proteins down and absorb them. If you don’t know what I mean by that, you should read this blog post here:

But let’s say you already know your stomach acid and digestion is a work in progress. You still need to upregulate your glutathione, which may very well be the case if you are doing a ketogenic diet for mental illness or neurological issues.

Luckily, you can take a balanced amino acid supplement that has already done the work of breaking the protein down for you. Don’t take a supplement that are just branch-chain amino acids (BCAAs) because that is not a balanced formulation and could upset neurotransmitter balance.

These are products that I recommend for clients for various reasons, and that you can use to increase your intake of these amino acids.

Balanced Free-Form Amino Acids (Hardy’s Nutritionals) – this is not an affiliate link but you can use 15% off discount code: MentalHealthKeto

“But wait a minute!” you might say. “This doesn’t have the rate-limiting amino acid cysteine in it! How will this help me make glutathione?”

Don’t worry! Cysteine is made from the amino acids serine and methionine that are in these formulations! But you need enough micronutrient cofactors to help that happen.  

You will also notice that the above amino acid supplements have a nice dose of glutamine, and that should make you very happy!

Glutamine is a non-essential amino acid, meaning our body can make it as needed. And when we are in a healthy body (with a healthy brain), our body has no problem doing that. But you do not have a healthy body (or brain) yet, so you can likely benefit greatly from supplementing with the glutamine in the supplement above. Glutamine can become depleted with chronic stress, and I think we can agree that having a mental illness or neurological disorder is a form of chronic stress!

Glutamine supplementation will help you upregulate your glutathione, but it also provides fuel for your gut cells that are trying to repair themselves. And that is just an extra bonus that will translate into gains for your mental health as your gut health improves. 

Glycine is also in the amino acid supplement Amino Replete (affiliate link) but in a smaller amount. I believe there is a benefit to supplementing glycine on its own and possibly in addition to the Amino Replete supplement. 

I like taking mine in my coffee as a collagen supplement (glycine is one of the amino acids provided). This is the one that I use (affiliate link):

I get collagen peptides from a local big box store (Costco) because it is cheaper. I take one scoop in my morning coffee and one in my second cup a few hours later (decaf usually, or in some tea). 

You can also supplement this using gelatin or just glycine. Most people do not get adequate levels of glycine in their diet, and so there is less concern with creating a neurotransmitter imbalance with it. Below is a brand my clients use, and I recommend just 1 a day for a total of 1,000 mg (1 gram). Again, we don’t want large amounts of any one amino acid taken without the assistance of a healthcare practitioner who knows your case. (affiliate link):

I have used glycine powder before, but I like the extra boost of arginine, proline, and hydroxyproline I get from a collagen peptide powder. That is how they come when consumed in whole foods, and so I think taking them as a collagen peptide is preferred.

And that wraps up our section on amino acids. In summary, you want to eat enough protein and be sure to do things to improve your breakdown and absorption of the protein you get in whole foods. Make sure you eat proteins that are as complete as possible, which is a major concern if you are vegan or vegetarian. 

Let’s move on to the micronutrients your body uses to make glutathione!  

Micronutrients

You can have plenty of amino acids but if you don’t have the micronutrients you need to make plenty of glutathione and glutathione enzymes your healing is going to be stymied.

Vitamin C

This micronutrient is used to glutathione from its oxidized state (used) back to its active state. You can get vitamin C from foods on a well-formulated ketogenic diet just fine, but as you are healing, you can give your glutathione production a nice boost with a little bit of supplementation, at least in the short term. 

Vitamin C can be the least expensive and easiest supplement to add, and it doesn’t have to be a very high dose to improve your glutathione recycling capability. You don’t need very much, and it is suspected your body is better at recycling vitamin C when you eat low carbohydrate diets. 

I just use the simple and inexpensive form for clients to provide a small boost. Liposomal Vitamin C is better absorbed, and if you feel you would like to try that, there can be a benefit in helping reduce early on in your healing process. You can supplement anywhere from 250mg to 1000mg a day. I have provided affiliate links below:

Vitamin E

I am not a huge vitamin E fan, but I think it has its place, especially if you come from a highly-processed diet high in industrialized seed oils. You will benefit from increased Vitamin E for at least a couple of years as you work those oils out of your system. And there is also some benefit to taking vitamin E if you are trying to upregulate your glutathione. You need vitamin E to ensure your glutathione enzymes can work properly. 

I generally choose this supplement for clients and provide about 30mg (approx. 45 IUs).

B vitamins

These water-soluble micronutrient cofactors help keep your glutathione enzymes functioning and are important in recycling glutathione back into its active form; you need plenty of vitamins B1 (thiamine) and B2. These B vitamins have a direct effect on glutathione production and enzyme function. But there are other B vitamins that have indirect effects that you will want to make sure you have plenty of, such as vitamin B6, B9 (folate), and vitamin B12 which help you make and use the amino acids we discussed earlier in this post.

I tend to recommend this one in my practice because they have good, bioavailable forms of b vitamins for my clients. You can purchase through this affiliate link below:

Selenium

If you are on a well-formulated ketogenic diet, you are likely getting plenty of selenium. But in the beginning, as your body is trying to heal, you may benefit from supplementation to help boost glutathione production. Selenium helps make the enzyme glutathione peroxidase (GPx) and speeds up how fast your glutathione works to detox free radicals. I like to think of them as little detox accelerators, and the faster that free radical is neutralized, the less damage has to be repaired later. And I think that is a good thing that benefits your healing journey. 

Selenium is an inexpensive supplement with great benefits. Particularly for this purpose. I recommend this one to my clients below (affiliate link):

Magnesium

I just cannot stress enough that you are very, VERY likely coming into your ketogenic diet for your mental health magnesium deficient. I could do a whole blog post on magnesium and how it influences your mental health and neurological functioning. Still, for our purposes here, you just need to know that it is very important for the enzyme gamma-glutamyl transpeptidase (GGT) and that this enzyme is directly involved in your body’s ability to make glutathione!

So please don’t mess around in your supplementation of it. Take it seriously. have clients take 400 to 800mg a day, up to bowel tolerance. If you find it makes your stools loose, back off a pill or two. But it is likely you are so deficient you won’t have that effect until far further down the road (if at all, our bodies need a LOT of magnesium). Break the doses up throughout the day to improve absorbability. 

I like this particular brand because I know there is 200mg of elemental magnesium in each capsule. This is an affiliate link: 

Zinc

If you are insufficient in zinc, it will reduce your glutathione levels. How? It is needed to make the enzyme glutamate-cysteine ligase (GCL). This enzyme is needed for the very first step in glutathione production of combining glutamate and cysteine. Many people are low in zinc, particularly if they do not eat a lot of bioavailable proteins. But most people are somewhat deficient in this nutrient or are taking in suboptimal levels. I recommend 1 of these, 2x per day with food. Zinc on an empty stomach can cause nausea. This is an affiliate link:

MSM (methylsulfonylmethane)

I really like this supplement because it can provide a source of dietary sulfur. If you are already eating a lot of sulfur-containing vegetables and meats with methionine you may not need this supplementation. But I find a lot of people could benefit from increased sulfur in their diet. Particularly those coming off of a vegan or vegetarian diet.

I add this supplement hesitantly to this blog post because some people have gut bacteria that make their own form of sulfur, and adding MSM to their stack can cause real stomach problems like cramping and diarrhea. Most of my clients do not have issues with taking MSM but once in a while someone does, and when that happens we just discontinue its use and deal with why their gut is making its own sulfur in the first place.

But I think MSM is an underutilized healing molecule in people trying to reduce oxidative stress by increasing their body’s own antioxidant pathways, and so I include it here so you can give it a try. I think it is super amazing.

Alpha-lipoic acid

Your body makes this antioxidant, and while it doesn’t help you make more necessarily, it plays a role in helping stimulate the enzymes involved in glutathione synthesis. It has other roles in helping you recycle vitamin c and E and getting cysteine in the cell where the amino acid will be used for glutathione production. 

If you eat a well-formulated ketogenic diet with bioavailable proteins and low carbohydrate vegetables, you are likely getting enough of these nutrients. But if you would like to supplement for additional healing purposes, or if you know that you have challenges producing glutathione because you have done genetic testing, this might be a good addition. This supplement plays a role in restoring and maintaining glutathione levels. 

Below is an affiliate link for alpha-lipoic acid for your convenience:

Multivitamins

If you do not want to supplement these higher doses individually, I completely get that. That said, I want you to be aware that if you were suffering from a mental illness or neurological disorder, you likely need many more nutrients than you think. You may have a higher need for them than other people because of genetic variations. And you are likely coming into your ketogenic diet with real deficiencies in important vitamins like B1 and magnesium, which may require very high supplementation for a short time to turn your mental health around and feel better. 

You may need personalized testing and supplementation for some of these micronutrients to correct deficiencies. If you are still not feeling well after about three months, be sure to reach out and contact me or another professional for an individualized nutrition and supplement plan. 

I know it is not ideal to be taking a lot of extra pills a day and spending a lot on extra supplements. But it might be really helpful to your healing if you do, at least for a while, until you have a better idea of what the minimum is you need to feel well, along with your improved food choices in your nutrient-dense, well-formulated ketogenic diet.

If you just want to take one formula as a multivitamin, I cannot recommend Hardy’s Nutritionals enough. I do not have an affiliate link for them, but I do have a 15% of discount code you are welcome to use: MentalHealthKeto

DAILY ESSENTIAL NUTRIENTS 360

These are 9 to 12 pills a day, broken up ideally into three times a day, but people definitely feel the benefit and get away with twice a day if they are busy humans. I recommend you work up to the recommended 12 a day if you are healing from mental illness or neurological disorders.  

If you are not healing from a mental illness or neurological issue, do not have any chronic health issues, do not have a history of or are taking medications that might deplete your nutrient stores, you may not need these higher levels of supplementation. You may want to just take a good multivitamin to help upregulate your glutathione production (on a ketogenic diet or not). If that is the case, I would recommend this multivitamin (affiliate link):

As you can see, these have all the micronutrients we have discussed in this article in different amounts, some smaller amounts, some equal, and some even higher. They are a good, general, all-purpose way to cover most of your bases if you intend to increase your body’s capacity to make and benefit from glutathione. You will still need to supplement magnesium.

Another potential supplementation is melatonin. If you are part of an older population and you suspect you are not making sufficient melatonin there is a possibility it could be affecting your glutathione production. Melatonin plays a role.

… we review the studies which document the influence of melatonin on the activity and expression of the antioxidative enzymes glutathione peroxidase, superoxide dismutases and catalase both under physiological and under conditions of elevated oxidative stress. 

Rodriguez, C., Mayo, J. C., Sainz, R. M., Antolín, I., Herrera, F., Martín, V., & Reiter, R. J. (2004). Regulation of antioxidant enzymes: a significant role for melatonin. Journal of pineal research36(1), 1-9. https://doi.org/10.1046/j.1600-079X.2003.00092.x

Melatonin can be tricky because if you take too high of a dose you can feel sleepy the next day. If I suspect melatnoin is needed I will supplement 0.25 mg and work up to perhaps 3mg in some populations. In older populations and in those with a history of Alzheimer’s disease in their family sometimes I will supplement 3-6mg. I like the sustained release versions over the quick release and sometimes I will have people take a combination of forms.

Conclusion

After glutathione levels are increased you need adequate levels of copper, zinc, manganese, iron, selenium, and magnesium to neutralize the free radicals that your glutathione “catches”.

I hope you have found this blog post helpful in learning how to increase your glutathione levels naturally or with direct supplementing with liposomal glutathione. Whether you decide to supplement with liposomal glutathione or increase your precursors to supercharge your ketogenic diet, rest assured that paying attention to your glutathione status is an important factor in attaining and keeping your mental health.                

Because you have the right to know all of the ways that you can feel better.


References

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Ketogenic Diet for Bipolar Disorder

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Can the ketogenic diet treat bipolar disorder?

Mounting evidence supports the use of ketogenic diets for bipolar disorder because of the ketogenic diet’s ability to modify underlying pathological mechanisms such as brain hypometabolism, neurotransmitter imbalances, brain inflammation, and oxidative stress. There are numerous anecdotal reports, published case studies in peer-reviewed journals, articles reviewing the literature on the topic, and randomized controlled trials being conducted evaluating the ketogenic diet as a treatment for bipolar disorder.

Introduction

Manic episodes in BPD are generally considered to be fairly well-managed through medications. But major depressive episodes are still considered to be recurrent and a significant clinical challenge. People with bipolar disorder suffer from a burden of significant depressive symptoms, even for those whose manic episodes feel well controlled with medication.

These phases can create persistent functional impairment and disability and increase the risk of suicide. Relying on ineffective medications to treat the depressive phases of bipolar disorder is both cruel and potentially dangerous. Even if it is the standard of care. Existing mood stabilizers for the depressive phase of bipolar disorder are only effective in 1/3 of bipolar patients and standard antidepressants repeatedly fail to show benefit in RCTs for this condition and may even worsen the condition. Atypical antipsychotics are reportedly more effective but have devastating metabolic disorder effects that make long-term use unhealthy and side-effects often intolerable for patients.

I write the above to illustrate the plight of many suffering from bipolar disorder, and to point out that even if someone with bipolar disorder has gotten their manic symptoms under control with medication (many have not), there is still a significant portion of the bipolar population suffering from residual symptoms.

And they deserve to know all of the ways they can feel better.

Several biological mechanisms have been proposed as potential underlying causes of BD. These include mitochondrial dysfunction, oxidative stress and neurotransmitter disruption.

Yu, B., Ozveren, R., & Dalai, S. S. (2021). Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments. https://www.researchsquare.com/article/rs-334453/v2

As we discuss glucose hypometabolism, neurotransmitter imbalances, inflammation, oxidative stress, and how a ketogenic diet modifies those factors, you will begin to understand why people are doing the ketogenic diet for bipolar disorder.

Let’s get started!

Bipolar Disorder and Hypometabolism

Key underlying metabolic pathologies thought to play a role include dysfunction in energy metabolism.

Yu, B., Ozveren, R., & Dalai, S. S. (2021). The use of a low carbohydrate, ketogenic diet in bipolar disorder: systematic review. https://www.researchsquare.com/article/rs-334453/v1

What is brain hypometabolism? And do people with bipolar disorder have hypometabolism?

Brain hypometabolism simply means that brain cells are not using energy well in some parts of the brain or in specific structures. 

  • hypo = low
  • metabolism = energy use

People with bipolar disorder have regions of brain hypometabolism, meaning those brain areas are not as active as they should be. Brain hypometabolism is really about mitochondrial dysfunction, which is basically how the brain uses fuel and how well it produces energy.

It is not just one particular area of the brain in which we see accumulated mitochondrial dysfunction play out as energy deficits. Some of the brain areas identified as hypometabolic through different neuroimaging technologies include the insula, brainstem, and cerebellum.

There is also ample evidence of hypometabolism causing disrupted connectivity within the frontal white matter. These disruptions of cell structure and metabolism occur deep in the brain’s white matter between the front-limbic network. For those new to all these brain structure names, your limbic system is an emotional center of the brain. But it is important to understand that your emotions can come from your appraisal of a situation (oh that’s a tiger and they eat people!) and that that message goes to your limbic system to initiate a response (RUN!). In bipolar disorder, we see white matter connectivity problems in major cognitive networks that include the dorsolateral prefrontal cortex, temporal and parietal regions. Which are basically all very important parts you need to function and burn energy well.

These identified areas of brain structure hypometabolism are not surprising when we think about the manifestation of affective and behavioral symptoms in bipolar disorder. For example:

  • disrupted connectivity between dorsal cingulate cortex, and precuneus, cuneus.
    • It is thought that this disrupted connectivity may play a role in subsequent over-reactivity during emotional processing in bipolar patients
  • dorsolateral prefrontal cortex
    • controls executive functions like planning tasks, working memory, and selective attention.
  • dorsal cingulate cortex
    • executive control (which you need to regulate emotion), learning, and self-control.
    • hypometabolism in the cingulate cortex is seen in individuals with substance use disorders
  • precuneus
    • perception of the environment, cue reactivity, mental imagery strategies, episodic memory retrieval, and affective responses to pain.

But wait a minute, you may say. Over-reactivity? How can that happen in a brain with hypometabolism when we expect not enough energy for over-activity to occur? And also, don’t some phases of bipolar disorder make everyone sort of hyperactive? Like they can’t stop or sleep? How does this apply?

Well, the answer is a little paradoxical. When some brain areas do not have enough energy to function, it can cause downstream effects that disrupt neuronal balancing in other regions. So hypometabolism in some parts of the brain throws the delicate system of the brain off, and it ends up perpetuating neurotransmitter imbalances throughout or in neighboring structures, causing hyperexcitability on a neurotransmitter level. which we will discuss more in later sections (see Neurotransmitter Imbalances). Hypometabolism in one area of the brain can cause the brain to make too many connections to other parts of the brain, trying to compensate. You can end up with connectivity between areas that don’t really belong being quite so connected.

The inability of brain cells to have adequate energy from a stable fuel source perpetuates mitochondrial dysfunction. Mitochondria are the batteries of your cells, and they are needed to accomplish all the things that a neuron needs to do. If your brain fuel is no longer working for you, which in the case of glucose and bipolar disorder may very well be the case, those batteries cannot work. The neurons do not have enough energy to function and start to just not work right! A malfunctioning neuron is unable to do basic cell housekeeping, make neurotransmitters, or even keep those neurotransmitters around for the right amount of time in the synapse, or even be able to communicate well with other cells.

Because they are in distress, they create their level of inflammation and oxidation, using up precious cofactors (vitamins and minerals) trying to fight the inflammation occurring because the cell is in distress from an energy deficit. Depleting the cell further and adding to the poor energy cycle in the neuron.  

One of the theories why this happens is that the metabolism of glucose is impaired in the brain due to poor conversion of an important enzyme called pyruvate dehydrogenase complex (PDC). Problems with converting glucose as a fuel source for energy in the brain have grave consequences.

This hypometabolism, and subsequent mitochondrial dysfunction, is so relevant in the bipolar brain, that researchers can make transgenic mice with specific brain mitochondrial dysfunction, and completely recreate the symptoms that a bipolar human experiences!

And, when they medicate these transgenic mice with lithium or even regular antidepressants, they respond in the same way as human bipolar patients do to those medications.

So my point is this. Hypometabolism is a HUGE factor in the creation and perpetuation of bipolar symptoms. It deserves attention as a direct target of intervention in bipolar disorder.

Now, let’s discuss how a ketogenic diet, a known therapy for metabolic disorders, can help.

How keto treats hypometabolism in bipolar disorder

Ketogenic diets are a neuron’s best friend. Not only do they provide an alternative fuel source to glucose in the form of ketones, this ketone energy just slips right into the neuron, bypassing any special enzyme processes or faulty transporter functions. This improved energy metabolism gives the bipolar brain energy to do all the things it needs to, much better than it could before.

As if having a better fuel source that brains could use better was not enough, the ketones themselves are gene signaling bodies. this means they can turn genes on and off in various pathways. And one of the things these ketones do is encourage the cell to make more mitochondria. Ketones literally increase brain energy by making more of those cell batteries and then providing the fuel to burn in them.

If you are still unconvinced that a ketogenic diet should be considered as a treatment for the hypometabolism seen in bipolar disorder, it may benefit you to learn about how some of the symptoms of bipolar disorder are similar to what we see in neurodegenerative diseases.

The pattern of hypometabolism in the brain in bipolar disorder, is so similar to Alzheimer’s disease, that in older patients a differential diagnosis is very challenging and sometimes not possible.

…our results unveil shared common neurocognitive features in bipolar patients with cognitive impairment of suspected neurodegenerative origin they suggest a participation of various underlying pathologies…

Musat, E. M., et al., (2021). Characteristics of Bipolar Patients with Cognitive Impairment of Suspected Neurodegenerative Origin: A Multicenter Cohort. https://doi.org/10.3390/jpm11111183

In fact, bipolar disorder features many of the same abnormalities, both in brain metabolism and signaling pathways as many neurodegenerative diseases, including Alzheimer’s disease (AD), Lewy Body Dementia, and even some aspects of Parkinson’s disease.

Ketogenic diets are an evidence-based treatment for Alzheimer’s disease, with several RCTs showing benefits. Why would it not help these same brain regions struggling with energy and metabolism? Especially when we can see that many of the very same brain regions are involved.

How do we know this? Do we have RCT brain imaging studies yet showing improved activity in the brain specifically in people with bipolar disorder who adopt a ketogenic diet? Not that I found. But I am pretty sure they are coming. Because we see a huge reduction in symptoms in many people with bipolar disorder that move to a ketogenic diet. And some of that symptoms reduction is defiantly coming from improved brain energy.

A ketogenic diet allows the bipolar brain to gobble up ketones for fuel and use them instead of primarily glucose for fuel. This increased fuel is a rescue mechanism for brain metabolism. Allowing more energy in the cell allows cell repair, maintenance, improved neuron transmission, better action potentials, you name it. Your brain needs adequate energy to do it.

There is a sweet spot in future research to tease out metabolisms’ relationship with different neurotransmitter systems. So until that research is done, we will have to discuss each in separate sections. It’s time to move from hypometabolism to neurotransmitter imbalances.

BIpolar Disorder and Neurotransmitter Imbalances

There are many different kinds of neurotransmitter chemicals in the brain. The neurotransmitters implicated in bipolar illness include dopamine, norepinephrine, serotonin, GABA (gamma-aminobutyrate), and glutamate. Acetylcholine is also implicated but will not be reviewed in this blog post. When we talk about neurotransmitter imbalances, it is important to understand that we are not just talking about too much or too little of any in particular. 

That might be the case to some extent, with the making less of one and more of another could be helpful. But what we are talking about is how neurotransmitters are made and used. Are the receptors designed to take the neurotransmitters into the cells working well? Can the cell membrane do its part in making the neurotransmitter or storing the nutrients it needs to make neurotransmitters? 

Are there too many receptors for one kind of neurotransmitter? If so, what does that mean for how long a neurotransmitter stays around in the synapse to be of benefit? Are there genetic polymorphisms that affect the enzymes that are supposed to make neurotransmitters or do the work of breaking them back down?

You get the idea. My point is that when I discuss particular neurotransmitters below, I am writing about a complex system. And system thinking takes a shift in perspective. So keep that in mind as you read about neurotransmitter imbalances in bipolar disorder.

Dopaminergic System

Dopamine (DA) receptor and transporter dysfunctions play a significant role in the pathophysiology of bipolar disorder in both manic and depressive states.
One very consistent finding comes from dopaminergic agonists in research studies. Dopaminergic agonists block dopamine receptors, so dopamine stays active in the synapse longer and exerts a more substantial effect. When researchers do this, they can simulate episodes of mania or hypomania in bipolar patients, or even just those who have an underlying predisposition to develop the disease.

Some studies have found that bipolar patients have higher dopaminergic system activity and that this activity may be due to increased release of the neurotransmitter and problems managing it through synaptic functions. These factors may be associated with developing manic symptoms in bipolar patients. And it is important to note that increased levels of dopamine have been associated with increases in oxidative stress. While this is not the oxidative stress section of the blog, oxidative stress is highly relevant to the neurotransmitter system. It interferes with important enzymatic processes and creates more reactive oxygen species, and this disrupts the environment in which neurotransmitters are trying to be made, having significant downstream effects.

Norepinephrinergic System

Norepinephrine is a key neurotransmitter in bipolar disorder. Dopamine is converted to norepinephrine by the enzyme Dopamine-β-hydroxylase (DβH). When there is less of this enzyme activity, and therefore less dopamine converted into norepinephrine, study participants report higher bipolar symptomology on checklists.

MHPG, a byproduct made by the metabolic process of creating norepinephrine (called a metabolite), is considered a potential biomarker for identifying mood states. This metabolite is proposed to represent clinical characteristics as a bipolar patient switches between depressed and manic states. And when lithium is used, there is a decrease in this very same biomarker.

Norepinephrine activity appears to fluctuate based on the bipolar phase. Lower norepinephrine levels and receptor (a2) sensitivity are reported during depressed states and higher activity during manic phases.

Glutamatergic System

Glutamate is an excitatory neurotransmitter with roles in many complex and essential processes. We see higher amounts of glutamate activity in bipolar disorder.

You want some glutamate, but not too much, and you want higher concentrations in the right areas. When conditions are not optimal in the brain, for whatever reason but most likely due to inflammation (as you will learn about later), the brain will make too much glutamate (up to 100x more than normal levels). Glutamate at these levels is neurotoxic and causes neurodegenerative aging. Too much glutamate causes damage to neurons and synapses and creates damage that the brain must then attempt to heal (and a workload of damage repair it will not be able to keep up with when high glutamate is chronic).

Studies consistently show a decrease in the expression of molecules involved in glutamate transmission between neurons in the brains of people who have bipolar disorder. One hypothesis is that the constant excess of glutamate in the brain of bipolar disorder patients changes receptors to reduce the damaging effects.

Glutamate is a neurotransmitter that affects mood. We see higher glutamate levels in a host of mental illnesses, like anxiety, pain disorder, PTSD, and bipolar disorder is no exception in sharing this common neurotransmitter imbalance. Except in bipolar disorder, instead of creating a panic attack as it might in someone with generalized anxiety, glutamate can be seen in elevated levels, specifically during the manic stage of the illness.

GABAergic System

GABA is an inhibitory neurotransmitter that acts as the brakes for excitatory neurotransmitters like glutamate. GABA is implicated in bipolar disorder and is associated with manic and depressive states, and clinical data indicate that decreased GABA system activity is associated with depressive and manic states. Psychiatrists will often prescribe GABA-modulating medications because this appears to have a mood-stabilizing effect on bipolar disorder.

There are consistently lower markers (measurements) of GABA in the brains of bipolar individuals, and while this is not exclusive to bipolar disorder and occurs in other psychiatric illnesses, it is a consistent finding. The use of drugs targeting the GABA system is used to help treat the depressive phase of bipolar disorder. Both gene association and postmortem studies show evidence of abnormalities in the GABA signaling system.

Patients who have a reduction in GABA present as having more significant cognitive impairments and specifically in inhibitory control of behavior.

Serotoninergic System

We know that serotonin plays a role in bipolar disorder. Evidence supporting that serotonin (also called 5-HT) deficits are involved in mania and that increasing or enhancing serotonin has a mood-stabilizing effect have been done in a variety of studies using different markers (e.g., tryptophan depletion, postmortem, platelet, and neuroendocrine).

The decreased release and activity of serotonin are associated with suicidal ideation, suicide attempts, aggression, and sleep disorders. There are all symptoms that are experienced by people with bipolar disorder. But as we discussed in the blog post introduction, medications that attempt to alter this system are often insufficient in reducing these symptoms in this population.

Cell membrane function and BDNF

You cannot discuss neurotransmitter balancing without a discussion of membrane function. As you already learned, cells need the energy to fire an action potential (cell firing). And important things happen when neurons fire, such as the ability to regulate calcium concentrations. You have to have a healthy cell membrane to have good energy production and control amounts of essential minerals the brain needs to generate action potentials, maintain the health of the cell, store nutrients for neurotransmitter production and enzyme function.

In bipolar disorder, the loss of sodium/potassium function and subsequent loss of (sodium) Na+/ (potassium) K+-ATPase Function (critical enzyme functions to create energy) occurs and contributes to cells’ energy deficit. Resulting changes in membrane function could influence manic and depressed states of bipolar disorder.

Brain-derived neurotrophic factor (BDNF) is a substance made in the brain that helps repair cells and makes new connections for learning and between brain structures. Remember how we discussed the neural circuitry abnormalities in the white matter? You need BDNF to help rewire something like that. And people with bipolar disorder do not have enough BDNF to do that well or to keep up with repairs needed from chronic states of neuroinflammation.

Hopefully, this blog post is beginning to answer the question of Can the ketogenic diet treat bipolar disorder? You can see how the effects on neurotransmitter balance make the ketogenic diet treatment for bipolar disorder.

How keto balances neurotransmitters

Ketogenic diets have direct effects on several neurotransmitters. There are plenty of studies showing an increase in serotonin and GABA, and balancing of glutamate and dopamine. There is some interaction between ketogenic diets and norepinephrine that is currently being investigated in research on epilepsy. There does not appear to be an influence of ketones on norepinephrine directly, but downstream as it is converted into dopamine.

Ketogenic diets balance neurotransmitter production and activity, so you won’t get too much of one or too little of another, and end up getting side effects as you sometimes would with medications.

The upregulation of certain neurotransmitters, such as GABA, is obviously beneficial to mood and its increase helps balance out excitatory glutamate production. This is likely a mechanism by which we see the improved mood in bipolar individuals, and could also directly influence a reduction in manic states.

Another important mechanism by which we see improvements in neurotransmitter balance is in improved cell membrane function. Ketogenic diets strengthen communications between cells and help regulate the influx of micronutrients (remember sodium, potassium, and calcium?) needed for cell firing. Improved membrane function also occurs through a mechanism that upregulates (makes more) BDNF, so cells and cell membranes are better able to repair themselves. And as an added bonus, this improvement in cell membrane function allows membranes to store important micronutrients needed to produce neurons and initiate repairs (using that fantastic extra supply of BDNF).

But as we will learn below, neurotransmitters cannot be made well or in balanced amounts in an environment that is constantly under attack and dysregulated by inflammation. And so we end our discussion of neurotransmitters but only in relation to the other pathological mechanisms happening in the bipolar brain, which include inflammation and oxidative stress.

Bipolar Disorder and Inflammation

Inflammation is such an issue in bipolar disorder that it is an important body of research all by itself and is identified as a significant underlying mechanism of the illness.

  • Micronutrient deficiency
    • resulting in the inability of the cell to maintain health and function)
  • Viruses and bacteria
  • Allergies
    • food or environemntal
  • Environmental toxins
    • pollution, pesticides, heribcide, plastics, mold
  • Gut microbiome
    • overgrowth of generally negative species that create gut permiability and inflammation
  • Inflammatory diets
    • standard American diet, highly processed carbohydrates, industrialized oils, uncontrolled high blood sugars

Chronic neuroinflammation is an immune response to one or more of these types of assaults. This immune response results in the activation of microglial cells that then produce inflammatory cytokines, particularly, TNF-α and IL-1β, to neutralize what is perceived as dangerous. But in doing so, there is damage done to surrounding tissues from these cytokines. The brain then needs to repair, which is challenging to accomplish when there is constant and nonstop inflammation.

One fascinating theory of the depressive symptoms seen in bipolar disorder has to do with the seasons. There is a higher rate of depressive symptoms in bipolar disorder in the spring. One interesting study found that depressive symptoms correlated with blood serum immune marker immunoglobulin E. It is thought that in the spring, as pollen goes up, symptoms of depression in bipolar individuals can become exacerbated due to the pro-inflammatory cytokine response triggered by allergies.

Microglial production of inflammatory cytokines is particularly relevant in bipolar disorder because they offer an explanatory mechanism for symptoms we see in bipolar disorder. Inflammatory mediators, like cytokines, shape synaptic transmissions and even strip away connections between brain cells (a usually normal process called pruning that gets out of hand with chronic neuroinflammation). These alterations in the brain impair attention, executive function (planning, learning, controlling behavior and emotion), and memory deficits. The hippocampus, which is a part of the brain with important functions in memory formation, is particularly hit hard by neuroinflammation. Unrestrained production of inflammatory cytokines results in premature brain cell death.

Increased inflammatory cytokine production has a strong role in why we see progressive worse dysfunction in the population over tie and in several areas of measurement. The overactivation of microglial cells leads to increased cognitive impairment, progressively worsened functioning, medical comorbidities that include chronic illness, and finally, premature mortality in those with bipolar disorder.

So inflammation and the reduction of inflammation, and hopefully fixing the root cause of inflammation for the individual patient, becomes a very important target of intervention on their journey to wellness.

How keto reduces inflammation

I don’t think a better intervention for inflammation exists than the ketogenic diet. I know that is a lofty statement but bear with me. Ketogenic diets create something called ketones. Ketones are signaling bodies, meaning they are able to talk to genes. Ketone bodies have been seen to literally turn genes off that are a part of chronic inflammatory pathways. Ketogenic diets are so effective at inflammation they are being used for arthritis and other chronic pain conditions.

But wait a minute, you may say, those are not conditions of brain inflammation. Those are diseases of peripheral inflammation so they don’t count. Touche.

But we know that ketogenic diets are so good for neuroinflammation that we use them with traumatic brain injury. After an acute traumatic brain injury, there is a huge cytokine storm in response to the injury, And this response does more damage often than the initial assault. Ketogenic diets quiet that response If a ketogenic diet can mediate brain injury neuroinflammation, I don’t see why it would not be a stellar option for bipolar disorder. We also use it for several neurodegenerative diseases like Alzheimer’s, Parkinson’s disease, and ALS. All conditions with a very significant neuroinflammation component.

So why wouldn’t we use a well-formulated, anti-inflammatory ketogenic diet to treat the underlying inflammatory mechanisms we see in bipolar disorder?

Bipolar Disorder and Oxidative Stress

Oxidative stress is what happens when there are too many reactive oxygen species (ROS). ROS happens no matter what we do. But our bodies know what to do about it. We even have endogenous (made in our body) antioxidant systems in place that help us deal with them and mitigate the damage of being alive and breathing, and eating. But in people with bipolar disorder, these antioxidant systems are not working optimally or cannot keep up with the damage going on. And so, in people with bipolar disorder, oxidative stress markers are consistently higher than normal controls in the research literature. It is not just one marker that is particularly high; it is many of them.

Oxidative stress, and the body’s inability to adequately quell neuroinflammation, are responsible for the hippocampal aging proposed to underlie the neurocognitive dysfunctions observed in BD patients. Oxidative stress causes accelerated brain aging in BD and is even responsible for high levels of mitochondrial (cell batteries) DNA mutations seen in post mortem studies.

But just giving people with bipolar disorder antioxidant treatments to reduce oxidative stress has mixed results, and researchers believe this may be because oxidative stress levels are being influenced by mitochondrial dysfunction. Remember what we learned about brain hypometabolism and the energy deficit and mitochondrial dysfunction we see in bipolar disorder? Bipolar disorder is a metabolic disorder of the brain, and there is just not enough energy for the brain to use?

That same issue may be responsible for the oxidative stress levels seen by researchers. At least in some portion of those with bipolar disorder and oxidative stress.

Regardless of whether it is the primary cause or a secondary mechanism of pathology in bipolar disorder, we know that oxidative stress is instrumental in creating the symptoms we see in bipolar disorder. And for that reason, we need an intervention that directly reduces oxidative stress, preferably by several mechanisms.

How keto reduces oxidative Stress

My favorite system is endogenous antioxidant system is glutathione. This is a very powerful antioxidant system that ketogenic diets actually upregulate. This upregulation in glutathione helps you reduce oxidative stress, and may improve the functioning and health of the bipolar brain. The improved nutrition that occurs with a well-formulated ketogenic diet also improves glutathione production. So added bonus.

Two types of ketones—β-hydroxybutyrate and acetoacetate—were found to reduce ROS levels in isolated neocortical mitochondria (Maalouf et al., 2007)

Further investigation is required to determine specific mechanisms of a KD on oxidative stress through influences on ROS and antioxidant levels. It is likely that the anti- inflammatory effects of ketone bodies are achieved by affecting multiple biochemical pathways.

Yu, B., Ozveren, R., & Dalai, S. S. (2021). Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments.
DOI: 10.21203/rs.3.rs-334453/v2

As the quote communicates so well, ketogenic diets are affecting multiple pathways that modulate oxidative stress. Besides ketone bodies, the improved neuronal health that occurs with a ketogenic diet, such as increased BDNF, balanced neurotransmitters that don’t cause neuronal damage (I am looking at you, glutamate and dopamine!), and healthier function cell membranes all do their part in reducing oxidative stress. That improved membrane potential and function, along with improved nutrient intake from a well-formulated ketogenic diet, really improve enzyme and neurotransmitter production, which play a role in fighting oxidative stress.

And you already know and understand that ketogenic diets upregulate the production of mitochondria, improving their functioning, but also encourage brain cells to make more of them. And imagine how much better a brain cell can manage ROS with so many more little cell powerhouses humming along making energy. This might be the mechanism by which oxidate stress has the potential to be reduced the most in the bipolar brain.

Conclusion

Now that you have learned the powerful effects of the ketogenic diet on brain hypometabolism, neurotransmitter balance, inflammation, and oxidative stress I will leave you with this quote discussing the current hypothesized around the disease processes we see in bipolar disorder.

A pathophysiological hypothesis of the disease suggests taht dysfunctions in intracellular biochemical cascades, oxidative stress and mitochondrial dysfunction impair the processes linke to neuronal plasticity, leading to cell damage and the consequent loss of brain tissue that has been identified in postmortem and neuroimaging.

Young, A. H., & Juruena, M. F. (2020). The Neurobiology of Bipolar Disorder. In Bipolar Disorder: From Neuroscience to Treatment (pp. 1-20). Springer, Cham. https://link.springer.com/chapter/10.1007%2F7854_2020_179

At this point, I feel confident you can make those connections and have a better understanding of how a ketogenic diet may be a powerful treatment for your bipolar disorder or that of someone you love.


I would have been afraid to write this blog post a few years ago, even though there were a lot of anecdotal reports coming out from people reporting significantly improved symptoms and functioning. I am so excited to see so much research being done.

The reason I am feeling more confident in writing a blog post like this is that there are peer-reviewed case studies showing remission of bipolar symptoms using the ketogenic diet and RCTs underway looking at the ketogenic diet as a treatment for bipolar disorder. There is even work by researchers analyzing in the comments in forums where people with bipolar disorder discuss using the ketogenic diet to feel better (see Ketosis and bipolar disorder: controlled analytic study of online reports).

There is an excellent table (Table 1) in the journal article Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments that neatly outlines the mechanisms by which a ketogenic diet could help treat bipolar disorder. Since you have just taken the time to read this article, you will understand so much better what this table is communicating! I have recreated it here:

BD MechanismsBD SymptomsPotential KD Effects
Mitochondrial DysfunctionDecrease in energy level productionInduces mitochondrial biogenesis
Na/K
ATPase loss of function
Impaired ATP production via Oxidative phosphorylationprovides alternative energy production pathway via ketosis
PDC DysfunctionUnsustainable ATP levels due to glycolysis-only productionProvides alternative energy production pathway via ketosis
Oxidative StressIncrease in ROS leading to neuronal damageReduces ROS levels with ketone bodies; Increases HDL cholesterol levels for neuroprotection
Monoaminergic ActivityChanges in behavior and emotion due to imbalanced neurotransmitter concentrationsRegulates neurotransmitter metabolites via ketone bodies and intermediates
DopamineIncrease in receptor activation inducing mania symptomsDecreases dopamine metabolites
SerotoninReduced levels inducing depressive symptomsDecreases serotonin metabolites
NorepinephrineReduced levels inducing depressive symptomsNo significant changes observed in prior studies
GABAReduced levels related to depressive and mania symptomsIncreases GABA levels
GlutamateIncrease in levels leading to unsustainable energy requirements and neuronal damageDecreases glutamate levels
GSK-3 Enzyme Dysfunction / DeficiencyApoptosis and neuronal damageIncreases antioxidants to provide neuroprotection
(Table 1) in the journal article Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments

If you found this blog post helpful or interesting, you may also enjoy learning how the ketogenic diet can play a role in modifying gene expression.

If you have comorbidities with other disorders, you may find it helpful to search my blog (search bar at the bottom of the page on desktops) and see if the ketogenic diet has beneficial effects on those disease processes as well. Some of the more popular ones that may be relevant to bipolar disorder include:

As a mental health practitioner who helps people transition to a ketogenic diet for mental health and neurological issues, I can tell you that I see improvements very often in those who are able to use the ketogenic diet consistently. And that is the majority of my patients. It is not an unsustainable therapeutic for bipolar disorder or any of the other disorders I treat using the ketogenic diet, psychotherapy, and other nutritional or functional psychiatry practices.

You may enjoy reading my small sample of Case Studies here. For some of my clients, it is about trying something other than medications to treat their bipolar disorder. For most, it is about reducing the prodromal symptoms they continue to live with, and many stay on one or more medications. Often at a lower dose.

You may also enjoy these other posts about bipolar disorder and using the ketogenic diet here:

If you would like to contact me you may do so here. I am happy to help you find resources or guide you on your wellness journey while coordinating with your prescriber. I hope this article has been helpful in your ability to know all the ways you can feel better!

Like what you are reading on the blog? Want to learn about upcoming webinars, courses, and even offers around support and working with me towards your wellness goals? Sign up!


References

Benedetti, F., Aggio, V., Pratesi, M. L., Greco, G., & Furlan, R. (2020). Neuroinflammation in Bipolar Depression. Frontiers in Psychiatry, 11. https://www.frontiersin.org/article/10.3389/fpsyt.2020.00071

Brady, R. O., McCarthy, J. M., Prescot, A. P., Jensen, J. E., Cooper, A. J., Cohen, B. M., Renshaw, P. F., & Ongür, D. (2013). Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder. Bipolar Disorders, 15(4), 434–439. https://doi.org/10.1111/bdi.12074

Campbell, I., & Campbell, H. (2019). A pyruvate dehydrogenase complex disorder hypothesis for bipolar disorder. Medical Hypotheses, 130, 109263. https://doi.org/10.1016/j.mehy.2019.109263

Campbell, I. H., & Campbell, H. (2019). Ketosis and bipolar disorder: Controlled analytic study of online reports. BJPsych Open, 5(4). https://doi.org/10.1192/bjo.2019.49

Ching, C. R. K., Hibar, D. P., Gurholt, T. P., Nunes, A., Thomopoulos, S. I., Abé, C., Agartz, I., Brouwer, R. M., Cannon, D. M., de Zwarte, S. M. C., Eyler, L. T., Favre, P., Hajek, T., Haukvik, U. K., Houenou, J., Landén, M., Lett, T. A., McDonald, C., Nabulsi, L., … Group, E. B. D. W. (2022). What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group. Human Brain Mapping, 43(1), 56–82. https://doi.org/10.1002/hbm.25098

Christensen, M. G., Damsgaard, J., & Fink-Jensen, A. (2021). Use of ketogenic diets in the treatment of central nervous system diseases: A systematic review. Nordic Journal of Psychiatry, 75(1), 1–8. https://doi.org/10.1080/08039488.2020.1795924

Coello, K., Vinberg, M., Knop, F. K., Pedersen, B. K., McIntyre, R. S., Kessing, L. V., & Munkholm, K. (2019). Metabolic profile in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives. International Journal of Bipolar Disorders, 7(1), 8. https://doi.org/10.1186/s40345-019-0142-3

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Are OPCs an option for treating depression without medication?

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Are oligomeric proanthocyanidins (OPCs) a natural option for treating depression without medication?

In psychiatric issues such as depression, the symptoms treated by the effects of oligomeric proanthocyanidins (OPCs) include inflammation, oxidative stress, and neurodegeneration. They improve blood flow and nutrient availability to cells and increase the health of the blood-brain barrier. This allows less prohibitive molecules to cross the barrier and cause an immune response that results in inflammatory cytokines. They also modulate the immune response and improve neurotransmitter balance. OPCs can be a good option for treating depression without medication.

Introduction

This blog post is one in a series about antioxidants that may be helpful for depression and includes Curcumin, Quercetin, and OPCs.

Oligomeric proanthocyanidins (OPCs) are a mix of naturally occurring antioxidant molecules, also known and searched for under the names proanthocyanidins, procyanidins, proanthocyanidolic oligomers (PCO), and oligomeric procyandins.

Oligomeric proanthocyanidins (OPCs) are derived from grape seeds or French maritime pine tree bark. They can also be found in red wine, green tea, Ginko Biloba, pomegranates, blueberries, and peanut skins. But please, if you are depressed, do not drink a lot of red wine and down a bunch of pomegranate juice trying to get more OPCs to reduce brain inflammation. The alcohol content in the wine and the blood sugar spike from the pomegranate juice will create much more inflammation. There are better ways to get your OPCs.

In psychiatric issues such as depression, the symptoms treated by the effects of OPCs include inflammation, oxidative stress, and neurodegeneration. In this blog post, you will learn about how OPCs can help you treat depression without medication. Or, if you are already on medication, they may be helpful in reducing your symptoms.

How do OPCs work to reduce neuroinflammation and depression?

The effects of oligomeric proanthocyanidins (OPCs) include protection of neurons and the promotion of their survival when under oxidative stress. They also are consistently found to improve memory and cognitive function. But what are the mechanisms by which OPCs can work to help alleviate depressive symptoms – and specifically, the brain (neuro) inflammation that we see as such a prominent factor? And how could they possibly be useful in treating depression without medication?

One creator of brain inflammation is a leaky blood-brain barrier. Substances that are supposed to be stopped and not allowed to enter the brain actually do when this barrier is not in a healthy state. When stimuli get through this barrier, it activates the immune system in the brain and creates inflammatory cytokines. Oligomeric proanthocyanidins (OPCs) are helpful in allowing the blood-brain barrier to keep its integrity and allow it to better protect the brain from inflammatory assaults like environmental toxins, infections, and immune-activating molecules like food allergens. This helps to reduce future assaults on the brain and decreases inflammation.

Your blood-brain barrier health directly affects your neurotransmitter balance. One example is tryptophan. If you are depressed, you need tryptophan to readily be transported into your brain so that you can make serotonin. If your blood-brain barrier is dysfunctional, you have reduced ability to transport tryptophan where it needs to be. This will cause issues with mood.

Oligomeric proanthocyanidins (OPCs) can cross the blood-brain barrier, provide protection to an already inflamed brain, and stop up the holes in a leaky blood-brain barrier to keep that stuff from going where it doesn’t belong in the first place.

Oligomeric proanthocyanidins (OPCs) also moderate the production and release of activating molecules from mast cells in the immune system. If any of your neuroinflammation is coming from hypersensitive immune system responses, as we see in allergies, OPCs may help reduce inflammation from this angle as well.

They also help keep endogenous (made by your own body) anti-inflammatories like glutathione nicely balanced. This also reduces oxidative stress load and reduce inflammation.

So you can see all the mechanisms of intervention that make oligomeric proanthocyanidins (OPCs) a very valid supplement to treat the underlying mechanisms of pathology happening in depression. It deserves consideration as an option for treating depression without medication.

How do I use OPCs to relieve the neuroinflammation that is causing my depression?

Take a combination of oligomeric proanthocyanidins (OPCs) if you are trying to treat a mental illness like depression. You are looking for 100 to 200 mg total combination per day, 1x to 2x per day.

For Curcumasorb Mind specifically, the dose is 1x per day, unless you are dealing with significant cognitive decline – then, 2x a day is used. You can determine your dosage better with this information. If you have a lot of cognitive symptoms that are a part of your depression, you may do best with 2x a day for this specific supplement.

For children, you would determine the dosage based on weight, calculating their weight in KG (not lbs; use an online calculator). You would then generally provide 1mg of an OPC combination per kg of body weight.

What are the best OPCs to take?

I highly recommend CurcumaSorb Mind from Pure Encapsulations because it has been used for decades in functional psychiatry practice with excellent results. It contains green tea extract, pine extract, and proprietary formulations of curcumin and other polyphenols like blueberry and grape extract. If you cannot find it available on Amazon (affiliate link), you can buy directly from the Pure Encapsulations website (not an affiliate link).

CurcumaSorb Mind at Pure Encapsulations

For some people, Curcumasorb Mind may be prohibitively expensive. If that is the case, I would recommend a less expensive but still third-party-tested option. Swanson Grape Seed, Green Tea & Pine Bark Complex (affiliate link) provides 125 mg each of grape seed, pine bark, and green tea.

Will OPCs cure my depression?

Let me be perfectly clear and upfront with you. NOTHING reduces neuroinflammation like a ketogenic diet.

Read what I wrote there. I did not say a low carbohydrate diet, which can produce very inconsistent levels of actual ketones. Doing a ketogenic diet for weight loss alone can be insufficient for the treatment of mental illness or neurological disorders. Sometimes, low carb in general does the trick, and sometimes, it does not. Some people need a stronger intervention, such as what happens when there is a sufficient and consistent supply of ketones available.

A ketogenic diet creates ketones that act as signaling bodies that turn down inflammation by helping turn genes off and on, helping to heal the gut, and does a host of other things that really should be and need to be happening if you are depressed. There is no supplement you are going to take that sustainably does for you what a ketogenic diet can do for your neuroinflammation and depression.

That said, oligomeric proanthocyanidins (OPCs) can be very helpful. And they also have some signaling properties. And if you have depression, they may really help your symptoms, particularly if you are someone who has decided they will not be doing the ketogenic diet. They can offer some real assistance with neuroinflammation. Will OPCs still work if you are eating a terrible diet, are nutrient deficient, and do not go to therapy?

Probably not.

But medication will not work well to treat your depression with those conditions either. Oligomeric proanthocyanidins (OPCs) can be a good option for treating depression without medication. Even if they do not cure your depression, they will likely significantly reduce neuroinflammation if you are also doing other things to take good care of yourself. And as an added bonus, French maritime pine bark can help treat the sexual side effects of antidepressant medications. So you may want to add them to your treatment regimen regardless.

But give them a try. Because neuroinflammation is a huge contributing factor to your depression. And I want you to know all the ways you can feel better!

Conclusion

As always, this blog is informational and not medical advice.

Be sure to check out these articles on the role of neuroinflammation in depression and what you can do about it!

If you want to learn more about the underlying mechanisms that cause depression in more detail, you will enjoy my posts on the topic.

If you currently have a prescriber that has no idea why you are bringing any of these natural treatments up, you may need to find a prescriber that practices functional psychiatry willing to talk about different options. I am not a prescriber. But I am a mental health counselor who practices principles of functional and nutritional psychiatry, so feel free to contact me if you would like help on your healing journey. You can learn more about me and my telehealth and teleconsultation work with clients here.

Like what you are reading on the blog? Want to learn about upcoming webinars, courses, and even offers around support and working with me towards your wellness goals? Sign up!

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References

Fine, A. M. (2000). Oligomeric proanthocyanidin complexes: History, structure, and phytopharmaceutical applications. Alternative Medicine Review: A Journal of Clinical Therapeutic, 5(2), 144–151.

Full article: Alternative medicine and herbal remedies in the treatment of erectile dysfunction: A systematic review. (n.d.). Retrieved January 27, 2022, from https://www.tandfonline.com/doi/full/10.1080/2090598X.2021.1926753

Mei, L., Mochizuki, M., & Hasegawa, N. (2014). Pycnogenol Ameliorates Depression-Like Behavior in Repeated Corticosterone-Induced Depression Mice Model. BioMed Research International, 2014, e942927. https://doi.org/10.1155/2014/942927

Smetanka, A., Stara, V., Farsky, I., Tonhajzerova, I., & Ondrejka, I. (2019). Pycnogenol supplementation as an adjunct treatment for antidepressant-induced sexual dysfunction. Physiology International, 106(1), 59–69. https://doi.org/10.1556/2060.106.2019.02

The Role of Phytochemicals in the Treatment of Depression. (n.d.). Great Plains Laboratory. Retrieved January 25, 2022, from https://www.greatplainslaboratory.com/webinars/2016/11/7/the-role-of-phytochemicals-in-the-treatment-of-depression

Trebatická, J., & Ďuračková, Z. (2015). Psychiatric Disorders and Polyphenols: Can They Be Helpful in Therapy? Oxidative Medicine and Cellular Longevity, 2015, e248529. https://doi.org/10.1155/2015/248529

How to fix neuroinflammation and heal your depression – supplements

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If you just came from the blog post Neuroinflammation and Depression, you may be asking what can you do to reduce it. This blog post will go over some of the best supplements for depression, targeted specifically to reduce inflammation and help alleviate your symptoms. While these supplements for depression focus on a reduction in inflammation, it is important to know that you may also have micronutrient deficiencies that contribute to your psychiatric symptoms. These deficiencies can be improved on broad-spectrum micronutrient therapies or in a more targeted manner with additional functional testing.

Introduction – Supplements for Inflammation

Supplements that can help alleviate inflammation and help with depression include magnesium, essential fatty acids, lithium orotate, and anti-oxidants such as Curcumin, Quercetin, OPCs, and Ashwagandha. (These antioxidants are super interesting and have their own blog posts on how they can help depression).

In this blog post, we will discuss magnesium, lithium, and essential fatty acids.

Essential fatty acids

Stop eating a low-fat diet. You need essential fatty acids. You can get them from your food, but you can also find high-quality supplements. Some essential fatty acids you should be supplementing if you have depression include:

  • Omega 3s
    • Alpha-Linolenic acid (ALA)
      • note; if you are vegan and relying on this to convert into DHA, this is not going to work. Only 0-9% of ALA will convert to DHA. You are likely fatty acid deficient.
    • Eiconsapentaenoic acid (EPA)
    • Docosahexaenoic acid (DHA)

If you eat a Standard American Diet full of industrialized seed oils like soy, canola, and vegetable, you are likely already very high in Omega-6 Fatty Acids. But if you are Vegan and not eating any animal products at all, you are not getting enough Arachidonic acid (AA), and your brain ABSOLUTELY needs this Omega 6. Find some algae supplementation STAT!

If you supplement with Omega 3s, be aware that it may take 10-12 weeks at a high dose for your brain to recover from chronic fatty-acid deficiency. Don’t take a giant dose of DHA or EPA for very long periods, and they can cause imbalances in the fatty-acid profile. DHA/EPA are not solutions to your high brain inflammation, and they are not necessarily fixing the source causing the inflammation (unless that source is a low-fat diet). Better to fix the source of what is causing the inflammation than just take a bunch of supplements so you can continue to mistreat your body or stay in unhealthy environments that are the cause of inflammation.

The two links below are brands I recommend to clients. They are affiliate links, but please do not feel obligated to use them. You may be able to find less expensive supplements for depression but remember that quality matters.

Nordic Naturals Ultimate Omega, Lemon Flavor – 1280 mg Omega-3-180 Soft Gels – High-Potency Omega-3 Fish Oil with EPA & DHA – Promotes Brain & Heart Health – Non-GMO – 90 Servings

Pure Encapsulations O.N.E. Omega | Fish Oil Supplement for Heart Health, Joints, Skin, Eyes, and Cognition* | 60 Softgel Capsules

This one is a nice combo of both Omega 3s and 6s Pure Encapsulations VisionPro EPA/DHA/GLA | Supports Natural Tear Production and Retention of Eye Moisture* | 180 Softgel Capsules

The dose can be between 1-3g. Consult with your doctor if you are on blood thinner medication. I am not your doctor, and I am just giving you a heads up on what might help that are not prescription medications. I don’t know your case, so this is not medical advice.

Vitamin D3

Vitamin D deficiency is associated with increased markers of inflammation. This makes sense. Vitamin D regulates your immune function. And as you just learned, cytokines are regulated by the immune system.

I promise you are probably NOT getting optimal amounts of Vitamin D. Most of our population in the US are either starkly deficient or have insufficient levels for optimal health. The ideal Vitamin D level you are shooting for is between 60-80 ng/ml. This level will also help you sleep better. But I have learned under functional psychiatrists that suggest a level between 75-100 ng/ml to get brain inflammation down and treat neuropsychiatric disorders.

Ideally, you need to get your Vitamin D tested. I like to use UltaWellness and get a blood draw close to home. There is no need for a provider or doctor to order it for you. You can find them here:

Your regular doctor can also order you a Vitamin D test, and it should be covered by your health insurance.

But if getting a blood draw is too inconvenient, you can find a Vitamin D test using a few blood drops and a kit from Great Plains Lab. A provider is required to order this test for you. This is a great excuse for you to contact me, as I am happy to order it for you.

Once you have your level, you can use a Vitamin D calculator to figure out the dose you need to get to the optimal range.

But be sure to recheck because everyone accumulates and metabolizes Vitamin D a little differently and you don’t want to reach levels over 100.

When you take your Vitamin D dose, pair it with at least 100mcg of Vitamin K2. It helps keep the calcium that increased D releases out of soft tissues like kidneys and arteries. Some good options that I recommend to clients are below (affiliate links). Choose one that makes sense for the dose the calculator has guided you to take.

If you take blood thinners please do not take K2 without consulting your doctor

NatureWise Vitamin D3 5000iu (125 mcg) 1 Year Supply for Healthy Muscle Function, and Immune Support, Non-GMO, Gluten Free in Cold-Pressed Olive Oil, Packaging Vary ( Mini Softgel), 360 Count

These are the brands that I take personally. Again, these are affiliate links. If you can find a better deal elsewhere, please do so.

And here is a nice Vitamin D3/K2 option in the same capsule:
Vitamin D3 + K2 | 5000 IU of D3 (as cholecalciferol) for Optimal Calcium Absorption | 100 mcg of K2 (as menaquinone-7) for Circulatory Health | Supports Bone & Immune Health | 60 Vegetarian Capsules

Magnesium

When you eat a highly processed food diet, magnesium is one of the first minerals to disappear. Even if you eat organic produce, the amount of magnesium found in those items is down about 30% from what it used to be due to industrialized agricultural processes. And if you are stressed for any reason at all, you use up magnesium stores very quickly. Your cortisol levels go up when you are stressed, and this triggers your immune system, and this increase in immune system activity depletes magnesium stores.

Add to this that if you eat a lot of carbohydrates, this further depletes your magnesium because molecules of magnesium are needed to unlock the energy from carbohydrates.

Is it any wonder that you are magnesium deficient?

No really. I promise you that unless you are supplementing, you are almost certainly deficient. And I am not even going to bother to tell you to test your levels of this nutrient. Most of your magnesium is hiding in your cells and bones. Only a tiny portion is floating around in your blood. So a blood test won’t really give you a good idea of your levels. You would have to go after some advanced functional testing with a provider to figure your levels out.

Just assume you need some. Especially if you are depressed and trying to modulate inflammation. Magnesium has direct anti-inflammatory properties in the nervous system, which is incredibly helpful for depression.

The form of magnesium I most often recommend for clients is magnesium glycinate. There are two brands that I recommend and will share below as affiliate links. For someone with depression, I will encourage 600-800mg daily. You cannot overdose on magnesium. If you do, you will just get loose stools. If you notice this, you would just back off a dose.

I take this one:
CanPrev Magnesium Bis-Glycinate 200, Veggie Capsules, 240 Count

This one is also good:
Pure Encapsulations Magnesium (Glycinate) | Supplement to Support Stress Relief, Sleep, Heart Health, Nerves, Muscles, and Metabolism* | 90 Capsules

Lithium Orotate

This is not a medication. The use of elemental lithium as a supplement provides levels no higher than what you would find in drinking water to varying degrees around the world. These small doses do not appear in blood tests and are not dangerous.

But supplementation with lithium orotate can be life-saving. Particularly if you suffer from depression and have suicidal ideation and/or substance abuse. Generally, you would supplement 1mg to 5mg, and people can start with 1mg and slowly work up to whatever dose they like. Don’t do this without a practitioner if you have kidney disease. It just would need to be monitored, but would still likely be very helpful. Some people need more lithium than what is provided in the drinking water they have access to in their area. You are not going to increase your lithium levels to any appreciable amount with dietary changes. Lithium is almost non-existent in food.

What is the mechanism of action thought to be at play with lithium and the treatment of depression?

You guessed it. Lithium reduces brain inflammation. Possibly by adjusting how the brain metabolizes existing Omega 3 fatty acids.

Below is the supplement I will suggest to clients. This is an affiliate link.
Pure Encapsulations – Lithium (Orotate) 1 mg – Support for Calmness and Behavior – 90 Capsules

After you work up from 1mg (if you choose), Weyland is a good brand with 2.5mg and 5mg options.

You may need higher amounts than this, and I encourage you to work with a knowledgeable practitioner to help guide you.

Conclusion

I would be happy to work with you on your healing journey. You can learn more about me here. I am licensed in Washington state but can work with people through consultation services. You may contact me here to set up an appointment.

Be sure to check out the other two articles in this series!

If you want to learn more about the underlying mechanisms that cause depression in more detail, you will enjoy my posts on the topic.

Great resources regarding supplements for depression can be found on Psychiatry Redefined. They provide free webinars and you may even be able to find a functional psychiatry provider near you.

Another great resource on eating to combat depression is Georgia Ede, MDs site diagnosisdiet.com

Like what you are reading on the blog? Want to learn about upcoming webinars, courses, and even offers around support and working with me towards your wellness goals? Sign up!

Free ebook

Because you have the right to know all the ways you can feel better!

Ketogenic Diets for ADHD

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Can Keto Help ADHD?

Ketogenic diets can help ADHD by treating several areas of underlying pathology identified as causing symptoms. These areas include glucose hypometabolism, neurotransmitter imbalances, low brain-derived neurotrophic factor, inflammation, and oxidative stress. A well-formulated ketogenic diet can also improve the nutrient status and treat cofactor insufficiencies seen in ADHD populations.

Introduction

Attention Deficit Disorder (ADD) and Attention Deficit Hyperactivity Disorder (ADHD) are seen to be primarily influenced by genetics in 80% of cases. However, as with all genes, the environment that turns those genes on and off is a potent factor called epigenetics. And lifestyle, diet, exercise, sun exposure, stressful environments, toxins are all compelling epigenetic factors. Meaning they can make some genes express themselves more and others express themselves less. So something like the ketogenic diet, which is a powerful dietary and lifestyle epigenetic factor, may help alleviate or reduce some of the symptoms of ADHD.

But let me be clear. No RCTs show that the ketogenic diet is helpful in ADHD and ADD. But they may be coming soon. As anecdotal evidence continues to mount, interests and funding in RCTs are more likely. Although we will never see them being done as robustly as we would for pharmaceuticals with high-profit potential. Still, if you search on Reddit for ADHD, ADD, and Keto, you get many people sharing their stories that the ketogenic diet has helped them. You can read some of them here. And as many have asked before, you have likely come to this page asking the question “Can keto help ADHD?”

This blog post will explore some of the mechanisms by which a ketogenic diet may help treat some of the symptoms of ADHD and ADD. In prior posts, we explored how the ketogenic diet treated the following four underlying areas of pathologies, in general. You can read these small but informative posts here, here, and here. In this post, we will explore these same four areas of pathology that are seen in ADHD and ADD and explore whether a ketogenic diet may improve symptoms that may come from these areas of dysfunction:

  • Glucose Hypometabolism
  • Neurotransmitter Imbalances
  • Inflammation
  • Oxidative stress

In this blog post, I will expand these potential treatment areas out slightly to include very general information regarding brain-derived neurotrophic factor (BDNF) and the role of the immune system in ADHD/ADD. Both are relevant factors to explore as you try to answer whether the keto diet can help with ADHD and ADD.

I will not be going into the symptoms or diagnostic criteria of ADHD in detail in this blog. It is not meant to be informational in that way, and there are plenty of articles on the internet providing this information. If you have found this blog, it is because you know what ADHD and ADD are, and you may be seeking out ways to treat symptoms for yourself or someone you love.

You may be wondering if you can treat ADHD without stimulant medications. Or you may be exploring whether or not adopting a ketogenic diet may allow you to need less stimulant medication. Less medication can be beneficial, especially since psychiatric drugs deplete nutrients.

Psychiatric medications, like the ones used to treat ADHD and ADD, deplete the following nutrients:

  • Magnesium
  • Iron
  • Folate
  • Omega 3s
  • B1, B2, B3, B6 and B12
  • Zinc
  • CoQ10

Micronutrient depletions from medication usage are compounded by appetite suppression found with ADHD and ADD medications. Appetite suppression caused by medication usage can cause you or a loved one not to eat enough to replenish these depletions. You may want to be able to take less stimulant medication for this reason alone. The above list of nutrient depletions is relevant and directly affects how well your brain can work. Whether your brain can fire action potentials to speak between neurons, make neurotransmitters, reduce inflammation, and repair itself are all dependant on adequate amounts of those nutrients listed above.

Ironic, I know.

You may be reading this blog because you have only ADHD or ADD, or you may be reading this blog because you have ADHD and some other comorbid disorder from which you are seeking relief. Many adults with ADHD suffer from comorbid conditions, which include:

  • antisocial personality disorder (14-24%)
    • Note: in children this diagnoses is often Oppositional-Defiant Disorder. If it persists past age 18, the diagnoses changes to antisocial PD
  • borderline personality disorder (14%)
  • affective disorders with depression (20%)
  • bipolar disorder (20%)
  • anxiety (up to 50%)
  • social phobia (32%)
  • panic attacks (15%)
  • obsessive-compulsive disorder (20%)
  • substance abuse (20-30%)

Regardless of why you are reading this blog, I hope that by the end, you will better understand how a ketogenic diet can be a primary or complementary treatment for your ADHD or ADD symptoms.

ADHD and Hypometabolism

Hypometabolism is a term we use to describe brain areas that do not use energy well (hypo=low; metabolism=use of energy). People with ADHD have areas of the brain that are not active enough and are identified as having brain hypometabolism in certain structures. Hypometabolism in the ADHD brain is seen in the prefrontal cortex (mostly right), caudate nucleus, and anterior cingulate. We can also see a very generalized effect in the uptake of glucose in the ADHD brains of those adults who have symptoms of hyperactivity.

Global cerebral glucose metabolism was 8.1% lower in the adults with hyperactivity than in normal controls. 

Zametkin, A. J., Nordahl, T. E., Gross, M., King, A. C., Semple, W. E., Rumsey, J., … & Cohen, R. M. (1990). Cerebral glucose metabolism in adults with hyperactivity of childhood onset. DOI: http://doi.org/10.15844/pedneurbriefs-4-11-4

In animal studies, one of the mechanisms of methylphenidate (sold as Ritalin and other drug names) is that the medication increases the uptake of glucose in the brain. Problems with glucose hypometabolism in the aforementioned brain regions exist in children, adolescents, and adults. Adults who were diagnosed with ADHD as children have regions of glucose hypometabolism in the brain as adults.

There is even evidence that genetic variations are what cause glucose hypometabolism to occur, specifically in the functioning of certain important receptors like GLUT3. When GLUT3 is working properly, it mediates the uptake of glucose in neurons and is found mainly in axons and dendrites. But in individuals with ADHD, we see that genetic polymorphisms impact the ability of GLUT3 to work properly and that this may be what results in the initial neurocognitive problems thought to contribute to ADHD risk.

How ketogenic diets help brain hypometabolism in ADHD

Hmmm. Wouldn’t it be great if there was an alternative fuel for the ADHD/ADD brain? One that did not rely on glucose or have to deal with faulty GLUT3 transporters? Luckily there is! It happens to be the ketogenic diet.

Ketogenic diets provide an alternative fuel for the brain known as ketones. These ketones go directly into the brain as a fuel source. No fancy GLUT transportation is required. Ketones use monocarboxylate transporters (MCTs), which you get plenty of with a healthy fat intake on a ketogenic diet.

And the crazy thing is, ketones not only help your existing mitochondria work better, but they encourage your brain cells to make more. And there is a lot you can do with that big of upregulation in brain energy. Especially if it occurs in the frontal lobe.

As if providing an alternative brain fuel for the hypometabolic brain was not enough, ketones also increase energy metabolism by upregulating neuronal cell mitochondria. Mitochondria are the batteries of your cells. Let me make it clear. These little mitochondria are like power reactors. The word “batteries” just does not do them justice.

But wait. There’s more.

Ketones produce MORE energy than glucose. To be exact, about 48 ATP vs. the 36 ATP you get from glucose.

There is a great little blog post about ketosis, mitochondria, and the mechanics of how ketones make ATP here (thank you, Siimland).

Research is completely confused and inconsistent about exactly how much ATP a cell needs, let alone what level of energy a cell needs to flourish as opposed to bare minimum functioning. And the research is even less clear about how much ATP a common neuron, astrocyte, or glial cell may optimally use. Just know that your brain uses 70% of all the ATP you create in your whole body. And you will begin to understand the importance of having access to ketones as an energy source in the ADHD brain.

“But wait a minute!” you may be saying to me as your read this blog. What does this have to do with my symptoms? ADHD/ADD has diagnostic criteria. And a subset of that criteria falls under what is called executive dysfunction.

Executive dysfunction, which is also called executive function deficit or disorder, is when the brain has a hard time with the skills of attention, memory, flexible thinking, and organization/time management.

https://www.verywellmind.com/what-is-executive-dysfunction-in-adhd-5213034

Executive dysfunction comes from broken frontal lobes. Broken frontal lobes can come from a head injury, a stroke, or from not getting enough fuel to run.

And that, my blog reading friend, is how a ketogenic diet can treat the underlying frontal lobe hypometabolism that is part of the disease process underlying your ADHD/ADD symptoms.

ADHD and Neurotransmitter Imbalances

There are several neurotransmitter imbalances in ADHD and ADD. These include serotonin, dopamine, noradrenaline, glutamate, and GABA. Additionally, there is a downregulation seen in an important substance called brain-derived neurotrophic factor (BDNF). While not technically a neurotransmitter, it exerts an influence on the glutamate/GABA system and so will be included.

Serotonin

Differences in gene expression found in those with ADHD alter the functioning of serotonin receptors. This means that how the nerve cell receives and uses the neurotransmitter serotonin is altered. Differences in these receptors and how it affects interconnectivity between brain structures are thought to influence some of the learning and memory impairments we see in ADHD persons. Reduced levels of serotonin are thought to be related to the symptoms of impulsivity seen in some manifestations of the disorder.  

Dopamine

Another major neurotransmitter dysfunction seen in ADHD is dopamine. Early theories suggested that low levels of dopamine, along with certain other neurotransmitters, were at the root cause of ADHD. This theory has since moved toward the thought that the problem is not because there is not enough dopamine but because there are higher levels of transporters for dopamine. Dopamine transporters allow dopamine to enter the nerve cell through a well-functioning presynaptic membrane.

Pay attention to what I just wrote. For dopamine to be used, you have to have a well-functioning presynaptic membrane. This will be relevant later as we discuss treatment.

Having too many dopamine transporters at work means that dopamine does not hang out long enough in the presynaptic cleft for the right amount of time. It gets vacuumed up into all those receptors. It can’t do its thing!

Because dopamine cannot do its job, the person with ADHD finds it difficult to seek pleasure and feel rewarded by normally pleasurable things throughout their day. They are wired to seek out more dopamine. It’s why ADHD people can develop problems with smartphone use, computer games, and even highly addictive processed foods. All things are carefully designed to provide a high dopamine response in the brain. There is a distinct sensation of being uncomfortable without these extra stimulating activities and foods. This all leads to feeling restless, behaving impulsively, and having problems with attention.

Among the neuro-chemical factors, there is a well-known dysregulation in the production of neurotransmitters; primarily dopamine and nor-adrenaline.

Fayed, N. M., Morales, H., Torres, C., Coca, A. F., & Ríos, L. F. Á. (2021). Brain Magnetic Resonance Imaging in Attention-Deficit/Hyperactivity Disorder (ADHD). https://link.springer.com/chapter/10.1007/978-3-030-61721-9_44

Several different genetic variations contribute to issues of dopamine function seen in those with ADHD and ADD. It is thought that genetic variations to differing degrees contribute to all the many presentations of the disorder we see in individuals. For example, COMT polymorphisms affecting the dopaminergic system are highly correlated with ADHD symptoms and social impairment.

Norepinephrine

Norepinephrine is a neuromodulator that has an important role, along with dopamine, in allowing the prefrontal cortex to function. Remember, we discussed the prefrontal cortex and what it does earlier in this blog post. A dysfunctional prefrontal cortex will lead to executive functioning deficits that are often a sub-class of symptoms seen in the diagnoses of ADHD/ADD.

Although most of the research likes to focus on dopamine, norepinephrine’s influences on the prefrontal cortex are just as powerful and are incredibly relevant to an understanding of ADHD symptomatology. When norepinephrine is working well, it helps with working memory and attention. People with ADHD/ADD report serious issues with working memory and attention.

We know that norepinephrine is involved, in part, because selective noradrenergic medications (e.g., clonidine, guanfacine) can help treat ADHD.

And again, we are dealing with an issue of transporters. It is not necessarily that there is too much or too little of norepinephrine, but that we see genetic variations that influence how what is already there is being moved around and used. And again, we see that certain genetic differences seen in ADHD and ADD are implicated in how the norepinephrine transporter (NET) works.

Glutamate and GABA

We discuss these two neurotransmitters together because they are part of an elegant system that works together. In ADHD, we see an imbalance in this neurotransmitter system. Glutamate levels in the prefrontal cortex, for example, will directly influence levels of dopamine and vice-a-versa.

In certain neurodevelopmental disorders, such as ADHD, we see an imbalance between the excitatory glutamate neurotransmitter and inhibitory GABA. Dopamine receptor (DRD4) dysfunction seen in ADHD creates an environment in which there is more glutamate in the brain. And we don’t want a ton of glutamate just hanging out in the brain, not being balanced by GABA. Because long-term, this causes damage to brain cells and brain structures.

Glutamate is an important neurotoxic brain marker. Excess of glutamate can produce neuronal death through excitotoxic processes. It is also assumed that glutamate in the frontal circuits is an important regulator of dopamine, and through a feedback mechanism the concentration of dopamine can influence the concentration of glutamate

Fayed, N. M., Morales, H., Torres, C., Coca, A. F., & Ríos, L. F. Á. (2021). Brain Magnetic Resonance Imaging in Attention-Deficit/Hyperactivity Disorder (ADHD). In Psychiatry and Neuroscience Update (pp. 623-633). Springer, Cham

Children with ADHD show poorer inhibitory control and significantly reduced GABA in the striatum, which is a brain structure involved both in determining what actions to perform and learning about which of those actions are worth repeating. Poor levels or utilization of GABA are thought to contribute to symptoms of behavioral inhibition seen in ADHD.

The contribution of this particular type of neurotransmitter imbalance is not insignificant. And the effects of these two neurotransmitters being out of balance are thought to contribute directly to the etiology of ADHD and the neurobiological effects that persist into adulthood.

Brain-derived neurotrophic factor (BDNF)

BDNF is found to be downregulated in ADHD. Some of this may be due to genetic variations found in this population. And people with ADHD/ADD feel this inadequate supply. Because your hippocampus, the brain structure that helps process short-term memories, is very active, and it needs a lot of BDNF to work properly. And this downregulation of this substance may be why we see issues with short-term and working memory in people with ADHD. You also need enough BDNF to just learn in general. You need it for signaling in the glutamatergic and GABAergic (ergic=making) synapses, and it also plays a role in serotonin and dopamine transmission between cells. The bottom line is people with ADHD do not have enough of this good stuff. And we need to find a way to increase it.

How ketogenic diets help neurotransmitter imbalances seen in ADHD

So how could a ketogenic diet improve symptoms of ADHD? After all, it looks like ADHD is mostly genetic. How could a ketogenic diet modify the expression of genes that determine how our neurotransmitters work (or don’t)? How could a dietary therapy change something big like that?

Dopamine, Noradrenaline, and Serotonin

I might have mentioned this earlier, but there are three types of ketones. One of those types is called beta-hydroxybutyrate (βHB). βHB generates more of an enzyme central to metabolism (energy production) called nicotinamide adenine dinucleotide (NADH). It does this through a complicated pathway that you can look at here (see Figure 3) if you are interested at that level.

For our purposes here, it is just important to know that this increases the synthesis of the neurotransmitters dopamine, noradrenaline, serotonin, and melatonin.

And if you remember your reading above, genetic variability in neurotransmitter receptors and transporter expression of serotonin, dopamine, and norepinephrine are issues seen with ADHD brains. Making more of each could be quite beneficial.

  • Increased serotinin could improve impulsivity, learning and memory impairments
  • Increased dopamine could alleviate restlessness and improve attention
  • Increased norepinephrine could improve working memory and attention

There would be more to go neurotransmitter goodness to go around, and it would mean there would likely be more to stay present in synapses where they can work their magic. And this upregulation of key neurotransmitters is done in a balanced way with a ketogenic diet.

Unlike medications in which certain neurotransmitters are increased or made to stay as long as possible in synapses, there will not be medication side effects. We are all well aware, for example, of the side effects people experience when taking SSRIs to increase the time serotonin stays in the synapses to be used. We know that gabapentin, designed to increase GABA levels in the brain can create side effects of drowsiness, for example. This type of thing just does not happen on a ketogenic diet.

But what about glutamate and GABA?

As discussed above, the ADHD brain struggles with too much glutamate and too little GABA. Ketogenic diets can increase glutamic acid decarboxylase activation, which encourages GABA synthesis and also alters enzyme activity that keeps GABA around longer in the synapses. So for the ADHD brain, this means more access to the inhibitory neurotransmitter needed to help balance out higher levels of glutamate.

In animal studies, one of the forms of ketone bodies known as acetoacetate was found to reduce excitatory neurotransmission at hippocampal synapses, which may improve or at least protect memory function. ADHD and ADD individuals often complain of problems with short-term memory and learning. Balancing neurotransmitter function in important memory structures such as the hippocampus could prove helpful for a reduction in symptoms.

Membrane functioning and neurotransmitter balance

You just cannot have a conversation about neurotransmitter balance without discussing neuronal membrane function. βHB helps neuronal membranes repolarize, and that improved ability to repolarize has plenty of benefits for the ADHD/ADD brain.

Repolarization of neuronal membranes, enhanced by βHB allows the cell to accumulate nutrients (often deficient in the ADHD/ADD brain) to make neurotransmitters in the first place. Remember when we discussed issues with neurotransmitter receptors and transporters in the ADHD/ADD brain?

Well, the construction of enzymes that determine how much neurotransmitter gets to hang out in the synaptic cleft, and for how long is something determined by membrane repolarization. The synaptic clefts’ ability to stay sensitive to the neurotransmitters appearing (such as dopamine, serotonin, and norepinephrine) also depends on healthy functioning repolarization.

Brain-derived neurotrophic factor (BDNF)

Ketogenic diets are known to upregulate the production of BDNF. It is thought that this may be an important mechanism that allows them to improve various neurological disorders, such as traumatic brain injury (TBIs) and dementias. Ketones upregulate BDNF in their role as a signaling molecule, turning genes on and off in such a way that more of this substance is created. So producing ketones, on a ketogenic diet, would create more BDNF in the ADHD/ADD brain.

Genes are not destiny

ADHD is considered highly influenced by genes. And anytime a disease is discussed in that way, people can get the wrong idea about whether they would be able to “fix” or modulate underlying pathologies associated with a condition.

We don’t know how much of the problems with these things in ADHD come from impaired neuronal membrane functioning due to epigenetic factors (e.g., hypometabolism due to diet, micronutrient deficiencies, chronic neuroinflammation, oxidative stress).

Even though problems with receptors and transporters are said to occur on a genetic level in those with ADHD brains, I want to go on record as communicating that I think it is quite possible that changing the environment in which those genes are expressed could mean symptom improvement. How genetic expression unfolds for serotonin, dopamine, and norepinephrine transporters and receptors may be amenable to epigenetic influences.

And epigenetic interventions, like a ketogenic diet, are quite powerful in influencing gene expression. Ketones are signaling molecules, meaning they have the power to turn genes on and off. Just because you have been told something is hereditary does not mean you are powerless in making changes to modify how that expression happens.

ADHD and Neuroinflammation

People with ADHD have significant levels of neuroinflammation coming at them from many different directions. Inflammation can be caused for a variety of reasons. A diet high in fructose (those sweet beverages at the convenience store) can increase inflammation. Pollution can increase inflammation. A leaky blood-brain barrier that lets toxins into the brain can cause inflammation. Acute stressors, like taking an exam or blowing a tire on the freeway, can increase inflammation. And immune system dysfunction can increase inflammation. Pay attention to that last one because the inflammation caused by immune system dysfunction appears to be highly relevant in ADHD.

So what does that mean? When our immune system becomes activated, something called cytokines is then produced. These are little signaling molecules that tell the immune system what to do to keep the “bad guy” they were just told is there in line. But cytokines are not subtle when they fight different intruders off. They do a lot of damage. Imagine a very chaotic police chase scene and all the damage that happens as they go after the bad guy with great intensity and high speeds.

That is how cytokines roll. They may or may not catch the bad guy, and there is a big inflammatory mess to clean up. And it takes a lot of labor, equipment, and resources to do that clean-up. For the brain, that means tons of spent energy (labor), other cells that are healthy and can pick up the slack (equipment), and a lot more micronutrients (resources) than you are probably getting in your diet.

Now imagine a lot of car chases all the time like nonstop (chronic). Eventually, clean up and repair would fall behind. The city and road would start to look like a hot mess. That’s your brain dealing with chronic neuroinflammation.

The best way I can illustrate how significant inflammation is in ADHD is to provide a quote from a research article I pulled to write this post.

While still limited, this evidence includes 1) the above-chance comorbidity of ADHD with inflammatory and autoimmune disorders, 2) initial studies indicating an association with ADHD and increased serum cytokines, 3) preliminary evidence from genetic studies demonstrating associations between polymorphisms in genes associated with inflammatory pathways and ADHD, 4) emerging evidence that early life exposure to a number of environmental risk factors may increase risk for ADHD via an inflammatory mechanism, and 5) mechanistic evidence from animal models of maternal immune activation documenting behavioral and neural outcomes consistent with ADHD.

Dunn, G. A., Nigg, J. T., & Sullivan, E. L. (2019). Neuroinflammation as a risk factor for attention deficit hyperactivity disorder. https://doi.org/10.1016/j.pbb.2019.05.005

So let’s review the significance of what we just read. People with ADHD are more likely to have inflammatory and autoimmune disorder comorbidities. In other words, something is wrong with the immune system, and it causes inflammation as a result. So not surprisingly, when they test people with ADHD for blood markers of inflammation, they find they have many more inflammatory cytokines than controls.

When we look at developmental factors for ADHD, we see early life exposure to environmental risks that cause inflammation. In animal models, they have identified the mechanisms between immune system activation during pregnancy and subsequent brain and behavior changes in the offspring similar to those seen in people with ADHD.

If all that is not enough to convince you that neuroinflammation is highly relevant in ADHD, allow me to tell you about the genetic polymorphisms they have found associated with the pathways that create that inflammation.

Whether or not all these associations are found to be causal or not, I would argue, does not matter. We don’t perfectly underly the causal mechanism of most things, and we slap a pharmaceutical on top to modify what we think is going on, and we do it all the time. So why wouldn’t we consider inflammation as a potential target to help alleviate symptoms of ADHD?

Luckily, a lot of really smart researchers already agree with me. I wouldn’t want you to think this is just something I came up with by myself.

Based on our hypothesis, targeting neuroinflammation may serve as a potential new therapeutic intervention to treat ADHD

Kerekes, N., Sanchéz-Pérez, A. M., & Landry, M. (2021). Neuroinflammation as a possible link between attention-deficit/hyperactivity disorder (ADHD) and pain. https://doi.org/10.1016/j.mehy.2021.110717

This neuroinflammation is also relevant to what we read in the last section regarding neurotransmitter imbalances. Inflammation creates more excitatory neurotransmitters and promotes the upset we see between glutamate and GABA. Inflammation creates an environment in the brain where it cannot make the appropriate ratios of GABA to glutamate. It is probably because it is under duress (from all those nonstop car chases).

It is unreasonable to think that you would be making neurotransmitters telling you to be chill and that everything is alright when you have chronic neuroinflammation. This is why it is important to pay attention to your symptoms. It is your brain’s way of telling you something is seriously wrong. It needs you not to ignore the nonstop car chases going on and doing damage. It requires you to pay attention. It’s probably not a fan of you trying to find prescriptions that help you pretend that the damage is not occurring.

Let’s make inflammation one of the core targets of intervention that we see contributing to symptoms in ADHD/ADD brains.

How ketogenic diets are a treatment for neuroinflammation seen in ADHD

As we discussed above, neuroinflammation seen in ADHD comes in part from dysfunctional immune responses. I do not usually discuss the effects of ketogenic diets on the immune system, but it appears to be highly relevant to etiology and symptom presentation with this population.

However, I am not well studied in immune systems, so I will be very general here and do further research if you feel the need.

Ketogenic diets upregulate and balance immune function. We use them to help treat some forms of cancer, in part, because of favorable immune response in T-cell activation. Researchers found enough positive effects of a ketogenic diet on immune system function that an RCT was initiated to see if it could be used to provide a protective factor against COVID.

Some people think that this upregulation of the immune system happens because of a ketogenic diet’s changes to the gut microbiome. One of the guts’ favorite fuels is butyrate, a component of certain ketone bodies and can be found in the highest amounts in butter. I always find this to be super ironic, given the focus so far seems to be all about prebiotic fiber as the superhero of gut health and wellness. I also have to point out that some healing happens in the blood-brain barrier when you go on a ketogenic diet.

Thus, beneficial effects of the ketogenic diet may depend on increased brain uptake of KBs to match metabolic demand and repair of a disrupted BBB. As the effects of KBs on the BBB and their transport mechanisms across the BBB are better understood, it will be possible to develop alternative strategies to optimize the therapeutic benefits of KBs for brain disorders where the BBB is compromised.

(KBs=ketone bodies; BBB=blood brain barrier)
Banjara, M., & Janigro, D. (2016). Effects of the ketogenic diet on the blood-brain barrier. 
DOI: 10.1093/med/9780190497996.001.0001

A healthy blood-brain barrier means fewer things floating up into your brain that quite frankly do not belong. And when you have toxins or substances that get through that blood-brain barrier that does not belong, it leads to a triggering of the cytokines and contributes to neuroinflammation.

So consider the effects a ketogenic diet has on immune function as a bonus that plays an important role in helping you alleviate your ADHD/ADD symptoms help alleviate your symptoms.

Another mechanism by which ketogenic diets reduce inflammation is by inhibiting inflammatory pathways. Ketones, which are made in abundance on a ketogenic diet, are signaling molecules, and being a signaling molecule means that they serve as a messenger, telling some genes to turn off and other genes to turn on. And ketogenic diets reduce inflammation in this very cool way. Like, directly.

In the next section, we will learn about how inflammation plays a role in oxidative stress and how decreasing this pathological mechanism might influence symptoms we see in ADHD.

ADHD and Oxidative Stresss

Oxidative stress occurs when there is an imbalance of the body’s ability to deal with byproducts that happen just by being alive. Lots of things can cause oxidative stress. Just breathing creates something called reactive oxygen species (ROS). So your body expects a certain amount of ROS, just from being alive. And it isn’t a problem when your damage/antioxidant systems are in balance. As we will talk about later in this blog post, we were made to deal with ROS, at least to some extent. But the levels at which we are exposed today are unprecedented in your evolutionary history.

We just discussed inflammation. Does inflammation make more oxidative stress? Yes. Yes, it most certainly does.

Inflammatory process induces oxidative stress and reduces cellular antioxidant capacity.

Khansari, N., Shakiba, Y., & Mahmoudi, M. (2009). Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. https://doi.org/10.2174/187221309787158371

These ROS have to be detoxed or neutralized. And for your body to do that, you need a lot of micronutrients (cofactors) and a good level of both endogenous (made inside your body) antioxidants. People also consume antioxidants (e.g., turmeric, quercetin, vitamins C and E), attempting to reduce oxidative stress.

Oxidative stress is no joke. Allowed to run unchecked over time, you get damage to your DNA. Let’s go back to our car chase analogy. It is as if the car chase has gotten so out of hand that buildings are falling and roads are crumbling. But now, the knowledge for fixing all these things has been lost in all the chaos. And now the people trying to rebuild the city, after all those car chases, can’t do it quite right or in a stable way. This is an analogy for the DNA damage that occurs with unchecked oxidative stress. As you can imagine, chronic diseases will develop as a result of this.

There are a lot of different ways that more ROS is created than what our body can handle. Besides just breathing and metabolizing energy, some of the things that can increase the burden of oxidative stress are environmental include:

  • UV and ionizing radiations
  • pollutants
  • heavy metals
  • plant constituents
  • drugs
  • pesticides
  • cosmetics
  • flavorings
  • fragrances
  • food additives
  • industrial chemicals
  • environmental pollutants

These all significantly increase ROS and cause this imbalance that we refer to as oxidative stress. Oxidative stress leads to cell and tissue damage, and brains, in general, are particularly sensitive to it.

But ADHD/ADD brains are even more so. No, really, and it’s in the research literature. But before we discuss that, let’s talk about medications used to treat ADHD.

On top of all those environmental sources of oxidative stress outlined above, people’s very medications to treat ADHD symptoms can exacerbate the problem. The use of ADHD medications like Methylphenidate (MPH), sold as Ritalin and other names, increases levels of oxidative stress.

In MPH there is evidence for increased OS, altered AO defense and neuro inflammation in ADHD children

Kovacic, P., & Weston, W. Attention-deficit/hyperactivity disorder–unifying mechanism involving antioxidant therapy: Phenolics, reactive oxygen species, and oxidative stress. https://www.biochemjournal.com/articles/23/1-2-10-853.pdf

In the research literature, we see high levels of oxidative stress in the ADHD brain, and this may come from a particular genetic vulnerability to ROS.

One example of this is Organophosphates, such as dimethyl phosphate (DMP; a pesticide). Genetic studies have shown that being exposed to higher levels of this substance in the environment created a significantly higher risk for developing some of the exact mutations we see in ADHD with dopamine receptors.

59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had … a significantly increased risk for developing ADHD

Chang, C. H., et al., (2018). The interactions among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children. https://doi.org/10.1016/j.envres.2017.10.011

So oxidative stress may very well be part of the etiology (how it begins) of ADHD. But does it play a role in its maintenance? I would say yes. There are polymorphisms in inflammatory-related genes seen in those with ADHD. Reduced antioxidant levels are seen in children, adolescents, and adults compared to control groups.

Oxidative stress is such an issue in the ADHD/ADD brain that one very popular and reportedly fantastic treatment is the use of OPCs. OPCs are particularly powerful antioxidants. I first learned about them in a free webinar at Psychiatry Redefined, which you can watch here. I don’t want to get off-topic, so I will not go into OPCs in this blog post. But I did want to point out that oxidative stress is a target of treatment in functional psychiatry. You may not have the benefit of a prescriber trained in functional medicine. So I leave this info here if you want to explore more for your wellness journey.

But as we are going to learn, there are many ways that a ketogenic diet helps treat oxidative stress, thereby potentially (and likely) improving your symptoms. One more way in which keto can help ADHD.

How ketogenic diets reduce oxidative stress levels in people with ADHD

There are many pathways by which are influenced by ketogenic diets. One example is that there is an increase in agmatine, a less popular neurotransmitter made from the amino acid L-arginine. This increase of agmatine in the brain that happens on a ketogenic diet has well-documented neuroprotective properties that help protect the ADHD brain from increased levels of oxidative stress.

Another thing to know about ketogenic diets, concerning their effects on oxidative stress, is that ketones are a very clean-burning energy source. Less ROS has created burning ketones for fuel than other primary fuel sources. Because of this, βHB (a type of ketone body) decreases ROS production and increases antioxidant defenses.

The other way that a ketogenic diet helps directly treat oxidative stress is that βHB alleviates oxidative damage due to excitotoxic insults (e.g., remember glutamate?) at the site where damage occurs. Somehow βHB helps dampen or repair the damage done by oxidative stress. And researchers think this may be due to the improved mitochondrial function or influencing gene expression.

But wait, there is even more that a ketogenic diet does to help reduce oxidative stress.

Ketogenic diets help us make more of an important antioxidant that we make in our own body. Remember, we talked about how your body knows that ROS will be a thing. Because you breathe and eat and move and stuff. So obviously, it has a way to deal with that. And it deals with that normal level of ROS with something called Glutathione. But as we learned, there are a lot of factors in our environment that push our ROS way past expected levels.

Glutathione is a vital antioxidant that can protect the cell from DNA damage. Ketogenic diets help you make more glutathione by increasing GCL, an enzyme needed to synthesize Glutathione. GCL is considered a “rate-limiting enzyme,” meaning that you only get as much glutathione as you have that enzyme. And so, the ketogenic diet making more GCL is what gives you more glutathione and is a very powerful ally in reducing oxidative stress in the ADHD brain.

Conclusion

So there you have it. Those are some of the many ways that a ketogenic diet can help reduce symptoms of ADHD and ADD. As you can see, a ketogenic diet is a multi-layered intervention.

It improves neuronal cell membrane health, improving communication between cells. Ketogenic diets upregulate GABA, helping to improve the glutamate/GABA imbalance seen in this population.

Ketones upregulate (makes more of) brain-derived neurotrophic factor (BDNF) to make neuronal cell repairs. Remember, those dopamine receptors don’t fix themselves. But perhaps more relevant is how the upregulation in BDNF can potentially improve working memory and learning in those with ADHD.

Ketogenic diets don’t stop there.

They reduce neuroinflammation and are neuroprotective, which will reduce oxidative stress in the ADHD brain.

Ketogenic diets improve mitochondrial function and create an excellent energy source for parts of the brain that are hypometabolic. This improved energy production stabilizes neuronal membranes (remember hyperpolarization?) and allows cells to function better. Possibly quite beneficial for the variability of expression in serotonin and dopamine receptors and transporters seen in those with ADHD and ADD.

These are all areas of potential healing involved in ADHD symptoms.

But wait, you may say. I don’t just have ADHD or ADD. I have comorbid issues, like mood disorders and substance abuse problems. This would not surprise me. When executive functioning is impaired, for any reason, people have trouble regulating moods. You need a fully functioning frontal lobe and neurotransmitter balance to control your emotions. And because ketogenic diets help with just that sort of thing, it should not surprise you that I have a variety of posts discussing how ketogenic diets also help treat anxiety, depression, and substance use disorder.

While the standard of care should always be offered to you, it is also important for you to know other options that are also evidence-based. So you can make informed decisions regarding their care.

Because you have the right to know all of the ways that you can feel better.

The ketogenic diet is one of them. And it is important to me that someone communicates that to you so you can make informed decisions about your treatment.

I want to encourage you to learn more about your treatment options from any of my blog posts. I write about different mechanisms in varying degrees of detail that you may find helpful to learn on your wellness journey. And you may benefit from understanding how working with a mental health counselor while transitioning to a ketogenic diet can be helpful here.

Share this blog post or others with friends and family suffering from symptoms. Let people know there is hope.

You can learn more about me here. If you would like to work with me to assist in your transition to a ketogenic diet, you can contact me here. I am, as always, very excited at the prospect that you could feel better.

Like what you are reading on the blog? Want to learn about upcoming webinars, courses, and even offers around support and working with me towards your wellness goals? Sign up!

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Can keto treat my depression without medication?

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How can a ketogenic diet help treat Depression?

Ketogenic diets modify at least four of the underlying pathologies seen in people with depression. These include glucose hypometabolism, neurotransmitter imbalances, inflammation, and oxidative stress. A ketogenic diet is a powerful dietary therapy shown to directly impact these four underlying mechanisms (and others) involved with depression symptoms.

Please note, there is an exponentially shorter version of this article with much less detailed information available here.

3 Reasons you are depressed and why keto can fix them

Introduction

In this blog post, I am not going to outline the symptoms or prevalence rates of depression and/or treatment-resistant depression. This post is not designed to be diagnostic or educational in that way. Other than to say that there are several levels of severity and chronicity when it comes to depression. This blog post is not going to discuss bipolar depression or mood disorders with psychotic features.

That is not to say that the ketogenic diet cannot be used for psychotic disorders. There are in fact, at the time of this blog post, published case studies in the peer-reviewed literature showing profound benefits and RCTs underway. I will very likely do a blog post on this topic in the future. In this post, we will discuss unipolar depression and how a ketogenic diet may be useful in treatment.

If you suffer from unipolar depression you may benefit from reading this blog post. Your depression may be chronic and severe enough to meet the criteria for major depressive disorder, and if so, you will also find this blog potentially helpful. If you have found this blog post, you know what depression is and likely you or someone you love may already be suffering from it.

If you have found this blog post, you are looking for treatment options. You are trying to find ways to feel better and heal. You are wondering if you can treat your depression with a diet.

By the end of this blog post, you will be able to understand some of the underlying mechanisms going wrong in the brains of people suffering from depression and how a ketogenic diet can therapeutically treat each of them.

You will come away seeing a ketogenic diet as a possible treatment for your depressive symptoms or as a complementary modality to use with psychotherapy and/or in place of medications.

What is the standard of care in treating depression?

Not surprisingly, the standard of care for depression is medication, therapy, or a combination of the two.

Medications most commonly used to treat depression include:

  • Tricyclic antidepressants (TCAs)
  • Selective serotonin re-uptake inhibitors (SSRIs)
  • Selective serotonin noradrenaline re-uptake inhibitors (SNRIs)

Less common ones include:

  • Adrenergic alpha-2 receptor antagonists
  • Monoamine oxidase (MAO) inhibitors
  • Selective noradrenaline re-uptake inhibitors
  • Selective noradrenaline/dopamine re-uptake inhibitors
  • Melatonin receptor agonists and serotonin 5-HT2C receptor antagonists

When one medication does not work, other medications from the same or different drug classes are added into combinations that the prescriber believes will reduce symptoms. We can look up any of these medications to learn their side effects, and imagine what side effects may look like for someone taking three or more of these medications. More prescriptions are then given to deal with the side effects of medications themselves.

However, a very large meta-analysis published in a peer-reviewed journal found that there is a lack of efficacy for SSRIs and that they significantly can increase the risk of serious side effects.

“SSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects.”

Jakobsen, J. C., Katakam, K. K., Schou, A., Hellmuth, S. G., Stallknecht, S. E., Leth-Møller, K., … & Gluud, C. (2017). https://doi.org/10.1186/s12888-016-1173-2

This is consistent with my experience of medications as a practitioner treating clients. You or a loved one may have similar experiences. They may have worked great for you or a loved one. Your experience may be that they not only saved your life but that you will need to take them continuously throughout the rest of your life. And you may feel completely ok with that option.

The people who have had great success using antidepressants or other psychopharmacology to treat their depression are not the people reading this blog.

This blog is for those people who are looking for alternative treatments likely to help where other interventions have failed, or who want to work to fix the root causes of unipolar depression. They want to explore if a ketogenic diet may be able to treat their depression without medications or reduced medications.

Psychotherapy is a key component of treatment for depression, whether with or without medications. According to updated treatment guidelines provided by the American Psychological Association (APA), some psychotherapies identified as being helpful to treat depression include the following:

  • Behavioral therapy
  • Cognitive therapy
  • Cognitive-behavioral therapy (CBT)
  • Mindfulness-based (includes ACT)
  • Interpersonal psychotherapy
  • Psychodynamic therapies
  • Supportive therapy

As a mental health counselor, I am partial to therapy. I use a combination of those top 4 and sometimes if depression is mild or more situational I will rely even on supportive therapy. I see it work great in most instances. But sometimes I get clients who are having a hard time responding to the therapy I am providing.

In those cases, my job is to send that client out for medication, as the research literature has found that in cases of moderate to severe depression outcomes are better when medication and psychotherapy are provided simultaneously. And sometimes this works well. But the client is often afraid to titrate down from the medication. Even though psychotherapy can change your brain chemistry and literally rewire your brain in healthier ways, there is almost always this idea that the pill did the trick.

Some of my clients believe they need the medication, even if it has side effects or may be difficult to titrate off of later. Yes, many clients do not receive adequate informed consent that withdrawal symptoms can be a part of taking psychiatric medications. There is an excellent article about it here.

Sometimes my clients come into therapy feeling numbed and having side effects that they are finding not tolerable. There have been times a psychiatrist will put them on so much medication I cannot do effective therapy with them.

Medications used to treat depression are designed to reduce the symptoms of depression. Medications for depression are not designed to fix whatever underlying process was going on that caused your depression in the first place, whether physiological, social, cognitive or some combination of all three.

Most psychiatrists are not going after the root cause of what is causing depression. The prescribing of medications is designed to help you continue your life as it was. To help you get back to work. Parent the kids more. Stay in that marriage. Deal with that difficult family member. Continue at that job. They are modulators of symptoms (hopefully, at their very best) but do not address the underlying pathologies that occurred to create the depressed state in the first place.

But medication and psychotherapy together are not always sufficient to eliminate symptoms, reduce symptoms, or keep them from recurring. You may be asking yourself if a ketogenic diet is able to treat depression without medication. For people who have decided to not use medications or even those who have, and are still suffering from depression, this is a legitimate question. People who are suffering from treatment-resistant depression are valid in their want to explore alternative therapies. You have the option to attempt to treat your depression using the ketogenic diet without medication or as a complement to psychotherapy. But first, you should learn more about why this might be a valid option on your wellness journey.

What are the neurobiological factors we see in depression?

A previous post went into detail about how a ketogenic diet can modify symptoms of anxiety. In this post we will see whether these same four areas of pathology are seen in depression:

  • Glucose Hypometabolism
  • Neurotransmitter Imbalances
  • Inflammation
  • Oxidative stress

In unipolar depression we see these same pathologies occurring. There are areas of the brain with hypometabolism (not using energy properly), distinct neurotransmitter imbalances affecting mood and cognition, and inflammation. The literature has identified oxidative stress as a component in exacerbating depression symptoms. Let’s review each of these. And consider how the ketogenic diet modulates all of these and may favorably improve symptoms.

In this blog post I will also discuss two other mechanisms by which a ketogenic diet may be helpful in the treatment of depression:

  • gut microbiome
  • brain-derived neurotrophic factor (BDNF)

Depression and Glucose Hypometabolism

Glucose hypometabolism is a prominent feature of depression. We see it in several areas of the brain. Hypometabolism means that for some reason, energy is not being used well. The term “metabolism” refers to how the cells are using, storing, or creating energy. This “hypo” (too low) metabolism in the brain can be caused by a variety of factors and are often the result of those factors causing inflammation and oxidative stress (which we will learn more about in this blog post).

Altered metabolism in insula, limbic system, basal ganglia, thalamus, and cerebellum and thus these regions are likely to play a key role in the pathophysiology of depression.

Su, L., Cai, Y., Xu, Y., Dutt, A., Shi, S., & Bramon, E. (2014). Cerebral metabolism in major depressive disorder: a voxel-based meta-analysis of positron emission tomography studies. https://doi.org/10.1186/s12888-014-0321-9

There are a lot of areas of hypometabolism involved in depression, and it is thought that these different areas of dysfunction reflect differences in subtypes of depression and different methods of study. For example, when we see decreased metabolism in the prefrontal cortex, particularly the dorsolateral prefrontal cortex, we see it associated with a reduction in problem-solving abilities and a higher likelihood for negative emotions to be acted upon.

Location of the dorsolateral prefrontal cortex

This tendency to be unable to solve problems and to react with negative emotions can put people with depression at risk for suicidality in those with Major Depressive Disorder (MDD).

Factors believed to contribute to the creation of hypometabolism in include the following:

  • aging
  • hypertension
  • diabetes
  • hypoxia/obstructive sleep apnea
  • obesity
  • vitamin B12/folate deficiency
  • depression
  • traumatic brain injury

Pay attention to that list. We will talk about it a bit more when we discuss ketogenic diets as a treatment for depression.

We are discussing brain hypometabolism as we focus in on brain dysfunction in depression. But me talking about hypometabolism must also be conceptualized as a metabolic disorder. Brain hypometabolism is a sign of metabolic dysregulation and disorder.

Three longitudinal studies among depressed patients found that a combination of multiple metabolic dysregulations contributes to the sustained chronicity of depression.

Penninx, B., & Lange, S. (2018). Metabolic syndrome in psychiatric patients: overview, mechanisms, and implications. . https://doi.org/10.31887/DCNS.2018.20.1/bpenninx

Remember this as we begin to discuss below how a ketogenic diet can treat this underlying pathological state in depressed brains.

How does a ketogenic diet treat hypometabolism in depression?

Now, let’s go back to the list we just reviewed showing the factors believed to contribute to the creation of hypometabolism in the brain. But this time, we will point out the conditions in which a ketogenic diet is used to treat and/or reverse those very factors.

  • aging
    • ketogenic diets are used to treat mild cognitive decline, Alzheimer’s disease, and other dementias (e.g., vascular)
  • hypertension
    • a ketogenic diet can get someone off hypertension medications in as little as 3 days
  • diabetes
    • ketogenic diets have been seen to reverse Type II Diabetes or put in remission to the point insulin is no longer needed
    • If you are surprised by this you may enjoy exploring Virta Health
  • hypoxia/obstructive sleep apnea
    • ketogenic diets help people lose weight, which can either reverse or reduce the severity of obstructive sleep apnea
  • obesity
    • there is a large research literature showing that the ketogenic diet can help reduce obesity and improve body composition
  • vitamin B12/folate deficiency
    • this can be due to genetic issues and may need special supplementation, however, a well-formulated ketogenic diet is high in these nutrients
  • depression
    • Why we are here reading about a ketogenic diet as a treatment for depression
  • traumatic brain injury
    • ketogenic diets are used as a therapy for traumatic brain injury

So before we even explore how a ketogenic diet helps reverse or improve brain hypometabolism, we can see that the ketogenic diet already has strong research and clinical base showing its use in conditions that are either associated with or create brain hypometabolism!

The ketogenic diet is, in fact, a treatment for metabolic disorders. Remember the quote from a few moments ago, from a research paper discussing how psychiatric illnesses are metabolic disorders? Ketogenic diets have the power to reverse metabolic disorders. Meaning they can reverse the mechanisms underlying metabolic disease. Even those that occur in the brain. We use ketogenic diets to improve the metabolic dysfunction in the brains of those suffering from Alzheimer’s Disease. Should we not be considering it to reverse the metabolic dysfunction we see in clinically depressed brains?

I would argue strongly that we in fact should.

But now we will talk about how a ketogenic diet can reverse or improve brain hypometabolism.

The most obvious way that a ketogenic diet improves hypometabolism is by providing an alternative fuel source for the brain. Sometimes, for a variety of reasons, the machinery used by brain cells to use glucose as fuel doesn’t work well anymore. Luckily, ketones, which are generated on a ketogenic diet, can bypass that faulty cell machinery and get right into those neurons to be burned as fuel. Ketogenic diets also upregulate the creation of something called mitochondria.

Mitochondria are the powerhouses of your neurons. They make energy. So your cells make more mitochondria and those mitochondria work really well when given ketones as fuel.

The other way that ketogenic diets help prevent and reverse hypometabolism is by helping cell membranes work better. Cell membranes working better mean healthy action potentials. Action potentials are what we call that moment when a cell fires. A firing cell, firing in a balanced way, without firing too much or too little, is an effect of ketogenic diets.

Ketogenic diets also upregulate (increase or make more of) important enzymatic activities (enzymes are essential in almost all things) needed to generate cellular energy.

The bottom line is that brains suffering from hypometabolism work better using a ketogenic diet. Got depression? You have hypometabolism. Need a treatment for that underlying pathology driving your depression? Ketones are a potential therapy.

Depression and Neurotransmitter Imbalances

It can be difficult to write about the effects of the ketogenic diet on mental illness, and on depression in particular, because each of the headings we will discuss influences the other. Here is a good example:

Thus, pro-inflammatory cytokines can interact virtually with all pathophysiological changes that characterise major depression and thereby influence neurotransmitter function, synaptic plasticity and ultimately neuronal structure.

Leonard, B. E., & Wegener, G. (2020). Inflammation, insulin resistance and neuroprogression in depression. https://pubmed.ncbi.nlm.nih.gov/31186075/

This section is not about inflammation. That comes later. But as you learn about how the ketogenic diet treats depression you will have to become a systems thinker. Keep in mind as we discuss neurotransmitter imbalances seen in depression, that the other categories of hypometabolism, inflammation, and oxidative stress influence the creation of those neurotransmitter imbalances. I will also do my best to wrap how these interact in the conclusion, but do your best to make these connections as you go.

The neurotransmitter imbalances we see in depression occur most likely because of neuroinflammation, often initiated by immune responses that create inflammatory cytokines. We will talk more about that later, but understand that when your brain is inflamed, it is an environment that is not in balance. And apparently, your brain needs to have a certain amount of stability in order to make neurotransmitters in the right amount and balance. To achieve neurotransmitter balance you need a brain that is not under a lot of excess stress, inflammation, or oxidative stress.

Neurotransmitters thought to be involved in major depressive disorder include serotonin, dopamine, norepinephrine, and GABA. Almost the entire psychiatric literature has been based on the idea that depression is a neurotransmitter imbalance, right? But let’s talk about how those neurotransmitters might be getting out of balance in the first place.

When your brain is suffering from inflammation (and yes, a high sugar diet can cause higher inflammation and immune system dysfunction that can lead to neuroinflammation), there is something called a tryptophan steal. This results in less serotonin, less melatonin, and less GABA being made. It also means more dopamine, which for some psychiatric disorders is not a good thing, as well as excitotoxic levels of glutamate. What does this mean to the depressed brain?

Tryptophan is an amino acid and gets made into neurotransmitters with a little help from cofactors such as important micronutrients. If your brain is inflamed at a time that neurotransmitters need to be made, this amino acid goes through a different pathway and makes more of an excitatory neurotransmitter called glutamate. Now, glutamate is not a bad neurotransmitter. you need glutamate. You just don’t need or want the 100x more glutamate that will be made when your brain is inflamed. That much extra glutamate is neurotoxic and ironically, creates even more inflammation through neurodegeneration.

Glutamate at these levels feels anxious. Or if inflammation levels get high enough probably feels depressed. Why? Because by going through the wrong pathway your brain has made much much less GABA than it was supposed to.

Was there some time in your life when you were feeling the opposite of overwhelmed? You felt chill and competent and exuded a sense of “I got this” as you thought about life and your future? That was your brain having the right amount of GABA. And that, my friend, is your natural state of being.

You are not your depression.

This tryptophan steal also reduces the amount of serotonin and melatonin you can make. So you get low, sad, depressed mood and terrible sleep. You start doing that thing where you don’t fall asleep at a reasonable time. And then you stay up late, possibly ruminating or feeling generally terrible, and then you have trouble getting up in the morning. So you call yourself a loser and reinforce the negative cognitive bias that develops and helps sustain depression. Which makes you sadder and worsens your symptoms causing more inflammation. Sound familiar?

You know what I am talking about. That is you living the consequences of an inflamed brain messing up your neurotransmitter balance. Depleting your micronutrients to upkeep your brain and make enzymes and neurotransmitters. And fixing this is actually more in your control than you would ever imagine.

Remember, medications do not help you make more serotonin. Only your brain can really do that. They just help what you can make hang out. And if you are not making enough because of this inflammatory neurotransmitter imbalance train-wreck and/or because of micronutrient deficiency (less likely on a well-formulated ketogenic diet), then those medications can only do so much.

How the ketogenic diet improves neurotransmitter imbalances seen in depression

Ketogenic diets significantly alter the neurotransmitters dopamine and serotonin but with a stable ratio, meaning it helps the brain make not too much and not too little. Something particularly useful in those with depression. Remember, you can be prescribed medication in the form of reuptake-inhibitors for both serotonin and dopamine. They will give you longer access to the neurotransmitters you have managed to produce and for a lot of people that will help to relieve symptoms.

What those medications will NOT do is ensure a balanced ratio, or be able to tell your complicated brain when it needs more or less. And that is why they often create side effects. Side effects can happen when a medication is trying to modulate something too far one way or the other, and it is affecting multiple systems. You do not get that with a ketogenic diet. There is just none of that nonsense going on.

And so a ketogenic diet, with its many pathways of intervention and its ability to regulate and balance neurotransmitter production and use, can make it an excellent treatment for depression. All by itself, or in addition to medications, under the care of your prescriber.

Depression and neuroinflammation

A lot of things can cause neuroinflammation. A high sugar or carbohydrate diet that your metabolism cannot deal with can cause inflammation. That high fructose drink you prefer? That can cause inflammation. No really, I am not making this up. Look here.

A leaky blood-brain barrier that lets toxins get up in the brain where they don’t belong can cause inflammation. A leaky gut that lets matter through for the immune system to freak out about can cause inflammation. An event that happens in your body, way far away from your brain, can trigger neuroinflammation, because the immune system in your body, talks to the one in your brain. A traumatic event can increase neuroinflammation, probably through mechanisms around cortisol. Having an immune response, whether viral or to injury, can cause neuroinflammation.

When we study depression and inflammation, we look for markers of inflammation. And the research literature is full of studies looking at these different types of markers for what are called cytokines. Cytokines are powerful and the way they play out in your brain is they control your behavior. Remember when you had a bad cold or flu, and you literally just laid down, and did not get up again for a very long time. You sat still. You had no motivation to go do anything or stimulate yourself overmuch with any sort of activity? That was your body’s immune system calling out to the separate immune system that is in your brain, to let it know to stay alert, that your body was under attack, and that you needed to rest. So that brain inflammation did just that, with inflammatory cytokines. So you rested.

How is this relevant to depression? Think about it like this. Are you motivated to get up and do things? Does being on the couch and not feeling motivated to move sound familiar? Your brain is inflamed. This inflammation is part of what creates your symptoms of depression. Signs of neuroinflammation include brain fog, anxiety, depression, headaches, and poor mental stamina. Do those sound like some of your symptoms?

Depression is not just neurotransmitter imbalances as you were led to believe, and told could be fixed with medication. It is also inflammation that is driving your symptoms. And inflammation needs its own special attention in the treatment of depression.

Chronic low-grade inflammation has been observed in major depression and other major psychiatric disorders and has been implicated in metabolic changes that are commonly associated with these disorders.

Leonard, B. E., & Wegener, G. (2020). Inflammation, insulin resistance and neuroprogression in depression. HTTPS://PUBMED.NCBI.NLM.NIH.GOV/31186075/

Let me use this as an opportunity to help you make connections. Remember when we discussed the need for the brain to not be inflamed in order to make the right combo of neurotransmitters? Remember our talk of the tryptophan steal? This is what the below quote from the research literature is talking about:

Thus, as a consequence of immune activation, the changes in the tryptophan-kynurenine pathway play a major role in the dysfunctional neurotransmitter systems in the brain and, in addition, contribute to the changes in the brain structure and function which characterise depression.

Leonard, B. E., & Wegener, G. (2020). Inflammation, insulin resistance and neuroprogression in depression. https://pubmed.ncbi.nlm.nih.gov/31186075/

Neuroinflammation sets the stage for your brain to not work well, which then creates the perfect conditions for that tryptophan steal to occur. And this consistent state of inflammation and imbalanced neurotransmitters starts to change your brain structures and the connectivity of those brain structures.

So as you can imagine, a powerful intervention to reduce inflammation is warranted if we want to treat depression. And I think you obviously know where I am going with this.

How ketogenic diets reduce neuroinflammation in those with depression

There is an excellent and well-written article on how ketones work here and one specifically about inflammation here. They are much more biochemically in-depth than the level discussed in this blog post. If you like the neurochemistry and biochemistry pieces you should definitely deep dive there for a more in-depth understanding.

But for the rest of us, it is just important to know that ketogenic diets are VERY powerful anti-inflammatory therapies.

First, the reduction in carbohydrates significantly reduces inflammation, because your body isn’t desperately trying to get your ideal blood sugar levels back down to about a tsp worth of glucose in your entire bloodstream. If you are insulin resistant (and you likely are because of how our diets are in modern times) then every second you are swimming in higher blood sugar levels for longer than they should be you are contributing to cell damage and inflammation. So ketogenic diets, with their restriction to low carbohydrates, really help that.

Second, ketones, which are produced on a ketogenic diet, are signaling molecules. This means they turn genes on and off. And some of the genes they turn on and off are those that manage inflammation in the body. And if that wouldn’t make them an effective treatment for the neuroinflammation that we see is rampant in depression, I do not know what would be. Perhaps someday gene therapies will occur for depression, that does the work of ketones. And you can wait for those, but I am not sure why you would want to when you have the ability to instigate your own gene therapy through a free, effective dietary therapy with no significant side effects.

Depression and Oxidative Stress

Oxidative stress, in general, works like this:

  • Cells make energy using ATP
  • ATP goes through a process called oxidative phosphorylation
  • This causes reactive oxygen species (ROS); which are destructive by-products of this very normal process
  • ROS damages DNA, and this damage can be cumulative
  • Oxidative Stress is what we call the burden on our system to repair this damage

It is not about whether you have oxidative stress, it is about what your levels of oxidative stress are and the burden and damage that occurs in your body as a result.

The brains of people suffering from depression have higher levels of oxidative stress. The higher your oxidative stress, the poorer your outcomes when using anti-depressants. Why would that be? Well, anti-depressant medications do not address this problem. As we discussed, medications for depression are about alleviating symptoms. Not causes.

If your inflammation is too high, you create more ROS. And too much ROS depletes the systems designed to reduce inflammation. This increases your level of oxidative stress. Oxidative stress is higher in those with depression. So we need an intervention that can address both inflammation and oxidative stress.

How ketones treat Oxidative Stress in those with Depression

B-Hydroxybutyrate, one of 3 types of ketones made in the body reduces the production of reactive oxygen species (ROS) and thereby improves mitochondrial function, which you experience as energy and better working everything. It also stimulates your own antioxidant system that uses endogenous glutathione production. I promise you, there is no antioxidant therapy you can take that will be as powerful as your own endogenous glutathione system that is upregulated with ketone action and plenty of glutathione precursors coming from a well-formulated ketogenic diet. I don’t care how much Vitamin C you are downing, you are not going to get the same level of anti-oxidant support you would get from your own well-working endogenous (made in your body) anti-oxidant system.

You were, after all, made to deal with reactive oxygen species. Seriously, you get them just by breathing. Do you think evolution didn’t think about that?

I am not saying our modern world with its pollutants, chemicals, current ways of eating, and the resulting chronic diseases, do not warrant some extra anti-oxidants or detoxification strategies. But I am saying that if you use ketogenic dietary therapy and upregulate your ketones you are going to treat the neuroinflammation in your brain that is contributing to, or more likely causing, your depressive symptoms. And it’s going to do it at a level you are just not going to get eating as you have and popping a lot of vitamin C and turmeric.

Glutathione aside, reducing your carbohydrate intake helps (immensely) to not deplete the glutathione you already make. Oxidative stress is a result of creating more reactive oxygen species than your current antioxidant systems (whether those you make or those you eat) can handle. And then we get cell damage, inflammatory cytokines, and quite frankly, serious DNA damage. And that DNA damage can never be fixed if you are constantly slamming your defenses with a diet (or environment) that creates a constant source of inflammation.

Usually, I stop with the above four mechanisms of action. But in depression, I thought it would be helpful to discuss two other ways that a ketogenic diet may be helpful in treating depression without medication (or with meds if you find a knowledgeable prescriber or mental health counselor).

Effects of ketogenic diets on gut microbiome and depression

There is a lot of research that I will not go into here about the gut microbiome and depression. There are some important nutrients involved in this (e.g., Vitamin D is HUGE) and it really warrants its own blog post. Also, what we know about the microbiome is very much in its infancy. There are a lot of educated assumptions going on as researchers are trying to figure things out.

But what I can tell you is that a well-formulated ketogenic diet makes for a happy and healthy microbiome. Beta-hydroxybutyrate is one of three types of ketones. The “butyrate” portion of this type of ketone is immensely helpful for gut healing and health.

Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders. Indeed, it is clear that host energy metabolism and immune functions critically depend on butyrate as a potent regulator, highlighting butyrate as a key mediator of host-microbe crosstalk. 

Stilling, R. M., van de Wouw, M., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2016). https://doi.org/10.1016/j.neuint.2016.06.011

I know what you are thinking. The benefits of the ketogenic diet just go on and on and on. It sounds like a scam. Like a too-good-to-be-true sort of thing. And I would understand if you were skeptical. But I promise I am not making this stuff up.

Do you know what food has the highest butyrate levels? Butter. That’s right. Your gut loves butter. Possibly more than it loves all the prebiotic fiber you are worried about getting. But don’t be concerned. A well-formulated ketogenic diet is full of that also in all those low-carb veggies you would be enjoying.

So don’t let people tell you the ketogenic diet is bad for your gut microbiome or it is going to “mess it up” or something like that. That is just not the case. If anything it can improve your gut health, help repair leaky gut, and as a result calm down that immune system activity that is contributing to inflammation, which then can cause neuroinflammation, and directly contribute to the imbalances in your neurotransmitters.

The gut microbiome is not my area of expertise at all. I am not up on my understanding of all those little bacteria and the effects they have on the body, or the metabolic pathways they may influence. But if you are way into that stuff and want to learn more about what kind of specific changes in the gut microbiome we see with ketogenic diets you can find a great blog post here.

Brain-Derived Neurotrophic Factor (BDNF)

Brain-derived neurotrophic factor (BDNF) is a protein encoded by a specific gene. It’s that important. It does some really important things:

  • enhance neurogenesis (new brain cells and parts)
  • brain cell proliferation and survival
  • an important role in learning and memory

It is required for a healthy brain. It is needed to grow, to heal, to make new connections, and to learn. Why does this matter if you have depression?

When you have a depressed brain the damage is progressive in nature and includes changes in brain structure and function. You are going to need nice high levels of BDNF to help restructure those pathways and to get the most out of any psychotherapy you use as an adjunctive treatment. When I sit down with a client using cognitive-behavioral therapy, I am there to help them restructure thought patterns. That is going to mean they need to make new connections of thought and memory.

Problems with BDNF have been identified as a factor in depression.

The maladaptive neuroplastic in depression may be related to alterations in the levels of neurotrophic factors, which play a central role in plasticity. Enhancement of neurotrophic factors signaling has great potential in therapy for depression.

Yang, T., et al. (2020). The role of BDNF on neural plasticity in depression. https://doi.org/10.3389/fncel.2020.00082

BDNF is this mysterious factor that is absolutely crucial for brain health and fixing broken connections, and it just happens to be upregulated quite nicely on a ketogenic diet. Seen, by the way, in both animal and human studies. The science on this is legit. Anyone saying the ketogenic diet as a treatment for depression is fringe just doesn’t know the research literature on its benefits. Because if they did, they would nod their head and say “yeah, I can totally see how that would work.”

Conclusion

So the reduction in carbohydrates that happens with a ketogenic diet is helpful because it reduces inflammation and it allows our bodies to make ketones. And as we have learned, ketones are a direct and powerful intervention for inflammation. Ketones, which are generated by employing a ketogenic diet, help you make more of your own anti-oxidants (glutathione). Ketones can help repair leaky brain and gut membranes to keep inflammation down from immune system over-activation.

There is even important research about how ketogenic diets improve immune function, but I had to have some limits on this post or it would go on forever.

Less inflammation helps your body hold on to more of its important micronutrients. These micronutrient levels could be boosted further in the choice to eat a well-formulated, whole foods ketogenic diet. These micronutrients would be used to repair damaged DNA, help cell membranes work better, and make neurotransmitters in sufficient and balanced quantities. The boost in cellular energy and power that you get with ketones helps your neurons repair themselves from the damage that has happened. That fuel helps them to do basic housekeeping and upkeep those cells and cell membranes.

I don’t know of a single medication that can do all of these things. And I do not believe a cocktail of medications could achieve these things without an awful lot of side effects. And it is for this reason that I really wanted you to know that a ketogenic diet might be used instead of medications for depression. I want you to know that many of the mechanisms by which ketogenic diets work are well-documented in research. As are their stellar effects. And I believe you need this information in order to make good treatment decisions, so you can live your very best life.

I want to encourage you to learn more about your treatment options from any of the following blog posts. I write about different mechanisms in varying degrees of detail that you may find helpful to learn on your wellness journey. You may enjoy the Ketogenic Case Studies page to learn how others have used the ketogenic diet to treat mental illness in my practice. And you may benefit from understanding how working with a mental health counselor while transitioning to a ketogenic diet can be helpful here.

Share this or other blog posts I have written with friends and family suffering from mental illness. Let people know there is hope!

You can learn more about me here. If you would like to contact me you may do so here. If you just have a simple question please do not hesitate to reach out. Or let me know in a comment if you have found this blog post to be helpful on your wellness journey.

I truly believe you have the right to know all of the ways you can feel better.

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Taylor, R. W., Marwood, L., Oprea, E., DeAngel, V., Mather, S., Valentini, B., Zahn, R., Young, A. H., & Cleare, A. J. (2020). Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines. International Journal of Neuropsychopharmacology, 23(9), 587–625. https://doi.org/10.1093/ijnp/pyaa033

Yang, T., Nie, Z., Shu, H., Kuang, Y., Chen, X., Cheng, J., Yu, S., & Liu, H. (2020). The Role of BDNF on Neural Plasticity in Depression. Frontiers in Cellular Neuroscience, 14, 82. https://doi.org/10.3389/fncel.2020.00082

Yudkoff, M., Daikhin, Y., Melø, T. M., Nissim, I., Sonnewald, U., & Nissim, I. (2007). The ketogenic diet and brain metabolism of amino acids: Relationship to the anticonvulsant effect. Annual Review of Nutrition, 27, 415–430. https://doi.org/10.1146/annurev.nutr.27.061406.093722

Obsessive-Compulsive Disorder (OCD)

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How can a ketogenic diet help treat the symptoms of Obsessive-Compulsive Disorder (OCD)?

Ketogenic diets are able to modify at least four of the pathologies we see in people with obsessive-compulsive disorder (OCD). These pathologies include glucose hypometabolism, neurotransmitter imbalances, inflammation, and oxidative stress. A ketogenic diet is a powerful dietary therapy that has been shown to directly impact these four underlying mechanisms that have been identified to be involved with obsessive-compulsive disorder (OCD) symptoms.

Introduction

In this blog post, I am not going to outline the symptoms or prevalence rates of OCD. This post is not designed to be diagnostic or educational in that way. Other than to say that OCD is highly related to other disorders such as Body Dysmorphic Disorder, Trichotillomania, Hoarding, and Excoriation Disorder (aka skin picking). If you suffer from any of those with or without a formal OCD diagnosis, you may also benefit from reading this blog post. If you have found this blog post, you know what OCD is and likely you or someone you love may already be suffering from it.

If you have found this blog post, you are looking for treatment options. You are trying to find ways to feel better and heal.

By the end of this blog post, you will be able to understand some of the underlying mechanisms going wrong in the brains of people suffering from OCD and how a ketogenic diet can therapeutically treat each of them.

You will come away seeing a ketogenic diet as a possible treatment for your OCD symptoms or as a complementary modality to use with psychotherapy and/or in place of medications.

Current psychopharmacology uses selective reuptake serotonin inhibitors (SSRIs), often (and hopefully) with cognitive-behavioral therapy (CBT) to treat OCD.

Katzman, M. A., Bleau, P., Blier, P., Chokka, P., Kjernisted, K., & Van Ameringen, M. (2014). https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4120194/

We can easily look up the side effects of any of these medications. The symptoms of OCD with and without psychotherapy can be so debilitating and chronic for some people, that enduring side-effects may seem a small price to pay for improved functioning. As a mental health counselor, I am quite biased toward the use of cognitive-behavioral therapy (CBT) and mindfulness skills as a treatment for OCD, seeing improvements in patients who do protocols with or without medication. But for some patients, medication and psychotherapy are not sufficient to improve symptoms. And some of my patients simply do not improve on current medications or do not tolerate the side effects of medications. And they are not alone.

Nonetheless, as many as half of all patients with OCD do not attain remission with current treatments, suggesting the considerable potential for further innovations in psychopharmacology for the disorder. 

Szechtman, H., Harvey, B. H., Woody, E. Z., & Hoffman, K. L. (2020).  https://doi.org/10.1124/pr.119.017772

Because over half of the people we attempt to treat with medication do not improve, it is our right and our responsibility to look outside of the standard of care for those suffering from OCD. To ask people suffering to wait until psychopharmacology catches up and provides effective treatment is inhumane. Especially when there are other interventions that could prove beneficial for this mental disorder.

So we are going to look at the literature to learn of some of the mechanisms of pathology we have seen in people who suffer from obsessive-compulsive disorder (OCD). We will discuss how the ketogenic diet can be a treatment for the underlying mechanisms found in symptom presentation with OCD.

What are the neurobiological changes seen in people suffering from OCD?

A previous post went into detail about how a ketogenic diet can modify symptoms of anxiety by affecting four areas of pathology seen in these disorders.

  • Glucose Hypometabolism
  • Neurotransmitter Imbalances
  • Inflammation
  • Oxidative stress.

In OCD we see these same pathologies occurring. There are areas of the brain with hypometabolism (not using energy properly), distinct neurotransmitter imbalances affecting mood and cognition, and inflammation. There is even a component of oxidative stress present in the obsessive-compulsive disorder (OCD) brain, exacerbating symptoms. Let’s review each of these. And consider how the ketogenic diet modulates all of these and may favorably improve symptoms.

OCD and Brain Hypometabolism

Changes in glucose activity have been documented in the orbitofrontal cortex (OFC) and the caudate nucleus and could correlate the presence and lack of obsessive-compulsive disorder (OCD) symptoms based on these findings. Neuroimaging studies using PET, SPECT, and fMRI have found that abnormally high activity occurs throughout the frontal cortex and connected subcortical structures. But that with successful treatment using SSRIs or behavior therapy this high activity returns to normal levels.  

Generally, we see hypermetabolism in obsessive-compulsive disorder (OCD). An increased metabolic rate in the left orbital gyrus and bilaterally in the caudate nuclei. But that is not to say that there is no hypometabolism component in OCD. It just may be more dependent on the course of illness and the activity being attempted.

Glucose hypermetabolism is later replaced by hypometabolism in the anterior cingulate cortex (ACC). This is thought to occur because the ACC eventually stops performing normal functions in this part of the brain. Why would the ACC do this? Because it redistributes functions to other brain structures because of abnormal circuitry that develops over the course of the illness. Brain structures will wire harder and stronger where there is increased activity. Brains are quite plastic, meaning if there is an area of overexcitability it will modify what brain structures are connected and to what degree.

Evidence from neuroimaging studies indicates that while there is one loop of hyperactivity, there is a second loop of hypoactivity between the dorsolateral prefrontal cortex (dlPFC) and dorsolateral caudate in patients with OCD. This hypoactivity is thought to underlie the cognitive inflexibility and deficits in executive function seen on neuropsychological assessments in OCD patients.

Thus, the prevailing hypothesis asserts that an imbalance between these 2 circuits is the underlying basis for OCD, as a hyperactive OFC generates obsessions and their associated ritualistic compulsions, while a hypoactive executive network prevents the individual from being able to switch to a new behavior.

McGovern, R. A., & Sheth, S. A. (2017). https://doi.org/10.3171/2016.1.JNS15601

We also see that OCD patients demonstrate working memory impairments that may be associated with glucose hypometabolism in the prefrontal cortex. These working memory impairments include not only simply trying to remember things for short periods, but also include problems with visual-spatial and executive functioning. These deficits in executive functioning, which are associated with brain hypometabolism, are part of symptom presentation. In order to have some control of our thoughts, or to move our thoughts away from more base thoughts devoted to fear and safety, we must have good executive functioning in the brain. For this reason, I would argue that hypometabolism is a relevant target of neurobiological intervention in those with OCD.

Also, I do not see many patients who do not have comorbidity with other disorders. Meaning, many of my patients have what is called dual diagnoses. Meaning they don’t just have OCD, but they have over mental illnesses that go along with it. And one comorbidity that I see quite often with OCD is depression. Depression is consistently seen to show a great deal of dysfunctional brain hypometabolism. This prominent hypometabolism component is correlated strongly and possibly causative of symptom presentation in depression in general, and is found present in those with comorbid OCD.

How a ketogenic diet treats hypometabolism in the OCD brain

Ketogenic diets are metabolic therapy for the brain. Ketogenic diets produce ketones. And ketones are used as an alternative fuel for the brain. Ketones can bypass broken metabolic machinery normally used to utilize glucose for fuel. Not only do brains love ketones, but a ketogenic diet helps neurons make more powerhouses for cells (mitochondria), increasing metabolism (energy expenditure) in important brain structures and connections seen in obsessive-compulsive disorder (OCD).

But wait, you may say. What about those other areas of hyperexcitability? Won’t a ketogenic diet rev all those up and make that loop (circuit) of the brain worse?

Absolutely not. Why?

our results suggest that brain network destabilization may reflect early signs of hypometabolism

Mujica-Parodi, L. R., et al., (2020). Diet modulates brain network stability, a biomarker for brain aging, in young adults. https://pubmed.ncbi.nlm.nih.gov/32127481/

Because the pathology of brain hypometabolism does not mean that the excitability is necessarily happening for the same reason. Ketogenic diets help to actually stabilize brain function by bypassing broken cell machinery that has resulted in the cell developing glucose hypometabolism. Also, supportive neuronal structures like astrocytes can upregulate their own ketone production, creating more energy overall in the brain. We will learn more about astrocytes later.

Hyperexcitability in some structures of the brain is much more likely due to neurotransmitter imbalance than glucose hypometabolism. Was I able to figure out exactly what causes the hyperexcitability? I don’t think the literature knows for sure. But we do see neurotransmitter imbalances that cause hyperexcitability and we know that unchecked inflammation can damage cell energy and cause areas of hypometabolism.

But because the ketogenic diet is not an intervention on a single component of mental illness, the way so many psychopharmacology treatments are, improving energy consumption in one hypometabolic structure is not going to cause another to rev up in a scary way.

recent evidence suggests that altering metabolism with a ketogenic diet enables a homeostatic state in the brain that is less excitable

Masino, S. A., & Rho, J. M. (2019). https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6281876/

Remember? This intervention works on at least four factors going wrong (with a few more thrown in we may discuss at the end), and the improvements on one system do not seem to imbalance or cause side effects with the others. The ketogenic diet appears to work holistically with all involved mechanisms of intervention.

OCD and Neurotransmitter Imbalances

Neurotransmitter imbalances we see in OCD include neurotransmitters, including serotonin, dopamine, glutamate, and GABA.

Serotonin imbalance plays an active role in OCD. So much so that at least half with OCD improve on medications that leave more serotonin available in the synapses (SSRIs) to be used by neurons. There are a lot of reasons why a brain may not be making enough serotonin. Some could be not enough cofactors like iron, vitamin D, or B6, and possibly not enough amino acid precursors (Vegans and those eating too many highly processed foods, I am talking to you). But in OCD the lack of serotonin is thought to create problems with obsessions. And when we treat some people with SSRIs their obsessions decrease in intensity and frequency. But it doesn’t work for everybody.

The clinical benefits of selective serotonin-reuptake inhibitors (SSRIs) have implicated serotonin, but a clear understanding of its role in symptom onset, aggravation, and resolution remains elusive.

Lissemore, J. I., et al. (2021). https://doi.org/10.1007/978-3-030-57231-0_13

While we don’t understand why this occurs in OCD, the consensus seems to be that low serotonergic activity alters the orbitofrontal cortex response and that people with OCD must be treated with a serotonin agonist. What if there was a way to produce a physiological reaction in favor of serotonin balance that was not a serotonin agonist in the form of medication?

When we evaluate neurotransmitter systems of dopamine in patients with OCD we tend to see problems with dopamine receptors (D2). But we do not see a significant correlation between the faulty D2 receptor function and disease severity. At least not consistently in the literature. But we do know dopamine is involved because, in a pharmacological fMRI study of reinforcement learning, the use of dopamine receptor antagonists with obsessive-compulsive disorder (OCD) saw an unexpected therapeutic benefit.

One neurotransmitter system that appears to be important for OCD is that between glutamate and GABA. Glutamate is an excitatory neurotransmitter that is important to normal brain function, but when out of balance can be neurotoxic. It is best described as a gas pedal. GABA is an inhibitory neurotransmitter and we generally think of GABA as a chill, feel-good, not overwhelmed sort of neurotransmitter when it is in balance. GABA can be thought of like the brakes. The two need to be in balance in a well-functioning brain. But we do not see these two balanced in OCD.

Imbalances between the glutamate and GABA neurotransmitter systems in certain structures of the brain are thought to create the repetitive behavioral nature of some obsessive-compulsive disorder (OCD) symptoms. Some researchers posit that glutamatergic hyperactivity (making too much glutamate) associated with over-activity of certain pathways may underlie the development of OCD. We have a ton of animal studies with mice showing this and even two human studies. Elevated levels of glutamate were found in both studies of those who were unmedicated suffering from obsessive-compulsive disorder (OCD).

There is a growing body of evidence from neuroimaging studies, which implicate glutamatergic dysfunction in OCD. However, the evidence is divided regarding the exact nature of dysfunction.

Karthik, S., Sharma, L. P., & Narayanaswamy, J. C. (2020). Investigating the role of glutamate in obsessive-compulsive disorder: current perspectives. 
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7173854/

It is not as simple that there is just simply “too much glutamate” although that could be the case in some brain structures. It is an issue of imbalance of glutamate. Because we have also seen evidence of too little glutamate in the thalamus in those with OCD. Again, the brain is a complicated system. That we are attempting to treat with single mechanisms interventions in order to attain that balance. And for a lot of people with OCD, this is not working.

Lower levels of the neurotransmitter GABA are seen to correlate with high symptom severity in those with obsessive-compulsive disorder (OCD). Lower GABA appears to exist in the rostral anterior cingulate cortex, which is thought to have a role in deficits in cognitive control we see with OCD (e.g., ruminating thoughts).

In a meta-analysis of neuroimaging studies conducted in 2021, it was found that there were reductions in D2 receptors (dopamine), GABA receptors, and cingulate 5-HT receptors (serotonin). These types of findings regarding neurotransmitter systems in OCD provide ample evidence there is dysfunction in neurotransmitter balancing. Would not an intervention that has been shown to improve neurotransmitter balancing, of several neurotransmitter systems, as opposed to just one or two, not be worthy of discussion in the treatment of obsessive-compulsive disorder (OCD)?

I would say yes. The discussion of the ketogenic diet as a way to balance neurotransmitters (and not just one of them willy nilly) is most definitely warranted.

How a ketogenic diet treats neurotranmitter imbalances in the OCD brain

Ketone bodies are signaling bodies. Meaning they turn genes on and off and help determine a lot of processes. One of those is neurotransmitter balance. For example, acetoacetate, one type of ketone body is able to inhibit glutamate release from neurons in some parts of the brain but will enhance its transmission in other parts that need and want it. Can you imagine a psychopharmacological treatment doing that? Being able to help your brain use it exactly when and where it is needed? Without somehow messing up all the ratios by trying to control how much is made, or how often it hangs out in synapses? I think not. But ketones can do that.

Ketones also exert influences that are considered indirect. As ketones break down, their byproducts are used in systems that regulate neurotransmitter synthesis. These downstream effects influence and regulate the neurotransmitters glutamate and GABA. There is less production overall of glutamate in those on a ketogenic diet, and we see more GABA. For example, children on a ketogenic diet for epilepsy have higher cerebrospinal fluid GABA levels than control groups. We also see this favorable increase in GABA when using magnetic resonance spectroscopy in human studies.

But what about glutamate? Well, we know that the decreases in neuroinflammation that happen with a ketogenic diet improve the environment in which the brain makes neurotransmitters. While we will learn more about inflammation later in this blog post, it is relevant here to note that when a brain is inflamed it can disrupt normal neurotransmitter production. And this has been seen in the production of glutamate, reaching up to 100x more production of glutamate than normal in the brain. Obviously, this has neurotoxic effects. So wouldn’t it be great if there were a way to balance this neurotransmitter system?

Ketones just happen to enhance the conversion of glutamate to GABA, which likely is a significant part of the balancing effects we see when people adopt a ketogenic diet. As for serotonin and dopamine, we see balancing effects of those neurotransmitters also with the ketogenic diet. We see an upregulation of serotonin and balancing of dopamine. We also see much-improved cell membrane function, which is going to improve how well those neurons communicate and use the neurotransmitters made. You can learn a little more about this here.

Ketogenic diets supply neuronal membrane stabilization. Ketogenic diets increase the amounts and actions of ATP and adenosine. ATP (needed for energy) and adenosine are critical for metabolic stability. Adenosine, in particular, is well known to be neuroprotective and promote homeostasis (balance), stabilizing cellular membrane potential, which you need in order to make the right amount of neurotransmitters, allow them to stay the right amount of time, and allow them to be broken down when they are supposed to. There is no successful balancing of neurotransmitters without healthy cell membrane function.

I could go on about how we do not have psychotropic medications for OCD, or other disorders, that provide this for people in a balanced way. But I won’t because that would be slightly off-topic and is better for a future blog post.

My very important point that is relevant to the reader of this blog, is that a ketogenic diet improves neuronal membrane function and allows your receptors to work better. It also helps you store cofactors, improves membrane potential, and a host of other positive brain benefits that I just have not seen advertised as being possible with psychopharmacology.

OCD and neuroinflammation

Inflammation is a process in which you are hurt or under attack in some way, and your body tries to make it right. It also does this in the brain. In the brain, neuroinflammation can occur because of things crossing a leaky blood-brain barrier, neuronal bodies not having adequate energy dynamics to maintain themselves, or microglial attempting to come to your rescue as a form of immune system activation. Chronic inflammation and neuroinflammation, in particular, are seen in psychiatric diagnoses including depression and anxiety, and neurological issues as in dementia. So it should be no surprise for us to learn that OCD has a significant inflammatory component.

OCD is associated with low-grade inflammation, neural antibodies, and neuro-inflammatory and auto-immune disorders

Gerentes, M., Pelissolo, A., Rajagopal, K., Tamouza, R., & Hamdani, N. (2019). Obsessive-compulsive disorder: autoimmunity and neuroinflammation. https://doi.org/10.1007/s11920-019-1062-8

Although many of the studies finding higher inflammation in those with obsessive-compulsive disorder (OCD) are considered associational (there is a relationship with one being with the other more often), there is enough evidence to suggest that there is a role in the pathogenesis (how the disease begins) of OCD. There is enough evidence of inflammation having a causative role that there is discussion in the literature suggesting anti-inflammatory drugs be developed and repurposing of immunomodulatory therapies to treat OCD.

And that is good enough for me. If inflammation is a component of OCD then we need to treat it. So let me tell you about the highly anti-inflammatory effects of the ketogenic diet.

How a ketogenic diet treats inflammation in people with OCD

Ketogenic diets reduce neuroinflammation in a variety of ways

  • reduces oxidative damage (we will learn more about this soon)
  • improved neural energy metabolism (remember hypometabolism above?)
  • epigenetic effects as signaling bodies that modulate or turn off inflammatory pathways (turn genes on and off!)
  • positive effects on gut microbiome that reduces inflammation

Ketogenic diets reduce inflammation in all of those ways. Ketones, which are produced in the body during a ketogenic diet, are what we call signaling molecules. And a signaling molecule can turn some genes off and some genes on, and in the case of inflammation, this action is quite favorable towards LESS inflammation. A ketogenic diet provides the conditions in which this favorable signaling can occur. But it is also a dietary strategy that reduces or eliminates problems with hyperglycemia.

You can have episodes of hyperglycemia even if you are not diabetic. And when you have hyperglycemia it affects immune cells in a way that causes more inflammation. You do not make ketones if you are eating a lot of carbohydrates that are causing hyperglycemia, because hyperglycemia means you have spiked insulin quite high, and ketones are not made in those conditions.

So eating a ketogenic diet in order to treat your OCD will take away the inflammation that would occur when eating a standard American diet higher in carbohydrates and processed foods. It would also reduce inflammation using the ketones you generate and the improved micronutrient availability in your food choices by eating a well-formulated ketogenic diet.

Because we are discussing how one thing influences the other, it is a good time to include the below quote. It does such a good job illustrating how a single approach to mental health that is not systemic in nature is just never going to be sufficient for wellness.

Recent studies display that inflammation processes and the dysfunction of the immune system are likely to play a role in the pathophysiology of OCD, indicating that the disturbances in neurotransmitters such as serotonin and dopamine cannot be alone involved in the development of OCD.

Ghasemi, H., Nomani, H., Sahebkar, A., & Mohammadpour, A. H. (2020). https://doi.org/10.2174/1570180817999200520122910

Obsessive-compulsive disorder (OCD) treatment using a ketogenic diet also improves the functioning of the immune system. As we see in the above quote, the inflammatory process is driven in part by immune system dysfunction. Research has suggested quite strongly that immune system function improves significantly on a ketogenic diet. The effects of the ketogenic diet on immune function are so positive that in a recent article it was proposed for use in COVID-19 as a preventative treatment. It is quite likely that improvements in immune system functioning could be instrumental in reducing the inflammation that exists in the brains of those who suffer from obsessive-compulsive disorder (OCD). Someone with OCD may wish to use the ketogenic diet for this purpose in place of medication.

OCD and Oxidative Stress

Oxidative stress occurs when the brain’s ability to upkeep itself or fend off assaults is no longer sufficient. This can happen from inadequate micronutrient stores, immune system responses, or toxins that make it through a leaky blood-brain barrier. Countless reasons really. Just being alive creates oxidative stress. There is an excellent diagram showing different factors related to oxidative stress here (seriously it is really good, check it out).

But a healthy brain and body are able to fight off these assaults using our own antioxidant production. But in people with obsessive-compulsive disorder, this is clearly not happening to a sufficient degree.

Recent studies have shown more activity of free radical metabolism and the weakness of antioxidant defense system in OCD.

Baratzadeh, F., Elyasi, S., Mohammadpour, A. H., Salari, S., & Sahebkar, A. (2021). The Role of Antioxidants in the Management of Obsessive-Compulsive Disorder. https://doi.org/10.1155/2021/6661514

Oxidative stress has such a strong role in OCD, that discussion is made of the use of antioxidant therapies in its treatment. But what a lot of people do not consider is the role of ketones in helping people be able to use their own antioxidant systems in the body. So let’s discuss that next.

How does a ketogenic diet treat oxidative stress in those with OCD?

Ok, let’s take a look at the figure I recommended you look at prior. It is just too good to not use in our explanation.

Baratzadeh, F., Elyasi, S., Mohammadpour, A. H., Salari, S., & Sahebkar, A. (2021). https://www.hindawi.com/journals/omcl/2021/6661514/

We already know from our studies that ketogenic diets upregulate mitochondria and mitochondrial function. So we know a ketogenic diet would inhibit the mitochondrial dysfunction we see in this figure that is a factor in causing oxidative stress.

We have also learned how a ketogenic diet improves neuronal membrane function. We see in this figure how impaired neuronal membrane functioning contributes to oxidative stress. So a ketogenic diet could very much keep this factor contributing to oxidative stress from happening in the first place.

We have discussed how ketones are signaling bodies, that are able to turn down inflammation by having a highly beneficial effect on inflammation pathways. This is not an assumption on my part. It is in the literature and provided to some degree in the reference list below. Ketogenic diets are powerful interventions for inflammation. And if we can keep inflammation down, we keep the oxidative stress down we see in OCD brains.

These are all very exciting aspects and show that ketogenic diets are a very powerful, multi-functioning holistic intervention. But the part of the figure that I like to focus on when teaching people about oxidative stress and its influence on psychiatric disorders pertains to this box here:

https://www.hindawi.com/journals/omcl/2021/6661514/fig2/ (I modified this figure with red circle)

I am a firm believer in the power of endogenous (your body makes it, you don’t eat it or swallow it as a supplement) antioxidants. And the most powerful one you make, under the right conditions, is glutathione. Glutathione is a very powerful antioxidant and ketones play a role in your body’s ability to make it and use it well.

Ketones have neuroprotective qualities that interfere with the formation of reactive oxidant species that create oxidative stress and they are also instrumental in tipping the balance of energy metabolism in such a way that it favors the destruction of oxidative products through the use of glutathione.

A well-formulated ketogenic diet also is nutrient-dense and will allow you to both increase and store (due to improved membrane function) those micronutrients that are needed to make glutathione in the first place.

Do you get it?

You don’t have to eat rainbow-colored vegetables and fruits or take a lot of vitamin C or E. You can have a nutrient-rich diet that provides the building blocks to create the most powerful antioxidant we know of, in your own body, and then use ketones to unlock their power.

And this can help you combat and/or completely eliminate the oxidative stress that is currently exacerbating your symptoms of obsessive-compulsive disorder.

What other ways do ketogenic diets help OCD?

Ketogenic diets do so many great things to a brain in distress, and to the OCD brain in particular. But there is another factor that really deserves mention.

Ketones upregulate brain-derived neurotrophic factor (BDNF). Why would this be important to a person suffering from OCD? Well, there are a lot of reasons. But first, let’s start by saying that part of the therapeutic effect that some people see from using SSRIs for OCD is that these drugs somewhat increase BDNF. We use them for traumatic brain injuries for this reason. Will they upregulate it as much as a ketogenic diet? I don’t think so but I have no data to support or refute that assumption. I mention it here because I want you to understand that BDNF is instrumental in your recovery from obsessive-compulsive disorder (OCD).

BDNF is what will help you rewire those brain structures together in new and healthy ways. BDNF is what is going to help you get the most out of that exposure-response prevention (ERP) work you are doing with your therapist. Need to learn new ways of thinking and being while doing cognitive-behavior therapy for your OCD? BDNF is needed. And ketones are excellent at increasing the amount of BDNF in your brain, which can only help and is yet another way that ketogenic diets can be a complement to psychotherapy work. So while BDNF is not one of the four factors I normally write about when discussing ketogenic diets as a treatment for mental illness, it deserves a strong and honorable mention.

Conclusion

It is my sincere hope that you are beginning to see how all the components of action in a ketogenic diet work together. That you have acquired an understanding that improved neuroinflammation reduces oxidative stress. That less oxidative stress improves the environment in which the brain is making and balancing transmitters and improves important membrane functions. That you now understand that reduced neuroinflammation and oxidative stress mean there are fewer nutrients being depleted, and more available precursors available to do important things, like making enzymes and neurotransmitters. I hope it is clear that the improved energy neurons get on a ketogenic diet allows them to function better overall. And that the improved energy of these cells along with an upregulation of BDNF allows those same neurons to do the basic housekeeping they need to stay in good repair and make new learning connections.

Again, there are no randomized clinical trials yet using a ketogenic diet specifically to treat obsessive-compulsive disorder (OCD). We can only extrapolate possible benefits to this population, based upon the results seen in other neuropsychiatric and neurological disorders. We can be open to the idea that an intervention seen to reduce oxidative stress in one or many different populations, both in animal models and with humans, may very well successfully do so in OCD. We should at least discuss the possibility, and more importantly, inform you of that possibility. So you can make the very best treatment decisions that make sense for you!

I want to encourage you to learn more about your treatment options from any of the following blog posts. I write about different mechanisms in varying degrees of detail that you may find helpful to learn on your wellness journey. You may enjoy the Ketogenic Case Studies page to learn how others have used the ketogenic diet to treat mental illness in my practice. And you may benefit from understanding how working with a mental health counselor while transitioning to a ketogenic diet can be helpful here.

Share this blog post or others with friends and family suffering from mental illness. Let people know there is hope.

You can learn more about me here. If you would like to contact me you may do so here. If you just have a simple question please do not hesitate to reach out. Or let me know in a comment if you have found this blog post to be helpful on your wellness journey.

I truly believe you have the right to know all of the ways you can feel better.

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References

Ahmari, S. E., & Rauch, S. L. (2022). The prefrontal cortex and OCD. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 47(1), 211–224. https://doi.org/10.1038/s41386-021-01130-2

Asl, M. A., Asgari, P., & Bakhti, Z. (2021). Treatment Approaches Based on Neuroscientific Data in Patients With Obsessive-Compulsive Disorder. International Clinical Neuroscience Journal, 8(3), 107–117.

Attwells, S., Setiawan, E., Wilson, A. A., Rusjan, P. M., Mizrahi, R., Miler, L., Xu, C., Richter, M. A., Kahn, A., Kish, S. J., Houle, S., Ravindran, L., & Meyer, J. H. (2017). Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder. JAMA Psychiatry, 74(8), 833. https://doi.org/10.1001/jamapsychiatry.2017.1567

Bannon, S., Gonsalvez, C. J., Croft, R. J., & Boyce, P. M. (2006). Executive functions in obsessive-compulsive disorder: State or trait deficits? The Australian and New Zealand Journal of Psychiatry, 40(11–12), 1031–1038. https://doi.org/10.1080/j.1440-1614.2006.01928.x

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Panic Disorder (PD)

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How could a ketogenic diet help treat the symptoms of Panic Disorder (PD)?

Ketogenic diets modify at least four of the pathologies we see in panic disorder (PD) and panic attacks. These pathologies include glucose hypometabolism, neurotransmitter imbalances, inflammation, and oxidative stress. A ketogenic diet is a powerful dietary therapy that will directly impact these four underlying mechanisms seen in panic disorder (PD) symptomatology.

Introduction

In this blog post, I am not going to outline the symptoms or prevalence rates of panic disorder. This post is not designed to be diagnostic or educational in that way. If you have found this blog post, you know what panic disorder is, and likely you or someone you love may already be suffering from it.

If you have found this blog post, you are looking for panic disorder treatment options. You are trying to find ways to feel better and heal.

By the end of this blog post, you will be able to understand some of the underlying mechanisms going wrong in the brains of people suffering from panic disorder and how a ketogenic diet can therapeutically treat each of them.

You will come away seeing a ketogenic diet as a possible panic disorder treatment for your symptoms or as a complementary modality to use with psychotherapy and/or medication.

It is not medical heresy to write the above statement. Why would we not consider using a ketogenic diet in place of psychopharmacology for panic disorder? Medications used for panic disorder include selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Early panic disorder treatment may include benzodiazapenes. After 4 to 6 weeks you could be put on any combination of medications with a stunning array of potential side effects.

The American Psychiatric Association Publishing Textbook of Anxiety, Trauma, and OCD-Related Disorders. (2020). United States: American Psychiatric Association Publishing. p. 391

In many cases, a significant proportion of those suffering from PD shows little or no response to standard pharmacotherapies, CBT and/or their combination. Many people continue to suffer from residual symptoms that significantly impair functioning.

The remission rates achieved with pharmacotherapy range between 20% and 50%, and approximately 20% of patients will remain substantially impaired despite undergoing a succession of pharmacological and/or psychosocial treatments.

Masdrakis, V. G., & Baldwin, D. S. (2021)

So why would we not consider alternative ways to treat panic disorder? When the rates of panic disorder treatment success using psychotropic medications with or without Cognitive-Behavioral Therapy (CBT) are so poor? CBT works to also change brain chemistry, all by itself. CBT is definitely an evidence-based treatment for panic disorder (PD). But why would we not consider alternative ways to change our brain chemistry and fix underlying pathological factors, with or without the benefit of psychotherapy?

We are told the only viable, science-based options are the standard of care. If there are no specific Randomized Controlled Trials (RCTs) yet looking at ketogenic diets and panic disorder (PD) in this specific combination, we are told it is not really a treatment option. That somehow, everything we know about how ketogenic diets work, the underlying mechanisms already identified, and the symptom profiles we have identified in panic disorder are completely unrelated logically in the absence of an RCT. And we are to wait for funding of such RCTs to occur in an environment that primarily funds research when there is psychopharm profit to be made.

What if there are people whose panic disorder symptoms are better on medication, but the medication side effects have their own significant burdens? Must they stay with the standard of care? What about those 20% of people who suffer from the terrible symptoms of panic disorder and have not been helped with medications and/or psychotherapy combinations. Shall we tell them they should just “hang in there” until Big Pharma catches up with an RCT they will not be financially motivated to make happen?

I think not.

What are the neurobiological changes seen in Panic Disorder (PD)? Where are possible pathways of intervention?

A previous post went into detail about how a ketogenic diet can modify symptoms of anxiety by affecting four areas of pathology seen in these disorders.

  • Glucose Hypometabolism
  • Neurotransmitter Imbalances
  • Inflammation
  • Oxidative stress

In panic disorder (PD) we see not only some hypometabolism between brain hemispheres but also hyperexcitability suggestive of significant neurotransmitter imbalances. The research also informs us that the panic disordered brain suffers from inflammation and oxidative stress. Let’s review each of these.

Hypometabolism in Panic Disorder (PD)

Actually, yes. We do see hypometabolism occurring in certain brain structures in people with panic disorder (PD).

Abnormal left/right (L/R) hemispheric ratios of regional cerebral glucose metabolic rates (rCMRglc) (hippocampus and inferior prefrontal cortex) have been noted in unmedicated panic disorder patients.

Nordahl, Thomas E., et al. (1998) https://doi.org/10.1016/S0006-3223(98)00026-2

Pay attention to that part about WHERE we see the hypometabolism in panic disordered brains. The hippocampus and the prefrontal cortex.

How does a ketogenic diet treat hypometabolism in panic disorder?

Neurons, oligodendrocytes, and even astrocytes have the ability to take in ketones as a fuel source. This is very important for brains that for whatever reason, are not using glucose well as fuel anymore or are just not able to meet energy demands. When a brain is using ketones as a primary fuel (and yes, there are some parts of the brain that need glucose provided by the liver, but not dietary glucose) it makes that brain more energy efficient. There are fewer steps and less energy needed to utilize ketones for energy than glucose. This helps a hypometabolic brain, one that is not using fuel well, be able to upregulate brain energy.

In humans, both acute and chronic increases in ketone body availability to the central nervous system cause massive changes in cerebral fuel metabolism.

Jensen, N. J., Wodschow, H. Z., Nilsson, M., & Rungby, J. (2020). https://doi.org/10.3390/ijms21228767

It is interesting to note, and now fairly well-known, that seizure disorders have been treated using the ketogenic diet for decades. The symptoms of panic disorder are so similar to those seen in some seizure disorders that differentiating between the two is of diagnostic importance in the field of neurology. For example, both temporal lobe seizures and panic disorder share the following symptoms:

  • paresthesias
  • derealization
  • dizziness
  • chest pain
  • tremor
  • palpitations 

If a ketogenic diet can be used to treat the symptoms of seizure disorders, why would it not be beneficial in panic disorder, which shares many of the same symptoms? Why wouldn’t we consider it?

Remember the parts of the brain found to have hypometabolism in panic disorder? The hippocampus and the prefrontal cortex.

© ISTOCK.COM, JAMBOJAM

Ketogenic diets enhance something called mitochondrial biogenesis. Mitochondrial biogenesis means that cells make more of their own batteries and create more energy. Ketones also elevate ratios of substances (phosphocreatine/creatine) that improve hippocampal metabolism.

Ketogenic diets improve symptoms of Alzheimer’s and other neurodegenerative diseases. Neurodegenerative diseases have many areas of the brain that suffer from hypometabolism. One of those very important areas is the prefrontal cortex. If ketogenic diets are used to improve hypometabolism in brain structures such as the prefrontal cortex in neurodegenerative diseases, why are we not using it for panic disorder, which also shows hypometabolism in the prefrontal cortex?

I would argue we absolutely can. And I have seen clients in my practice who have improved significantly using the ketogenic diet for panic disorder treatment, and even more so with the addition of Cognitive-Behavioral Therapy (CBT) in conjunction with ketogenic dietary therapy.

Panic Disorder and Neurotransmitter Imbalances

We actually see over-activation in the right amygdala, left and right insula left inferior frontal operculum, and left inferior frontal gyrus when we attempt to use behavioral extinction (the B in CBT stands for Behavioral) on various anxiety-provoking stimuli compared to healthy controls.

There is strong evidence for the importance of serotonin in the neurobiology of panic disorder (PD). In panic disorder, we see issues with serotonin binding to receptors and studies generally confirm that serotonin is inhibitory of symptoms in panic disorder. There are “functional and clinically relevant alterations in various elements” of the serotonin system that affects the neurocircuitry of panic (Maron, E., Shlik, J., 2006). There are also theories that the functioning of norepinephrine, dopamine and gamma-aminobutyric acid (GABA) neurotransmitter systems play a role in panic disorder symptoms.

In addition to serotonin imbalances, we also see problems in the use of norepinephrine in panic disorder (PD). There is a hypersensitivity in the presynaptic activity of norepinephrine in those with panic disorder (PD) and this is that is believed to be a factor in the expression of PD symptoms. Dopamine plays a role our experience of unconditioned fear responses. While there is not a large literature specific to panic disorder and dopamine neurotransmitter imbalances, we definitely see them in the expression of other anxiety disorders. Both dopamine D1 and D2 receptor mechanisms are important in mediating anxiety and we see a wide distribution of dopaminergic innervation over structures responsible for fear-related circuitry in the brain. Dopamine balance has an important role to play in panic disorder treatment.

How does the ketogenic diet help treat neurotransmitter imbalances in panic disorder (PD)?

We see hyper-excitability! The neurotransmitter balancing effects of a ketogenic diet are all the more important for the panic disordered brain. Reviews of the literature looking at neurotransmitter balancing in animal studies have shown improvements between glutamate (excitatory) and GABA (inhibitory) balances.

Neurotransmitter function was frequently reported in the included studies as a change within the nervous system favouring a reduction or restoration of normal levels of neuronal excitability. 

Field, R., Field, T., Pourkazemi, F., & Rooney, K. (2021). doi:10.1017/S0954422421000214

Glutamate has been shown to play a fundamental role in the onset of anxiety-related disorders. While increases in the availability and function of GABA have been shown to decrease panic. For example, your psychiatrist may prescribe you a GABA reuptake inhibitor, hoping to allow the GABA you are making to hang out longer between cells. This increased availability of GABA for longer will be used to hopefully keep your brain from reaching a state of panic (panic attack).

This is well-intentioned but short-sighted. A GABA reuptake inhibitor will not help fix the other ways your brain is not functioning the way a ketogenic diet can. A GABA reuptake inhibitor will not influence brain structure hypometabolism, overall neurotransmitter balance, oxidative stress, and neuronal inflammation. But a ketogenic diet does.

When we look at the effects of the ketogenic diet on dopamine balance and function we see beneficial effects. We know that dopamine plays a role in learned and unlearned fear responses, which are relevant to the symptoms that people with panic disorder endure. A ketogenic diet is shown to influence dopamine receptor activity through its ability to influence the expression of an inhibitory neurotransmitter called adenosine. Issues with dopamine receptors (D1 and D2) are seen in panic disorder (PD) specifically. But luckily, the ketogenic diet exerts what appears to be a beneficial influence on the dopaminergic systems involved in anxiety.

How does improved cell membrane function contribute to improved neurotransmitter balance with the ketogenic diet?

Ketogenic diets improve cell membrane function. As we learned here in a previous post, improved cell membrane function leads to improved sensitivity to neurotransmitters.

It leads to decreased hyperexcitability and improved enzyme reactions. Enzymatic reactions are needed to make neurotransmitters, keep neurotransmitters around the right amount of time, and degrade them appropriately.

Improvements in neuronal cell membranes mean improved neurotransmitter binding to receptors. This matters to people with panic disorder because people with panic disorder (PD) show poor binding of serotonin to receptors. This means their brain cannot use serotonin as effectively as they would if their neuronal membrane health was working properly.

But wait, you say. When I look at the literature you pulled in your reference list, I see that there are genetic predispositions to panic disorder. That some of these issues with serotonin binding are because of my genes!

I need you to understand that ketone bodies turn genes on and off.

Ketones are known signaling bodies able to turn genes on and off, influencing the expression of genes all up and down their pathways of expression. . That’s right. I am not exaggerating in the least. Your genes are not your wellness destiny. There is something called epigenetics, meaning internal and external factors can turn genes on and off. Ketogenic diets have been shown to modulate genes for neurotransmitter production and function and synaptic transmission in a very beneficial way.

Ketogenic diets are also seen to upregulate serotonin and balance levels of other neurotransmitters like GABA, glutamate, norepinephrine, and dopamine. And not in a way that can make too much of any given one of these, and then give you weird side effects. Ketogenic diets help your brain make just the right amount of neurotransmitters and allow your brain to use them well.

There are no side effects when a ketogenic diet balances your neurotransmitters and improves your neuronal functioning. Medications often come with side effects that are bothersome or challenge long-term health and then lose efficacy over time. For this reason alone, ketogenic diets should be considered a favored or even preferred treatment for panic disorder and other psychiatric and neurological conditions.

Panic Disorder and Oxidative Stress

Oxidative stress is the impairment of cell membrane functions due to insufficient antioxidant capabilities to deal with free radical damage. Those with panic disorder have been found to have higher oxidative stress levels than normal controls, with the highest levels of oxidative stress seen in those who have panic disorder with agoraphobia. Disease severity in panic disorder is positively correlated with serum levels of markers showing higher oxidative stress.

We do not know the extent to which oxidative stress contributes to specific clinical symptomatology of psychiatric disorders, let alone specifically panic disorder. The causal role of oxidative stress in anxiety disorders is still being figured out. Finding out the causal role will be important for early treatment and target for preventative intervention.

But if you have panic disorder we know you have higher markers of oxidative stress. And even higher markers of oxidative stress if you suffer from panic disorder with agoraphobia. Is it too late to target oxidative stress for intervention? Absolutely not.

Ketogenic diets and oxidative stress

Remember how in prior sections of this blog we discussed how ketone bodies were signaling molecules? That ketones are able to turn some genes off and some genes off in a variety of cellular functions? Well, that is a big part of how ketogenic diets help reduce oxidative stress. One ketone body, in particular, β-hydroxybutyrate (BHB) upregulates antioxidant defenses to combat inflammation and free radicals.

β-hydroxybutyrate functions as a stress response molecule and orchestrates an antioxidant defense program to maintain redox homeostasis in response to environmental and metabolic challenges

Rojas-Morales, P., Pedraza-Chaverri, J., & Tapia, E. (2020). https://doi.org/10.1016/j.redox.2019.101395

So what can the ketone body BHB do for the oxidative stress of panic disorder? Perhaps a better question is what can’t these little ketone bodies do when it comes to upregulating our antioxidant capabilities.

BHB works to protect your brain against oxidative stress through direct and indirect mechanisms such as:

  • being an antioxidant for hydroxyl radicals
  • suppresses mitochondrial reactive oxygen species (ROS)
  • activates SEVERAL antioxidant programs through different gene expressions

For those that want to nerd out on these direct and indirect mechanisms, there is a great article here.

Inflammation and Panic Disorder

Chronic inflammatory markers are seen in those with panic disorder. Chronic inflammation is like a slow burning fire, pumping out various inflammatory substances that do cellular damage and affect cell function. These substances are often referred to as inflammatory cytokines. Inflammatory cytokines are found to be so consistent in those with panic disorder, that there are suggestion that they be investigated as a potential causal factor.

Systemic inflammation can access the brain, and enhance pro-inflammatory cytokine levels that have been shown to precipitate direct and indirect neurotoxic effects.

Won, E., & Kim, Y. K. (2020). https://doi.org/10.3390/ijms21186546

Untreated chronic inflammation ages the brain and causes negative changes in brain structure, function, and connectivity of prefrontal and limbic structures. Prescriptions of SSRI’s have some mild anti-inflammatory properties, but in severe panic disorder where we see higher levels of inflammation, a case could be made that the effects are insufficient.

Ketogenic diets for Inflammation

Ketogenic diets as a treatment for panic disorder could be beneficial because ketones offer anti-inflammatory and neuroprotective properties. It is almost as if our bodies planned for ketones to come to the rescue. Our neuroinflammatory cells already come with receptors (HCA2) to take in the completely endogenous (your body makes it) neuroprotective ketone body β-hydroxybutyrate (BHB)!

Ketone bodies act as signaling molecules that inhibit inflammation pathways, turning genes on and off along the way to accomplish this aim.

Ketogenic diets also help treat inflammation by improving metabolic health. The elimination of refined carbohydrates and reduction in carbohydrate intake overall leads to less metabolic stress on the body by treating hyperglycemia (high blood sugar) and hyperinsulinemia (insulin chronically high and causing cells to not burn glucose properly). Metabolic disorders can occur in people who do not yet have a Type II Diabetes diagnosis from their doctor. You can be thin and have a metabolic disorder. Ketogenic diets keep you metabolically healthy, which reduces your risk of increased oxidative stress.

Conclusion

The ketogenic diet is an effective intervention to treat glucose hypometabolism, neurotransmitter imbalances, oxidative stress, and neuroinflammation. These are all pathological states we see present in panic disorder (PD). People suffering from panic disorder should be given the option of a ketogenic diet as a primary or complementary treatment protocol that can include medication and/or psychotherapy as the client so chooses.

While the standard of care should always be offered to you, as someone who suffers from panic disorder, it is important for you to know other options that are also evidence-based. So you can make informed decisions regarding their care.

You have a right to know all the different ways you can feel better.

The ketogenic diet is one of them. And it is important to me that someone communicates that to you so you can make informed decisions about your treatment.

I want to encourage you to learn more about your treatment options from any of the following blog posts. I write about different mechanisms in varying degrees of detail that you may find helpful to learn on your wellness journey. You may enjoy the Ketogenic Case Studies page to learn how others have used the ketogenic diet to treat mental illness in my practice. And you may benefit from understanding how working with a mental health counselor while transitioning to a ketogenic diet can be helpful here.

Share this blog post or others with friends and family suffering from mental illness. Let people know there is hope.

You can learn more about me here. If you would like to contact me you may do so here. If you just have a simple question please do not hesitate to reach out. I am excited at the potential of you feeling well!

Like what you are reading on the blog? Want to learn about upcoming webinars, courses, and even offers around support and working with me towards your wellness goals? Sign up!


References

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Post-Traumatic Stress Disorder(PTSD)

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How could a ketogenic diet help treat the symptoms of Post-Traumatic Stress Disorder (PTSD)?

Ketogenic diets are able to modify at least four of the pathologies we see in PTSD brains. These pathologies include glucose hypometabolism, neurotransmitter imbalances, inflammation, and oxidative stress. A ketogenic diet is a powerful dietary therapy that has been shown to directly impact these four underlying mechanisms that have been identified to be involved with PTSD symptoms.

Introduction

In this blog post, I am not going to outline the symptoms or prevalence rates of PTSD. This post is not designed to be diagnostic or educational in that way. If you have found this blog post, you know what PTSD is and likely you or someone you love may already be suffering from it.

If you have found this blog post, you are looking for treatment options. You are trying to find ways to feel better and heal.

By the end of this blog post, you will be able to understand some of the underlying mechanisms going wrong in the brains of people suffering from PTSD and how a ketogenic diet can therapeutically treat each of them.

You will come away seeing a ketogenic diet as a possible treatment for your PTSD symptoms or as a complementary modality to use with psychotherapy and/or in place of medications.

It is not medical heresy to write the above statement. Why would we not consider using a ketogenic diet in place of psychopharmacology for PTSD? Psychopharmacology treatment for PTSD has been acknowledged as ineffective and sorely lacking since 2017, by a well-known Consensus Statement of the PTSD Psychopharmacology Working Group. Psychopharmacology as a treatment for PTSD has essentially been a failure.

Despite this high prevalence and costly impact, there seems to be no visible horizon for advancements in medications that treat symptoms or enhance outcomes in persons with a diagnosis of PTSD.

What are the neurobiological changes seen in PTSD? Where are possible pathways of intervention?

A previous post went into detail about how a ketogenic diet can modify symptoms of anxiety by affecting four areas of pathology seen in these disorders.

  • Glucose Hypometabolism
  • Neurotransmitter Imbalances
  • Inflammation
  • Oxidative stress.

In PTSD we see these very same pathologies occurring. There are areas of the brain with hypometabolism (not using energy properly) and we see overexcitability in others. There are distinct neurotransmitter imbalances affecting mood and cognition and extreme oxidative stress and inflammation documented as occurring in the PTSD brain. Let’s review each of these.

PTSD and Hypometabolism

Brain hypometabolism means that the brain is not using energy correctly. Areas of the brain that should be active and using energy are not. Brain hypometabolism is indicative of a metabolic disorder in the brain.

Brain imaging studies consistently find areas of reduced energy consumption in the brains of people suffering from PTSD. These areas can include the occipital, temporal, caudate nucleus, posterior cingulate cortex, parietal and frontal lobes. It is theorized that hypometabolism contributes to the dissociative states reported in PTSD symptomology.

“…only patients with PTSD showed hypoactivation in the dorsal and rostral anterior cingulate cortices and the ventromedial prefrontal cortex—structures linked to the experience and regulation of emotion.”

Etkin, A., & Wager, T. D. (2007). https://doi.org/10.1176/appi.ajp.2007.07030504

How does a ketogenic diet treat hypometabolism in the PTSD brain?

Ketogenic diets are specifically a therapy for brain hypometabolism. So much so that it is used for other neurological disorders such as Alzheimer’s Disease and Traumatic Brain Injury (TBI) for just this exact purpose. Ketogenic diets produce ketones which can be used as an alternative fuel for the brain. Ketones can bypass broken metabolic machinery normally used to utilize glucose for fuel. Brains love ketones. And a ketogenic diet may improve energy expenditure in these important brain structures being affected by PTSD pathology. A brain with fuel will always have improved functioning than one without. And that is why a ketogenic diet may be an excellent therapy for this mechanism of pathology present in the PTSD brain.

PTSD and Neurotransmitter Imbalances

While hypometabolism occurs in some parts of the brain with PTSD, we also see some areas of hyperarousal and excitability. This hyperarousal and excitability are likely occurring due to the types of neurotransmitter imbalances we see in people suffering from PTSD.

PTSD patients have been found to have increased levels of dopamine and norepinephrine which are thought to be responsible for symptoms seen such as higher resting pulse rates, blood pressure readings, and startle response. Decreased levels of serotonin affect communication pathways between the amygdala and hippocampus, reducing the ability of the PTSD brain to modulate anxiety. These decreased levels of serotonin are thought to contribute to the increased hypervigilance, impulsivity, and intrusive memories experienced as symptoms.

Additionally, several studies have found decreased levels of the neurotransmitter GABA. GABA is a neurotransmitter that is crucial in helping a person deal with stress and anxiety. But not only is there a decrease in GABA but there is a large increase in the excitatory neurotransmitter glutamate and norepinephrine. These neurotransmitter imbalances are thought to help explain symptoms of increased startle responses and even disassociation.

How does a ketogenic diet treat neurotransmitter imbalances in the PTSD brain?

Ketogenic diets improve neurotransmitter imbalances by improving the metabolic environment of the brain as it is making neurotransmitters. The neurotransmitter balancing effects of a ketogenic diet are well known. Perhaps the best example of this is its assistance in the making of more GABA and its ability to reduce neurotoxic levels of glutamate. This same pathway that is beneficially influenced by the ketogenic diet can increase levels of serotonin and reduce an overabundance of dopamine. Each of these changes is relevant to the treatment of PTSD symptomatology. A well-formulated ketogenic diet is also nutrient-dense, providing multiple important cofactors to not just produce neurotransmitters but improve their ability to function in the brain. Ketones do this with improved cell membrane function, which improves communication between neurons. So not only do you get balanced levels of neurotransmitters, you get better functioning neurons ready to use them well.

PTSD and Oxidative Stress

Oxidative stress is a significant area of pathophysiology in the PTSD brain. There are decreased levels of important enzymes that help internal antioxidants, like glutathione, do the job of reducing oxidative stress. Oxidative stress that is chronic in nature, as we see with PTSD, has real neurobiological consequences that include accelerated cellular aging and the progression of neurological illnesses seen in aging brains. The powerhouses of our cells, known as mitochondria, cannot function in a brain that cannot manage its level of oxidative stress. The very machinery and function of the cells are impaired and under great duress.

Currently, the role of oxidative stress and associated neuroinflammation in … PTSD is well established. Increased production of free radicals and/or reduced antioxidant defenses under challenged conditions result in excessive levels of free radicals in the brain, leading to mitochondrial dysregulation, microglia activation, and neuronal death. These mechanisms are suggested to play a key role in helplessness, anxiety, and inappropriate retention of aversive memories.

https://doi.org/10.3389/fnut.2021.661455

How does a ketogenic diet treat oxidative stress in the PTSD brain?

The ketogenic diet treats oxidative stress in at least three ways.

The first is by reducing inflammation in the brain by interfering with pathways that produce a lot of inflammation (see the section on inflammation in this blog post below).

Ketogenic diets improve brain energy by providing an alternative fuel for brain cells that improves mitochondrial functioning (how much energy your brain has to burn) and this improved functioning allows the neurons to do a better job of fighting inflammation and maintaining neuronal health.

And finally, ketogenic diets upregulate (helps your body make more of) the most powerful antioxidant known as glutathione. You can take glutathione and precursors to glutathione as supplements, but you will never absorb and utilize the levels that your internal machinery can provide with the right dietary and nutritional environment. Which is what a well formulated ketogenic diet is and provides.

PTSD and Inflammation

In a recent (2020) meta-analysis, they reviewed 50 original articles examining inflammation in the PTSD brain. They found elevated levels of serum proinflammatory cytokines (inflammation) in individuals suffering from PTSD. Type of trauma did not matter. All had this pathological level of inflammation occurring and the level was much higher than those not suffering from PTSD. They also found through neuroimaging that this increased inflammation was associated with changes in brain structures and how those structures functioned. These changes were in brain regions responsible for our ability to regulate stress and emotion.

Inflammatory cytokines disrupt brain function in all kinds of ways, but one of those ways is our neurotransmitter balance. They trigger the activation of an enzyme that degrades serotonin and the amino acid precursor tryptophan. These types of complicated mechanisms are involved between inflammation and the neurotransmitter imbalances seen in depression/anxiety disorders.

Finding ways to reduce this level of inflammation in the brain is already being conceptualized as a target of intervention, through the use of antioxidants and psychopharmacology. Albeit unsuccessfully.

How does a ketogenic diet treat inflammation in the brain?

The ketogenic diet is amazing at reducing inflammation. While the exact mechanisms are not yet known, the data coming in consistently show that for a variety of populations the ketogenic diet significantly and dramatically reduces inflammation. We do know that ketones act as signaling bodies that inhibit the expression of inflammatory gene expression. Ketogenic diets are so anti-inflammatory that they are often used for chronic pain syndromes. One mechanism in which ketogenic dietary therapy provides symptoms relief is thought to be ketones’ ability to block the activation of inflammatory pathways as a signaling molecule, turning some genes on and other genes off.

Ketones also help us make more of a very powerful internal antioxidant. That’s right. You don’t ingest this antioxidant. You make it on your own, under the right conditions, in your own amazing body. It is called glutathione. This increase in glutathione provided by ketones may be a very important modulator of inflammation in the PTSD brain, improving the other pathological factors involved such as hypometabolism, oxidative stress, and neurotransmitter imbalances.

Conclusion

Ketogenic diets are shown to modulate disease at least four of the pathological mechanisms observed in Post Traumatic Stress Disorder (PTSD) symptomatology. Using the ketogenic diet as a primary or complementary treatment with psychotherapy is one based on the mechanisms seen in the scientific literature regarding this disease. The use of this dietary therapy is one based on the science of neurobiology and pathophysiology.

RCTs using the ketogenic diet for PTSD would be nice, and I really hope we get them. I think we eventually will. But I see no reason to deprive you of this knowledge in the meantime. I see no reason to allow unnecessary suffering when such a treatment might do wonders for your symptoms. The ketogenic diet for mental illness, and PTSD specifically, is not a fad, quackery, or mumbo-jumbo. It is based on an understanding of real biological mechanisms in mental illness and the conditions required in order to heal.

The real question is why wouldn’t you consider a ketogenic diet as a treatment for PTSD in you or someone you loved?


I am a mental health counselor that works with dietary and nutritional therapies to treat mental illness and neurological issues. You can learn more about me here. Feel free to contact me on your journey to mental health.

Like what you are reading on the blog? Want to learn about upcoming webinars, courses, and even offers around support and working with me towards your wellness goals? Sign up!

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References

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How do ketogenic diets help anxiety disorders?

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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.

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 of inflammation sets the stage for severe 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 for 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 is wanting 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 of 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 because 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 of 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 power-house 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 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 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 sugars 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, 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 brain. 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!

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 your anxiety disorder.

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.

As always, please feel free to contact me if you have any questions or if i can help you on your mental health journey.

Like what you are reading on the blog? Want to learn about upcoming webinars, courses, and even offers around support and working with me towards your wellness goals? Sign up!


References

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