Passion Struck with John R. Miles - Dr. Scott Sherr on GABA: The Unsung Hero of Brain Health and Stress Resilience | EP 575

Starting point is 00:00:00 Coming up next on Passion Strike, GABA amino butyric acid is one of our primary inhibitory or relaxing neurotransmitters in our brain. And it's the unsung hero of the brain, John. Most people think of the superstar neurotransmitters when we're thinking about the brain or neurotransmitters in general. We're thinking about dopamine, norepinephrine, and serotonin. And these are important, obviously, but in much smaller quantities compared to how much GABA we have in the brain. Methylene blue itself actually works on a system called the monoamine inhibitory system. It actually prevents the breakdown of norepinephrine, dopamine, and serotonin. As a result of this, you get more of those neurotransmitters and you get a mood boost, you get more focused, a little bit more endurance.

Starting point is 00:00:48 But the key also is to. Welcome to passion struck. Hi, I'm your host, John R. Miles. And on the show, we decipher the secrets, tips and guidance of the world's most inspiring people and turn their wisdom into practical advice for you and those around you. and turned their wisdom into practical advice for you and those around you. Our mission is to help you unlock the power of intentionality

Starting point is 00:01:09 so that you can become the best version of yourself. If you're new to the show, I offer advice and answer listener questions on Fridays. We have long-form interviews the rest of the week with guests ranging from astronauts to authors, CEOs, creators, innovators, scientists, military leaders, visionaries, and athletes. Now, let's go out there and become passion struck. I am so excited today to welcome back my friend, Dr. Scott Schurr. Hey, Dr. Scott, how are you doing? I'm fantastic, John. Thanks for having me back.

Starting point is 00:01:46 It's good to see you. I have to tell you, you are now the only guest I have ever brought back three times. And I have to say on my YouTube channel, you have the most popular episode we have ever done. Is that right? And it was talking about methylene blue and nootropics. I know people are really intrigued by your works, just had to have you on again. It's a pleasure on that topic.

Starting point is 00:02:11 What advancements or insights have emerged in the use of nootropics since we last spoke? Well, I mean, the nootropics gives a big category in the sense of there's lots of different definitions that people use as to what a nootropic is and what it isn't. I think we actually dove into this a lot during our last podcast. If anybody's interested, they can go check this out.

Starting point is 00:02:33 There's things like health optimization nootropics and performance optimization nootropics. I've been very interested, as always, in the kind of integration of nootropics with more of a comprehensive understanding of mental health, physical health from a macroscopic scale, from what it looks like when you're talking to somebody or how you feel personally, but also from a microscopic scale, the vitamins, minerals, nutrients, and co-factors that are responsible for truly optimizing our cellular

Starting point is 00:03:03 biology. And then within that, I've been, a lot of my interest always and continues to be on mitochondrial health and how improving mitochondrial health overall is going to raise your cognitive and physical bar all the time so that maybe you don't need nootropics all the time, but maybe you can only use them in more of a targeted way rather than more comprehensively or more often depending on the situation.

Starting point is 00:03:27 And I know one of the key ingredients that people have been most intrigued about in your work has been methylene blue. And that's probably where we on that YouTube channel have gotten the vast majority of the questions. Have there been any shifts in how people are integrating methylene blue with lifestyle or diet to maximize its effects?

Starting point is 00:03:50 So it's super interesting. Methylene blue, as we talked about, it has been around a long time. But we're really starting to dial in the dosing of it, understanding that very low doses of this particular compound are fantastic for those mitochondria that we were just discussing. So what's interesting about the US right now is that 94% of the US population has some

Starting point is 00:04:12 element of mitochondrial dysfunction. This means that they cannot make energy effectively or they cannot detox with the energy that they make. So just to back that up for a minute for people, when you have these mitochondria in our cells, they are the powerhouse, they are what make energy. And so we have a lot of mitochondria in some types of tissue and very few mitochondria in other tissue. In fact, the most mitochondria we have per cell are in our ovaries or in our sperm, depending on our gender,

Starting point is 00:04:42 our brain, our heart, our liver, and our musculos muscular skeletal tissue. So in fact, I've talked to Gabrielle Lyons about this and she likes to remind everybody that you have your most mitochondria per cell in reserve actually in your muscle skeletal tissue so you can run when you need to run. Now the problem though is that if 94% of the U.S. population has mitochondrial dysfunction, this is going to show% of the US population has mitochondrial dysfunction, this is going to show itself in the various tissues depending on where those tissues are having the most effect

Starting point is 00:05:12 with that mitochondrial dysfunction. So is infertility an issue now, John? It's a huge issue, right? More and more people cannot get pregnant, men and women. And that's a major reason why is because of mitochondrial dysfunction. If you have issues with your brain, if you have concentration problems, fatigue issues, if you have difficulty with your memory or verbal fluidity when you're speaking,

Starting point is 00:05:31 this is all potentially a mitochondrial issue. So cardiac issues, detoxification issues, exercise-induced fatigue, this is all related to mitochondrial dysfunction. And so what methylene blue can do here, and this is what's cool about the dosing is that we have like low doses of Methylene Blue for a 16, maybe 25 milligrams of Methylene Blue, where you're actually improving that mitochondrial function itself, where you go to higher doses,

Starting point is 00:05:57 around a milligram per kilogram, which is around 50 to 70 milligrams, depending on the person, maybe higher. That's more of an anti-infective dose and also really good for significant acute mitochondrial stress. And one other piece of this is that mitochondria make energy and make ATP.

Starting point is 00:06:16 And this is our energy currency. We make a lot of ATP. I can't remember, but it's like almost a couple of kilograms of ATP a day. It's a lot of ATP that we make. Now, not only do we make ATP or energy, but we also have to be able to deal with the quote-unquote waste products of making energy. And those include some of the things that we know, like carbon dioxide, water, but we also make something called reactive oxygen species or free radicals. These free radicals are

Starting point is 00:06:44 very important because they're signaling molecules that tell the mitochondria to make more energy, not making as much energy and things like that. But in essence, what you see here is that you're making more energy and you have to detox from the energy that you make. And if your mitochondria aren't working very well, it could be either or it could be or that you're having a problem. Now you bring in methylene blue and methylene blue what it can do is it can help on both sides. It can help on the side of helping you make more energy and it can help on the side of helping you detoxify from the energy that you make. And the problem with making energy for many of us now is that we have these complexes

Starting point is 00:07:21 on our mitochondria. There's four of them in total. And many of us, especially complex one and complex two, but especially complex one, are not working very well. I didn't say why people have mitochondrial dysfunction, John. Why is that? So the number one cause is insulin resistance. This is people that are obese, morbidly obese, super morbid obesity, where you have insulin resistance.

Starting point is 00:07:43 That's the number one reason why people have mitochondrial dysfunction, and it affects that complex one. The second reason is medications, the third is toxins, and the fourth is infection. So COVID infections, for example, were very notorious for affecting complex one, and complex two, and also complex four,

Starting point is 00:08:01 but definitely complex one mostly. So what Methylene Blue can do is it can bypass various complexes in your mitochondria if they're not working very well, help regenerate some of them, help you make energy more effectively. And at the same time, like I mentioned, you're helping with the detoxification side.

Starting point is 00:08:17 So you're not getting a huge amount of stress in the system, even if you're making more energy. And has there been any advancements in using it for neurodegenerative diseases or to fight things like chronic fatigue, which I know is directly tied to that gut function as well? So when it comes to neurodegenerative diseases, there are a couple of studies that

Starting point is 00:08:37 have been ongoing looking at methylene blue specifically for Alzheimer's. And it was a very interesting initial study that they did where they used very low doses, methylene blue, eight milligrams twice a day. And this is their placebo group, which again is not a placebo. This is very common in a lot of these studies

Starting point is 00:08:54 because when you're giving somebody methylene blue, you're also trying to make sure that people know that they're getting it, or if they're getting it, like if they're getting a high dose, low dose, they really know but the idea with methylene blue and the challenge in this case is that methylene blue makes your urine blue so what they tried to do was give a very low dose of methylene blue to the placebo group or the sham group and a much higher dose to the treatment group okay and so in the study in this group of population this population

Starting point is 00:09:25 Methylene blue actually improved cognitive function in the placebo or sham group much more than it did in the treatment group interestingly enough and so This is not actually surprising to me because what happens if you give a very large dose of nothing blue very quickly It might be too much for the system to be able to handle. And this is very common, unfortunately, in brains that are already under significant stress. So if your brain's already under significant stress because you have myocognitive impairment, because you have Alzheimer's, as it were, then you're going to be more susceptible to the requirements for the need. You have higher requirements of things like antioxidants for example

Starting point is 00:10:06 And if you give a very high dose of methylene blue very quickly You're going to induce the capacity the brain to try to make more of that antioxidant But you're not going to be able to do it is what it comes down to so the key with methylene blue and neurodegenerative disorders is to really focus on low dose and titrating that dose over a over a period of time dose and titrating that dose over a period of time. There's a researcher at the University of Texas Austin named Dr. Francisco Gonzalez Lima who's done a lot of great work on neurodegenerative disease and Alzheimer's models looking at the use of methylene blue and if you can optimize energy production, if you can optimize the capacity of that those protein complexes, the electron transport

Starting point is 00:10:42 chain to work better, you're going to see improvements in cognitive function. And then if also you're improving the capacity for detoxification by using these low doses of methylene blue, you also see benefit there. Now when it comes to the other population, what did you mention? You mentioned neurodegenerative and the other one was, what was the other one? The other one was those experience in brain fog. Right, so the chronic fatigue, in brain fog. Right. So the chronic fatigue, the brain fog, those patients. And so in the end, what that really is, John, is a mitochondrial dysfunction.

Starting point is 00:11:12 And so what we are seeing now, at least clinically, is that you're seeing improvements in cognitive function in all varieties of patients that are coming in with cognitive dysfunction. Is it chronic fatigue? Is it post-viral syndrome? Do you have mold? Do you have infection? You're going to see improvements in mitochondrial function because of this amazing compound. Thanks to you, I got to test the product myself and I found if I really. I'm needing to concentrate on something like, let's say I need to, to focus on, uh, writing my book. Or I'm doing deep preparation for an interview, something like that. It's a really been mind blowing how much it helps you concentrate for me, micro periods of time that I need to use it.

Starting point is 00:12:09 And I'm curious if you're a person who uses these new tropics, maybe two to three times a week for cognitive enhancement, what changes might you expect to see with consistent use for over six to 12 month periods? If you're using it in an intermittent way, especially at low doses of methylene blue, it's gonna be very supportive most of the time. And the reason is because it's supporting that mitochondrial function. And most of us are having some element of that

Starting point is 00:12:30 on a regular basis. If you have stress in your life, does anybody have stress? Does anybody? That's also gonna stress your mitochondria. Do you have, excuse me, do you have exposure to toxins in your environment? Anybody have exposure to toxins in their environment? Is anybody going on an airplane tomorrow or the next day or in the next couple months?

Starting point is 00:12:48 These are all stresses on our mitochondria. And so what I've found is that if you're using something supportive like Methylene Blue, you are in a good place to use it regularly over a long period of time. Low doses, of course. With other types of neutotropics, you might wanna be a little bit more careful in the sense that if you're using a nootropic that has a lot of stimulation capacity, so if you're using something like nicotine every day or even caffeine every day, it may be something that starts depleting you

Starting point is 00:13:17 of vitamins, minerals, and nutrients, and even hormones over time because it's stimulating the system, it's clocking the system without giving it the support that methylene blue can do at the same time. The amazing thing about methylene blue is that not only is it enhancing production of energy, but it's also helping with the detoxification side. Most neutropics are going to be, at least the classic neutropics that we think of, are going to be giving you more energy and more focus, but they're not going to be giving you the

Starting point is 00:13:45 the supportive detoxification side of things as well. Now this isn't always the case if you're using caffeine of course in coffee, caffeine and coffee also has polyphenols which are also going to be supportive in antioxidant at the same time as you're you know drinking the caffeine that's in the coffee or in tea for example. So it's not always the case that a nootropic that's stimulating you is only going to have that capacity. In fact, coffee is great for that reason, and tea is that great for that reason as well. What's also nice about tea, for example, a lot of tea has L-theanine in it, right? L-theanine is something that works on the GABA side of life as well.

Starting point is 00:14:21 If you are supporting the GABA side, which GABA is a neurotransmitter that helps relax the brain, calm down the firing of the brain, and increase what's called the parasympathetic nervous system or the rest, relax, digest, recover nervous system, then that's also going to be supportive as well. Tea and coffee are great examples of nootropics that can be used over the long term because they have antioxidants in them at the same time. So I'm a big fan of using Methylene Blue regularly, especially in my clients and patients, because it's a great way to support that mitochondrial function. And as you described, John, what you'll find when you take it, when you find the right dose is that you feel like you have just brighter focus.

Starting point is 00:15:00 You have a little bit more endurance. You just feel like you can sustain yourself for longer. And even on the other side of this, like on the athletic side, endurance, elite athletes, I've been working with a lot more of them using Methylene Blue because it can help in that capacity. In fact, I just worked with somebody recently that ran the Leadville Ultra Marathon race over here in Colorado.

Starting point is 00:15:22 That's 100 miles through, I think, 12,000, 13,000 foot peaks. This is an intense race. It takes a long time. And I work with somebody and we were using, this time around, we used methylene blue for him, 36 milligrams every four hours. And he shaved three hours off of his time versus the year before. And there were certain other things that we did as well. We supported his, actually his GI system a little bit better using an amino acid called glutamine, which we can talk about if you're interested.

Starting point is 00:15:52 But in essence, the methylene blue was able to increase his endurance capacity because he was allowed, he was able to maintain his heart rate for longer without having to slow down. This is because methylene blue can act just like oxygen in the cells and become that final electron acceptor. So you can maintain an elevated heart rate for longer when you have methylene blue around because you have the extra capacity, the extra

Starting point is 00:16:18 aerobic capacity as well. So interesting. And today I heard you bring up GABA and that's going to be our main focus today. What is the connection that you see between methylene blue, nootropics and GABA? As I was describing GABA amino butyric acid is one of our primary inhibitory or relaxing neurotransmitters in our brain. And it's the unsung hero of the brain, John. Most people think of the superstar neurotransmitters when we're thinking about the brain or neurotransmitters in general, we're thinking about dopamine, norepinephrine, and serotonin. And these are important, obviously, but in much smaller quantities compared to how much GABA we have in the brain. And so methylene blue itself actually works on a system called the monoamine inhibitory system, so it

Starting point is 00:17:15 actually prevents the breakdown of norepinephrine, dopamine, and serotonin. And so as a result of this, you get more of those neurotransmitters and you get a mood boost as a result of having more of those neurotransmitters and you get a mood boost as a result of having more of those neurotransmitters around, you get more focused, a little bit more endurance just because of that piece as well. But the key also is to understand that not only do we wanna be on and focused and energized,

Starting point is 00:17:39 we also wanna have time to rest, recover, detox and digest our food. And so it's very important to be thinking about the GABA system. And the problem in our world, in America especially, is that we're a hustle culture as John. We want to be on all the time. We want to be hustling all the time. It's very difficult for us to just shut down and relax. And that's the responsibility of the GABA system. And so a lot of my focus these days with my patients and the work that I do is, okay, let's support mitochondrial function. Let's improve your performance.

Starting point is 00:18:13 But at the same time, how are we going to support this GABA urgic system in the brain? That is so important for us to rest, recover, relax, digest, and detox. Okay. Well, I think that is a great introduction to it. important for us to rest, recover, relax, digest, and detox. OK. Well, I think that is a great introduction to it. If someone's listening to this and GABA is like a foreign language to them, what might be some of the top symptoms

Starting point is 00:18:39 they could be experiencing that indicate a GABA deficiency? Ah, so this is a great question. And this is one I actually I talk to a lot of my fellow clinicians about, because what it comes down to is that GABA deficiency is so prevalent, and most of us have no idea that we're GABA deficient. If you're anxious, if you have anxiety,

Starting point is 00:19:01 it's very likely that GABA's playing a role here, and your GABA deficiency may be a part of this. If you have anxiety, it's very likely that GABA is playing a role here and your GABA deficiency may be a part of this. If you have depression, GABA is often a cause of depression and rumination or perseverating thoughts. Do you have trouble sleeping? If you have trouble sleeping, GABA may be also involved here because GABA is here to help you relax, recover, and rejuvenate. Other kinds of things, anxiety, fear, depression,

Starting point is 00:19:25 short temper, phobias, impulsiveness, disorganization, addictions, migraines and insomnia, they're all associated with GABA deficiency. And if you're having some of these symptoms, it could be that you're GABA deficient and don't know it. Unfortunately, most clinicians aren't going that route. If you have anxiety, they're thinking about giving you maybe something that affects the GABA system,

Starting point is 00:19:49 like a benzodiazepine, like Xanax or Ativan or Valium, but they're not thinking about how you can support the GABA system so that you can work on your anxiety without using those potential very challenging and very addictive medications. The same thing goes with depression. We know now that depression is not a serotonin deficiency. Certainly we know that taking something like an SSRI

Starting point is 00:20:14 can be helpful in patients with depression. There's no doubt about that. There's good studies to show that, but we also know that depression is not a serotonin deficiency. This is actually something that came out over the last couple of years, and it's shocking in the sense that we thought

Starting point is 00:20:26 we were giving a medicine to help with depression because people had a serotonin deficiency, but they do not. However, do these patients have a GABA deficiency? The answer is very likely possible. In fact, a new drug was just approved over the last six months to be used in postpartum depression, and it's a GABA-A agonist, meaning it works on the GABA system and it works extremely fast. Unlike SSRIs and SNRIs, these other

Starting point is 00:20:53 newer generation antidepressants, GABA medications work very fast to optimize the inhibitory side of the brain. And what's also interesting as well is that if you have anxiety or depression, you have about double the number of thoughts that an average person has in a day. Now, the average person in a day has about 70,000 thoughts per day. If you're anxious or you're depressed, you have 120,000- 140,000 thoughts per day. Please don't believe everything that you think. Yeah, this is a lot of thoughts, John. And so what the GABA urgic system is doing,

Starting point is 00:21:34 GABA is doing it's like the gate. It's like the, it's the way lay station. They're called inter neurons, I N T E R neurons. They are the gate between the sensory information that's coming from the rest of the world and our brain and our processing. So if you can imagine, if we were processing and trying to process at least

Starting point is 00:21:56 all the stuff that was coming into our brains or into our senses at any moment, it would be hugely overwhelming. So the problem with people with Gabbard efficiency is that they start being unable to process all that information. They just have too much going on. They don't know how to gate that information. They get anxiety, they get depression, they get insomnia and everything else. Yeah, and I guess a follow on that to that is since it has such an effect on all of those things, what is its correlation to potential suicides?

Starting point is 00:22:34 As far as we have here understanding that the GABA system is responsible for regulating mood, regulating our cognitive stability, like the GABA deficiency side is likely very much playing a role here. But it just, as far as I'm aware, hasn't really been studied in the sense that can you optimize somebody's GABA system and make them not suicidal?

Starting point is 00:22:55 The answer is probably yes, because if you're regulating your mood and you're regulating their anxiety and their thought patterns and being able to decrease those thoughts from 120,000 thoughts to 70,000 thoughts, that their anxiety and their thought patterns and being able to decrease those thoughts from 120,000 thoughts to 70,000 thoughts You likely are gonna see significant benefit and it all goes together right in the sense that if you're looking at

Starting point is 00:23:15 Suicide you're looking at people with severe depression with severe PTSD with severe anxiety that aren't able to Create any distance or any space from the thoughts that are in their mind. It's one thing that, you know, it's very important is that, is to help people realize that the thoughts in their mind are not them. But it's very difficult to be able to demonstrate to that to people when their mind is going so fast or when they're down, so down, so deep. And so what I've seen, at least, is that if you can enhance the GABA system, to that to people when their mind is going so fast or when they're down so down so deep. And so what I've seen at least is that if you can enhance the GABA system, you can regulate the flow of information better. You can slow down those thought processes. Then you can have the conversation with people and bring in a new perspective. And that's actually,

Starting point is 00:24:01 it's a very important perspective. And one that I think is very impactful is just to remind people that they are not their thoughts, that thoughts are happening in their mind, but there's some other part of their brain that's not having those thoughts at the same time. So if they're having another part of their brain, not have those thoughts at the same time, then they can't be those thoughts. There's something else that they have to be if they can observe those thoughts and observe the part of their, of their brain that's not having those thoughts at the same time. And it's like this, it's like sort of meditation ninja in some ways. It's like in the sense of trying to, but that's really difficult and really difficult

Starting point is 00:24:34 in people that are so down or so anxious. Right. So that's why like enhancing the GABA system and like turning off anxiety or shutting it down 50% can be huge to have this kind of conversation. So I think it very much plays into all of that. And I was also, as I was preparing for this, I saw that GABA activity also plays an important role in several diseases, including neurodegenerative disorders in which the body's nerve cells break down, including Huntington's disease, epilepsy, and also potentially Parkinson's disease.

Starting point is 00:25:08 Can you speak to any of those? So when it comes to epilepsy specifically, GABA regulates the flow of information within neurons and neural networks. And so what happens with epilepsy is that there is an overabundance of this other neurotransmitter that's always in a balance with GABA. So it's called glutamate. So glutamate is your primary excitatory neurotransmitter and GABA is your primary inhibitory neurotransmitter. And they're

Starting point is 00:25:38 always in a balance. And in fact, glutamate actually turns in to GABA in the brain. There's very little GABA outside of your brain itself. And so glutamate, again, you're excited to run neurotransmitter, has to be in balance and actually convert into GABA in the brain. You need two cofactors to be able to do this, magnesium and vitamin B6. So if you're magnesium deficient, you're gonna have a hard time converting. If you are B6 deficient, you're also going to have a hard time converting that glutamate to

Starting point is 00:26:10 GABA. So what happens in epilepsy and a lot of these other conditions as well is that you have an overabundance of this glutamate. And so glutamate is excitatory. It makes you feel on, it makes you feel connected. It makes you feel like you have you have control of like your executive function you can think and think clearly and think fast and The problem also though, but if you have too much glutamate causes excitotoxicity causes too much excitability in the brain It can cause seizures. So one of the main reasons why people have seizures is as a glutamate toxicity and a glutamate overload. And getting more GABA involved can be very effective here. And this is why a lot of the drugs that are involved in treating epilepsy

Starting point is 00:26:51 are working on the GABA receptors themselves. Things like gabapentin, for example, which is a drug that works on the GABA receptors in a pretty novel way. And actually we don't really understand exactly how that drug particularly works, but that's an example of that. There's also some degeneration in Parkinson's and in Huntington's as well that you were describing that's also affecting the glutamate and the GABA balance, and that's why you get choreic movements with Huntington's, which is like these movements that Huntington's patients will make are because of a imbalance between your glutamate and your GABA levels. And so this is what's happening in Parkinson's, we think, as well. There's also some studies that show that there's a dysregulation of

Starting point is 00:27:31 the GABA neurons as well in schizophrenia at the same time. If you have an imbalance between your glutamate and your GABA systems, you're going to have excitability of the brain that is hard to control. It can be disease pathology like Parkinson's, Huntington's, schizophrenia, but it can also be in mental health time kinds of conditions as we're describing. Your depression, anxiety, insomnia, irritability, tremors as well. So all these can be a part of agglutimate overabundance versus GABA deficiency. And it's that GABA deficiency that we really need to focus on more. We've done a great introduction to the science of GABA.

Starting point is 00:28:14 Can you break down a little bit deeper the structure and function of the GABA receptors, particularly GABA-A and GABA-B and how they contribute to brain activity? Yes, of course. And so those are the two main types of GABA receptors. GABA-A is the more common one. GABA-B is also very common. So GABA-A receptors have what are called these subunits. They have five subunits on them that change depending on where they are in the brain. GABA-A receptors are everywhere in the brain, but some are more focused on anxiety relief,

Starting point is 00:28:46 some are more focused on sleep, some are more focused on sensorial gating, like in the thalamic area, for example. The thalamus has lots of GABA-A receptors. And so the GABA-A receptor, the way it works is that it has a central channel called a chloride channel. And what happens is when GABA binds to the receptor, this channel opens. When this channel opens when this channel opens

Starting point is 00:29:07 Chloride channels go the chloride goes in sorry the chloride goes out Excuse me, Cory goes out and when the chloride goes out what happens is that the GABA Receptor and the GABA receptor itself, which is on a neuron Remember is going to what's called hyper polarized which means that it stops firing. So that's what happens here. So I misspoke. So chloride's going in, not out. Okay, so chloride's going into the channel. So GABA-A receptors have chloride channels that go in. Chloride goes in. It hyperpolarizes the membrane there that the receptor is in, and as a result of that, the neuron that's on what's called the postsynaptic side stops firing. So that's on what's called the postsynaptic side stops firing.

Starting point is 00:29:45 So that's why it's called an inhibitory neurotransmitter because when GABA binds to its site, it opens up the receptor. It prevents the firing of the neuron on that postsynaptic side. So most of the drugs that we know of affect the GABA receptor, the GABA A receptor, and most of the drugs don't bind to where GABA binds, but they bind on what are these called, these allosteric sites, these sites around, on those subunits that either enhance the affinity

Starting point is 00:30:13 for GABA to bind or decrease the affinity for GABA to bind. The most common one that all of us know about that we have on a regular basis in across the United States and the world is alcohol. Alcohol binds to an allosteric site on the GABA-A receptor, increasing the affinity for GABA to bind, increasing the chloride going in, and inhibiting that neurotransmitter,

Starting point is 00:30:36 inhibiting that neuron from firing. There's lots of other ones that we can talk about. There's lots of drugs, there's lots of natural plants that do it as well, but we can talk about, I think, that in a little bit. When it comes down to the GABA-B receptor, GABA-B is a little bit different. GABA-B is called a G protein couple receptor.

Starting point is 00:30:51 And it just basically means it has something on the presynaptic side and the postsynaptic side that are working together. Calcium, potassium, those are the electrolytes that are going on there. And that basically has the capacity to decrease the firing of that postsynaptic neuron as well. So the major drug that works on the GABA-B receptor that most people know of is Baclofen, which is an anti-spasmodic drug. So it works mainly in the spinal cord actually to

Starting point is 00:31:15 decrease spasm of muscles. And the other drug that's very commonly used or not very commonly used but very commonly known as the date-rate drug is GHB, or gamma hydroxybutyric acid, which is GHB. And this is a, it's known as a date-rate drug, but it's actually a really great drug used for spasm, used for narcolepsy, used for sleep as well. And so it's got some medical benefit. So you have your GABA-A receptor, and you have your GABA-B receptor,

Starting point is 00:31:40 and the GABA-A has all these subunits that other kinds of compounds can bind to that help the GABA itself bind to its site on the receptor. And then you have the GABA-B receptor as well, which is this G protein couple receptor a little bit different. So if I understand this, what you were saying about alcohol, for example, it promotes the GABA receptor activity, which creates that temporary feeling that anyone who's had alcohol

Starting point is 00:32:10 gives that feeling of calm and relaxation. But the effect is artificial, right? You don't get the same effect every time, correct? Well, the thing about what happens is that alcohol binds very tightly to the GABA receptor, to the site where it binds on the receptor, which is again, this allosteric site, tightly to the GABA receptor, to the site where it binds on the receptor, which is again this allosteric site, so not where GABA binds, but it increases the affinity for GABA to bind, but it does this in a very strong way. And as a result of that,

Starting point is 00:32:36 you have this strong binding of alcohol to the receptor, you have this strong affinity for GABA to bind. And what happens over time very quickly is that your body tries to compensate for this. And this is why you have tolerance. Eventually you have withdrawal when it comes to alcohol as well. But the tolerance part is because with alcohol bind so tightly,

Starting point is 00:32:56 it starts depleting GABA very quickly. And when you start depleting GABA, the body tries to compensate that for decreasing the number of GABA receptors available and also decreasing the number of GABA sites that you have available on the GABA receptor. And so as a result of that, you need more of the alcohol to get the same effect. The other problem with alcohol, John, is that binds very quickly and tightly, but then it unbinds very quickly as well. And so this is why if you drink alcohol before you go to bed, you wake up, most people wake up like two or three hours later and they feel like wide awake or they feel terrible.

Starting point is 00:33:30 This is how I used to feel when I was a kid and drinking alcohol. I could wake up two or three hours later with the worst headache ever. Why is that? Because now you've all of a sudden have this overabundance of glutamate as well because you've screwed up the balance between the two of them. And so that GABA unbinds very quickly, the GABA gets depleted, and then all of a sudden you have all this glutamate around and then you feel terrible, you get headaches, you get irritable, all those things.

Starting point is 00:33:53 And so that's why alcohol is terrible for people who wanna, in general, alcohol's not very good for a lot of different reasons. But for sleep, it's very bad because it really affects the whole aspect of you trying to it may help you fall asleep But it will not help you stay asleep and you will not get good sleep if you drink alcohol So you want to avoid it for those reasons at least other reasons to avoid alcohol of which there are myriad as yes Well, if you were a regular alcohol

Starting point is 00:34:20 User and then you abstained from drinking for two to three weeks. When it comes to this, what would be some of the positive effects you would start seeing? Well, as long as you weren't drinking too much when you first started, the problem if you're drinking a lot and you stop cold turkey,

Starting point is 00:34:39 you could potentially have a very dangerous situation here, right, where you can have severe withdrawal, you can get what's called autonomic instability, where your blood pressure gets crazy, your heart rate gets crazy. This is all that overabundance of that glutamate, that excitatory neurotransmitter, because the body's so depleted from GABA

Starting point is 00:34:57 from so much alcohol use for such a long time. So that's one thing to mention. So if you're gonna stop alcohol, and you've been drinking a lot of it, don't drink it, don't stop abruptly. You could potentially hurt yourself. The same thing goes with like benzodiazepines, for example. So the other drugs that affect the GABA receptor that are very common, your Ativan, your Xanax, your Valium, these are your benzodiazepines,

Starting point is 00:35:16 along with your alcohol, of course. Like those are the main ones that we think of. But if you don't want to stop those drugs, cold turkey either, because you've got the same problem. They cause such a tightly bound increased affinity for GABA to bind that you get a depletion of those GABA neurotransmitters over time or the GABA neurotransmitter itself and also the GABA receptor as well. So now if you're going to do this in a slow way you're going to want to make sure that you're thinking about increasing your GABA production at the same time, if at all possible. Nobody's really thinking about this,

Starting point is 00:35:49 but that's why we're talking about it. And so what, how do you do that? And so what you want to do is thinking about the precursors that are responsible for you be making more GABA in the system. So what's the precursor to GABA we talked about is something called glutamate, right? But what's the precursor to glutamate and that is the amino acid glutamine. So we talked about glutamine and we've heard a little bit about glutamine before. I think many of your listeners, like glutamine is an amino acid and glutamine is extremely important for a lot of different things.

Starting point is 00:36:18 It actually is the fuel for your small intestine at the same time as it is a precursor for glutamate, which then gets converted into GABA in the system. So the first thing I think about when I'm working with my patients that have been drinking a lot of alcohol or if they've been on benzodiazepines and we're thinking about supporting their GABA system is looking at making sure they're getting enough glutamine in their diet, not only for their gut, if they have leaky gut, they even need more than if they have not a leaky gut. But then also thinking about the cofactors that are responsible for the conversions of your glutamine into your glutamate into your GABA. So you're thinking of vitamin B6 and magnesium mostly. But I alluded to it earlier, if you have a leaky gut, if your

Starting point is 00:37:01 gut's not doing well, if you're having a hard time there, you're going to need more glutamine to support your small intestine before you even get over to make enough glutamate and make enough, make enough GABA. So there's lots of glutamine containing foods as well. Your meat containing products are going to be your highest in glutamine. And so your meat, eggs, poultry, dairy, those kinds of things are going to be the highest in glutamine overall. And, but. But there's a lot of benefits of supporting your GABA system while you're starting to wean yourself off of things like alcohol and benzos. Yeah. I understand that also there are certain foods, you mentioned meats and stuff like that, but they're foods that boost GABA such as broccoli, peas, beans, grains like rice and oats, tomatoes, sweet potatoes, spinach, etc. How do you recommend incorporating that into the diet to maximize the positive impacts?

Starting point is 00:37:59 Those are great foods to use. I mean, what it comes down to for me is looking at a holistic picture, right? When somebody, in my estimation, is GABA deficient, which is very common these days, you wanna think about it holistically. You wanna think about what are the types of foods that are gonna support GABA and glutamine production? What are the minerals that you're gonna require to be able to create that conversion very easily?

Starting point is 00:38:23 And then how are you gonna prevent yourself from stopping the depletion of GABA so quickly? Now we talked about the drugs, we talked about things like alcohol or benzodiazepines, but if you're stressed all the time, your cortisol, the stress hormone in the body is going to deplete GABA very quickly. You're also gonna deplete minerals as well

Starting point is 00:38:40 when you have high cortisol levels for long periods of time. And are any of us stressed? Of course, we have stress in our family, we have stress with our work, as well when you're when you have high cortisol levels for long periods of time and are any of us stressed of course we Have stress in our family. We have stress with our work. We have stress with just the types of exposures that we have if we're on airplanes we're stressed on an airplane not only because of being on an airplane with 200 other people that you have never met before Coughing all over you but also because you're in tin box tin can up in the sky with more radiation exposure

Starting point is 00:39:05 and things like that. So stress is everywhere and it's depleting GABA like crazy. And I think that's the main thing that I always emphasize with the people that I work with and is that if we're going to enhance the GABA system, we have to figure out ways to improve our capacity to decrease stress. And one of the main ways that we do this is trying to find ways that we can engage people

Starting point is 00:39:30 to become parasympathetic or relax and digest, right? One of the ways actually you can do this, interestingly enough, is have people sit down for a meal and eat. Eating actually makes you more parasympathetic. As long as you're not eating on the run and trying to feed your four children and eating at the same time. I'm not guilty of this at all ever of course but if you're resting and eating you're actually going to become more parasympathetic if you can work on your

Starting point is 00:39:56 yoga your mindfulness and your breathing techniques and increasing your exhale so shorter inhale Longer exhale that's all also going to make you more parasympathetic. And if you can do that on a regular basis, you're going to improve your GABA system. Interestingly enough, exercise also enhances the GABA system too, because exercise is going to help with the balance between your sympathetic and parasympathetic nervous system. And as a result of that, you're going to reset your parasympathetic nervous system, which is great.

Starting point is 00:40:27 There also is the release of a factor called BDNF, brain-derived neurotrophic factor, which is extremely important as well for a lot of different reasons for neuroplasticity, for new growth of neurons, but also for increasing GABA in the brain. And so these are some of the things I think about. I also think about sleep a lot too, because if you're going to enhance releasing GABA in the brain. And so these are some of the things I think about. I also think about sleep a lot too, because if you're going to enhance the GABA system, you need to reset your nervous system. And the best way to do that is by getting better sleep

Starting point is 00:40:53 overall. The challenge that we have, of course, is that not everybody can do this immediately. And so what are we going to do to support the GABA system very quickly while people maybe are on the longer path of trying to optimize their vitamins minerals nutrients There are stress levels. Maybe they'll get a sleep divorce. You know what a sleep divorce is John. Have you heard of these that this is when people Decide to sleep in separate bedrooms because their partner is snoring or keeping them up or kicking them in the face Or things like that and then that's a huge stress too

Starting point is 00:41:22 But what that that's a difficult conversation to have with a partner sometimes, hey, you know what, sometimes maybe we shouldn't sleep in the same bedroom because you're snoring or because you keep punching me in the face or something like that. So anyway, this stuff takes time. Like it takes time for people to make these kinds of changes and to see these kinds of manifest benefits while they're enhancing the GABA system.

Starting point is 00:41:42 So sometimes what we need to do is support the GABA system with natural equivalents, plants, fungi, other kinds of things that can work in conjunction with diet, with lifestyle, with supplementation. And that's really the key, I think, is that you have to look at it all at different angles to really help people. Okay, maybe we can just think about this

Starting point is 00:42:04 in terms of habits. I mean, you've mentioned a lot of things about physical activity, different foods, etc. But I would think building the proper habit loops plays a critical role in the regulation of GABA. So what would be some of your advice for steps that a listener or viewer could take? Habits are where everything starts and ends, right? I think they say 90% of what we do on a day-to-day basis is a habit I read a great book by Charles Duhigg a long time ago called habits and how we make them how we break them and I think it's a great book if anybody's interested and

Starting point is 00:42:40 When it comes down to habits in general that we want to cultivate are ones that increase our capacity to become more parasympathetic, to relax. Our default as humans these days now is to be on-on. But how do you turn on your off switch? How do you do it? That is the GABA system. So creating habits that help you turn on your off switch are going to help you in so many ways.

Starting point is 00:43:09 So what are some of the things you can do? Well, first thing you don't want to do is wake up and the first thing you do is check your phone immediately for all the messages and all the other kinds of notifications that you might see there. Finding a way to create space from the world around you, just a little bit, can go a long way.

Starting point is 00:43:28 And this is what we were discussing earlier, we were talking about 70 to 120,000 thoughts per day. The human organism is not evolved to do this. Our human organism is evolved for two things, if you believe this. Some people believe more, but in general, we're evolved for two things. If you believe this, some people believe more, but in general we're evolved for fitness and for function. Meaning we're evolved to be able to do certain things

Starting point is 00:43:53 for a certain period of time so we can procreate and pass on our genetics. And then the rest is just, in our world it would be icing on the cake even now, but especially in Paleolithic times, if you live longer than 40, 50 years old, it was a gigantic thing, right? So it takes a lot of intention for us to take the time

Starting point is 00:44:15 and realize that being parasympathetic is going to give us longevity. It's going to allow us to live a much longer, much healthier life, because if we're always in sympathetic dominance, we're not gonna be able to rest, recover, heal, detox, and so if you can't detox, you're gonna build up with toxicity over time and you are not going to live as long.

Starting point is 00:44:36 Cardiovascular disease, neurodegenerative disease, these are associated with stress. So some of the habits that I like to talk to my patients about, one of them is actually very simple. We just described taking time in the day when you're not looking at phones or screens. This could be five minutes, it could be 10 minutes,

Starting point is 00:44:53 it could be longer. I like this in the setting of meditation and people will do it. Or if they're just gonna do some deep breathing, increasing your exhales is going to increase your GABA sympathetic, your GABA tone and decrease your sympathetic tone That's a very simple thing that you can do. Nothing you can do is have fun play enjoy yourself

Starting point is 00:45:12 I have four kids at my house, especially when they were younger They're still pretty young but especially when they were younger if you're rolling around the floor with your kids You're not in sympathetic dominance. You are in parasympathetic mode. You unrest recover. Another great way to do this, and this is the Italian way, this is the Mediterranean way, John, is to have great meals with friends, family, and laugh like crazy. Laughing is a great way to reset your sympathetic and parasympathetic tone because laughing engages your diaphragm, and then you release your diaphragm, and all of a sudden you have this relief, this relief.

Starting point is 00:45:48 And that is the same way that you can increase your parasympathetic tone. There's so many things you can do, even just one of the things I like to have a lot of my patients do is take walks. Not crazy walks at huge paces, but just walk in nature, getting outside, getting sunlight. There's so many things you can do behaviorally to improve your

Starting point is 00:46:06 parasympathetic tone. And those are just some examples. I was going to ask you about adult play, which is one of the most popular. Articles I've ever put out on my blog is it's importance to so many things in our lives. But I have to tell you, man, earlier this morning, I go out for a walk early. I was out at 5 15 AM and it's pitch black. And then all of a sudden the whole East side of the sky just lights up out of nowhere.

Starting point is 00:46:34 I was like, what is going on? Turned out to be a SpaceX launch. I love getting out and that being the first thing I do every morning and trying to incorporate as much nature as I can even though sometimes it's pitch black when I go out, I still find listening to the sounds in the morning, the birds waking up, everything, it does give you such a calming mechanism in your life. Yeah, it's a great meditative event in essence, because what they teach in meditation often times is that the sound that your feet make when you hit the ground is just as important as those

Starting point is 00:47:11 thoughts in your mind. It's all just things happening in conscious awareness in space and so nothing really gets more weight unless you choose it to so you can in those sounds that you're hearing when you're walking, you don't have a choice of whether you hear those sounds or not. But you can actually create this sort of internal presence of those sounds and understand that it has a huge, this ecosystem that you're creating inside your mind

Starting point is 00:47:39 is anything you choose it to be. And you can put any weight on these certain things that you choose to make. And having time off of computers, off of phones, be and you can put any weight on these certain things that you choose to make and having time off of computers, off of phones, or in my case, as with my kids is a great way to remind yourself that there's more than those thoughts in your mind. And when you start doing this and you start putting these things into practice and your patients in my case, start doing this, their health transforms and it may not be overnight.

Starting point is 00:48:03 That's for sure. It may not be tomorrow where you take one walk in nature and then the world is an entirely different place for you. But you can start getting inclinations here. And then and this is where supplementation things like enhancing the GABA system can be very helpful to along with changing mindset along with the nature along with breath work along with meditation. If you just start giving people like a little bit more of an accelerated capacity, that's where the power is. I think so much of what you were talking about is a topic that I've been trying to put out there a lot on this show. And then that is the disease of disconnection because we are losing our sense of self because we're connecting to these external communities

Starting point is 00:48:47 instead of doing the inner work that we need to. And I think it's having so many ramifications across the globe. And it got me thinking as you were talking, if your GABA is out of balance, one of the things that I'm seeing around the world is a big gap in people losing their sense of meaning. And I'm wondering if our gut health is so screwed up, our GABA transmitters are so screwed up, it's influencing our mood and our ability to manage stress, which are underlying factors that contribute to life's purpose and meaning. Do you think there's any correlation there?

Starting point is 00:49:29 100%. We are just, we're living in a whack-a-mole triage setting at every moment of every day. And that is just because we're getting so many inputs, and then we're getting depleted on things that are helping us Maintain a stability and mood in function, especially gaba as well So you'll find and I see this clinically once you start enhancing the gaba system Once you start becoming more parasympathetic then you start getting more grounded you feel more grounded You have more space between your thoughts your emotions and your, and then you show up better in your life, both for yourself, which is probably the most important, but of course with the people around you. And one of the things that I often like to ask my patients about is, actually, I like to ask my patients' family members about this, is how are they doing?

Starting point is 00:50:21 How are they, are they, because that's one of the best ways for people, a lot of us don't realize when we're improving, actually. And it's actually very common in men specifically, is that men don't realize, they're just not as observant in general. We just don't have the same capacity as women, just naturally overall. And women have these superpowers as we know.

Starting point is 00:50:42 And so, but asking family members how they're doing can be very indicative on these journeys that people are having once they start Doing some of the things that we're talking about and and then I'll be like well, and then I'll be like well Tell me about your day yesterday. How many times did you scream? How many times did you get so angry that your mind just went completely blank and you couldn't think for X amounts of minutes? that your mind just went completely blank and you couldn't think for X amounts of minutes. Think about in the last three months, how many times does that happen?

Starting point is 00:51:08 Ask your kids, how many times have I yelled at you last week? If you can't remember yourself. And I've done this actually myself personally, just in various experiments that I've done. We're a very bad judge of how, in general, how we're doing. So sometimes, especially in the beginning, when you're starting to create more of that sense of grounding, it's helpful to have those extra conversations is how am I doing really, and I found that to be helpful when I'm on that path of optimizing these kinds of things.

Starting point is 00:51:42 could do the focus on nature, et cetera. If there was one lifestyle change that you would recommend listeners or viewers start out with to optimize their GABA levels, what would it be and why? I think the best and the easiest way is to learn a breath practice. And it doesn't have to be something that's too crazy at all. People have heard of box breathing, for example,

Starting point is 00:52:04 that's a very easy way to become more parasympathetic. I have my kids do what's called three five, three seconds of breath in and five seconds of breath out. Just lengthening your exhales, just doing that for two to five minutes will make you extremely impressed at what breath can do if you start doing it consistently. So I think that's the simplest thing for people to do from a lifestyle perspective. The other thing to do that can be helpful is start exercising because exercise can also help balance

Starting point is 00:52:37 the sympathetic and parasympathetic nervous systems. But I hesitate for that to be my first because that can also be, if you're just going to Exercise and then going to do something else and then something else and something else that's not going to be very helpful but I think When I talk to my patients the one thing I emphasize a lot is the breath work piece now If that's part of a meditative practice all the better, but I don't even think it's necessary to start off with to be honest I mean if people think meditations to woo I get that. It's not about not having thoughts. It's just about observing your thoughts really in meditation. And then there's other stages, of course, if you want to go there. But in general, breath work and just prolonging your

Starting point is 00:53:15 exhales. So there's the three breathing patterns I teach my patients are either box breathing, something called four, seven, eight. So you breathe in for four, you hold for seven, you breathe out for eight, or I do the three, five, the three minutes, the three seconds in and five seconds out. There's a lots of other permutations of this and there's lots of other ways to do it. I have a good friend of mine named Brian Mackenzie, who does a lot of work with CO2 tolerance, and these are called breath holds. And so you can learn about doing this and increasing your CO2 tolerance. And that also improves your stress over time. But I think that's secondary to just learning how to exhale for longer than you inhale. That will be transformative if you can do it on a consistent basis.

Starting point is 00:53:58 Well, Scott, I always love having you come on the podcast because we deep dive the most interesting topics. If listeners want to learn more about you, the Neutropic products, et cetera, where's the best place for them to go? So, Troscriptions is the company that we created about four years ago and it's the for-profit entity of a non-profit organization called Health Optimization Medicine and Practice. And that's Home Hope for short. Home Hope is training practitioners, licensed practitioners, non-licensed practitioners on how to optimize health of their patients and clients without the optimizing health without focusing on treating disease.

Starting point is 00:54:36 And that's the framework shift that's very different. In the seven module certification course, the first module is metabolomics actually. And that's what's so foundational to my own practice and to a lot of the work that we're doing. Metabolomics has been called the 21st century stethoscope for a reason. It's robust, but with AI, as you were alluding to John, now we're looking at all these levels and how we're going to be able to integrate all this data together is going to be, you know, transformative. So if you're a practitioner looking for more training, we have it's all at homehope.org.

Starting point is 00:55:07 You can check out our seven module certification. With TROscriptions, we have products there that can help people right now while they're on the path to optimizing their health. And we have ones that are based on Methylene Blue. Those are helping with energy, with focus, with endurance, with inflammation. But we have a whole suite of products

Starting point is 00:55:24 that are based on the GABA system. We have one called Trocom, we have another one called Trozee, Trocom for anxiety stress reduction, and we have Trozee one for sleep and sleep optimization with eight different ingredients. So our focus with those products is helping you turn that on switch off.

Starting point is 00:55:41 And so if you're interested in learning about more of these products, more about the GABA system and how it all integrates with anxiety, with stress, with sleep, insomnia, depression, you can go to Troscriptions.com or you can go to Instagram at Troscriptions and find out more information. And then if you're interested in learning more about me, I'm at Dr. Scott Scherr, D-R-S-E-O-T-T-S-H-E-R-R on Instagram. I do a decent amount of posting there. You can also go to drscottsherr.com

Starting point is 00:56:08 and I have a bunch of my own resources there. I do work with patients directly. I do remote consulting in the worlds of health optimization medicine, which I have my own practice, hyperbaric medicine. I think that's enough for you. I know this, Mr. John, I think that's good. That's great.

Starting point is 00:56:23 Scott, thank you so much again for joining us. It's always an honor to have you here Thanks for being back. I was pleasure to be back number three. I look forward to number four. We'll have to do it That's all good. Take care John. Thanks for having me

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Passion Struck with John R. Miles - Dr. Scott Sherr on GABA: The Unsung Hero of Brain Health and Stress Resilience | EP 575

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