305. Methylene Blue Health Benefits & Beyond With Hans Amato
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Thank you for listening to the Boost Your Biology podcast. My name is Lucas Owen. I uncover the most cutting edge health information on the planet, ranging from hormones, nutrition, supplementation, fat loss, biohacking, longevity, wellness, and a whole lot more. Welcome to the Boost Your Biology podcast.

What's up, ladies and gentlemen, and welcome back to the boost your biology podcast. Today I have a special guest joining me back in the studio. Hans Amato. Hans, welcome to the podcast. Thanks, man. Thanks for having me back.

Awesome. Awesome. So today, I'm really keen to dive deep into methylene blue to start off with. That is becoming extremely popular on social media at the moment since we saw RF Kennedy using it on an airplane. Did you see that video, Hans? I have not, but I've heard about it, yeah.

Yeah, he was, apparently he was, I mean, he was using quite a big dosage. I think he did like two full plunges of the methylene blue in his water. So let's get into that. Methylene blue, explain to my audience what it is, maybe the historical significance, like how it came about and why people might be using it. You're throwing me into the deep end. Maybe you know more about like,

Not in depth, but it's a synthetic dye that's been discovered like a couple of decades ago. And it has a really good safety record. But it was discovered that it's really good for mitochondrial function. So if you want to fill in more like of the background of it, which I'm not like excessively familiar with, feel free to jump in.

All I know about the historical significance was that it's like the very first synthetic drug ever developed back in like 1876, initially to treat like malaria and also some sort of like blood disorders. But apart from that, there were definitely no real...

There was no emphasis on its effects on the brain until later on, like understanding how it can actually cross the blood-brain barrier and disassemble like tau proteins in the brain and help with like potentially offsetting early signs of Alzheimer's. But I mean...

From what I also understand is that methylene blue has a really wide dosage range. There's like the micro dosing, then there's like the actual 100 milligram plus range where they're actually using it to treat advanced sort of blood disorders. But have you personally used it yourself?

I have in various doses I've used or what I would consider more like the micro dosing like less than one milligram and then I've also gone up to like over 60 milligrams and when I was like really like into my unhealthy state that's when I was using like high high doses like 60 milligrams plus and to me it just had like a really good mood uplifting no tropic benefit it wasn't like insane I wouldn't say like I've noticed

anything like I wasn't doing extensive blood testing at that time so like I can't talk about that aspect but in terms of how I felt how I slept just general health everything was okay I felt good but I haven't noticed like significant magnificent anything really like how about you yeah pretty similar man I when I first tried it I remember I was using it specifically to enhance memory

And like for its distinct nootropic effects. So what I did was I had like, I think it was 0.5 milligrams, so 500 micrograms. And I remember going to like, I went to like a really well known library in Melbourne. It's called the State Library of Victoria. It's like a really awesome place to study.

And I remember like I've got a pretty good gauge on whether or not I can actually notice something improving my working memory because the sort of work that I was doing back then, I think I was studying like biomechanics. So I had to understand and memorize like different body parts and like the names of different bones, the names of different joints and things like that. And I do recall...

it having a pretty pronounced effect on like just comprehension speed and sort of like generally feeling like I can just pick up on like different words and memorize different pathways a little bit better. But apart from that, I also do think I eventually I started to titrate the dosage up.

And I think I started going up to like three, four, five milligrams. And that's when I was starting to notice like a little bit of a detriment to my workout performance. I was like looking down at my arms. I'm like, how come I'm not getting a pump today? Like, why am I not getting an actual pump in the gym? And that's when I looked up some research on how it can actually inhibit nitric oxide production. Yeah, that's interesting.

when it comes to nitric oxide because it seems to be a non-selective inhibitor of all of the nitric oxide synthase enzymes. So you would expect people to have experienced loss of morning wood or struggling to get erections and then struggling to get a pump and those kind of stuff. But even when they use it in surgery and they use like 100 milligrams plus, these people don't get vasoconstriction. So there's not an excessive decrease in nitric oxide leading to vasoconstriction, which I found interesting.

so like i'm not trying to discount every uh yeah just kind of like everyone that is like experiencing that i just let's find it interesting that if it does that how can it not cause vasoconstriction despite like significantly lowering natural side so i think there's a there must be another mechanism how it's then also promoting vasodilation at the same time yeah in terms of like mechanisms like just from a basic biology perspective like

Would people consider methylene blue as like a, do you think like an ATP stimulating compound or what are your thoughts there? It's just in the mitochondrial function, the electron transport chain specifically, and in higher and higher doses, it will do that process better and better and better. But ultimately it's,

There's a hormetic effect where lower doses is more effective at stimulating it. Higher doses, there will be a stealing of the electrons from it, which can then actually have a detrimental effect on your energy production. So everyone is different in like where that threshold is for them. And you have to figure out like, okay, this is where my working memory, for example, is the base. This is where I feel like a drop off. And then it's like, okay, I'm going to stay in this range specifically. Yeah.

And what about in terms of because obviously, a lot of people are conscious of the ability for any compound to impact serotonin. Do you think it's like a pro serotonergic compound? Or do you think it like might actually inhibit serotonin? Because I've always actually been a little bit confused there.

Yeah. So it's a mono-minoxidized A inhibitor. And this is what I found interesting is that when you use it on its own and even in surgical circumstances, like no one has ever really gotten serotonin syndrome from it. Serotonin syndrome is when people have just so much serotonin, start to cause like all kinds of serotonin related issues in access. Like have you seen maybe a case report of methylene blue causing that on its own without an SSRI or tyramine inhibitor?

No, never. Not by itself, but yes, I've heard about it when combined with like an antidepressant. Yeah.

Yeah. Yeah. So for me, it's like, okay, anything that's going to promote serotonin, like adding short the front of five HTP and then adding methanol blue on top of that, that might be a bad idea. Or especially if you use another more than mine oxidized inhibitor or something that increases serotonin, that's not a good idea. So like what I found very interesting about methanol blue is that I think there's a lot of like compensation mechanisms that's going on. We don't know about where it inhibits nitroxide, but these people don't get a passive constriction.

It inhabits monomine oxidase A, but on its own, people don't get serotonin syndrome. There's so many, I think, compensation mechanisms that we don't exactly know what's going on. Yeah. In terms of its ability to support mitochondrial function, do you think its effects could be also achieved through other compounds? You might think there are better ways to achieve the same job through different compounds. Yeah.

Yeah, I think methane blue, there is some controversy on how many complexes of the electron sample chain it supports. But let's say it's one, two and three, maybe complex four as well. So there's some theory that can support all of the complexes.

So there's a study where if you use vitamin C with vitamin K2, the MK4 version, it can support complex one. Coenzyme Q10 is going to support all of the complexes. Vitamin B2 is going to help the assembly of the complexes. Vitamin E is going to make sure like the cardiolipin or the lipid structures that's connecting the electron transfer chain complexes so it doesn't disintegrate.

But in terms of effectiveness, I would say like Methanol Blue is definitely on top. But you want to make sure like you're supporting whatever the body uses by default, like Coenzyme Q10, Vitamin B1, Vitamin B2, Vitamin B3, like those stuff should be there. Like it's not going to compensate for that kind of deficiency. But there are other ways you can work around it. But I would say like Methanol Blue is a really good general supportive compound for the electron transport chain.

And do you feel like it's non-depleting of any specific nutrients? You just sort of mentioned like the B vitamins being complimentary, but do you think it might actually like speed up the rate at which we're using these B vitamins?

I honestly don't think so. Unless someone has a low-grade efficiency, it might. But the doses that people are using is going to be so small. So let's say, for example, we have vitamin B3 or NAD. So NAD and NADH, it just like interconverts. Or coenzyme Q10, the reduced form and the oxidized form is just going to interconvert.

so it's not really going to deplete those which is like crucial for energy production but all of the other cofactors like vitamin b6 or alpha lipoic acid can also each convert b1 for um i would say obviously just make sure your diet's nutrient dense but i don't see there's research to support the fact that it's going to deplete nutrients interesting and what about any specific effects on like any other unique pathways maybe that you think that my audience

Might be surprised by the fact that methylene blue has some sort of affinity to some other pathway when you were doing your research on it. So in general, anything that supports ATP production is going to enhance the body in like an indirect way.

The methylation cycle, the retention of nutrients, like your nutrients, the uptake into cell, the retention to self recycling, all of those requires ATP, the production of dopamine. You've talked about this before. There was a study, I think it was a correct me if I'm wrong, alethiamine that increased dopamine, right? So the mechanism of action was primarily by stimulating pyruvate dehydrogenase.

And we just want to have the right limited enzymes when it comes to glucose oxidation. So technically anything that's going to stimulate the proper oxidation of glucose is then going to help to increase your dopamine. And so Methyl Blue can do that as well by recycling your NAD to NADH ratio, like increase NAD. So glucose oxidation improves, dopamine is going to go up as well. So it doesn't just inhibit monomide oxidase A, it can also increase your dopamine. So I think it has a vast effect on all of your neurotransmitters.

neurotransmitters. And just the fact that increases ATP is just overall going to support bodily functions and like chloride channels, calcium channels, like all of those channels relies on ATP to work better.

Yeah, yeah, that makes sense. Like, basically improving the overall net efficiency of many different enzymes and processes in the body, it's very hard to look at it like in a reductionist mentality where it's like it's just inhibiting monoamine oxidase A. Like what you're saying is that it's having a broad spectrum effect across many different enzymes, pathways, organs, tissues, like it's

And this is why I think when people first try, let's say somebody has never used methylene blue before and they decide to use it for the first time ever. You know that like initial, it's like the honeymoon period. You get that with methylene blue. I think that would be one of the reasons behind that would be because people are,

There's something wrong at some point somewhere in the mitochondrial function sort of pathway where methylene blue just fixes it. And they're like, wow, like all my brain fog is gone. Maybe like it reduces neuroinflammation. Do you think that might be what's happening?

Yeah, that's for sure. Just what I would like to also emphasize is that let's say someone has an NAD deficiency because they don't have enough niacinamide or like vitamin B3 or they're drinking alcohol, which is depleting their NAD levels or they don't eat enough red meat, they don't have enough coenzyme Q10. Like methadone blue is not going to fulfill those pathways. It is, it can help to enhance your energy production. Your mind is going to work better. You might think this is fantastic.

but it's never going to fit in like solve those issues that someone has. And chances are, when you fix those issues, your response to Methan Blue is probably not even going to be as good anymore. Because like your baseline and in the way your body's already operating is going to improve so much that a micro dose of Methan Blue is like going to be like me. Like for me at the moment, like if I were to take Methan Blue, I wouldn't say notice anything. But

I primarily notice it when it comes to endurance workouts. If I take, for example, sodium bicarbonate with methane blue, and this is high dose, like 20, 30 milligrams, like I noticed like a profound endurance enhancing effects, primarily when it comes to endurance, not strength.

Interesting. Yeah, I was sort of thinking about some different stack ideas just before I was like, all right, if we had to, like, let's just go through a hypothetical because it's always fun to like brainstorm different stacks. And I know my audience loves hearing about like, what can we combine together to enhance exercise performance and stuff like that. So yeah.

From my perspective, let's sort of jam on that. So let's say we're trying to look at developing the most epic endurance enhancing stack. These are the compounds that I would potentially consider. I would do, yes, a little bit of methylene blue. I would definitely consider like some sort of like either beta alanine or L-carnosine.

I would also put in a little bit of acetyl-L-carnitine because I know that that does have a pretty good effect on endurance from my perspective. I would also add in that TTFD, so that vitamin B1 that really ramps up glucose oxidation. And then also astaxanthin is a unique antioxidant. From an endurance perspective, it does help a lot because it does blunts. I feel like it delays the...

hydrogen ion accumulation. So it does a pretty good job in that regard. So these are like compounds and then maybe even like coenzyme Q10 and a little bit of creatine monohydrates. Like that full stack there is like ticking off. I feel like that would supercharge someone's ATP levels

Um, I, if I had to simplify it, it's going to come back to, like, let's say you, you got your, all your basics covered, right? Your diet's nutrient dense. You don't have any gut inflammation. You're absorbing all of your nutrients. Then like, I love B1. Um, that's going to stimulate proper glucose oxidation. You have the carnitine because carnitine doesn't just enhance fat oxidation. It actually supports proper glucose oxidation as well. So that's really good with the bicarb or beta alanine to support like the acidity of the cells. Um,

what was the other one and then mithril blue to support the electron transfer chain like if you have to simplify it i think that would be it like there's so much more you can go into like for example would you do would you would you add caffeine to that mix as well i think caffeine is like taste it and try it like it's one of the best things you can use if someone tolerates it well yeah i would just go ham on it yeah fair enough yeah i i would as well i mean if i'm trying to break a personal best like

Yeah, caffeine. Well, the thing is like I've got such minimal tolerance to caffeine because I don't use it. So that when I do use it, I actually go way above baseline. So it's always there as like a little...

Yeah, that's interesting. My tolerance to caffeine seems to be quite high. Like in the past, when I tried caffeine, I wanted to see how high I can go before I got anxiety from it. And I was up to 900 milligrams before I started to feel like a little bit jittery, not even like excessive jittery. So like I wasn't even using caffeine before that. What was your body weight when you were like, was it similar to what you are now? I think it was like low 90s.

Yeah, and my body fat percentage was roughly around 15%, maybe slightly lower. Okay. So let's go back to that stack. So you're a fan of the vitamin B1. Do you remember the very first time you tried vitamin B1 in like a high dose? I do. But I can tell you, I noticed more from vitamin B2 than I did from vitamin B1, actually. Okay.

Was there any particular reason as to why you think you responded well to the vitamin B2s when you first tried it?

Likely. So, so vitamin B1, B2 and B3 are very rapidly depleted by stress. And some people just need more vitamin B2 for proper fat oxidation. And at that time I was very intolerant to fasting or low carb diets, which would indicate that you can't properly oxidize your fat. So if someone can't go very long between meals, they wake up during the night, they just can't burn their fat very well. And that can indicate carnitine and vitamin B2 or like other nutrients as well, but those are kind of like the primary ones.

And so for me, I would say like that definitely that's a thing because like I could eat high carb and I was fine. I never got like diabetic symptoms like high blood sugar or like carb intolerance, you know. So I think that was just me in terms of like how my body is working at that time. And with vitamin B2, I mean, from a food source perspective, like do you think that if somebody were to eat like quite a lot of like raw milk, like liver, like what are some of the other B2 rich foods?

Yeah, exactly. Like B2 is one of the rarest nutrients. Like if you don't drink milk or eat liver or organ meat, like you're not really going to get B2. But some of the B vitamins can be produced in the gut from certain bacteria. But that amount is still relatively small. But your body can become very effective in how well it absorbs, uptakes into cells and retains it and recycles it.

Some people just not that effective. And I think like I wasn't one of those effective people. Other people just aren't effective. So some people can get away with a low B2 diet and they're just fine because their body's just more effective at retaining and utilizing. Interesting. Going back to NAD, um, let's look at different strategies. I mean, like NAD is very well studied now. Like we have a lot of research about what it does, you know, how it supports healthy aging, um,

When you first came across or like when you were studying NAD, like what were some of the strategies you were figuring out to be like, okay, these are definitely the biggest needle movers to actually support NAD levels in the human body? Right. So you want to provide a precursor, as we all know, that's something like niacinamide, niacinamide. There's a lot of debate on which one is best, but let's say niacinamide and NAMN is kind of like equally effective when it comes to those.

Then you want to make sure that the NAD to NADH recycling is on point with the electron transport chain, specifically complex one. So that's like coenzyme Q10. And let's say vitamin B2, because it helps with the assembly of the complexes. Because it's not just complex one, complex two, complex three. It forms super complexes. So vitamin B2 is effective for that.

Then you can use quinose that helps, there's an enzyme called NQO1 that also helps with the recycling of NADH back into NAD. So that's the ways to recycle it. So you want to provide something that is going to increase NAD. Then you want to recycle it properly. Methylene blue can also play a role. And then you want to prevent the excessive catabolism of NADH.

So that is inhibiting the PARP enzymes or the CD36, I think it is. Correct me if I'm wrong. Maybe it's like 38, right? 38, yeah. Like apigenin.

Yeah, yeah, yeah, exactly. So like people would say, you know, you've got to inhibit the PARP enzymes. But it's like, okay, why is PARP upregulated? Because you have DNA damage. Like, so it's kind of like this black and this give and take thing where you're inhibiting PARP. So you're sparing your NAD, but now your DNA is not getting repaired. So like ultimately what you want to do is prevent oxidative stress that's happening in the first place. So you don't get a DNA damage. So your PARP doesn't even become upregulated.

So I'm not really a big fan of just like going ham on all of these CD38 and PARP inhibitors. And then the other one is, you know more on this than I do, the 1-amino-MQ or something, like maybe you can find out on that. Yeah, the 5-amino-1-MQ. Yeah. NMT inhibitor.

Yeah, exactly. So like the research is looking like a really solid on inhibiting that enzyme because that enzymes become upregulated age and disease and whatnot. And so when you look at that compounds like, wow, this is really amazing. But then when you look on Reddit and people that use it for whatever purposes, in my opinion, like the regular show is like, oh, well, damn son, like this doesn't look all that great. Like I'm so, so I'm not too enthusiastic about it. Like that's why I haven't pulled the trigger on it, but maybe you have like a different experience with that compound. Yeah.

Yeah, it's interesting. From what I've heard about from clients when they've used the 5-Amino-1-MQ, a lot of them are saying that they notice improvements in general endurance, just general stamina, a little bit more energy. And some people have said that it's also somehow improved their HIV. Now, the HIV enhancement, that surprises me.

And also what I think is happening is a lot of people are buying like fake 5-amino-1-MQ as well because that's like you've seen the prices. Like let's say you compared vitamin B3 to like simple niacinamide versus 5-amino-1-MQ. Like it's like almost like 20 times the price or probably even more like 200 times the price. But yeah, I do find it pretty interesting and I do think that NNMT inhibition pathway works.

It's something that I would like to see more research on in terms of it also affecting things like circadian rhythm because I know NAD does play a pretty dramatic role in like circadian rhythm. And also whether or not it can offset like the typical insulin resistance that's induced by like a high fat, high sugar diet sort of thing.

Yeah, for me, like every time I, the way I rather think about it is like instead, like why does NNMT become upregulated in the first place?

you know, why does oxidative stress happen? Why does the PARP enzymes become unregulated? So instead of focusing on PARP, like all of these enzymes, just like go back to the root cause you have like bacterial overgrowth, slow transit time, improper digestion of nutritional deficiencies, go all the way back to the beginnings. Like why is all of this stuff happening? And then fix all of that. And chances are, you're not even going to be needing these compounds unless you want to go super physiological, maybe.

Because if you're an elite athlete, you are going to be inducing an excessive amount of oxidative stress due to the training that you're subduing yourself. And I was also thinking about like all of these synthetic compounds and this might, like, I think all of us love supplements. Like me and you, we just love supplements, supplement fanatics. We want to be on the cutting edge of stuff. But then ultimately it's like, how much of this, like,

what does it really mean? Like how effective is this stuff really when you are already optimized? Like, is there something you can do before? Is this a patch or is this a root goal solution? That's, that's also what I think about is like, if someone is older, what would you rather focus on? A root goal supplement or just something that might temporarily increase endurance? And this might seem really rude, but it's like, okay, who are you?

What is your goals in life and what are you accomplishing? Are you just sitting by your desk and want more energy? Well, bro, maybe you shouldn't be looking into elite compounds because, right? So it's like being realistic with what you are doing and what you're trying to accomplish. Go back to the very first. So that...

Yeah, you got a good point. It's like, all right, let's look at the person's objective, right? If they're trying to dial in their work performance and they don't necessarily care about their health per se, they just want to achieve a state of hyper attention, being able to just smash through their work so that work no longer feels as difficult.

Then it's like, okay, let's leverage stimulants. Let's leverage mitochondrial enhancers. Let's take a shitload of like nootropics and like let's jack them up and get them like hyper primed for work. But then it's like, then they decide to go home and they're just like, they'll sit down on the couch. They'll just, you know, eat whatever they want basically.

That's like a different, it's like priming the body for what I like that because you're basically saying, what is the objective behind this nutrient or compound? How is it supporting me in my in my daily living? And how does it fit into my entire lifestyle sort of thing? Yeah, like, for me, it's all about like, elevating your baseline to a point where you don't really need supplements. And I understand exactly what you're saying. Like, you want to be using supplements.

to just crush your work like i completely get that i'm also for that um but if you're going to go back to a diet where you eat bufa that's inflammatory right you're not sleeping really well you're taking caffeine too close to bed your sleep is going to be poor now the next day you're just going to be needing more nootropics in the first place more methyl blue more nad boosting compounds and like it's just a feeling like you're spinning your wheels on that like how long can that honestly last five years max couple of weeks because every supplement protocol has like a honeymoon phase

Put them on a protocol, bro, this is amazing. Two weeks later, it's like, bro, can I get a new stack, please? Yeah, no, definitely. There's definitely been some like over the years, like understanding. Well, what I might mention as well, Hans, is like there have definitely been compounds that have elevated my baseline to the point where you no longer need that particular substance or compound. So like, I mean, it's happened before.

quite a lot with some of the newer compounds that I've started playing around with recently. Things like, I mean, versions of like inositol, inositol, really, really high dosages. I think that's had like a semi-permanent effect on

blood sugar management for me and this is coming from someone who my dad is like mid-60s right and he's very fit and lean like he looks great for his age but he has higher blood sugar and higher cholesterol than my mom who's actually obese like and he's he's um obviously type 2 diabetic and he says like oh it's just genetics you know he lives a pretty healthy lifestyle but

From like a blood sugar management perspective, I'm always like, if there's a compound out there that can support that, I'm all for it. Because I also just don't want to give up my carbohydrates. I just love my carbs. Yeah. Like, you want to talk about that for a second? Because it fits into the mitochondrial stuff, right? Yeah, for sure. All right. So when it comes to blood sugar, because I've also had some issues in regards to when I wake up,

My first fasting blood sugar is roughly 98, 99, 100, roughly. You would perceive me to be close to pre-diabetic. Have a meal, 60 minutes later, it's down to low 80s. Bam, back to insulin sensitive. When you look at my HbA1c, it's like below 5.3%. It's like really good. I'm insulin sensitive, right? My glucose disposal is really fast. If I were to eat

I once did this experiment. I was having 150 grams of uncooked rice with a bunch of ground beef, 9% ground beef. My blood sugar spiked only to 120. And within 60 minutes, it was back to less than 100. So like very insulin sensitive with large amounts of like high GI carbs. So yet my fasting glucose is elevated.

So the emphasis I'm trying to put here is that the reason why people oftentimes, most oftentimes, have elevated fasting glucose is not because they're insulin resistant. It's because they have elevated gluconeogenesis, which is the process where amino acids is being converted into glucose. So we knew, for example, and this is studies on it, people can check it out, DCA, and we talked about vitamin B1. So DCA is a drug that stimulates pyruvate dehydrogenase.

It's a pyruvate dehydrogenase kinase inhibitor. So the kinase enzymes inhibit pyruvate dehydrogenase from working. So your glucose is only being converted to pyruvate. Then the pyruvate can't be converted into acetyl coenzyme A. So it's not entering into the TCA cycle. So you kind of get stuck there. Pyruvate staying pyruvate. And then pyruvates convert to lactate or alanine. And then lactate and alanine, it feeds and creates back into glucose. Your glucose is elevated.

So you never want to check only your fasting glucose in the morning. You want to check during the day and to see like what's the fluctuation there. Some people just stay high. Some people don't.

And very often when someone goes on a low carb diet, their fasting blood sugar goes up or it stays at like at 120, 140. It doesn't go low. It's like, I'm not eating carbs. What's going on? It's because gluconeogenesis is elevated, right? But the additional point I'm trying to make here is you don't just want to look at your glucose. You also want to look at your triglycerides. You want to look at lactate levels. How is your body converting that pyruvate into lactate? Because this is what I've seen with myself.

is that um let's say i'm eating uh beef and honey my blood sugar is like literally back to normal like low 80s within 60 minutes like spike down to normal it's like it's amazing i love it but then you check my lactate it's like okay my lactate's going up like the normal range is going to be like 1.5 after eating mine was like three like why is my lactate so high why is my body converting into lactate

Like that immediately going to give you an idea. Okay. So my body, my dehydrogenase is my electron transfer chain. Like I'm really trying to emphasize for people like you, you got to do testing, like never check your glucose without checking your lactate. You've got to do like an organic acid, organic acid taste. You can't just do that. It's like when people say like, I tested my testosterone issue. And I'm always like, what? Like, okay, what does that mean? It means nothing because it doesn't tell me like why, right.

Like we're talking about mitochondrial function, we're talking about Methadone Blue, we're talking about NAD. And you have to do testing to figure out like, okay, what's really missing? Methadone Blue can actually help. And I've seen people lower their blood sugar by using Methadone Blue because ultimately now your cells actually working better recycling your NADs so your body's able to better utilize the glucose. Like there's so many variables going on, but you have to properly do these tests to figure out like which nutrients deficient. So you can solve that.

And there's going to be no cookie cutter program for this. That's all I can say. It's like you honestly have to taste and figure out like where's my deficiency. And this is the difficult part of it all is like you do the taste and it's like, okay, so my hypothesis is this, this, this, and now I'm going to taste this, this, and this to see what's going on. So that's kind of like the enjoyment of like this whole process.

You know, I'm glad you brought up like the testing element and looking at like, I was going to mention before,

like to not just rely upon blood tests and to do something like the organic acids test, because that's more of a comprehensive breakdown on different metabolites, different pathways that just can't be analyzed through a blood test, right? So for example, let's say somebody did decide to use methylene blue. If we circle back to that,

pre organic acids tests and then post organic acids test following methylene blue, what are some of the I don't know, like key markers that you think would would be altered? Yeah, all right. So I would say like, given that methylene blue supports electron transfer chain, you want to look at the extracellular the cytosol NAD to NADH ratio and the mitochondrial NAD to NADH ratio. So this is not perfect measures because it's a urine test and the kidney can utilize lactate and kind of kind of throw off your markers.

But when you look at the pyruvate to lactate ratio, that can give you an idea of the cytosolic NAD to NADH ratio. So when glucose has been broken down into pyruvate via glycolysis in the cytosol, it consumes NAD to create NADH. Then NADH is transported into the mitochondria so it can go to the electron transfer chain to be recycled.

Right. So if it can't go into it, so there's two phases there. If it can't go into the mitochondria via the malate aspartate transporter, or it can't go to the electron transport chain to be recycled, then the cytosolic NAD will stay high. The only way for the body to recycle it then is via lactate dehydrogenase.

So it's going to recycle NADH back to NAD by converting the pyruvate into lactate. So this is where you can check your lactate, the pyruvate to lactate. If lactate is high, pyruvate is low, you likely have insufficient NAD to NADH. There's an issue there. You have to do further testing why. Then you also want to look at the acetone, at the acetone acetate. This is ketones, acetone acetate to beta hydroxybutyrate ratio.

So if the NAD to NADH ratio is high, you will have higher levels of acetones to beta-hydroxybutyrate. If beta-hydroxybutyrate is really high, you will have, in relation to the other one, you will have high levels of NADH, right? So it's a reduced state. So that could mean that the electron transfer chains are not working properly.

So like, that's kind of like the main stuff. If you want to look at the organic acid, that's how you determine the NAD to NADH ratio. But it gets much more complex than that. But that's like the simple thing that you can look at. And then, so just to answer your question, in terms of methane blue, you'd expect those ratios to improve. Yeah. So the ratio between like, so you mentioned like the ratio between pyruvate and lactate, that sort of ratio, you're saying it'd be more so skewed towards which direction? Yeah.

So you would expect your lactate to drop and you would expect your beta hydroxy, BHB to drop. And then you would also expect that the TCA metabolites working better. Right. Okay. Interesting. In terms of like complimentary, I mean, like you mentioned before about your fasting blood sugar, you mentioned the fact that some reasons behind why some people get elevated fasting blood sugar might be due to this process known as gluconeogenesis or

Are there specific is gluconeogenesis a prime target for certain, like anti diabetic compounds that specifically block gluconeogenesis? Like, did you want to sort of elaborate on that? So I'm not 100% sure maybe you know more about this, because I think you said your dad is a pharmacist or something like that. So maybe like, you're more aware of that kind of stuff. Like, I'm not too big into drugs, but

I'm more like the root cause kind of guy. It's like, okay, why is gluconeogenesis elevated? Well, it could be cortisol. It could be even something like you have leaky gut, right? So there's inflammation in the body, stimulating gluconeogenesis, the immune cells need more glucose. It could be a variety of different reasons. So that's why I said like hypothesis, hypothesis, hypothesis, test, test, test, all of these to see like where your root cause is coming from. And then I fix that with like fixing nutritional deficiencies instead of using a drug because the drug is not going to fix the deficiencies. But yes,

Drugs do target that, but there's multiple diabetic drugs and everyone target different things. Yeah, that's basically it. Yeah, yeah. I think there's definitely a lot of crossover between, like, for example, I know Metformin does inhibit gluconeogenesis. And so there's a bunch of other like, well known type two diabetic medications that are prescribed.

And then sort of look at different like botanicals, I believe like berberine might have a suppressive effect on gluconeogenesis. I would imagine that cinnamon probably has some inhibition on gluconeogenesis. But you mentioned before about sort of the cortisol awakening response, that CAR, cortisol awakening response.

Personally, I've gone through my fair share of experiments and I've also played around with compounds that lower cortisol pretty dramatically at nighttime. I think I even shared this in your forum in Testo Nation, the school tribe, that taking zinc at night before bed will make me feel really fatigued and groggy in the morning.

Now, do you want to sort of talk about this cortisol awakening response? Like, have you personally ever experimented with compounds that like drop your cortisol so far to the point where you're like, you feel like really groggy in the morning?

I have not. I think I'm more a guy that's hyper responsive to cortisol than anything else. I'm a more sympathetic driven guy where I think like you're more of a parasympathetic dominant guy, which is why you've got negative side effects from the ashwagandha. So people love to say ashwagandha is an adaptogen, but adaptogen means that if it's too high, it lowers, if it's too low, it increases. That's an adaptogen, you adapt.

But ashwagandha is not that. Ashwagandha drops your cortisol regardless if it's low as well. So what happens is that it drops your cortisol low. And when you get a stress, the body's like, I don't care. And then cortisol just stays low.

And that's why people get anadonia because the cortisol just stays low. Like there's in, in a medical setting that will test your cortisol response to ACTH. So ACTH is the precursor hormone from the pituitary stimulates the adrenals to release cortisol. So they inject that, inject the drug into you or give it orally to see how high your cortisol is going to spike the adrenal responsiveness. And what they've seen is like when you take excessive monohylogandhan, if someone's predisposed to that,

people don't get the cortisol response at all from ACTH. So it just stays like, boom. And for some people, that's great because like that makes you anadonic to stress, which is fantastic because if you're like an anxious guy, you want to be anadonic to stress, right? But if the cortisol is dropping too low, you're just going to be anadonic in general, which is not good. Well, it's just like a bomb could be exploding around the corner and you're just like, ah.

No, no problems. Like you just don't care. There's like a lot of, there's a lot of videos on like TikTok. I don't know if you've seen them, but there's like a lot of guys that go through like really hardcore breakups and then they take ashwagandha to like nullify them. Crazy. But yeah, what you're talking about there is like the hypoadrenalism. So the hypo cortisol responsiveness. Yeah, I've definitely seen that.

It's even been pretty well documented in clinical trials. There's been some case studies where patients have experienced hyperadrenalism from using ashwagandha for only three, four weeks or so. It's almost like there's some compounds found within ashwagandha that have an epigenetic, some sort of mRNA expression changes on that pathway where it's like even though...

you would think that it normalizes after stopping ashwagandha for some people it just lingers and lingers and stays for months and months and months um because you know i'm still i mean i'm still getting you would probably get messages as well from guys saying the same thing as well like they just they stopped they still don't feel the same yeah so i would say like my theory um is i would like to see more research on this but before i go there

The reason why cortisol is so important is because cortisol stimulates the conversion of norepinephrine into epinephrine. So I've seen it with people with Cushing disease, like Cushing disease. No, sorry, Addison's disease. Addison's is where you have very low levels of cortisol. These people have normal levels of norepinephrine. So dopamine converts into norepinephrine, help it focus, all of that good stuff. And then they have very low levels, like about 50% or less of epinephrine.

So you need a good balance between norepinephrine and epinephrine to have libido, penile sensitivity and erections and anxiety, for example. So in that case, you will have sexual dysfunction, low libido, poor penile sensitivity. So it's really difficult to check the ratio there because like most of the neurotransmitter tests only check the metabolite coming from norepinephrine and epinephrine. So you can't really see the difference between those two, which makes it difficult.

In terms of ways to accelerate that conversion, are there known... I'm just trying to remember. I know there's ways that we can block the conversion, but in terms of accelerating the conversion of norepinephrine into epinephrine,

Yeah. What are you sort of leveraging there? Yeah. So that enzyme is part of the methylation cycle. It uses SAMe. So using SAMe might be helpful or just stimulating it with DMG, for example, might be helpful. But ultimately, it's cortisol. That's the enzyme that stimulates it. But you can have all of the cofactors. But if you don't have the stimulant, it's probably not going to be that helpful. So using something like... Something that's going to increase your cortisol, ultimately, should have a really good effect. Something that might...

Oh, yeah, that's the other thing I wanted to mention. Like you talked about the epigenetic modifications, and it's kind of the same thing with PFS, right? People use finasteride, they get the same thing, right? The same issues. And like, why does finasteride cause that? And I think a lot of it's related to gut issues.

They don't have enough butyrate. This is typically what you see. It just messes with the bacteria that produces butyrate. And so these epigenetic modifications, together with low NAD, can cause these permanent changes. And the moment you start optimizing your gut health, get butyrate back up, get your NAD back up, these reverse changes can be reversed.

Interesting. Yeah, that's like a definite complaint is, well, not always, but I've definitely heard about guys that have used finasteride that just can, they'll describe their symptoms as like this cluster of different, like bodily changes that have that have occurred for months after even after stopping, like, so you mentioning they'll get like IBS, even just their general, like,

the way that they look, I can almost tell guys that use finasteride, they have like a less androgenic, just general, like body shape, right? Like they just don't look androgenics. Yeah, yeah, that's for sure. Like some people rebound, some people just don't. And that's one of those things. In terms of I mean, at the moment, are you still doing your DHT maxing protocols? That's pretty much finished?

No, I'm doing it basically on a monthly basis. So if people want to join, you have one week to sign up. It's going to be a deadline. I want to make sure I leave that linked in the podcast show notes for those guys. But anything else in the past, like maybe month or so that you're like heavily interested in? There might be like a particular research area or like something that's like you're really keeping your eye out for.

Yeah, I'm just becoming more and more like for a really long time, I came to the conclusion that it's basically nutritional deficiencies and oxidative stress or some kind of toxin burden that is causing all kinds of issues in the body. And most oftentimes the toxin burden is going to come from the gut.

So something is going on that's creating that toxin burden. And then you have to fix your nutritional deficiencies. And like I've seen this multiple times before, it's like you can fix all of your deficiencies. It doesn't mean you're going to be on top of the world because there's something that's still inhibiting mitochondrial function. So you can be using Methyl Blue, increasing your NAD, but you have this toxin that's like inhibiting mitochondrial function. You have to do it both ways. What's inhibiting me?

Like what's a toxin and where do I have deficiency? Like both of those. So I've just gotten deeper into the gut aspect of it and the nutritional deficiencies aspect of it. So that's like where I am at the moment, but it has to be both ways. Just can't be like single focused. Yeah, no, I love that. And in terms of like things that could like rob the body of like NAD or like act as like a toxin, you mean things like mold, parasites, like bad gut bacteria, like,

um like endotoxin that's what you're referring to yeah so anything that is going to cause oxidative stress heavy metals molds pesticides um and endotoxin which we spoke about like if if your gut is not leaky you can have issues in the gut and that's going to be fine because it's just you're just going to poop it out right but the problem comes in when someone has slow transit time

That's going to allow for pathogenic bacteria to grow, which is then over time going to inflame the intestinal wall, which is over time going to create leaky guts. Toxins are going to go into the body. And this is why it's not just like this, right? It's a slow process where people's like, I'm feeling worse and worse and worse and worse and worse over time. It just takes time. So the gut was a big one that I see. Speaking of the transit time, that's definitely a complaint that I've heard about a lot of people saying,

sort of describing post-COVID. So a lot of guys are saying they're getting, they just feel like their gut is not the same following COVID. Have you heard that as well? Yeah, like this is one of my main hypothesis. Like why do people have post-finasteride syndrome? Why do people have post-COVID, post-SRI? There's something that's happening to the gut. And because the gut is not bouncing back

It's staying in that dysfunctional state because COVID is inducing intestinal inflammation. And when you have inflammation, it allows pathogenic bacteria to grow. And now it's staying there. You fix the COVID, but the pathogenic bacteria is there. And that's why you have post-COVID syndrome or post-PFS because it hasn't gotten back to the healthy state. That's what's going on.

Yeah, recently I've been megadosing lactoferrin and I'm also going to do some blood work looking at my iron levels because I know historically I've had issues with iron. I completely fixed that and corrected that. But I'm really curious to see what impact. Like I've been taking maybe like 1,000 milligrams to like 1,500 milligrams of lactoferrin spread out across like three different dosages.

And yeah, I'm also really curious to see how that impacts. Yeah, like the ferritin, the transferrin, the iron. I've been eating my normal red meat intakes. I've just been having red meat almost like five days a week, basically. Almost probably every day, actually, which I'm sure you're probably similar. And so basically just using pretty high dosages of lactoferrin

But also the thing is I have also been using quite a lot of, I recently got a hyperbaric oxygen chamber. So I've been using that also quite a lot. So I know there's a lot of variables at play, but I think that something in my stack, whether it's the hyperbaric oxygen therapy, the huge doses of inositol, we're talking like 10 grams a day.

And then, or the lactoferrin, something has definitely elevated my baseline energy. I'm not exactly sure what it is. It could be the fact that from what I read is that like anytime we eat any food as humans, and this would explain why people that undergo extensive periods of fasting, anytime we consume any food, it does automatically increase levels of endotoxin in the gut. Like they do go up. I found that pretty interesting.

What was that? When you eat food for a prolonged period of time, your endotoxins go up. Or any time you actually eat a meal, like per se, it does appear to increase endotoxin levels.

Yeah, yeah, yeah. So that all really depends on what bacteria you have in your gut. Do you have like a gut and how effectively your body is going to clear the endotoxin? Like people would say like, do not eat saturated fat. It's going to enhance your endotoxins. Okay, but the saturated fat is just helping to clear the endotoxin from the body. It's not causing inflammation. Who the hell cares? It's not actually causing a pathological condition. Just because it's enhancing the absorption of endotoxin doesn't mean anything.

So like usually, so like back to the things, like if you're eating foods enhancing by endotoxins, like so what? Is it causing inflammation? Is it messing with your lipids? Is it messing with your cellular function? No, like, okay, who cares?

So if that process becomes inflammatory in the body, you have to ask yourself, like, why is that happening? Why do I have an excessive amount of bacteria that's producing endotoxin? Do I have leaky gut? Is my liver not clearing the endotoxin fast enough? Right? Is my bile not flowing the way it's supposed to? Like, there's so many things you can go into before, like, making a claim, like a broad claim. Anyone, I'm not talking to you, like, I'm talking about people should be making broad claims like that before, like, addressing so many things before that.

Do you feel like, I mean, I think you also had this response as well, but like with starch, you think that's a most likely culprit for something like to trigger endotoxin? Yeah. So this is the funny thing because like, I actually want to make a post about this, but I want to do a little bit of a deeper dive before I do that. So yeah,

You have monosaccharides, which is like glucose, fructose, like the individual sugars. Then you have the polysaccharides, which is like starch, like multiple molecules combined into long chains, right? So people would always say, you've got to eat fiber, you've got to feed the bacteria, but did you know pathogenic bacteria is also feeding on polysaccharides? So if you're having a negative response to eating high fiber foods, don't do it because you're feeding bad bacteria as well.

Like, this is the funny thing is people always love to say you have the beneficial bacteria is crowding out your pathological bacteria. When in fact, the beneficial bacteria can feed the bad bacteria based on the postbiotics they're making. So in reality, there's never something as a beneficial bacteria. There's just something that's less harmful and something that's more harmful.

So something can easily change. Even acromantia can become a danger in high doses where it's creating an endotoxin. It's degrading your mucus. You do not want an overgrowth of acromantia. Like anything that's good can be bad in excess as well. So like I'm just trying to emphasize like complexity. And I was actually talking to my wife about this. It's like eat a diet that makes you feel good. If you feel good on beef and fruit juice,

do that. And if you don't feel good, right? If you don't feel good on beef and beans, like don't do that. That's a reason why you're not feeling good. I think that's a really good like takeaway for people listening in is like,

Yes, we can look deep into the science, the metabolic pathways, understanding the chemistry. The reason why we do what we do is because we love to understand, right? We just love soaking up information. We love to try and make connections between different pathways. But ultimately, if somebody is listening to this and just thinking like, all right, I want to just really get on top of my own health, I think a good proxy would just be like,

Like literally what you just said, if I eat just meat and fruit, how do I feel? Do I feel like I have good energy? If not, then don't do it. And if it is good, keep doing it basically. Yeah. Like I, I, um, uh, sorry, this is the antidote. Um, I just want to throw in here before we end this, but, um, there was a guy that supposedly didn't have any gut issues or indigestion. Like this, this is really important people to understand.

just because you don't have any gut issues doesn't mean you don't have any gut issues or pathological bacterial overgrowth. So he went on elimination diet and then suddenly he started getting gut issues. So was it the diet that caused the issues or was that dormant bacteria just becoming more active that was already there? It was just like masking his issues. Like I've had this with the guy, I was going to make a joke about it. I made someone gluten intolerant. So he loved to go to the bakery

get himself a pastry every single day. He started the fat loss journey about a month later. He's like, man, I want to have a pastry. He went to the bakery, got himself a pastry, ate the pastry, felt horrible. It's like, okay, so eliminating pastries makes you feel bad. Or you were just used to feeling bad all the time, right? So your baseline was so low and that's how you felt all the time, which is why I'm such a big proponent of elevate your baseline,

Now you feel 10 out of 10. Now you know what's actually making you feel bad because if you're here, you don't really know what's making you feel bad. Yeah, no, that's a really good takeaway for people listening in about that. Elevate your baseline so that when you do get exposure to things that are somewhat toxic for you, you can really distinctively notice it.

And then you're like, why am I doing this? Like, it's completely not worth it in the end. So that's a definitely good, a good takeaway. But Hans, if my audience thanks so much for coming back on the podcast. Again, if my audience wants to connect with you, where can they do so? All right, so X as per use, I'm just checking out Hans and Marto. And if you want to join the DHC transformation, you can check out school as I mentioned, my tester tribe community. You only have like one week to join.

So you've got to make it quick if you want to join. Awesome. Awesome. I'll leave those in the podcast show notes, but otherwise, Hans, great chatting as always, man. We'll definitely be in touch. Thanks, man.

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