How could a ketogenic diet help treat the symptoms of Panic Disorder (PD)?
Ketogenic diets modify at least four of the pathologies we see in panic disorder (PD) and panic attacks. These pathologies include glucose hypometabolism, neurotransmitter imbalances, inflammation, and oxidative stress. A ketogenic diet is a powerful dietary therapy that will directly impact these four underlying mechanisms seen in panic disorder (PD) symptomatology.
Table of contents
- How could a ketogenic diet help treat the symptoms of Panic Disorder (PD)?
- What are the neurobiological changes seen in Panic Disorder (PD)? Where are possible pathways of intervention?
- Hypometabolism in Panic Disorder (PD)
- Panic Disorder and Neurotransmitter Imbalances
- Panic Disorder and Oxidative Stress
- Inflammation and Panic Disorder
In this blog post, I am not going to outline the symptoms or prevalence rates of panic disorder. This post is not designed to be diagnostic or educational in that way. If you have found this blog post, you know what panic disorder is, and likely you or someone you love may already be suffering from it.
If you have found this blog post, you are looking for panic disorder treatment options. You are trying to find ways to feel better and heal.
By the end of this blog post, you will be able to understand some of the underlying mechanisms going wrong in the brains of people suffering from panic disorder and how a ketogenic diet can therapeutically treat each of them.
You will come away seeing a ketogenic diet as a possible panic disorder treatment for your symptoms or as a complementary modality to use with psychotherapy and/or medication.
It is not medical heresy to write the above statement. Why would we not consider using a ketogenic diet in place of psychopharmacology for panic disorder? Medications used for panic disorder include selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Early panic disorder treatment may include benzodiazapenes. After 4 to 6 weeks you could be put on any combination of medications with a stunning array of potential side effects.
In many cases, a significant proportion of those suffering from PD shows little or no response to standard pharmacotherapies, CBT and/or their combination. Many people continue to suffer from residual symptoms that significantly impair functioning.
So why would we not consider alternative ways to treat panic disorder? When the rates of panic disorder treatment success using psychotropic medications with or without Cognitive-Behavioral Therapy (CBT) are so poor? CBT works to also change brain chemistry, all by itself. CBT is definitely an evidence-based treatment for panic disorder (PD). But why would we not consider alternative ways to change our brain chemistry and fix underlying pathological factors, with or without the benefit of psychotherapy?
We are told the only viable, science-based options are the standard of care. If there are no specific Randomized Controlled Trials (RCTs) yet looking at ketogenic diets and panic disorder (PD) in this specific combination, we are told it is not really a treatment option. That somehow, everything we know about how ketogenic diets work, the underlying mechanisms already identified, and the symptom profiles we have identified in panic disorder are completely unrelated logically in the absence of an RCT. And we are to wait for funding of such RCTs to occur in an environment that primarily funds research when there is psychopharm profit to be made.
What if there are people whose panic disorder symptoms are better on medication, but the medication side effects have their own significant burdens? Must they stay with the standard of care? What about those 20% of people who suffer from the terrible symptoms of panic disorder and have not been helped with medications and/or psychotherapy combinations. Shall we tell them they should just “hang in there” until Big Pharma catches up with an RCT they will not be financially motivated to make happen?
I think not.
What are the neurobiological changes seen in Panic Disorder (PD)? Where are possible pathways of intervention?
A previous post went into detail about how a ketogenic diet can modify symptoms of anxiety by affecting four areas of pathology seen in these disorders.
- Glucose Hypometabolism
- Neurotransmitter Imbalances
- Oxidative stress
In panic disorder (PD) we see not only some hypometabolism between brain hemispheres but also hyperexcitability suggestive of significant neurotransmitter imbalances. The research also informs us that the panic disordered brain suffers from inflammation and oxidative stress. Let’s review each of these.
Hypometabolism in Panic Disorder (PD)
Actually, yes. We do see hypometabolism occurring in certain brain structures in people with panic disorder (PD).
Abnormal left/right (L/R) hemispheric ratios of regional cerebral glucose metabolic rates (rCMRglc) (hippocampus and inferior prefrontal cortex) have been noted in unmedicated panic disorder patients.Nordahl, Thomas E., et al. (1998) https://doi.org/10.1016/S0006-3223(98)00026-2
Pay attention to that part about WHERE we see the hypometabolism in panic disordered brains. The hippocampus and the prefrontal cortex.
How does a ketogenic diet treat hypometabolism in panic disorder?
Neurons, oligodendrocytes, and even astrocytes have the ability to take in ketones as a fuel source. This is very important for brains that for whatever reason, are not using glucose well as fuel anymore or are just not able to meet energy demands. When a brain is using ketones as a primary fuel (and yes, there are some parts of the brain that need glucose provided by the liver, but not dietary glucose) it makes that brain more energy efficient. There are fewer steps and less energy needed to utilize ketones for energy than glucose. This helps a hypometabolic brain, one that is not using fuel well, be able to upregulate brain energy.
In humans, both acute and chronic increases in ketone body availability to the central nervous system cause massive changes in cerebral fuel metabolism.Jensen, N. J., Wodschow, H. Z., Nilsson, M., & Rungby, J. (2020). https://doi.org/10.3390/ijms21228767
It is interesting to note, and now fairly well-known, that seizure disorders have been treated using the ketogenic diet for decades. The symptoms of panic disorder are so similar to those seen in some seizure disorders that differentiating between the two is of diagnostic importance in the field of neurology. For example, both temporal lobe seizures and panic disorder share the following symptoms:
- chest pain
If a ketogenic diet can be used to treat the symptoms of seizure disorders, why would it not be beneficial in panic disorder, which shares many of the same symptoms? Why wouldn’t we consider it?
Remember the parts of the brain found to have hypometabolism in panic disorder? The hippocampus and the prefrontal cortex.
Ketogenic diets enhance something called mitochondrial biogenesis. Mitochondrial biogenesis means that cells make more of their own batteries and create more energy. Ketones also elevate ratios of substances (phosphocreatine/creatine) that improve hippocampal metabolism.
Ketogenic diets improve symptoms of Alzheimer’s and other neurodegenerative diseases. Neurodegenerative diseases have many areas of the brain that suffer from hypometabolism. One of those very important areas is the prefrontal cortex. If ketogenic diets are used to improve hypometabolism in brain structures such as the prefrontal cortex in neurodegenerative diseases, why are we not using it for panic disorder, which also shows hypometabolism in the prefrontal cortex?
I would argue we absolutely can. And I have seen clients in my practice who have improved significantly using the ketogenic diet for panic disorder treatment, and even more so with the addition of Cognitive-Behavioral Therapy (CBT) in conjunction with ketogenic dietary therapy.
Panic Disorder and Neurotransmitter Imbalances
We actually see over-activation in the right amygdala, left and right insula left inferior frontal operculum, and left inferior frontal gyrus when we attempt to use behavioral extinction (the B in CBT stands for Behavioral) on various anxiety-provoking stimuli compared to healthy controls.
There is strong evidence for the importance of serotonin in the neurobiology of panic disorder (PD). In panic disorder, we see issues with serotonin binding to receptors and studies generally confirm that serotonin is inhibitory of symptoms in panic disorder. There are “functional and clinically relevant alterations in various elements” of the serotonin system that affects the neurocircuitry of panic (Maron, E., Shlik, J., 2006). There are also theories that the functioning of norepinephrine, dopamine and gamma-aminobutyric acid (GABA) neurotransmitter systems play a role in panic disorder symptoms.
In addition to serotonin imbalances, we also see problems in the use of norepinephrine in panic disorder (PD). There is a hypersensitivity in the presynaptic activity of norepinephrine in those with panic disorder (PD) and this is that is believed to be a factor in the expression of PD symptoms. Dopamine plays a role our experience of unconditioned fear responses. While there is not a large literature specific to panic disorder and dopamine neurotransmitter imbalances, we definitely see them in the expression of other anxiety disorders. Both dopamine D1 and D2 receptor mechanisms are important in mediating anxiety and we see a wide distribution of dopaminergic innervation over structures responsible for fear-related circuitry in the brain. Dopamine balance has an important role to play in panic disorder treatment.
How does the ketogenic diet help treat neurotransmitter imbalances in panic disorder (PD)?
We see hyper-excitability! The neurotransmitter balancing effects of a ketogenic diet are all the more important for the panic disordered brain. Reviews of the literature looking at neurotransmitter balancing in animal studies have shown improvements between glutamate (excitatory) and GABA (inhibitory) balances.
Neurotransmitter function was frequently reported in the included studies as a change within the nervous system favouring a reduction or restoration of normal levels of neuronal excitability.Field, R., Field, T., Pourkazemi, F., & Rooney, K. (2021). doi:10.1017/S0954422421000214
Glutamate has been shown to play a fundamental role in the onset of anxiety-related disorders. While increases in the availability and function of GABA have been shown to decrease panic. For example, your psychiatrist may prescribe you a GABA reuptake inhibitor, hoping to allow the GABA you are making to hang out longer between cells. This increased availability of GABA for longer will be used to hopefully keep your brain from reaching a state of panic (panic attack).
This is well-intentioned but short-sighted. A GABA reuptake inhibitor will not help fix the other ways your brain is not functioning the way a ketogenic diet can. A GABA reuptake inhibitor will not influence brain structure hypometabolism, overall neurotransmitter balance, oxidative stress, and neuronal inflammation. But a ketogenic diet does.
When we look at the effects of the ketogenic diet on dopamine balance and function we see beneficial effects. We know that dopamine plays a role in learned and unlearned fear responses, which are relevant to the symptoms that people with panic disorder endure. A ketogenic diet is shown to influence dopamine receptor activity through its ability to influence the expression of an inhibitory neurotransmitter called adenosine. Issues with dopamine receptors (D1 and D2) are seen in panic disorder (PD) specifically. But luckily, the ketogenic diet exerts what appears to be a beneficial influence on the dopaminergic systems involved in anxiety.
How does improved cell membrane function contribute to improved neurotransmitter balance with the ketogenic diet?
Ketogenic diets improve cell membrane function. As we learned here in a previous post, improved cell membrane function leads to improved sensitivity to neurotransmitters.
It leads to decreased hyperexcitability and improved enzyme reactions. Enzymatic reactions are needed to make neurotransmitters, keep neurotransmitters around the right amount of time, and degrade them appropriately.
Improvements in neuronal cell membranes mean improved neurotransmitter binding to receptors. This matters to people with panic disorder because people with panic disorder (PD) show poor binding of serotonin to receptors. This means their brain cannot use serotonin as effectively as they would if their neuronal membrane health was working properly.
But wait, you say. When I look at the literature you pulled in your reference list, I see that there are genetic predispositions to panic disorder. That some of these issues with serotonin binding are because of my genes!
I need you to understand that ketone bodies turn genes on and off.
Ketones are known signaling bodies able to turn genes on and off, influencing the expression of genes all up and down their pathways of expression. . That’s right. I am not exaggerating in the least. Your genes are not your wellness destiny. There is something called epigenetics, meaning internal and external factors can turn genes on and off. Ketogenic diets have been shown to modulate genes for neurotransmitter production and function and synaptic transmission in a very beneficial way.
Ketogenic diets are also seen to upregulate serotonin and balance levels of other neurotransmitters like GABA, glutamate, norepinephrine, and dopamine. And not in a way that can make too much of any given one of these, and then give you weird side effects. Ketogenic diets help your brain make just the right amount of neurotransmitters and allow your brain to use them well.
There are no side effects when a ketogenic diet balances your neurotransmitters and improves your neuronal functioning. Medications often come with side effects that are bothersome or challenge long-term health and then lose efficacy over time. For this reason alone, ketogenic diets should be considered a favored or even preferred treatment for panic disorder and other psychiatric and neurological conditions.
Panic Disorder and Oxidative Stress
Oxidative stress is the impairment of cell membrane functions due to insufficient antioxidant capabilities to deal with free radical damage. Those with panic disorder have been found to have higher oxidative stress levels than normal controls, with the highest levels of oxidative stress seen in those who have panic disorder with agoraphobia. Disease severity in panic disorder is positively correlated with serum levels of markers showing higher oxidative stress.
We do not know the extent to which oxidative stress contributes to specific clinical symptomatology of psychiatric disorders, let alone specifically panic disorder. The causal role of oxidative stress in anxiety disorders is still being figured out. Finding out the causal role will be important for early treatment and target for preventative intervention.
But if you have panic disorder we know you have higher markers of oxidative stress. And even higher markers of oxidative stress if you suffer from panic disorder with agoraphobia. Is it too late to target oxidative stress for intervention? Absolutely not.
Ketogenic diets and oxidative stress
Remember how in prior sections of this blog we discussed how ketone bodies were signaling molecules? That ketones are able to turn some genes off and some genes off in a variety of cellular functions? Well, that is a big part of how ketogenic diets help reduce oxidative stress. One ketone body, in particular, β-hydroxybutyrate (BHB) upregulates antioxidant defenses to combat inflammation and free radicals.
β-hydroxybutyrate functions as a stress response molecule and orchestrates an antioxidant defense program to maintain redox homeostasis in response to environmental and metabolic challengesRojas-Morales, P., Pedraza-Chaverri, J., & Tapia, E. (2020). https://doi.org/10.1016/j.redox.2019.101395
So what can the ketone body BHB do for the oxidative stress of panic disorder? Perhaps a better question is what can’t these little ketone bodies do when it comes to upregulating our antioxidant capabilities.
BHB works to protect your brain against oxidative stress through direct and indirect mechanisms such as:
- being an antioxidant for hydroxyl radicals
- suppresses mitochondrial reactive oxygen species (ROS)
- activates SEVERAL antioxidant programs through different gene expressions
For those that want to nerd out on these direct and indirect mechanisms, there is a great article here.
Inflammation and Panic Disorder
Chronic inflammatory markers are seen in those with panic disorder. Chronic inflammation is like a slow burning fire, pumping out various inflammatory substances that do cellular damage and affect cell function. These substances are often referred to as inflammatory cytokines. Inflammatory cytokines are found to be so consistent in those with panic disorder, that there are suggestion that they be investigated as a potential causal factor.
Systemic inflammation can access the brain, and enhance pro-inflammatory cytokine levels that have been shown to precipitate direct and indirect neurotoxic effects.Won, E., & Kim, Y. K. (2020). https://doi.org/10.3390/ijms21186546
Untreated chronic inflammation ages the brain and causes negative changes in brain structure, function, and connectivity of prefrontal and limbic structures. Prescriptions of SSRI’s have some mild anti-inflammatory properties, but in severe panic disorder where we see higher levels of inflammation, a case could be made that the effects are insufficient.
Ketogenic diets for Inflammation
Ketogenic diets as a treatment for panic disorder could be beneficial because ketones offer anti-inflammatory and neuroprotective properties. It is almost as if our bodies planned for ketones to come to the rescue. Our neuroinflammatory cells already come with receptors (HCA2) to take in the completely endogenous (your body makes it) neuroprotective ketone body β-hydroxybutyrate (BHB)!
Ketone bodies act as signaling molecules that inhibit inflammation pathways, turning genes on and off along the way to accomplish this aim.
Ketogenic diets also help treat inflammation by improving metabolic health. The elimination of refined carbohydrates and reduction in carbohydrate intake overall leads to less metabolic stress on the body by treating hyperglycemia (high blood sugar) and hyperinsulinemia (insulin chronically high and causing cells to not burn glucose properly). Metabolic disorders can occur in people who do not yet have a Type II Diabetes diagnosis from their doctor. You can be thin and have a metabolic disorder. Ketogenic diets keep you metabolically healthy, which reduces your risk of increased oxidative stress.
The ketogenic diet is an effective intervention to treat glucose hypometabolism, neurotransmitter imbalances, oxidative stress, and neuroinflammation. These are all pathological states we see present in panic disorder (PD). People suffering from panic disorder should be given the option of a ketogenic diet as a primary or complementary treatment protocol that can include medication and/or psychotherapy as the client so chooses.
While the standard of care should always be offered to you, as someone who suffers from panic disorder, it is important for you to know other options that are also evidence-based. So you can make informed decisions regarding their care.
You have a right to know all the different ways you can feel better.
The ketogenic diet is one of them. And it is important to me that someone communicates that to you so you can make informed decisions about your treatment.
I want to encourage you to learn more about your treatment options from any of the following blog posts. I write about different mechanisms in varying degrees of detail that you may find helpful to learn on your wellness journey. You may enjoy the Ketogenic Case Studies page to learn how others have used the ketogenic diet to treat mental illness in my practice. And you may benefit from understanding how working with a mental health counselor while transitioning to a ketogenic diet can be helpful here.
Share this blog post or others with friends and family suffering from mental illness. Let people know there is hope.
You can learn more about me here. If you would like to contact me you may do so here. If you just have a simple question please do not hesitate to reach out. I am excited at the potential of you feeling well!
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