Unlocking Health Through Your Genetic Code: Healing from Veganism, Chronic Pain & Stressors - Chris Masterjohn : 1090

You're listening to the Human Upgrade with Dave Asprey, formerly Bulletproof Radio. You're listening to the Human Upgrade with Dave Asprey today. It's going to be a really, really cool interview because we're at somewhere around episode 1080, depending on whenever this comes out. And I asked a guy who I really should have had on before now, someone I mentioned in my last book in a Smarter, Not Harder, who was guest number 17 on the show in the very early days of podcasting. And he is a PhD nutritional science holder from back then actually in 2012, and has been an assistant professor of health and nutrition at Brooklyn College. I've always liked the way he thinks mechanistically about biology, about nutrients, about what to eat. He's a biohacker from before the word biohacking came to be, which is episode 17, when I was just getting that movement started, because he not only pays attention to how stuff works in the world and academic research and all that, but he hacks his own body, which is particularly interesting. So there are many people, for instance, Dr. Nicotine from Vanderbilt has been on the show studying nicotine as a reversal agent for Alzheimer's disease. Not smoking, but actually nicotine for 30 years and has never tried nicotine one time in his life. I'm like, how can this be? So Chris Masterjohn is the opposite of that, where he's like, well, I tried. It didn't really work. So I did all the research and I wrote a 58 page paper on it in my spare time while protesting against government intervention in our health and things like that. So, Chris, you stood up like a boss during the last three hellish years and really just put hard science out there, which I appreciate, wanted to call you out to say thanks and just welcome you back to the show.

Thank you so much, Dave. That means a lot.

I mentioned, I believe it was your reference on minerals in food in Smarter, Not Harder, because I've written a lot about the importance of minerals in food and you just put together a great resource there that had like the right information all put together. That's actually very hard to find. As a researcher, I can see why you did it because you probably couldn't find it either. So you just did the hard work so that I could then just look at it. And you saved me like 20 hours on writing that chapter, which is why I referenced you. And it was like, hey, thanks, this is a good thing. So what did you think of the Breaking Bad finale that would have happened right after our first interview?

Oh, my God. I don't remember. I honestly don't remember the. What happened in the finale. I literally watched the show from beginning to end, and I just, like. I remember, like, highlights of the characters and I.

You don't remember the last one where, like, the machine pops up and he ties up every loose end all at the last minute in one episode? I would have thought that would stick in your head.

No, no, no. TV shows and movies don't stick into my head unless I watch them, like, two or three times.

I think your academic credentials just went down, like, three points. I mean, one of the biggest compliments that I've ever received was in a heavy metal magazine that I don't normally subscribe to. And one of the. Because I'm forgetting right now, this was probably 18 years ago. One of the guys in a band was using bulletproof coffee just to have his energy when he tours. And a lot of really big bands do that just to keep their energy up so they can sing and be on stage night after night. And he said, dave Asprey is the Heisenberg of coffee. Okay? My life is done. So, anyway, I was hoping that, you know, we'd get that tied up. But enough fun. Tell me, what's different about your nutritional research versus the stuff you typically see in academia? Like, what's your perspective on it?

Well, my perspective has changed a lot over the last year, even from what it would have been the last time I was on your podcast. It's the culmination of the last five years of working with clients who have highly unusual health problems that they went everywhere to try to fix until they came to me and we started figuring stuff out, and me having to really do the research to try to figure out what was wrong with people who just had things that were going on so rare the doctors couldn't figure them out. That was not something that came easy to me five years ago. This was something where I said, geez, like, I think it's this, but I gotta go research that now and figure that out. And then also me suspecting for the last two decades that there was something different about my own health compared to other people's, because many people. I probably shared this story the last time I was on your podcast. But basically I had gone vegan, and it really wrecked my mental health. It wrecked my teeth.

You too. Isn't that so weird? When did you do that?

Probably it would have been definitely early 2000s, probably somewhere circa like, 2000 to 2002, something like that.

But the thing is, Like I also went vegan back then and it wrecked my teeth and wrecked my health. Like shocking. We were early adopters of punching ourselves in our kitchen.

Yeah, well listen though, so I know many ex vegans and I'm sure you know many ex vegans as well. I would say I'm in the upper like 0.1 percentile of the degree of harm that happened to me when I was a vegan. And the night and day like just astonishing revolution of my health when I went from vegan to Weston A. Price style, nose to tail, animal based eating. And I know many people that did that. Like I've been, I went to the Weston A. Price conference every year since 2003 and I'm constantly surrounded by people who if they experimented with veganism, did terribly on it and if they switched animal foods, did great on it. That's why they're at that conference. And I just like, I very strongly suspect there was something that was making me much worse on a vegan diet than all the other ex vegans that I knew and, and like much more able to heal myself with a simple switch of foods. And so I finally started doing research into my genetics over the last year that led me down a path of self experiments and biochemical optimization that I've started writing about. Although honestly my last big post about it was called self experiments in the Biochemically Unoptimized State, which was the six months of data that I collected before I did anything. This gets to the heart of what you were saying about the nicotine guy, right? Because I thought there was something wrong with me and I deliberately just studied myself for six months so that I would be able to exactly describe what I was fixing on the back end of that. And I now I have, I'm nearing, I'm like basically transitioning into phase two of, phase three of that right now. And I have so much data that I'm going to be writing out about over the next few months. But I, the things that I've done for myself over the last year are incredible. So for example, I identified a rare gene that is 0.08% frequency. And even though I'm only heterozygous for this gene, the severity and the rarity are such that I knew that biochemically optimizing around that one thing would probably do wonders for me. And I could give you a whole list of things that happened, but I completely abolished my seasonal allergies within two days of starting riboflavin supplementation because of that genetic. And now with clients and myself. And then the research, there's now data that are coming out that are showing that what I'm saying about rare stuff is actually common, not that rare. Right, exactly. So here's the conundrum. Things that are rare, that are genuinely rare, are collectively common. Okay, so there was a recent paper that came out from the million exomes study where they looked at whole exome sequencing, which is basically the second best type of genetic sequencing. So what most people are getting like 23andMe and ancestry is SNP chips. The big problem with SNP chips is they're great for common polymorphisms, but they're horrible for rare things. And the methodology, if you want me to, we can get into the details, but I don't think we need to. The methodology is such that if the thing is rare, it's more inaccurate than it is accurate. So it's basically worthless for anything that's found in fewer than one in a thousand people. And then there's whole exome sequencing, which is much better quality for rare things, but only looks at 2% of the genome. And there's whole genome sequencing, which is 90% of the genome. So none of these are whole anything. But it's almost whole genome sequencing. And what I found is that you have to go to the whole genome sequencing to find the rare things. But it's not rare to need to do that. Everyone is carrying two or three extremely rare things. It's just that there are so many rare things that you can spread it around for everyone. So I really think that everyone has something like me where going in and finding that number one thing or number two thing is after you get to the low hanging fruit that, you know, everyone should do, that's their next unlock to get to the next step. And I think that's where I'm going differently than pretty much anyone and also way differently than where I was like a year and a half ago.

This is where biohacking gets really interesting because there are like algorithms and things that work for most people, right? And for instance, I'm just gonna plug something I created, bulletproof coffee. Like there's a large number of people who drank that and weren't hungry and lost weight, like millions of pounds of weight collectively across the country. And I've, you know, six different reasons I think it might have worked. But there are also some number of people where just didn't do anything. And like, what the heck is going on? And where I am now is I like to look at genetics, I like to look at genetic expression through rna, like the stuff that VIOME is doing and look at every other data point that I can get, which is stuff we're getting from upgrade labs and put it all together into an AI learning model and, and say given what we know and what you want for you as allergies. But someone else might say, I don't care about my allergies, I just want abs. Right. Just different goals. So then we have to map out the best path to get there. And I think you're doing some of the more, the more cutting edge thinking about how to do that because you had to deal with it. In my case, I think I have more than a few of those weird things. There's something called like RCCX phenotype, like I have low cortisol that I've had for my whole life, which is just weird. And even diagnosing that requires very weird genetic stuff that I haven't done. I just have all the symptoms and when I do the things that work for that, it works for me. So there you go, you can figure out stuff like that. So people are getting better at and better at using ChatGPT to bypass what you do. There was just an article today that came out where a mom who'd taken her son to see 17 specialists like doesn't work, goes into chat GPT, asks around, puts in some MRI data and comes back with a tethered cord syndrome and then gets it treated. So we're already getting to that point, but we're 5% of where we can go. And your way of thinking is unique from what I've seen. Thank you.

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I guess another thing that I would add that I think is important perspective is there are a lot of things that you can look at. And so if you ask people what they want, you're going to get questions that are at surface level, explanations. I think a good analogy for this is the operating system versus the apps, right? Like if you're using your phone or you're using your computer and you're noticing a problem, you are not thinking about what's really genuinely under the hood. Three levels beneath what you're looking at. You're thinking about like, why does PowerPoint shut down every time I open it up? Or like, why is Google Maps lagging? And it thinks that I'm back there when I'm up here. And yes, you can always have problems that are in the software apps, but the reality is that because so many of us have at least a couple problems in our operating system, it's all the apps that are dysfunctioning. So we might notice our skin does not look shiny and smooth like we want it to wear, or we might have an autoimmune condition, or we might be waking up in the middle of the night, or we might be fatigued during the day or crashing after Lunch and you can go on and on down the list. These are all app level things. And the real operating system in my view is the system of energy metabolism. Because if your cells cannot produce energy, they don't have the. You're laughing because you see it the same way.

Well, I'm just. Yeah, I mean, most of my work has been around mitochondria as being at the root of things which are energy metabolism. Like, you fix mitochondria, autoimmunity goes away. Fix mitochondria and almost every bad thing stops happening.

I completely agree with that.

Yeah, yeah, but you're. I think that the mitochondrial centric viewpoint that you already had a little bit when we talked 10 years ago, you've become far more into that. And certainly I think I, I developed my mitochondrial fetish in about 1996 when I had chronic fatigue syndrome. And I'm like, my energy is so dead. Like I feel really bad. I just need to have my energy back. And so I said, where do you get energy? And I started hacking on that. And what I didn't understand was how interconnected it was with all the other stuff that we think is much higher up. So if your PowerPoint isn't opening, most people aren't going to look at the power supply to their computer to make sure it's delivering consistent voltage. But that might be the problem. And I think it is in our bodies most of the time.

Right, yeah, yeah, no, I agree. So I think what you need to do is you need to systematically analyze what is the. Basically a three pronged approach. So you're looking at what are the biggest things. And one of the problems with the gene sequencing, why you have to go to whole genome, is by definition the severity correlates with the rarity. Right. So you can have, you can identify 500,000 polymorphisms that are common. But if they're all, take something like mthfr where only 13% of people in the population do not have any of the common MTHFR SNPs. If 83% of people have one of these SNPs, the severity can't be that bad. Whereas if you have something that's one in a thousand or one in one thousand, it's much more likely to be big potatoes rather than small potatoes. So you want to look for the severity and rarity and then the next step would be how root cause is it. So you don't want to be ideological about this. You know, mitochondria is root cause and cytosol is not root Cause. But you want to know the biochemical mechanisms so that you can say, well, if I found these five things, I know that this one is the one that fuels the other four. Therefore, I'm going to go there first. And then you filter it by how actionable is it? Right. So there are some defects where it's just. That thing's not going to work. And you can try to get around it, but you can't fix it. But if you can find something where. So, for example, the gene that I was talking about is a combined respiratory chain disorder and fatty acid oxidation disorder, where in the most severe form, almost all the babies with it die. But if they just give them riboflavin, 90% of them live.

Right.

Now, obviously, I didn't die as a baby, so my severity is nothing like that. But if riboflavin can fix it that easily, then it's probably gonna do something for me.

And it's funny, because a bunch of listeners just ran out and ordered riboflavin, which is a cheap.

No, they didn't get it. Let's fix this right now.

Well, I'm. So they probably just did. But here's the thing. It probably won't do that for you because it's relatively common in foods. And unless you have a specific deficiency. When I started.

Wait, hold on a second. Not just the deficiency, but you can have a mutation that decreases the affinity of an enzyme for riboflavin such that it only works correctly when you supersaturate the system.

Right.

So for me, I don't have a deficiency. I just have two of these enzymes, one from my mother and one from my father. One of them works normal at 3.6 milligrams of riboflavin a day. And the other one does, like, does not do jack unless there's 75 milligrams of riboflavin.

Wow. Yeah. So you figured this out because you have a PhD and because you're curious if a listener was dealing with something like that, what do they do?

Right now I think that what I'm doing is something that requires deep analysis on my part. So I'm actually starting a new program based around the work that I've been doing in the last year. And it's going to be launched@biopt health.com so I will, in the short term, I will be accepting people who want to go through that process with me. But obviously this also needs to scale in a way where we can take what I'm doing and automate it in, I think the way that you were just talking about.

Yeah.

And I think that there's a desperate need because I think this is something that affects approximately 8.1 billion people. And so scaling it is important.

Well, I guess on the positive side it's 8.1 billion people and falling. Right. We want to say, we want to say why, but you.

I have, I'm more optimistic about the scaling part.

Now we can scale it up. I'm just saying that the scope of the scale might not be as high because of some massive declines in, for instance, the expected lifespan of people in.

The U.S. well, no, I mean, I'm optimistic about the pace of the scaling which will reverse the anti fertility trend. As long as people stop listening to the public health authorities.

Ah. That's the thing. When I wrote my fertility book before our first interview, after I did that, people would say, what about if you make people live longer, the world will have too many people. I said, no, it won't. You just have to wait. Because fertility trends are so disturbing and now it's 12 years later and testosterone levels are half where they were before. So, yeah, we've got to stop listening to the public health authorities. You shouldn't rely on the government for your health. That's not their job. And magically when you do that, we'll probably fix it, but you can scale your knowledge in a new way, which is really cool. Yeah. Now there's a couple points I want to go deep with you on. Yeah. And before we get to those, it, there's another common area that I want to explore with you. So I, I did fix my mitochondria. I fixed tons of problems with my biology. I recovered from the damage that I did to myself with a vegan and then a raw vegan diet, at least mostly recover. There's a couple things I'm working on, one of which you had a little data point that was helpful. But the other thing that happens though, when your body runs on such low energy for so long, small stressors feel like big stressors and end up creating behavior patterns and even trauma patterns. And people like me have been exposed to toxic mold repeatedly. Until you do the work on rewiring your stress response and your psychology, you'll walk into moldy hotel room and you will feel like you're going to die. Like a full on panic attack. Right. And it's also possible to walk into that same room to acknowledge that it's not a very healthy space and walk out without a panic attack. Right. So there's some degree of Psychological rewiring, that happens. And I think you need to have enough mitochondrial energy to be able to psychologically rewire. At least that's my experience at my neuroscience clinic. What is your practice for rewiring your own psychology? What do you do?

That's fascinating that you brought that up, because that goes very well with my own experience in ways that I haven't written about anywhere yet. So my basic perspective on the psychology is that psychology is not all biochemical. There are absolutely elements where the way you think is important, the way you train yourself to respond is important, but the biochemical milieu, which, you know, you could look at it at a neurotransmitter level, but I think the energy metabolism level is where the real gold mine is. Just because your body's ability to regulate your own neurotransmitters is so energy dependent, I think that biochemical milieu is basically making it, whether it's an uphill battle or a downhill battle, for you to do the cognitive work. What I found really fascinating, like some of my, what I'm going to be writing about, my experience with riboflavin has almost like a mystical bent to it because a lot of it reminds me of. I don't do psychedelics, but a lot of it reminds me of what people say the benefits of doing ayahuasca was only, yeah, I didn't have any trips. And, like, what basically what happened was as I started the riboflavin supplementation, it feels like all the cognitive work that I had done in the past all started bearing fruit almost immediately, as if my brain had done so much work to get to the destination that as, like, as soon as there was enough energy, it could just go in and fix it. So one really interesting example where the work that I did was very systematic and the benefit was very immediate after post riboflavin is that I'm very scared of heights and I love snowboarding. And so every time that I. In my life where I've gone like five or six years without snowboarding, I get very afraid of the chairlift to the point where the last time this had happened was maybe five years ago. I hadn't gone for five years, and then I just stood at the base of the chairlift for 45 minutes before I talked myself into getting onto it. And so I listened to a bunch of podcasts on cognitive behavioral therapy and hierarchical exposure. And so. And then I also, I had a study on the dose of GABA that could reduce the stress response while people who were afraid of Heights were walking over suspension bridges. And what they showed was that with, I think it was 800 milligrams of GABA, they would not get the salivary IgA suppression, which was basically like a stress response. Raises the cortisol, suppresses the immune system, and you can measure that by the antibodies dropping in the saliva. So what they showed was 800 milligrams would abolish that response. So what I did was I found the shortest chairlift that I could go on, which was a two minute chairlift. And I used that as my playground for hierarchical exposure therapy. For example. Like, this went from being like right next to someone to make me feel better and holding on and not looking down to riding it by myself with no hands, like staring down at the ground. And the way I used GABA to bridge the gap. So it was, if I was real afraid of it, I would suck on a GABA gummy. And the GABA gummy would. The reason I sucked on a gummy is that it also had the benefit of the association with the flavor feeling in the mouth. So it could produce like an immediate psychological placebo effect that I could leverage. And then as I got to be able to do something, I would take the GABA out to and then just like slowly remove all those crutches. And so I did a lot of that work. But I'm telling you, before I started riboflavin this past season, I started snowboarding at the mall in the American Dream mall in Jersey. It was like 45 minutes from where I was living in New York City. And so go there and they have this chairlift and I was, I was riding it by myself and practicing not putting the bar down until I went over the last jump in the terrain park. But I would always get kind of anxious and I'd like look back at the bar to make sure it was still there. I didn't go for a few weeks. When I started taking riboflavin, I went back there and I was riding with other people and I'm like, well, I'll let them put the bar down. And people weren't putting the bar down. And then I was like, maybe I could do this. Oh, no. What happened first was I'm riding on the chairlift and I'm just thinking about stuff and I. I forget to look where I am. And I looked down and I realized that the jump that I usually aim to put the bar down at had disappeared a long time ago. And I'm like, wait a second, where did my anxiety go? And So I put the bar down and then I just started like just never put the bar down. And I don't recommend this for safety reasons, but to me it was like I immediately was riding it without the bar down. I was like, how, how did, where did. What happened? And it's not that riboflavin just abolishes fears. It's that I did so much cognitive behavioral therapy that was saved up in my brain that that my brain did not have the energy to realize the fruits of and then once I fixed the energy problem, boom. All that work paid off.

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You nailed it with fixing the energy problem. When the brain's at low energy, small stressors look like big stressors, small challenges look like Everest. And it feels kind of truthfully like you can't do it right. So then it doesn't take much to put you into the anxiety state. And when you do the things that increase the amount of energy in your brain, it could be having some exogenous ketones, whether they're MCTs or salts or esters or any of the different ways. It could be acetyl l carnitine, like any of these energizers. If you do that and then you do exposure therapy, your capacity to experience something and then feel safety afterwards gets better. And right now, I believe the reason that most of the US in particular and Canada were so programmable over the last three years is because our nutritional status is so bad. It doesn't take very much to turn off our brains and, and put us into a reactive mode. And as you fix mitochondrial respiration and energy production, then all of a sudden things that are dumb, you can see that they're dumb, and you just actually have more power. You know, who knows what you might do? Kind of a state. And for you, it was riboflavin. For most people, it's something. And there's some general principles that raise the energy status of enough people that then you can do. I was running at this baseline. A stressor happened, and then I returned to baseline. And that's what drives adaptation. It makes the body improve. In the case of things like cardio or weights, it's the rate at which you exhaust a resource and then the rate at which you return to baseline. As long as those two curves are very steep, then you adapt very quickly. But if it's a steep curve up and then you stay in a stress state because you don't have the ability to return because you energetically can't do it, then you don't get any progression from exposure therapy. So what I found, I started in my mid-20s, when I started becoming aware of my brain state and my energetic state and started to do what's now biohacking to improve them. I systematically set out to do every single thing on earth that scares me because I'm like, I don't like this. I also was afraid of heights. So once my brain was working well enough, I could stand at the edge of a cliff and look down. I have no fear of heights anymore, but if I was nutritionally challenged, I wouldn't have been able to adapt that way. And when people come and do this kind of work at 40 years end with neuroscience and EEG feedback, they intentionally induce a feeling of something that was a trauma, and then they go into a certain state that you can learn that cancels, cancels out a trauma. But I have to feed them a very certain way and give them a handful of supplements. Otherwise they can't do the work for the amount of time I need them to do it in, over five days. So in the world of psychology, I've asked a few different psychiatrists and psychologists over the years, what percentage of anxiety is driven by physiology versus psychology. Right. And our conversation is making it pretty clear to me that maybe it's not like a either or. It's because the psychology stuff starts to go away when you fix energy. But what would your answer to that be like, is half of trauma because you can't make enough energy and you're tired and it's in the tissues and half is in your brain?

Or I don't think you can put a number on it, because for one person it's going to be 70, 30, for another person it's going to be 30, 70, and for another person it's going to Be 50, 50. My default would just be to say, like, look, everyone has psychological trauma of some sort and everyone has an energy metabolism problem of some sort, and hardly anyone's eating perfect nutrition. I think a large part of it is, how much work have you done in one area versus the other? Because by the time someone's listening to a podcast like this, they've probably done a lot of at least one type of work. And so the question is, like, how far have they moved along? Right? So if someone's optimized their nutrition 98%, they're probably not going to get any psychological benefit from optimizing the next 1 or 2%. But if they've done no psychological work, they're probably going to get all the benefit from doing the psychological work. I guess I would just by default say it's probably 50, 50, but at the population level. But when you're talking about individuals, it all depends on the context of where they come from.

Highly variable on an individual basis, for sure. I am certain now, having had about 1500 people come through 40 years since then, we have quantitative measurements of brain voltage and qeegs and things like that, that there's a correlation between ability to improve your brain and to let go of traumatic patterns and respiration of themselves. Like, I know that because I've just seen it so much over the last eight years and in my own life, six months of electrodes. There's times I want to do the work and my biology isn't where it should be and I'm just too tired. You just can't bring it. It doesn't matter if you want to improve. Like, the bar is going to keep calling out to you on the chairlift. It's not a willpower thing, it's not a moral thing. It's an energy thing. Thanks for sharing your perspective on that because for people who are working on personal development things right now, this reminded me of rejection therapy. I think it was it UJ Ram Dass. I'm pretty sure that's who it was. Who came on, on the show a while ago and upgrade collect. If you guys remember, tell me this is a guy who was so terrified of being told no. This is a very common fear. That's where approach anxiety happens for guys or for women who just, you know, won't, won't walk up and tell someone, hey, you're attractive, you want to go out because like, oh no, they might say no and then no one will love me and it's the end of the world and all this nonsense that our, our meat operating system feeds us. Well, he decided he was just going to ask for ridiculous things every day until he got a no and wrote a book about it. And I interviewed him about it and just ridiculous. Go to the donut store and ask for Olympic ring donuts. And they're like, okay, damn it. I was trying to get a no to the point that after 30 days he was much less afraid of rejection and trying to do that. If you've just breathed toxic mold and you've taken something that reduces your mitochondrial respiration and you're mineral deficient, you probably won't work. You'll just feel like shit at the end of 30 days. So there's something for everyone listening right now. If you're going to do the personal development difficult work that is necessary to evolve as a human, you must pay attention to your nutritional status and your ability to make energy. And maybe you have a big problem there. Maybe you have a little problem, but you almost certainly have a problem. And it's probably bigger than you think. Would you agree?

Yeah, I would definitely agree with that.

This is fun to be able to chat with you about it because you have this cool way of thinking about it. All right. There's two things you've written about lately that made me happy. Actually. One of them made me scratch my head. But the first one, you and I were both vegans. And were you a raw vegan or just a regular vegan?

I was actually a soy zone vegan. So the Barry Sears wrote a book called the Zone Diet, and then he came out with a book called the Soy Zone.

Yeah, I remember I had been a.

Fan of the Zone Diet before I went vegan. And so then when I found that he had the soy Zone, I think that probably net hurt me a bit that I was trying to do the 40, 30, 30 with more soy protein. I was using soy protein to make muffins and stuff the flour. So protein, flour.

I did it too back then.

So definitely, like, if I were to do veganism again, I would do it better than I did it then in a lot of ways. But I would not do veganism again because it's not just that I did a bad job of it, it's also that it's just not very nutritionally robust.

But, well, even when you do a good job, it's a bad job nutritionally.

Yeah, exactly.

That's what I found. I was running an anti aging nonprofit education research group, interviewing top experts in that setting, and had every possible type of vegan food and blending tool and ratios and tables and sprouters and dude, even if you do it well, it's still not very good. So one of the things I learned was that there's these multiple plant toxins and they're actually in chapter one of the Bulletproof Diet, which I think for a 2012 book was pretty groundbreaking. So I'm like, well, there's lectins, there's phytic acid, there's oxalate, there's histamine, there's mycotoxins and omega sixes. These are the problems we're dealing with in our food. Not all of those are from plants. Histamine is actually more from animals, but also from soy and high protein plants. And I said, it's probably one of these or two of these that are slowing you down, so you should be aware of them. And I went pretty heavy on lectins and very much on Omega 6, but I didn't pay as much attention to oxalates or phytates. And for listeners, if you haven't read my most recent book or any of Chris's work, phytates Stop you from absorbing minerals or bind to minerals, so you can't do that. And oxalates, which is what I want to ask you about. Oxalates are those things in spinach and in kale. And there's some debate about kale, but I've gone really deep on that. And yes, there's 33 milligrams of oxalate in Lacy kale. Same thing I said on the Joe Rogan show seven years before he quit drinking kale smoothies because of oxalates. So. And spinach is worse than kale. And raspberries are a problem. Sweet potatoes are a problem. Yeah. And I. I recommended sweet potatoes in the bulletproof diet because they don't have lectins anyway, and they have about the same amount of oxalate as white potatoes.

Real quick. I once ate one to two sweet potatoes a day for a week, and I had a limp by the end of the week, and it went away within three days when I got rid.

Of the sweet potatoes. There you go. And I still love sweet potatoes. I just don't eat very much of them because I realized through my time as a raw vegan and even some of the paleo kind of stuff, I was eating an insane amount of oxalate. And it builds up in your muscles, it builds up in your joints, it gives you 70% of kidney stones, and there's links to autism. And I had Asperger's syndrome as a kid. I would eat a lot of raw spinach salads when I was trying to lose weight. In my early 20s, I used to have to go to the dentist three times a year to just scrape tartar off my teeth. It was all oxalate tartar. So I'm to the point now where in my most recent book, I went deeper on it. And I know that I have excess oxalate in my tissues because if I eat high oxalate foods, the place where I had a surgery on my foot hurts, my knee hurts, and, like, my neck gets sore. And if I don't do that, I can feel a difference in my. The way my teeth feel. And my body's really just. It feels great. So many people who have chronic pain, I believe, have oxalate overload because we're eating almonds and things like that all the time. You're the first person to talk about how to possibly reverse oxalates. There are people who say citric acid, things like lemon juice, which I think does help, can help to dissolve it. But you proposed using biotin and some other Nutritional approaches to remove oxalate from the body. Can you tell me what you know about oxalate toxicity and what to do about it?

Yeah, so if we get into the chemistry, which is kind of how, where you have to get into in order to make sense of what I was writing. So oxalate is just two carbon dioxide molecules joined together. And when we metabolize stuff, the main thing we're doing is breaking them apart and releasing them as carbon dioxide. So just looking at this molecule, you're like, wait a second, we can have all these complex amino acids and really long fatty acids and all kinds of stuff that gets broken down to CO2. And we can have like 7 or 8, 9, 12 enzymes in a pathway just to take this funny looking thing and turn it into CO2. But we can't take two CO2 and split it apart. You gotta be kidding me. This looks so easy. This is the sense that I get just looking at the molecule, right? And so if you look at how bacteria break apart oxalate, generally what they do is they release one CO2 and then what's left has some extra electrons stuck to it. So it's actually formate or formic acid rather than CO2, and that has to get oxidized to CO2. And then now you've broken it down into the two CO2. And so I know for a fact that it's textbook that humans can turn formate into CO2. So we definitely have the second step that would be required to mimic the oxalate detoxification that bacteria do. And what I proposed that is unique is that everyone, not everyone, but everyone who knows about the metabolic poison aspect of oxalate, which is, you know, believe it or not, almost never talked about except by Susan Owens and Sally Norton and those folks. But like, mainstream medicine is just like, it's kidney stones and that's it.

Which is crazy, by the way, if you go to mainstream medicine before 1920, they knew all about oxalic acid and poisoning from it. Then they just stopped in the 20s.

Right back then they might have known at a very high level about its poisonous role. But like, biochemistry wasn't the basic textbook. Biochem wasn't really worked out until the mid 20th century. And there are papers after that in the 70s and 80s showing that because oxalate inhibits the pyruvate carboxylase enzyme, which feeds the citric acid cycle, the high level of the normal range of oxalate in human plasma decreases citric acid cycle activity by 48%. And that's considered normal by medicine. And so everyone who knows about that says that oxalate inhibits that enzyme. But I went into the enzyma logical literature, and I'm looking at, they've shown in crystal structure, oxalate binds over here, it has the properties that would make it do this, et cetera, et cetera.

It.

Everything lines up to make it look like the reason it inhibits pyruvate carboxylase is because pyruvate carboxylase converts it to formate. So if I'm correct that that is true, it's competing with normal metabolism to get metabolized to formate, in which case our methylation system then takes over to allow us to oxidize the formate and Release that as CO2, which means that we can metabolize oxalate to 2 CO2. Now, one of the problems with oxalate absorption and distribution studies is the same problem that applies to every other nutritional study of absorption, which is that no one who's studying live humans wants to look at their feces. And so we have all these nutrition studies looking at absorption from plasma response, often just from plasma response, which is insane. Like, that tells you what went into plasma at what time. It doesn't tell you what got absorbed, or sometimes with plasma and urine. But absorption studies almost never measure feces, even though by definition, literally, literally, not literally, figuratively, but literally, literally, by the definition, absorption is what did not go into the feces.

No, that's not true. You can also breathe it out.

No, that's.

That.

That's not true. If you breathe it out, that means you absorbed it.

Well, couldn't you have absorbed it and then re. Added it? Your feces as well? It seems like they're kind of. They're both excrement pathways.

Okay. Absorb means to go from the intestinal lumen into the enterocyte and then usually to be transferred into the circulation. Right.

So if you talk about, say, zinc, if you find zinc in the poop, it could have been absorbed. Zinc that was then re. Excreted in poop is what I'm saying.

Oh, no, I agree with that. I thought you were saying. Maybe I misunderstood you. I thought you were saying you could if you had exhaled it. I'm saying if, like, if you exhaled it.

Fair point. You absorbed it before you exhaled it. And in poop, some of what's in poop was absorbed and then. And then let go again.

Yeah. Well, with zinc, it helps that we understand the physiology a little bit better than oxalate so, like, we know that there's an enterohepatic circulation of zinc. So my. If you. If you never measured feces, you really have no idea if what you saw in the blood was the extent of the absorption.

That's my point.

So. So in other words, if I'm right, that oxalate is routinely converted to CO2. That means if. If the. If you study something and say, like, normally 10% is absorbed because of the plasma and urine response, it could easily be the case that 90% is absorbed and 80% is converted to CO2. If you never fed labeled oxalate to look for the label in the breath, CO2, and if you never looked at the fecal, it could be yes, 10% or it could be no, 90%.

You have this question that runs through all of your thinking, which is, what's really going on in there, which is so foundational. And my question is, if I do this, will I get this result? Because I want the result. And I'm really hopeful that someone like you is like, walking right next to me going, I wonder why that is, and that you're going to do another layer of digging. I wanted to feel better now and. And I want the mechanism, but I'm okay to have the mechanism next year. And you're simultaneously curious about both, which is unusual and cool.

What, what's your. Do you know your MBTI type?

Do what?

Do you know your MBTI type? Like the 16 personality stuff and the MBTI is the way.

Oh, yeah, the Myers Briggs. I got you. Yeah.

You're an extroverted thinker, and I'm an introverted thinker.

I'm ENTP and ENFP right on the border.

Yeah, interesting. So, yeah. Well, anyway, I think as I grow, I try to do more of what you do and think about the effects that things will have. But I'm always better off building the model and then learning from the people who study the effects on. How can I make the theoretical model more useful to people who are focusing on that?

You're very good at model building just in your writing and the things. I mean, I've looked at your stuff on and off over the last 10 years, and you really have a unique perspective and you communicate it well, which is why I'm like, hey, we got to talk about. So back to oxalate. My supposition is that anyone who has been living off nuts and seeds instead of gluten, or anyone who's been living off grains which are also full of oxalate or buckwheat or like me as a raw vegan, raspberries are quite high in oxalate. And I used to eat two boxes of raspberries a day when they were in season at the farmer's market. And I was in California, so it was like a lot of the year. And I had just terrible, terrible urinary problems. I'd have to pee 25 times a day. I went to the urologist, they put a camera where no camera should ever go, and we don't know. But I finally figured out the correlation with raspberries and I quit eating them. But I didn't also know, oh, here's the other things that I'm doing that also have oxalate, because I figured it was a lagic acid, which is in raspberries. And they are irritating because of that as well as. So it turns out tons of people listening to the show who eat raspberries instead of blueberries and have to pee all the time, especially women with interstitial cystitis. Dude, step away from the spinach, kale, raspberries, almonds, maybe sweet potatoes, certainly beets and a few other types of foods in there. And all of a sudden like, oh, I don't have to pee anymore, but it gets stuck in there. And then you have this problem. And if you eat one bite of something with oxalate, then, oh, look, my neck hurts the next morning. So how do we guide people using Most Likely to Work? Given that there probably aren't enough studies, given what, you know, how much biotin do you take? How much citric acid do you take? Do you stand on one leg? Like, what's the best practice?

So, yeah, I mean, I only have anecdotes of people that have responded in the comments to the articles that I've written to go on. And if I were to. And there's not a lot of anecdotes, right? Because it's like many people find this interesting, but very few people have a specific story to share about it. So when I wrote the article, the reason that I wrote it was in response to several comments on other stuff that I was writing about biotin, where people were getting oxalate dumping symptoms from biotin in milligram doses. In one case, it was someone who was getting it from five milligrams, or maybe it was two and a half, I forget. But in another case, it was someone whose kids did great on 5 milligrams but got Oxaly dumping symptoms on 10 milligrams. And if you look at Sally Norton's book Toxic Superfoods, she has a table of all the dumping symptoms as well as a table on all the different things that can help with dumping symptoms. And both. And Norton follows Susan Owens in arguing that biotin can help with dumping symptoms because the oxalate will inhibit the biotin dependent enzymes. Like I was just talking about pyruvate carboxylase, that's a biotin dependent enzyme. And so their perspective is that if you have dumping symptoms, you are poisoning your pyruvate carboxylase and that is a biotin dependent enzyme. So if you compensate for that with the biotin, you can help normalize your metabolism. But that does not explain why high dose biotin would elicit dumping symptoms in some people because they're like Owens and Norton are talking about why it would help. But I'm getting comments from people that are saying I got the dumping symptoms from, from too high of a milligram dose of biotin. And so I think that what I'm saying can explain those milligram doses causing dumping symptoms. Because what would happen is you would clear the oxalate, it would go down, you'd stimulate more, release, it would recirculate, and then you get the symptoms. In response to that, I found someone who had longstanding, very highly sensitive to oxalate with joint pain and things like that on a low oxalate diet for like seven, 10 years, something like that, did not have zero symptoms. He was still at a point where he had symptoms. And he was also very sensitive to slight fluctuations in his oxalate intake. And he added biotin at somewhere around 150microgram dose over and above his existing diet. So maybe bringing his total up to say 300 micrograms a day, which is a small dose. Well, it depends. Like it's very small compared to most of the supplements that are out there. But it's very large compared to food.

Right, okay.

Which is, this is the way it is for many supplements, like the riboflavin. For me, for example, like I'm taking 75mg very low compared to the average supplement, very high compared to like you could not obtain that from food. I mean, my perspective is like a lot of these supplement doses have no rational basis whatsoever and are just pulled out of like either really poor interpretation of studies or are just totally random. And and so, you know, as a result of that, you can have everyone missing the fact that maybe the ideal dose to help with existing oxalate symptoms is actually somewhere around 150 micrograms which is, if your diet wasn't irrelevant in the first place, then why not? Why would doubling the biotin in your diet not be irrelevant?

Right.

Like if the a hundred micrograms you can get when you eat a high biotin diet is doing something, then for sure an extra 100 micrograms is capable of doing something. And so to answer your question, I have three stories to base this on. And if you just try to pretend it's all reconcilable, I would say you get into trouble in the high milligram dose and you get help in the sub milligram dose. But honestly, I doubt that's like, true in a general case because even if you go to Norton and Owens, they're talking about milligram doses helping people with dumping symptoms. So I think it's one of those things where I believe that 1 in 30 people approximately have a requirement for milligram doses of biotin and everyone else needs microgram doses of biotin.

That that makes sense. And, and for our listeners, dumping symptoms means that when you eat a food that's high in oxalic acid and it forms these razor sharp crystals that can cause gout in the kidney stones or vulvodynia or urinary problems, or all sorts of weird things like rashes or. What I used to get a lot of was these subcutaneous pimples, like boils that take like a long time to come to the surface. That can come from these things forming just very, very low in layers of your skin. So there's also like flushing and there's a whole bunch of symptoms that could be caused by oxalate. But if you're not eating oxalate at all and your body starts trying to let go of oxalate, well, it can basically let go of some that then recrystallizes and causes symptoms again. And that's called dumping. And what I found was I actually was taking a lot of biotin, like 20, 30 milligrams of biotin, because I had 10,000 individual hair follicles a few years ago, moved around on my head because I'm going to lift 180, I want to have my hair. And I said, all right, I'll do some more biotin there. And I did for the first couple months get those sort of deep skin things, and then they stopped. And I feel like I do really well on that kind of a dose. But I played around with more or less or not taking any. And the moral of the story here is the inverted u Shaped response curve is common in drugs and in vitamins and in nutrients. And for listeners, what that means is if you're too low, you don't get very many results. You get into the Goldilocks zone at the top of the inverted U and like, it's perfect. But if you take more because more is better, then you actually don't get the results. And we see that in a lot of these things. So I don't know how to exactly tell you when you're listening, hey, this is the right amount of biotin to take. But if you've been vegan or you've been eating a ton of nuts and seeds and kale and all that kind of stuff, especially green smoothies, the beginning lethal dose of oxalate is about five grams a day. And you can get one to maybe one and a half grams in a really big spinach kale smoothie. And there are at least a few cases of people who've gone on green smoothie cleanses that are all spinach and kale ending up in the hospital or even dying after a week or two doing that, because this is a thing that is toxic to our kidneys especially. So if you're recovering from being a vegan, like, was it Liam Hemsworth who's got kidney stones after four years of being a vegan, like, oh, gee, calcium oxalate, there's. What do you want to do? Well, it feels like some amount of biotin, to your point. Maybe start with micrograms and move up if you need to. And there's a pretty clear case for lemon juice, like the lemon juice and salt water in the morning, citric acid helping certainly with symptoms. So I do about a half a cup of lemon juice a day in smoothies or just in water and things like that. And I am actively working on lowering the amount of oxalate in my system so that I can eat sweet potato fries when I want to. Any other advice for me?

Well, I think part of the. The sort of like the biotin is like the first step in oxalate detoxification. And then you get into the methylation stuff where in order to use like when. If you convert oxalate to formate and CO2, half that CO2, you just breathe out the formate has to get metabolized. If it doesn't, you're going to wind up with methanol poisoning symptoms which are driven by formic acidic.

Do you need TMG for that? Or some sort of glycine donor.

So, like the biggest thing that you need is a very well recycled folate cycle. So what you want to happen to the formate is that there's actually several fates of the formate, but one of the bottlenecks will be can you use that formate to become the. To donate the carbon of what becomes methylfolate. And so one of the problems that you could have is a B12 deficiency where your methylfolate does not pest the methyl group to the B12 because it's not there. And then the methylfolate accumulates and then you have no more unmethylated folate to move that carbon from the formate. So you can have folate getting stuck in somewhere in that folate cycle because there's a missing other nutrient and that's you're really looking at. Most of the B vitamins play some role in making that happen. And then the other enzymes that act on that are the aldehyde dehydrogenase enzymes. And zinc can be helpful there.

It starts to get complex, which is why when people attend your master classes or read your stuff, well, you might have to do this, you might have to do that. What I've found with a lot of these things, there's an 8020 principle. So it sounds like here then, if you wanted to try what's most likely to work but may not work for you, you make sure you have some methyl B12 or hydroxy B12 plus some methylfolate, plus some biotin.

I mean, I mean if you want a generally applicable principle, it would probably be just be like do a screening for B vitamin deficiencies. I really don't think the generally applicable principle can be broke, burnt like, broken down into like, by like the base cases. Take 20 milligrams of biotin a day. I actually think there are more people who will be harmed by 20 milligrams of biotin than there are who will be helped, even though there are definitely people who will be helped by it. And I'll even say that I had wrongly identified myself as someone who would benefit from milligram doses of biotin at the beginning of this year. And I actually developed pretty significant neurological problems from taking 10 milligrams of biotin a day by the end of five weeks. So I'm quite sensitive to the possibility of people kind of playing with fire when they're just taking what is definitely like. It's definitely an edge case to need 20 or 30 milligrams of biotin a day. I can almost guarantee you that. And maybe you already know this, but I can almost guarantee you that you have genetic mutations that are, you know, one in 200, one in 30, one in a thousand or whatever that where like the high dose of biotin is normalizing an enzyme that in other people does not need that dose. And so what you're talking about is very much a 1 in 30 people phenomenon. And so if you're talking about like the other 29, it's like you should just like look at a list of B vitamin symptoms and like have your doctor run a panel of B vitamins on the screening or do it yourself.

And if, if you didn't want to spend money on that, there's these two weird foods that are on the bulletproof diet that we've eaten for a while and egg yolks and raw beef liver full of B vitamins, full of biotin. And as long as you're not eating raw egg whites, which deplete biotin, and you, so you, you cook your whites a little bit soft, you'll probably like, like, again, we're playing the rules, it's probably going to work, but if it doesn't, it means that you need to do more of those, more of that kind of work.

Yeah, for sure.

What about chelation therapy? Because I've seen some people talking about how the calcium that forms in your arteries is actually calcium oxalate. So these are depositions here. This is for calcified plaque, not soft plaque, which comes from gut bacteria metabolites. So if you do chelation therapy, like with EDTA intravenously or rectally, that dissolves the calcium, what happens to the oxalate?

I don't think that would even work. If you've got crystals, EDTA I don't think is going to be very effective at removing crystallized calcium oxalate deposits in arterial plaque. So whenever you have a crystallization phenomenon, it's an exceedingly simple calculus of calcium. But you know, you go back to a General Chem 101 class. If people are forgetting this, look at the Wikipedia page for LE Chatelier's principle. It's, if you have a reversible reaction, A plus B equals ab, then it can go in either direction. And so if you increase A, you get more ab, and if you decrease A, you get, it goes the other way. Right? Like all you have to do is decrease the circulating concentration of free oxalate and you will drain calcium oxalate crystals. And, and so I, I don't see why on earth you would risk mineral deficiencies with intravenous EDTA when you could just eat less oxalate.

No, you wouldn't do it for oxalate. You would do it for calcified arteries or because you have lead poisoning.

Yeah, but you, you said, what if those are calcium oxalate? And so I'm, I'm addressing that. But I mean, if they're not calcium oxalate, they're calcium phosphate. And the principle is exactly the same, like, you should stop eating processed foods full of phosphorus additives. You know what I'm saying? Like the calcium in conventional medicine, they'll talk about, especially with people with kidney disease, they'll talk about the calcium phosphate product of the blood being the key driver of soft tissue calcification. That literally means the product. Like in elementary school math, where you multiply the concentration of calcium times the concentration of phosphorus and the product of that.

Right.

Something just sum is adding product is multiplying. The product of multiplying those two numbers together is the driver not just of the calcification, but also the decalcification. Right. Because that's a reversible reaction that follows Le Chatelier's principle. All you have to do is decrease the calcium phosphate product in the blood. You will drain those things right out there. And now I, I happen to think atherosclerosis is a little bit more complicated than that because you have nucleating factors driven by cell death and all things like that. So I just feel like EDTA should not be a first resort.

Not for oxalate. No. I, I was just thinking if you have calcium in there. So that's probably a bit of a. Bit of a. It was a question from the Upgrade Collective about that. And I do want to boil all this down because it got pretty technical. So people who have oxalate symptoms like sore joints, muscle, musculoskeletal pain, all the time, fur on the back of your teeth, like a calcium tartar plaque that comes off and some of the other symptoms that you can easily find by searching around for oxalates. Just give me the three bullet points that are most likely to work. Knowing that there's a lot of individuals variety.

Well, I mean, definitely the first bullet point is eat less oxalate.

Okay, there you go.

That's not the convenient answer, but it's.

The step away from the beats. Gotcha.

It's the tested answer. Right. Like, there's way more anecdotal documentation about that than there is about what I'm saying. I'm trying to take it to the next level where I'm trying to think Outside the box with this, where there's very few people who have something to say to support it. But I think the potential for people to take a look at those things and test them out, I think is quite high. And you were talking about the citric acid and the lemon juice. I think that's at the level of solubilizing the oxalate. I'm thinking more at the biochemical level. And so I guess the. I would just say I'll add the third bullet point.

Right.

That everyone who talks about it is talking about the first bullet point. You are emphasizing the second one. I would just say I'm bringing to the table the third, which is that you want to not be deficient in B vitamins. Like three A is, don't be deficient in B vitamins. And one good way to do that is like you mentioned, eat B vitamin rich food. And then if you want to take that to the next level, do a basic nutritional screening to make sure that your diet adds up and that your blood markers look normal for all of them. And then step 3B would be if you want to take that to the next level, you can try supplementing with certain ones that have some anecdotal support, like biotin, but you probably want to stay in the lowest dose you can get easily on, on the market is like 600 micrograms. So maybe start with that. Test it out. As you were saying that you got that U shaped curve. If it's not working, you don't know whether that's because the dose is too high or too low. So give it a little bit of time, like open up the capsule and cut it in half and see if that works or see if doubling the dose works for you to just to get a sense of where you are on that curve before you try something else. And then try things one at a time and see if you get something that helps. Try layering in some of the other things. Like B12 would be my next step and folate would be very important as well. But really all the, pretty much all the B vitamins play some role in that process.

Okay, so we're going to say stop eating high oxalate foods. You won't get away from all oxalates, just eat lower ones. Yep. And you're going to say lemon juice and you're going to say broad spectrum. Probably methylated B vitamins or a B vitamin test would be your top three recommendations.

Yeah, methylated's not important. What you're actually after is the unmethylated form of folate, which does not mean that you want to take folic acid, but it does mean that you're not trying to like, stuff methyl groups into the system to get better methylation.

It's just that a third of people who are gonna follow this protocol need methylated B vitamins, so we might as well get.

Yeah, I'm not, I guess I'm not trying to say that you don't want methylated B vitamins, but I'm just saying, like, this particular application is not a reason to take, say, methylcobalamin versus hydroxycobalamin.

Agreed. It, it's just like given that hydroxy will work for almost everyone and cyanocobalamin won't work for a lot of people, I just always recommend this.

That makes sense. I'm not a big fan of cyano for sure.

I do want to call out too. Viome and full disclosure, I'm an advisor for a long time and an early investor. My viome test shows that I, in fact, the only metabolic pathways that aren't working well for me right now are my oxalate pathways. So they're doing something. And I haven't had a chance to talk to the research team there about how they're determining that. And it could just be from bacteria in the gut, but the science I've seen says that gut bacteria in humans don't contribute much to reducing oxalate in the diet. So. But apparently they can see it somehow. And I don't know whether mechanism is for that, but that's another little way of testing it. All right, well, I think we've, we've beaten the oxalate crystals to death and hopefully now if you are a person who was a vegan or replacing healthy animal based foods with unhealthy oxalate rich plant based foods because you thought it was good for you, by now you're actually a former vegan and I congratulate you in moving into a stronger future where you can be less anxious, as we talked about earlier, because now your metabolism will work so you'll be able to deal with your fear and then you'll stop yelling at people about eating healthy animals. There. Did I trigger anyone? How about we trigger some biohackers? You up for that? All right, you want to start sometime around the late 90s because I'm an old school anti aging guy and hang out with people three times my age. When the first papers about methylene blue came out, we were very cautious on dosing. It took one drop, diluted in a vial of water. And you just have one little bit of that to enhance mitochondrial function. And over the years, the amount that's been recommended has gone up and up. And you've seen pictures of me with a blue tongue experimenting with methylene blue, I've had it intravenously even, which can have really good effects with light therapy. And it's an interesting compound. I also know that it's an MAO inhibitor, which means it's an antidepressant, which means for people who take ayahuasca or dmt, you should know that if you're a biohacker in doing that, that could kill you because it can cause serotonin syndrome where your blood pressure goes through this. And if you're one of the jungle shamans who listens to this, who's trained with the Shipibo people or something, you know who you are. You should also ask your clients if they're using methylene blue and take it off the protocol. And if you're a neo shaman who isn't trained with Aya, but you've done it five times and now you're offering it to people. Number one, you should go meet a jungle shaman. And number two, you should also ask your clients about methylene blue. So that's a little side note, but you just published like a 50 page paper with some pretty serious conclusions about methylene blue and different dosages. Can you summarize the paper in three sentences or less? This is the challenge for research scientists.

Sentence number one. Methylene blue has three primary effects. One is to generate hydrogen peroxide, which has a general hormetic effect that is very non specific. One is to inhibit MAO A and which has the antidepressant effects that you were just saying. And the third is to rewire the respiratory chain in a way that is good for you if you have a fundamental impairment in it and bad for you if you don't. That's one sentence. I mean, that's basically it.

So there's a damn good summary. That was the most concise thing I've ever heard you say.

I spent a lot of time on that article. So I'm very good at like summarizing things that I've gone very deep into. But for me to say something simple is on the back end of me computing down the real the 58 pages into like, before I write out the 58 pages, I can't write a summary. But after I make the 58 pages and I spend my own time digesting it, I can think about this is the simple way to put it. So the practical implication of that is because it's an antidepressant, you have to be very careful about interpreting your experience. You can't just say, I feel better because maybe you feel better because you're killing off your anhedonia from some unrelated thing. The fact that it generates hydrogen peroxide raises the question of, is this really a specific benefit over on top of the other hormetic stressors you can add.

Let me help. To structure. Let's go through each one individually, which will be useful for people to understand this. But upgrade collective. One of the words drop there. And he was saying if you have specific mitochondrial problems. So number one, methylene blue creates hydrogen peroxide, which makes your cells stronger because they become better at making their own antioxidants. You could also do IV hydrogen peroxide, which is something that I wrote about from Frank Shallenberger, but so there's probably a beneficial effect from that. Would you agree that it's probably not harmful at those doses? Just from a hydrogen peroxide perspective when.

You say those doses, what are you talking about?

Even if you're taking antidepressant doses, which are the higher ones, you're not going to get that much hydrogen peroxide that is harmful. So it'll probably just be a hormetic stress.

I, Yeah, I don't, I don't agree with that. I think at, I think at 200 milligrams a day you have a wildly variable response. Response. So one of the things that concerns me is that in the phase two Alzheimer's trial, there was a 5.6 fold increase in reported injuries from falls, despite no benefit in any of the Alzheimer's trials to the Alzheimer's. And there's a whole body of literature critiquing the doses used. But you asked me about those doses, right. So I'm very concerned about up to 5% or so of people getting neurological doses harm from 200 milligrams a day.

Because they're getting too much hydrogen peroxide in the brain.

I mean, I don't know for sure that that's the mechanism, but I mean, that would be my hypothesis. Right, but, but there's also the fact that if you don't have a respiratory chain block, you don't want your respiratory chain rewired because it's been very fine tuned by much evolution to be exactly the most efficient thing it can be. And so if you're. What methylene blue is doing at the respiratory chain is, I feel like it's very analogous to the TV not working, and you. You smack it upside the head and then it pops back on. It's like at the biochemical level, it's just able to transfer electrons. So non specifically, that if you have a fundamental impairment, what should be the path of least resistance is blocked. It will create a new path of least resistance for you, which is better than not having a path.

Let me translate this for less scientific mitochondrial nerd listeners, and I'm sure there are a few. So your mitochondria make energy and then they basically transfer electrons. And many of us, including me, who have had chronic fatigue syndrome or toxic mold poisoning or metabolic insufficiencies or toxic metals or other genetic stuff going on, you can have a block. And what that means is that those electrons aren't moving very efficiently. And you take methylene blue. It basically allows the electrons to move quite efficiently in all sorts of different pathways. And you will feel better from that if you had a block. However, if you don't have a block now, you've taken the electrons from the channels they're supposed to be going on that are most efficient evolutionarily. And just saying, why don't you just blow them out there? In other words, instead of the river going down the riverbed, let's just have the water go everywhere. Well, at least the water got there, but it might have been better to keep it in the banks of the river. Good analogy.

That's a very good analogy. Yeah.

Okay, so that was your third point, was that if you have a specific blockage, it'll help. If you don't, it kind of lets the water out of the banks of the river. And we talked about the antioxidant thing, which was the first one. And then your second point there was that it's an MAO inhibitor. And what were your concerns there?

Well, I mean, that's. There's the obvious, sort of, like everyone will say this in the literature concern that you could interact with an ssri, for example, to produce potentially lethal and certainly horribly suffering serotonin toxicity. And there are some case reports of that happening from people who are on SSRIs who had injected methylene blue prior to surgery. And it was. It was just very clear that the extent of their serotonin syndrome could not be explainable by the SSRI alone. And that's why they did the research on whether methylene blue is an MAO inhibitor. And it is. But my. What I would add to that is just that if you're taking an antidepressant, it's kind of hard to judge whether you feeling better is a sign that your energy metabolism is improving, because ideally, you want to be able to listen to your body and use what your body is telling you as a gauge of whether you're improving it. But there are confounders, right? Like I, I'm gonna, if I'm tired, I'm gonna feel better after I had coffee, but that doesn't necessarily mean I fix my mitochondria. I'm not saying that like, I mean, I have coffee next to me, I'm not against coffee, but I'm just saying if you have caffeine that's raising your rate, that is inhibiting your adenosine, and whenever you have something that's acting like a drug, you have to take into account that you are feeling different because of it. And you, it's just a confounder, right? It just means that it's harder to interpret what you're doing for your mitochondrial health.

So what, what I heard there is that everyone has a coffee deficiency and should get danger coffee right away.

That's exactly what I meant.

Well, your, your point there though, is that if you don't have a mitochondrial deficiency that you know about and you take methylene blue and you suddenly feel better, you might just be less depressed, even if you weren't very depressed before. It can be mood elevating. Just like you could take Wellbutrin if you're healthy and you might be a little bit mood elevating. The reason I'm bringing this up is I'm certainly the very, very old methylene blue stuff comes from like, esoteric longevity circles. And I brought it into the biohacking world. And one of our upgrade collective live audience members, Mandy, says, you know, if I do my methylene blue, my allergies go from 10 to three. Like, there are people who get benefits from this that probably aren't antidepressant based and maybe in her case she has a, a respiratory chain blockade, we don't know. So I'm not saying methylene blue is bad. I'm just saying that if you're going to do psychedelics, you might want to be careful. And I've, I, I don't notice a great difference from methylene blue now. I used to feel a huge difference when I was mold, toxic and like, my body works pretty damn well. I'm like, I'm in the best shape I've ever been, so. And I'm not working hard for it either. It just works the way it's supposed to work. So I said, well, I'm just going to travel around. I'll bring the damn vial. Hope it doesn't leak in my luggage. And it was taking, you know, a dropper full or two a day, which I don't remember dosage, but a meaningful amount. And what is a common side effect of SSRIs? Could you predict that one?

Well, with respect to the serotonin syndrome, it's generally a mix of like just feeling sick. So you like throwing up could be part of it. Having a fever could be part of it.

Oh goodness, I didn't go there. I mean, serotonin syndrome, your heart rate goes up, blood pressure goes up.

Yeah, general, general overstimulation of all the systems is, is like the general response.

I could have probably handled that. I don't mind stimulated systems. It was the other side effect that so many people on SSRIs don't read the literature about. It's Ed. So for this month I'm doing that. I'm like, what is going on? Like, where's the morning kickstand? And so I found a correlation between, you know, a dropper full or more of methylene blue and waking up without a kickstand. And that wasn't a very pleasant side effect. So if you're taking methylene blue, I'm not suggesting that you stop. I'm suggesting that you read Chris's 50 something page paper where he makes a really convincing and well thought out scientific case that if you're feeling it, either it's because you have a substantial problem with your mitochondria or it's because you're taking antidepressant and you don't know it. I still think it's useful for phototherapy. If you have problems with your bladder, you should probably have someone hit it with red light therapy.

That's probably an antimicrobial effect. I think so too because the combination with light is. It makes it extremely antimicrobial.

Awesome. Well, Chris, you've definitely over the last 10 years done a lot of really curiosity driven research which sometimes seems to be missing from academia these days. Like, I wonder why that is. It must work this way because it works. It has to have a reason for working in steps on how it works. So I'm definitely a fan of your work, which is why I mention it. Well, episode 17 and now episode 1000 and whatever, but also one of my books because, like you've really thought about it. You know a lot about minerals and metabolism and if people want to learn more about the kind of stuff you're doing. What's the best place for them to go?

Well, the best place, if they really want to dig deep into the biochemical optimization program, is my website that's going to be launching by the time this podcast comes out, which is biopt health.com and then of course all my personal writings@chrismasterjohnphd.substack.com.

You got it. Bioptealth.com and Chris Masterjohn and once I said at the beginning, but you were very evidence based during the three years of government occupation of our immune systems. And just again, thanks for that because not a lot of people sort of believe that.

Well, on the topic of what we've been covering, not injecting yourself with a mitochondrial toxin is also helpful.

Yeah, that should be somewhere in the top 10 lists of biohacks. Not punching yourself in the face with needles.

Yep. Yeah. Well, thank you very much. I appreciate the appreciation.

If you like today's episode, you know what to do. Keep biohacking and you leave a review. You could check out Chris's work or if you really liked it and you really like amazing coffee, you could head on over to dangercoffee.com and every time you pick up a bag of my new coffee full of trace minerals, it does help to support the show and having cool conversations like this. I appreciate your listenership. You're listening to the Human Upgrade with Dave Asprey.

The Human Upgrade, formerly Bulletproof Radio, was created and is hosted by Dave Asprey. The information contained in this podcast is provided for informational purposes only and is not intended for the purposes of diagnosing, treating, curiosity, curing, or preventing any disease. Before using any products referenced on the podcast, consult with your healthcare provider carefully, read all labels and heed all directions and cautions that accompany the products. Information found or received through the podcast should not be used in place of a consultation or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of guests are their own and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or warranties about guest qualifications or credibility. This podcast may contain paid endorsements and advertisements for products or services. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein. This podcast is owned by Bulletproof Media. A Human Upgrade, formerly Bulletproof Radio, was created and is hosted by Dave Asprey. The information contained in this podcast is provided for informational purposes only and is not intended for the purposes of diagnosing, treating, curing, or preventing any disease. Before using any products referenced on the podcast, consult with your healthcare provider carefully read all labels and heed all directions and cautions that accompany the products. Information found or received through the podcast should not be used in place of a consultation or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of guests are their own and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or warranties about guest qualifications or credibility. This podcast may contain paid endorsements and advertisements for products or services. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein. This podcast is owned by Bulletproof Media.