94% of Adults Have Mitochondrial Dysfunction — How Methylene Blue Restores Energy | Dr. Scott Sherr

94% of US adults have mitochondrial dysfunction. I see this on an everyday basis in my clinical practice where we start low doses of methylene blue and see fantastic benefit across the board. Anything from pain, inflammation, brain fog, mental health disorders, and all these other kinds of things because it's all at the edge base related to mitochondrial dysfunction. The most common places to have this dysfunction are you're on complex one or complex two. In complex one and complex two of the complexes that are taking the electrons from your food and bringing them to the electron transport chain so that you can make energy. So if you don't have working complex one and complex two, you're not going to make energy effectively. You're not going to feel good. And so what methylene blue can do is it actually can compensate by bypassing some of those dysfunctional complexes and allowing electrons to get further down the chain to be able to help you make energy. It also can recycle and renew parts of those protein complexes and actually can help recycle and renew your NAD supply as well. So insulin resistance is actually one of the major causes. The other major cause of mitochondrial dysfunction is the sympathetic spiral of doom. You also have toxins in the environment that cause mitochondrial dysfunction directly. Infections, medications, these are all causing significant mitochondrial stress and as a result of that, you're not making energy effectively. It's one of those things where once you start taking it, you will realize that you probably needed it all along.

>> Dr. Scott, my goal with you today is to create an in-depth master class on one of your favorite compounds, methylene blue. Are you with me?

>> I'm with you. Let's do it, Jesse. Exciting.

>> All right. Well, let's start out talking about what you're most excited about in the world of Methylene Blue as of late.

>> Oh, well, that's an interesting place to start. So what I would say is that I I continue to be very excited about how much capacity it gives us to support, enhance, regenerate mitochondrial function. And I see this on the macrocosmic scale on an everyday basis in my clinical practice where we start low doses of methylene blue and see fantastic benefit across the board. Anything from pain, inflammation, brain fog, um you know, mental health disorders and all these other kinds of things because it's all at the edge base related to mitochondrial dysfunction. So, I'm very excited for continuing to be able to, you know, work on an ecosystem where we really discuss and educate around methylene blue and really kind of give you more of a signal from the noise. And and in 2025 it was there was definitely some signal in there for sure, but there was a ton of noise and that's I'm I'm grateful for both because it was because of all the noise that the signal rose and now people are like wow this compound really does have some potential right? But as a result of the noise it was it's sometimes difficult to kind of understand what to do right? You know, a good example of this to give context right is in 2020 there was a headline that was in the New York Post that said biohackers drinking fish tank cleaner to reverse their age. Okay. And this this is about 6 months after we released our company transcriptions and some of our friends were actually featured in that article. Now fast forward to like September of 2025. The New York Post runs a story again on the how amazing Methylene Blue is and they link out to a company selling the worst quality methylene blue that we found on Amazon um with potency terrible u meaning this liquid had much less methylene blue in it than it said on the label. In addition, it was also contaminated with heavy metals like lead, mercury, cadmium and arsenic. And I was just, it was kind of this full circle moment for me to to be honest where I was like, this is where we've gone, right? Where, you know, the fish tank cleaner clickbait headline to everybody should be taking methylene blue, but then linking out to a like an affiliate where they were making money on a very cheap liquid methylene blue that was supposed to have all these benefits. And so it's it's been I think what I'm hoping I guess in 2026 is that we can really I guess dial in that signal, you know, dial it in really really strongly. And I'm excited to do that with you, Jesse.

>> All right. Well, you touched on fish tank cleaner. Let's take a step back and talk about what methylene blue is and its history.

>> Yeah. So methylene blue is it's a textile dye that was developed in the 19 in the 1870s 1870. So it's not uh it's one of the first fully it was actually the first drug registered with the FDA back in the 1890s. And so the 1870s they were making all these different types of dyes to see what they can make for manufacturing. And so methylene blue as many of you likely listening know is a very very blue color. And so as that was happening though in other places around the world they were looking for actual compounds to help with infection because there was no antibiotics at that time. Antibiotics didn't come around until the 1950s. And so if you had a toe infection and it traveled up your leg and your leg got very swollen and you got in went into septic shock, you would die, right? Because there was no antibiotics around. And so they were looking for antibiotics or antimicrobials at all that could potentially help. And they found out that methylene blue specifically had very interesting antimicrobial capacity. And you could give it at very very high doses, very high doses. And you would actually kill pathogens, but you wouldn't harm the normal cell, the the actually the normal host, the human host. And that's why it actually got the name the magic bullet around the 1890s or so, around the turn of the century, because it had this amazing capacity to be an anti-infective. And this is typically at high doses of methylene blue. So in 1897, as I mentioned, it was the first drug registered with our nent FDA in the United States for malaria specifically. And it's actually the first fully synthetic drug, meaning it's not from the ground. It comes from biochemical pathways that are made with, you know, with precursors and things like that, but it's not something that comes from a plant or it comes from a fungus or something like that. And that's in itself one of the arguments against using methylene blue, which we can certainly talk about. And I have lots of ways to to frame that to make to make it easier for people to understand why you might need something synthetic. Living in a synthetic world, we do. Uh the greatest example of this is if you're a diabetic, a type 1 diabetic, and you're taking insulin, guess what? You're taking something synthetic to keep you alive. If you have a severe infection and you need to go to the hospital to get antibiotics, guess what? You're taking something synthetic to keep you alive, right? And so we live in a synthetic world. And as a result of that, we need sometimes we need things that are not actually entirely from the ground as opposed to or the the other sort of the other side of the argument or the other side of the conversation is that not everything natural is good for us either, right? You can have the wrong mushrooms. You can forage for the wrong ones in the in the wild and die of liver failure because I've seen this. And so the dose makes the the actual therapeutic benefit. The dose can make the poison for both natural and synthetic compounds. So that's that's how it started in 1897 way back as the first drug for malaria. Then it has a very very storied history from there that I'm happy to to delve into any way you'd like.

>> Well, let's just keep going then. Let's take it right from where you are and bring it right to current day.

>> Okay. Well, we'll have the way I like to talk about it in this capacity is like the epochs or like the chapters of of methylene blue. Fish tank cleaner gets in there um in the biochemistry lab using it for cyanide poisoning. So, just to give you a little bit of a foreshadowing, right? So, but in the beginning between 1897 until about 1950 or so when antibiotics really started becoming more available, it was one of the most primary antimicrobials available in the world and it was used for urinary tract infections, for fungal infections, for other types of bacterial infections. Later on, it was understood that it could help with viral infections as well. And the dosing of methylene blue for this was on the relatively higher side. It was around about um a milligram per kilogram ideal body weight and above which is about 50 to 70 milligrams of methylene blue or more to treat these kinds of infections. Okay. And even if you were a World War II soldier and you were actually being shipped to the Pacific to to fight there, you were taking prophylactic methylene blue in the jungles to prevent fungal infections. And they actually even had songs about methylene blue going blue in the L actually. And so this is because the Lou is the bathroom for those who don't know. And you your urine when you take methylene blue, the higher the amount of methylene blue you take, the more blue your urine is going to be. And so as a result, they'd have these songs about, you know, urinating blue as a result of taking methylene blue. And so it was very well known that you would use it for these infections and it worked very well, but at the same time it did make your urine blue and not everybody liked that. Of course, at very very high doses of methylene blue, it could also turn other secretions blue, including your poop and things like that. But we're talking like much higher doses like around 2 milligrams per kilogram and above which is like over 150 milligrams 200 300 milligrams which is very unusual to use in in sort of in modern day practice which we can talk about. So that was the first major epoch or chapter of methylene blue as an antimicrobial and then what happened in the 1950s as antimicrobials came around like penicillins of the world it got sort of relegated in that antimicrobial world to the world of fish tank cleaner. So, if you get fish tank cleaner from the fish tank store, you will get fish tank cleaner typically has methylene blue in it. And it's not actually cleaning the fish tank. It's actually an antiseptic for the fish. Meaning that it's an antifungal, antibacterial, antimicrobial for the fish themselves. Okay? But fun fact, just to get this out of the way, nobody should be drinking fish tank cleaner. Okay? Maybe his fish tank cleaner not only has methylene blue in it, it'll also have often times very high quantities of heavy metals like lead, mercury, cadmium, and arsenic. And so you don't want to take and go to your local fish tank store and drink any methylene blue. There's much better sources of it, especially now. I mean, there weren't actually that many great sources of it until our company transcriptions came around and in 2020. We were the first commercial uh company to make a commercial product using methylene blue. Before that you were going for to like industrial places and looking at like chemical locations and USP was was available which is pharmaceutical grade but it was still very difficult to find good stuff. So that's the sort of the first chapter of methylene blue. Um, and then the next chapter um after that is that it was found out it was understood that methylene blue also had this other quality which is called monoamine oxidase inhibition. And what that means is that methylene blue would prevent the breakdown of certain neurotransmitters especially norepinephrine serotonin and at higher doses of methylene blue dopamine as well. And so the first antipsychotics actually were derived from methylene blue. So these are for psychiatric medications. And then what they would do was actually they would compound they would combine a methylene blue uh the methylene blue itself with these antipsychotics in the same uh pills for patients with psychiatric disorders to make sure that they were taking their drugs because if they were taking their drugs their urine would turn blue, right? If they weren't taking their drugs, their urine would not turn blue. So so it had this very significant story within the psychiatric psychiatric world. Not only being that uh the the first drugs derived from methylene blue but also being compounded with methylene blue so that the psychiatric patients were actually known to be taking them and they could be actually um followed over time excuse me while they were taking these drugs. Um so from there we come to like the third chapter or maybe the fourth chapter really of methylene blue. First is a textile dye now is as second is an antimicrobial. Third is it's something that derived antipsychotics and also compounded with antipsychotics. And the fourth would be in the sense of understanding that something was happening in the cells when you used methylene blue and you dropped methylene blue on a cell on like under a microscope. And what you notice is that methylene would stain would actually concentrate in certain parts of the cell and it would actually be concentrating most primarily in a part of the cell called the mitochondria. And as a result of that, it became very interesting. Well, in chemistry lab because you can in when I was in in chemistry lab in in college, we used methylene blue to to to actually look and and to visualize the mitochondria inside the cell. um that it took a number of years to understand what was actually happening at the mitochondrial level. And that really has become like sort of like the golden age of of of methylene blue which is understanding all the many mechanisms that are happening inside the mitochondria which we can talk about in detail but for now just to know is that methylene blue has a fantastic capacity to support mitochondrial function both on the energy production side and on the detoxification side as well compensate for significant amounts of issues that happen with modern society. Um and it was around that time that methylene was also starting to be used um as an antidote for things like cyanide poisoning um which can destroy part of the mitochondria as an antidote for something called methemoglobinemia which is a condition where your cells can't carry oxygen effectively um as a result of the state of iron and methylene could change the state of iron to a state that can allow you to to carry oxygen easier um and then get it to your get it to the red blood cells to carry oxygen easier to get to your cells. Um, and then from there, there's also some very significant interest of using methylene blue in also the world of medical marking. So, if you um are going to get a biopsy, if you're going to get a procedure done, sometimes they'll use methylene blue in those situations to actually use a uh use the the methylene blue to visualize an area of where there might be an issue. Could be in the mouth, could be in the intestines, could be in the breast. And you can actually stain the area with methylene blue to use and to utilize that as a way to understand what's going on from an oncological perspective from a uh some sort of other inflammatory area as well. So that's still used in medical marking. I have a friend of mine who's a transplant surgeon. Um what he does is that he does pancreatic and kidney transplants. He does liver transplants and things like that. And when he's done with the transplant, what they do is that they actually inject they uh infuse methylene blue into the bladder. And what they're looking for inside the body is that if there's any uh breaks in the bladder, do they nick the bladder anyway with a needle or with a knife that would be causing extravasation of the urine into the actual abdominal cavity. So it's still used in that way. And I remember when I first he's a good friend of mine, his name is Joe. And and he and I played in a band in medical school called the airport rocking chairs. Go ARC. Um, and so when he and I were chatting about this a number of years ago, he's like, "Scott, you're using that really?" He's like, he's like shocked because he uses it, he uses it in transplant surgery, um, still. And so it's got this really interesting now history, right? Where it's used in the medical world. Um, it's been around a long, long time. It's got all these potential utilities. It's also something that is prescribed in emergency rooms. It could be used in the transplant surgery um, surgery suite, right? And can also be, you know, purchased on Amazon, right? And so you have a very interesting ecosystem now where and especially over the last year or so since we're recording this in early 2026, you know, it's there's been a significant amount of more interest in what methylene blue can do. And really what I've been focused on is trying to, you know, really kind of again, as we mentioned, let's create that signal from the noise and really discuss how we can use it in modern day.

>> You mentioned in undergrad using in chemistry class as a stain as a doctor though. When did this come back on your radar and your interest get sparked in it again as something therapeutic?

>> So I work with a very very smart physician. His name is uh Dr. Ted Aoso and he's the the founder of our company transcriptions. He's also the founder of our nonprofit. So I met him in in 2017. He created a framework called Health Optimization Medicine and Practice or HOME HOPE. And he was really looking at uh really understanding health from a very different lens. Looking at it from how can we optimize health rather than treat disease and creating a foundational framework that we have and clinicians are able to take and like via online courses that we have. And at the same time he was creating that he was looking into some various compounds that could help with cognition, could help with brain function, um nootropics as it were. So like this is the the this is the conversation we had a little bit last time actually Jesse talking about nootropics and and what that all meant and how you can think about them. And what he came across was some studies that were being done using methylene blue in various ways. It was being used in stroke. It was being used in traumatic brain injury is being used in some studies with Alzheimer's and Parkinson's disease. But there was one study specifically that he saw that was that actually used methylene blue on normal adults and did some actual MRI scans of their brains before and after and saw significant benefit in various areas of attention, memory, focus um and cognition and that really got his attention alongside some of the work that was being done with a researcher um that it was his name is Dr. Francisco Gonzalez Lima who was doing a lot of research and still does at the University of Texas Austin on methylene blue in models of Alzheimer's. And so we looked at the dosing together. We looked at the the potential therapeutic applications. And then that's really why we decided uh to go ahead and and create uh a first product using methylene blue. The first product we created was not pure methylene blue. Actually, it was a methylene blue product combined with caffeine, nicotine, and CBD called BlueBoost. We didn't think initially actually that people would want a pure methylene blue product because it doesn't have a stimulatory effect. It's not like a nootropic per se. Although it does work that way with increasing cognition, it's not going to give you like that Adderall kind of feel, right? It's not going to give you that like holy crap, I'm on something that's helping me focus right now because it's gives you this elevation feel. It gives you more sustainability. It gives you more cognitive capacity. But in some people, it's more like a rearview mirror effect, which is like after the day's gone, you're like, "Oh, wow. I had a better day today than I would typically if I hadn't taken the methylene blue. I felt like my cognition was better. I felt like I had more energy throughout the day. I didn't feel like I had a really like any dips. I didn't yell at my kids when they came home." Or, you know, something like that where you're actually like, "Well, actually, my day was better." Or if you're using it for exercise, you might see from an endurance perspective, you're keeping your heart rate up and lots of other reasons why um methylene could be helpful. But in the beginning, we didn't know that that's what people were going to want. And so we in about 6 months after we launched the company, we actually came out with our first pure methylene blue product called JustBlue. And that was at the request of people that were using our products. Actually, it was like, can you please come out with a pure methylene blue product that they can trust because at that point again, we were the only company that was available. And this is during COVID times and things like that where things were a little weird. Uh a little being an understatement of the century, right? And so as a result of all that um it came into our radar and we kind of knew that you know and and almost honestly Jesse I was pretty skeptical initially you know when I when I read about it um I was learning about it we were talking about it and I was like are we really going to see people interested in this particular compound because it is you know very shocking in some ways and not something that's coming from the ground and is it something that people are going to be you know that resonates with them and in the beginning um again I was skeptical But we got stories rolling in very very quickly from people starting to take it that m changed my mind almost immediately. I mean, I remember it must have been maybe two or three months after we launched, maybe even earlier than that, maybe like within the first month. I got a call uh from a practitioner, a friend of mine um that started taking it and she had been sick for a long time with I think it was, you know, chronic pain, I think chronic mold illness. Um and she said that had, you know, nothing had helped her and then she started taking methylene blue and over a couple weeks her pain was completely gone. We had somebody that had given some methylene blue to her grandmother. It was a lady that bought it. Maybe she was in her mid-20s I think. Gave it to her grandmother and grandmother had mild cognitive impairment. And the grandmother started telling stories about her childhood in Mexico where she grew up that nobody had ever heard of before in the family. And then I kept getting more stories like this and people telling me about their brain fog, about their mental health issues, about their pain, about their inflammation. Um, many just across the board. And I I was pretty well converted very quickly that this is going to be something that was going to be truly truly helpful.

>> As you were going through the history there, when you talked about its antimicrobial effect, it got me thinking about our own microbiome since it has this impact on the microbes. What is it doing to us?

>> Yeah, it's a great question, Jesse. I think what it comes down to understanding a little bit is the dosing of methylene blue. So the higher the dose you go up when you start to getting about around a milligram per kilogram or above which is about 50 to 70 milligrams or more you do start getting antimicrobial capacity of methylene blue and what happens there is that you're having an effect on microbiota and also other organisms that are in and around you that are affected by methylene blue at those kinds of doses. And so you have to be aware of that, right? And this is one of the reasons why, you know, we're so emphatic at lower doses being most effective for most people is that lower doses don't really have any effect like that that we've been able to see clinically. So if you're taking four to 25 milligrams of methylene blue on a regular basis, we haven't seen any major changes to the microbiome. And so you have to understand why you're taking methylene blue and you have to understand what your goal is and and looking at the benefits versus the possible risks, right? So if you have gut dysbiosis for example if you have parasitic infections if you have bacterial overgrowth these are sometimes reasons to use higher doses of methylene blue for a short period of time because it's going to help address those and I've seen this in clinical practice many many times I've also seen it used for gut biofilms and so biofilms are these films that that develop they have normal biofilms we have normal biofilms on our teeth for example we have biofilms in our gut that are kind of these ecosystems where uh you have a the capacity to keep the system healthier when they're normal gut biofilms, but they also can be pathogenic where certain types of pathogens can actually hide themselves in biofilms. A good example of this is Bartonella, which is one of the sort of Lyme co-infections and also there can also be infections in the bladder itself in the bladder wall that get hidden in there and very difficult to treat. And this is one of the reasons one of the uh one of the ideologies or that happens or that this it's a it's a it's a medical condition called interstitial cystitis where you get severe bladder pain and you can have these infections that hide in the bladder wall and methylene blue can help actually uncover them. So you can actually treat them with other types of antimicrobials for example. So the answer is that methylene blue is an antimicrobial at higher doses and you have to be aware of that right? And so if you are taking it for higher at higher doses you are going to have a decrease in your commensal bacterial colonies most likely which are the commensals are the types of microbiota in our gut that we want right? But again, are you doing this because you have pathogenic bacteria you have gut dysbiosis and you just have to rebuild your gut bacteria gut microbiome microbiota over time you can certainly do that and I've done that over time as well. So it's really an important distinction between the dosing and that's something that a lot of people don't really understand is that they you know always think you know more is better like if a little bit of methylene blue is good you should take more methylene blue because it's going to be better but the answer is not not at all that that's the case like most people that I work with the dosing I use is around 4 to 25 milligrams for mitochondrial support and then if they have a chronic infection sometimes I'm getting into a milligram or a milligram and a half per kilogram so that's like 50 to maybe 80 to 100 milligrams for a period of time but it's typically for a short period of time and then we're watching them very carefully and then rebuilding the gut if we have to. And if you have more of an acute infection or acute trauma, acute inflammation, sometimes the dosing can be even even higher like up to around 2 milligrams per kilogram, which can be like around 150 milligrams of methylene blue for five days, but you're not doing it for a long period of time. And again, you're weighing the benefits versus the risks. And like an example would be my my mom who lives in New York was bit by a tick. Okay. And if you're in New York and you get bit by a tick, well your risk of getting Lyme or co-infections is, you know, kind of high, right? And even around the country, most Lyme ticks, I mean Lyme ticks are everywhere now, not just on the Northeast as they used to be. And so in this case, well, I had we had two options, right? We could we were thinking about well does she use just methylene blue here or does she use in combination with something like doxycycline which is an antibiotic that's well known to be good for acute Lyme and co-infections. So in her case we gave her doxycycline along with high doses of methylene blue for for 5 days. I gave her 150 milligrams for 5 days. She felt like a million bucks actually. She felt fantastic. Um and she had you know no no no no symptoms and no issues afterwards. So in some cases you use them in combination like that. some cases you're using methylene blue at those high doses along with antibiotics and I've done that before. I've also used methylene blue on its own at high doses for urinary tract infections in some patients that are very compliant in my practice where I know we can watch them closely and if they don't improve over two to three days and we can start giving them antibiotics if needed. So as it compares to antibiotics though I would say though though this Jesse is that you know a lot of antibiotics are nuclear bombs right? They're just going to completely destroy your microbiota um either in your mouth, your gut, or wherever your skin. Um methylene doesn't tend to do that to the degree that um you will see with antibiotics, especially if you're giving like on that lower dose scale of of the methylene blue. So if you're giving super high doses of it, it might do that, right? But lower doses like around the 50 to 70 milligram mark, I don't see like complete annihilation of gut microbiota typically. I just see a decrease in it and that's something that can you know particular usually very easily be mitigated over the long term as well.

>> Okay. So dosage matters. It sounds like it's still kind of early on to determine the full effect on the microbes,

>> right?

>> We know can kill off the bad ones and again dosage matters. Does route of administration matter a lot when it comes to that because the product you guys have created is something that dissolves in the mouth. We also have an oral microbiome versus swallowing that which is another option with your product and you could do that on an empty stomach.

>> Yeah.

>> So just riff on those ideas and how that might impact different microbes.

>> Right. So the thing about methylene blue that's important to to know is that it's very highly bioavailable which means that whether you dissolve in the mouth or you swallow it um or you get it in the IV, I mean IV is going to have the most absorption throughout the whole body. of course um the bioavailability but orally or in if you dissolve in the mouth or you swallow it the bioavailability is actually not that far behind which is pretty unusual. Most supplements that we take they have a bioavailability that dramatically decreases um compared to an IV for example. So methylene blue doesn't have that. It's um it's still very highly bioavailable. When it comes down to its antimicrobial properties depending what you have in your mouth or you you swallow it. you think about the the way you have to think about this is is the more you have of a concentration of something in a certain area, the more antimicrobial it's going to potentially be at a lower dose. So, this is something you have to be aware of, right? So, often times we don't recommend dissolving more than you about 8 milligrams of methylene blue in your mouth um at a time. If you if you do higher than that for longer periods of time, you likely do have some antimicrobial capacity. But interestingly enough, I'm actually starting to work with some dentists who are looking at using these higher doses of methylene blue as a part of the teeth cleaning process. Interesting. And also because of plaques and things like that and biofilms that might break up. And so we're still that's still very nascent for very early, but there still might be some indications to using a little bit of higher methylene blue especially if you have significant gingivitis and other dental issues that require more antimicrobial capacity. Um, but but in essence what I'm thinking about typically when I'm using methylene blue as an antimicrobial is typically swallowing it. You know, typically swallowing it on an empty stomach and then the dosing anywhere as I mentioned around a milligram a milligram and a half per kilogram of a methylene blue which ends end ends up being around 50 to about 100 milligrams of methylene blue. But oftentimes you don't want to start people at those kinds of doses. Right? Typically uh if you have a chronic issue there's also significant amount of mitochondrial dysfunction that's ongoing as well. So it's very important to support the system and go slowly because what what methylene blue and the way it works as an anti-infective actually is it increases the production of something called hydrogen peroxide and hydrogen peroxide many of you know you can go buy it at your local store but our cells make hydrogen peroxide. Our cells make it as an anti-infective. Our cells make it as an anti-cancer. They make it as a way to kill off cells that aren't supposed to be there because they're not working as effectively as they should. When you increase the amount of hydrogen peroxide in production, you're also upregulating, you're also increasing the the uh the all these other fat others these pathways in our body to increase the amount of antioxidants to help actually um to neutralize that amount of of hydrogen peroxide in the system because hydrogen peroxide is what's called an oxidative stress. It's a reactive um it's a reactive molecule that causes destruction of of things, right? And so you have to have antioxidants that are reactively increasing in the body to be able to neutralize that. And the most important one is glutathione in this case because hydrogen peroxide increases a pathway called the NRF2 pathway. And that increases glutathione production. That is if you have the capacity to make glutathione because not everybody does, right? And so if you give somebody some methylene blue at too high of a dose for example and they they feel like crap most likely one of the reasons is because they're making hydrogen peroxide and they don't have the capacity to have enough glutathione that produces itself or that is produced as a result of that you know having the hydrogen peroxide on board. So you always have to be thinking about this and I'm always thinking about this a lot when I work with patients is that you know I'm always going slow almost always going slowly with their methylene blue dose. Not starting them off at 50 or 70 milligrams for an infection. I'm starting all them off at eight or six or 12 or 16, seeing how they do for a couple days and increase it to every 3 or 5 days until they find a dose that starts working for them. Then we have then when I mean by working for them, I mean that they're actually seeing some mitochondrial support, but that's typically at lower doses and that that's that four to or 8 to 25 milligram dosing range. That mitochondrial support is good, but that's not kind of maybe the entire picture. If we're looking for an anti-infective capacity, we might want to be increasing the dose even more from there. So that we can actually see that anti-infective capacity as well. So initial benefits mitochondrial, then additional benefits would come as an antimicrobial. But you have to be careful, right? Because as you increase, you're increasing the amount of hydrogen peroxide. That's going to upregulate the NRF2 pathway to increase your capacity to make glutathione if you have that capacity. If you don't, then you're not going to feel very good, right? And this is why often times just kind of empirically I mean I get testing on my patients and try to understand their antioxidant capacity and things but even still I'm almost always giving people additional antioxidant support when we're giving them higher doses of methylene blue along with binders making sure they're pooping every day and these and so they can detoxify right adding sauna adding other things that could be helpful because you are causing more inflammation in the system when there's more hydrogen peroxide around and so you have to always be considering that when you're using the higher doses of methylene blue.

>> What do you consider a higher dose? Because one of the interesting things that you're touching on here is the fact that methylene blue has different rules depending on dosages.

>> Yes.

>> And you've talked about the lower dose being for the mitochondria, and I want to get into the specifics of what's happening there in a bit, but where is that switch when it becomes more creating the hydrogen peroxide and fighting infections?

>> It's around a milligram per kilogram ideal body weight, which is going to be around 50 to 70 milligrams for most people. It might be a little bit lower for some others. It might be more for other people, right? It's going to be a little bit different, but that's the range that we've really kind of understood is when you're still going to have like the most uh you're going to see that shift over from mitochondrial support to more antimicrobial support. Um, and but everybody's a little bit different as you said and as I said, and so as a result of that, you have to be, you know, nuanced with your approach. But the problem with a lot of the the products out there is that they're telling you to start taking that kind of dosing out of the gate, which can be too high and and too stressful for the system and then start causing some antimicrobial capacity, which is not what most people need. Um, at least not that's not what their their goal is to use methylene blue. And so that's why lower doses can be so much more effective. You know, for the majority of people, I'm using much lower doses as I mentioned.

>> So when it comes to delivery, you mentioned in the end it's pretty similar for swallowing it or letting it dissolve in the mouth. How does somebody determine route of administration?

>> I almost always lean towards swallowing it these days just because most people don't want a blue mouth and I totally understand that. It does take some time to go away. The more methylene blue you have in your mouth, the longer it's going to take and the bioavailability as mentioned is very very good. The only two groups of people that I typically recommend considering methylene blue in the mouth are going to be those with a lot of brain fog and concentration problems and memory issues because even though the bioavailability meaning the amount that's getting in the body is around the same. How fast it gets in the body is going to be it's going to be much faster if you dissolve it in the mouth compared to if you swallow it. It can start doing its work because it goes directly into the bloodstream of the mouth from the mouth from the buccal mucosa into the mouth within about 15 to 20 minutes as opposed to if you let it swallowed if you let it on an empty stomach it's going to take at least 30 minutes or 45 minutes to start working. So I do have some patients and some of my colleagues that only use it in the mouth because it works faster that way. But in general, most people don't need it to work that fast. And it'll have the same benefit by swallowing on an empty stomach. And then if you eat about 15 or 20 minutes after you swallow it on an empty stomach, it's actually going to be more rapidly metabolized that way as opposed to just waiting for a couple hours on an empty stomach. And so that's because when you start eating something, your your intestines and stomach go into like what's called peristaltic mode, which is they start pushing things forward and starting to help digest things faster. And so as a result, um, you will see a little bit of a faster uptick instead of waiting on an empty stomach for a couple hours or something like that. So in essence, the other group of people that I recommend in addition to those that have more chronic brain fog to consider using in the mouth isn't people that are using it more for dental issues, right? And we talked about this. This is relatively newer where we don't have a lot of data here because it's something that I'm just starting to explore with some dentists now. But the goal of using higher amounts of methylene blue in the mouth during dental procedures, right? And then having actually hygienists go in there and and just clean off your teeth afterwards, for example, or something like that. And using as an antimicrobial as an anti-plaque in the mouth as part of a hygienic procedure. But but those are really the two the two exceptions to the rule. I think the majority of people get the same mitochondrial benefits, certainly the antimicrobial benefits of swallowing it um and without having to have a blue mouth in in the process.

>> You mentioned the ideal there having it waiting 15 minutes and then having some food.

>> Yeah.

>> If somebody forgets to take it before they eat and they have food in the stomach, is it still absorbed pretty decently that way too?

>> It's going to be absorbed that way. It's just going to be slower. So you might not get the same blood levels of methylene blue that you would have gotten because it's going to be like just a slower absorption over a longer period of time rather than a higher absorption giving up higher for a while and then bringing it down. So the half-life of methylene blue is about four to six hours. It's going to be a little bit extended in the sense of how the where your peak of effectiveness is going to be if you if you swallow it with with food. But in some people that are super sensitive to methylene blue, they're super sensitive uh because of energy and detoxification issues related to mitochondrial dysfunction, I will have them take it with food initially just to get them used to getting a little bit on board and then from there trying to transition them off to where they're having an empty stomach ideally uh because they're going to get higher blood levels of the methylene blue that way.

>> For somebody that wants to time their dosage for performance, whether it be speaking on stage or something physical, it sounds like taking it relatively soon before that would be ideal. But let's get into the nuance there. How somebody specifically dosages that to get the most benefit. And this can be for somebody that's taking it on a daily basis or somebody that's just taking it periodically.

>> So, I mean, I think what the the way to describe it is that your peak effect, whether if you've used it in the mouth or you've dissolved it in the stomach or you've swallowed in the stomach, is probably between about 1 to two hours after you've ingested the methylene blue. So, the the half-life again is four to six hours. Um, but the the peak effect is going to be around in the two hour mark, one to two hour mark. And so, if you're using it for something for cognition, for energy, for endurance, that's how I like to think about it. Um, you can also synergize it with things like red light for example and that could help boost the capacity for that time frame as well because red light also works on the mitochondria in a very specific area. Methylene blue works on the mitochondria in a very in multiple areas but can work in the same area that red light does as well. So that's another way to kind of synergize it and and how have like a compounding effect. But in general, I have people typically dose methylene blue in the mornings around seven or eight o'clock in the morning and then maybe another dose around 12 or 1 o'clock in the afternoon if they need it. Again, on an empty stomach, they can eat 15 to 20 minutes later. Um, I typically don't dose it later in the day because I mean, although some people can tolerate it well, some people will find even though it's not a stimulant, they will have a difficult time potentially going to bed at night if they take it too late in the day. Um I do actually but on the other side of things I have some patients and colleagues of mine that have talked about their patients that actually take it before they go to bed. Um because it actually helps them sleep better. Sleep is not a you know we're not like dead when we sleep in a coma. We're actually very highly metabolic and that metabolic support could sometimes be very helpful when people are sleeping as well. So that's another option although not one I typically start with. Typically start with people taking it in the morning um seeing how they feel and then depending how they're doing maybe taking another dose early in the afternoon. But yeah, I think from a maximal effect perspective, you're talking about one to two hours after taking it. But it's a sustained kind of feeling. It's not something where you feel like you're sort of really high and then

Really, and go down kind of thing. It's more like you come up and you stay there for a while, and then then you slowly kind of go down from there without any come down or crash or anything. But it's, but that's typically the the kind of the arc of it.

I think you said the half-life is four to six hours. Somebody taking, say, four, eight milligrams, a lower dose on a daily basis, does that eventually get cleared out of the system if they're just on that kind of dose?

Absolutely, yeah.

Okay. And then what kind of dosage would eventually start building up?

When you get to above around 80 to 100 milligrams of methylene blue per day, that's when it starts building up in the system, and that's when it could become absolutely detrimental. So you have to be very careful of that because if you get high doses of methylene blue, instead of becoming mitochondrially supportive or instead of actually being helpful for the system, it actually becomes stressful on it and actually causes some of the things that it actually treats at lower amounts. And something, you know, called methemoglobinemia, which I was talking about earlier. That particular condition is, uh, something that methylene blue can treat at lower doses, but actually can cause it at higher doses. And so anybody that's usually above about about, usually for me, I'm conservative of like around 30 milligrams a day, but certainly around 50 to 70 milligrams a day, I start making sure they're taking at least one day off per week when they're not taking methylene blue. And above 70, twice a week that they're not taking it. Although, again, it's pretty rare that I have people on those higher doses for longer periods of time. I do, I do have some colleagues that do use those higher doses for longer periods of times, and they are giving them higher breaks.

But, uh, the the half-life of methylene blue between four and six hours, the dosing, if you're keeping it like less than 30 milligrams a day, there's, as long as you have normal kidneys, I think that's the main thing. So if you have any kidney dysfunction, uh, where your kidneys aren't allowing the system to process and detox as easily, then the methylene blue is going to stick around for longer. So you have to be aware of that. But as long as your kidney function is normal, um, it should be out of the system way below 24 hours if you're keeping the dose less than 30 milligrams. Um, above 30 milligrams to 50, probably fine for most people, but I start giving them a day off a week. And then above the 50 to 70 milligrams, I typically start giving them two days off per week, just to be sure.

One of the challenges with methylene blue is the fact that it can dye your mouth. It can dye your hands. Dealing with it can be a little bit of a challenge. We know now we can swallow it and basically get the same benefit.

But if somebody is using say, a liquid, or they're putting it in their mouth, the troche, I guess this would be more for the liquid. I've heard you can take vitamin C and reduce methylene blue where it loses its color. Is this true? And then does it still have the same benefit?

So methylene blue has this effect called being a redox cycler. And this is how it works in the mitochondria. And what that means in essence is that it has the capacity to both accept and donate electrons. And then in the real world, or in real, to give you an example of that and how that really works is that that's what's happening in our mitochondria all the time. Our mitochondria are this redox cycling machine where they're actually donating electrons, accepting electrons, there's there's there's protons, there's antioxidants, all these things kind of going on in the mitochondria to help you make energy, make 150 pounds of ATP every single day. So, a huge amount of energy is required. And you know, fun fact, you know, most of us, 94% of US adults, I'm sure it's not that dissimilar in our northern neighbor, um, have mitochondrial dysfunction. So, it's a huge amount of this. And then what I mean by that on the mitochondrial dysfunction side is that they can't make energy effectively, or they can't detox from the energy that we make. We're more like a gasoline-powered car, Jesse, than we are an electric car, because we, we make waste products. We make ATP, but we also make water. When we make energy, we make carbon dioxide. And we have these electrons that are flowing through our electron transport chain in our mitochondria that leak out. As we get older, it gets worse, and we make these what are called reactive oxygen species. This is normal to some degree. We need to have some of these. It's not like you want to take like huge amounts like, you know, huge loads of truckloads of antibiotics, excuse me, antioxidants every day. Not antibiotics either, but definitely not antioxidants either, because that's going to actually have a detrimental effect. You need some of these to help signal the mitochondria to know what to do. Okay? But most of us are antioxidant deficient, and then we have a buildup of reactive oxygen species. Okay? And so, and then we, because we're antioxidant deficient, we have more reactive oxygen species. We have more of those electrons that are leaking, and then we get more stress in the system. So in any way you shape and form you take it, you see that the mitochondria are under significant stress. And so what methylene blue can do is it has this capacity to both help with the energy production side, helping you make energy more more effectively, and at the same time help with detoxification. So I like to think of it more like an electric-powered car where you have energy going in, but there's no exhaust because it, it works as its own exhaust. It works as its own capacity enhancer for antioxidants. So as an antioxidant itself. And so you bring it methylene blue in there, and it doesn't give you the stress of making energy because it actually actually neutralizes that stress itself.

Now, back to your question, to give you more, that was a little bit more of a preamble here. So methylene blue has these states. It either can have an oxidized state or reduced state. An oxidized state when it has a free electron, so it can pick up electrons. And a reduced state when it has another electron, um, on it and actually can donate that. So, it has this capacity to either accept or to donate electrons. That's why it works on both sides of the mitochondria. It can help with donating electrons to make energy, or accepting electrons to neutralize reactive oxygen species. That's really what it's doing. Now, when it's in its oxidized form, when it has the capacity to to accept electrons, it is a blue color. Okay? When it's in its a reduced form, which means that it now has accepted the electron and actually can donate it again, it is in a colorless form. Okay? And so vitamin C is an antioxidant. What are antioxidants? Antioxidants have a capacity to donate electrons to free radicals, to reactive oxygen species, and neutralize them without becoming free radicals themselves. Okay? Vitamin C is the classic example of that. So if you combine methylene blue with vitamin C, what happens is that vitamin C donates electrons to the methylene blue, changing it from blue to colorless. Is this a good thing? Is this a bad thing? Or is this a neutral thing? The answer is that we don't know for sure. However, my sense of things here is that what often times we need is more mitochondrial cleanup initially, then we need more energy production in the mitochondria. So, if you're bringing in the methylene blue and you've used it directly with vitamin C, now you have a methylene blue in a state where it's already picked up those free electrons, right? And so, it doesn't have that capacity to be an antioxidant directly. It can get that capacity back because it's always going to be cycling. So, we don't know for sure, but my general sense and clinical experience over the years is that it seems to be better if you use methylene blue as a blue compound and then allow it to do its thing in the body and take vitamin C separately. You know, take it, you know, a couple hours later, couple hours before. So, in general, I usually recommend not taking antioxidants at the same time as taking your methylene blue, that you allow methylene blue to do its thing, you know, to go to the mitochondria to do what it's required. Because what it feels like methylene blue can do from a clinical perspective is almost work like an adaptogen in some ways, which is that if it needs to give you more energy, that's what it's going to do first. But if it needs to help you with detoxification first and it'll clean up oxidative stress, those reactive oxygen species, then that's what it's going to do if you allow it to kind of come in the body in the blue shape, in the blue form, and kind of do its thing. Um, I don't know for sure though. You, and this is one of those things where, um, we don't have a lot of data to compare, you know, it's called leuco methylene blue, which is its reduced form, versus methylene blue and looking at in clinical, in clinical practice, we just don't have a lot of data. There were, there are actually a couple pharmaceutical companies that were looking at using leuco methylene blue derived something derived from leuco methylene blue in various pharmaceuticals, um, to see if that would work in in actual, in in in animal models and also some human human studies looking at Alzheimer's disease, for example, some actual some pharmaceutical drugs. So, in essence, you can look it up if you're interested, it's called the blue bottle experiment. You can take methylene blue, you can combine it with vitamin C, and voila.

Now, this is also a separate but also important point here is that if you have methylene blue at your house, liquids are the messiest. No doubt about it, because they can get everywhere. We make troches with these dissolvable lozenges, which are very precision dosed. You can take a quarter, you can take a half, you can take a full. Um, but methylene blue is going to be blue, no matter how you swing it. If you're cutting one of our troches, you want to do it on a dark surface on a paper towel. Um, that's what, you know, that's a very, very important thing. Um, however, or in addition, I have buffered vitamin C at my house because if it gets on a surface, you can scrub it out of the surface very, very quickly using buffered vitamin C, and you can save your marriage, like I have a couple times, like because I've gotten my sink with methylene blue, of course, and my my washing machine, my floor, you know, all these places where if I have a little bit, scrubbed, you know, buffered vitamin C, I can get it out very, very quickly using it. So, it's, it's a very good thing to have in your home if you're going to be having methylene blue around. Again, when it comes to the liquids, I don't recommend it for a number of different reasons. Obviously, we're talking about how messy it is. Um, the second part of it is that they're very difficult to dose. You don't know exactly how much you're getting every single time. Like, my one of my biggest pet peeves, Jesse, is that somebody tells me, "Hey, doc, I've been taking methylene blue and it's made me feel terrible." I'm like, "Well, what are you taking?" "I'm taking liquid." "Well, how much are you taking?" "I'm taking 10 drops twice a day." I'm like, "Well, how much is that a milligram dosing?" I'm like, "I don't know. I'm just taking drops, right?" And nobody ever knows how many milligrams you're taking. And even if they did, the likely potency is about half of what it says on the label. And every bottle is different. Every dropper is different. Um, it's just kind of all over the map. So, it kind of drives me crazy clinically because I have no idea how much you're actually taking. And so, I get it. It's like it's cheaper, but you're, you pay for what you get. You get, you know, you pay for what you get. That's what we talk about all the time, right? And that's kind of what's happening with most liquids out there on the market. So, yeah, fun fact, make sure you get vitamin C, buffered vitamin C for the house. Um, so you have it just in case anything gets anything on there, but don't take it at the same time as methylene blue. I think for the reasons I just laid out.

What do you think about taking ascorbic acid powder in water, say 15 minutes after your tongue and mouth is blue? For one, would that work? And two, would that have any negative effect on the methylene blue?

So, it won't take the methylene blue off of any of your mucosa. Sorry to say, it will help your teeth. Your teeth will have less blue on them if you take your ascorbic acid 15 or 20 minutes later, um, after dissolving in your mouth, but you can always just brush your teeth. You can always, you know, you can always wash your mouth out with some baking soda. Those are better ways to do it. Or even hot liquids. Hot liquids will help get rid of the blue faster. The mucosal blue does take longer to go away, and vitamin C has no effect on that when it gets into the mucosa itself. But the good news is it's not permanent. It goes away. It's a low dose. It's not going to be there forever. The higher dose may be longer. Okay? But again, we're not talking. For my patients, nobody is using more than 12 milligrams of methylene blue in their mouth. Anything more than that, they're swallowing. Even 12 and a half is a lot. Usually, I, I like to do four or maybe eight milligrams at most in the mouth, but some people will go up to 12 and a half, almost always. Anything above that is going to be swallowed. And again, mitochondrial effects are the same. It's just how fast it's getting to the system, right? So you don't have to worry about the effectiveness of it. It's just about how fast it gets in. And, and that could, but look, I understand like that's like during COVID, for example, nobody cared if their mouth was blue, and it wasn't a big deal because everybody's wearing masks. Thank goodness that's not the case anymore. So we can, you know, hang around without having masks on. And nobody, and not that very many people want having a blue mouth. And I understand that. And, and I don't either, you know, most of the time. And, and so I mean, for like the first couple years, I had a blue mouth like almost every day. And my, my wife started looking at me and, you know, initially it was funny. And then, you know, when I didn't have a blue mouth, she was surprised, kind of thing, right? And, and so in the beginning, when we came out with with our with our products that were methylene blue and we were talking about in the mouth, we talked about, you know, blue being the new smart. It wasn't, you know, why my mouth, why my mouth was blue. Was why your mouth wasn't blue, right? That was the, that's kind of how we did it. But look, in the end, what I care about is clinical relevance and clinical application to what we do. I'm a physician, right? I'm a clinician. I still have a clinical practice. And I really care about how it's working with patients. And over the years, it just became very evident to me that it wasn't necessary to have the blue mouth. You could swallow it. You could have the same mitochondrial benefits. And it was just, it was just really important that you kind of did it in the context of understanding, well, we're really focused on mitochondrial function here mostly. How are we optimizing mitochondrial function? What are the synergistic therapies we're doing on top of that? What are the optimization strategies? What are the foundations that we're kind of bringing alongside the use of methylene blue? And then that would be the long-term strategy.

Early in the conversation, you mentioned the fact that the first product wasn't pure methylene blue. We know now we can take methylene blue and absorb it in the stomach. But what about the other products that contain things like nicotine, GABA? Are all those absorbed in the stomach well as well?

So, we have a suite of products that have methylene blue in them, and then we have another suite of products who do not have methylene blue in them. So, when and when we have a combination product, and we have many combination products, including something called Glucanotine, which is the combination of nicotine, caffeine, methylene blue, and CBD. That one is better in the mouth, and that will make your mouth blue. But the amount of methylene blue in there is much lower than our pure methylene blue product, the Just Blue, which is 16 milligrams. In Blue Canotine, the amount of methylene blue in there is five milligrams in a full troche. And the average dose is about a half of a troche, which is going to be about 2.5 milligrams of methylene blue. So, it's not a huge amount. And the amount of methylene blue, as a result, does not make your mouth blue for very long. And the key for that is that you keep it in one location and don't move it around. You don't talk when it's in your mouth. You don't swallow anything if you can. You just all the way back, you park it between your upper cheek and gum. You let it dissolve over about 15 to 30 minutes. And what's nice about that particular product is that it's very, very fast acting. Within about five to 10 minutes, because of the nicotine and caffeine in there, your brain is going to feel the difference, and people love that, right? So, you can certainly swallow the Glucanotine as well, but if you do that, you are risking the bioavailability not of the methylene blue, but of the other compounds in there. And then we have a GABA suite of products that are based on the GABAergic neurotransmitter system with troches that are kind of putting the brakes on the brain. It's the GABA system itself. Mouth. Those are combination products that are better dissolved in the mouth, but they don't turn your mouth blue because they don't have any methylene blue in them.

Got it. Yeah. I was just curious cuz I think I've done orally and swallowing with all the different products, but I was just wondering the effectiveness.

Yeah, good, good example here. I was doing a podcast or some sort of interview, and I was demonstrating on the podcast that you can, you don't have to dissolve it in the mouth. You can swallow your Just Blue, just like you could, you know, put in the mouth. And I thought it was just blue, but I realized about an hour later that I had swallowed a full troche of Blue Canotine. And to give you a sense, my dose of Blue Canotine is typically one quarter. Okay? So I don't take a lot, but I took a full one. And I definitely, definitely felt the stimulation. It was like 4:00 or 5:00 in the afternoon, and I was like, "Oh man, here we go." Right? Because it was, it was much, much more than I typically take. Cuz I was up till like 2:00 or 3:00 in the morning, and I was very, very productive that evening. Not that easy to wake up the next day. It wasn't ideal, but it did give me a come down or crash. It was just more than I really needed, right? And so what I often recommend is in our combination products like Blue Canotine, for example, you may need more to get the same effect if you swallow it, and it's going to take longer to see that effect. So, the ramp-up is going to be be slower, right? So, you're not going to see an improvement in cognition, productivity, focus, verbal fluidity in five to 10 minutes. It's going to take you 30 minutes or an hour to see that kind of thing. And, and that's okay. You know, you may just need a little bit more, and you won't have the blue mouth, but it's not as blue to dissolve Blue Canotine in the mouth. And so, that's what I typically recommend people do if they can.

Okay. Throughout the conversation, we keep talking about mitochondria and mitochondrial support. Let's take this right from the top, get into the details. Somebody swallowing methylene blue into the body. Talk about the impact on the mitochondria and the details there.

Okay, so let's do a quick biochemistry lesson for everybody just to get us on the same page. And I'm not going to get crazy here. My daughter is doing her biology class now. She's in nth grade, and she just finished her, like, her last unit on oxidative phosphorylation, which is the capacity for our mitochondria to make energy from oxygen. Okay? She did it in plants, she did it in animals. I didn't remember anything about plants, actually. I was learning it with her again with chloroplasts and all these other kinds of things that I had totally forgotten about. But for our purposes, let's talk about these mitochondria, right? So mitochondria are the engines of our cells. They are the parts of our cell that help us make energy. Um, as I was mentioning earlier, we make about 150 pounds of ATP, our energy currency, every single day. And we have some cells in our body that have a huge amount of energy demand. And we have other cells in our body that don't have as much and don't need as much mitochondria per cell. So we have some cells in our body that have thousands of mitochondria per cell. And we have some cells in our body that make very, that have very few mitochondria because they don't require as much energy. So the cells that have the most mitochondria per cell are eggs and sperm. Right behind our reproductive organs, which again, fertility rates, they're not going up, right? They're going down. And this is kind of like the lowest common denominator, which is mitochondrial dysfunction. Just after the eggs and sperm, we have our brain. Then our heart, our liver, our musculoskeletal tissue, our kidneys. So we have a lot of areas in our body that require a lot of energy on a regular basis. And our brain is typically where most of us are going to feel this. We have brain fog, concentration problems, mental health disorders, attention problems, right? Mood issues. These are all at its base related to mitochondrial dysfunction. So the question becomes, what's causing all this mitochondrial dysfunction, right? 94% of US adults, as I mentioned earlier, have some element of this. Well, a lot of things. A couple things to to mention here that are really, really important. The first one is insulin resistance. Because if you're have high blood sugars all the time, what's happening that's causing a lot of inflammation in the system, and this includes the mitochondria, because what the mitochondria uses to make energy is glucose or fat, which I'll talk about in a minute. And as a result of that, if you have a lot of glucose going to the mitochondria, you're making a lot more energy. If you're making a lot more energy, you're also making a lot more waste. You have a lot, have to have a lot more antioxidants around to combat that. And if you don't, if you have a lot of that going on for a long period of time, you deplete your antioxidants and you cause a lot of more stress in the system. So insulin resistance is actually one of the major causes. The other major cause of mitochondrial dysfunction is what I call the sympathetic spiral of doom. It sounds quite ominous, but this is what I, I mean is that your body is always in fight or flight. Your body's always in a hypervigilant place. Most people are living here more of the time than they realize. The other area, the other, the other aspect of our nervous system is called our parasympathetic nervous system. That's our, and compared to our sympathetic nervous system, which is our fight or flight. We were supposed to be in parasympathetic more than we are in general. Um, but being in sympathetic causes a lot of hormones like cortisol to be released, neurotransmitters like epinephrine and norepinephrine that put a lot of stress on the mitochondria over time and cause mitochondrial dysfunction. You also have toxins in the environment that cause mitochondrial dysfunction directly, infections, medications. These are all causing significant mitochondrial stress, and as a result of that, you're not making energy effectively.

So with all that in mind, what's actually happening in the mitochondria is that the mitochondria are taking energy. You're taking actually electrons from your food, mostly carbohydrates and fats, and those electrons are being donated or transferred into the part of the mitochondria called the electron transport chain. The carriers of these electrons are things like NAD and FAD. F is in Frank. Many people have heard of taking NAD supplements, right? NAD is this really important carrier of electrons from our food to bring it into the mitochondria to help us make energy. Okay? And how is this all working, right? So the electrons go to the mitochondria, the part of the mitochondria called the electron transport chain. Electron transport chain has four different proteins aptly named 1, 2, 3, and 4. Complex 1, 2, 3, and 4. Electrons flow through these protein, protein complexes creating a gradient of protons. A gradient basically that allows you to, as a result of this gradient, to go first, you're going against the gradient to make it, and then you're allowing some of these protons to go through the gradient back, and that's what actually makes ATP. So, short story, electrons flow through, they create a gradient, and then we release this gradient, and while we release this gradient, we're making ATP. We make ATP, we make water, we make carbon dioxide, and we also make those free radicals, the free, the reactive oxygen species, because not all those electrons make it all the way through. Sometimes actually they leak across those proteins and cause a reactive oxygen species. And then oxygen, oxygen's required because it's the final electron acceptor. So, as those electrons are going through the chain, they need a place to go at the end, and at the end, they get picked up by oxygen, and that's how we make water in our cells. Okay? And this is the structured water that everybody cares about. This is the deuterium-depleted water that people talk about all the time, right? And so this is a very important type of water for how our cells maintain electrogradients and and proton flows and and everything like that. Okay. So that is your ninth-grade chemistry lesson on how to think of what mitochondria are.

So, as we're now understanding mitochondria, they have this electron flow. They're making energy. They have this, um, the other side of it, which is the reactive oxygen species. They're making water and carbon dioxide. And that's where the antioxidants come in to help neutralize that reactive oxygen species. Okay? Now, the problem is, I said 94% of of us adults have some element of mitochondrial dysfunction. So, what does that mean? It means that either you can't make energy effectively. Those electrons aren't flowing effectively and causing energy to be produced effectively, or you can't neutralize the stress of making energy effectively. So, you've made energy, but now you have those reactive oxygen species that are hanging around, and you don't have enough antioxidants to be able to neutralize that. Okay? Um, just to give people like more of a a basis of this in a real-world sense, a lot of people hear about metabolic health these days, right? Um, and what I like to describe here is that metabolic health is mitochondrial health. Okay? And what metabolic health really means, if you're metabolically healthy, it means that you can make energy effectively from the food that you eat, and you can then neutralize the stress of making energy in your mitochondria effectively. Just what I said about mitochondrial function is the equivalent of metabolic dysfunction. So, you'll find out there people talking about metabolic health all the time. Well, really, what they're talking about in essence is mitochondrial health. It's the same thing.

Now, you have all these things that are stressing the mitochondria, causing challenges. Now let's talk about methylene blue. Methylene blue, we very well know, concentrates in the mitochondria. As I mentioned earlier in our conversation, we found this out because they were looking at cells under a microscope. They put methylene blue in the cell, and suddenly it was concentrating in this really cool part of the cell called the mitochondria. What is it doing there? It has the capacity to both enhance energy production and also be directly and indirectly an antioxidant. And there is no other compounds out there that really do this in the same capacity. Maybe, maybe hydrogen itself, taken like orally or inhaled, can have a similar effect, and I can talk about that if you're of interest. But in essence, methylene blue is one of the few compounds on the planet that we're aware of that, what's called redox cycles, has the capacity to help you both make more energy and detoxify at the same time.

If you have mitochondrial dysfunction, the most common places to have this dysfunction are on complex one or complex two. And complex one and complex two are the ones of the complexes that are taking the electrons from your food and bringing them to the electron transport chain so that you can make energy. So if you don't have working complex one and complex two, you're not going to make energy effectively. You're not going to feel good. All those symptoms I mentioned, infertility, brain fog, concentration issues, cardiac issues, detoxification, uh, issues, muscle issues, pain, inflammation, these are mitochondrial issues, you know, when it comes down to it. And so that's what you're going to feel if you're not making energy effectively. And so what methylene blue can do is it actually can compensate by bypassing some of those dysfunctional complexes and allowing electrons to get further down the chain to be able to help you make energy. It also can recycle and renew parts of those protein complexes and actually can help recycle and renew your NAD supply as well. So you don't have to take NAD supplements. You can just have some methylene blue. And there's, you know, a controversy about NAD supplements themselves anyway, as you likely know, Jesse. And so for me, that's one of the big components of it, right? Right. Is because so many of us have such energy production capacity issues, and methylene blue can come in there and compensate for that. In addition, as I mentioned, the redox side is that it can help with the detoxification side, too. So, you're bypassing complexes that aren't working very well. You're renewing the complexes over time. You're making them more optimized. And at the same time, while you're doing that and making more energy, you're also helping with the detoxification side, too. So, you're not causing a lot of stress on the system. But low doses are key here. If you start giving high doses, then you're making that hydrogen peroxide again and causing more stress on the system that the, that, you know, that the mitochondria may not be able to tolerate. That's why these lower doses are so, so important and titrating the dose over time. Starting off at four milligrams, staying there for three or five days, and saying, "Oh, go, how do I feel? Am I feeling a little bit better? Am I not?" Like, then if you're feeling great, then you stay there. But if you're not feeling like you have an effect yet, then increase it. Go additional four milligrams. See how you feel. Then start there or stay there for about three to five days. It's important to realize as a corollary to this that methylene blue is not one of those things that builds up in your system over time and starts working. It's not like you take it for like 30 days and see how it feels. No, if it doesn't work after about three to five days, you don't feel like it's having an effect, then you go up in the dose and you go up the dose again. Then when you find the dose that seems to be working for you, you could be like, "Well, should I try a little bit more?" And then you can try it. Typically, if you do that, you won't see any additional major return on your investment there. And you'll just kind of go back to the dosing that you were at before. And that's how I typically dose it with my patients. I start off at low doses and increase the dose over time. Don't wait too long. Long, if it's three or five days and no major effect, keep going up on the dose until you find a benefit there. And that really does mitigate the the the potential for you causing, you know, too much stress on the system and and having where you you're getting symptomatic like detox kinds of symptoms or headaches or and things like that. But it does, it does still happen for sure, but like, but much less often if you start at the lower doses and increase it from there.

Okay, so very high level here. 94% have challenges with their mitochondria.

Yep.

Methylene blue can come in and help facilitate. What about that 6% that don't? Are there certain benefits for those people?

I had a friend of mine recently, um, actually, I was recording with him on a podcast, and he said, "Scott, what you really mean is that 100% of people have mitochondrial stress, but only 6% of those people have enough resilience to be able to neutralize and to be able to be optimized with that kind of mitochondrial stress." And I said, "That's probably a better way to think about it." But even those 6% are going to have mitochondrial stress that's not going to be easy for them to tolerate, you know, at for periods of time as well. Think about like severe, like stress at work, maybe being an example, but more likely things like travel or sickness or a severe stress that's out of the norm for them, right? So, if you're healthy and your mitochondria are optimized, it's unlikely you need to take methylene blue on a regular basis. You can take it periodically when you have more mitochondrial stress. And this is what I do with my patients that they're pretty well optimized. I'm giving them blue when they're traveling, uh, when they're super stressed at work, when somebody's sick at the house, um, when they're doing significant amounts of endurance racing or really challenging themselves physically. Uh, because methylene blue has this capacity to also work like oxygen to some degree, where it can actually, uh, maintain your, you can maintain your capacity with aerobic respiration for longer when you have methylene blue on board and reach your lactate threshold later as a result of having methylene blue on board. So you actually can do more work, uh, from an oxygen, uh, from an oxidative phosphorylation perspective. Meaning you can make energy from oxygen for longer if you have methylene blue on board because it can work just like oxygen. And so this also correlates to not only endurance racing but also travel. Right? If you're on an airplane and you're pressurized to 8,000 feet above sea level, which is what you are on a on a regular airplane, you're hypoxic. You're low oxygen on that airplane. We've went from on average at sea level, it's about 21% oxygen in the air. At 8,000 feet, you're really about 17 or 16% oxygen in the air that you're breathing, and that's immediately a hypoxic stress where your body's like, "Oh crap, now I don't have enough oxygen." Around those electrons start backing up, you get more inflammation, you know, the methylene blue comes in, and you can actually rescue that capacity for longer and decrease inflammation and actually neutralize some of that reactive oxygen stress that's happening. So you have, again, somebody might be pretty well optimized, but they're still going to feel better if they had some additional support while they were traveling or while they were doing endurance racing and things like that. So, in essence, the more mitochondrial support you need, the more often you're going to need to take methylene blue, especially in the beginning. And hopefully, over time, you can decrease the amount that you need by optimizing your health in various ways, optimizing vitamins, minerals, nutrients, and cofactors, your diet, your lifestyle, your stress, all those things, right? But if you're pretty well optimized to starting off with and you use it periodically, use it as needed when you have, you know, higher stress related events where you know you're going to be under more stress for a period of time where having methylene blue on board could be certainly, you know, significantly helpful.

When somebody's taking methylene blue, obviously it's really targeting the mitochondria as you're getting into here. How much of that benefit is temporary as it's in our system and on board versus actually fixing mitochondria, if any?

So, what I usually tell my patients is that there is some evidence that methylene blue does have some capacity to renew and to increase, uh, the density of a certain, of certain complexes of the mitochondria. So that even if you stop the methylene blue, that benefit should likely continue. But the majority of what I emphasize to patients is that this is not, for the most part, for most people, a long-term solution to support mitochondrial function as the only thing that you want to do. Because what happens if I give somebody methylene blue, oftentimes, and they're doing nothing else different to optimize their health, they stop the methylene blue, and their symptoms are going to come back, mostly. Okay? And so I don't think about it as a fix-it pill that you take it and then you're done after you take it. I think of it as something that's supporting you because life is freaking stressful. Life is going every which way for many people. We are busy under bad lighting. We have bad food. We travel. We have stressful, you know, relationships with our spouses, with our kids, with our parents, you know, like there's all these things that are happening at all times. We're not living in a world where we're hanging out in parasympathetic mode most of the time, right? So that's why I think methylene blue can be fantastic because it has this capacity to support you. But, and this is the big but, right? It's like I get the question, which is kind of similar to your question, is can you become dependent on methylene blue, right? And the answer is that you can only become dependent on it if you're not doing anything else to optimize your health, right? In the sense that if you stop it, you're not doing anything else to support your health. Your symptoms are going to come back. No doubt about it. You know what I mean? So, there is some evidence that can enhance and optimize, especially complex 4 on the mitochondria. Clinically, what I've seen is that, um, if people stop methylene blue and they haven't been doing anything else to support their system, their symptoms are likely going to come back over time. So, my framework here is that we're using methylene blue in the capacity to help you right now while you're on the longer path of optimizing your health. And over time, yes, you're, everybody's going to have all the things that I just mentioned in their life with stress and life, right? And so it's going to be periodically helpful to take your methylene blue so that you can support yourself through those moments and days or weeks, whatever it might be, but you shouldn't need it every day. Um, and if you do, that's probably because you're not doing some of the other work that really could be helpful long term. Like, why are you stressed all the time? Do you need to get out of a a toxic relationship and get divorced? Do you need to sleep in a bed, same, a different bedroom than your spouse because they're snoring? Do you need to get out of a bad job? Do you need to work on your own stress response and figure out, well, maybe I need to figure out how to get into parasympathetic mode? I wouldn't, I wouldn't recommend telling anybody to calm down because that doesn't typically work, by the way, especially a spouse or a partner. Please don't tell your spouse or partner to calm down. It never works. Um, believe me, I'm sure many of you have tried, as have I. It doesn't, it doesn't work, right? So, you want to have, you know, these long-term strategies for patients. And, and I think about this a lot because I think about this from the capacity of the energy production side and the detoxification side, and what's all happening on both sides of this all the time for my patients, and how I can work on that to support them. How can I support mitochondrial dysfunction so that their insulin resistance is better? So that their stress is better, so they're not taking medications that are affecting their mitochondria, so that they're not exposed to toxins or whatever it might be, right? So, you have to be thinking about all those things. Those are the inputs, right? You have to be thinking about also how you can support detoxification because that's also very important too. But a big thing here, Jesse, is that a question that I get a lot is that, well, why don't, why can't I just take antioxidants? Isn't that going to be helpful? And I go, yeah, you, you antioxidants can be helpful to support that antioxidant capacity that we've been describing, but what if you still can't make energy effectively? You're still going to feel like crap. Yes, you've taken your glutathione and your binders. A great example of this is I was talking to a practitioner a couple months ago now, and she's like, "Well, I was, I'm on this detox protocol myself." She was on a detox protocol. I've been taking my binders. I've been taking my antioxidants. I've been doing the sauna, and I, I just felt wasted, just washed out, you know, and because I had all this toxicity, and I've been working on it, but as soon as I started adding methylene blue into my, my, my protocol, I didn't feel washed out at all." And, and she asked me why. And I, and there's a very obvious reason. I was kind of foreshadowing it here, which is that she still had energy production capacity enhancing because she had methylene blue on board. So even if she was getting detoxification and she was getting that part of that side, she wasn't getting enough energy support. And that's why she was feeling so tired afterwards. But as soon as she started adding methylene blue, what happened? She started actually feeling actually much better after getting out of her sauna. She felt energized after she got out of her office because suddenly she had more energy and she had the garbage collection was all good. Right? One of the things I, a great analogy that I like for garbage collection for people. This is your reactive oxygen species. This is your oxidative stress. This is your lack of antioxidant capacity. All those things. Think about a city where garbage collection stops. The garbage just starts piling up and piling up and piling up, and then starts smelling, and then you know there's animals and there's everything like that's what's happening in your cells if you don't have enough antioxidant capacity. But you also need to have the energy producing capacity as well to actually see the benefit over the long term, right? So if you have garbage, have garbage trucks, but they don't have electricity, like what's, you know, what's the, you know, what's the difference afterwards, right? So, like, there's the analogy I'm still working on, but you get my point.

Earlier you talked about incorporating red light with methylene blue. Now that we understand the physiology and what's happening under the hood, talk about what's happening there.

Yeah.

And how somebody can go about using that to their benefit.

So, red light therapy is typically a nanometer wavelength around 680 or so, 680 nanometers. So it's red in color. And there's been some good studies looking at combining red light with methylene blue. Uh, you can use low doses of methylene blue with low intensity red light to enhance complex 4 specifically in the mitochondria. So this is enhancing the capacity to donate electrons and photonic energy directly to complex 4. Methylene blue donates electrons. Red light donates photonic energy, uh, to complex 4. And as a result of that, enhances your capacity to make ATP. So, what you'll find is if you use your methylene blue, you take it, and then you go in front of your red light panel 30 minutes, an hour later, depending on how you took your methylene blue, or you go out in the sunlight. Sunlight has red light as well, you're going to feel a synergistic capacity go up. Your energy is going to go up. Your focus is going to go up. You're going to feel better. You're just going to, your mind is going to feel more clear. And this is, you know, this has been shown, um, countless times anecdotally around around the world. And, and there was also, you know, with people taking it. And there's also a study looking at this in animals combining methylene blue with red light at these levels and at higher doses of methylene blue, the milligram per kilogram dosage that I talked about for antimicrobial dosing.

milligram to milligram and a half or so, combining with more intensity, high-intensity red light lasers, you get a significant anti-infective capacity. Because what methylene blue does here is it becomes a photosensitizer. So it actually increases the production of these reactive oxygen species like hydrogen peroxide, hydroxyl radicals, um, oxygen, singlet oxygen, as well, that also are fantastically antimicrobial and anti-cancer as well.

So there are some studies that have looked at methylene blue combining it with what they call photodynamic therapy. So when you have high-intensity lasers, it doesn't become red light, it, it changes its name, even though it's the same wavelength, to being what's called photodynamic therapy. So in this case, methylene blue becomes a photosynthesizer, photosensitizer, excuse me, not photosynthesizer. Going back to my daughter's uh science class, photosensitizer. And so that it sensitizes um the tumor, for example, in this case, to the combination of methylene blue with the high-intensity laser. So it's super cool and it's being used in this way. I've actually, there's a couple clinics outside the country that are using intra-tumoral lasers with, so like, like actually putting a laser in, inside a tumor itself, a high-intensity red light, combining with methylene blue together and seeing some fantastic benefits.

So I mean, mostly what I use clinically is the lower doses, right? The lower doses of methylene blue. We go around four to 25 milligrams. Combining that with red light is a fantastic way to support and enhance your mitochondrial capacity to make energy. And again, the cool thing is that you're not creating more waste because the methylene blue works as an antioxidant directly as well. All right. So, red light, methylene blue, good combo.

Any other modalities or substances that work well with methylene blue?

It's a good question, and there's a lot of ways to answer that. I would say that when you're looking at methylene blue and how it does help you make more energy and increase metabolic rate in that capacity, what I'm often doing is giving additional co-factors of energy metabolism. That's typically B vitamins, typically minerals. Um, if somebody has a lot of oxidative load ongoing, typically antioxidants at the same time, although it's separate times of dosing, as we talked about earlier, so that you don't have an effect on the capacity of methylene blue to do its redox thing. Those are the sort of my mainstays when it comes down to it.

I, there are people that are combining methylene blue with NAD, for example. I'm not sure that's necessary. Um, I do think that some of the precursors, I usually use vitamin B3 specifically, which turns into niacin, and then that'll help regulate your NAD supply. I don't usually give direct NAD. Um, some of the other precursors like NMN or NR might be interesting in some cases. I, I found um, I've also from another other compounds perspective. Um, one other that that's kind of important to talk about, I think, is nitric oxide as well. Um, it's one that gets talked about a lot in the setting of methylene blue because, um, nitric oxide itself is very, very important. There's different types of nitric oxide. There's nitric oxide that's very important for our blood vascular wall, which keeps our, you know, vascular system healthy, our heart healthy. There's nitric oxide that's in our mitochondria that helps with energy production. There's nitric oxide in our brain as well that helps with energy production, detoxification, excuse me.

And so one of the things that's pretty well known is that methylene blue does have an effect on nitric oxide. But what's not well known is what that effect exactly is. And so I'll tell you how I use it first, and I'll tell you why. At higher doses of methylene blue, like about a milligram and a half, milligram or milligram and a half, so like 50 to 70 milligrams or above, I'm typically using nitric oxide support at the same time as a preventative, potentially to the decrease in nitric oxide that may happen at higher doses of methylene blue. Endogenous nitric oxide is a type of nitric oxide that's released in the mitochondria in the vascular walls, okay? When it comes down to looking at lower doses of methylene blue, I don't typically use nitric oxide as a support. And this is why. There's a different type of nitric oxide that we really do really care about. There's the endogenous supply that comes from the vascular walls, from the mitochondria, but there's what's called inducible supply of nitric oxide. This is a type of nitric oxide that's released when you have infection, inflammation, severe stress, and this is a circulating type of nitric oxide that's released and causes pain, inflammation, inflammatory cascades, um, and uh, it causes low blood pressure as well.

So, this is the type of nitric oxide that's important at low doses. But oftentimes is vastly disregulated in people with chronic complex medical illness where they have low blood pressure. Like POTS, for example, is a very common uh disorder where you have positional hypotension, you have orthostatic issues, you have tachycardia, so you can't maintain your blood pressure, you have high blood, high, you have high heart rates. So this is a condition where you have a lot of inducible nitric oxide floating around. All doses of methylene blue, whether it be low doses of methylene blue or high doses, have a neutralization effect on the inducible supply of nitric oxide. This is a good thing, okay? Because you have less inducible nitric oxide around, you have less pain, less inflammation, less low blood pressure. Okay, so this is a good thing.

Now, higher doses of methylene blue will have an effect on that inducible supply and they may have an effect on that endogenous supply as well that's in your mitochondria in the vascular walls. But the lower doses will not have this effect. Okay. So that's why lower doses of methylene blue are not, then it's not required to take nitric oxide with it because you're not having an effect on that endogenous supply. So maybe in summary, because I don't want to confuse people, is that endogenous nitric oxide supply is not affected by low doses of methylene blue. Higher doses of methylene blue will potentially have an effect on that endogenous supply. So as a result of that, it's important to think about using nitric oxide in combination. And so if we have patients that are on higher doses of methylene blue for chronic infection, for example, I will be giving them nitric oxide as a supplement in combination. But the low doses of methylene blue will not have an effect on the endogenous supply. Um, and and and as a result, I don't think about having to use it. If they do have an effect, it's going to be on the inducible supply, which is actually a good thing because it's going to neutralize the inflammatory and pain cascades that happen because of inducible nitric oxide around for a long period of time.

Got it. Really important. I definitely wanted to go here. So, just to be crystal clear, what kind of dosage wise are we talking when you'd want to start including supplementing with NO?

I typically start anywhere above around 30 milligrams or so, just to be absolutely conservative about it. The data when I looked at it recently, again, there really is no evidence that you have a major effect on endogenous nitric oxide supply until you get to around about 2 milligrams per kilogram orally. If you're taking IV methylene blue, that's different. Not something that I'm as familiar with, but certainly above a milligram per kilogram. So just for, you know, for numbers for people, we're talking anywhere between, you know, 50 to 70 milligrams to 150 milligrams of methylene blue. So 50 to 70 is about a milligram per kilogram and 2 milligrams per kilogram is about 150 milligrams. So the the the major studies out there really don't show any major effect on endogenous supply until you get to about 2 milligrams per kilogram orally. But to be as conservative as possible, I typically will start adding an NO in protocols when somebody's about 30 milligrams or above methylene blue taking it regularly. If they're taking it at a less of a dose than that, somewhere between, you know, anything less than 30 milligrams, I'm typically not using endogenous, you know, oral NO to support them.

And say you're fighting an infection and it's just a temporary use of 30 plus milligrams, say 2, 3 days. Are you going to worry about it?

Absolutely not. Actually, in this case, you're not going to worry about it because you want there to be some, you want there to be inducible supply that's neutralized, and it's okay if there's some of the endogenous supply as well, as well, because it's going to cause some vasoconstriction. It's going to cause a little bit of mitochondrial stress that's actually going to be beneficial to treat the infection. So methylene blue is actually used at these higher doses in very severe cases in septic shock, um, people with cardiopulmonary arrest, um, because it can cause a significant amount of vasoconstriction at these higher doses.

And so there was a great fantastical paper that was uh that was sent out around the internets about mid-2025 talking about blue brains, um, specifically. And they talked about, they had, they showed these autopsies of these patients that had died, obviously, um, that had gotten very, very high doses of methylene blue and said, well, if you take methylene blue, you're going to get a blue brain, you shouldn't take methylene blue. These patients were getting very, very high doses of IV methylene blue as a rescue agent, a last-ditch agent to try to save their life. Septic shock, cardiopulmonary arrest, severe, you know, severe other presentations. And they died. They'd gotten around 300 milligrams of methylene blue IV over about a three to four hour period. So that's a huge amount of methylene blue and not clinically, clinically relevant at all. And to for most cases that that are going to be outside of like, you know, from normal waking life here, right? These are people that are, that there are no other choices. They're trying to save their life, right? And so these patients, when they did the autopsies a couple hours after they died, had blue brains, which is not surprising. That is a huge amount of methylene blue. You taking methylene blue right now between 4 and 25 milligrams or even 200 milligrams dosing. This is not going to cause your brain to be blue. Your brain is going to redox cycle the methylene blue, right? It's going to go from blue to colorless and eventually it's going to come out of your system. It's not going to stay there. It's going to come out of your kidneys and you're going to urinate blue. The more methylene blue you've taken, the higher the dose, the longer it's going to stay blue. Okay? Um, but it's not going to make your brain blue. It's not going to stain it blue. This was just an autopsy of people that got very, very high doses.

So, in essence, I don't use those high doses at all. Um, that, and I don't use it IV personally. But I do sometimes use two milligrams per kilogram, which is around 150 milligrams of methylene blue, and I'll do that for three to five days. I've used that for acute viral infections, acute bacterial infections, acute trauma as well. I've used it for things like traumatic brain injuries and concussions. And um, all of my patients have higher doses of methylene blue in their medicine cabinet just in case they need it. But most of the time they don't need it, but they have it just in case. So I'll have them take 2 milligrams per kilogram if they get an acute injury, if acute, if they have an acute infection. They do it for three to five days and they do well. They do very, very well at those doses and I don't worry about nitric oxide. But I will worry about it if somebody's on a longer term protocol where they're on, they're on 50 or 70 milligrams a day for a period of 7 to 14 days or longer. I'm, I am thinking about using nitric oxide support absolutely so that, you know, we're not depleting it over time. And so that's the nuance there.

So, and and and the blue brain thing is, it was a, you know, it was a great, you know, clickbait headline as well. And there's really no clinical relevance to it that nobody has, and nobody has to worry about getting or having a blue brain when you're taking methylene blue, especially, you know, at doses that we're talking about here, super low doses.

To get into more nuance on the blue brain while we're here. In your opinion, if those people wouldn't have died, would the brain have gone back to its regular color?

Yes, it would have. But it would have taken a while because that's a lot of methylene blue. And so, but it would have taken time for methylene blue to do its redox cycling thing, go to blue to colorless, blue to colorless, and eventually come out of the system. So yes, in my opinion, is that if they had lived, that their brains would not have been stained blue. It would have come out as all methylene blue does out of the urine in the kidneys, no problem. And and it was, it was one of those things where, um, I, I understand why people would be scared, right? Because it's, it seems very scary to have a blue brain, right? And and I would agree with them. I don't want, nobody wants to have a blue brain. But in essence, it's not really the conversation that's really appropriate, right? The appropriate conversation is, well, what is actually, what are we doing clinically and what's clinically relevant here? And like giving a little bit more of a of a backstory as to why they were using that kind of dosing.

Would you say even at 4 milligrams temporarily, there is blue dye getting into the brain that is quickly leaving?

Yeah. I mean, it's getting into the mitochondria. It's going to be blue in there. It's going to be colorless. It's going to be blue. It's going to be colorless. Uh, it's going to be doing this for a while and then it's going to stop and it's going to come out of the system, right? It comes out. That's why the half-life is between four and six hours. Like that's what's going to happen. So yes, if you were looking at the mitochondria, like a very small amount, but think about like we have, you know, so many cells in our body, right? And like the amount of methylene blue that's doing this per cell is minuscule. It's not like it's going to be lighting up blue like you're like, you know, a Christmas tree or a light bulb or something like that, right? And so it's not like that. It's not a lot of methylene blue. And and the cool thing about, right, there is going to be more mitochondria percolating in your brain. So that's where it's going to go. There is more mitochondria in your musculoskeletal tissue. That's where it's going to go if you're exercising, right? So, there is, you know, this triage effect that happens, which is super cool. And so, that's all happening, but I'm not worried about, you know, long-standing blue coloring anywhere in the body using methylene blue.

Is there anywhere in the body that it can't get? Obviously, it's crossing the blood-brain barrier to get to the brain. Anything walled off where it's not actually penetrating?

Not that I'm aware of. So methylene blue is one of these compounds that's very, very permeable everywhere in the body. So it gets across the blood-brain barrier, no problem, as opposed to things like GABA, for example. GABA is a supplement that people take all the time. GABA does not get across into the brain. So if you take GABA and it works for you, you have a leaky brain and a leaky gut, typically corresponding to that. And so it's could be diagnostic. Um, I have patients that, you know, I've worked with many years that have a leaky gut. We optimize. They were taking GABA supplements that were working for them, and then they stopped working because you optimize the gut and the brain. And so, so methylene blue itself is highly permeable. It goes pretty much everywhere. And so I, I don't know of any place that it wouldn't potentially go because of its its lipophilic and hydrophilic capacity. So it's a very cool compound like that. And and and that's why it's so has so many like a spectrum of therapeutic benefit, I think.

All right. But one of the beautiful things about a long-form conversation like this is we can get into discussing the nuances on topics like this. So we've gone into blue brain, NO. Another one in this realm is serotonin syndrome.

Yeah, let's talk about that and any safety concerns there. Yeah, there's one non, well, he's a physician, but he doesn't practice that, um, he talks a lot about, you know, a lot of different topics and things like that. And one of his arguments about methylene blue was that the only reason people feel any better when they take it is because it increases serotonin. Um, and that is kind of funny, you know, from somebody that hasn't been, been using methylene blue in clinical practice for for any time and doesn't have any clinical relevance to it and just reading some off that his researchers gave him to read on, uh, on a video. Um, even though the the study that he quoted about methylene blue being detrimental, um, to to normal cells, which he can talk about, actually, his other argument was that you shouldn't take methylene blue if you have normal mitochondria. And I can talk about that too. The the study that he that he quoted was a study that was giving like five milligrams per kilogram of methylene blue to animals, causing mitochondrial stress, which was nothing at all that was clinically relevant at at any level. So the serotonin argument is interesting, right? So, so methylene blue does increase serotonin. It does this by becoming, and it is a monoamine oxidase inhibitor, meaning that it increases serotonin, norepinephrine, and at higher amounts, it also increases the amount of dopamine that's going to be around too. Now, this is in a dose-dependent manner, meaning that methylene blue will increase serotonin and norepinephrine a little bit at low doses, and it'll increase it more the higher the dose you get. And so the concern is that if you already have a drug on board like an SSRI, an antidepressant, or you have like the newer antidepressants around like called SNRI, which is serotonin-norepinephrine reuptake inhibitors, that you've now combined methylene blue with these drugs and like, oh no, what's going to happen? You're going to get something called serotonin syndrome. Serotonin syndrome is extremely rare. It is a syndrome where you have too much serotonin around and as a result of that, you get what's called hemodynamic instability. Basically, your blood pressure, your heart rate kind of go wacko, and it can be, it can be dangerous. It actually can be deadly. But if you ask like a room full of doctors that have been in clinical practice for 20 years, how many have seen serotonin syndrome? Maybe one or two will go and raise their hands, and one of those people will actually not have seen serotonin syndrome. So it's extremely rare. It's only been described with the use of IV methylene blue, not with oral methylene blue. Um, that being said, people that are on these drugs, SSRIs, SNRIs, and things like that, and they want to take methylene blue, they really should work with a provider to make sure that they are safe to take it. It's typically not serotonin syndrome that I'm worried about. It's all, it's actually where most of your serotonin is made, which is actually in your gut. So, you make about 95% or more of your serotonin, not in your brain, but actually in your gut. And so as a result of that, some people that increase serotonin acutely will have some GI distress, some diarrhea, for example, can happen, or some, you know, gas and things like that. I have seen people that are on SSRIs have a little bit of a higher risk of having headaches when they first start methylene, excuse me, methylene blue as well. So that's possible. Um, although it's typically fleeting and not a big deal. If you have high blood pressure and you're on anti-hypertensive medications and you're also on an SSRI, that combination seems to increase your risk of having a higher blood pressure when you take methylene blue as well. So, if you have high blood pressure on its own or or and/or if you have high blood pressure on an SSRI, you should definitely work with a provider to make sure that your blood pressure remains okay when you start taking methylene blue and there's no issues. So in the end, serotonin syndrome is not something that I worry about, but it is something that people should be aware that there is a combination increase in serotonin that can cause GI distress, can cause headaches, cause high blood pressure if you already have high blood pressure. So these are the reasons why you want to work with a provider, but it's certainly not the reason why methylene blue works. Okay? It's certainly not because of high serotonin or increased serotonin that methylene blue works. No, because it works for all the reasons we just mentioned before. The the the the rash, the sort of the epidemic of mitochondrial dysfunction is just so significant where there's such a significant need for mitochondrial support, and that's really where methylene blue comes in. And it's this serotonin piece that certainly can help a little bit with mood, you know, for some people when they're taking methylene blue. And I do have some integrative psychiatrists that I work with that are weaning their patients off of antidepressants and using methylene blue instead. But that's not just because of the serotonin part, that's also because of the mitochondrial support part because we know depression, bipolar, mental health disorders, there's a significant component of mitochondrial dysfunction here. And this is why you change them to a ketogenic diet and all of a sudden their depression goes away, right? Like we know that that's the case. And we also know on the other side of things, to get a little passionate here for a second, is that the serotonin is not the cause of depression. So if you have low serotonin levels, that's not correlated to depression. In fact, we know that when I went to medical school, that we were told that people with depression had low serotonin levels. They don't. People with depression have no lower levels of serotonin than anybody else. The only time you'll have low serotonin level is when you just went and had your MDMA session and then you all of a sudden have low MD, low serotonin because you just flooded the body with it or something like that. But people with depression do not have lower levels of it. So that's another reason why a lot of the newer psychiatrists, the more integrative ones, are actually taking people off of their SSRIs, weaning them off and getting them on something like methylene blue, which does have a little bit of serotonin support, but the major thing is the mitochondrial support there too. And then, you know, even even kind of going even further, there's even more of a correlation with depression with GABA levels than there are with with serotonin levels. So, people are working on the GABA system here and optimizing the GABA system and seeing fantastic benefits with anxiety, with depression, and also with insomnia and things like that. That's much more correlated to GABA levels than it is serotonin levels. So, in the end, I'm not worried about serotonin syndrome with with methylene blue unless you're using IV methylene blue. So certainly you shouldn't be taking methylene blue IV along with those drugs, but orally I'm not worried about that. But I am, you know, considering that there are some other potential things that you want to be considering there that we discussed.

Earlier you talked about your daughter. At what age would you introduce this to kids?

Well, you know, it depends. I, I think that it really depends on what's going on with the child and and what's the the motive of of what are we trying to accomplish, right? What's the goal in essence? Most children shouldn't need methylene blue. Okay. Most children should be relatively mitochondrially optimized because they're healthier in general. Now, that's maybe kind of a blanket statement that's, you know, filled with filled with holes these days. Um, there are clinicians that I work with that use methylene blue in kids, especially those with attention issues and and um, and hyperactivity and things like that because it can regulate mitochondrial function. Be very helpful. But I wouldn't recommend doing that unless you have practitioner supervision. We do know it's safe in kids. Um, and that's for sure. Once kids get through puberty, then they become, you know, mostly like sort of adult physiology and then certainly they can benefit from methylene blue the same ways that we've been describing throughout this podcast. With kids, it's more nuanced. I mean, the dosing has to be lower for sure, but I do have, you know, some practitioners that are working with some significant neurodevelopmental challenges in children and seeing significant benefits using methylene blue in those capacities. So, I absolutely think it could be used that way. I wish I, you know, the the statement earlier that I said that, you know, kids are more mitochondrially optimized, uh, was a blanket statement that I could say across the board. It is true compared to adults, but compared to kids, you know, 20 or 30 years ago, it is not true. Right? So, it's, it's, it's a hard, it's hard, right? Because like some of just the exposures we get on a regular basis, the toxins, the, you know, everything else, people being on, you know, getting medicated for ADHD when you're 5 years old and, you know, all these other, even being on antidepressants and antipsychotics. Like, it's, it's crazy what we're seeing. And so, it's like, it's a very difficult, difficult time for children. And I, and I do think methylene blue can play a role here. But again, it's, it's one where I'm like, really trying to like zoom out and go, okay, really what's happening here? Like, what's like, why do we need this? And like looking at really trying to work on those exposures and optimizing mitochondrial function from a diet, lifestyle, you know, sympathetic activation perspective, the majority of the time, because the good thing about children, you know, the many good things, but the, the really good thing is that they're very resilient typically. So once you start working on the system and giving them the support they need, they will see significant shifts very, very, very fast compared to adults.

What about pregnant, breastfeeding, other special populations?

So methylene blue is is not, uh, it's, it's called contraindicated in breastfeeding women and and women that are that are pregnant. Um, I have an interesting idea when it comes to fertility and methylene blue and and how it could potentially be helpful there. Talked about how methylene blue is a really great mitochondrial support, right? And then we also talked about the the number one cell with the most, well, the cell with the most mitochondria per cell is the eggs. Uh, and so eggs and then sperm behind that. So there's a significant amount of energy demand to make a baby. Um, men, you guys don't count really. I mean, it's the women that are doing most of the work here. Although sperm have a lot of mitochondria per cell to get to the egg itself. So, I mean, my my thought here is that, well, could methylene blue come in and potentially be a support for mitochondrial function in the eggs themselves and help with fertility rates? And so, I haven't been able to test that quite yet, but I have a couple fertility doctors that are interested. So, we're going to be working on checking that out. But even in those cases, I would be recommending stopping the methylene blue about 48 to 72 hours before, you know, trying to have the baby, before conception, just in case. The the data for risk in pregnancy and breastfeeding is actually kind of low. Um, but still enough where I would not recommend doing it. Um, I would also recommend not taking methylene blue if you do not have normal kidneys or if poorly functioning kidneys because methylene blue is going to be excreted in your kidney. So if you're on dialysis, you cannot have methylene blue. If you have chronic kidney disease, you probably can take methylene blue. Methylene blue is not going to make your kidney function worse, but if your kidney function gets worse, worse over time, the methylene blue is going to stick around for longer. So, I do have another theory here which I haven't been able to substantiate yet, that there could be a possibility that methylene blue actually could help kidney function over time because again, working on mitochondrial function. I haven't seen that yet in clinical practice. So, I don't know for sure. That's just a theory and I wouldn't do it unless you were working with a provider very closely, just to again monitor your kidney function because that's how methylene blue gets excreted is through the kidneys. So the major people that I that I talk about to not use methylene blue would be people that, if you have, you know, that have kidneys that don't work, dialysis patients, um, and then also pregnant or breastfeeding women. But outside of that, the other, and I talked about this, people with high blood pressure as well. If you have high blood pressure and you're on anti-hypertensive drugs or you have prehypertension, so your blood pressure tends to rise easily although you're not on medication yet, you may see a rise in your blood pressure using methylene blue. This is from a combination of reasons actually. Um, but one of them is that potential inducible nitric oxide that we talked about. That's pretty not usually the common one. The other one is uh because of increased norepinephrine that happens with methylene blue. And so as a result of that, you have to watch very carefully and monitor your blood pressure if you're going to be taking methylene blue. It's dose-dependent, like low doses do it a little bit, increase your blood pressure if you have that issue, and higher doses will do it more. So just watch your blood pressure closely and work with a provider if you have high blood pressure. But the main issues when people taking methylene blue typically are going to be more like detox kinds of symptoms, like your healing kinds of symptoms, your your GI distress, your headache, your your uh, irritabilities, like some sleep issues. But if you start off at low doses and you increase it over time, you typically don't have those kinds of symptoms and um, you tolerate very well.

Okay. So, we went over serotonin syndrome, other safety, blue brains, nitric oxide. Any other nuance subjects related to methylene blue that we should get into?

Yes, thank you for reminding me because one I did want to mention was the question of whether you should take methylene blue if you have healthy mitochondria because the mitochondria are going to be detrimentally affected by the methylene blue if you have healthy mitochondria. In fact, there was another guy, a PhD on a podcast recently using an analogy of like a um, a crazy taxi driver through the city, uh, and how methylene blue would do electron flow through various places and make things worse if you had normal mitochondria. Okay, first of all, again, 94% of US adults have some element of mitochondrial dysfunction. So, it's very unlikely, right? Only 6% people are metabolically healthy that you have optimized mitochondria to start off with. It's just the name of the game. Okay. So, taking that off the table, let's say you're in that 6% of people that have optimized mitochondria. Will methylene blue make your mitochondria function worse? The answer is that we have no clinical evidence that this is the case. We only have some animal studies looking at very high doses of methylene blue. Those doses that I mentioned before, four or five milligrams per kilogram. So huge amounts. That's the equivalent in humans. That's not the amount in animals. That's the equivalent of of the dosing that they used that would be in humans. This was in animal models where it showed that if they had normal mitochondria, what they what they did is they they did a study on animals with and they gave them a stroke. Okay? And when they did is that they looked at the mitochondrial function. They looked at the and the outcome of this animal that had a stroke. Okay? The animal that had a stroke had a significant benefit using methylene blue at these high doses actually with stroke mitigation. So they had less stroke area. They had better perfusion. This had better outcomes from the stroke. But in the normal area of the brain where they there wasn't a stroke, there was evidence of mitochondrial dysfunction. Okay. And so like, well, the they transpose this data and say, well, if you're if you have normal mitochondria, you shouldn't take methylene blue because it's going to mess up your mitochondria. I'm like, no, look at the study, man. Like, look what they did. They're using high doses and that's what they found. And then clinically, I've been using methylene blue for the last six years now. I have not seen this. I use it in optimized people all the time. Not all the time, every day they're taking it, but they're taking it when they need it. When they have more mitochondrial stress, when they're traveling, when they're doing endurance work, when they have high-intensity cognitive load, they do better using methylene blue. They don't use it all the time, but they use it as needed. And they use it for aerobic training. They use it for anaerobic training. Training. I have a friend of mine that uses it and notices that his capacity to recover is better at a higher heart rate than it was before. He actually can maintain energy production at a higher capacity for longer and then he can recover without having to go down as far from a heart rate perspective. And he notices this with his Aura rings and with his Whoops and all the things that he tracks with. So we know clinically that this is not relevant information. Now, if you're taking super high doses of methylene blue, yes, this is a different story. We're talking about doses at four, eight, 16, 25 milligrams. Those are the doses I'm talking about. I'm not talking about like ridiculous dosing of methylene blue. So, this is where it's so important, signal from the noise, as we talked about in the beginning, right? To be able to change the the the conversation to what's the signal here. The signal is what's most important, not the noise. Okay? Yes, there's lots of researchers that will tell you that methylene blue is not good for these reasons that we just described before, but they're not working with it clinically. They're not seeing what we're seeing on a regular basis and understanding, okay, this is what's actually happening with patients. This is what actually we can actually observe, not some, you know, theoretical researcher saying that this is what's going to happen if you take something in a certain way. So, I'm a big fan of taking that noise. Let's let's let's just, you know, calm it down a little everybody and let's let's focus on that signal and how beneficial this particular compound can be under the right circumstances.

Early in the conversation, we talked about ideally taking methylene blue orally and then 15 minutes later having food to help with absorption.

Sure. Before we close here, for somebody that fasts and does intermittent fasting or longer fasts, how can methylene blue be used there? Is there any benefit to fasting? Obviously, given what we said about absorption, bring that in. Yeah, fasting plus methylene blue. Your thoughts?

Yeah, so it's, it's a good question. In the end, you don't have to eat for methylene blue to work. It's going to go through the system and get digested and metabolized and it's going to go in. It'll be slightly slower than if you had eaten 30 minutes after taking it. So I think that's that's kind of the question there. The additional aspect which you which you asked, which is interesting, is how do you think about methylene blue in fasting? Well, what is methylene blue going to do actually? It's going to help with the cleanup. It's going to clean up you up. It's going to clean up faster. So you're going to actually clean up the system faster that way. So, I have a lot of um people that I know that use methylene blue during fasts. It helps with the cleanup phase and so it actually helps tolerate the fast a little bit better. Um, it actually gets you into the ketosis state a little bit faster too. This is working on energy metabolism and detoxification. And so it has the capacity to really enhance your fast in many ways. Not break it, not make it more detrimental. It's actually going to enhance it because it's working on cleanup. It's helping with the bypassing of of complexes that aren't working well. It's helping with the energy detoxification side. So, absolutely, we can use it inside of a fasting protocol.

All right. Last question for you. Somebody that's tuned in to this point, they've never tried methylene blue, they're on the fence, they're intrigued. What would you say to them?

I would say that it's one of those things where once you start taking it, you will realize that you probably needed it all along. And that's because most of us have mitochondrial dysfunction, right? And once you start feeling better, you'll feel more energy, more focus, more clarity, your brain fog will be better. You'll feel like your just attention is improved and your sustainability. Then you might be going, "Well, I didn't know I could do this. What else can I do to optimize my health to get my brain and my body feeling this way on a regular basis without taking this all the time?" So, think about it as like a gateway into understanding how well your cells are working right now. If you take it and you find a dose that works fantastically well for you, that's fantastic. And it also means that you have a lot more you can actually have in capacity that would not require methylene blue over the long term. If you optimize your health, if you optimize your foundational biomarkers, if you look at things from a a foundational perspective, and that's what I do in clinical practice. I, I give people the overarching vision here, which is I have a practice, it's called Health Optimization Medicine. It's a focus on foundational health biomarkers. We optimize health and we look at optimizing people to an age range between 21 and 30 years of age. That's when we're most optimized typically. Hormones, nutrients, gut, neurotransmitters, everything to that age range. But that takes time. It's not going to happen overnight. Six months, a year, sometimes longer. It took you 50 years to get to how you feel. It's going to take you some time, right? But what are the things along the way that can give you energy, give you focus? Methylene blue is just one of those major levers for my patients. And that's what I would say to somebody asking is like, well, I think I'm doing all right. You know, maybe that I don't know if I need methylene blue. Like my energy's pretty good. Or or maybe like, well, I get a little more energy. Like, I feel like my my my afternoons aren't as good as they used to be. Like sometimes I yell at my kids and I don't know why. Or sometimes I don't recover as well from the gym as I used to. Or I get on an airplane, it takes me a couple days to recover. It used to be like the day after. I mean, just, you know, down the line, down the line. I'm drinking two cups of coffee instead of one, or I'm on my third and I'm crashing. Like I just have more brain fog than I used to. Like these aren't things that that pop up like acutely. They're happening and slowly building over time. It's the slow burn. But if any of that sounds like it resonates to you, then taking methylene blue could be like this window to be like, "Oh, now okay, now I realize yes, there is more capacity that I have and let's let's let's get on it. Let's see what else I can do to optimize that capacity." Um, or if you're an athlete and you're in and your endurance or you're doing really hard stuff and you want more capacity, you want to get that extra edge, then methylene blue can help you potentially do that, too. You can maintain your heart rate up for longer. You can see your recovery get better because you've had it on board with mitochondrial support. And so, all across the spectrum, I use it. And that's why I think it's something that as long as you're getting good quality methylene blue and you're not taking liquids that that from an Amazon seller that says it's from the United States, but it'll take three weeks of time to get through customs when you first purchase it. This is something that I've heard from a couple people. Get good quality stuff. That's what we make at our company at Trescriptions. We we really do go to the ends of the earth to check quality. And that's kind of the biggest thing I would talk about in addition to think about taking it is get good stuff. If you're not getting good stuff, you're you might be getting contamination with heavy metals. You might be getting less than you think you are. You might be making a huge mess in the process. And so, you know, we really care about that. We have we have manufacturers of the methylene that we've been using for a long time, but the certificates of analysis that we get from those companies, we test again with another independent lab before we use them. It's very rare to have companies do that. But if they don't, you just don't know what you're getting. And this is not not just with methylene blue. This is with other companies and other products as well. I mean, there was the recent creatine gummy scandal that came out. No creatine in the gummies, everybody, right? Because because manufacturers can say whatever they want on some level and then it's up to the companies themselves to do the extra work. And that's what we've done at our company.

Dr. Scott, really enjoyed round two. We're going to link up to Trescriptions, the discount, your other website, social media. Thank you.

Thank you for having me, man. This has been fun.

Now that you're done, you're going to want to stick around here and catch this other incredible episode. You don't want to miss it. I'll see you over there. I don't think that there's one better anti-aging, life-enhancing substance or biohacking thing that you could do than supplementing with melatonin. Sleep is just a little piece of melatonin.