Nutritional individuality, I remember now. Roger, what stage of Roger Williams? Yeah, you

know, so Roger Williams is,

should be the father of this field, documenting

many ways in which the biochemistry of different people resulted in different nutritional needs, for example. One thing that he probably would have recognized about me is that my eyes are light blue. I've got greater UV destruction of retinol inside the eye, and so I'm likely to require a higher amount of vitamin A. And I think there were many people in between then and now who have tried to come up with ways to determine, should you eat high carb, should you eat low carb, and all these different things. But I think we are now entering the realm where we can get a lot more precision on the hundreds of ways, really thousands of ways that we are different. And I think there are a lot of nuances that we can, that we are just now being able to come to, where it really takes a lot of work to get incredible precision, but we can now start thinking about things that people can self -experiment with at home, such as how different metabolic pathways might be altered and why you might need to get most of your nutrients at just levels that might occur in a whole food, but maybe one particular person needs a lot of extra riboflavin and another person needs a lot of extra thiamin. of those people do the opposite, they're going to wind up in a lot of trouble. And so I think where we are now is really at the place where we want to start getting deeper into the precision that's becoming available. Okay.

And what is the technology that allows that precision?

So in the modern day, I think what we have now is the development of the ability to look at this issue with a lot of precision that we did not have in past eras of trying to individualize people's diets. One of the major advances that we've had over the last year is that as whole genome sequencing has become affordable to apply at mass scale. We now have studies, for example, the million exome study, which actually didn't use the full technology, full genome sequencing that looked at whole exome sequencing, which is an approximation of that. And what it found is that essentially genetic mutations are skewed such that any given one that you would think would be too rare to care about, the average person has one or two. And I think that's an underestimate. I think it's really three to five. And what that winds up doing is creating a situation where instead of five years ago when you would think nutrigenomics is understanding whether I have MTHFR or I have COMT or I have one of these other polymorphisms that are common, where you can take a report and you can share it with 20 other people that at a conference or that you're friends with and three of you will be like, Oh, I have that one. And the other six will be like, Oh, I have that one. We really have a skew where the highest impact genes are so rare that you are likely to go to a conference and talk about yours with someone else and not run into someone that has the same that you have. And what that means is a lot of times the most impactful mutations that someone has are, first of all, you've got 14 million. You can throw the most out because they are so little in their impact that they're just noise. And if you boil it down to - Two million what? Mut mutations or not genes? Sights of variation. Okay. So there's, you know, so there's, so in the human genome, there's 14 million sites of variation. And if you look at something like 23andMe, they are looking at hundreds of thousands of those 14 million. So they're missing a lot of, they're missing most of the sites of variation.

But number three in me is not a human genome though, it's just a partial

sequence,

right? They don't do the whole gene. What

it is is a SNP chip test. And so what they do is they have a chip that represents each polymorphism that they're looking for. And they want to ask the question for each one, are you this one or that one? And

just for those who don't know, a SNP is a single nucleotide polymorphism or a mutation, so to speak. Right.

So before whole genome sequencing became affordable at mass scale, the most recent iteration of what people were doing to try to understand their DNA was doing something like 23andMe or Ancestry, and then often running those through third -party reports. And those are extremely limited in what they're testing because they're only capturing a couple hundred thousand out of the millions of variations. but way more importantly than that, the nature of the SNP chip test, the methodology that they're using, loses all of its accuracy when you're looking for something that is present in fewer than one in a thousand people. So the way that the test is done is it's dependent on the stats that you from large numbers of people in your batch being both polymorph, one or the other that you're looking for. And so the reason that this is important is because what whole genome sequencing has taught us is that each person is most impacted by somewhere around one to five super rare genes that they have. Which means the older testing from 23andMe is not giving you anything accurate at that level. So the way that I think of it is like each... The way we should think about our health is kind of like a double layered cake. Not that cake is the best thing for your health, but you've got one layer of the things that everyone should be doing, right? So like we should all be, you can make some parameters around what is a healthy diet that anyone should be following. And we argue all the time about where those parameters are, but there's certain things that everyone would agree on, like eat mostly whole foods, make sure that you're getting all your, meeting all the basic requirements for your nutrients and so on. And then we can argue about carbohydrate and fat or whatever, but then there's other things that everyone should be doing like stay active, get outside, get sunshine, et cetera, et cetera, et. You know, but then there's this other layer where it's. Things that are unique to me are going to be extremely unique to me. Because I've got a small handful of mutations that. I could talk to 100 other people at a health conference and no one's going to have the same ones that I have. And that I think is where you can unlock the big step after where all that commonality stuff gets you. None of it invalidates the things that we should all be doing, like getting the type of exercise we should be doing and eating a healthy diet. But it does make for us to be able to say, all right, I've done everything that I can. I've achieved, you know, seven out of 10 for my health. How do I get to 10 out of 10? And I think understanding those deep idiosyncrasies is how to unlock that last mile of the run. Well,

I'd like to challenge that supposition.

Yeah, good.

You mentioned 14 million perturbations or anomalies, but there's only 23,000 genes. It makes it sound like there's more than there is. You can only have 23,000 genes that are impact. Each Yeah,

that's fair. I mean, that's true. Yeah. So, it's a variation in a... I mean, it depends how you look at it, right? So, there's one for numerous proteins. And so, there's about 100,000 proteins. There's about 20,000 genes. There's about 14 million sites of variation. Yeah. So 20,000 genes that make a

hundred thousand genes. I mean, obviously there's an enormous complexity that we won't even begin to learn in multiple generations after we're dead because it's way too sophisticated and refined. But I think Bruce Ripton had a really good take on this in this epigenetics, which is not so much that we're committed to some final complication because of our mutations, but it's the expression of those genes and the modulation of those genes. And we had talked on our last phone call, my recent fascination with carbon dioxide, how it modulates the function of proteins depending on the level of carbon dioxide in your body. It's a really important, pretty much unrecognized variable in optimization of health. And I understood that from Ray Peat and he had an incomplete picture because when I listened to a lecture from Don 2010 with Bud Weiss, he was saying how carbon dioxide modulates the ex - modulates DNA and carbon dioxide only attaches to proteins, specifically the lysine and histidine residues. So I wonder how that could work and then I realized it's the expression of the proteins on the DNA, it's the histones that are modulated, that the histones modulate the expression of the DNA. So if you can modulate in some way, we have no idea how or what they do and how it's done. It's just an enigma. We just know that it does that. So the supposition is that if you have this anomaly in the 14 million potential cases of the 23,000 genes, that's almost admitting that this is almost a fatal flaw when it may not be. It may be there's other mechanisms that can bypass that, that we don't even know aren't aware of because of the modulation of the histones. So that's my retort. Okay.

Well, I think that definitely is super important. But epigenetic, so genetics has a stronger impact on how each of us are different. And epigenetics has a stronger impact on, for example, if you have a unique problem, when in your life does it onset and what is the power to resolve it? And it really doesn't have that much of an impact on how individual we are because the types of epigenetic regulations are relatively narrow. So there are, I mean, you could say, for example, like. stress is going to impact your epigenetics. But even though there might be, like, if you look at like, people's trauma, right? There are, no, sure that will. Everyone's trauma can be very, very unique in terms of the experience of it and what it, like, what the content of it was. there's not that many different types of stress response to trauma in the body. And so the resulting epigenetics are largely narrow. So - Well,

I would challenge that. Okay, go ahead. I'm not accepting that as a fact because the implied assertion is that we understand everything there is about this and we don't. We don't know more than we know. We both have been in this long enough to realize that there's innovations that are realized every year that turns our understanding of the situation upside down. And especially something as complex as the expression of our genes and behavior and even with stress. I mean, I've seen many people, I mean, you even had a clinical practice I have and I've seen literally stress destroy people, absolutely destroy them in ways that the most disciplined, motivated person is simply unable to recover from. Until the neurological consequences of that stress, the circuits that got facilitated in their brain are resolved. There's energetic ways to do that that are really astonishing and close to miraculous. But we don't know how it works. No one knows. So I think it's almost a bit hubris to suspect, to imply that we do. I mean, we just don't know. I'm

not implying that we know everything there is to know. I'm implying that we've learned some things that are valuable. Yeah, I mean, I think that when I say genetic, you are reading that as genetic determinism. Yes.

I think you're accurate. That was one big preps I'm confused on your argument.

I'm not saying that, I mean, if anything, I would argue against genetic determinism because the point is to find the points of actionability. And if something's actionable, then by definition, it's not deterministic because your action is changing it. So what I'm saying is I'm not talking about determinism, I'm talking about uniqueness. So what I'm saying is, granted, there are things we discover all the time. Just a few days ago, it was discovered that mitochondria in axons of the brain do not produce ATP with a proton gradient as describing the textbooks. They do what bacteria do and they consume ATP to generate a proton gradient, to generate proton. So they work backwards according to what's in the textbook for humans and they work, like if you go to Wikipedia, it says ATP. That's a mistake. Don't go to Go to molecular biology of the cell by L -1.

Yeah, that would be

better. It says that ATP synthase is an F ATPase running in reverse because the original one consumed ATP to make a proton gradient in bacteria and we flipped it around. But they just discovered it last week. The they do it the original way, right? So I'm not saying that we've reached the end of the road and we now know everything. I'm so glad. I thought you were smarter than that. All I'm saying is that there are valuable things that we've learned very recently about the skew of genetic mutations in people that have actionable implications, which means that there's nuances you can add to how you do things to optimize and maximize your health. And my point about epigenetics is like obviously these things interact, but the epigenetics I really don't think adds as much about the uniqueness as the genetics do, because, you know, we, we all can get stressed but we're like generally stress is quite similar in what it's doing right there's a handful of stressors that we can experience, psychological and emotional work, metabolic, not eating enough, like exercising too much. Like there's a bunch of them, but they're relatively small. Whereas if you look at the, if you look at the skew big bottlenecks in metabolic pathways, you're looking at 30 -ish essential nutrients that could be altered. You're looking at three major macronutrients that could be altered, and you're looking at combinations that come from those. And that can give you really like, you're really looking at thousands of possible individual bottlenecks that have maybe dozens to hundreds of implications of how you could uniquely tailor your diet. And it's not displacing all the other knowledge that we have, it's just adding something to it.

Okay, well, let me ask you a clarification question. Yeah. Because the actionable items are going to be influenced by this, and that is the confidence you have in the reliability and reproducibility of this assay. I've read or heard some discussion that there's an issue there, that it's not accurate as you may believe. What's your experience with that? I

think that you have to look at it in a couple ways. So what I do with my clients in very small scale is in depth looking at agreement between many, many, many different types of genetic and biochemical data and the person's experience. What I think that people can do, themselves in a more DIY approach is look at it as a hypothesis forming experiment. So to take an example, let's say that... I'll take an example from me. So I found out that I have a riboflavin responsive mutation and I'm heterozygous for it, and in infants who are homozygous for it, there's a almost 100% infancy death rate and they supplement them with riboflavin and it abolishes 90% of that death. So I look at that and I'm like, well, I obviously don't have that disease, I didn't die in infancy, but this might raise my riboflavin requirement. And I just stumbled into the fact that supplementing about 75 milligrams of riboflavin immediately abolished my seasonal allergies, for example. Like, I literally have not had any allergies since I did that. And that, you know, that's, there's many things that you should look at, but one of the things you can look at is just, if you develop a hypothesis around it and you test it, what is the outcome?

Yeah.