Secrets of Melatonin and Methylene Blue with Dr. John Lieurance

Content By: Ari Whitten & Dr. John Lieurance

In this episode, I’m speaking with Dr. John Lieurance who is widely recognized as one of the top clinical experts in the world on the use of melatonin and methylene blue, as well as EndoNasal Cranial therapy. He runs the Advanced Rejuvenation Center in Sarasota, Florida. In this podcast, we do a deep dive into melatonin and methylene blue and how they both are critical for mitochondrial health.

Table of Contents

In this podcast. Dr. Lieurance and I discuss:

  • The role of melatonin and methylene blue in mitochondrial health
  • Is melatonin only produced in the pineal gland?
  • Why some people find melatonin stimulating
  • Methylene blue – what is it and what are its benefits?
  • The #1 therapy that boosts the effect of methylene blue (hint: it is one of my favorite topics)

Listen or download on iTunes

Listen outside iTunes


Ari Whitten: Welcome back to The Energy Blueprint Podcast. In this episode, I’m speaking with Dr. John Lieurance who is widely recognized as one of the top clinical experts in the world on the use of melatonin and methylene blue, as well as EndoNasal Cranial therapy. He runs a clinic in Sarasota, Florida called the Advanced Rejuvenation Center. In this podcast, we do a deep dive into all things melatonin and methylene blue.

Two compounds, two substances that tie into the story of mitochondrial health and therefore, of course, energy production and longevity, disease prevention, resilience, sleep quality, brain function, mood, and so much more. I think you’re going to get a lot of value out of this episode, so enjoy. Dr. Lieurance, welcome to the show. Pleasure to finally connect with you.

Dr. John Lieurance: Thank you, Ari. It’s a pleasure to be here.

Ari Whitten: First of all, you run a clinic in Sarasota, Florida called the Advanced Rejuvenation Center. Can you describe what you do there because it’s a long list of many, many things that you do? I’m curious to have you give listeners a sense of all the work that you do, rather than me try to describe everything.

Dr. Lieurance: Yes. I’ve been in practice for nearly 30 years. My history is I’ve had a number of struggles with my own personal health journey. The earliest aspect of that was being in [unintelligible] in my first two years of life in Camp Lejeune, which a lot of people who are watching the news now see attorneys are really looking for people that were living on Camp Lejeune. It’s the worst water contamination in US history.

This created a situation for me personally where I had a lot of challenges growing up with dyslexia and learning disabilities. It’s almost like a traumatic brain injury, really. A lot of kids and babies were stillborn. I would say I was probably lucky to make it out of that. It has set the stage for me to be very sensitive to a lot of different fluctuations in my own health. That in combination with just being in holistic medicine, I always feel like we were the original biohackers in that it has come out, and eating granola, and hugging trees now is all of a sudden really sexy when you call it biohacking, right?

Ari Whitten: Indeed.

Dr. Lieurance: Being in that area for so long, you could just imagine that you would be able to have experienced so many different aspects of health and healing and being able to put a lot of these things together. That’s, I think, the culmination of Advanced Rejuvenation, and why we have such a diverse amount of different therapeutic and physical medicine, different healing devices, and so forth.

The types of therapy Dr. Lieurance uses in his clinic

Ari Whitten: Give listeners a sense of what conditions you work with or specialize in and what kind of therapies you’re engaging in the process of working with patients.

Dr. Lieurance: The two main books I have out on Amazon, one’s on methylene– I’m sorry. There is an ebook on methylene blue, Melatonin: Miracle Molecule, and also more recently, I released a book on a very little-known physical adjustment called EndoNasal Cranial therapy. The specific form that I have developed and I teach to other doctors is called functional cranial release. This is something that I started using very early on. I feel like it is an aspect of what we do here that may allow us to get results in a lot of cases where other people might not, just because of the impact that that has on the central nervous system.

Basically, what it is, it’s an expansive pressure where we use a small balloon placed in through the nasal passage. It releases a lot of bound tissue in and around the cranium. By doing this, it allows the expression of life force, really. It almost sounds a little fufu to talk about life force and universal intelligence. This is basically information that runs through our body. It’s the energy frequencies and information that provide the healing for our body and the regulation and the adaptive mechanisms to stressors. This is something that diminishes with a lot of people for a couple of reasons. I think one is because the life force is low in the body, but also there are so many stressors these days.

Ari, look at all the things that we didn’t really have to deal with in the ’50s. You talk to practitioners that were working back then, and they said it was easy, especially within chiropractic profession, “Oh, we would adjust patients and everybody got better.” Nowadays you have to do all these other things with people in order to achieve that same goal. That’s another, probably another reason why we’ve created these combination therapies here at the clinic. The EndoNasal, I really love, we use a lot of high-dose melatonin, which goes a bit against the narrative that people will typically hear about melatonin with, where we’re going into the hundreds of milligrams–

Ari Whitten: I definitely want to talk to you about all of that stuff too, so we’ll get there.

Dr. Lieurance: Methylene blue is another substance that I think is poorly understood, and higher doses of methylene blue, I think, have been more helpful than lower doses. We can dive into methylene blue. We do a number of IVs, we use a lot of ozone in our practice. We can talk about the synergy of ozone and how it works to improve, again, life force, which is mitochondria. If we want to get more technical, we can call it life force or we can call it mitochondrial energy. What are some other things we do? We were one of the first clinics to do stem cells where we were actually pulling bone marrow and we were doing liposuction and taking the stem cells off of fat. Literally, almost 20 years ago, we were doing it out here.

Ari Whitten: Wow.

Dr. Lieurance: We were using prolotherapy even another 10 years before that, which is a form of regenerative medicine, which is a sugar that’s injected into damaged platelet-rich plasma using the blood. All these things can be really powerful for the physical body because this is the way we heal. We heal with regeneration, whereas we need building blocks to create new cells and tissues, and that’s carried by circulation, and many times, the denser aspects of our body don’t get circulation.

You think about when you’re eating steak and you get gristle caught between your teeth and that gristle is connective tissue. Connective tissue and cartilage are the two most densest, poorest vascular, meaning that there’s not a lot of bring in the groceries, take out the garbage type of circulation, so it gets injured, and 70% of the time it stays injured. That’s what leads to a lot of these degenerative problems that cause us to lose function, where we can’t go out and play the sports and we can’t lift as much weight, and we can’t be in as much comfort in our body and move around with as much grace.

By taking different tissues and cells from one part of the body, from, say, the bone marrow, or just from the blood and using high-definition ultrasound and injecting it into specific areas, this can be miraculous. What I love about it, Ari, is that it’s actually healing the body the way God intended the body to heal. It’s fixing it at the root cause. It’s not the pain, it’s not the inflammation, but the pain and the inflammation is following the instability and the damage, and so we fix the damage, the pain and the instability goes away.

Dr. Lieurance’s experience of God

Ari Whitten: You’ve mentioned God a couple of times, and I know that you have something called the three legs of a stool, vitality of the body, mind mastery, and a direct experience of God. Can you describe what you mean by that and how you help patients achieve a direct experience of God?

Dr. Lieurance: Sure. I believe that for any individual to express the full potential in their life, that those three things are important to have addressed, the three-legged stool. The more vital the body is, the higher levels, I believe, of consciousness that we can achieve. The happier we are, the better we treat our friends and family, the better we treat ourselves. Just overall, that is a very important aspect of health. The second one is dealing with identity. The way that we identify ourselves is relation to our environment and other people, relationships to the earth, to the planet. There are so many different great conversations you can have just within this context of identity.

We store our identity within our brain in what’s called the default mode network. When we do different types of therapeutic work, it could be deep breath work, there could be the endonasal balloon incidentally lowers that default mode network. We use that in a ceremonial fashion called bliss release, where we have an access to get people to step out of that identity. This is self and me, and then everything’s separate, when you’re really identifying with the self. You can step out of that and see things more globally. There can be a tremendous amount of transformation and healing that can occur there, especially if you can surround it with the intentionality of gratitude and acceptance, and compassion.

With the direct experience of God, I believe that that is defined differently for everybody. Sometimes people get caught up on the word God, and it could just be life force, or it could be universal intelligence, or it could be the divine, or it’s a higher power. Often they use that term in, say, AA or NA. This is basically just believing that there’s something greater than ourselves. However, for me, I didn’t fully really understand that for most of my life. Maybe about five years ago, I was invited to go to a ceremony with plant medicine.

This was a very unique specific form of medicine and ceremony called the chlorogenic protocol, which that word’s getting thrown around a lot. I know Ben Greenfield talks a lot about it. When I was introduced to this chlorogenic protocol, I had a mask on. I was listening to music, very specific music. I took some medicine, I was laying in a bed, and it was all about the inward journey. I was instructed to do a lot of different forms of breathwork. For me, personally, it was an experience that I’ll never forget. I felt like I was with angels and I had this just overwhelming feeling of just being one with everything and just a tremendous amount of love.

I just imagined that when people at, say, church or any type of religious event, whatever they’re talking about, was that. That was what I experienced. It was so deep and profound for me that it’s changed my life ever since then. I’ve seen this type of affect with many. I’ve even seen this when I’ve worked personally with people with the bliss release. It’s this just mystical experience. I think putting those three things together, that was the recipe that worked for me personally.

I’ve seen that working for a lot of other people throughout my work. I believe that some sort of a psychedelic medicine in the form of a plant medicine journey could be probably one of the most consistent and easily accessed method for people to experience that third leg of the stool.

Ari Whitten: Yes, absolutely. Can I ask what specific plant medicine it was? Was it 5-MeO-DMT?

Dr. Lieurance: That wasn’t. However, I did experience the 5-MeO twice, and that was probably my greatest teacher because it was another level of experience in God that I experienced. It’s hard to describe. It’s just a complete death of the ego. The first experience, it was a heart opener, so it was based on the sassafras tree, which is something that’s– it’s a heart opener, so you feel a lot of love and compassion, and then there was Ketamine involved as well. It was the combination of those two medicines.

Common misconceptions around melatonin

Ari Whitten: Very cool. Okay, so let’s get back into some of the biochemistry stuff, methylene blue, melatonin, all this stuff, and how it works. First of all, let’s talk melatonin. You’ve written a book on this called– what was it called, The Miracle Molecule?

Dr. Lieurance: Miracle Molecule.

Ari Whitten: Okay. You sell products as well as suppositories, some interesting methods of delivery using some very high dose melatonin. Melatonin is something that– I don’t want to use the word– I guess I will use the word a little controversial at certainly high dose protocols and what context they’re being used is controversial. Let me see if I can paint a brief picture for listeners of the range of takes on this. We have lots and lots of research showing that very high dose melatonin is very useful in certain contexts, neurological diseases, cancers, gut conditions, a number of other medical conditions.

Yet, we also have certain health experts who warn against the use of melatonin, particularly in already healthy people. We have everything from people in the high dose melatonin camps, so like 100 plus milligrams a night even, and some people recommending that even for the general population, to people– I’ll give an example, Andrew Huberman is out there really advising against the use of melatonin and talking about how using melatonin can really screw you up and make you dependent on it. What’s your take on that landscape and why there’s so much controversy and difference of opinion on this topic?

Dr. Lieurance: There’s misinformation and there’s research that I think at first glance, one might glean the wrong idea from it. Let’s just go through it a little bit. I loved how you summed it up, by the way, so I think this is really going to be a great conversation for people to hear. The first thing I’d like to address is, melatonin, we need to think about melatonin beyond just sleep. We have the pineal and then there’s extra-pineal melatonin.

The gut produces a tremendous amount of melatonin. There’s 400 times more melatonin in the gut than the pineal. There’s a great need for melatonin throughout the whole body. In fact, every single cell produces its own melatonin within the mitochondria. In order to understand melatonin, we really ought to take a little bit of a look at some of the science within that, but let’s save that for a little bit later.

Melatonin production

Ari Whitten: John, if you don’t mind me interrupting just for listeners’ sake, what you just mentioned in passing is actually a pretty new scientific discovery that all of the cells of our body are producing their own supply of melatonin in mitochondria. This is really only come out in the last couple of years, that information is like that that’s happening. Prior to that, everybody thought, “Oh, it’s produced in the pineal gland.” Maybe people were talking about the gut production, but there was almost no awareness of this production in every cell by mitochondria. I think that’s a pretty huge aspect of the story, and I just want to make sure to emphasize it for listeners.

Dr. Lieurance: This is why there’s this knee-jerk reaction when discussing melatonin to just be myopically thinking about it for sleep and the circadian rhythm. When you have that thought, then you start to lose the interest in why you might take it other than, “Hey, if you’re sleeping fine, and blah, blah, blah, you might want to take a small amount within two or three milligrams or less.” Let’s take a couple steps back, so is melatonin toxic? If there’s any toxicity to melatonin, this would be something that would be really interesting.

The other thing would be, does your body get used to it? In other words, if I take melatonin, am I going to stop producing my natural melatonin because this would be a really big headwind? This is something that would be really considered now with testosterone, there’s a negative feedback loop. With estrogen, progesterone, with cortisol, most hormones, thyroid, they all have this negative feedback. Both of those questions are negative with melatonin, there is no toxicity that anybody has been able to find.

They have gone up to doses that would be up 150,000 milligrams for someone about our size. They just stopped the study. The word toxicity in melatonin shouldn’t even be used in the same sentence however they are. There’s been some things even recently that have come out suggesting that it’s toxic to kids where there’s no toxicity. There’s no research that’s ever shown that melatonin has a toxic effect. The other thing is there’s no negative feedback loop. We produce melatonin based on sun hitting our eyes, and so every day that starts brand new.

Ari Whitten: Pineal gland melatonin.

Dr. Lieurance: Right, that’s in the pineal. There’s no negative feedback loop, so we’ll produce just as much melatonin. If you were to take even large amounts for extended periods of time, you could stop in just the very next day. I take hundreds of milligrams every night, and I’ve gone through months and months of taking it religiously every night, then I’ve not had it. I’ve been traveling and it’s like, “Oh, I forgot my melatonin.”

I don’t feel– it’s nice to have melatonin when I travel because this is where I feel there’s more stress on my system and that’s where melatonin really shines, by the way, is if you don’t have a lot of stress in your life, then you take melatonin, you might not feel a big difference.

Melatonin is an adaptogen

If there’s a lot of stress, then melatonin is the greatest adaptogen ever known to man. We talk about adaptogens like ginseng or ashwagandha. There’s all these different herbs that are great adaptogenic herbs.

Adaptation is simply the ability to respond to a stress and be able to endure that stress. Depending on if that stress is enough to trigger this strong adaptation response, we can be stronger. Exercise or cold therapy or sauna or fasting, all these stressors if they’re within a certain window called the hormetic window, there’s enough of a stressor that’s going to activate the adaptation response, but not too much where it’s going to overly exceed our ability to adapt.

What’s interesting is melatonin opens that window up more because what defines that barrier where, “Oh, it’s too much stress,” then we have a problem to our system. We can get disease or injury like a sunburn. There’s a certain amount of sun that we can get to our skin before the sun becomes damaged. If one takes higher doses of melatonin, you’ll find that you can go out in the sun all day long and you won’t burn.

This is a very obvious outward expression of physically seeing what melatonin’s doing throughout your entire body with all of your cells throughout your gut.

There’s been research on melatonin for ulcerative colitis and Crohn’s disease and it’s incredible because it allows the stress to exceed what would normally shut down our energy. This is where we get into the science of this a little bit, and I’m going to try to make it as basic as I can.

The relationship between melatonin and mitochondria

Think about within our cells, we take sugar and oxygen. These are the two main things that we convert our energy into within that powerhouse of the cell called the mitochondria.

This is called Krebs cycle or the electron transport chain. This is just the way that we normally make energy. When we have too much stress, that system shuts down and we go to make energy from an entirely different way, which is a very primitive, and they call that fermentation, is one word for it. This is the way that they think cells made energy before the mitochondria was introduced into the cell, which some people think it was almost like a parasite or it’s like an infection. Then it became in symphony with the cell, which allowed us to be able to make more energy more efficiently.

It’s this synergy that incorporated into the cell. This switch to this primitive form of making energy is without oxygen, and they call that anaerobic versus it’s aerobic when we make it in the mitochondria. The problem is anaerobic fermentation is much less efficient and you only get about 10% of the energy. If we have what defines that barrier of that hormetic window is our ability to maintain making energy within the mitochondria. What shifts when we get to that barrier is that we’re not able to make enough energy to buffer the stress.

Our mitochondria stop making energy, they shut down, and that’s called the Warburg effect named after Otto Warburg who won the Nobel Prize for– and this is why cancer cells are so really terrible because they hog a lot of energy. They need a lot of energy but they make energy through this primitive form of making energy. What melatonin does, is it sits in the mitochondria and it allows it to absorb more stress and adapt at a deeper level without switching. That’s why there’s great research on melatonin with cancer. There’s great research with melatonin against virtually every disease known to man because every disease has one thing in common, is there’s a stressor that’s exceeded the body’s ability to adapt. Full stop.

Ari Whitten: One thing I might add just to what you were saying on mitochondrial energy production versus anaerobic glycolysis just for listeners’ sake especially because this podcast is so focused on energy and fatigue is, in general, the less fit a person is and the less healthy a person is, the more that they will tend to shift towards a predominance of anaerobic glycolysis rather than mitochondrial respiration as their baseline mode of energy production– predominant mode of energy production.

I should also mention, there’s a number of studies that have shown that in chronic fatigue syndrome and in fibromyalgia, there’s a shift in that direction, meaning there’s a decline in the ability of these people to do mitochondrial energy production and a shift towards a predominance of anaerobic glycolysis. You’re saying that melatonin interplays with that by facilitating mitochondrial respiration, facilitating a shift back towards the more ideal, more optimal state of mitochondrial respiration rather than anaerobic glycolysis?

Dr. Lieurance: Not only does it shift it back but it prevents it from shifting, to begin with. That’s by taking exogenous melatonin so you can take it as a supplement. You think about kids and when you’re younger how resilient you are and how much that might be the response because you’ve got all this– you have all this melatonin, and you look at the graph and melatonin and how it really falls off, especially after the age of 40, which is right when we typically start becoming less resilient to stress.

I think that people will find it really interesting to utilize higher doses of melatonin during periods of stress. Some people that might be in challenge situation might want to take higher doses of melatonin on a daily basis. There’s not any set way to look at this as a strategy. It could be used periodically or it could be used on a daily basis. There’s no problem with doing it daily, that’s what I think people really need to understand is that there’s no reason to be afraid of taking higher doses of melatonin.

You had mentioned Andrew Huberman who I’d love to get an audience with him. I don’t listen to all of his podcasts. I’ve listened to ones in particular that people have forwarded me where he talks about melatonin. With Andrew Huberman, his opinion on melatonin lowering testosterone’s a little flawed because it’s based on a rodent’s study. What’s interesting about rodents is– in fact, there’s been a lot of studies showing that it’s quite the opposite that melatonin actually can support the hormones, and so rodents are nocturnal and during certain seasons of the year there’s shorter days and there’s longer nights, and so there’s more of a need for them to have lower melatonin levels and how that reflects in their testosterone.

I think that that one particular study to base this opinion on melatonin is not accurate. I personally take, as I mentioned before, quite a bit of melatonin and my testosterone is on the high side. I have not seen any decline with any– we work with a lot of patients. We do coaching, and so we work with patients all over the country, and we’ve not seen that show up. Besides that, no negative feedback loop, no toxicity, I just don’t see any reason. Like I said before, I would love to maybe even go on. Andrew, if you’re listening to this, I would invite you to maybe let’s do a podcast on melatonin together.

Ari Whitten: Cool. One other thing I’ve heard my friend, maybe your friend also, Dr. Ben Lynch, who’s a genetics expert and biochemistry, he also warns about high dose melatonin interfering with estrogen. Have you heard anything on that or seen any effects like that in patients that are using high-dose melatonin?

Dr. Lieurance: No, I’m not familiar with any of his work.

The paradoxical effect of melatonin

Ari Whitten: Okay. I have some personal anecdotes here I’d like you to comment on as well. I’ve read, for several years now, a lot on melatonin, and I think the research is so impressive, as you’ve outlined here, that I was very high on it and I started trying to take melatonin. Anytime I take more than a microdose, I experience pretty significant side effects. I’m under the impression that I’m in the minority of people here, but my dad experiences the same thing which leads me to believe there might be a genetic component to this.

What I experience is that it profoundly disturbs my sleep. I sleep horribly with anything more than about a milligram of melatonin. If I take 3 or 5 or 10 milligrams, I will wake up feeling extremely ill and nauseous, and extremely groggy in the morning for about an hour. I got to lay in bed for an hour to let all of those symptoms wear off to the point where I can walk around and function.

I’m not somebody who’s sensitive to supplements in general or sensitive to anything as far as stressors or anything like that, but there seems to be an extreme sensitivity to melatonin for some reason. I’m curious– and from polling my audience– I was curious, so I polled my audience to get a sense of if other people are experiencing that. It seems to me that maybe 5% to 10% of people have this reaction to melatonin hypersensitivity to it. I’m curious if you know anything about that, you’ve experienced people who have that reaction, and what physiology might explain it?

Dr. Lieurance: A few things. One is, it sounds like you’re having what’s called a paradoxical effect which you’re getting energized which would explain the loss of sleep and maybe waking up feeling groggy, although waking up feeling groggy can happen with some people that don’t metabolize quickly. Sometimes if you’re sensitive to caffeine, you might consider that you’re not going to be breaking down melatonin as well either. It’s the same gene pathway. What we’ll have people do is dose the melatonin earlier like maybe around dinnertime or even before dinnertime so that their bodies had an opportunity to clear that out by the morning.

The paradoxical effect where people get energized with melatonin does happen from time to time, and when we have people that have that effect, we’ll dose them during the day if it’s somebody that has a medical situation that we’re looking to dose them with melatonin. It is interesting, there’s nothing really clear in the research on why that happens. With regards to maybe feeling ill, it’s possible that you might have some heavy metals. One of the things that melatonin does very nicely is it chelates and causes the brain to dump heavy metals and toxins.

Sometimes people have some side effects and they’re not willing to continue on, like, “Oh, well, I’m going to try melatonin.” They might try it once or twice, they have a negative experience and then that’s it. They don’t go back. Whereas it could be because it’s charging up the cells so much, it could be that there’s a bit of what’s called a Herxheimer reaction. This is a name for a healing reaction where the body goes through a process where there could be die off if you have an infection like maybe you have chronic Epstein-Barr and the body starts to clear out that.

Then you might start to have some inflammation or some side effects associated with that die off or if you’re toxic and the body, it all of a sudden gets deep cellular energy like we talked about, then it starts to throw off some of those toxins. Then there could be some side effects there. Those would all be some potential possibilities. Have you done it more than just a couple of days or–

Ari Whitten: Yes, many times. I don’t think it has to do with a Herxheimer or anything related to toxins. I’ve done many different types of binders and chelating agents and I’ve never had any effect like that.

Dr. Lieurance: Have you tried the suppository?

Ari Whitten: I have not.

Dr. Lieurance: Yes. We produce a suppository. It’s got 200 milligrams and I’ve had a number of people that have had challenges with the oral and they’ve had great results with the rectal delivery. That could be worth trying, but at the same time, there’s been some people that still reacted to the suppository. It’s a process of trying things.

Ari Whitten: Yes. I like using micro doses of it, and that’s where I find that it enhances sleep and I generally feel better from it. A couple other questions with melatonin. One is, you mentioned earlier about negative feedback loops. For example, using testosterone. If you take as many bodybuilders to take exogenous testosterone that it downregulates your own internal production of testosterone, you get shrinkage of the testes. This idea, as you mentioned earlier, has been tested with melatonin, and the research generally doesn’t support the idea that there is a negative feedback loop that taking exogenous melatonin suppresses your own internal supply.

I’ve even heard some researchers, for example, Doris Lowe, whom you’re probably familiar with who specializes in melatonin argue that taking exogenous melatonin, if anything upregulates and enhances internal melatonin. However, there’s one thing that I see consistently reported that doesn’t mesh with that, which is, many people report that when they use melatonin consistency consistently 3, 5, 10 milligrams, and then they go off, usually, they sleep poorly for at least a night if not a week or two which is consistent with the idea that there is a negative feedback loop like symptomatically. As I said earlier, the research doesn’t support that. What’s your take on what’s going on there?

Dr. Lieurance: Well, imagine if you had just low melatonin levels, to begin with, and you’re taking it and it’s giving you better sleep. Then there’s probably some systems in the body when you stop taking it that might get engaged but have a delay. Since there’s no change in the melatonin itself, it has to be some other system in the body. There should be more research done in this. I don’t have a good answer for you, but yes, I have seen that with some people. If there’s ever a situation where you’re getting something that’s helping you and then you take it away, that the body has to then recalibrate for a bit-

Ari Whitten: Yes.

Dr. Lieurance: -but that’s outside of the actual production of melatonin.


Can God and "Evolution" coexist?

Ari Whitten: Got it. A broader, more abstract question. Particularly, in the context of the discussion of God that we had earlier in this. Can I ask you if you believe in evolution? I know some religious people who speak of God generally see that as at odds with the idea of evolution. I’m just curious where you land on that spectrum.

Dr. Lieurance: Wow. It’s an interesting conversation. I try to stay relatively neutral. In my mind there’s a possibility, there’s a number of possibilities– I see the argument with some of the gaps in that where we are not seeing some of the– We’re not digging up enough bodies that fill some gaps. The idea that there’s some sort of an extraterrestrial involvement to me makes some sense. I’m not real rigid with that, so I couldn’t answer saying, “Hey, this is exactly what I believe.” I’m kind of open and I find all the conversations very interesting.

Ari Whitten: Okay, so I’ll ask it in a way that won’t matter which direction you believe in. Some context first, before I ask this question. We have in our bodies at the cellular level, a redox balance. We have our own internal production of reactive oxygen species, and we have our own internal supply of antioxidants, melatonin being one of them, glutathione, superoxide, dismutase, catalase, heme, oxygenase, et cetera. For a long time, it was thought that the oxidants were the bad guys and that we need to sort of oxidants bad, antioxidants good. This idea has been around for a long time, 80 years Harmons, free radical theory of aging, many, many decades of testing.

For the most part, this simplistic model has largely been debunked. It’s not that simple, that reactive oxygen species oxidants are the bad guys. The more antioxidants neutralizing them, the better. We know now that the reactive oxygen species serve vital roles in the body and are there for a reason, immune defense, signaling for mitochondria to grow bigger and stronger, and mitochondrial biogenesis in response to hormetic stress, many, many other roles.

We know that the cell is trying to maintain an ideal redox balance, balance of oxidation to antioxidants, and it has, again, its own internal supply of both oxidants and antioxidants to try to maintain that appropriate balance. Given that– and there’s lots that we could delve into this, this could be an hour-long discussion by itself, but just to simplify it. Given that context, what is the logical argument for the use of high-dose antioxidants? Meaning why wouldn’t God or evolution have designed us with those higher level of that supply of internal antioxidants if that was the optimal state of human physiology?

Dr. Lieurance: Well, I’m in-line with your philosophies. If you look at ozone in clinical practice, it’s the most oxidative substance on the planet. Yet, we inject this into patients and people get better, they feel better. It’s a signaling. Oxidation becomes a signaling for our antioxidant systems. When you’re just throwing antioxidants at the systems, it’s like the negative feedback loop with testosterone. It’s like your [unintelligible 00:43:29] as well. We’ve got enough in that, we don’t need to make any more, so by constantly quenching all the oxidation, the body’s like, “Well, things are pretty good. We don’t need to have to deal with much stress here.”

Then when stress hits, then there’s not a defense system. I can’t help but appreciate the fact that back in primitive days that the oxidation level was extremely high. We didn’t have the ability to eat the rainbow back then. You weren’t eating a lot of fresh fruits and vegetables and eating a variety. You were eating more mono diet. You’d probably just eat meat for a month or so. We were more designed to endure and thrive with bouts of oxidative stress, that’s pretty evident.

This is becoming extremely well embraced by the medical community in general, biohacking community. You don’t want to be afraid of oxidation. It used to be such as you pointed out that it was the enemy, I remember every commercial would be talking about how many antioxidants this has or that has. It’s failed so many other things that they’ve done: the food pyramid, you have to turn that upside down for it to make sense.

Ari Whitten: It’s interesting. Unfortunately, most of the population, and I find even most of the medical community is still under the impression that they don’t understand the value of oxidants, yet. Yet, we have so much research showing that many different antioxidant supplements have failed to prevent disease, extend lifespan, and paradoxically many oxidative strategies or interventions or lifestyle practices such as for example, exercise or other Hormetic stressors like sauna that are profoundly oxidative do ward off disease and extend longevity.

What’s going on is that there’s an interplay as you were alluding to with the internal redox balancing systems. Where these oxidative methods exercise and other Hormetic stressors create a response internally that builds up the internal antioxidant system. Also, just a new paper from Russell Reiter, who’s one of the top melatonin researchers in the world, shows us that it is those oxidative practices particularly exercise and light therapy, that up-regulate the cellular production of melatonin, mitochondrial production of melatonin.

There’s this balancing act that’s going on that when you expose your body to the oxidative practices, the body responds by boosting melatonin levels. We also know that when you use lots of antioxidant supplements exogenously, as you alluded to, it downregulates the internal supply. It says we don’t need to produce our own, we’ve got lots being supplied externally.

Dr. Lieurance: One interesting gene pathway PGC-1α. This is like the one of the main pathways activated with oxidation. This is where our body gets to regulate the production of more new healthy mitochondrial biogenesis. It’s not pseudoscience. I remember early on, Ari, we were doing ozone and I would have my medical doctor friends that I would talk to, and they were so close-minded. To be honest with you back then– I didn’t have the languaging that I do these days, so I was like, ”well, no, but it’s working. It’s all this oxygen and blah, blah, blah,” and it was like, “Well it’s very oxidated. Why would you want to put that? It’d be extremely dangerous.”

Nowadays we have so much research and information to carry these conversations. Even with the most discriminating scientists such as Russell Reiter probably one of the biggest inspirations I’ve had especially with melatonin, he’s a genius.

How methylene blue affects the body on the physiological level

Ari Whitten: We’re quickly running out of time here. I would love to spend another hour talking to you about melatonin, but I want to make sure that we go into methylene blue. This is something that has become very popular just in the last six months or a year especially, it’s skyrocketed in popularity. I have a lot of practitioner friends of mine that are seeing profound results, both in experimentation on themselves and with their patients.

This is also something that is understood in an over-simplistic fashion as purely just an antioxidant and nothing beyond that. There’s some more sophisticated stuff going on. Can you talk about what Methylene blue is doing physiologically? What it is, first of all, for people who are unfamiliar with it and what it is doing physiologically?

Dr. Lieurance: Sure. It’s a brilliant blue salt and it has an affinity to the mitochondria. Their nerve tissue is incredibly mitochondrial dense, it was originally used as a stain and so that they could see certain structures in the body very clearly. It was also used as a stain for clothing and fabric. That’s what the initial name of the substance was Methylene blue.

Ari Whitten: By stain just for listeners who don’t have a science background for microscopy, for histology, for pathology, looking at tissue samples under a microscope and staining it with this chemical to visualize certain structures better?

Dr. Lieurance: Exactly, yes. Paul Ehrlich was looking for a cure for malaria. What they would do is they would stain the bacteria or the parasite or whatever they’re looking at and then they could see it. Then they could use different drugs and substances to see the effect that it was happening. They could see things dying or thriving or whatever. They were using the stain throughout their experiment. As soon as they added the stain it killed the parasite to malaria. They had their cure to malaria.

Since then, it’s been shown to be a very powerful antimicrobial for virtually every virus, bacteria, fungus, we’ve used it with even COVID. It’s been shown to have anti-cancer effects. When we start to talk about how it works and what it’s good for it almost sounds impossible. I get that. I hope anybody listening to this doesn’t shut down thinking how could it possibly be something that has that much of a profound effect in the body, and it leaves the body virtually unharmed. In fact, the word “magic bullet” was coined based on Methylene blue and this fact that it’s so powerful.

Because it’s so brilliantly blue it reflects blue, and it absorbs red and specifically red in the 660  nanometers because of that Methylene blue can be used with light therapy. It can magnify the effects because once the Methylene blue gets into the mitochondria it can start to absorb these photons. Methylene blue acts as both a prooxidant and an antioxidant and it does this independent of oxygen. There’s an average of 30% upregulation in mitochondrial function. There are a number of different studies out there on mitochondria– on Methylene blue for a variety of different types of conditions.

Methylene blue for depression?

One interesting condition is depression. One of the things that a lot of people will find when they take Methylene blue is that their mood will be elevated because it has some benefits somewhat like an SSRI would have on mood. They did studies where they started out with smaller doses of Methylene blue, and they increased it. They went up to as high as 500 milligrams per day. This was for a year and they had very little side effects, and they found that the more they increased it the better the results were on the depression.

Yet, there’s also some research showing that very small amounts of Methylene blue can be of benefit for mitochondrial function. My experience clinically has been that dosage can be unique for each individual. Especially when you get up under four milligrams per kilogram of body weight, you’re well within a safety zone and probably individuals can go more. That’s the rule of thumb that I hear from a lot of the experts out there is between half a milligram to four milligrams per body weight.

Potential contraindications of methylene blue

Ari Whitten: The one I’m remembering there’s one medical condition that’s a contraindication. It’s glucose, six phosphate deficiency, or something like that.

Dr. Lieurance: Yes, very rare genetic disorder. Typically, people know they have that.

How to dose methylene blue

The dosing, it can be taken orally. A lot of people will take it in a sublingual because there’s a company out there that sells it with different blends and those can be a benefit on the lighter dose. I haven’t found as many patients and as many clients respond to the lower dose as they have to the higher doses. Typically, your urine will turn blue. That’s what I’m looking for. Then the urine, the half-life of methylene blue is about 12 hours. Each time you take it, it’s going to have a half-life of 12 hours. It can be taken twice a day fairly easily. What else?

Methylene blue for like an infection, let’s say that you’re coming down with something or you’re fighting a chronic issue with like, say lyme or Epstein-Barr or something like that. I would definitely say that you’re going to want to do a couple things.

Combining red light therapy with methylene blue

One is probably go in the higher doses of it and then you’re going to want to utilize light therapy to get the maximum antimicrobial effect as much as you can go into the sun. You can use LED panels. They have these panels. We sell some. We didn’t preface this, but I have a company called M-I-T-O-Z-E-N. We sell high-dose melatonin. We sell methylene blue, we have some red light products, different rectal delivery products, and such.

The LED panels don’t absorb deeply into the body. They’re good. They do supply a lot to the skin. Some of the incandescent lamps can be more penetrating because they have more near-infrared, but of course, the sun is the best, intranasal laser, and intranasal light is just fabulous. We’re working on getting this little laser that– You can find intranasal products out there, but they’re like five millivolts, and they’re effective. It’s better than nothing, but it’s really light. We’re working on a device that I’m calling a mi mitotorch, which is like a stronger laser that’s about 300 millivolts.

We’re getting some of our clients using that intranasally intraorally. You can do transcranial, there’s just some fantastic applications of methylene blue, different lasers, and different types of light therapies. Then if you want to have fun, you can stack oxygen therapies on top of that with like, say, at the very low-end breath work. Moving a little bit more extreme, you can do like, EWOT or exercise with oxygen. There’s some different devices out like that or you can start to get into hyperbaric.

Here, at the clinic, we have something called a CVAC, which stands for Cyclic Variation and Adaptive Conditioning. It’s like this pod. We use that with a lot of our protocols, but I’ve not seen any other combination work as powerfully at really ramping up people’s metabolism and their energy and life force.

Ari Whitten: Then than methylene blue plus light therapy.

Dr. Lieurance: Methylene blue light therapy and then some oxygen therapies.

Ari Whitten: Okay.

Dr. Lieurance: Then if you can throw on some grounding or some PEMF, you got something.

Ari Whitten: What’s interesting is that both these molecules that we focus this podcast on, methylene blue and melatonin interact with a subject I’ve written a book on, which is red light photo biomodulation and 660 nanometers as you said seems to be the magical wavelength, or around that. It’s not going to be only that, but there’s going to be some range near that wavelength, which is in the red-light therapy zone. As Russel Reiter has found, this red-light frequency increases mitochondrial production of melatonin at the cellular level, extra penile melatonin production. Their synergy as you’ve said, with methylene blue.

Now, the specifics of that are interesting because this is something that is used, for example, in blood transfusions. They take the bag of blood and they put methylene blue in it and they irradiate it with 660 nanometer red light to kill any microbes that are present. This is because the red light, as you said is absorbed by the methylene blue and then it creates singlet oxygen which is an oxidant. We have this thing that’s commonly thought of by most people and framed as an antioxidant. When you combine it with red light, it’s producing lots of oxidants.

Now, the story is, as we’ve said earlier, more complex than just oxidants are bad because we’ve already said that many things that are oxidative in nature are actually beneficial. There’s antimicrobial effects to me that make sense. You’ve got the methylene blue, red light, creating singlet oxygen now you’re killing viruses and bacteria and things like that can be used intraorally. There’s studies to show it kills bacteria, pathogenic bacteria in the mouth, as I said. Even studies on COVID showing it kills COVID in blood transfusions.

It’s reasonable to think it might also interact internally in the same way. What do you think is going on outside of the antimicrobial effect? What do you think is going on with a combination of methylene blue and red light as far as the energizing effect or brain-enhancing neotropic effect? Do you think it’s similar to ozone and that basically what you’re doing is creating a burst of reactive oxygen species that’s then creating a beneficial adaptive response? What do you think is the physiology underlying that?

Dr. Lieurance: The electron transport chain is– the mitochondria moves electrons. That process of moving electrons is exothermic, it produces heat. What methylene blue does, it gets in there and it acts to donate electrons. It’s just like here, here, here. It lubricates that chain so that it goes more efficient. There’s four complexes in the mitochondria, and they’re all named based on the numbers Complex I, II, III, and IV. There is a fifth, but for this conversation, we’ll just focus on the four.

Methylene blue upregulates the first, second, and third by 110%, yet it only upregulates the fourth by 70%. That fourth complex is called the cytochrome C. Cyto for cell and chrome meaning light. When you add light, it supports that last protein so that it fully lubricates that whole system.

Ari Whitten: Since red light photons interact directly with cytochrome C. That’s interesting. We’ve got the singlet oxygen antimicrobial effect and this other mechanism interacting with cytochrome C. Very interesting. I know you said it’s individual, but what do you think as far as dosage range, that’s ideal for working with methylene blue? It used to be thought several years ago when I first started experimenting– Actually, I first started experimenting with methylene blue when I was a kid in my fish tank to help cure my fish of– they call the disease ichthyosis or something like that, of certain fish diseases, where methylene blue is the predominant treatment.

The optimal dosing parameters when starting out with methylene blue

When I started experimenting it with it in my own body instead of my fish tank, what was common back then was to recommend these tiny microdoses of– I forget– in the range of around 1 mg or 1 to 3 mg a day, 0.1 mg, stuff like that. As I remember, I started to go and explore the studies, and a lot of the animal studies were using doses that were 50 or 100 times or 200 times more than that. What do you think are some optimal dosing parameters to give people to maybe play around with experimenting with methylene blue?

Dr. Lieurance: Between 40 and 80 could be a good area for people to start. When you start getting some issues with, like I said, if someone was dealing with an infection, and, of course, I should probably preface this, that this is not medical advice and that if you were looking at taking methylene blue, you should talk to your healthcare provider before you start. This is just for educational purposes that– in our practice, we will have people take sometimes even 500 mg in a day. This is not anything new. This is something that’s been done in many studies.

Something that a lot of people are going to find online is this idea that taking methylene blue along with anything that deals with serotonin, SSRIs or psilocybin or MDMA, or St. John’s wort even, so all of these work on serotonin. There’s a concern that someone would get a serotonin storm, which can be lethal. What I found is that these warnings were based on five cases and those cases were receiving a thymectomy, meaning that they were having their thymus gland surgically resected.

As we talked about before that the methylene blue likes to go to very metabolically sensitive tissue. Well, the thymus accumulates a lot of methylene blue and so you can see it very clearly. The IV protocol for these surgeries is very, very high, so 1000, 2000 milligrams plus. These patients did not do well that were on SSRIs. After that, Mayo Clinic came out and rescinded this warning saying that we only warn SSRIs if you’re getting this one surgery with these high doses of methylene blue.

Well, the FDA has maintained that warning. That’s just basically vanilla saying no SSRIs along with methylene blue. I can tell you that we’ve seen this with a number of patients. Even the expert, Francisco Gonzalez Lima, made a statement that he’s very disappointed with the way this was all handled. He feels like hundreds of thousands of people could have benefited. The research was so good on depression that all of the psychiatrists and psychologists could have been using this as a tool that could work potentially much better than any other therapy available.

Yet, they’re all afraid of it because of these warnings. The FDA has not rescinded that warning, even though Mayo Clinic came out and that it’s not founded on anything. The whole country of Canada has rescinded this warning. Anybody listening to this just know that it’s taking it in the doses of half a milligram to four milligrams per kilogram body weight. It’s safe according to experts, even if you were taking SSRIs.

Ari Whitten: Dr. Lieurance, I’ve really, really enjoyed this discussion. I’ve been looking forward to having you on the podcast a long time. I want to thank you for taking extra time, going 12 minutes over our allotted hour. I appreciate that. Is there anything you want to leave people, any final words you want to leave people with and let people know where they can find your work, your products, your clinic, or get in touch with you?

Dr. Lieurance: Yes, sure. If people want to take a bit of a deeper dive on Methylene blue, you can go to You can find me on Instagram at Dr. John Lieurance or @DrJohnLieurance. Then we also have where we have educational material. My clinic is and we’re in Sarasota, Florida. Then our store is, soon to be, which is going to be a private membership which will be interesting. We’re going to be able to have more freedom of speech where we’re going to get more into some detail such as some of the things that we’re talking about here with you, Ari. Thank you so much for having me. It’s been a pleasure.

Show Notes

00:00 Benefits of methylene blue
01:40 – Guest Intro Dr. John Lieurance
04:55 – The types of therapy Dr. Lieurance uses in his clinic
10:35 –  Dr. Lieurance’s experience of God
16:40 –  Common misconceptions around melatonin
19:35 – Melatonin production
23:10 – Melatonin is an adaptogen
25:10 – The relationship between melatonin and mitochondria
32:25 – The paradoxical effect of melatonin
41:00 – oxidants and antioxidants
51:00 – How methylene blue affects the body on the physiological level
54:10 – Methylene blue for depression?
55:30 – Potential contraindications of methylene blue
55:50 – How to dose methylene blue
57:15 – Combining red light therapy with methylene blue
1:04:50 – The optimal dosing parameters when


Recommended Podcasts

Like this article?

Share on Facebook
Share on Twitter
Share on Linkdin
Share on Pinterest

Leave a comment

Scroll to Top