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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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Glutathione and the ketogenic diet

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How does the ketogenic diet’s upregulation of glutathione play a part in healing your brain from mental illness and neurological disorders?

Glutathione is the brain’s main antioxidant system. The ketogenic diet’s ability to upregulate glutathione production is particularly helpful for people with mental illness or neurological disorders. Ketogenic diets increase the production of glutathione in the brain. Other mechanisms in which glutathione treats mental illness and neurological issues are leaky gut repair, reduction in brain inflammation through improved immune system response of macrophages, enhanced repair of the blood-brain barrier (BBB). Upregulation of glutathione production also improves liver function, which reduces the load of assaults in the body that could later impair brain function (e.g., heavy metals, xenoestrogens).

Introduction

If you have read very much at all on this blog, you have learned about inflammation and oxidative stress, and how those can create symptoms of mental illness and neurological disorders. You may also have read what I have written about the amazing anti-oxidant system you have in your own body that helps combat inflammation and oxidative stress. This endogenous (your body makes it!) antioxidant is glutathione and your production of glutathione is increased when you go on a ketogenic diet.

This post will discuss why the upregulation in glutathione that you get on a ketogenic diet is so important in treating your mental illness or neurological issues. We will specifically talk about why the ketogenic diet’s ability to upregulate glutathione is one of the major ways it helps treat your symptoms.

Other blog posts (coming soon!) will discuss what glutathione is, how it is made in your body, and what you can do to increase your endogenous glutathione production that will supercharge the already healing effects of your ketogenic diet for mental illness.

But first, let’s talk about why you need the upregulated glutathione you get on a ketogenic diet, specifically to treat your mental illness and reduce your symptoms.

Glutathione heals your Leaky Gut.

You may have started your ketogenic diet with digestive issues of varying severity. When they study people with irritable bowel syndrome, they find signs that glutathione is diminished. This is likely because it is being constantly depleted in its efforts to combat oxidative stress in the gut.

Suppose there is not enough glutathione to reduce inflammation and combat oxidative stress. In that case, you get cell damage, which gives you those awful digestive symptoms. As glutathione levels diminish, the gut cannot repair itself, becoming leaky. A leaky gut over activates the immune system in your body, increasing brain immune activity and neuroinflammation.

Neuroinflammation is an underlying factor in the pathology of every mental illness I have written about on this blog thus far. We all know that the health of our gut affects the health of our brain and our mood. 

So while you are on your ketogenic diet and your glutathione is being upregulated, you will keep oxidative stress down in your gut. That is going to help your gut heal (finally) and, in turn, reduce your neuroinflammation and oxidative stress levels in your brain. And that is one of the ways a ketogenic diet will help you treat your mental illness. 

Glutathione and your immune system

close up of an isolated macrophage

People on a ketogenic diet remark that they are much less sick and get illnesses less often. You may be wondering what that is all about. There are a lot of important ways that a ketogenic diet improves immune system function. But specific to how a ketogenic diet increases glutathione and how that improved production of glutathione enhances the immune system, we need to talk about macrophages. Adequate glutathione is required to make white blood cells (macrophages) an important immune system component.

Healthy macrophages in a sufficient number produce a swift and crucial defense in attacking bacteria and viruses. You want a strong, immediate, and crushing immune reaction to invaders. What you don’t want is a long, drawn-out, and ineffective battle that keeps inflammatory cytokines high and continues to create brain inflammation for long periods. 

Glutathione and your blood-brain barrier

Rhea, E. M., & Banks, W. A. (2019). Role of the blood-brain barrier in central nervous system insulin resistance. Frontiers in neuroscience13, 521. https://doi.org/10.3389/fnins.2019.00521

Your blood-brain barrier may very well be leaky if you are suffering from a mental illness or a neurological disorder. And this is a huge problem. You need that blood-brain barrier intact and working well to protect your brain from toxins. Otherwise, molecules that were never supposed to get near your brain do exactly that. This triggers an immune response in your brain to fight off those molecules that should not be there. This immune response in your brain produces inflammatory cytokines. These cytokines produce cellular damage as they attempt to combat the threat. Which would be fine if we did not have a constant barrage of molecules entering the brain that should not be there due to a leaky blood-brain barrier. The chronic neuroinflammation that develops because of nonstop brain immune system activation because of your leaky blood-brain barrier is an underlying cause of your symptoms.  

It just so happens that ketogenic diets enhance the repair and maintenance of the blood-brain barrier in various ways. First, they enhance the creation of nice, tight gap junctions, which is the part of the BBB that becomes leaky. Ketogenic diets also increase energy production in astrocytes, which is one of the primary neuronal bodies responsible for the health of the BBB.  

Thus, the beneficial effects of the ketogenic diet may depend on increased brain uptake of [ketone bodies] KBs to match metabolic demand and repair of a disrupted [blood-brain barrier] BBB.

CellKBs up-regulate cell migration and expression of gap junction proteins Banjara, M., & Janigro, D. (2016). Effects of the ketogenic diet on the blood-brain barrier. Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease; Susan, AM, Ed, 289-304. DOI: 10.1093/med/9780190497996.001.0001

The upregulation in glutathione on a ketogenic diet helps maintain and repair the blood-brain barrier. 

Glutathione and your liver

Cline, J. C. (2015). Nutritional aspects of detoxification in clinical practice. Alternative Therapies in Health & Medicine21(3).

Your liver cannot detox your body from environmental assaults without adequate levels of glutathione. Unchecked environmental assaults, regardless of whether or not they get through your blood-brain barrier, can create neuroinflammation. 

The liver requires glutathione to help detox you from the following inhibitors to your mental health. Each of these deserves a separate post to explain how they contribute to the development of psychiatric disorders. 

  • drug metabolites
  • mycotoxins
  • heavy metals
  • pesticides
  • herbicides
  • xenoestrogens   

You need the upregulation of glutathione that happens on a ketogenic diet to help your body detox from the things that impair your brain health and create your symptoms. 

Glutathione and your brain

Let me be perfectly clear. Glutathione is THE MAIN ANTIOXIDANT that your brain uses to keep itself healthy and functioning. It’s not Vitamin C and it’s not Vitamin E, although those are used as cofactors to make glutathione. If you want a healthy brain, you want as much glutathione as your body wants to produce to protect and repair neurons from damage.

Suppose you have a mental illness or neurological disorder. In that case, you likely have parts of your brain that are particularly low in glutathione. Some of the areas of the brain found to be particularly low in glutathione in specific disorders include the following:

  • Lower posterior cingulate cortex in Obsessive-Compulsive Disorder (OCD)
  • Substantia nigra in Parkinson’s Disease (PD)
  • Occipital and prefrontal cortex in Depression
  • Prefrontal cortex in Bipolar Disorder and Schizophrenia
The brain, vintage engraved illustration.

Increasing glutathione production could help combat oxidative stress in particular parts of the brain relevant to your particular diagnosis. Thereby possibly reducing your symptoms.  

Even if decreased glutathione levels have not been found in particular brain structures for your disorder, there is an overall consensus in the literature that psychiatric and neurological diagnoses have increased levels of oxidative stress and lower glutathione levels in general. 

Glutathione (GSH) is arguably the most important endogenous antioxidant in the brain. In recent years, aberrant GSH levels have been implicated in different psychiatric disorders, including stress-related psychopathologies.

Zalachoras, I., Hollis, F., Ramos-Fernández, E., Trovo, L., Sonnay, S., Geiser, E., Preitner, N., Steiner, P., Sandi, C., & Morató, L. (2020). Therapeutic potential of glutathione-enhancers in stress-related psychopathologies. Neuroscience and biobehavioral reviews114, 134–155. https://doi.org/10.1016/j.neubiorev.2020.03.015

And so, using a ketogenic diet to increase glutathione levels in the brain specifically is one of the mechanisms by which it is a valid potential treatment for your mental illness or neurological disorder. 

Conclusion

There are a lot of benefits for someone struggling with mental illness or neurological symptoms to increased glutathione production. And the ketogenic does exactly that!

Now, you may have some genetic differences that interfere with your ability to make and recycle glutathione. It may be harder for you to make it, and that would be helpful to know. If you want to deep dive into your own body’s ability to make glutathione I would recommend a test through 23andMe (affiliate link). Remember, a portion of your 23andMe can be paid for with your health savings account (HSA) or (FSA) if you have that benefit.

Once you have your 23andMe data you can subscribe to this amazing website Genetic Life Hacks (affiliate link) which will analyze it and report how well your genes support your ability to make and reuse this important endogenous antioxidant your healing brain needs so badly!

No matter what you find out, don’t despair. There are things we can do to increase your glutathione production, even on a ketogenic diet which does such a great job making more of it in the first place.

You need to read this article about thiamine deficiency because a thiamine deficiency can get in the way of your ability to make glutathione. And you may be entering your ketogenic diet thiamine deficient! 

Be sure to get plenty of magnesium, as that activates thiamine, so it can do its thing to help make glutathione.

If you found the above article helpful, you may also like this other blog post talking discussing glutathione.

I am a mental health counselor who practices functional and nutritional psychiatry principles, 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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keto diet rules for mental health

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I am well aware that using the word “rules” is an unpopular stance. That some of you immediately have the urge to argue about what the rules are, should be, and whether the concept is even valid. Writing a post titled keto diet rules is just looking for trouble.

So let me begin by clarifying that by keto diet rules, I mean guidelines. By keto diet rules, I mean these are the considerations I have seen that need to be addressed and the best practices I have seen with clients attempting to use a keto diet to improve their mental health.

For many people, having keto diet rules really helps. And saves them from months and months of difficult adjustments, stops and starts, and general discouragement. Not things that people already struggling with mental illness have a lot of bandwidth for.

My first rule is if you are using the ketogenic diet for mental health, you must use a nutrient-dense and well-formulated ketogenic diet. Eat with the intention to heal your brain.

My second rule is that your carbohydrate restriction level must be low enough to consistently and generously produce ketones that your brain will use for fuel and healing.

My third rule is that you take the time to weigh the pros and cons of going down in your carbohydrates quickly or slowly. There may be some factors around this you have not yet thought about that are very individual to you but can make or break your initial attempts at success.

My fourth rule is that if you are on medications, you do not go into it without a prescriber ally. Someone who can help you modify your medications as needed. You deserve this very basic level of care.

Let’s talk about each of these rules in more depth.

What is a well-formulated ketogenic diet?

Before we talk about how fast or how slow you should go in adopting a ketogenic diet, it is essential that we define what a ketogenic diet to treat mental illness is and is not. When doing a ketogenic diet for mental health, doing the well-formulated version is crucial.

A well-formulated and nutrient-dense ketogenic diet by my definition that I use with my patients is as follows:

It includes plenty of animal foods with highly bioavailable nutrients, including fish, eggs, beef, lamb, chicken, turkey, or other meats.

It can, but does not have to, include ingestion of dairy. If it does include dairy, it will have cheese, butter, and sometimes heavy whipping cream (usually the liquid form, not the fluffy sugar bomb you used to put on pie)

It includes plenty of healthy fats that brains love and include tallow, lard, butter, ghee, coconut oil, avocado oil, and olive oil.

It includes low-carbohydrate nuts like pecans and almonds, in moderation.

It includes low-starch and low-carb vegetables such as cabbage, cauliflower, green beans, and a whole lot of other ones that are delicious.

It includes keto desserts using low-carb sweeteners that do not affect blood sugar levels. Sometimes not in the first few weeks, but eventually if that is something you want to enjoy.

It completely excludes industrialized seed oils like canola, vegetable, soybean, and sunflower oils.

It completely excludes grains such as wheat, barley, and corn. It excludes legumes such as lentils, split peas, and all beans (that are not green and actually a vegetable).

Doing a well-formulated ketogenic diet for mental health is not an “if it fits your macros” kind of situation. For those that do not know what that means, the “if it fits your macros” version includes inflammatory oils, grains, and forms of processed sugars as long as one is keeping their carbohydrate level within a specific range. As you can imagine, if you are trying to heal a mental illness and have read anything about neuroinflammation, you know that keeping those things out of your diet is going to be best for your healing.

If you are using a ketogenic diet to treat a mental illness, it is likely not simply a “low carb” diet that many people use primarily for weight loss, although you may find significant symptom relief from those versions alone. If you are doing a ketogenic diet specifically to treat a mental illness, you are doing so as though you are treating a neurological disorder.

How low in my carbs do I have to go?

Low-carbohydrate diets are well classified by dietdoctor.com in this post here. They discuss three ranges of carbohydrate consumption by measuring NET carbs. The lowest range they discuss is 20g net carbs a day.

Net carbs are the total amount of carbs minus the fiber. However, there are people who have gut microbiomes that are somehow able to use fiber to produce their favored fuel of carbohydrates. People with mental illness are often also trying to change their gut microbiome to a healthier mix of bacteria. And so for that reason, when I work with clients, we work with total carb measurements.

I keep my clients to 20-30 grams TOTAL carbs per day. This means about 10g of total carbs per meal. Or some clients will save up their carbs to have with their dinner. I do not generally support the use of NET carb counting but instead, suggest total carb counting. I want the carbs very, very low so that the patient can begin to make ketones and feel the effects as soon as possible, and there is no danger of an energy roller coaster for a vulnerable brain to experience.

So you will look for and evaluate foods and recipes from a ketogenic lens as opposed to a low-carb lens because sometimes the carbohydrate levels of “low-carb” are too high for many people to reliably and consistently produce ketones. This post is about how to do a ketogenic diet to have higher ketone levels to be used for brain fuel and body healing. It is about eliminating as many inflammatory influences as possible from the diet and providing nutrients and building blocks needed to improve your brain health.

This is why we use keto diet rules, especially if we are treating mental illness. It’s not because we enjoy being told what to do. It is about following some guidelines to make the outcome as positive as possible and to reduce the likelihood of problems along the way.

How fast or slow in my carbohydrate restriction should I go?

Knowing what a well-formulated ketogenic diet that is nutrient-dense entails may be part of what makes you decide how fast or how slow you want to adopt the diet.

For example, if you have budget concerns, you may want to begin stocking some of the staple items and foods over the course of a few weeks or months. You may want to start looking at recipes and meal plans or begin discussions with a spouse about how meals in the household will be changing to support your treatment.

If you are in no hurry for symptom relief, you can most certainly go slower in your transition and swap carbs out in your diet more slowly. The average daily carbohydrate intake from the standard American diet is a bit over 300 grams of total carbs (often much higher). So if you want to begin by learning how to count carbohydrates, and then start to lower them to 100 net total, then 40 to 60 net total, and finally down to 20 net total, that is a very valid option and a steady state of behavioral change and improvement.

I do have some clients that reduce their carbohydrate intake slowly. We make weekly net carb goals, and they strive to meet them. We work on behavior changes, problem-solving, and mental adjustments needed for a lifestyle change for their health.

There are many pros to doing it this way. You would learn to adjust your shopping, entertainment, and cooking habits and there is less possibility that there will be any noticeable electrolyte imbalances to deal with.

But a significant con is that it can take you several more weeks to get symptoms relief. And the several more weeks that one does not experience a substantial reduction in symptoms can cause motivation to stay with the dietary therapy to reduce.

Other clients want to jump in right away and feel better. You may not want to commit to going down in carbohydrates over many weeks to see if the therapy will work for you. You may not be functioning well enough for a bunch of meal planning or have the energy to do any kind of extensive meal prep. And that’s OK. You don’t have to. It can be kept amazingly simple for the first few weeks. If you are truly miserable and in great distress, you may want to want to get started with minimal preparation, get into a consistent level of ketosis, and see what is possible.

So this particular keto diet rule is not one that I make for you. It is one that you make for yourself and then you stick to the plan. You can come up with this rule based on what works best in your life, what you know about the level of difficulty you have in making behavior changes, and by evaluating your support system and what needs to be in place for success.

Are the very low carb rules forever?

The thing that always seems magical is that no matter how my clients decide to approach the adoption of the ketogenic diet, the benefits seem to continue and improve as time goes on.

This makes perfect sense. If they are staying relatively consistent on a ketogenic diet and are producing and using ketones as fuel, the brain continues to heal. The improved level of energy in the brain provided by ketones allows cell membranes to continue to repair, upregulate BDNF to facilitate connections and learning, and upregulate memory function in the hippocampus. Because ketones keep neuroinflammation down, the brain can catch up steadily on repairs. And because the client is using a well-formulated and nutrient-dense ketogenic diet, they have micronutrients to make these critical repairs. So it is no wonder that I have people continue to see improvements well past their first or second year of using a ketogenic diet.

As your brain and metabolism heal, it is possible that you will be able to move to 40 to 60 total grams of carbohydrates a day and still have plenty of ketones for a beautifully functioning brain.

You are used to a medical model that tells you that you will always have to take this or that medication, that you will not likely get better from a variety of conditions, and that has the word “chronic” is in almost all disease definitions.

And so when I first put my patients on 20 to 30 total grams of carbohydrates, they despair a little, thinking that they will have to eat that low of carbohydrates their entire life. And it is because they have been part of a medical model for so long that doesn’t show them healing. But I see people I have worked with be able to increase their carbohydrate intake after one or more years.

Never have I seen them go back to the huge amounts of carbohydrates that likely contributed to their original disorder. But with additional lifestyle changes that include sleep and exercise, many can go up to moderate or even sometimes liberal low-carb ranges using whole food that gives them more ideas for recipes and more access to a variety of food choices.

Medication rules of engagement

One of the most important keto diet rules for mental illness has to do with medication.

Regardless of your intention to follow the above rules, or whether you decide to restrict carbohydrates quickly or slowly, it is vital that if you are on any medications, you both research what types of medications you are on and talk to your doctor.

Dietary changes that are implemented quickly often need much quicker medication adjustment, and there is the danger of potentiation effects if you are already taking psychiatric medications.

What often happens is with a ketogenic diet, your brain begins working better. And because your brain is working better, your current dose of psychiatric medication may be too high for you, and you will start to get side effects at your current doses. You or your prescriber may believe that it is the ketogenic diet causing your symptoms when in actuality, it is much more likely a sign that your brain is healing.

Not all prescribers have experience working with people on ketogenic diets for mental illness. And so, it becomes important for you to learn what you can about your medications so you can have a collaborative relationship with your prescriber about the possible need of adjusting medications.

If you are taking any kind of diabetes medication that influences your blood sugars, drugs for heart disease that could affect your electrolytes or blood pressure medication, you need to have your prescriber available to make adjustments, sometimes quite quickly.

Because of these issues, this may also help you determine how fast or how slow you should begin to reduce your carbohydrates. It is part of the decision-making that will happen as you start to work towards symptom reduction, improved functioning, and better health.

You may find the following posts helpful in finding a prescriber to be your ally during your transition to the ketogenic diet for mental illness.

As always, this post is not medical advice. I am not your mental health professional, and I am not your doctor.

But if you want to learn more about me or contact me for a consultation I am happy to help you on your journey to know all the ways you can feel better. You may also want to sign up to receive announcements about webinars, workshops, and group wellness opportunities on these topics here.

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

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Do I need help doing keto if I have a mental illness?

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Changes in diet can be hard and challenging even for people who do not identify as having a mental illness. There are a lot of reasons you may benefit from professional help transitioning to a ketogenic diet and many different kinds of professionals that can help you. Some of these include ketogenic nutritionists, ketogenic dieticians, ketogenic informed mental health counselors, nutritional psychiatrists, functional psychiatrists, or other low carb diet informed prescribers who work in the mental health space.

Introduction

In this blog post, we will discuss some of the factors you might want to consider if you have a mental illness, and how they inform your decision about whether or not to use a ketogenic diet specialist. And, if you decide that a professional would be helpful, you can read on and learn about the different types of professionals you could work with as you use a ketogenic diet as a treatment for your mental illness.

Reasons you may want a ketogenic diet professional

A lot of people do the ketogenic diet on their own, often to lose weight or to improve their diabetes. They do all kinds of variations on the ketogenic diet with carbohydrate intakes varying from 20g total to 100g total per day. And as long as they are producing at least a little bit of ketones throughout the majority of their day, we call it a ketogenic diet.

Psychiatric symptoms need the right macros

But people using the ketogenic diet for mental illness (or neurological disorders) often need a slightly stricter version, at least in the beginning. Sometimes if we are not careful with the carbohydrate consumption we recommend for someone with mental illness, they may not have levels of ketones at high enough or for a long enough period of time to truly test the diet out as a treatment for their symptoms. We are changing the primary fuel source for the brain. And so it becomes very important to produce enough ketones through dietary fat to keep the brain happy and not exacerbate symptoms because of an energy deficit in the brain.

So if someone goes to any of the many excellent diet coaches out there, they may be told that 50g of total carbs a day is “doing keto” because they are focusing on your weight loss, and perhaps not on the diet it must be used for the treatment of mental illness. They may even recommend you restrict your dietary fat intake prematurely because they are focusing on that weight loss and trying to help you lose weight.

I wouldn’t want you to think you had tried a ketogenic diet to treat your psychiatric symptoms and that it was unsuccessful when all you may have needed was some help to find the right type of ketogenic diet to find relief. The ketogenic diet may not work for you. But it would be a shame to walk away prematurely without the benefit of the customization and support you both need and deserve.

It takes a good three weeks of very consistent therapeutic carbohydrate restriction, in the form of 20g (maybe 30g max), for you to get some idea of whether a ketogenic diet might be helpful for your individual psychiatric symptoms.

Keto and medications are a big deal

Another reason you may want to work directly with a ketogenic diet professional is if you are on psychiatric medications. This is a very important factor in your decision-making and should weigh heavily in your decision about whether to attempt keto on your own or with professional help. Ketogenic diets are such powerful mental health interventions, that your medications may need to be adjusted during the first few days or weeks of the diet. Keto and antidepressants; or keto and other medications for diabetes, blood pressure, and a few others need to be monitored carefully.

Sometimes you need to go down on a few medications simultaneously, and that’s complicated. And sometimes, if you are not working with a professional and you have a worsening of symptoms, you will not have anyone helping you watch out for side effect potentiation and you will give up early, thinking the diet is making you worse. There are some instances when it is in fact your ketogenic dietary therapy creating symptoms and you need some additional supportive bridge medications or supplements to support your healing journey.

So you can see, if you are on psychiatric medications, it is particularly wise to work with a ketogenic professional who is able to modify your medications or work with a prescriber who will, and has experience with the ketogenic diet and psychiatric medications. And if you cannot find a prescriber, you can find a ketogenic mental health professional to coordinate and work with a prescriber with whom you already receive care. This could be a ketogenic dietician or even a ketogenic informed mental health counselor (like me).

Lifestyle change is hard

You may also really benefit from working with a ketogenic informed mental health professional to assist you. They will be able to help you work through any issues that come up while making a big lifestyle change like the ketogenic diet. Sometimes big lifestyle changes bring up feelings of resistance and it can be good psychological work to explore those with someone who knows how to move you through those potential obstacles.

I have written some blog posts about some of the psychological aspects of the lifestyle change involved in ketogenic dietary therapy, and how mental health counseling can help. You can find those here:

If you have decided that it would be helpful to find a ketogenic dietary professional, then read on. I will go through the different types of mental health professionals you may find trained in ketogenic dietary therapies that could help you on your journey to better mental health.

Ketogenic diet professionals

Luckily there are a lot of different types of mental health professionals trained in ketogenic diets that can help you. We will go through and describe each one, and provide resources below that could help you find one to help you on your mental health journey.

Ketogenic nutritionist or dietician

A ketogenic nutritionist is a nutritionist that has been trained to use the ketogenic diet to treat neurological disorders. As you may have read before, the ketogenic diet has been used for over a century to treat epilepsy, and it is now used for diseases like Alzheimer’s disease, Parkinson’s disease, and ALS.

A ketogenic nutritionist may also go by the term ketogenic dietician. Many work in hospital settings, but many provide services outside those institutions. A ketogenic nutritionist or dietician cannot help you adjust your medication, but they can work closely with your prescriber. And they are often very clever at addressing any issues you might have in implementing your new diet (e.g, shopping, meal prep, budgeting). These professionals will be able to give you the correct macros that will ensure you have plenty of brain energy and the nutrient support you need to feel better.

If you choose to work with a nutritionist or a dietician, be sure to clarify with them that you are looking for someone with experience providing help with ketogenic diets specifically. Not all nutritionists and dieticians understand that ketogenic dietary therapy is being used outside of epilepsy treatment for mental illness. Find one that is not going to discourage your use of it because they are not keeping up with the research literature on this topic.

Nutritional psychiatrist

A nutritional psychiatrist is an MD or Licensed Psychiatric Nurse Practitioner, who is able to monitor your medications and adjust them as needed. Some focus on dietary interventions and medication, and others include psychotherapy work with patients. One of my favorite nutritional psychiatrists, Georgia Ede, MD has a great quote:

The most powerful way to change your brain chemistry is through food, because that’s where brain chemicals come from in the first place.

Georgia Ede, MD – https://www.diagnosisdiet.com/blog-parent/category/mental-health

This is how a nutritional psychiatrist will approach your ketogenic dietary treatment for mental health. There will be some baseline tests run, and there may be supplements, but there will not be a focus on supplements as the mechanism by which you will change your brain chemistry and function.

Functional psychiatrist

A functional psychiatrist may or may not be well-trained in the use of ketogenic diets, but many of them are. They may have a focus on tests and supplementation over dietary therapies and you will have to ask them if they are comfortable helping you try one for your mental illness. They work to evaluate and correct what is causing your mental illness and they will likely have some advanced and well-thought-out recommendations for supplementation, both as a primary treatment and to support your ketogenic diet. They are good at ferreting out underlying causes of mental illness that traditional psychiatry does not. Functional tests and supplementation can become expensive, as they are not usually covered by insurance in the US. If you want to explore using a ketogenic diet or just explore options to traditional psychiatry on your mental health journey, a functional psychiatrist is a great potential resource.

Mental Health Counselor

A mental health counselor (or therapist, they are called different things in different places) can be an excellent choice. A keto counselor of sorts!

Full disclosure, this is the kind of ketogenic professional I am (About Me).

A mental health counselor can see you bi-weekly or weekly, which will help you monitor your symptoms and help you overcome any practical or even psychological obstacles you are facing as you attempt a ketogenic diet for your mental health. A mental health counselor can practice both nutritional psychiatry and functional psychiatry (without the medication component; I know, because that’s what I do). They can coordinate your care directly with your prescriber regarding possible needs for medication adjustments and even preliminary medical testing that might be helpful in tracking your progress.

Using a ketogenic informed mental health professional like a mental health counselor or therapist means that you can get evidence-based psychotherapy while you are using your ketogenic dietary therapy for your mental illness. The two are very complimentary. You can read more about how they can work together here. Be sure to find a mental health therapist that understands ketogenic diets. There can be problems finding one that is current in their understanding of the use of ketogenic diets for mental illness. You can read more about why that would be a problem here.

Finding a Ketogenic Professional

  • Chris Palmer, MD’s website has a directory of ketogenic dieticians here
  • The Charlie Foundation has a list of ketogenic dieticians here.
  • Society of Metabolic Health Practitioners Provider Directory is a directory of all kinds of ketogenic informed healthcare practioners. If you want someone who can help with medication adjustment be sure to find someone who is a prescriber, such as an MD, DO, Licensed Physcians Assistant, or Licensed Medical Nurse Practioner. Bonus if you can find one near you or via telehealth that specializes in psychiatric or neurological conditions.
  • Find a Low-Carb Doctor at DietDoctor.com also is a directory of ketogenic informed healthcare practitioners. Just like the directory above, you will want someone who can either adjust your medications, or help you knowledgably monitor your symptoms with you and help you advocate with your current prescriber as needed.
  • You can search for a functional psychiatrist in your area or via telehealth at a great organization called Psychiatry Redefined.
  • If you want to see someone in person, you can type in the search term for what you are looking for and add “near me” next to it into your favorite search engine.
  • Don’t beccome discouraged if you cannot find someone near you! Lots of independent ketogenic practioners us telehealth. Just type in the search term for the type of professional you are looking for. You will find a variety of great telehealth professionals able to help you meet your goals.

Conclusion

Finding a ketogenic health professional like a nutritional or functional psychiatrist, ketogenic dietician or nutritionist, licensed mental health counselor, or another ally with training in mental health can be really helpful.

I want you to know all the ways you can feel better.

But more importantly, I want you to know that you deserve a higher level of support and encouragement as you try to make big changes to help treat big issues.

If you are curious about how a ketogenic diet might help treat the underlying mechanisms of specific disorders, I have written carefully researched individual posts on Depression, Anxiety, ADHD, Alcoholism, PTSD, OCD, GAD, Panic Disorder, Social Anxiety Disorder, and many more. I add new ones all the time. So if you do not see the disorder you are interested in, please search the bottom of the main page.

Please feel free to reach out to me if you have any questions or I can help you on your wellness journey. You can contact me 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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Why are you irritable on keto

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Why does keto make me irritable?

It can take 3 to 6 weeks to adapt to a ketogenic diet. During that time irritability may occur from insufficient electrolyte supplementation (especially sodium), potentiation effects of existing medications causing side effects, or psychological factors related to making big lifestyle changes. You are not irritable because you are not eating carbohydrates. Your brain is supplied plenty of glucose endogenously through gluconeogenesis.

Introduction

Sometimes I do keyword searches to try to figure out what to blog about. And I came across a snippet that was so misinformed and downright misleading my stomach sank. That this snippet came from a revered institution made it all the more egregious. I was so upset by the damage such a snippet could do, that I actually reported it to Google as misinformation.

Misinformation Snippet provided by Harvard Health

I am not arguing with you that you feel irritable. It is quite possible you are feeling irritable while transitioning to the ketogenic diet. There are a lot of reasons this may be happening.

But it is NOT because your brain is not getting enough glucose. I promise you. Your liver makes all the glucose your noggin may want or ever need, right on-demand, from a process called gluconeogenesis. This process is not stressful for the body or damaging in any way. Your liver happily does it for you.

So why might you be irritable on the ketogenic diet? Let’s go through the many reasons you may feel irritable on keto.

You are irritable on keto because you are taking medications that need to be adjusted or discontinued

As always, this is with the help of your prescriber. But if you are doing keto and you are feeling irritable, this could be because you are still taking medications that are being affected by the diet. These can be psychiatric medications, medications designed to lower blood sugar, or even medications that are supposed to help other conditions but that raise your blood sugar as a side effect.

Medications that lower blood glucose

If you are on ANY kind of medication designed to lower your blood sugars, and using those in addition to a ketogenic diet, you are likely becoming hypoglycemic. And this could be making you quite irritable (hangry). Sometimes we need to adjust medications very quickly on a ketogenic diet.

Medications that raise blood glucose

Some medications actually RAISE your blood sugar, all by themselves. Actually, a lot of them do. And so it is possible that one of your other medications, not designed to lower blood sugar, is potentially getting in the way of your keto-adaptation or causing you to go in and out of a ketogenic state. Popping in and out of a ketogenic state early on, makes you feel awful and as your energy goes up and down unnecessarily it can make you feel irritable.

Here is a resource that will help you figure out which medication may be messing with your blood sugar and you can ask your prescriber about whether it is ok to lower it or even temporarily discontinue it as you work towards your keto-adaptation.

Drugs That Can Affect Blood Glucose Levels

So check with your prescriber and ask about reducing your medications.

Psychiatric medication side effects

As someone who helps people transition to a ketogenic diet to treat mental illness, this is an area I watch carefully with clients and their prescribers. A ketogenic diet is a powerful therapy and it changes how your brain works. Because it makes your brain work better, the medications you usually take for psychiatric issues (SSRIs, mood stabilizers, anti-psychotics, etc.) can begin to cause side effects.

This is called potentiation, and it basically means that because your brain is working better, your current dose of the medications use to help yourself feel better is now too high. The easiest way to be on the lookout for potentiation effects is to look up the side effects of the medications you currently take. One of those side effects may very well be irritability. If you see that you are having these side effects, it may be your current dose and not the keto.

You are irritable on keto because you are not being diligent about supplementing your electrolytes

The best way to do this is to get a good quality sea salt (I like Redmond) and measure out 5-7g in a small dish and make sure that you have salted your food or taken in that amount by the end of the day. If you are using pink salt, you must double this, because it only contains about 40mg of sodium as opposed to sea salt which contains 90mg.

I cannot stress this enough! Your brain cannot work well without enough sodium. You literally have sodium-potassium pumps that make your brain (and other cells) work. If you feel poopy or irritable or even just a little off while on the ketogenic diet, your first go-to is always electrolytes.

Some people need more than this 5-7g guideline. For people who get migraines for example you may need 13g. Keep salting until you feel better. I have clients take a 1/4 tsp of salt every few hours and chase it down with some water. Often they feel better in about 20 minutes. If you are someone who wants or needs to have a flavor to drink water you can use a lower carb electrolyte drink and add a good 1/4 to 1/2 tsp of salt to it, or you can purchase LMNT, which has a good amount of salt already in it, as any good electrolyte drink should.

You also may be needing a lot more magnesium than you think. This is an important mineral for EVERYONE and just about everyone walking the planet is insufficient in this nutrient. So please, get a good magnesium glycinate supplement, and don’t be afraid to take it generously. Some of my clients do really well with 600-800mg of elemental magnesium in glycinate form. You can even supplement with a small amount of potassium, but usually, this is not necessary because the sodium helps your body protect and manage your potassium levels. But if you are feeling irritable, possibly from low electrolytes, a tiny bit of potassium is not a bad thing.

You are irritable on keto because you need to eat more

A lot of people do keto to lose weight, which is great but they cannot get out of the calorie restriction mindset. During the first 3 to 6 weeks, their body is figuring out how to switch fuel sources. It is learning to adapt by turning genes on and off, upregulating certain enzymes, and doing a whole lot of other impressive things. The body needs adequate energy to do that, and if you are still manifesting a deep down phobia of eating fat you are going to struggle. You are going to be hungry and irritable.

If you restrict energy too much then your body releases stress hormones. This can make you irritable. Don’t calorie restrict for those first 6 weeks. Just enjoy your ketogenic foods. Sometimes it takes our body a little while to get good at learning to unlock our fat stores, particularly if we have insulin resistance. And so in the meantime, it is ok to use dietary fat to fuel your body. Don’t worry.

You are irritable on keto because you need additional supports for the brain

As someone who helps people use ketogenic diets for psychiatric and neurological conditions, I know that this can be a real thing. Sometimes we add supplementation with medium-chain triglycerides (MCTs) that the liver immediately makes into ketones. Sometimes we add ketone salts. Both of these provide an immediate increase in ketones, that the brain can then use for fuel. This can help a brain struggling with psychiatric and/or neurological issues. It allows them to maintain energy in areas of the brain that are no longer using glucose well (hypometabolism). Psychiatric issues are often brain metabolism issues, and sometimes getting ketone levels up with MCT oil or ketone salts can really help.

You are irritable on keto because you have not adjusted emotionally to the change

It is also quite possible that you are feeling irritable on the ketogenic diet because of how you are experiencing it and how your change in what you eat interacts with your environment. As a mental health therapist, I can tell you that our thoughts about things drive our emotions. Any of the following could create automatic thoughts that make you feel irritable while on the ketogenic diet. Remember, anger is often a defense against feeling sadness. And so your irritability may be coming from feeling a sense of loss or even fear about how the diet will or might change your life and relationships.

You are mad or sad to do this diet in the first place

Many people do the ketogenic diet to reverse chronic diseases such as psychiatric, neurological, or other metabolic disorders like diabetes, high blood pressure, or even chronic pain conditions. All those pills and medications did not work or had side effects that made you feel even worse. And so now, here you are, having to implement a particular dietary therapy in order to try to feel well, while other people seem to be fine just eating all the carbohydrates all the time. It feels really unfair. And perhaps you have not radically accepted that you were sick and/or miserable enough to have to do this in the first place.

You don’t feel supported by your family or environment

Your spouse keeps bringing Oreos into the house or your children demand highly processed packaged foods. They demand that you make two types of meals each night, one low carb and one reflecting the standard American diet, which you cannot have anymore. You are having a hard time finding keto-friendly foods at the grocery store, or the processed keto foods most like what you used to eat are expensive and not even very keto.

Someone keeps bringing donuts to the office or having Birthday cake, and you cannot figure out how to go out to eat or be social with friends. And even when you do go out to be social, your friends keep trying to tempt you with higher carbohydrate choices or get moody and offended when you won’t eat what they brought.

This may be why you are irritable on keto. These are all situations that require an adjustment and for which you deserve support and help problem-solving. Feelings of sadness and anger, dare I say irritability, are understandable and valid emotions while learning how to be on a ketogenic diet.

You miss the flavors of certain foods

There are a lot of well-loved foods that you need to restrict on a ketogenic diet. You may miss the taste of banana in your morning smoothie. Sometimes you really want the taste of salted caramel. And you don’t know how to taste those things again and you just really miss it. Again, this is an example of where anger (or irritability, a lesser intense form of anger) is masking sadness and loss.

There is a learning curve with keto. You probably didn’t know that you could get banana extract and add it to your morning smoothie. Or that you can find salted caramel bars with a ketogenic recipe (like the one here).

Conclusion

There could be a lot of reasons you are feeling irritable on keto. And those should all be addressed. I want you to feel amazing. You deserve to feel amazing.

It might be a good idea to work with a keto diet coach or find a low-carb informed physician (see the resources page) to help you with medication adjustments. You may benefit from seeing a mental health counselor (like me) help you make such a big lifestyle change. You may enjoy this post I wrote about how psychotherapy can help you stay on keto to improve your mental health.

Just make sure that the counselor is in some small way keto informed (see the blog post about that here).

Otherwise, they may tell you such a diet is dangerous without knowing better, or tell you that you suffer from an eating disorder, without a proper understanding that therapeutic carbohydrate restriction is a research-based medical and psychiatric intervention.


Below are links to some of the resources discussed in this blog post. A few are clearly labeled Amazon affiliate links. I use them to help pay for this blog. Please do not feel obligated to use them.

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Ketogenic Diet Treats Alcoholism

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Can the ketogenic diet be used as an effective treatment for alcoholism?

A 3-week RCT done by the National Institute of Alcohol Abuse and Alcoholism found that a ketogenic diet could reduce the need for detox medications, reduce alcohol withdrawal symptoms, and reduce alcohol cravings. The researchers also found that brain scans of participants using the ketogenic diet decreased inflammation and had positive changes in brain metabolism.

Introduction

In this blog post, I am not going to outline the symptoms or prevalence rates of chronic alcoholism. This post is not designed to be diagnostic or educational in that way. What I will do is tell you about a very well-done, high-level study using the ketogenic diet as a treatment for chronic alcoholism. And we will then discuss what the underlying mechanisms of treatment using a ketogenic diet could be based on what already exists in the research literature.

Ketogenic diet treats alcohol withdrawal symptoms in humans

The National Institute of Alcohol Abuse and Alcoholism did a 3-week inpatient study of chronic alcoholics. Participants were admitted to a hospital unit and detoxed. They were then randomly assigned to either a standard American diet or a ketogenic diet to see if it could make a difference.

They found that those who got the keto diet needed less detox medication (e.g., benzodiazepines), fewer alcohol withdrawal symptoms, fewer cravings for alcohol, and their brain scans showed decreased inflammation and changes in brain metabolism. (You can read the study here.)

As if those results were not stellar enough, there was an animal arm of the study that showed that rats given a ketogenic diet reduced alcohol consumption.

People are confused about how a ketogenic diet could help people who are chronic (hardcore) alcoholics, who cannot stop drinking, ruining their lives, relationships, and bodies. How could a dietary intervention like the ketogenic diet help to this degree?

What could some of the underlying mechanisms of treatment be?

Let’s apply some of what we already know about how the ketogenic diet can help treat mental illness from prior blog posts.

What are the neurobiological factors we see in chronic alcoholism?

In a previous post, we discussed the mechanisms by which a ketogenic diet could modify symptoms of anxiety. In another post, we discussed how it can treat depression. In this post we will see whether these same four areas of pathology are seen in alcoholism:

  • Glucose Hypometabolism
  • Neurotransmitter Imbalances
  • Inflammation
  • Oxidative stress

Alcoholism and Glucose Hypometabolism

Glucose hypometabolism is well-established as a pathological mechanism in alcoholism. We see hypometabolism in the fronto-cerebellar circuit and Papez’s circuit and in the dorsolateral, premotor, and parietal cortices. When brains cannot use fuel properly we will often see shrinkages in brain structures. A shrinkage in brain structures is a consequence of long-term brain hypometabolism. In the alcoholic brain we see severe shrinkage in the following brain structures:

  • cerebellum (balance, posture, motor learning, movement fluidity)
  • cingulate cortex (executive control, working memory, and learning; a connecting hub of emotions, sensation, and action)
  • thalamus (several functions, including Circadian rhythms)
  • hippocampus (memory)

When someone is a chronic alcoholic, their brain’s fuel source switches from using primarily glucose as fuel to something called acetate.

It has been known that a major source of acetate in the body comes from the breakdown of alcohol in the liver, which leads to rapidly increased blood acetate.

https://www.news-medical.net/news/20191024/Acetate-derived-from-alcohol-metabolism-directly-influences-epigenetic-regulation-in-the-brain.aspx

How would a ketogenic diet treat glucose hypometabolism in chronic alcoholism?

Acetate does not have to be made just from alcohol being broken down in the liver. It is also one of three ketone bodies that are made in ketosis. And so for the alcoholic brain, which has serious glucose hypometabolism and that relies on acetate for fuel, it makes sense that a ketogenic diet may provide energy rescue for the hypometabolism we see in this population.

We reasoned that the abrupt transition form the brain’s consumption of ketone bodies, which occurs in Alcohol Use Disorder (AUD) as an adaptation to repeated alcohol intake, to the use of glucose as energy source, which reemerges with detoxification, may contribute to the alcohol withdrawal syndrome.

https://www.science.org/doi/abs/10.1126/sciadv.abf6780

In other words, if your brain is used to one fuel (acetate) and then you completely withdraw the source of its preferred fuel, it makes sense that your cravings for that fuel would increase. That an energy crisis would occur in the brain. But if you replace that fuel in another way, that doesn’t destroy your body and your brain, through a ketogenic diet, your brain gets to have fuel while your body and brain are doing the hard work of healing. And eventually, as the metabolic health of your brain and body improve, your brain may be able to use glucose better as a substrate. But until that happens, you need a rescue fuel that is similar. And the ketogenic diet provides that.

Alcoholism and Neurotransmitter Imbalances

Some of the neurotransmitter imbalances seen in alcoholism include dopamine, serotonin, glutamate, and GABA.

Dopamine fuels our motivation and has important functions in our reward centers. It is seen as having a role in both acute intoxication and increases simply at the anticipation of ingesting alcohol. When people go through alcohol withdrawal there is a decrease in dopamine functioning, which may contribute to withdrawal symptoms and alcohol relapse.

The brains of alcoholics are seen to be depleted in serotonin, and it is thought that this contributes to behaviors around impulsivity and drinking alcohol.

Alcohol consumption increases GABA activity. GABA is an inhibitory neurotransmitter that we usually want a little more of because it makes us feel relaxed. But in the alcoholic brain, as they go through withdrawal, GABA is downregulated, meaning you cannot make enough of it.

The GABA systems in the brain are altered in situations of chronic alcohol exposure. As an example, in some regions of the brain, the expression of genes that encode components of the GABAA receptor is affected due to alcohol.

Banerjee, N. (2014). Neurotransmitters in alcoholism: A review of neurobiological and genetic studies. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4065474/

The receptors are dysfunctional from chronic alcohol consumption. This is why we so often give benzodiazepines to help with withdrawals in people attempting to abstain. It is an attempt to temporarily correct the neurotransmitter imbalance that comes from withdrawal.

On the other hand, glutamate is downregulated during alcohol consumption. In other posts on other disorders, particularly anxiety disorders, we see glutamate dominate neurotransmitter state. This could be why so many people self-medicate anxiety disorders using alcohol (e.g., social anxiety). In the alcoholic brain, glutamate is thought to contribute to the rewiring of the brain that creates hyperexcitability and craving during alcohol withdrawal.

How would a ketogenic diet help treat neurotransmitter imbalances seen in chronic alcoholism?

Ketogenic diets upregulate the production of several neurotransmitters for the alcoholic brain going through withdrawals. Ketogenic diets are shown to increase serotonin production, increase GABA, balance glutamate levels and dopamine levels.

One of the ways this is accomplished is through decreased inflammation, which we will discuss in the next section. When brains are suffering from neuroinflammation (spoiler: the alcoholic brain definitely has inflammation) it disrupts the balances and functions of neurotransmitters. Another way chronic alcoholism can disrupt neurotransmitter balance is through malnutrition. B vitamins, magnesium, and several other important micronutrient cofactors are depleted and not easily restored. Alcoholics may not prioritize a healthy diet, and even if they do there are changes that occur to the gut microbiome that can reduce the absorption of important vitamins and minerals. A lack of amino acid intake resulting from choosing alcohol over nutritious food can and will disrupt the brains’ ability to create neurotransmitters and produce enzymes that regulate neurotransmitter function.

Alcoholism and Neuroinflammation

Neuroinflammation occurs when there is some assault on the neurons. This can be from head trauma, substances getting through a leaky gut-brain barrier, or chronic alcohol use. This inflammation, when it gets out of hand, will cause the death of cells, usually next to one another. These cells swell up and their internal cell machinery breaks down. Eventually, these cells that are irreparably damaged from inflammation, will rupture and spill debris where they do not belong. This is not a normal or healthy cell death process. So the debris will then lead to a local inflammatory process as the body attempts to clean up the mess.

There are very specific effects that alcohol (aka ethanol) has in the brain that trigger neuroinflammation.

The neuroimmune system response to ethanol intake, in specific brain regions such as amygdala, hippocampus and frontal cortex [in mice], is involved in addiction and in behavioural deficits observed in alcoholism.

Haorah, J., Knipe, B., Leibhart, J., Ghorpade, A., & Persidsky, Y. (2005). Alcohol‐induced oxidative stress in brain endothelial cells causes blood‐brain barrier dysfunction. http://dx.doi.org/10.14748/bmr.v28.4451.

Neurodegeneration seen in chronic alcohol abuse comes from chronic neuroinflammation. This neuroinflammatory response is due to signaling by glial cells (TLR4) who initiate this form of cell death.

How does a ketogenic diet reduced neuroinflammation in those with chronic alcoholism?

A ketogenic diet has been shown to specifically decrease TLR4 cytokines, as well as regulate the inflammatory process. It does this by being a signaling molecule that is able to turn genes on and off to balance inflammation. This keeps inflammation down. And a brain that has been exposed to chronic alcoholism is one that is on fire.

Ketogenic diets can help quickly reduce this inflammation, improving the brains’ ability to repair, restore and heal. As we learned in the neurotransmitter balance section, inflammation must be down in order for neurotransmitters to be made in the right amount and balanced.

Neuronal membranes, which are an important part of brain cells, cannot function well if they are swollen and are dealing with impending cell death. Getting inflammation down with a powerful anti-inflammatory intervention, like the ketogenic diet, could only be beneficial. Study participants experienced much less inflammation than the control group and this reduction in inflammation may have been what helped these study participants to have such favorable results as they went through alcohol withdrawal.

Alcoholism and Oxidative Stress

Severe levels of oxidative stress occur in alcoholism. Oxidative stress refers to the burden that occurs when the body’s ability to deal with reactive oxygen species (ROS) is out of balance. People who do not consume alcohol create a certain amount of reactive oxygen species just breathing and creating energy and being alive. But in healthy individuals, this normal load of ROS is well-managed and does not seem to contribute to acute disease states (although we still age, unfortunately). As you can imagine, chronic alcoholism tips this balance in such a way that ROS is increased.

Less oxidative stress would be good for anybody, but it is particularly good for alcoholics. Why? Because alcohol is particularly good at damaging the blood-brain barrier.

Thus, oxidative stress resulting from alcohol metabolism in brain microvascular endothelial cells can lead to blood-brain barrier breakdown in alcohol abuse, serving as an aggravating factor in neuroinflammatory disorders.

Abbott, N. J., Patabendige, A. A., Dolman, D. E., Yusof, S. R., & Begley, D. J. (2010). Structure and function of the blood–brain barrier.  https://doi.org/10.1189/jlb.0605340

And that the blood-brain barrier is crucial to healthy brain functioning. It is the protection from assaults that the brain depends upon, and when those tight junctions get loose and let substances through that would not be, it causes a dangerous neuroinflammatory response. Chronic non-stop neuroinflammatory responses deplete nutrients trying to fight them, blow cells up, and cause inflammatory cytokines to increase inflammation. As reactive oxygen species goes up the body’s ability to handle it goes down, causing an increase in oxidative stress.

Alcoholics have a lot of oxidative stress going on in the brain, but they also have it in their bodies. Alcoholic fatty liver disease, a devastating disease process that happens in chronic alcoholism, is seen to create large amounts of oxidative stress.

Acute and chronic ethanol treatment increases the production of ROS, lowers cellular antioxidant levels, and enhances oxidative stress in many tissues, especially the liver.

Wu, D., & Cederbaum, A. I. (2009, May). Oxidative stress and alcoholic liver disease. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0029-1214370

How could a ketogenic diet reduce oxidative stress in those with alcoholism?

Ketogenic diets reduce oxidative stress in several ways, some of which we already discussed in previous sections. Less inflammatory cytokines lead to reduced inflammation and create less reactive oxygen species to be neutralized. One of the ways it does so is to upregulate (make more of) an endogenous (made in our body) anti-oxidant called glutathione. This is a very powerful anti-oxidant that you get more of on a ketogenic diet.

Cerebral metabolism of ketones has been shown to improve cellular energetics, increase glutathione peroxidase activity, reduce cell death and possesses anti-inflammatory and antioxidant capabilities in both in vitro and in vivo models.

Greco, T., Glenn, T. C., Hovda, D. A., & Prins, M. L. (2016). Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5012517/

Ketones do this by increasing something that cells really need and that can be decreased in chronic disease states like alcoholism. This important something is called nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and you can think about it as a co-factor, meaning cells need it in order to do something. More of this co-factor helps your body to use enzymes to activate powerful antioxidants in your body, such as glutathione.

Other ways a ketogenic diet improves oxidative stress are the improved cell membrane function we already reviewed. This improved cell membrane function leads to better synaptic regulation, creating better neurotransmitter balancing. The increase in mitochondria, the powerhouses of neuronal cells, gives the cell more energy for improved cell signaling and enough energy to clean and maintain the cell and all its parts.

Conclusion

The ketogenic diet is not just a theoretical treatment for alcohol use disorder anymore. It is my hope that people will use this powerful dietary and nutritional intervention to help them in their recovery journey. Particularly in those who have struggled or failed in the past using the current standard of treatment.

With the help of a medically supervised detoxification, the ketogenic diet treats alcoholism and likely, according to the animal study arm of this research, helps improve the likelihood of relapse prevention.

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. It is my honor to tell you about all the different ways that 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!

Free ebook

References

Acetate derived from alcohol metabolism directly influences epigenetic regulation in the brain. (2019, October 24). News-Medical.Net. https://www.news-medical.net/news/20191024/Acetate-derived-from-alcohol-metabolism-directly-influences-epigenetic-regulation-in-the-brain.aspx

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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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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

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Pearlman, D. M., Vora, H. S., Marquis, B. G., Najjar, S., & Dudley, L. A. (2014). Anti-basal ganglia antibodies in primary obsessive–compulsive disorder: Systematic review and meta-analysis. The British Journal of Psychiatry, 205(1), 8–16. https://doi.org/10.1192/bjp.bp.113.137018

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Generalized Anxiety Disorder (GAD)

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How could a ketogenic diet help treat the symptoms of Generalized Anxiety Disorder (GAD)?

Ketogenic diets are able to modify at least four of the pathologies we see underlying Generalized Anxiety Disorder (GAD). 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 Generalized Anxiety Disorder (GAD) symptoms.

Introduction

In this blog post, I am not going to outline the symptoms or prevalence rates of Generalized Anxiety Disorder (GAD). This post is not designed to be diagnostic or educational in that way. If you have found this blog post, you know what GAD is and likely you or someone you love may already be suffering from the debilitating symptoms associated with 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 GAD 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 Generalized Anxiety Disorder (GAD) symptoms or as a complementary modality to use with psychotherapy and/or in place of medications.

Current psychopharmacology for Generalized Anxiety Disorder (GAD) includes selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). These antidepressants are first-line medication options for all anxiety disorders. Additional medications can include calcium modulator pregabalin, tricyclic antidepressants, buspirone, moclobemide, anticonvulsants, and atypical antipsychotics.

Why are these drugs prescribed for Generalized Anxiety Disorder (GAD)?

These drugs attempt to modulate complicated neurotransmitter systems that include serotonin, norepinephrine, and GABA. These are the most common targets of psychopharmacological approaches to these disorders. These are some of the neurotransmitter imbalances we see in patients suffering from Generalized Anxiety Disorder (GAD). 

However, patient responses to these medications designed to affect these neurotransmitter systems can often fall short of symptom relief.

Despite the efficacy of available pharmacological approaches, many patients do not achieve full remission, and novel treatment approaches are warranted.

Melaragno A., Spera V., Bui E. (2020) – https://doi.org/10.1007/978-3-030-30687-8_13

So what kind of pathology in the brain do we see in Generalized Anxiety Disorder (GAD)?

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.

Let’s explore which of these may or may not be present in the pathology of Generalized Anxiety Disorder (GAD).

Glucose Hypometabolism in the brain of those with Generalized Anxiety Disorder (GAD)

Hypometabolism of the brain means that some brain structures are not utilizing energy properly. People with Generalized Anxiety Disorder are seen to suffer from hypometabolism in the basal ganglia and white matter. Hypometabolism of the basal ganglia can be seen in sleep disorders in which people struggle with their sleep-wake cycle. Could hypometabolism of this brain area contribute to the inability to fall asleep or stay asleep due to worry? Possibly. I was unable to find where this possible connection was explored in Generalized Anxiety Disorder populations.

Primarily the basal ganglia are involved in motor learning, sequencing, and movement behaviors, and memory. While movement or motor issues are not part of the diagnostic criteria for Generalized Anxiety Disorder (GAD), there are complaints about working memory as a cognitive symptom of the disorder. Research has found abnormalities in brain metabolism in those with GAD, who attempt to recall from working memory while under emotion-inducing distractors.

This is not surprising, as the basal ganglia are also used for attention and filtering out distractions. For people with generalized anxiety, the act of worrying becomes an automatic behavior. There is an inability to determine what concern deserves attention and to worry constantly, even about possibilities that are highly unlikely. Would improvement in brain metabolism in these areas help reduce some of these symptoms of Generalized Anxiety Disorder (GAD)?

Female Basal Ganglia Brain Anatomy

This could mean that people with the disorder have a harder time discerning truly worrisome situations from mild annoyances. At the same time, the amygdala was more connected to a cortical executive-control network previously found to exert cognitive control over emotion.

https://med.stanford.edu/news/all-news/2009/12/brain-scans-show-distinctive-patterns-in-people-with-generalized-anxiety-disorder-in-stanford-study.html

Interestingly, in the brains of people with Generalized Anxiety Disorder (GAD), we also see issues with interconnectivity between brain structures.

Problems with interconnectivity occur between the amygdala and other brain structures. In the brain suffering from GAD, it has less connectivity to targets generally seen in normal brains. And when the amygdala was “over-connected” to these other brain structures, it seemed to influence where and how they in turn connected to other parts of the brain. These other structures are seen to then atypically connect to areas of the brain not normally seen to be so connected. Meaning, more connectivity was seen between areas there should not be. At least not in healthy brains with normal connectivity.

Of important note was that the amygdala region had less connection to the part of the brain responsible for evaluating the importance of a stimulus. It is hypothesized that this may be what causes GAD people to not know what to place importance upon regarding their concerns. And so people with GAD tend to worry about everything, as opposed to an actual likely threat or concern.

How could a ketogenic diet assist with hypometabolism and possibly even problems with interconnectivity?

Hypometabolism and keto

Ketogenic diets are used to improve brain metabolism in Alzheimer’s Disease and other neurological disorders. It improves insulin sensitivity in the brain for cells that are still able to use glucose. For parts of the brain no longer utilizing glucose well as a primary fuel, it provides the alternative fuel of ketones. Ketones are able to increase the functioning of existing mitochondria. These mitochondria are the powerhouses of neuronal cells. Not only do ketones help your mitochondria work better but ketones help your cells make more mitochondria. Which makes more energy for the brain. Which increases metabolism in the brain in a beneficial way.

Brain-Derived Neurotrophic Factor (BDNF) and Keto

Another powerful benefit of ketogenic diets is their ability to upregulate (make more of) something called Brain-Derived Neurotrophic Factor (BDNF). BDNF allows the brain to repair and grow new connections. If there are problems with interconnectivity in the brain, is it not logical to assume that an intervention that upregulates this factor would be an important part of recovery? Would not a ketogenic diet used in conjunction with cognitive-behavioral therapy (CBT) designed to change thinking patterns not be a powerful combination? An ample supply of BDNF could only be a positive factor in the treatment of Generalized Anxiety Disorder (GAD).

Neurotransmitter Imbalances seen Generalized Anxiety Disorder (GAD)

Just as with other mental disorders, we do not see a disruption in just one neurotransmitter. We instead see a disruption in the delicate balance of the neurotransmitter system. These include decreased GABA, increased glutamate, and decreases in serotonin. There is also some dysfunction in the neurotransmitter dopamine.

Decreases in GABA with an increase in glutamate are seen in other anxiety disorders, as described in this blog post here.

This neurotransmitter imbalance often occurs due to the environment in which they are being made. A brain suffering from inflammation and oxidative stress, which we will discuss more later in this post, is not a brain optimized to make and use neurotransmitters effectively.

A brain high in inflammation, for whatever reason (but it could very likely be due to eating highly processed carbohydrates), will cause something called the Tryptophan steal. Tryptophan is an amino acid that is a precursor to other neurotransmitters. When the brain is suffering from inflammation it will create less of (downregulate) the neurotransmitter GABA. And instead, it will take tryptophan and make more of an excitatory neurotransmitter known as glutamate. Which by itself would not be bad, except we are supposed to have adequate levels of GABA with our glutamate to keep our neurotransmitters in balance. Also, too much glutamate is neurotoxic to the brain. It ages the brain and causes damage. The tryptophan steal that occurs when the brain is under distress can cause up to 100x more glutamate in the brain than normal levels.

Cellular membrane function is crucial to maintaining neurotransmitter balance. Cell membrane function in neuronal cells allows the creation of neurotransmitters, how fast they fire, and how long a neurotransmitter stays around to be used within the synaptic cleft. This is relevant for those with Generalized Anxiety Disorder (GAD) because the reuptake of Dopamine in certain brain structures (e.g., striatum) is seen to be significantly lower in GAD patients than in healthy controls.

How could a ketogenic diet assist with neurotransmitter imbalances?

Mostly a ketogenic helps with neurotransmitter imbalances by reducing inflammation, so that the environment in which they are being made is a healthy environment to do so. But ketogenic diets have also been seen to restore neurotransmitter and ion channel functioning, which have very strong effects on how well neurotransmitters can work. In this small post, we discussed the importance of improved cell membrane function.

What it means for your brain is that all the work of making the right neurotransmitter balance is not enough. Your brain still must be able to use those neurotransmitters in a functional way. That means the ability to store important nutrients (cofactors) so neurotransmitters can be made, being able to break some neurotransmitters down, and being able to allow neurotransmitters to hang out in the synapses for the right amounts of time. Ketogenic diets allow these functions to be restored and allow neurotransmitter balance to occur through improved neuronal functioning. And if improved neuronal functioning accomplishing all that doesn’t sound like an important therapeutic target in an anxiety disorder like GAD, I am not sure what would be!

Oxidative Stress is seen in Generalized Anxiety Disorder (GAD)

We have all heard the term Oxidative Stress but may be unsure what it is and what it means for our body, other than it is “bad” and we need to avoid it. Oxidative stress happens. If you are alive then oxidative stress will occur just because your body is doing a lot of different biological processes that create substances your body has to deal with. And that is just what is happening internally. That does not even consider the impact of our environmental exposure outside of our body (e.g., chemicals, pollution, lifestyle).

Having a healthy lifestyle allows you to manage the amount of oxidative stress your body has to go through and it will even do things that help improve your ability to deal with what does occur. Exercise is a good example of this. It upregulates our ability to make antioxidants from pathways that exist in our own bodies, such as glutathione.

When we look at those with Generalized Anxiety Disorder (GAD) we see that there is a great deal of oxidative stress in this population.

Generalized anxiety disorder patients have higher oxidative stress index levels.

Ercan, et al., (2017); https://doi.org/10.1016/j.ajp.2016.10.008

They are still trying to tease out if oxidative stress causes GAD, or if GAD, because of the stress that is caused on the body with excessive worry, causes oxidative stress. And I would argue that it doesn’t matter. Let’s figure that part out later and do what we can to decrease oxidative stress. Let’s have it be a target of biological intervention and let’s also do our best to reduce worry in our thoughts with Cognitive-Behavioral Therapy (CBT).

oxidative modifications to proteins have actually been proposed as a potential factor in the onset and progression of several psychiatric disorders, including anxiety and depressive disorders

Fedoce, et al., (2018), https://doi.org/10.1080/10715762.2018.1475733

The inability to deal with these levels of oxidative stress in the brain destroys neurons. In the literature, they actually call it “extreme neuronal trauma” and as you can imagine, these traumatized cells are broken and cannot do all the functions they need to do to keep your brain working. They are not going to make neurotransmitters well, they are not going to have good working neuronal membranes, and they are not going to be able to store the nutrients they need in order to do cell maintenance or make needed enzymes that manage those neurotransmitters. Why we would expect that we could throw a serotonin reuptake inhibitor (SSRI) into such a complex system as a treatment? Throw all the neurotransmitters you want in there but if the membranes and machinery are busted it’s not going to work. Neuronal cells are being severely damaged and annihilated by oxidative stress. Talk about a band-aid mentality to mental illness. Why wouldn’t we just help people fix the synapses?

How could a ketogenic diet decrease oxidative stress?

Ketogenic diets are excellent for oxidative stress. This is not a speculation on my part. And this is not an assertion made only due to animal studies. This is a real-life and powerful effect seen in humans, in studies with actual human beings.

Cerebral metabolism of ketones has been shown to improve cellular energetics, increase glutathione peroxidase activity,15 reduce cell death16 and possesses anti-inflammatory and antioxidant capabilities in both in vitro and in vivo models.1720

https://doi.org/10.1177/0271678X15610584

One of my favorite things to talk about is glutathione. And not the kind you take in a pill that is given to you by your naturopath or functional medicine doctor. Oral glutathione isn’t used by the body so well and it’s expensive. Sometimes they will give you precursors in the form of vitamins and minerals, hoping your body will make more of its own glutathione, which is better and of which I completely approve. But nothing is going to upregulate (make more of)the production of endogenous (made by your own body) glutathione like a well-formulated (meaning nutrient-dense) ketogenic diet.

So treating oxidative stress in the GAD brain with a ketogenic diet should not be such a revolutionary and controversial stance. And quite frankly it is not. As you can see, there are some already identified mechanisms and clear effects of its use for the very underlying pathological processes we have identified with scientific inquiry.

Inflammation is seen in Generalized Anxiety Disorder (GAD)

Let’s discuss neuroinflammation. Neuroinflammation occurs for a lot of different reasons. Cognitive influences, like our interpretations of a situation, can cause inflammation. What we eat can cause inflammation, whether because our blood sugar levels are too high or we are having an immune reaction to a particular food. Inflammation can occur because something has crossed the blood-brain barrier that should not have. These all trigger an immune system response. And our brains have their own immune response and they respond with something called microglia.

Microglia tries to fix what is going wrong by releasing inflammatory chemicals. One type of inflammatory chemical that microglia release is cytokines. There are different types of cytokines. And they can be measured with serum blood tests. Your doctor may have ordered a CRP or a high-sensitivity CRP test for you. This is a marker of inflammation. But it is important to understand that there are a lot of different types of cytokines that increase inflammation. This can make research difficult. Some types of cytokines may be studied over others. Some will be studied in some populations but not in others. We do not have a nice clear picture. Particularly for Generalized Anxiety Disorder (GAD) populations

Inflammation and its association with people suffering from GAD are a little all over the place in the literature. Some studies have found people with GAD to have higher markers of inflammation. This is not surprising given that they tend to have more oxidative stress. Some people with GAD and certain genetic markers were seen to have more inflammation than others. This is again, not surprising. How our body manifests disease under the right epigenetic conditions would of course have a genetic component.

But higher markers of inflammation are not always seen in the literature for people with GAD. In fact, some have shown that people with GAD do not have higher inflammatory markers. But some studies are teasing out differences in subpopulations of those with GAD. For example, women who developed GAD later in life have higher markers of inflammation than those who develop it earlier in life. And we cannot seem to figure out if inflammation has a causative role in the etiology (creation) of GAD.

So I would say this. If you have only Generalized Anxiety Disorder (GAD), and no comorbid depressive symptoms, or comorbid Panic Disorder (which DOES see higher inflammatory markers), the role of the ketogenic diet on inflammation may not be of interest to you in your recovery. As a mental health counselor, however, I do not see too many patients with just pure GAD without any comorbidities. So inflammation may not be an issue in GAD, or it could be that it is an issue and there are not enough studies that include GAD as part of research with other comorbidities and this topic.

But just in case you have GAD and are suffering from dual diagnoses with other mental illnesses, I will discuss the effect of the ketogenic diet on inflammation.

How do ketogenic diets fight inflammation?

Ketogenic diets are metabolic interventions. Brain metabolism has direct effects on immune function in the brain. And as we know already from reading this blog post, immune function in the brain has direct effects on inflammation. High-fat, low-carbohydrate ketogenic diets create ketones, which decrease microglial activation and pro-inflammatory cytokines. Ketones are actually a signaling body, influencing gene expression, that can exert positive influences on the pathways that modulate inflammation. If you are wanting to dive a little deeper into exactly how ketogenic diets fight inflammation there is a most excellent article here.

Other ways that a ketogenic diet may help with reducing inflammation include gut microbiota modifications. We are still learning about all the ways ketogenic diets help fight inflammation. But regardless of whether you choose a ketogenic diet to help treat Generalized Anxiety Disorder or some other mental illness or neurological disorder, it is important to understand that neuroinflammation is toxic to brains. It breaks down the blood-brain barrier your body has put in place to try and protect your brain. It damages neuronal membranes and makes it difficult for neuronal cells to communicate with one another and function on their own. And it ultimately leads to cell death. And ketogenic diets have shown direct ways that they provide neuroprotective and anti-inflammatory benefits in human beings (not just animal studies).

Being that you are a human being, I submit this for your consideration in evaluating all the different options you have for feeling better.

Conclusion


A ketogenic diet is a viable option for those with Generalized Anxiety Disorder (GAD) as a treatment modality of consideration. Its effects in improving or treating brain hypometabolism, balancing neurotransmitters and improving neuronal function, and protecting the brain from oxidative stress and neuroinflammation are all mechanisms based on the scientific literature. These are also factors seen in populations suffering from Generalized Anxiety Disorer (GAD). The ketogenic diet may be a good option as a primary or complementary therapy that includes psychotherapy and./or medications. It can also be considered as a treatment for those wanting to avoid medications, for those whose medications are no longer working well, or who would like to take less medication in an attempt to reduce side effects.

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

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