Mental Health Plartform.

Can keto treat my depression without medication?


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


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).

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.

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. .

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.

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.

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).

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.

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.”


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!

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