S3:Ep29 – Optimizing Our Three Brains to Improve Migraine


Voice-over: Welcome to Spotlight on Migraine, hosted by the Association of Migraine Disorders. Join us for fresh perspectives by medical experts and advocates as we explore the spectrum of migraine and dig deeper into this complex disease.

In this episode, Dr. Trupti Gokani briefly describes the connection between migraine and the gut. Dr. Gokani also explains the responsibilities of our three brains — the thinking brain, the feeling brain, and the doing brain — and how each one can be optimized to improve migraine.

This episode is brought to you in part by our generous sponsor, AbbVie.

Dr. Trupti Gokani: Hello, everyone. I am so grateful and thankful to be able to present “Optimizing Your Three Brains to Improve the Migraine Condition.” My name is Trupti Gokani. I’m a board-certified neurologist, director of the Zira Mind and Body Center. First, I’m going to discuss migraines and the gut, and then I’ll get into our three brains and then take you into the goals of optimizing these three brains to create harmony, specifically looking at the migraine condition.

What do we know? Well, we know a lot, my friends. When you look at the facts, 90 percent of those with migraine have nausea. Seventy percent have vomiting with their attacks. Constipation is a common complaint in those who have migraine. Fifty-four percent of those with migraine have IBS, irritable bowel syndrome. Migraine individuals suffer with stasis during and in between their migraine cycles. Migraine individuals struggle with dysmotility-like dyspepsia. And the theme here is that migraine patients have impaired gut function during and in between the attacks of pain.

So my question to you all is, What can we do about it? We know that 70 percent of individuals with migraine respond to triptans, right? Yet combination therapy has been used for decades because not everyone responds effectively, and each time, with their attack, do they have the same response. And it’s interesting because when you look at this combination therapy, tools such as metoclopramide, a promotility agent, has been used with ergots to allow faster gastric absorption and better outcomes with pain, proving that there’s a gut-brain connection here.

For those of you that have been in this space for a while, you remember the RRT technology? Sumatriptan, as it shifted over the years from injectable, nasal spray, oral tablet, there was an understanding that it was inconsistent, not always working. Thus, RRT, rapid release technology, was developed to help the medication become more absorbable at the gut level.

So this was done because there’s an understanding of the gut link to pain. So as individuals started to realize that the triptans weren’t always consistent, they may not have always worked, and other agents may have augmented [inaudible], practitioners started changing, right? You saw providers and yourself and myself included transition to augmenting triptans with nonsteroidal anti-inflammatories like naproxen to get rid of the pain, to break the acute cycle of pain.

Yet, now that we’re in this space and we’ve been doing this for a while and we’ve seen what’s happened with these pharmaceutical medications, those meds have an effect on the system as a whole. Even though we’re targeting the acute pain, we’re having longer-lasting effects on the digestive system, on the liver, on the kidneys, because of the untoward effects of those add-on medications.

So we must ask ourselves, “Are we doing more harm than good?” especially when we’re creating rebound because the medications are not adequately treating the pain or the meds are leading to further need of medications to quiet the pain down. So it is a time to look at all that we’ve done and ask ourselves, “Can we do better?” And I do believe we can.

So digestive symptoms do occur with migraine. When you think of your migraine patients, I’m sure you’ve heard them come in complaining of reflux, burning, and acid, and maybe they’re taking over-the-counter PPIs or getting a prescription for them. They have nausea — that’s part of migraine — and maybe they’re taken the Phenergan or Zofran often to quiet down the nausea.

Are those two things safe for them to be doing, taking proton pump inhibitors and nausea medications? How about those that have these different infections? I just had a patient with UTIs, recurrent UTIs, who had been on six months of antibiotic therapy for her UTIs. What do all of these meds have? What effect do they have on the gut?

And if we know there’s a gut link to migraine — I think of that Steven Covey quote from The 7 Habits of Highly Successful [sic] People, “Begin with the end in mind.” It’s the second habit. If we’re allowing patients to continue to take these products, what’s going to happen 5 to 10 years down the road?

So let’s think about the migraine-specific medications that are now on the market, specifically the CGRP antagonists. We understand that some of them work on the receptors. Some work on the ligand. Some are for acute treatment. Some are for prevention. What is the effect of these medications with the gut?

Because you want to ask yourself whenever you’re prescribing and whenever you’re monitoring medications, even if they’re medications that you are not prescribing — maybe the primary care doctor’s prescribing these medications — “Are these medications helping or hurting?” Are they doing more harm or good for the patient when you’re not looking just at the acute but long-term effects of these medications?

And this is why we need to focus on a bigger picture, not just focus on the acute pain. Yet think of the risk of long-term effect of medications. And it’s not that we won’t use these tools. Yet can we use them more wisely by thinking about the bigger picture and thinking about the entire spectrum of pain?

So, over the years, as we focus on the pathophysiology of migraine, I think many of us are comfortable with this picture, looking at the acute-medication targets on the right, specifically thinking about triptans, binding the type 1B and D serotonin receptors at the blood vessel, binding to the nerve endings, and blocking that neuropeptide release, CGRP, especially. And these triptans work in the brain stem serotonin type 1D receptors in really quieting down that central sensitization, and preventative medications really quieting that wind-up of the brain, blocking all of these important — like glutamate, and quieting down the excitable brain to prevent headaches from coming on.

Yet when you really think about the pathophys of migraine, we’ve spent a long time on the first brain, a lot of time on the acute and the prevention targets, focusing on the first brain, that central nervous system that’s within the head. Well, I’m going to ask you to start allowing yourself with me to think about a bigger picture. 

Hippocrates said thousands of years ago, “All disease begins in the gut.” And if all disease begins in the gut, then maybe we need to expand our view of migraine outside of the central nervous system and the brain and think about a more expansive three-brain model, which is what I’ve created here. 

So the first brain, as we know, is the central nervous system, including spinal cord, and the second brain is the enteric nervous system. The third brain is the microbiome. And we’re going to go through each of these.

So when you think about the first brain, that’s the thinking brain, OK? Of the three brains, that’s the thinking brain. And that, as I mentioned, is the central nervous system and the spinal cord. The second brain is the feeling brain, and that’s the enteric nervous system. The third brain, I call it the “doing” brain. It’s the microbiome. And after two decades of working with migraine patients, I’ve learned that all three of these brains play a role in the pathogenesis of migraine, and we’ll go through each one and how to optimize each one.

So let’s start with the first brain. So when you think about the first brain, the central nervous system, there’s the neocortex, which is the prefrontal cortex. It’s the thinking brain, right? It’s the part of the brain where — kind of allowing ourselves to operate, the center of executive function and regulation of hormones and regulation of our system, movement, and sensory body.

Well, there’s the left and the right side of the brain. Remember, the left brain is that logical, very analytical part of the brain, and the right side is that creative, artistic part of the brain. The goal is to create balance in the thinking brain, have our thoughts be in alignment with us, work for us, not against us, have our right and left hemisphere be in alignment for who we are, for our nature, for the way we’d like to live.

The limbic brain is what I call the emotional thinking brain. It’s that ancient brain, the hypothalamus, the amygdala, the storage of fear. It is basically the storage center of all your emotions, early life trauma that has happened. That goes into that area. It’s linked to the drives that we have for food, for sex, for control. It’s connected to our five senses.

Now, the reptilian brain, it’s the part of the brain that aligns us with the reptiles. And the reptilian brain is there, thank goodness. It keeps us surviving, right? It allows us to maintain our heartbeat and our rhythm and maintain digestive function without really thinking about it. It’s that automatic part of the brain.

Well, the goal is for the limbic brain to also have harmony, harmony of emotions, for the reptilian brain to be in harmony and to maintain our physiology, yet not turn on too often and too quickly and for too long. So, within the first brain, the neocortex, the thinking brain with the thought brain, along with the emotional brain and the reptilian brain, all should be aligned for our first brain to be operating coherently.

Unfortunately, for a lot of migraine patients, that doesn’t happen. We’re all exposed to external events, and you could think of the external events being anything that are really kind of in your awareness. And what happens is that we are exposed to 2 million bits of information per second. Yet our system — because the five senses takes all this in — our system can only take in about 126 bytes of information of the 2 million. We’ve got to distort, delete, and generalize, clear some of that information coming in up, so we can only process what we feel is important for our needs.

Now, I’m going to ask you something. Think about what you take in and what I take in. If we’re looking at the same scene, the truth is what you’re going to pick up is going to be different than what I pick up because we have different filters. We’re brought up with a different environment. We have different programs. 

What I’ll tell you is the thinking brain allows you to perceive what you perceive as dangerous and alert your system if it needs to turn on the reptilian brain or not based on your program. And this is where I find it fascinating because a lot of migraine patients have an internal representation. They have an interesting filtration system where they pick up danger a lot more than those that do not have migraine. 

So let’s think about this thinking brain a little bit more, the first brain, and specifically with response to treatments. You’ve all heard of the nocebo and placebo response. Take a moment and think about who are the ones that are able to mount that placebo response. We’ve all seen the studies with different pharmaceuticals that come to market, and we’re like, “Wow, look at that placebo group.” And, isn’t it interesting, with the pain individuals, they tend to mount a really high placebo response. Well, who are they, and why are they allowed to do that? And how come not everyone mounts a placebo response?

How about those that have a nocebo effect? You’ve seen that. You give them something, and they have this really interesting outcome, and you’re like, “I’ve never seen that before.” How come they developed twitching and tingling and a headache and all these things, where you haven’t seen that in other patients? And maybe there’s a little bit of a nocebo effect. Maybe they were worried about the effect of that medicine, and they created that response. How about those individuals?

And how about those that are unable to create a placebo response due to previous failures or treatments? So if you’ve failed a lot of medications, you’re less likely to respond to prescriptions. And why is that important? 

Well, I’m going ask you, What is the belief system your patient has around pain and about treatments? This is all part of that first brain thinking and the program they have. If they believe that the meds won’t work, quite frankly, they may actually not respond to medications you give them. Isn’t that important for us to think about, this first brain?

How about their belief system of the world? What if they believe the world is a dangerous place, and they perceive everything as dangerous, and they’re always on, they’re always active, their adrenal system is always mounting cortisol response? How do you think they’ll respond to a change in weather? Probably seeing that fluctuation in barometric to be perceived as danger for them. 

How about take it even bigger? Maybe they view the world as not being trustworthy. Maybe they think, “Will I even be able to be taken care of by this provider, because everyone else has failed me?” All of this comes into the outcome you’re going to have with that patient in terms of their response to prescriptions, their response to all the modalities you offer them, even a dietary change recommendation. The first brain has a huge effect.

So who’s in control? The first, the second, or the third brain, right? Who’s really in control? Well, the central nervous system is really a control center in many cases, directing the action of the end organs, right? 

So when you look at some studies, short-term stress can impact the microbiota in as little as two hours. The brain regulates the motility of the gut, the secretion of stomach acid, the mucus layer, and the biofilm production where bacteria grow. And look at this: norepinephrine released during surgery can lead to growth of pathogenic pseudomonas, meaning surgical stress can change the microbiome. 

Now I want you to think about this. Under stress, your blood flow shifts. Normally, when we’re in a relaxed state, when at rest-and-digest state, blood flow is nicely flowing to the gut. Yet when we start to perceive danger, blood flow shifts from the gut to the extremities because you’re supposed to run from the bear.

So what happens when you eat and your mind is not in harmony? I don’t know, you’re watching something stressful on TV, or you’re having a stressful conversation at the dinner table. Thirty percent of your digestion is called cephalic digestion. It’s happening at the thinking-brain level. And yet I don’t believe we spend enough time talking to our patients about the importance of how healthy their thoughts are and how healthy their first brain is. And, to me, it’s a very important area to assess, especially for those patients that are challenging their treat.

So here are the goals for first-brain optimization. Shift the internal representation to balance and quiet that reptilian, reactive brain — improve the prefrontal and enhance the prefrontal cortex to be in alignment with the system so that what they’re perceiving is working for them and not against them. The patient isn’t always perceiving danger, because that’s going to affect the second and third brain, which we’ll get into. 

Creating coherence of the right and left hemisphere is really important. I feel a lot of patients I meet are left-hemisphere dominant, too logical, too intense, too perfectionistic, very on-alert, and high-intensity. And that, unfortunately, creates a program which then turns on the reptilian brain and impairs gut function. And if the gut is the origin of disease, we’re going to have a hard time improving the gut when the first brain is off. 

So the goal is to evaluate which patterns of thought are leading to challenges in work, home, family, relationships, and thus leading to a brain in conflict. And I use techniques such as meditation. I work with language patterns. Patients say, “I must. I have to.” If you notice that, that’s coming from the reptilian brain. And having them even recognize that pattern of operation, that pattern of “languaging,” can actually shift them out of that pattern of thinking and move them more to prefrontal balance-framed behavior. 

Hypnotic techniques — see, I’m trained in hypnotherapy now — can actually help shift the mind program. And I find it fascinating to actually allow patients to shift out of that way of thinking to balance out the first brain. I believe that migraine really is a brain in conflict, and the goal is to create harmony of the first brain and then to balance out the second and third brain. 

So, the second brain. What’s really fascinating about the second brain is it’s the brain that’s been forgotten. It’s the enteric nervous system. Now, there are two sets of nerves that help maintain the gut functions. We’ve talked about the central nervous system. Now we’re getting to the enteric nervous system. 

And as we talked about, the central nervous system is made up of the brain and the spinal cord — the first brain and the spinal cord, specifically. The enteric nervous system is intrinsic to the digestive system. It’s the gut-brain. It’s actually that brain that’s sitting there within your gut. It’s made up of 200 to 600 million neurons. It’s incredibly dense, and it’s a really rich source of neuronal activity. 

Why is the enteric nervous system considered to be the second brain? Well, get this: if you disconnect the first brain and the gut through a vagotomy procedure — cutting the vagus nerve — it does not stop the gut from working autonomously. Can you believe that? The enteric nervous system can still work even if you disconnect it from the brain in your head. It’s fascinating. 

The gut, the enteric nervous system, is the only organ which contains an intrinsic nervous system that is able to mediate reflexes in the absence of input from the brain and the spinal cord. Isn’t that fascinating? The first brain doesn’t need to be in control of it. It kind of works on its own. 

The gut really has a mind of its own. And the belief was that the autonomic nervous system has two divisions, sympathetic and parasympathetic. Yet there’s this belief that there’s actually a third division, which is the enteric nervous system — the sympathetic, parasympathetic, and the enteric — because it’s that vast and that dense in terms of neuronal activity.

They’re systems that are fascinating because when you see the sympathetic and parasympathetic nervous system, it is actually directly connected to the gut through the vagus nerve. The enteric nervous system, because it’s part of the autonomic nervous system, it is actually believed that the enteric nervous system is a peripheral extension of the limbic brain, the emotional brain. So that ancient brain, the limbic brain, which is really the regulator of our emotions, it is really believed now that the limbic brain, its peripheral extension is the enteric nervous system, which sits within the gut. Isn’t that fascinating? 

When you think about the second brain, I’d like you to think about it as the feeling brain because it’s connected to our intuition and, as I mentioned, our emotions. Have you ever had a gut feeling? How about butterflies in your stomach? Yeah? Well, that’s the vagus nerve, and it conveys visceral information to the brain. We call that bottom-up. And 90 percent of its fibers send information from the gut to the first brain, versus from the first brain down to the gut. Isn’t that fascinating? 

So when you think about it — ha ha, where are you thinking from? — the gut is actually talking to the first brain quite a bit. There’s a lot of conversation, and a lot of it’s happening at almost a subconscious level. We’re not even aware of it, but it’s happening. We’re perceiving things around us. We’re reacting to things around us. We’re feeling, Do we like a situation? Do we not like a situation? Do we not like a person or a food item? It could be anything. And this is the origin of the gut instincts.

And asking our patients, “Hey, do you follow your instincts? Do you follow your gut instincts?” So if you’re talking to someone that you feel isn’t really harmonious with you, do you step away from the conversation or do you continue to engage? If you’re in a job that you don’t think is serving you, do you stay with the job or do you move on? 

Ayurveda, which believes that the cause of disease is something called pragyaparadh, which is a mistake of the intellect, meaning that we choose things and we do things not in alignment with our gut intuition. And the belief in Eastern medicine or Ayurvedic medicine is that if we can get connected with our gut intuition, we can actually start to make better decisions for ourselves and live in alignment and, according to Ayurveda, reduce disease. 

An imbalanced second brain leads to a lack of intuition because if you’re having imbalance — meaning you’re really angry, you’re anxious, you’re depressed — you’re not able to connect with the intuition because the emotions overwhelm you and don’t allow you to get connected with your intuitive center. And there’s actually data to prove this. 

There’s a study that shows that intuition is not perceived for those that have depression. There’s even rat studies looking at disconnection of the vagus nerve to the gut leads to less innate fear — that fear of open spaces — and longer retention of learned fear from the past. The vagus nerve helps send signals of danger to the brain.

And we can modulate that response by doing what? Oh, I don’t know, some deep breathing, positive self-talk, change the language patterns. The gut vagal afferents help us recover from previous learned fearful situations. So even if you’ve had trauma in the past, you can enhance this pathway, enhance the vagal pathway, to really reduce that limbic energy, to reduce that amygdala, to reduce the stored emotions that are holding us back from connecting with our intuition.

So if you’re in a grounder [sic], calmer state when you enter a fear-provoking situation, your gut will send less signals of danger to the brain. Isn’t that fascinating? And some more data is showing that the gut-amygdala axis — remember, the amygdala is a storage center for your emotions, right? The gut-amygdala axis may be of importance linking the stress system to migraine predisposition. We’re starting to see how early trauma and all the stored emotion can actually increase and predispose people to migraines and even more chronic pain.

“So, second brain, how do you optimize it?” you’re probably thinking. Well, start with aligning — it’s interesting — aligning with your circadian rhythm. How do you do that? Well, getting to bed at the same time — Ayurveda loves a 10 pm bedtime — waking up at the same time every day.

Setting mealtimes — really important to establish the circadian rhythm because that starts to allow the emotional body and the intuitive center to come into balance, thus really quieting down the enteric nervous system and the vagus nerve. The vagus nerve likes peace. It likes regularity. It likes us to be in alignment with ourselves. And that actually helps the enteric nervous system balance out. 

Connecting with emotions — asking patients, “Hey, do you express your emotions? Do you have healthy expression of your emotions? Or are they trapped? Are they suppressed or repressed?” Helping them express their emotions is very important to helping clear the baggage of the enteric nervous system so they can connect with their intuition and actually improve their microbiome. We’ll see how that happens. 

Movement exercises like tai chi, yoga, even getting a massage, can actually help the enteric nervous system because we tend to store trapped emotions in our physical body. And doing meditation, compassion meditation, forgiveness meditation, really can help clear the second brain and balance it out, along with breathwork. When you think about all these brains, each one has an effect on the other.

Now, let’s go through the third brain. The third brain is the microbiome. It’s a complex community of microbes, mainly bacteria inside and on your body. It’s 100 trillion microbial cells that are in your gut. Yes, 100 trillion. And what’s interesting is our human body contains more microbial cells than human cells. I know that’s a scary thought, but, thankfully, the microbial cells are a lot smaller than the human cells.

It’s a complex organ — yes, it’s referred to as an organ — that’s responsible for development and function of other organs and systems. It’s determined by your genetics, yet also by your lifestyle, your nature, and what you do and how you think. The microbiome can be affected by your thought patterns, your foods, your sleep patterns. All of that can actually affect it along with your genetics.

It plays a role in vitamin synthesis. When you think about B vitamins, a lot of vitamins are actually produced. Vitamin K2, made at the gut level. Neurotransmitters — you’ve probably heard that 90, 95 percent of your serotonin is stored in your gut. Energy production occurs at the gut level. Digestion and fermentation of substances — really important role of the microbiome. And stimulation of the immune system — incredibly important to have a healthy microbiome so your immune system will be healthy. Seventy percent of your immune system is located within the gut. 

The microbiota are intimately connected with the GALT, the gut-associated lymphoid tissue. And what happens is the microbiome produces these metabolites. SCFAs are short-chain fatty acids. I bolded that because it’s so important. Secondary bile acids, tryptophan, for example, all these microbial metabolites, what they do is they interact with these cells called enteroendocrine cells and enterochromaffin cells. We won’t get to all that detail today, but just so you know, these metabolites interact with those cells to help with creating neurotransmitters and help with the operations of the gut. 

The metabolites actually also interact with the immune system. Yes, they interact with the immune system at the gut level and help the immune system either stay balanced or become provoked. If the bacteria are imbalanced, the immune system will be imbalanced. Some of those metabolites, like short-chain fatty acids, can actually cross the intestinal barrier and even the blood-brain barrier, thus having an effect there. And it’s really incredible to see. 

This is the healthy gut on the left side and the leaky gut on the right side. And what you’ll find is the healthy gut on the left, the very bottom is your bloodstream. And, really, what you find is that the colonocytes and the enterocytes, the gut lining is only one cell layer thick. And there’s those different enterocytes and colonocytes, and interspersed within them are those EECs and the ECCs — enterochromaffin and enteroendocrine cells — that are helping create the neurotransmitters I just talked about. And above that is the mucosal layer. And then above that — this is going into the gut, the very top of the picture — is the inside of the gut.

You have all the different bacteria, a lot of microbial diversity, if you have a healthy gut, on the left; and very low level of pathogens, again, if you have a healthy gut, on the left; and a really nice, thick blue mucosal layer. The right side, that’s the leaky gut. That’s the imbalanced gut. There’s low microbial diversity, a lot of pathogens. There’s a breakdown of the mucosal layer. The tight junctions on the left, that really tight junction that keeps the cells nicely tightly bound together, are loose and leaky.

So all of the inflammation, maybe there’s foods that haven’t been broken down, there’s toxins, there’s pathogens, can actually move their way into your circulation, trigger immune cells in your circulation, and create inflammation upwards and in your body, which is really interesting. That’s how the gut is the origin of disease, because, as we’re seeing, a lot of diseases are linked to inflammation.

One thing I have to go over is an endotoxin, and some of you may not know what an endotoxin is. It’s a toxin that’s produced within the body — most commonly LPS. It’s lipopolysaccharide. It’s a component of the Gram-negative bacteria of the outer cell wall, and it circulates at a low level in healthy individuals.

The challenge is when it starts to really get in a higher amount and move from within the lumen of the gut into the bloodstream, it becomes an inflammatory immunogen. And these endotoxins then create a whole systemic response system. You’ll see LPS being talked about with Alzheimer’s disease. A lot of neurodegenerative diseases now, there’s trying to see these links between the gut integrity, LPS, and disease. And it’s fascinating to start studying this and looking into this in migraine too.

So the gut microbiome, what we do know is that it interacts with the HPA, the hypothalamic-pituitary axis. There isn’t just one system working on its own. Every single system is talking to each other. So the first brain talks to the second, talks to the third, and upwards. An example, maybe, in this study, well, you’ll see stress and the perception of stress. The internal representation of stress from daily living induces endotoxemia by increasing gut permeability. So, yes, your thoughts can affect your health directly. 

There’s a bottom-up approach, too, third brain to the second and first brain. So, for example, dysbiosis, meaning if you tend to carry some not-so-healthy bacteria — I don’t know, maybe you’ve been on antibiotics for a long time, maybe you’ve been on proton pump inhibitors or different steroids, or your patients have been taking lots of these products — well, it can lead to dysbiosis.

And those bacteria can actually shift, and you can have more pathogens, and those bacteria can lead to this increased link to bacterial peptides inducing macrophages and T-cells to produce cytokines and LPS, and, hey, maybe even CGRP. Ha ha ha, we talk about that, and we know CGRP is present in the gut. So maybe the altered microbiome can actually shift the immune system in the gut, thus leading to an excess expression of these pro-inflammatory cytokines and create problems.

Low-level exposure — there’s a really interesting study of immune cells, those actual immune cells, to bacterial-cell-wall components. The LPS, for example, has an effect on sleep patterns. They found that these different cell-wall components, these breakdown of the cells of the bacteria that are floating around in excess, and that low-level exposure that’s there can actually affect your first brain, can affect your sleep patterns. There’s data to show that it can even affect your thinking and memory. Fascinating, fascinating data to show this.

So one thing I have to just share with you is the importance of food intolerances and migraines. This is something, it’s very dear to my heart because my daughter, when she was 5 — she’s 19 now — used to struggle with headaches. And I remember learning about food intolerances many years ago through my Ayurvedic and functional-medicine training. 

And what a food intolerance is — it’s not the same as a food allergy. A food intolerance is an IgG antibody response. It’s considered a delayed sensitivity reaction. It occurs between 4 to 72 hours after exposure to the food, so it can happen after a few days after exposure to the food. And, interesting, how long do migraines last? Four to 72 hours. Hmm, isn’t that interesting? 

It’s referred to as a hidden food allergy because people sometimes don’t even link the exposure of the food to development of a symptom, such as problems focusing or headache or neck pain or sleep issues. And what you find is that when there’s an excess of foods that are intolerant in the body, it can actually lead to symptoms that, yes, can be headaches, focusing issues, bedwetting, rashes on the body. These symptoms, even though they’re generated — the antibodies generate at the gut level, can actually affect the system as a whole.

I published this abstract in the Journal of Headache in 2012. And what I found — I looked at 500 patients — when you look at IgG reactions, moderate to severe reactions only are included. I’m not even including the mild to moderate reactions. These are moderate to severe reactions. 

What I found was that these groups — look at this — the dairy group, the grain group, and the eggs were the highest. Dairy — 60 percent of individuals had moderate to severe reactions. Grains, including gluten and other grains, about 50 percent. Eggs in 35 percent. Thirty-six percent had an egg intolerance. And this is looking at 500 patients, and what’s interesting is the reason it’s called “hidden” food intolerance, most people don’t even know that it’s triggering symptoms. 

Microbiota are so important. Those bacteria are so important. They actually metabolize those dietary compounds we just talked about. Mainly what they metabolize is carbohydrates, sugars, and they tend to digest ones that are not digestible to humans. And this is done through fermentation. 

And these specific foods are known as prebiotics. Different kinds of leeks and different types of plant fibers, they’re prebiotics. And what they do, they have high fiber. They actually get broken down, and they create energy for the cells. And these microbial metabolites that are produced from the bacteria of digesting the carbohydrates and creating metabolites, those metabolites serve as messengers throughout the gut and distant organs, like the brain, I mentioned earlier.

One of the most important ones is short-chain fatty acids. And it’s known as a short-chain fatty acid known as butyrate, and I’ll get into that in a moment. And this is probably the primary source of energy for the colonocytes, all those short-chain fatty acids. And, as I mentioned, butyrate is the most important one. And the reason why it’s important is it not only works locally within the gut; it actually crosses into the blood-brain barrier and has an effect there.

There’s some studies that actually show that Depakote may have an effect by creating a butyrate-type metabolite, which is interesting because if Depakote works for migraine and maybe it’s through this butyrate mechanism, well, if you can improve gut function, improve gut microbiome, and improve butyrate production at the gut level, hey, that may be a way to improve migraines without taking the Depakote. Kind of interesting, right?

Butyrate also has a really important role of maintaining that gut barrier integrity. Remember, I talked about the tight junctions getting loose and creating leaky gut? Butyrate actually improves the tight junction. It upregulates the melatonergic pathway, so there’s a link there. It has an anti-inflammatory effect in the immune system. It supports mitochondrial functioning and energy. So really important, important, important in the system.

So, big picture here. When you have impaired digestion, what ends up happening is — and why does digestion become impaired? Yeah, some of it could be genetic. Some of it could be toxin exposure, medications. We talked about foods that are really not tolerated well. Unfortunately, it could be stress. We talked about this earlier, thoughts.

And then, unfortunately, there’s a shift in the microbiome and then a reduction in short-chain fatty acids, neurotransmitters like GABA, serotonin, and, hey, maybe an increase in CGRP, and, boom, we have a migraine there. So, again, our goal is to get people over to the left, to the healthy gut, by using this approach, either first-, second-, and third-brain approach.

But the third brain, the goal here is to evaluate your patient’s microbiome and the presence of food intolerances. And this can be done in different ways. You could eliminate foods. You could do testing. I do a specific quiz. I’m happy to share with you this quiz that helps evaluate the three brains to see where the imbalance is and how much imbalance is in each of these brains, and maybe all three are imbalanced, and where to start with that. 

And then I incorporate foods and spices. What’s cool about spices is spices actually increase microbial diversity. So one of the things about Ayurvedic medicine is it’s important to have six tastes in every meal. The goal is to rebuild that leaky gut using whatever tools are comfortable to you. It could be having them take some ghee in every day. Another thing is to cleanse out toxins: toxic thoughts, holding on to baggage; toxic pathogens that are in the gut level — all of this creates disharmony of mind, body, and spirit.

Three brain questions I want you to think about as we close up. So the first one is, Where in the cortex does the thinking brain — your emotions and thoughts — have inputs into the stomach? Where does that occur? What pathways does the gut use to send abnormal proteins to the brain? How do the bacteria interact with the gut and influence well-being? If your bacteria are imbalanced, maybe you’re not making enough serotonin. So there’s so many levels we can work on: top down, bottom up. 

So my theory is that stress of migraine attacks and anticipatory anxiety has an effect on the microbiome leading to dysbiosis. Gut dysbiosis increases inflammatory cytokines and LPS. The first attack may have been influenced by imbalanced microbiome, foods, and stress; yet when the migraines continue, the first brain becomes involved. So keep all that in mind.

I’m going to ask you, Is there a genetic predisposition to certain types of bacteria in the gut predisposing to migraine? Hmm. Gut dysbiosis drives some of the central-sensitization processes linked to migraine with aura. There was a study on that. Microbiome was linked to our emotions, as we’ve gone through. The bacteria communicate directly with the enterochromaffin cells to produce serotonin.

How well do your migraine patients handle stress and their emotions, I ask? How balanced is the microbiota of those with migraine? A lot to think about, my friends. 

Migraine evolution is linked to imbalances which may or may not be obvious because these gut imbalances, quite frankly, my friends — food intolerances, digestive imbalances — a lot of individuals don’t even know they have an imbalanced gut. The first-brain thinking patterns and processing of external events influences pain and the second- and third-brain function. The second-brain emotional processing is linked to our intuition and ability to live in alignment. Optimizing all three brains leads to improvement in the migraine condition. 

If you’d like additional information, you can go to my website, TruptiGokaniMD.com.


Voice-over: Thank you for tuning in to Spotlight on Migraine. For more information on migraine disease, please visit MigraineDisorders.org.

*The contents of this podcast are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The speaker does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.