Today, I am excited to connect with Dr. Scott Sherr, a board-certified internal medicine physician certified to practice health optimization medicine. He is the COO of Troscriptions, a range of physician-formulated, pharmaceutical-grade precision-dosed supplements containing innovative ingredients like methylene blue, with various formulas for energy, focus, sleep, stress, immune support, and more.
Our discussion today focuses on the GABAergic system, the parasympathetic system, and maladaptive responses to stress. We explore the importance of GABA and its interaction with progesterone, looking at the impact of stress, lifestyle, alcohol, and benzodiazepines on GABA health. Dr Sherr also explains the role of methylene blue and shares his insights on supplements that support GABA.
This insightful show is the first in a series of valuable and informative podcasts with Dr. Sherr.
IN THIS EPISODE YOU WILL LEARN:
Dr. Sherr describes the autonomic nervous system, highlighting the sympathetic (fight or flight) and parasympathetic (rest and digest) systems.
The two major types of GABA receptors, GABA A and GABA B, and their roles in the brain
How GABA calms the firing of neurons and regulates information processing
The link between GABA deficiency and conditions like depression, anxiety, and insomnia
How progesterone increases GABA tone and leads to better sleep
Why women need to support the GABA system during perimenopause and menopause
Lifestyle strategies to support the GABA system
How most GABA supplements are too large to cross the blood-brain barrier
Why GABA supplements can work for those who have leaky gut or brain
How alcohol negatively impacts the GABA system
How methylene blue enhances mitochondrial function
The problem with modern world as it is that many of us have leaky brains because we have leaky guts.
-Dr. Scott Sherr
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Connect with Dr. Scott Sherr
Transcript:
Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness Podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.
[00:00:29] Today, I had the honor of connecting with Dr. Scott Sherr. He's a board-certified internal medicine physician certified to Practice Health Optimization Medicine. He is the COO of Troscriptions, a line of physician-formulated, pharmaceutical grade and precision-dosed supplements with novel ingredients like methylene blue as well as others and formulas for energy focus, sleep, stress, immune support, and more.
[00:00:55] Today, we discuss the GABAergic system and the role of the parasympathetic system, maladaptive responses to stress, the importance of GABA, its interaction with progesterone, the impact of stress and lifestyle, the impact of both alcohol and benzodiazepines on the health of our GABAergic system, specific supplements that can support GABA in the body, health optimization medicine, the role of methylene blue and more. This is the first of a series of podcasts with Dr. Sherr and I know you will find this information invaluable.
[00:01:35] Welcome. I've been so looking forward to this conversation, largely because you have such a breadth of experience and your genuine love for teaching and education is so evident. Welcome.
Dr. Scott Sherr: [00:01:47] Thank you. It's really nice to be here. Cynthia.
Cynthia Thurlow: [00:01:49] Let's initiate the conversation around something that I feel like women in middle age really struggle with is balancing their autonomic nervous system. In particular finding ways to stimulate the parasympathetic rest and repose system. Most of these women are high functioning, are individuals that have a long to-do list, they want to get all the things done. But I feel like in perimenopause and menopause it becomes even more critically important that they're able to activate and stimulate this rest and repose side of their autonomic nervous system. Has that been your clinical experience as well?
Dr. Scott Sherr: [00:02:26] Oh yeah, 100%. I mean it's not just perimenopausal women and menopausal women that are having this issue. The way that society is designed is for us to hustle, hustle, hustle get as much done, be as time efficient as possible. So, we know how to turn on our on switch. We have things like caffeine, the widestly used nootropic or brain enhancer in the world. But none of us, not a lot of us know how to turn on our off switch, this is what you're describing, which is your parasympathetic nervous system. And so, we have our autonomic nervous system, which you describe, which is composed of our sympathetic nervous system and our parasympathetic nervous system.
[00:03:06] So, our sympathetic nervous system is our fight or flight. Get things done, hustle, move, get things off that to do list, get your kids to 75 places, make sure that everybody's fed, make sure everybody's in bed, and then what? Then it's supposed to be your parasympathetic nervous system that takes over and that this is classically called your rest and digest nervous system, but it really is rest, digest, detox, and recover nervous system. And this is the system that many of us are just not thinking about because we're so busy doing the other things. And so, we don't give it a lot of time. And then what we'll do is that we'll try to initiate this with things like alcohol, for example. We'll try to find ways to relax. But we're having to use unhealthy kinds of modalities or things like alcohol to help us relax.
[00:04:00] It's not very common. Put your kids to bed, have one to three glasses of wine and then, go to bed or try to go to bed. And the idea is not wrong in the sense of trying to find ways to relax. But there are so many better ways than alcohol to optimize this parasympathetic nervous system. And I think that's really where we need to focus. I think many of us have been focused on the to-do lists and getting things done. And especially a lot of people that are listening that are, very high functioning people in their lives, and working with companies or even just running a household. “Look, I, I have four kids.” I get it. My wife works full time and we have four kids and I work full time. So, it's a big deal. But I think the focus on the rest, digest, recover, detoxification, that's where we can spend so much time. Today, as well and in our lives in general and see such huge benefits even with just a little bit more focus.
Cynthia Thurlow: [00:04:55] Yeah, so it's interesting to me, it's our modern-day lifestyles that drive a lot of this disconnect for our bodies. And I know what I got away with in my 20s and 30s, especially as working in ERs, trauma bays, cardiology as an NP would not be the healthy environment for me to be in at this stage of my life when I'm already a little overly amped up type A personality. Let's speak a little bit to this GABAergic system in the body that you speak to as a very important way to regulate neural activity. We're really speaking to this neurotransmitter of GABA, inhibitory neurotransmitter. And I feel like, well intentioned, many individuals are probably taking GABA supplements.
[00:05:40] And we were speaking before we were recording about how it's such a large molecule that it actually doesn't cross the blood brain barrier. Let's speak to GABA and why it's so important and why so many of us that are amped up, if you say sympathetic, dominant, really struggling in this modern-day lifestyle to support our bodies in a better way.
Dr. Scott Sherr: [00:06:00] So well said and great introduction. The GABAergic system is your brain's brakes. Just like the brakes of a car. It's the same kind of deal. We need to have the brakes on the firing of our neurons so that we can calm the firing of our brain. GABA is the most important neurotransmitter, so the brain chemical, the brain compound that does this. Now the other neurotransmitters get most of the press. What we call the superstar neurotransmitters, things like dopamine and norepinephrine and serotonin. But it is GABA really that rules them all. Because what GABA does, it again calms down the firing of the brain. But it's also what it's called an interneuron. So, I-N-T-E-R, meaning it's the way station, It's a gate. It prevents and regulates information that comes from the environment into your body.
[00:06:55] So, your sensorium, things that are going around you. If we were bringing in everything from the environment that's around us at all times, we would be overloaded. And what GABA is able to do is really help calm down and gate that information. So, it's extremely important for information processing, for skill acquisition, for learning, for memory. GABA neurons are all over the brain and they change depending on what's required in those particular areas. There's called the GABA-A system and the GABA-B system. These are different, the two major types of GABA receptors in the brain. And the GABA receptor is extremely interesting. What it typically does is it's usually on. If you think about two neurons together, one's called the presynaptic neuron, one's called the postsynaptic. So, the presynaptic is one that fires the signal, the postsynaptic neuron is the one that grabs signal and does something about it.
[00:07:52] When most the GABA-A system, specifically, this receptor inside that neuron prevents the postsynaptic neuron from firing. So, it has this capacity to be activated. It activates by GABA binding to it. And then when GABA binds to it, it prevents the firing of that neuron. So, as a result of that, you get the decrease in firing overall. GABA-B works a little bit differently. It works with the presynaptic and postsynaptic together. But in essence, the same thing happens, which is that you stop the firing of your brain.
[00:08:25] Now, the problem and we were alluding to this already, Cynthia, is that so many of us are actually GABA deficient. And it's not something that clinicians like me or like you are really looking for because it's not something that's taught in medical school or even thought about really in clinical practice. But the issue, the problem is that when you're looking at GABA deficiency, GABA deficiency is so common. It's associated with things like depression. It's associated with things like insomnia, anxiety, tremors, and so many more conditions that are very common. Many people are coming into the doctor's office and say, “I don't feel good. I have depression. My mind won't stop. And I have anxiety or I can't sleep.” It's also associated with mental health conditions like even schizophrenia and bipolar disorder are associated with GABA issues.
[00:09:15] But when you go to your doctor and say, “Doctor, I'm feeling anxious all the time.” I don't know how to calm down. They're going to give you an SSRI or something like that. And so, the problem, and we know this, is that, depression is not a serotonin deficiency. This has been recently published in the last couple years, they looked back and retrospective studies and looking at serotonin levels in depressed patients, and their levels were not lower than the average person without depression. So, it wasn't just like, that you just would give somebody an antidepressant because they were serotonin deficient, and you could give them this SSRI and increasing serotonin could help them, but it wasn't the major underlying reason for why they were depressed.
[00:09:59] GABA, on the other hand, is shown directly to have correlations with, as mentioned, depression and anxiety. And a good example of this is that the average human has about 70,000 thoughts per day. Now, if you are anxious or depressed, that number goes up to 120,000 thoughts per day. That sounds like a lot of thoughts. It is a lot of thoughts. And even on average for 70,000, that's a lot of thoughts. So, I always tell my patients and my friends that'll listen to me or my wife sometimes when she listens to me, [Cynthia laughs], or my kids that you don't want to believe everything that you think. If you believed all of those 70,000 thoughts per day, you'd be in serious trouble. So, the key to think about here is that we need to be thinking about the GABA system because it's correlated with all of these, potential conditions. And there's so many things we can do to support that GABA system, which in turn is going to support your parasympathetic rest, digest, recover and detoxification systems.
Cynthia Thurlow: [00:11:01] I guess, so much about perimenopause, the hearkening of perimenopause is this de-evolution, this ovarian senescence of less progesterone being produced in the ovaries. And so, progesterone and GABA really do interact with one another. Let's speak to that, because I find this so, so interesting. And I think for many listeners that are experiencing an upregulation in anxiety and depressive symptoms and more insomnia or trouble falling or staying asleep at this stage of life, this complex interplay between these two hormones is very important.
Dr. Scott Sherr: [00:11:37] Oh, it's huge. It's huge. And I'm glad you mentioned it because progesterone is directly increasing GABA tone. So, when you have more progesterone around, you will sleep better. If you don't have as much progesterone around, you are not going to sleep as well. That's just how it goes. And you'll actually notice this if you're still having regular periods, you'll notice at certain parts of the times of the month you'll sleep better than other times. And this is when you're more progesterone dominant versus when you're more estrogen dominant. So earlier in your cycle, when there's more estrogen predominance, you're going to feel more awake, alert, because estrogen actually has the opposite effect.
[00:12:13] Estrogen blocks the GABA receptors so you feel less tired typically, you can go on less sleep overall and you feel pretty good, especially around ovulation. But when the progesterone starts being more on the balancing higher than the estrogen, that's when you're going to need more sleep. Are you going to feel like you need to an extra 30 minutes in bed? You can't get out of the bed in the morning and things. But this is very important during the perimenopausal, menopausal time because this is one of the reasons why women will have a much harder time sleeping. So, it's so important to support the GABA system in this capacity. I mean, of course, giving progesterone is an option and that depends on the situation. And, and of course, what your perspective is on HRT and things.
[00:12:55] But in essence, at least for me personally, I think it's a good idea, but along with a battery of other things. But my overall perspective is here is certainly HRT is something to think about, but how are we supporting the production of GABA? How are we making sure that you're not depleting it as well? I mean, one of the major things that's depleting it all the time, that all of us know this intuitively is stress. If you’re always stressed, your cortisol, which is like your stress hormone in your body, it's your steroid hormone-- steroid hormone cortisol depletes GABA in the system.
[00:13:27] And so it also depletes some of the co-factors, which are these other things like B6 and magnesium specifically, that are responsible for the conversion of GABA from its precursor. The precursor to GABA in the brain is something called glutamate. Glutamate is our excitatory neurotransmitter. In fact, it is in combination with GABA. The total between the two of them is 80% of your brain's neurotransmission. Okay, so the rest of the other ones, norepinephrine, dopamine, serotonin, only 20% compared to glutamate and GABA. But glutamate in which is super interesting, is that the way we've evolved is that glutamate is our excitatory neurotransmitter and GABA is our inhibitory. And there's always going to need to be a balance between these two. And there has to be conversion of these two from glutamate to GABA, you need B6 and magnesium to do this.
[00:14:15] So, if you're B6 or magnesium deficient, you're going to have a hard time making that conversion. If you're actually not making enough glutamate in the first place, then you're going to obviously have a hard time making enough GABA. If you're depleting GABA so fast that you're having a hard time making that balance shift fast, then you're going to get a glutamate overabundance. And then what's that going to happen? It's going to be like this downward perpetual cycle spiral where you're stressed and then you can't get unstressed and you feel worse because you don't have enough of that, GABA there and you have too much glutamate around.
[00:14:48] I mean, the most common example of this that people know of, that they've had the experience, is that you go to a Chinese restaurant and you have MSG in your food. MSG is monosodium glutamate. And this is a direct source of glutamate to your brain. So, this is why you get headaches, you feel irritable, you can't sleep. It's because all of a sudden you have this overabundance of glutamate in the brain. This is happening to all of us on a regular basis just because of anxiety, stress, nutrient depletion, gut issues can do it too. If you have a leaky gut as well, if your gut's not working very well, the main fuel for the small intestine is something called glutamine, which is an amino acid. And then glutamine is also the precursor to glutamate in the brain. So, as you can see, this is all connected. But the key here is to understand that, if you're GABA deficient, we have to support that system.
Cynthia Thurlow: [00:15:41] What are some of your favorite ways to support the GABA system from a lifestyle-related measurement?
Dr. Scott Sherr: [00:15:49] Lots of different ways that we all can use. The most important ones are find ways to relax. That sounds like a tall tale for a lot of people. But the easiest thing and I teach my kids this, and it's just learning how to breathe. We all think we know how to breathe because we do it reflexively. But if you learn how to spend two to five minutes just prolonging your exhales. And so, I teach my kids either like a box breathing technique or what's even easier for them is a 3-5 technique. So, breathing in for three seconds, breathing out for five seconds for two to five minutes. Because once you can increase your exhales, your exhales are going to help you reset your nervous system so that you come out of that fight or flight, you decrease that sympathetic tone.
[00:16:38] I'm a huge fan of meditation in general, and I don't think that everybody is going to want to meditate. I totally understand that. But even just doing breath practices can be really great. If you're not into just doing that. I have even some light stretching or if you're into yoga, even just holding some yoga poses for a couple minutes like isometric kinds of exercise can be really helpful. So, if you're doing just a very easy kinds of yoga poses breath work, interestingly on the other side of it, exercise can be very helpful here too. As long as you take time after exercising to let yourself recover and you don't go like immediately into the day and like all of the crap that you have to do, that's like a big thing over the last four or five years has been the Wim Hof breathing, for example. That's not relaxation breathing, okay, [Cynthia laughs] that is sympathetic breathing.
[00:17:31] Now can you use that as your exercise and then relax afterwards? Absolutely. But you still have to work on your breath practices or do some meditation or some other ways. And so, I find that for me, the breath practices are pretty easy for my clients and patients to work on. There's other ways that I try to help with the resetting the nervous system. There is some vagal nerve stimulators. I work with people. So, you can work on your vagal nerve, a lot of places to get it. But like, your neck is easy. One thing you can do actually this is fun is just do some humming or singing if you like to sing. That's also a great way to reset your nervous system.
[00:18:07] So, I have my guitar over there. Sometimes, I'll just like, if I'm really just a bit like, going, going, going. If I can take like five minutes and do some humming or something like that, or even blowing it into a straw, we'll do it too. If you have straw and some water, like when you're a kid and you're blowing bubbles in the water, that's actually prolonging your exhale so you can do that. If you have kids, you can pretend you're a kid for five or 10 minutes, your kids will love it. And you just get into play mode. That's really helpful too. So those are some of the ones that I use. I mean, I have others, obviously, like your diet, your nutrition is really, really big here, your relationships. If you're sleeping with a partner that's snoring all night, they've done studies that every time your partner snores, your cortisol level goes up just a little bit each time, even if you don't remember waking up.
[00:18:55] So, address that. Sleep divorce, it sounds nasty, but if you're sleeping in a separate bed and you're both sleeping better, all the power to you. So, there's a lot of other things, but these are some of the highlights.
Cynthia Thurlow: [00:19:05] Well, I love that you touched on the vagal tone piece because the vagus nerve is the longest nerve in the body. And in cardiology, we used to have a lot of people that would inappropriately stimulate their vagus nerve and then pass out or have other things that occurred. But being able to hum, being able to sing, gargle, all these things can stimulate that nerve. The concept of sleep divorce, I have a husband who will occasionally snore, and he, of course, remembers nothing about it. He now mouth tapes. But I can appreciate why and how if an individual is sleeping next to a partner who's snoring, your cortisol goes up. Because I know how irritating it can be. As much as I love my husband, I always tell him, you need to be on your side, otherwise the statistical likelihood you're going to snore more is going to be problematic.
Dr. Scott Sherr: [00:19:50] Indeed.
Cynthia Thurlow: [00:19:51] When we're talking about progesterone, probably worth even mentioning that progesterone even has a role in men. It's not just a female hormone. I think, unfortunately, a lot of individuals assume it's just a female hormone, much like testosterone, just a male hormone. How do you find progesterone to be helpful for men in terms of supporting this GABA system?
Dr. Scott Sherr: [00:20:14] Yeah, it's actually really important, and I'm glad you mentioned it. I mean, we know that from like a milligrams per deciliter level, there's more testosterone in women than estrogen. There's a lot of testosterone. I mean, it's not as much as men, of course, but women need testosterone and just like men need progesterone as well. So, as you just alluded to, it can be something you use to support the GABA system in men if they're having a hard time sleeping. It's not usually my first go to for most men because the challenge with progesterone sometimes is that it can cause erectile dysfunction in some men, and so you have to be careful with the dosing. Now, there's some evidence, however, interestingly enough, that you can actually use progesterone for things like BPH, like benign prostatic hypertrophy.
[00:20:59] So, if you have a large prostate, progesterone's actually going to shrink that. And so, you can use it, rectally. You can use it as a suppository. I know not all people like the suppository way of using. Using various types of compounds, but that's another option. But you know what? I think that it with men, what I would typically do. So, I work with a decent amount of men in my own practice, and I do hormone optimization for men. What we're often trying to do actually is look at the whole adrenal axis, look at all the hormones that are coming from the adrenal glands. The adrenal glands are these glands on top of your kidneys, and they produce a whole lot of steroid hormones for men and for women.
[00:21:36] For men and for women, there's a majority of hormones that come from there, but there's also majority of other hormones that come from ovaries for example. In testicles, you have obviously testosterone that's mostly coming from the testicles in men, but a small amount that's coming from the adrenals. And obviously, women don't have testicles, so they're getting their testosterone from their adrenals, for example. In men, the testosterone that we make gets converted to estrogen and that's a similar process, actually, that's happening in women. It's just happening primarily in women because they don't have obviously testicles.
[00:22:10] So, it's important for me when I do the testing to look at a whole battery of these things, look at their growth hormone axis, look at their thyroids, look at their adrenals, look at their gonads, their testicular hormones and then create a plan together that's going to be optimized and it's more difficult to do in women, because women when it comes to especially perimenopause, you can't really trust or really look at hormones as a way to hormone optimize. You have to do it by symptoms and how they feel. Women are more complicated as we know, as far as being four different women throughout the month when having periods and then going through perimenopause.
[00:22:45] But men do have andropause too, which is when our hormones slowly decrease over time. And so, after about the age of about 30, 35, all of our hormones start declining as well. So, in essence I'm thinking about progesterone in the ecosystem of hormone optimization for men. I'm not typically supplementing it with it, but sometimes I will, especially if they have a hard time with sleep, especially if that BPH. These can be very, very helpful. But usually what I'm thinking about for men when it comes to the GABA system is looking at how I can support that GABA receptor in making sure we have enough GABA.
[00:23:21] But then also what other supplements other than the diet and lifestyle things that we mentioned before, what other supplementation can I use to support that receptor in a very holistic way. And I think about this for women as well, of course, but that's my mode of operation typically.
Cynthia Thurlow: [00:23:36] With that being said, when were initially talking before we started recording, you mentioned that GABA is such a large molecule, it does not cross the blood brain barrier. So, when you are working with your patients, whether they're male or female, and you are first working on lifestyle, then consideration given to supplementation that can support this system. What are your go tos or what are your high level things that you're considering utilizing?
Dr. Scott Sherr: [00:24:04] So yeah, GABA supplements are too big. GABA, the molecule is too big by itself to get across the blood brain barrier. So, this is a barrier that's evolved to keep things out as much as possible to protect our brain. If we have systemic infections or inflammation, the brain tries to protect itself. The problem with modern world as it is that many of us have leaky brains because we have leaky guts. If our gut is not doing what it's supposed to do, keeping things out, there's a significant amount of inflammation that happens in the system. The immune system starts getting revved up in ways it's not supposed to get revved up. This can lead to things like autoimmunity in some cases. We saw a rash of this and we're still seeing it a lot now post pandemic as well.
[00:24:46] And so if you take a GABA supplement and it works for you, it's likely because that barrier is not doing what it's supposed to do. So, it could be diagnostic in this capacity. So, I don't recommend doing this, but it is a way to say, “You know what, I need to get some more help with some additional testing and work with a practitioner or do my own,” research as to why this may be the case. And so, what's interesting about the GABA receptor though, is that it typically, so the GABA A receptor specifically, which is a more common one, it has five subunits, and on those subunits are all these binding sites where other things can bind. They can bind and increase the affinity for GABA to bind to where it binds on the receptor or it can have the opposite effect where it can decrease the amount of GABA that binds to the site of where GABA would bind on the receptor. So, these are called allosteric modulators of the GABA receptor.
[00:25:35] And we already alluded to one earlier when we talked about alcohol. Alcohol, benzodiazepines, these are very commonly used to modulate the GABA receptor on these allosteric sites, increasing the affinity for GABA to bind. But what's the problem with these particular compounds? What happens with alcohol? Alcohol binds very tightly to where it binds on the receptor, increases the affinity for GABA to bind so much that you actually start seeing a depletion of the GABA very quickly. And what also happens is that it unbinds very quickly after it's bound so tightly.
[00:26:10] This is the common scenario that I'm sure many of your listeners have had where you drink some alcohol to go to bed or before you go to bed, you fall asleep very easily, but you're up like two hours later and you can't go back to bed. So, what just happened? You bound to the receptor very tightly, you depleted a whole bunch of GABA, very quickly, you unbound the receptor. Now you have this glutamate overload compared to GABA, and that's why you feel irritable, you get headaches. I used to get the worst hangovers when I drank alcohol. And it was like two or three hours after I went to bed. I'd wake up with this pounding headache and everybody knows what I'm talking about unless you have very significant Irish blood or something like that [Cynthia laughs] There are those few people out there that don't get hangovers. But in essence, that's what's happening with alcohol and what's happening with benzodiazepines like Ativan, Xanax, Valium, these bind so tightly to the receptor as well that they cause the same issue over time.
[00:27:03] And what that issue is, what we call tolerance, withdrawal, and significant dependence. Because what the GABA receptor will do over time is it will try to protect itself. And it does this by decreasing the number of those receptors and trying to have less capacity for you to bind GABA there because you're flooding the system with this need for more GABA, and so you're depleting GABA over time. So, the system's trying to compensate for itself.
[00:27:31] So, what you really want to do is work with compounds that don't do this, obviously. And then if you're working with compounds that don't do this, you want to be thinking about this in two different ways. The first way is that there's all these other compounds, and we'll talk about some of them, that can bind to the GABA receptor and increase the affinity for GABA to bind, cool, but they don't bind as strongly, they're much more safe, they've been around for thousands of years and I'll give you a couple of these in a minute.
[00:27:56] But the other thing you want to think about, even so, is that if you're giving something that's going to increase the affinity for GABA to bind, you want to make sure you're not depleting GABA in the process, even if these are more natural compounds, because it can still happen. So, what are some of these compounds? One of the most common ones that many people have heard of, and I think recently as well, is something called kava. Kava is something that's been around for thousands of years. It's been used in the Pacific Islands. It is something that modulates the GABA receptor by binding to one of these allosteric sites, and then it increases the affinity for GABA to bind. So, Kava's one of them.
[00:28:32] Another one that we eat that I like a lot is something called magnolia bark or Honokiol, which is another one that binds to one of these sites on the other, on the GABA receptor, but not where GABA would bind. So, it’s called a positive allosteric modulator. There's actually the endocannabinoids-- sorry, the cannabinoids themselves, not endocannabinoids. Those are the ones that are internal. The ones that we take themselves, like CBD, CBG, CBN, these all bind to allosteric sites in the GABA molecule or GABA receptor and increase the affinity. Now, interestingly, THC is different. THC actually is a negative allosteric binder. So, it binds to the GABA receptor and it prevents GABA from binding. This is why people that use THC typically, especially in the beginning, will get anxiety. You have that, you get that anxiety when you take THC.
[00:29:23] Interestingly, opioids, things like morphine, heroin, and all the derivatives of those, they actually decrease the sensitivity of that GABA receptor to bind GABA itself. So, they actually cause the issue with the GABA system being more deficient and more issues with the GABA system because of the opioids as well. So, there's other things that deplete GABA over time. Things like even caffeine will do it, even other stimulants will do it as well. But anyway, so these are all things that are binding and we can talk about more of those because there's a lot, if you're interested. But they're all binding to these allosteric sites. And then there's a couple cool things that can bind to where GABA binds on the receptor.
[00:30:07] The first one that I love to talk about is something called agarin. Agarin is a one of the ingredients or one of the compounds that's found in the Amanita muscaria mushroom. This is a psychedelic mushroom. It's well known across the world, especially for Christmas mythology. So, if you're in Europe right now, or especially in northern, in Scandinavia, you will find tons of pictures of this mushroom. The mushroom is the red capped mushroom with white dots. Alice in Wonderland, Mario Brothers there's a lot of Christmas mythology that's around this mushroom because if you take this mushroom, you get psychedelic experiences. Especially, if you take the mushroom that's been detoxified in some way because it's actually a pretty toxic mushroom.
[00:30:54] So, what they used to do is actually drink reindeer urine. Reindeer love this mushroom. And then the shaman would actually collect the urine of the reindeer, drink it and then have shamanistic experiences in the Siberia area actually. And so, anyway, that's a little bit of a side note, but the idea with the mushroom is it has two ingredients, two main compounds. One is called Agarin, the other one's called ibotenic acid. Ibotenic acid is the neurotoxic ingredient that causes the psychedelic experiences and some of the GI disturbances that can happen with this particular mushroom. Agarin is a long-acting GABA agonist, which means it works on the GABA receptor at the GABA site, binding to where GABA would bind. So that's my favorite one because it's got a great story and it's also long acting.
[00:31:39] So, in some of the products that I use, we use it for sleep because it's stays on the receptor for about six and a half hours, seven hours. So, it's a great for its half-life. And the other one that I use is something called nicotinoyl-GABA, vitamin B3 attached to the GABA molecule, and that's vitamin B3 has a receptor that gets across the blood brain barrier, so you can have B3 and lead the charge through the blood brain barrier, taking GABA with it. And as a result, you get B3 and GABA in the brain. B3 is mildly activating, which is nice, especially if you want to take some relaxation thing during the day but not feel too tired. So, you have this vitamin B3 attached to the GABA and GABA binds to where the GABA would bind.
[00:32:22] So, in summing up all of this, I know, I spoke for a long time, is that like when I'm thinking about GABA supplementation, I'm thinking about these allosteric sites, these sites on the GABA receptor that can enhance GABA binding. Kava, CBD, CBN, CBG, Honokiol or magnolia bark, along with something that's binding to the site where GABA would bind on the GABA receptor and that's something like Agarin or nicotinoyl-GABA, vitamin B3 GABA.
Cynthia Thurlow: [00:32:48] This is fascinating. So, a big picture to recap some of the things you talked about. If you are taking GABA assuming that it's working effectively, it probably is a reflection of leaky gut equating with leaky brain. So that explains a lot as someone who has a couple autoimmune conditions and very likely still has persistent leaky gut. Because I was like, GABA works really well for me. Well, so that's a tell. Number two, we just did a podcast last month talking about benzodiazepines. And I think about 25 years of being in clinical medicine, and there's a time and a place to utilize them, but I had many, many patients that were on them long term, like years and years and years. Lot of my little old ladies had been on them since the 70s as an adjunct to help them sleep.
Dr. Scott Sherr: [00:33:37] There's little helpers, right, so.
Cynthia Thurlow: [00:33:38] Exactly, exactly. But alcohol and how it offsets these receptors is GABA receptors. Can we speak to this a little bit? Because I'm thinking about individuals that utilize alcohol either to help with sleep or generalized anxiety disorder or social awkwardness. I'm speaking about a family member specifically. I think this is where they started utilizing this and how they utilize the alcohol to be more comfortable socially. But yet ultimately, it is unwinding the role of GABA. It's making it harder for GABA to do its job. Is there a threshold with which the utilization of alcohol can become problematic? I know that really become a movement as of, they're calling it sober curious, where people are becoming more curious about not drinking alcohol.
[00:34:30] But in your clinical experience, when we're speaking specifically to alcohol and its effect on this GABA system, where is the fine line? One glass of alcohol may not be problematic, but where is that fine line for you when people are trying to address sleep or trying to support this other side of their autonomic nervous system more proactively?
Dr. Scott Sherr: [00:34:51] Yeah. I have a colleague and friend that always says that when somebody asks him if he drinks alcohol, he says, “There's many better drugs than alcohol, [Cynthia laughs] so why would you still be drinking alcohol?” And it really comes down to me when I talk to patients. It's like, well, why are you drinking the alcohol? And try and understand, like, what's the reason? Is it for sleep? That's just a bad idea, right? Is it to wind down after dinner? Let's talk about it. Let's talk about some other ways that you can use. I mean, do I think a glass of wine for most people a night is going to cause a problem? The answer is probably not as long as it's not affecting your sleep. I do also know that-- there's been a number of studies that have come out recently that really is no safe amount of alcohol to drink. There's been associations with brain shrinkage, which we don't want, shrinkage anywhere. Nobody likes the word shrinkage in general or moist. Nobody likes that word either. I don't know, but those are bad words.
[laughter]
[00:35:45] But my brother always hated that word. That's like the one that I never like to say except when we're trying to be funny. But when it comes down to it, also is that we don't know from an individual perspective what the safe threshold is for you versus for me. In general, women are more sensitive to alcohol and the effects on the GABA system than men. So, for the same amount of alcohol that a woman's drinking versus a man, it's going to be a very different scenario. Now, what your heritage is? If you are native American and you are on a reservation, your capacity to tolerate alcohol is going to be much different than somebody that grew up in Ireland where the water wasn't safe to drink, so they drank beer instead? And so back 200 years ago, the beer was safer than the water? And so, you have to think about heritage. And I had a college roommate that could drink like a fish the night before he could pass out an elevator, vomiting on himself, and then the next day he could run a marathon. It was completely impressive. He had Scottish heritage.
[00:36:49] So that's why I like to say that. I don't really think there's a safe level of alcohol per se. Do I think that having, a nice glass of wine on one night and every evening is going to be bad for you? The answer is “Probably, if you could do it less than that that would be great.” But I think the always the question for me is why? Why is alcohol needed? And it comes back to the beginning of our conversation because when most people are going to say is just, I just need to relax. It's very difficult for people to change their behaviors, to change their lifestyle. It can seem impossible, right?
[00:37:24] If you have four kids in a job and things are just going 100 miles an hour. It's like, “What am I going to do?” And so, I see the role for supplements in this case in helping to modulate that GABA receptor we talked about, like a little bit of kava, CBD or a little bit of CBG at night. These are much more supportive to the GABA system and can have a very similar effect. You talked about social lubrication too. You talked about a lot of people use alcohol, as many of us did when we were younger as well as a social lubricant. I get it. There are safer options now.
[00:37:59] If you live in Los Angeles, if you live in the bigger cities, there's all these places you can go now where you can get the mocktail kinds of things, or you can get these functional beverages. I have a friend of mine that started a facility in LA and he was one of the first people that talked about, like, “Oh, I forget the name of it,” but it was like a social wellness kind of thing. So, you bring people together, and alcohol is not the focus and that's a big shift for a lot of people.
[00:38:25] I mean, for myself personally, I remember even being in medical school, and you go out with your friends, you go to the bar, and you have beer and whatever that's just what you do. At some point, I decided I didn't want to start keep drinking, and it's not like if I had alcohol, it wouldn't be a deal. But I don't see the reason, but I really understand how it's difficult to get out of those patterns. But there are so many other ways to be able to engage now in community without alcohol. And I think that's so important for people to think about too.
Cynthia Thurlow: [00:38:53] Yeah. And I appreciate you're such a thoughtful response. And I think for so many of us, whether it's maladaptive patterns that people start as teenagers and young adults that just potentiate and continue. I went to my 30th high school reunion a few years ago, and what was hilarious to me, I don't drink. But I was at my reunion, and in my typical introvert fashion, I'm kind of watching all the interplay between people and one of my male friends leaned over and he said, “It's amazing how many people in this room still act like they're 18 years old.” And I said, “Yes.” And there's no judgment. It was just fascinating to watch, whereas most of us were like, “I either have to drive, I have to get up in the morning,” the cost benefit is just not there anymore.
[00:39:37] I'd love to pivot and speak a little bit about your nonprofit. I found it really interesting as I was preparing for this conversation and then perhaps, before we end our conversation today, I definitely want to speak about methylene blue and then I want to have you back because there are so many different avenues, nooks and crannies we could have discussed.
Dr. Scott Sherr: [00:39:57] Sure. So, everything that I do typically from a clinical perspective starts with a foundation. And the foundation, I didn't know what it was going to be for a longer time than I realized. I am a son of a chiropractor, I grew up very alternatively, very militantly against the conventional medicine for a long time, but interestingly was counseled by that same father that medical school was a great option because get the MD, you can do anything you want to do, kind of deal. And so, when I went to medical school, it was under the guise of trying to bridge that chasm between-- There was no such thing as functional integrative medicine at that point. It was just alternative medicine.
[00:40:37] And over the years, I gravitated towards a lot of different things, but I focused really mainly on something called hyperbaric oxygen therapy, which is a big field on its own. And I know you were interested in maybe talking about that another time, but as I was creating an integrative practice around hyperbaric therapy, I really realized that I needed to have a foundation to that because I found that if people weren't well optimized before they went into the chamber, especially from an energy metabolism perspective, could they have the optimized levels of vitamins, minerals, nutrients and cofactors that are responsible for helping you make energy and also helping you from the detoxification side, because many people don't realize that and you make energy, you also make these things called reactive oxygen species or free radicals that in low doses, but your body needs to have the ability to neutralize those overtime. And when you go into a chamber, short stories, you make a lot more of those.
[00:41:26] I would refer people over to functional medicine and then integrative. I met a mentor and colleague named Dr. Ted Achacoso. And Dr. Ted is one of these brilliant physicians that has done many things in his life with an IQ over 180, like, very, very, very smart guy. And he had created this framework called Health Optimization Medicine and Practice. He had really just nailed it in his own clinical practice over about a decade, figuring it out, honing it, and then he wanted to make it a nonprofit.
[00:41:53] I met him in 2017 and the perspective shift is really what got me when it comes to Cynthia, he's like, instead of focusing on preventing and treating disease, why can't we optimize health instead? It sounds simple, but even functional medicine, for example, which I have a lot of respect for and I have a lot of friends that are involved in it, is still looking for the root causes of illness instead of looking for how we keep people healthy. And as a son of a chiropractor, this very much aligned with me. I very much said, “Well, this is what we're doing. This is what my father was doing so many years he's trying to align the body in various ways, take things away.”
[00:42:28] He always was doing dietary things back in the 80s when it wasn't cool, like taking people off of dairy and other kinds of things and seeing people get better. So, what was nice about this framework, Health Optimization Medicine and Practice, was that it was data focused, but it was also holistic enough to look at all these other inputs that were happening, your diet, lifestyle, behavior, circadian rhythms. And so, we created a seven-module certification course for practitioners, either licensed or non-licensed, that are looking to work with their patients or clients in a holistic way.
[00:43:00] And so these seven modules include things like something called metabolomics, which is a long word, but basically, it's the real time understanding what's happening in your cells right now versus genomics, which is maybe might happen in 50 years. This is what's happening. This is like the brass-tacks kind of thing. So, metabolomics, epigenetics, chronobiology, which is study of circadian rhythms, exposomics, which is study of toxins in the environment, bioenergetics, which is study of your mitochondria, the gut immune system, and something else that I'm missing because-- whatever, but you get the idea. So, the idea is like a holistic understanding.
[00:43:32] So, we have a non-profit that trains practitioners on how to do this and then our for profit company called Troscriptions was developed because when we're trying to optimize our health and when we're working with clients, all of our patients want to feel better tomorrow. But if it took you 40 or 50 years to get here, it's going to take some time to feel better. If you're lucky, it'll be six months, usually it's a year, sometimes longer before you start really seeing the benefit of changing things up. So, how can you help people right now while you're on that longer path to optimizing your health? And that's where our company called Troscriptions came around, where we have products for immune system health, for energy, for focus, and a bunch of things on the GABAergic side supporting the GABA system the way we were describing earlier.
Cynthia Thurlow: [00:44:16] No, it's so interesting. And I think, certainly as someone that was trained in traditional allopathic medicine and after 16 years in clinical cardiology, got really tired of writing prescriptions for lifestyle-related issues and pivoted into integrative medicine, from my perspective, they can coexist. Both realms can coexist. Obviously, if you are urgently or emergently sick, that's where allopathic medicine shines. But I agree with you that kind of looking at the body as a system can be helpful. Now, we haven't talked about methylene blue on the podcast, but I would love to at least touch on this and then we can [crosstalk] the conversation. What is it? Why is it helpful and how do you utilize it with your patient population?
Dr. Scott Sherr: [00:45:01] Yeah, it's a really, really cool compound and it goes along with the story that I was just painting in the sense that working with patients or clients, depending on your orientation here is a challenge. And one of the major challenges that we have is that-- and the statistics are pretty grave, about 94% of the US population has some element of mitochondrial dysfunction. And mitochondrial dysfunction means that you cannot make energy effectively or you cannot detox effectively from the energy you make. We kind of alluding to what I said earlier there. This is kind of how I got involved in Health Optimization Medicine. So, the process of Health Optimization Medicine Practice HOMe/HOPe is, that's what we call it for sure HOMe/HOPe is the process of optimizing metabolomic data. A big part of that is in your mitochondria. So fun fact, do you know where we have the most mitochondria per cell. Cynthia?
Cynthia Thurlow: [00:45:54] I'm guessing maybe the heart.
Dr. Scott Sherr: [00:45:56] So that's close. I mean you have a prejudice or a bias there because you have a lot of cardiology work. So, actually, the place where the most mitochondria per cell are ovaries in women, sperm in men.
Cynthia Thurlow: [00:46:08] Oh that makes sense.
Dr. Scott Sherr: [00:46:09] And then from there you have the brain, the heart, liver, and your musculoskeletal tissue. So, if you can think about where mitochondrial dysfunction is, you're seeing it in the world right now. Infertility rates shooting through the roof. Why? Lots of different reasons why, but the main common denominator is mitochondrial dysfunction. If you have issues with mitochondrial dysfunction in the brain, brain fog, fatigue, concentration problems, memory issues, verbal fluidity issues, cardiac issues that you well know, liver issues, with [unintelligible [00:46:41] detoxification, musculoskeletal issues, exercise-induced fatigue, like these are major issues. So, what's causing mitochondrial dysfunction? Number one reason is actually something called insulin resistance and many of us know this. The majority of humans on this planet basically, but especially in the US I think like 75% of adults now are obese, morbidly obese or super morbid obese, that's a thing. I'm sure you know about it, but super morbid obese is, I think it's a BMI greater than 40, I believe. And I see many of those patients or I used to in the hospital.
[00:47:14] And then not only is it insulin resistance, but you also have people that are taking medications that affect mitochondrial function. There are many. And also, you have toxins in our environment. Anything from the water that we drink to the food that we're eating, the cosmetics we're putting on our face, to the other exposures that we're getting in, around us all the time. And then of course, infections. So, infections also affect mitochondrial function. And then post infectious kinds of syndromes like your post Covid of the world or your people that have like post mold and all these other things, these are affecting mitochondrial function.
[00:47:44] Now with all of that preamble, what methylene blue does is significantly enhance, improve and support mitochondrial function. And this compound's been around a long time, it's got a long history that we don't have time for today. But in essence, at higher levels, higher doses, it's a fantastic anti-infective. In fact, it was the only anti-infective antimicrobial round for bacteria, fungus and virus before antimicrobials were invented in the 1950s. And it used in this way. It became out of favor though, when all those other drugs came around.
[00:48:19] And the other major reason is that because methylene blue concentrates in your urine and as a result of that, it makes your urine blue. At very high doses of methylene blue, it will make other secretions blue as well, very high doses. But in essence, the antimicrobial dosing is around a milligram per kilogram, which is about 50 to 70 mg and above is like anti-infective doses, but the lower dose is like 4 mg, 8, mg 16 mg, 10 mg. These are doses that are significantly supporting mitochondrial function. And we know this after the last several decades where there's been a lot more research and interest here. And what's really cool about methylene blue is that it's something called a redox cycler. That's a big or a small word, but it's a strange word for most people.
[00:49:04] What that basically means is that methylene blue can compensate for any dysfunction in the mitochondria that's preventing you from making energy. It's a complicated discussion there, but we have four complexes on our mitochondria. They're all really important for helping make energy. Many of them can be damaged because of infection, because of toxins, because of insulin resistance, all those things. And methylene blue can compensate for all that and also regenerate one of those complexes, complex IV. And that's why, interestingly, very well, synergizes with near infrared light. So red light therapy, near infrared, specifically 680 nanometers, donates electrons or works on that complex IV of the mitochondria, just like methylene blue can. And so that's why they can be very synergistic.
[00:49:46] So, not only can methylene blue on the first side enhance energy production by supporting all that side of the mitochondria, but on the other side of things, it can help and work directly as antioxidant. This is actually so mopping up the free electrons, if the oxidative stress, the inflammation that's happening. So, there's very few other compounds in their own right that can do both. And that's why it's so supportive for people to take as a way of enhancing mitochondrial function. And the reason why I use it so much in clinical practice, especially when I'm starting to work with people that have significant mitochondrial dysfunction, it's going to take them a long time to see the improvements of diet, lifestyle, behavior. But we can see an improvement almost right away when we start using low doses of methylene blue.
Cynthia Thurlow: [00:50:28] So out of curiosity, if you're looking at a patient with a lot of chronic health issues, maybe chronic Lyme, etc. etc., versus someone that's coming to you that's otherwise pretty healthy, they're just looking to optimize their health. I'm assuming, the person who has the chronic issues, it's a longer trajectory of utilization of this as a nootropic agent versus maybe if someone's otherwise healthy, are they taking it daily or is it something they take as needed? Like how does that work?
Dr. Scott Sherr: [00:50:57] Well, if you're otherwise healthy, then typically it's more of an as needed kind of basis. I work with a lot of athletes. I worked with somebody that just did a hundred-mile race here in Colorado, where I live, and that's a significant amount of endurance. There is some evidence that methylene blue does enhance endurance because what it can do, we talked about that electron transport chain and these complexes. So, what methylene blue can do is act just like oxygen in the mitochondria and be the final electron acceptor. So, we need oxygen specifically because it helps with that electron transport chain in our mitochondria. So, if we're running out of it, if we don't have a lot of it, the system's going to try to slow you down, make you stop doing what you're doing.
[00:51:31] And so if you take methylene blue, though, what we've noticed, at least clinically, although it hasn't been shown in the research yet, is that, these people that are taking it for endurance can maintain their heart rate for longer at a higher level when they're using the methylene blue. So, I work with a guy, he took 32 mg of methylene blue every four hours. And he did this along with a couple other things that we did differently from the year before. And he saved his time for about three hours compared to the year before doing a hundred mile race and so, there's definitely utility there. And then also if you're relatively well optimized, it's also really nice to use when you're going to not be as well optimized.
[00:52:07] So, if you're traveling on an airplane, you're at low oxygen levels, radiation exposure, because you're closer to the sun, there's more infections around, your mitochondria aren't going to be very happy. And so, as a result of all that, like having some methylene blue on board can be very, very helpful. And so, I have the various ways of working on these travel, jet lag protocols for patients. But I find that can be very helpful in those capacities. And then, yeah, I mean if you don't have to be an elite athlete to be able to benefit from it. But I do have a lot of the moms that I work with, they'll use it on their treadmills, on their Stairmasters and whatever it might be in the mornings or whenever they use it. So, they can exercise for longer, keeping their heart rate level higher while they do it.
[00:52:43] So you are correct though, like if it's more of a chronic, complex medical condition, oftentimes it's more of like a daily type of dosing, especially in the beginning and titrating that dose, starting at a low dose and increasing the dose incrementally to see where the benefit is and then maintaining that dose for a period of time and then at some point starting to wean it off as well. So, we have high, two strengths of this at my company. Like one's like a lower strength for more mitochondrial optimization. Then like higher strength, that's for practitioners only to use with their patients. But that's more of like the anti-infective dose more for significant mitochondrial support needs.
[00:53:15] But if you don't have an acute issue, I don't recommend starting off in very high doses of methylene blue. I recommend starting out low doses, like 16 mg slowly titrating there. However, if you have more of an acute issue, you can go and go for higher doses. I like to give example of my mom who lives in New York and was bitten by a tick. There's a lot of Lyme ticks in New York. And so, what are we going to do? I'm not going to mess around. I gave her 2 mg/kg of methylene blue to take for the first day and then a mg/Kg for four more days. She still took antibiotics because she was worried about Lyme and that's okay. I can support her other ways.
[00:53:52] You can use up to 2 mg/kg. I use this not infrequently in people with acute viral syndromes or in an acute bacterial or fungal situations, but usually in synergy with other directed modalities or directed therapies for that particular thing. But you get a sense that for an acute issue you can likely tolerate a higher dose. If you have a chronic issue, it's going to be like a smaller dose that you titrate over time.
Cynthia Thurlow: [00:54:14] Oh, so interesting. Well, I would love to have you back and have you go more into depth on this and then also talk about hyperbaric oxygen. Please let listeners know how to connect with you, how to learn more about your companies.
Dr. Scott Sherr: [00:54:26] Sure. So, well, thank you first for having me, Cynthia. This has been a lot of fun and happy to come back, talk about hyperbaric therapy or whatever you'd like. So, personally, where you can find me on Instagram, I'm pretty active @drscottsherr. D-R-S-C-O-T-T-S-H-E-R-R. You also can find me like by searching my name in any platform. I've done a lot of media over the years. As you mentioned in the beginning, I really do try to educate on these topics as best I can. If you're interested in the nonprofit work, if you're a practitioner, you can get trained with us we have a seven modules certification course.
[00:54:58] It's called Health Optimization Medicine and Practice, HOMe/HOPe for short, it's homehope.org. The for-profit company the one that makes the products in the GABA space. We talked about one called Tro Calm and Tro Zzz a little bit. The Tro Calm was the one with nicotinoyl-GABA, the Tro Zzz the one with the agarin and the psychedelic mushroom compound is not psychedelic, that's at Troscriptions. It's the Troscriptions. You can find us on Instagram @troscriptions. You can find us@ troscriptions.com and I think, yeah, I mean that those are the main places to find us. And yeah, it's been a pleasure to be here. Thanks for having me.
Cynthia Thurlow: [00:55:31] Absolutely. If you love this podcast episode, please leave a rating in review, subscribe and tell a friend.