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#13 – A Genetic Explanation for Success on the Carnivore Diet, Debating LDL, Protein Metabolism and more with L. Amber O’Hearn

The carnivore diet is all the rage right now, with some outspoken advocates telling us that all plants are “bad for us” and that meat heals. I’ve written a blog post titled Why the Carnivore Diet is Probably Unhealthy and What to try Instead, so my views on carnivore diets as they apply to most people are no secret. Having said that, it’s clear the carnivore diet offers significant benefits for some people as well, Jordan and Mikhaila Peterson being notable examples. Why would certain individuals be healthier eating nothing but meat? In this episode of the podcast, we go beyond the usual diet wars and instead focus on genetic traits that could signal either success or failure on a carnivore diet. Our guest, L. Amber O’Hearn is one of the original carnivores. She created the Carnivore Diet Conference and credits an all meat diet with improved mental health. Amber was a great sport to come on the show and there is a lot we can learn from the research she has done. Tune in for a nuanced discussion on the carnivore diet.

Listen on Google Play Music


This Episode Covers:

  • Amber’s journey towards healing bipolar disorder [10:30];
  • A day in the life of the carnivore diet [21:21];
  • The energy model of lipids, LDL debate, and Mikhaila Peterson’s blood work on an all meat diet [32:00];
  • Amber’s LDL-P on a carnivore diet [41:10];
  • A genetic explanation for success on a carnivore diet [42:30];
  • Carnivore diet and gut health [50:30];
  • People poorly suited to a carnivore diet, protein metabolism, and the urea cycle [57:00];
  • How important is ketosis on the carnivore diet? [1:05:00];
  • Autophagy, cancer pathways and mTOR [1:10:00];
  • Factory farming and the carnivore diet and balancing health vs. environmental externalities [1:17:00];
  • Uric acid, gout and the carnivore diet [1:20:00]


Amber’s website

Dave Feldman’s website – The Cholesterol Code

Peter Attia / Dave Feldman interview (recommended)

Mikhaila Peterson’s blood work on the carnivore diet

VLDL as an independent risk factor for heart disease beyond TG count

Sitosterolemia overview

Sterols of coffee

LDL-C of over 190 mg/dl sitosterolemia?

Blood type and hydrochloric acid 

Urea cycle variability


Amber: If you’re in a position where your health depends on meat, and you’ve got limited resources, you have to put your own mask on first. If I think back to kind of mental state that I was in before I found carnivore, I was dysfunctional, there’s no way I could have made a positive impact on the world. It was hard enough for me to just live my day-to-day life. There’s a bit of a bootstrapping thing, where you have to get your nutritional elements in place however you’re going to get them before you worry about just iteratively one step at a time, make it better.

John: Welcome to the “Gene Food” podcast. I’m your host, John O’Connor. Hey guys, today we are going to cover a very controversial topic in the nutrition world. A lot of you have probably heard about the carnivore diet, it’s gaining in popularity, there’s a lot of marketing behind the carnivore diet. A lot of people swear by it. There’s some very famous and well-known public figures out there who have put autoimmune disease, into remission eating nothing but meat. Here at “Gene Food,” we don’t necessarily think the carnivore diet is for everybody, or maybe even for most people. I think there’s a lot of health challenges associated with eating that way over the long term.

Having said that, we wanted to have a nuanced discussion about the carnivore diet to try to get the perspective of somebody who the diet has helped. So we brought on Amber O’Hearn. Amber is one of the original movement generators of the carnivore diet, she started the Carnivore Diet Conference, and she’s been blogging and researching the carnivore diet for a number of years. We’re really excited to talk to Amber, mainly because we were able to have a nuanced discussion surrounding a diet that I think is very polarizing. We talked about when the carnivore diet can be a healthy intervention, there’s some genetic circumstances that we’ve identified that we think could point people in the diet that was more carnivorous. And we also talked about the concerns that we have and the times when we think the carnivore diet could potentially be suboptimal for people’s health as well.

So if you’re in the mood for a deep dive, and then a more nuanced conversation about the carnivore diet, we get into a lot of the science, cholesterol, lipids, uric acid, all that good stuff. So without further ado, here is Amber.

John: I’m so fascinated by just the topic of the carnivore diet, and all the stories and all the characters that are involved in the carnivore diet. And I was gonna try to make it out to your conference because you’re the founder of the Carnivore Diet Conference, which is cool. I ended up not being able to make it and you were very pleasant about refunding my tickets. So I appreciate that very much.

Amber: Yeah, you know, it’s funny, because I was just looking up in my e-mail to find the number for this conference call and noticed that when I put in your name, a refund request came up, and I hadn’t put the two together until just now.

John: Yeah.

Amber: And I hope you get a chance to come to the next one. I’m actually really excited about it. I’m really glad that I put that together because there’s so many people talking about the carnivore diet. And there’s a set of people who are just really enthusiastic about it but don’t have a very good understanding of what’s going on with it scientifically. And there are people who are advocating for it without really…I don’t know, just saying things that go beyond the evidence. And what I really wanted to achieve with this conference is to reel it back in and say, “Hey, what do we actually know? What do we not know? What do we wanna know more about and what’s going on in the scientific basis of this?” I wanted to rescue it from what I saw was this over-enthusiasm, it happens with everything, just to figure out what of value we can take from what we’ve learned so far and what’s the right direction to go forward to get the most value out of what we know?

John: Yeah, absolutely. I mean, I one of the things that I had in my notes to discuss with you is it’s funny to watch in the diet wars, you know, the kind of the desire to sort of like win, you know. Because it’s crazy to watch them we have this election cycle that’s coming up. And with the diet wars, it gets the same. I mean, you get people and people like to be part of a group and they like to affiliate with a group. And I feel like it’s probably something having to do with like social media algorithms or just the way that our news feeds are kind of curated by the people that we subscribe to and follow on Twitter and the conversations that we take part in. And you have these literally opposite conversations taking place.

You have these plant-based groups that are having conversation A, and they are just totally dismissive of and skeptical of any of the low carb stuff. And then the low carb stuff is exactly the same with the plant-based group. And it’s all this crossfire. And what we’re interested in doing is trying to come up with some frameworks. So it’s like, “Okay, if this is something that you’re struggling with or you this lab marker that showing this, then you might wanna consider a carnivore diet.” We’re gonna get into some of that here in a minute. But before we do, I just think your story is so interesting. So if you could just kind of tell the audience how you came to be a follower of the carnivore diet, why? What a typical day looks like for you eating-wise and all that good stuff.

Amber: Sure, yeah. And I just wanted before I go into that really reiterate what you just said about the desire to win. And it seems almost like people are more worried about their status and about being right than actually creating value, which is, of course, what we all want to do, ultimately. So I actually grew up on a primarily vegetarian diet. So my mother, she was she didn’t grow up vegetarian but when she got to be a teenager, she decided that, for ethical reasons, she couldn’t participate in this direct taking of another life, another animal life, particularly mammals, in order to eat. And so we were brought up vegetarian. And I think in a really good way, as far as vegetarianism goes, in part, because we were pretty poor. And so most of what we lived off was legumes and greens that were properly soaked. And because you know, we didn’t buy stuff that was pre-made, we had to do it all at home.

So I grew up on home-baked bread, and we had books on our shelves about how to properly compose a diet to make sure you combine proteins properly and all that stuff. We did have eggs and dairy at our home, and even occasionally fish, and maybe even more rare, some poultry. And it wasn’t that I didn’t have any meat at all growing up because when I went to my grandparents, I wasn’t forbidden from eating that way. It’s something my mother wanted to support in her own kitchen. So that was my upbringing and that was my bias growing up.

So when I went to live on my own as a teenager, I did eat meat. And I was also very financially constrained, I basically ate what I could get my hands on. And then when I went to university, my circumstances changed a bit because I started dating someone who had the means to feed me. And so I just started eating a lot.

John: Let’s go out on some dates, get some steaks here. Yeah, okay.

Amber: Yeah, and actually, steak wasn’t…because it wasn’t something I grew up with, it was never something that I really chose. It’s not that I avoided meat but a meat-focused meal just wasn’t the kind of meal that I would have chose because it just wasn’t what I was used to. But I did I eat a lot and I gained 30 pounds in probably the first 6 months of my university experience, which was really distressing to me for a variety of reasons. And so I thought, “Okay, I’ve got to fix this.” And I had the idea in my mind that diet and exercise were the way to go, I don’t know where I got that idea.

But so I started looking into diet a bit. And this was 1992, so we didn’t have the World Wide Web, we did have the internet and there were discussion groups online. And the two big diet discussion groups were actually a low-fat discussion group and a low-carb discussion group. And that was the first time I’d ever heard of low-carb. I looked at it for, I don’t know, maybe 20 minutes or something. But I pretty much immediately dismissed it as the craziest thing I’d ever heard of, like, why would you throw away the foundational base of our diet, where all our health comes from? And I just didn’t even…there were too many barriers for me to even understand why it might be okay.

And eventually, I decided that the reason may be that I had gained all this weight was because of my diversion from my vegetarian upbringing. So I immediately went vegetarian again, and I started exercising a lot. And this may have actually stalled my weight gain, but it didn’t cause any weight loss. And so then I decided I should eliminate all animal products from my diet. So I had I did have a stint of pure veganism.

All of that stopped when I went on a trip to Russia as part of my studies. And I could have, I think, if I cared about it enough, like if it were an ethical position that I was taking, I might have taken more steps to just continue to do that while I was there. But because it was so difficult, and because I thought, “All right, this experience of being in this other country will be enhanced by my eating the way people are eating here. And I can put my own health concerns on hold until I get back home.” And what actually happened was that when I got home, I had lost some weight. And there are a variety of reasons that might have happened that might have had nothing to do with adding meat back into my diet. Like, for example, I drank a lot of vodka. And I probably just did different things.

John: You probably also just kind of stopped worrying about it too, for a while. I feel like getting so deep in the weeds on the concern over just eating the perfect diet is kind of part of the problem with the whole diet issue in the first place, right? I mean…

Amber: That’s a really good point. Yeah. So I just wanted to emphasize, I don’t really think that adding some meat back into my diet caused the weight loss, although it may have, it might have been the case that I was protein deficient, for example. But what happened was it caused me to rethink it caused me to say, “Okay, something about my whole conception of this must be wrong.” And something made me think about the low-carb diet again, I don’t know why I thought of it. The seed had been planted a while ago, as I said, but it happens that in that year 1997, the book “Protein Power” by Dr. Mary Dan and Michael Eades came out. And so I saw that on the bookshelves, and I read that book, and that completely changed my life. And so that’s when I started a low-carb diet back in 1997.

John: Okay.

Amber: But my low-carb diet, it was very full of plants, like, as you know, you can do a low-carb diet, even with no animal products at all. There’s a huge spectrum, as long as you’re carbohydrates are low enough, it’s a low-carb diet.

John: Or low-glycemic, high-carb diet relatively.

Amber: Right.

John: Yeah.

Amber: So I did that diet for a long time, 12 years before I discovered the carnivore diet, and over that time, so my weight immediately normalized. And probably lots of other things changed in my life. But then over the course of those 12 years, I aged and I had 2 children. And every time I gave birth, every time I went through the process of having a child, I gained weight, which I didn’t completely lose even though I returned to a low-carb diet after the pregnancy. I didn’t stay low-carb during the pregnancies not because I was worried about the health of it but because I had…well, for one thing, I have hyperemesis gravidarum in my family. So I had extreme nausea. It was just really important to eat whatever I could get down. And sometimes that was the highest carb thing I could think of.

John: Is that a condition that…I hadn’t heard of that. Is that a condition that’s associated with increased nausea during pregnancy?

Amber: Yeah, to the point where people often have to be hospitalized to be rehydrated because it’s not just nausea. A lot of people experience nausea in the first trimester and maybe even some morning sickness vomiting. But my mother, for example, always lost weight through her pregnancies and had to be hospitalized because she just literally couldn’t keep food down.

John: Wow.

Amber: Yeah. So I didn’t have it nearly as bad as she did, or as other women in my family have had. And I don’t know why if that’s a genetic difference or because of things in my environment, but I still had a really hard time with food. Regardless, over the course of these years, my weight was increasing, despite the fact that I was on a low-carb diet. And it was really distressing to me because from the moment that I had found that book, I was so persuaded by the science behind the healthiness of it, that I couldn’t understand how I could possibly be gaining weight. And I felt more and more like there was a discordance between what I believed and what my body was showing me. And that was very uncomfortable.

And I started to become really desperate in a way like I would research things online, I would get hold of some idea like of some kind of deficiency, or some kind of nutrient, or some kind of infection or something and say, “Oh, maybe I have that.” And so I would buy like a bottle of creatine and use that before I worked out. Or I would, you know, just…I spent so much money on so many different crazy interventions, it’s really embarrassing.

But so I was at that point of desperation when I first encountered what was being called the “ZC” or zero carb diet at the time and some people still call it that. I tend to not use that word, all the words that I that I’ve come up with are also confusing, it turns out. But what they meant was not literally zero-carb because you wouldn’t eat plant oils, even though they have no carbs. And you would eat eggs or shellfish or liver even though they’re not zero carbohydrates. But the idea was just animal foods, no plant foods.

And I had discovered this forum called Zeroing In On Health, where some people who were a lot like me in background, it seemed, where they were are on a low-carb diet and either didn’t get them to where they wanted to be, or they had some regain. And going on this all animal food diet had solved that problem for them, along with a bunch of other things, which is why ultimately it was called Zeroing In On Health and not zeroing in on weight, for example. These people were sharing these kinds of bizarre stories about things that were improving for them that they didn’t expect.

So for me, though, it was all about vanity, I didn’t consider myself to have any health problems, although I did have a really serious health problem. And that was that I had had at the same time that I gained all that weight in my freshman year, I was diagnosed with clinical depression for the first time. And that had continued through all this time. And had even been re-diagnosed as a form of bipolar disorder, type two bipolar disorder, which is different from type one in that you don’t have psychotic breaks. So you would have the depression part and you would have something leading up to mania called hypomania, just a small mania where there’s excitability and a lot of the same characteristics, but it never goes to the same degree. So I had that new diagnosis, but I didn’t consider that to be a health problem in the sense of something that diet could address because, well, it just was never talked about that way. To everything that I knew, a psychiatric problem was purely a genetic problem, purely something that you’re unlucky about, and that has nothing to do with the environment. So that didn’t even occur to me as something that the diet could solve.

But what happened was, when I decided to try this all-meat diet, purely for vanity reasons, I was nearly 200 pounds. I might have actually been 200 pounds, I think I kind of didn’t wanna look at the scale anymore. I know it was over 195 at one point. So I tried this diet and within a couple of weeks, not only was I losing weight rapidly, and feeling really good, but my mood seemed to be stable and qualitatively different way from just being good. Now, of course, if you got the bipolar disorder, your mood changes a lot. And you don’t at two weeks, you don’t say, “Oh, my bipolar is cured.” And of course, I didn’t even go there but I noticed it. And ultimately, the reason that I’m still on an all-animal food diet today is because after that experience, actually, there was a diversion because immediately after that, I started a zero carb diet. I got pregnant again and I wasn’t zero-carb throughout the pregnancy. But as soon as the baby was born, I went back on this all-meat diet. And I had had to go off my psychiatric meds because I was pregnant.

John: Right, okay.

Amber: So because my safety was unknown, right? So I gave birth to the baby, went right back on this diet, and I never needed meds again. So that’s my story.

John: That’s fascinating. I mean, people like you and I, who are deep in the weeds on nutrition and who do a lot of self-experimentation. We understand I think uniquely, just how much your food choices can impact on your mental health. And it’s incredible when you start looking at, you know, eating this way and I feel this way, I’m eating this way and I’m feeling this way. And there’s actually a lot of studies out there, you know, for somebody who’s listening who’s saying, “Well, you know…” I’m not saying it’s like dispositive of every situation but there are studies out there that do link vegetarian diets and vegan diets with mental health problems, and there’s more than a few.

And it’s something that people go on these diets because there’s a lot of marketing behind them. And for some people, there’s tremendous health benefits behind them as well. But you never really get the caveats of like, “Okay, hey, if you’re going on this day, you might become very deficient in DHA, you might have this problem, this problem, and this problem.” In fact, what happens instead, is the commentators who are kind of, you know, the thought leaders in those spaces, they tend to deny the existence of those types of issues, which basically takes people off the scent when they go on those diets that they could be having these kinds of problems. And you hear it over and over again, you know, some people when they go on vegan and vegetarian diets, it exacerbates, you know, mental health problems.

Amber: Yep.

John: We had on Chris Masterjohn a few episodes back and he blames basically a cholesterol deficiency. I think it’s like Smith-Lemli-Opitz, one of these genetic disorders he thinks that he may have that’s associated with cholesterol deficiency, and that gave him all these mental health problems when he went on a vegan diet.

Amber: That’s interesting.

John: Okay, so that sets the table, you’re in this situation where this made a drastic improvement in your health and a drastic improvement in your mental health. What does a day on the carnivore diet look like for you right now? Like, are you doing three meals a day? Are you doing intermittent fasting? Where do you…I’m sure, in Boulder, you can probably get nice quality beef and all that. So like, what does the logistics of it look like just on a daily basis?

Amber: Yeah, that’s a good question. So I’ve been doing this a long time. And it’s definitely changed over the years, I sort of go into phases where I’ll be really into this food or into that food. But the basic pattern is that I’ve settled out almost always at two meals a day. I usually don’t eat breakfast. I feel that it’s very important to pay attention to physiological signals of hunger. So if I’m hungry in the morning, I’m just gonna eat breakfast, it’s not really about trying to eat a certain way, as far as that goes. But that’s what naturally kind of came out for me.

And I eat a combination…I eat a lot of different animal foods. I eat a lot of beef and lamb, those are probably my favorite, but I also eat pork, and chicken and eggs and seafood. I love oysters. I like organ meats. I don’t get a lot of…there isn’t a lot of variety to be had in organ meat if you go out specifically looking for it. But I’ll eat liver now and then. I love brain, it’s one of my favorite organ meats.

John: Brains almost very trendy right now. There’s a lot of people that…I know there’s like even desiccated brain supplements that are out there that people are like, “This is gonna, you know, ramp up your mental…you know, your cognition, you gotta have the brain.” Okay, so you’re doing nose to tail basically.

Amber: Yeah. And again, it’s not something that I’m really going out of my way to do. I’m not 100% persuaded that nose to tail is exactly how we developed eating meat. And we can get into that if you want at some point, like how humans started with scavenging and eating after the big carnivores. But it’s mainly because I just I’ve always loved food and I like a variety of food. And so that’s my main motivation for eating that way.

John: Since you went on the carnivore diet, have you done bloodwork? Are your biomarkers meshing with the benefits and mental health that you’re seeing? Like, how do you see the whole lab workpiece playing into the carnivore diet? That’s one thing we’re probably gonna touch on here, I have some very nerdy things to get into on that front for us in a minute.

Amber: Well, this ties into how my food has changed as well because, I meant to say this when you originally asked it, what I ate when I first started a carnivore diet where I was much more financially constrained than I am now. and so I ate only, like, regular, conventional meat. And that, in itself, was sufficient to get me past my mental health problems. So I think that’s really important to take note of you don’t have to be a perfectionist. But of course, the longer that I’ve been eating meat, the more I have appreciated the role of the meat industry, the care of the animals, the care of the earth, all those things have become more important to me. And because I have the ability, and because like you said, I live in Colorado, where I’m surrounded by farms, like, I can probably…if I look out the right window, I can see cattle somewhere. So I do go to different farms to get good meat now.

So likewise, early before I started my carnivore diet, I was not in the habit of taking regular lab work at all. And there’s one thing that I would suggest to anybody who’s gonna take on a new diet, try to find out something, get before labs because you’ll be kicking yourself. And it wasn’t until I’d been doing the carnivore diet for five years before I got my first set of lab work. And I was really fortunate in that because at least what I got at that time, my doctor’s office had a deal that no longer exists in which I got a really comprehensive view of a lot of different things. So I have some lab work from that time when I was feeling really great. And then I’ve done some lab work a lot more in the last couple years. And that was greatly influenced by my friendship with Siobhan Huggins who works at the Cholesterol Code with Dave Feldman.

John: Yeah, we know Dave, I’m a big fan of Dave. I’ve studied his model and listen to a bunch of interviews that he’s done. He is a fascinating dude. And seems like a really cool guy too, by the way, just seems like a very friendly…he’s like kind of guy you wanna have a beer with, you know.

Amber: Oh, my gosh, I couldn’t say enough good things about him from both a professional and personal standpoint, he is total minch [SP] and Siobhan is as well. And because of their influence, I got more and more interested in taking more lab work, both for the purposes of troubleshooting things in my own life, for getting baselines, and what I felt was even more important to maybe is to just start getting data collection from our community…

John: Yeah, absolutely.

Amber: …because it’s absolutely absent from all the data sets that we look at. So if you’ll allow me to rant for just a second, we have all these huge studies that look at maybe diet, or maybe not diet, but maybe biomarkers, and then correlate them with a bunch of different diseases. Imagine if you had a huge data set and you knew that 99% or 100% of the people on it were on a green-based diet. And you looked at people who were showing ketones in their urine or in their blood, that’s gonna be always correlated with severe health problems, right? Like risk of heart attack and risk of diabetes. But that’s because, on a high-carb diet, you should never be showing ketones. But then if you use that data set to say, “Oh, look at you, you’ve got ketones in your urine, something is terribly, terribly wrong.” You can’t do that because you just don’t have the base of data. So part of what part of my motivation to start collecting more data came from this realization that if we’re gonna be able to understand what actually correlates with risk, we have to start getting data now.

John: For sure, I think that’s great. I know Dave and his team are mad scientists just doing all these…you know, for the people that don’t know, we’ll link to Dave’s website but he documents everything that he eats. And then he has this very specific, he calls it the Energy Model, which is a model that, in his view, explains why people that are basically in a state of ketosis or on a low-carb diet often see…and this group is called lean mass hyper-responders who often see this huge uptick in cholesterol-rich LDL particle. Now, to be fair, you know, our team here doesn’t necessarily follow Dave’s model or agree with it. But I will say that it’s very cool that he has a model in the first place, I certainly don’t have a model of lipids. So I tip my hat to him for the work. But let’s talk a little bit about lipids. So…

Amber: Sure.

John: Where do you come down on this whole thing? I mean, I know you have basically a lot of the people in the low-carb camp are very skeptical that LDL plays a role in heart disease. Of course, I think we know that it’s more complicated than just LDL. Then there’s some people who are like, “Geez, man, you need to get your LDL, you know, cholesterol, you know, below 50 or you’re gonna drop dead,” kind of a thing. So what’s your sense of all this lipid-wise?

Amber: Right. So it’s kind of a perfect analogy to what I just said about finding ketones in somebody who’s eating a high-carb diet. Like, we would know that in that context, that would definitely indicate a problem. But because something like LDL has different mechanisms that can cause LDL to be, then you can’t necessarily tell which of those mechanisms is responsible if you do see LDL. And so that’s a danger of looking at one marker in context. So if you look at even the epidemiology that is all presumably based on high-carbers and you look at the LDL, it doesn’t seem to be…it is definitely associated with heart disease if you look at it just as an isolated marker.

But I think that that’s…you know, I have some background in data science, actually. And I think they if you look at that in isolation, you’re being misled by the weight of the people who are not representative of what you’re really interested in. If you look at only the cases where…and there’s no intervention from drugs, but only the cases where triglycerides are low and HDL is high, in other words, where there is not a disorder of insulin resistance, as far as I can tell, that correlation between high LDL and heart disease and other problems goes away. And so I’m very skeptical for that reason that LDL could be a problem.

The other reason is that going back to different mechanisms that can cause LDL to be high. There’s an idea that heart disease…that LDL is actually causal in heart disease. So you see this association over and over again, it’s very tempting to believe that this is reinforcing a particular causality structure that may have been an assumption in the first place. So if you look at the different roles of LDL in the body, one thing that’s not even controversial, it’s just hardly ever talked about is that LDL actually has a role in the immune system. It binds to pathogens. It takes on oxidation. And we know that what’s even more correlated to heart disease than high LDL is high-oxidized LDL. But the reason it’s being oxidized is that’s a sign that there’s damage there, that the LDL is being used to mop up that oxidation.

And so the hypothesis that I think is the most likely they would explain the correlation between high LDL and heart disease is that heart disease is endothelial damage. And the LDL is bringing cholesterol and bringing itself to the site to try to repair the damage, and that damage is ongoing in the end. So what I’m seeing the hypothesis or the school of thought that I would place my bets on is that the reason we see LDL there is because it’s actually a mechanism of protection. And if we blame the LDL, we’re actually blaming, you know, the firefighters.

John: Sure, yeah, no, I think that’s a very eloquent, you know, recitation of kind of the low-carb position on LDL, there’s a lot to get into in that statement. I think one of the interesting things is that you have this breach of basically the cells of the artery wall by sterol, so the LDL delivers that sterol to the artery wall. And it’s really the subsequent inflammation that causes heart disease in terms of the immune system reacting to something that’s not supposed to be there.

Amber: Right.

John: So I hear you there. My thing is…two things. One, I have never understood how you can through diet control for some oxidation in LDL particle, number one. Number two, I don’t understand in Dave’s Energy Model, how the cholesterol remnant…his model is basically you’re insulin sensitive, your triglycerides are low, but your LDL particle is spinning so much triglyceride for energy that at the end stage of that…because when VLDL particle basically drops off its triglyceride load, at the end of that process, it morphs into an intermediate-density lipoprotein. And then it becomes an LDL particle like an LDL apoB-carrying LDL particle.

Amber: Right.

John: And it maintains some of its cholesterol, you know, its predominant payload is triglycerides, but it maintains some of its cholesterol.

Amber: Right.

John: So that LDL that’s morphed from of a VLDL particle now into a cholesterol-carrying LDL particle is, in Dave’s model, responsible for the increasing cholesterol that you see in the low-mass hyper-responders. But the problem is, is that if you look at the science, as the patient becomes more triglyceride…the triglycerides go lower and the individual becomes more insulin sensitive, their VLDL production actually goes way down. And so I don’t understand how you can have remnant cholesterol be responsible for massive upticks in LDL cholesterol in these hyper responders because of the fact that it doesn’t respect mass balance. And I listened to Dave’s interview with Peter Attia, which I would recommend to our audience probably eight times. And I just couldn’t resolve for myself to answer this simple question, which is, where’s the extra cholesterol coming from in these lean mass hyper-responders?

Now, that’s a very technical point, we’re not gonna see eye-to-eye on that point, and that’s fine. But the question then becomes, were you comfortable having an LDL particle count or an LDL cholesterol number sitting? Because of the fact…and I asked it just to bring it back to a real-life example, Mikhailaa Peterson.

Amber: Right.

John: So Mikhaila Peterson, and this is where I’m so excited to just get very nerdy and talk about sitosterolemia because nobody wants to talk about it with me. And I know you’re gonna be willing to chat about it for a little bit. So it’s gonna be a nice thing to just be able. But Mikhaila Peterson, for the audience that doesn’t know, she’s a famous carnivore dieter, she has a very similar situation to yours, she’s obviously healthier on a carnivore diet, her father’s obviously healthier on a carnivore diet. And then she published her bloodwork, and her LDL particle’s in like in the 600s, which, I mean, that’s much better than my LDL particle, right? And I’m being very cautious about what I’m eating, you know, I’m somebody who’s more of a lean mass hyper-responder, like, I’m lucky if I can get my LDL particle into the 900s. She’s on a carnivore diet and her LDL particle’s in the 600s.

Problem is, the people that are in her camp, ideologically, would almost have to concede based on that number that she’s at an increased risk because she has low LDL particle because as we know, LDL particle has this crucial role in the immune system. And it’s so good for you and you wanna have it at 1500, 1600, 2000. So is Mikhaila Peterson somebody who’s thriving on a carnivore diet or who is immunosuppressed because she’s on the carnivore diet?

Amber: Right. So there’s a whole lot there that I wanna respond to. But let me first just say, I’m not pretending I know the answer to this, like, we have these different hypotheses. And I think the best thing what we can do right now is to figure out how to test the hypotheses because we don’t know, we just don’t know. I wanted to say something about the LDL production going down when you’re on a high-fat diet. That’s true and it’s not.

John: When you’re insulin sensitive. I know Dave…

Amber: When your insulin sensitive, right.

John: Right. I know Dave would say that if you’re in ketosis, you’re spinning out so much of the LDL particle. Yeah.

Amber: Right. So one of the things that he did in his work that was really eye-opening to me is to show the difference between…because we’re already talking about a low-carb baseline background. But the difference in LDL, which, as we talked about, is kind of a marker of there having been the LDL, it goes way down if you eat a whole lot of fat compared to if you fast, right, those ends of the spectrum. So I think that that’s really part of the crux of his whole theory. And I probably, I mean, I definitely don’t understand it as well as he does. And he’ll certainly correct me if he listens to this and I say something wrong. But I think part of the essence of that idea is that when you’re very athletic, so you’re the lean mass hyper-responder, kind of, quintessential, stereotypical type, what that means is you’re doing a lot of exercises, and you’re really making use of your fat stores as the source, just like in fasting. Whereas if you’re a high-carb dieter who is either sedentary or who eats a lot of fat, your LDL will actually go down relative to that phenotype.

And in fact, if you look at the data from Paleomedicina, which is a clinic in Hungary where they treat patients with a plant-free diet that is actually highly ketogenic, so it’s a limited protein, very high-fat version of a carnivore diet, they actually see what they call normalized LDL readings in their patients. They say that this very high LDL is actually something that they don’t see in their patients, it becomes normalized when they have patients who go from the regular carnivore diet to the very high-fat version. So maybe that’s too much of a diversion.

John: No, I don’t think…no, your point’s well taken. I mean, look, the more I researched, the more I realized just how much I don’t know, and lipids is a terribly, terribly complex topic. I think you’re right on. I mean, you know, I don’t we’re resolving the issue here. But I think it’s an interesting conversation to have in light of the popularity of the carnivore diet. And I feel like it’s my job for the people that listen, to say that our view is, is that you probably don’t wanna be walking around with an LDL particle count that’s heightened, even if you are in a low-carb, high-fat diet and feeling great. Because of the fact that, again, in our view, not your view, we respect your view, we respect Dave’s view, in our view, you’re at an increased risk for heart disease. And if the particle account gets high enough, you’re probably at an increased risk for death, in that condition, walking around in that condition, especially if there’s other biomarkers that are present.

Amber: Right.

John: And, you know, because at the end of the day, it’s just about clueing people in and saying, “Hey, believe me, don’t believe me, call me an idiot. Go ahead, fine.” You just have to decide, you’re gonna have to decide who you believe. And then you’re just gonna have to just roll with it, you know. And so it’s just another little piece of the puzzle in a much broader conversation.

Amber: Absolutely. So when I had those labs done in 2013, after 5 years on a carnivore diet, and I was, I feel like, one of the healthiest times in my life, actually, my LDL-P was over 2000.

John: Okay.

Amber: Right now, the latest reading that I’ve had in the last few months, it was, I think it was around 1400.

John: Okay, that’s…

Amber: So that may have been a peak for me. But yeah, I’m definitely walking around with a high LDL-P. And I don’t know if that’s increasing my risk of heart disease. As we’ve already discussed, my hypothesis is that I’m not, but I could totally be wrong. And anyone who wants to try a diet that is going to put their LDL-P high has to make a decision for themselves. Either they don’t believe that it’s a risk, or they believe it’s a risk and it’s worth the trade-off, or don’t do it, you know.

John: Right, for sure. Absolutely. I mean, yeah, well, in your case. I mean, look, you’re somebody who one of the things I was so excited to have you on the show is it’s obvious following you watching the interviews that you do, you take a very measured position, you do a ton of research, you are obviously very knowledgeable. And you’re somebody who said, “Hey, look, I need to make this intervention so that I can feel good, and I can feel happy.” And you know, 100% respect to that. LDL particle 1400, it’s not even that high. I don’t know percentile-wise, like, where that sits but that’s not like an off-the-charts high LDL particle. But speaking of that, so I mean, Mikhaila Peterson is somebody who is, you know, one of the poster children for it, and I know she spoke at your conference.

Amber: Yeah.

John: What do you think…So one of the things that because there’s that show “Diagnosis” where I believe it’s like you basically have these strange conditions and then people just kind of throw their ideas into the hat and guess, hopefully in an educated way, what the issue could be. And when I heard about that, having done a bunch of research on like the ABCG8 and ABCG5 genes, which are basically just like how you’re absorbing plant sterol…

Amber: Yeah.

John: ..I thought, “Man, I wonder if like Mikhaila Peterson and the Bell brothers who have complained about these joint issues have this rare genetic condition called sitosterolemia.”

Amber: Right.

John: Which is characterized by absorbing…because usually, you’ll eat avocado, there’s sterol in the avocado plant fat, you temporarily absorb it, and then your gut kicks it back out.

Amber: Right.

John: But in people that have this mutation, they just mainline it, they’ll just keep absorbing it, you know, in perpetuity, and they get these xanthomas which are these fatty deposits in their joints, and it messes up their tendons. And there’s a lot of history of joint problems, which is exactly what Mikhaila Peterson had.

Amber: Right.

John: Have you seen anything around like sterol absorption? Is that about been on your research radar at all?

Amber: Not really. So I have a few things to say about that idea. One is, it’s a really neat idea. And it could be part of the answer for why carnivore diet is so helpful in these specific cases, like, definitely Mikhaila seems to fit that picture. A lot of people have joint problems that get resolved through a carnivore diet. My hypothesis heretofore about why a carnivore diet would help with joint problems is from a kind of more general relief of autoimmune-like conditions tied into intestinal permeability, but it could be a combination. I personally have never had joint issues and definitely never any xanthomas. I did get…you know, I mentioned that my first bloodwork was very comprehensive. It didn’t have everything that I wish that it had but I did get some sterol markers.

John: Oh, you did?

Amber: Yeah. I’ll tell you the numbers, I don’t know if it would mean anything to you off the top of your head. But I have four markers here, campesterol was at 3.29, sitosterol at 1.71. And those are both marked as in the optimal range, not the hypo range. And then I have, I’m not sure if it’s pronounced cholestenol [SP] or cholestenol, that’s marked high at 7.21. Yeah, I guess the others are just ratios.

So in the context here, I had been on a carnivore diet for five years, but I was drinking coffee. And I’ve been drinking coffee most of the time on this diet. So I don’t know like, where did those even come from? If you’re on a carnivore diet, the only thing I can think of is that they came from coffee. And I don’t know, this is another place where, gee, I wish I had the before picture. But that’s what I’ve got. So if that’s interesting to you, I can send you those if you haven’t written them down or you have more questions about it.

John: I think it’s interesting, I have the same reaction as you do is like where would you get the sitosterol?

Amber: Yeah.

John: Because for the people listening at home, there’s I think there’s some controversy in the field as to whether some of the sterol markers are used as proxies for how much cholesterol you’re making, you’re synthesizing. And then some of the sterol markers are basically for how much cholesterol you’re absorbing, but also how much plant sterol you’re absorbing. So that’s really interesting that you would have even…you’d think they’d be, like, in the basement floor.

Amber: Right.

John: Well, that’s beyond my knowledge on that one.

Amber: Right. And that’s something maybe we can get more information about later if we try some targeted experiments. Are these levels as high as they are because I have sitosterolemia and if I had any more, they’d be through the roof? And this is like, they’re low because that’s as low as they get with coffee, I don’t even know. I think what’s really important here, what’s really cool is you’ve got this idea and now we can try to come up with some way to test it, test the hypothesis, and figure out who it’s affecting and how we would know.

John: Maybe we can try to do something at the next Carnivore Conference like bring some…because we have some ABCG8 and ABCG5. We have a sterol absorption report on our custom nutrition plan reports that gives you a window into some of your status for how you might be…of course, at the end of the day, you have to get your labs done. But you can diagnose sitosterolemia with just a genetic test. There’s some researchers around the country that are doing work on that.

You know, and then just another interesting little thing for listeners at home, I found a researcher in Utah who believes that if you have LDL cholesterol above 190…I think you could probably exclude the lean mass hyper-responders because that’s either coming from cholesterol remnant or it’s coming from greater synthesis of cholesterol or both. But he thinks that if you’re eating what would presumably be a diet that included some plants and sterol, that if you have an LDL cholesterol of over 190, then you have a prima facie case for sitosterolemia, which is super interesting. Because one of the things people don’t realize is, is that in your LDL cholesterol number, when you look at the massive cholesterol like in your particles, it’s not just cholesterol, it’s also sterol.

Amber: Interesting.

John: So you’re seeing like Mikhaila Peterson, like Aaron and I, who’s the geneticist and head of research of “Gene Food,” like prior to this show, we’re doing some chatting. And, you know, he’s not as in love with the sitosterolemia theory as I am, to be candid because he thinks it’s very speculative, but you just wonder what if Mikhaila Peterson had really great ability to clear LDL particle, like some kind of special, you know, maybe PCS-K9 variant that was very favorable for metabolizing fat, and then she had tons of absorption on the flip side of sterol? So I wonder what her LDL, you know, particle and cholesterol would look like if she was eating a bunch of avocado? That would be…I mean, she’s never gonna do it, obviously. But we could get some of those people tested for sterol absorption.

Amber: Right. So I guess there’s kind of two scenarios. One is sitosterolemia is really rare. And if you find out you have it, then you’re a good candidate for a carnivore diet. The other situation is, “Oh, it’s a lot more…it’s more graduated or more common or both than we thought it was. And so maybe there are more people who could benefit.”

John: Yeah, there is a case to be made. And you know, plant-based people and vegans who are listening are like literally like punching their car steering wheel and freaking out, but there is actually a case to be made. The problem is, you know, like you said so well, it’s like, you know, you’re lucky, you have these labs that you had a friend in Dave and his team that could get these labs. Most people don’t have access to these labs. Nobody’s getting their sterol panels done because those sterol panels on the sitosterol side, again, proxy marker for cholesterol absorption, maybe not even that reliable. But what it does straight up tell you is it tells you that you have this plant sterol in your blood. And if you have a lot of it in your blood…I mean there’s a good “New England Journal” medicine study that shows that basically, oxidized plant sterols bind preferentially to LP(a) which is a particularly dangerous form of the LDL particle. So it’s like, yeah, this is stuff that…And in that case, avocado and nuts and seeds, and all the plant fats are not really that good for you.

Amber: Right.

John: They’re not, you would be better off eating more meat, and you probably would be, you know, better on a diet that was more carnivore.

Amber: Right.

John: Let’s get into some of these other issues because you’ve done a ton of research on, for example, gut health. You know, I know there’s a lot we can learn from you on butyrate production. Tell us because a lot of people are thinking, “Well, where are you getting your fiber from?” I know, that’s a big one for you and there’s…yeah. So tell us your research there.

Amber: Sure. So, fiber is a funny one because, again, we have this whole epidemiological base that says, “If you’ve got more fiber in your diet, it looks like you might be better off.” But there are so many reasons why that might be true, what my favorite explanation actually is that fiber is itself a marker of lack of processing, or refinement of carbohydrates. And so my favorite theory about why the epidemiology might show a preference for higher fiber diets is that it’s not so much the fiber itself that’s actually creating the benefit. It’s not refining your carbohydrates in the fiber would be a marker for that.

Of course, we also have evidence from other societies, if you look at you know, just historically, the Inuit obviously didn’t have a very high-fiber diet. The planes’ Mongolians didn’t have a very high-fiber diet, it’s definitely not a deal-breaker for health. And then you could also look at carnivores, like real carnivores, the other mammals that eat only meat, they have colons, you know, felines have colons, it’s definitely not the case that they’re suffering from their lack of fiber.

So I think that kind of information is at least enough to make you pause and think, “Wait a minute, where’s this assumption coming from?” But most of the benefit, if you look at the research that is used to advocate for a high-fiber diet comes from the short-chain fatty acids that are produced by the microbes in your gut. And people talk about especially be butyrate how important those short-chain fatty acids are.

I would argue that, first of all, you don’t need plant fiber to get butyrate because your microbes are very much adapt to what the environment you give them is. And so there are many kinds of microbes that can produce butyrate that don’t do it from plant fiber, they do it from amino acids. Or from, I’m losing the word, collagen-like materials that are in animals, for example. Or even achromasia, which goes higher in people who are on fasting or a ketogenic diet is butyrate, it’s actually a butyrate-producing microbe that then can give that butyrate to the gut.

There are many…I’ve written about this, and I’m trying to remember exactly all the pieces. But if you look at, for example, Crohn’s or IBD-related diseases, there was this hypothesis that butyrate in fiber specifically would help with that. But what you actually find is that once you get to the point where you have that kind of problem in your colon, your colon is not absorbing the butyrate, that’s the real problem. So adding more fiber at that point tends to be more of a hindrance than a help. And then the other part of the picture that I find really fascinating is that a lot of the benefit that comes from that butyrate seems to come from the metabolites of butyrate once your colon has absorbed it, and guess what that metabolite is, it’s beta-hydroxybutyrate.

John: I saw some of the stuff you wrote about that. It’s really interesting.

Amber: I don’t think we know all the answers. But I think there’s enough questions that I would need to see a lot more evidence to show that fiber was actually necessary, in the way that mainstream health suggests that it is.

John: Right. So what I hear you saying is that what you’re seeing with people that eat a ton of fiber is that they’re not eating a lot of refined grains, pancakes, pretzels, etc.

Amber: Right.

John: And I also understood as I was looking, reading some of your stuff for the podcast, that you’re basically saying that in a state of ketosis, we’re gonna have adequate butyrate, is that accurate? Or is that expressing the theory properly?

Amber: Well, not exactly, and there is a bit of a disconnect. So you’ve got the side where the butyrates coming in, you can’t really get ketones there. You can get ketones on the other side, like on the bloodstream side. So what I was suggesting in that article is that maybe the benefits that we’re seeing that are associated with butyrate have to do with the beta-hydroxybutyrate, that it is immediately metabolized into as soon as it gets across the cell wall. And so for example, part of the mechanism that we think is important with butyrate is that it’s an H deck inhibitor, but so is beta-hydroxybutyrate.

John: Okay.

Amber: So, if you drill down into where the mechanism of benefit is, it seems like in many cases, at least, the beta-hydroxybutyrate, the end result of that butyrate is actually where the benefits coming from. And we know how to raise beta-hydroxybutyrate.

John: Ketones.

Amber: Right.

John: Or being in a state of ketosis.

Amber: Right.

John: Okay. That’s a great theory. Now, let me hit you with this. This is something that we traded e-mails about prior to the show. And this kind of jives nicely with the…so we came up with this individual that we think would do better on a more carnivore-style diet, which is somebody that has high sterol absorption or somebody that even has sitosterolemia. So Aaron and I came up with an individual, again, not a theory, just like let’s say this person is walking around. So they have low stomach acid, low hydrochloric acid levels in the stomach. And we’ve done some blogs on this, like, when you actually dust off the blood type diet, one of the super…one of the interesting things that you notice is that, although that diet doesn’t have a lot of, you know, evidence behind it, your levels of hydrochloric acid tend to correlate with your blood type.

So somebody who has type O blood is more likely to have more hydrochloric acid than somebody who has type A+ who’s likely to have the least. So let’s say there’s somebody that has type A+ blood type, and they do indeed have low levels of hydrochloric acid. They take an HCl supplement, they don’t feel any burning. You know, that’s one of the tests that some functional docs say you can do. So they have that, they have low levels of an enzyme called diamine oxidase which clears histamine, so they’re more prone to histamine issues.

And then this is the big one that I wanted to…for people listening, one of the interesting things about nutrigenomics is that you find these different levels of enzyme activity based on people’s genetic variability. So there’s a process called the urea cycle, which was responsible for removing all of the waste from animal protein, the nitrogen molecules, and animal protein. It’s turned into ammonia in the liver, and then it’s turned into urea in the kidney, and then you basically pee it out. Well, there are children that are born with zero urea cycle function, meaning they cannot metabolize any protein. So the minute that they have any protein at the beginning of their lives, they get very sick. And there are some theories of nutrigenomics out there, there’s markers like CPS1 that tend to indicate that we as a population have wide disparities in how much urea recycle function we have.

So, Amber, you might be able to effectively break down these waste products of protein metabolism very well. Me, John, I might not do as good of a job. So I might start to have an ammonia build-up. You have Amy Yasco’s [SP] theory about basically ammonia neutralizing BH4, which is a nitric oxide precursor. So you have that person. So they’re eating the animal flesh, they’re not digesting it, it’s getting into the colon intact, just as the fiber does, which is one mechanism for producing butyrate, it ferments and it starts to give off putrescine and it starts to irritate the lining of the colon and it starts to produce histamine. And that is something that has been theorized to be very deleterious to colon health. And that’s a person who’s walking around in a state of pain and anxiety after having gone on the carnivore diet, right.

So that’s the message that we wanted to bring to this conversation because there’s so much marketing that’s going on, you know, and on the vegan side too. Look, there’s all these propaganda films, but it’s happening now on carnivore, and people are just out there like, “All plants are bad for you, never eat them.” And what about this person who’s like, who shouldn’t be on the carnivore diet? And if you have anything to say about the urea cycle, any of that, that’s great as well.

Amber: Yeah. Okay, so, so many things there. First of all…

John: I hit you with a long…it’s a very long list. I’m sorry, we can take it one at a time.

Amber: It’s okay. I took a couple of notes while you’re talking so maybe I’ll be able to hit everything.

John: Okay.

Amber: So first of all, definitely, if someone’s got some kind of inborn error of metabolism, you all bets are off for like what everybody else should do for a healthy diet, right? You have to address it. If you’re phenylketonuric, you can’t have phenylalanine, that’s just end of story, right. So definitely, for people who have rare metabolic issues, you’ve got to address that, you’ve got to do what you’ve got to do.

Low hydrochloric acid is an interesting one, I don’t know that much about it, I know a little bit about it. What I think I’ve understood from the literature is that it’s actually pretty adaptable. And that you can get into a cycle where your hydrochloric acid is low and that makes it hard for you to absorb the nutrients to make more hydrochloric acid, and you can get into a bad feedback loop with that. So there’s some possibility that if you’re starting out with low hydrochloric acid, you may be able to improve that. I know nothing about the connection between blood types in hydrochloric acid at all, so I can’t really comment on that.

John: We’ll put in the show notes, we have an infographic that we did on it.

Amber: Okay, cool. The urea cycle thing, I want to just distinguish two things about function. If you have…if you do a measurement of creatinine in your urine, that can be a flag for poor kidney function, right? But it can also just be a marker of high protein intake. So it’s really important to understand the context if you see like, if you see measurements, that would indicate to you if you were an average person with average protein intake, that would definitely be a marker of poor function. But if we knew about you that you were eating high protein, then that worry goes away because that’s not the etiology of that marker. So I don’t know what your…

John: Do you mean, creatinine or creatine?

Amber: Oh, I’m sorry, creatinine, yes.

John: Okay.

Amber: Beyond that, though, and I also wanna emphasize that you can do a carnivore diet at a high protein level or at a low protein level, it all depends on how much fat you’re eating, right? So I mentioned Paleomedicina already, they are at the very end, high-fat end of the spectrum of recommendation, they think that high protein is actually…And when they say high, I think they would recommend that a person have no more than…okay, I’m gonna have to draw a figure out of the air, but maybe somewhere between 80 and 100 grams of protein a day. Whereas someone on a carnivore diet, the way that a lot of people practice it here in the U.S. it might be more like 200 or 250 grams of protein a day. So that’s a huge range of different kinds of ways of doing carnivore diet.

So you’re talking about this hypothetical person who has a hard time dealing with protein for various reasons, you can definitely…if they need to, I mean, we’ve got a lot of different things to balance here, but if this person decides that for some reason they would be better off without plants, they can still design a carnivore a diet that would not be stressing their ability to use protein. That’s all I wanted to say about that part.

John: Although protein, a more ketogenic-style carnivore diet.

Amber: Right. Now, it wouldn’t be super low protein. But I guess, you know, the difference between 20% protein and 35% protein could be a lot for certain individual.

John: Sure. Yeah, that’s a good point. On the urea cycle thing, that’s very exploratory. It’s just something that, you know, it’s a genetic explanation for why one person might thrive on a very high-protein diet and why somebody else might not. And it’s out there, you know, Harvard’s written some stuff about this and there are studies that are out there about some of these genes and how they can impact on blood pressure and things like that. So we’ve kind of talked about this whole butyrate beta-hydroxybutyrate issue. We’ve talked about high-fat, lower-protein carnivore diets. How important do you think it is when you’re on the carnivore diet to be testing to confirm that you are in ketosis if at all?

Amber: Ah, yeah, that’s a really interesting question. I think ketosis itself is more important for some people than other people. I mean, definitely, if you’re epileptic, you’re gonna want to keep those ketones high and you’re not gonna do any chance taking. I would say that most people who go on a carnivore diet and eat [inaudible 01:05:32] come to approximately something like 70% fat by calorie, and that’s usually mildly ketogenic. It’s not super ketogenic. But I think it’s over the point where Finney, for example, used to say that therapeutic benefits of ketosis start at around 0.5 millimoles. Last year, I heard him say that he thinks that, based on what they’re seeing now, he thinks it might be as low as 0.4. And, you know, this is just an arbitrary made-up number. But the point is that it’s not necessarily true that the higher the ketones, the better.

One thing that I’ve noticed in the carnivore community is that the people who seem to be getting the most benefit don’t see a correlation between ketosis and, like, low ketosis and high ketosis. And so for them, I think most of the benefit has something to do with removing something that for them is causing ongoing damage, which requires inflammation in order to heal it.

On the other hand, I’m fascinated with ketosis, I have been for a very long time just because of its amazing effects on the brain. And I think even someone who’s on a carnivore diet could probably experience extra benefit from being in ketosis sometimes, even if they don’t need to be in ketosis all the time to get, you know, the lion’s share of the benefit. I’d like to kind of decouple these ideas, the ketosis, I think most people are gonna be in mild ketosis on carnivore. Oh, and that kind of brings up another whole area, a whole can of worms. And that’s, I guess, the difference between fasting and a carnivore diet and the whole idea of timing and protein. The connection between all of those is how deep in ketosis can you get, how much autophagy can you get if you’re eating high levels of protein?

This question comes up a lot. And I think that one of the main ways to answer that has to do with how close you are to ketosis on your default diet, and how long you go between meals. So if you look at all of the literature on the benefits of fasting, or intermittent fasting, almost all of it is done in this high carb context. So in order to get to this space, where you’re getting autophagy, and cellular renewal, and all of these benefits that you would get from fasting, you have to stop eating for like three whole days before that really starts to come into effect.

So some people say, “Well, if you’re on a carnivore diet, you’re eating so much protein that you’re negating the benefits that you would otherwise have gotten.” But if you think about the fact that your diet is mildly ketogenic, say, and you eat a big meal maybe at 5 p.m. and then you don’t eat again until the next day, I would postulate…because you don’t have any of that glycogen, all of this postprandial kind of many-day process that you would have to go through from the point of a high-carb diet down into that sort of maximal ketogenesis where you’re starting to get these benefits, I would postulate that even on a high-protein, low-carb diet, you’re gonna be getting intermittently overnight the same kinds of benefits that people in a high-carb diet would have to go, you know, several days of fasting a month to make up for.

John: Interesting. Yeah, so for people playing along at home who might not have recognized that term autophagy, it’s basically this idea that you have, like, your unhealthy immune cells will die off and they’ll be replaced by healthy cells. And you’ll have a regeneration of stem cells when you go on like a…I think it’s like Valter Longo, you know, this, it takes days to do that. And what I hear you saying is because of the fact that you don’t have to go through the period where you get rid of all the glucose that’s in your system, all the kind of the sugar fuel, you can get…your theory is that you would be able to get into a state of autophagy faster basically in like a fat-adapted state than you would in somebody who eats carbs.

Amber: Right. And, you know, the mTOR and the autophagy thing is something where I think, to your purpose at the beginning of the sho where there’s this cross-talk between low-carb and veganism, there’s a sense in which we’re looking at different…we’re blind men feeling the elephant parts, right? Because mTOR can be inhibited by reducing glucose all by itself and mTOR can be inhibited by reducing essential proteins all by itself. And so I actually think that one of the benefits of going on a whole food plant-based diet can actually be this increased…Like I said, what really is happening is that AMPK is being up-regulated, in order to get some of those essential proteins out of your muscle tissue. But that whole process is the same pathway that leads to autophagy. And so I think this is one of the explanations why we can see some of the exact same benefits from a low-carb diet and from a vegan diet on the other hand.

John: Yeah, that’s it. That’s a really interesting point that you make, I think it’s a good one. I mean, as a layperson, when I read the research of people that have done research on, you know, mTOR, which is known as the, like, cancer, like, growth pathway in the body…And the even Valter Longo’s research, who’s the head of Longevity at USC, some of our listeners may have heard us mention him before, he has a theory that basically certain amino acids are pro-inflammatory because they increase insulin-like growth factor, and then that turns on the cancer pathways. And that’s his case against eating a diet that’s high in protein. But at the same time, you know, Amber’s point is well taken, which is that you know, spikes and insulin tend to do the same thing.

To zoom out from a less kind of biochemical focus perspective, the way I always read that research was, is what I hear the researchers saying is they say, “Spikes in insulin will do this and these amino acids and protein will do this, like methionine and leucine and the branched-chain amino acids. They’ll both do it but, you know what, we think that the protein amino acids probably do it a bit more. And so we’re gonna side, in our view, on protein rather than carb restriction. We’re basically just gonna say manage your insulin spikes by not having super high glycemic carbs. But then keep the real bad guys or the inflammatory amino acids found in these proteins.” Is that a conspiracy theory on behalf of plant-based movement to destroy and dominate the world? It could be, I don’t know. That’s how I’ve always read that. But I think that’s a great point.

Amber: You know, it’s really funny because I think you’re exactly right. I think the plant-based people say, “Oh, it’s the protein,” and the keto people say, “No, it’s the glucose.”

John: Yeah.

Amber: And they’re actually both right. But they’re both right in this beautiful way in that it’s not that you need to reduce both, you need to reduce one or the other, either one actually works.

John: Huh. Okay. Interesting. So pick your side and go with it.

Amber: Yeah, and then you’ve got consequences to deal with on either side. So obviously, I don’t think personally that a vegan diet is sustainable in the same way that a carnivore diet that I think a carnivore diet is, and one of the reasons is that the way that a plant-based diet…There’s a paper, 1999 McCarty, I think, showing that the way that protein deprivation in vegans can have this positive effect is through up-regulating glucagon. But the problem is you need to have the anabolic phases, you can’t just never grow, you can’t just continue to deplete your protein resources. So that’s why I think that long-term veganism can have an issue that long-term carnivore wouldn’t have. Long-term carnivore might well have other issues, and we just don’t know them yet. But that’s the lens through which I’m viewing it.

John: Well, you mentioned that word anabolic because, I mean, that’s part of the reason why some of the kind of the more like CrossFit kind of bro community loves carnivore because you know what carnivore will do for you? It’ll put muscle on you, that’s what it will do. I mean, it definitely well. If you start eating a bunch of chicken and steak, I mean it’s just like, that’s a definite. So I mean, that’s one bonus, like you said, is that that a trade-off? I don’t know, I feel like another part of these conversations is nobody wants to acknowledge there are trade-offs.

Amber: Right.

John: You know what I mean? It’s like, everybody’s diet has to be perfect. And anybody that brings up, they’re like, “Well, this could be a trade-off.” It’s like, “No, that’s not a trade-off, that’s junk science. That’s a terrible study. That’s epidemiology or, you know, that was funded by X and Y study, we’re throwing that out, just go away with that.”

Amber: There are trade-offs. And there are personal trade-offs that have nothing to do with wellness actually. Like, if I really value being able to eat some kind of traditional food or going and visiting some country and eating what they eat or having a cake on my birthday, you know what, that’s my decision, like, it doesn’t make my diet worse like, it’s just a choice that you personally get to make.

John: For sure.

Amber: I’m really pro-choice.

John: I agree. It’s a very kind of, you know…I have in my notes, there’s basically two topics I wanna close on. One of them I wanna get to at the end is gout because I think it’s just an interesting…and you’ve talked about your [inaudible 01:15:59] and all that. I definitely wanna get into that. Just to riff on that, though your point you just made it, I mean, is this issue of freedom, I feel like a lot of the really hardcore carnivore stuff that’s out there on YouTube, I don’t know if you’ve dipped your toe in that water, it’s some crazy water. It is some stormy seas. Like, carnivore YouTube is crazy. Vegan YouTube is crazy. But I feel like it’s sort of a backlash against what people perceive as being…you know, it’s almost like second amendment carnivory, right. Like, you’re not taking our meat away from us, we’re gonna eat our meat. Like, don’t you even think about it. And not only are you gonna think about it, but I’m gonna kick your ass on the science too. And I’m gonna dig up, you know, 15 studies they contradict your sort of like agenda and boom, like, take that nutritionfacts.org, like, see how that tastes. You know, I feel like that’s part of the deal here.

Ambre: Yeah, I haven’t actually spent a lot of time in either those YouTube communities.

John: Good, don’t start. Don’t do it, it’s not a good idea.

Ambre: Okay. Thank you.

John: Yeah, you’re not gonna like what you see, yeah.

Ambre: Reinforcing the idea that I don’t need to.

John: But then the last thing I’ll say is I do have concern for…because you’re in Boulder. You know, Boulder is like the mecca of all these different health…I mean, you can walk out your front door and I’m sure you find like amazing acupuncturists and farmers markets. I love coming…my buddy and I were in Telluride a few weeks back, like Colorado is such an amazing place for wellness and such an awesome state. People that go onto these diets, though, like you said, the expense of it, it’s gonna, by definition, have to support factory farming. And I think even the people that are very pro ability to eat meat in pro-regenerative farming using animal agriculture have to admit that there are externalities that are not accounted for with the way that these animals are raised. And they’re raised in incredibly brutal, awful, terrible ways. And not only that, they’re being given antibiotics at such a rate that that’s probably the place where some kind of superbug would originate, would actually be from, you know, raising pork or raising beef. So how do you square that whole environmental piece with this lifestyle?

Amber: I definitely think that there are problems with factory farming and that we need to address them. No question. I do think that animal livestock is a really important part of the global ecology and that we shouldn’t try to throw that out. And I don’t know, I think there’s a lot of work to be done. But I think there’s a lot of work that can be done to make farming more sustainable. But I also think that if you’re in a position where your health depends on meat and your you’ve got limited resources, you have to put your own mask on first. Because, you know, if I think back to the kind of mental state that I was in before I found carnivore, I was dysfunctional, like there’s no way I could have made a positive impact on the world. It was hard enough for me to just live my day-to-day life.

Whereas now, I feel like I’m in a position where I can help solve, I mean, in my own small way, whatever I’m gonna do, help make the world a better place. But until…there’s a bit of a bootstrapping thing where you have to get your nutritional elements in place, however you’re going to get them, before you worry about like just iteratively one step at a time, make it better.

John: You know, you have to take care of yourself before you can care for others. I think that’s a really thoughtful point there for sure. It’s almost like we’re kind of advancing towards maybe a day when you used to have your medical marijuana card, maybe now you’re gonna have like your carnivore diet card. Like you have the reasoning behind why you’re eating this diet and it’s kind of like you’re gonna get more of your meat ration once all the meat gets taken away and we’re all eating, you know, tofu and the impossible burger for the ballgame.

Okay, so last thing we’re gonna touch on is uric acid. When I first started digging into this, I was like, you know what, it’s very simple, uric acid is…you know, putting my smart hat on, I’m like, “Well, uric acid is a metabolite of purine. And purine is in purine-rich foods. And if you eat a ton of purine-rich foods, you’re gonna have high uric acid and that’s gonna lead to gout, and that’s gonna be terrible.” And then once I did my research, I realized actually, the body makes two-thirds of its own purine. And Aaron dug up these genetic markers where, you know, if you have one of them, you have like a 32 times increased risk for developing gout and another marker where it’s based on uric acid reabsorption. Another one you had, like it’s a haplotype, like 3 genes, 92 times increase for gout.

And then the last thing before I pass the mic is on carnivore YouTube, he vacillates back and forth, this guy’s channel is called the “Vegetable Police.” And he’s hilarious, he basically does all these diets. He’s been trying to heal colitis. And he went on the carnivore diet for nine months and he got gout. And he had to be on crutches and the whole nine, right. So you’ve lectured on this at conferences, what’s your take on the whole meat to gout to uric acid issue?

Amber: This is one of my favorite topics, in part because I did just give a presentation on it at AHS in San Diego. So it’s a little fresh in my mind, but I didn’t talk a lot about gout. But gout is one of the first things you think of with uric acid because it’s associated with high uric acid. But the truth is that high uric acid itself does not prove that you’re gonna get gout. Most people with high uric acid don’t have gout. And people with gout, there’s a large minority of people with gout who don’t have high uric acid. So there’s definitely more to the picture than how high your uric acid is. In fact, lowering uric acid can predispose people to getting gout.

And I think that unless I just haven’t found the right area or pocket of research, I think we don’t know a lot about what causes the uric acid to crystallize into the joint, which is what gout actually is. So you could just have high uric acid and be humming along fine but once a crystal forms then it attracts more crystals to it and then it deposits in your joint. And then that’s absolutely, I’m told, excruciating. It’s been compared to childbirth. In fact, it’s been compared as worse than childbirth…

John: Wow.

Amber: …by some people.

John: For the kidney stone or for the…?

Amber: No, for gout.

John: Okay, wow.

Amber: So there’s some unknows about that, like you said, the amount dietarily from eating purines only contributes a small amount. It can definitely contribute. One thing…So humans, one of the reasons I got really interested in Uric acid is that humans, in large part because we’re primates, we have high uric acid because we don’t…on the one side of it, we don’t have uricase, none of the primates, none of the great apes, that is, have uricase. So we don’t break down uric acid into allantoin to get rid of it. And so that puts us at higher risk. And there are all these theories about what was the advantage to not breaking that down? And there are all kinds of theories. One is that it’s kind of an intellectual stimulant, it’s related to caffeine. And there’s some evidence that it could be contributing to a certain kind of use of intelligence in that way.

Another is that it’s very connected with our vitamin C. So another thing that primates don’t have, that most mammals do, is the ability to generate their own vitamin C in their bodies. And it turns out that animals that don’t have uricase have really high proportions of uric acid compared to vitamin C, and there seems to be this reciprocity of function that’s happened. And uric acid potentiates vitamin C, so it makes a small amount go a longer way.

But there’s one other species or set of species that is similar in that way, and that’s birds don’t have uricase. And some birds don’t have vitamin C synthesis either. But even the ones who do, so if you look at carnivorous birds, they have high uric acid like all birds do. I looked at one study, they were looking at peregrine falcons. And their baseline measurement for a couple of falcons that they were looking at was similar to very high-end uric acid for a human around 6.5. And that bird ate a meat meal, a typical meal for them, and their uric acid shot up 3 times the level to like something like 24. And then, of course, no gout, presumably they do this over and over again. So that’s another example of high uric acid not necessarily being a problem.

John: I see. Okay.

Amber: The focus of my talk was to think about uric acid gets a bad rap because it’s associated, again, with metabolic syndrome. And in the context of that dysfunctional insulin sensitivity, it may actually be exacerbating things. But there are three ways that we can raise our uric acid. One is from eating it. One is from tissue damage because tissue damage, like if you’re going through chemo, your uric acid might skyrocket into dangerous levels because basically, you’re eating the same purines except they’re from your own tissue, or from the tumor tissue.

John: Or you’re “endogenous,” the purines you make are going up, basically, is that…or they’re being spun off by some cell repair or something?

Amber: So it’s like you’re eating your own tissue and you’re eating the tumor tissue because it breaks down but it goes immediately into your bloodstream. So it’s kind of the same as if you had eaten some organ meat, but you’re eating it from the inside. It’s not a normal thing but tissue damage can do that.

John: Okay.

Amber: Then you’ve got heightened uric acid just from up-regulated gluconeogenesis. And I think that this is what explains…there’s been at least some study of different diets and what their uric acid was like. And you might have expected that meat-eaters, not carnivores because, of course, they didn’t have those, but like omnivores who eat meat to have the highest levels of uric acid, and they did have a higher than vegetarians in the study, but they didn’t have higher than vegans. And the authors didn’t suggest this, it’s just my own speculation, but I think it comes back to that same thing that I mentioned in that other study where if you’re not getting the same level of essential proteins, your glucagon goes up, it causes your gluconeogenesis to go up, and you’re basically breaking down your own tissue. And that’s what I think is the source. The same thing happens in diabetes. Diabetes is actually characterized by out of control glucagon that’s causing you to breakdown your muscle tissue for energy when it should be getting it from other places.

But then the third way that you can have high uric acid, and we only see in this transient adaptation either to fasting or to a ketogenic diet, you get this initial rise in uric acid. And this is actually if you are prone to gout, this can be a dangerous time. If you’re just humming along and then you go into a ketogenic diet, your uric acid levels are gonna go up higher in that period. And if you’re prone to gout, I would highly recommend that you take potassium citrate or something to equalize.

John: Right, alkalize the urine. Yeah.

Amber: Right. But in this case, it’s not a matter of purines coming in, it’s a matter of the kidney excretion competition. So suddenly, your kidney’s filled with the normal level of uric acid that you had all along, maybe more if you’re also adding more meat. And then ketones, at the same time, they’re competing for these transporters to get them out. And so Stephen Finney has actually suggested that this period, which takes maybe around six weeks, of which uric acid goes up and then it goes down back to baseline and sometimes actually a little bit lower, that is the true marker of keto-adaptation when your uric acid is finally normal again, that’s when you’re keto-adapted.

John: Okay. So you’re saying you could basically go on a carnivore diet, keto carnivore diet, and you would…and just I hadn’t mentioned this, but it’s just my opinion, but I think a carnivore diet where you’re at least in ketosis part of the time, it seems like the ketones have a protective effect. So that would seem to be the healthiest option. And then your uric acid normalizing is a sign that your body, like, metabolically has adapted to that. That’s really interesting.

Amber: Yeah.

John: Because that was one of my big concerns. I guess the way that I have always kind of thought of like, even like a vegan diet, I think there’s different landmines out there on a vegan diet, there’s obviously been more studies that have been done on plant-based diets than on carnivore diets. But I see them both is kind of like it’s like a playing field that has landmines. And a lot of people are gonna go through that whole playing field and not hit a single one of those landmines and they’re gonna be fine. But there becomes a greater probability that you’re gonna hit one of the landmines as, you know, these issues kind of come on the table.

I think gout and uric acid seems like…again, I know it’s a fructose metabolism thing, all the points you’re making about, you know, the way it’s metabolized in the body and how tissue repair and insulin resistance can cause all this stuff. But it seems like if you’re just mainlining the system and then you had a predisposition to begin with, you can end up like that “Vegetable Police” kid who, you know, was walking around on crutches on his YouTube channel after going on the carnivores diet for nine months.

Another thing to watch out for, I think, for people out there is even if you don’t develop gout and you have high uric acid, uric acid inhibits nitric oxide, the creation of nitric oxide in the body, so it could actually cause high blood pressure too.

Amber: Right. In fact, one of the earlier theories about why we have high uric acid in the first place, it was because we evolved in a low-salt environment, it was in order to keep our blood pressure up. And there’s some connection to maybe that would be more important in the transition to bipedalism.

John: I mean, we could go on and on about this for a lot longer, I know. And one of the things…definitely when I come to Boulder, we’re gonna meet up and have a steak for sure.

Amber: Sounds great.

John: I guess, like, what’s your final message to the audience in terms of…because you’re one of the very original people that was out there with the carnivore diet, you created the Carnivore Diet Conference. What’s the framework people can take away from all this conversation about, you know, when to try the carnivore diet and when not to try the carnivore diet? Because my sense of things is it comes down to whether you want the carnivore diet to be included as a nutrition policy, of course, there’s a ton of N=1 success stories. But it’s like, for me, I’m not yet ready to endorse it as part of policy because I don’t think there’s enough out there kind of showing that it’s safe in enough cases. So where would you…you’re gonna be obviously more favorable. Where would you draw that line?

Amber: Well, I have very mixed feelings about policy. And, yeah, I think that if we’re gonna build policy around advocating for something, then you need a very high level of evidence. But what I do think is that there are certain types of diseases that we have noticed that people seem to be getting benefit from. Those are autoimmune-type diseases, digestive disorders, and psychiatric disorders. And so I think if you have one of those diseases, a carnivore diet is an interesting experiment to try. I don’t know, of course, whether it’s safe in the long term or what kind of problems we might anticipate. But one thing that I’m quite sure of is that if you try it for 30 days, for example, you’re very unlikely to run into a nutrient deficiency or any kind of, you know, problem that you can’t recover from. And it could be extremely informative.

I also I wanna emphasize that I don’t think everyone needs to go carnivore. And I also don’t think that we should be worshipping this pure form of carnivory, like if I find out that I can regularly have cucumbers and lettuce and I wanna do that and it doesn’t hurt me, or even if it does hurt me and I decided that that’s the trade-off I wanna take, there’s no shame in that. I don’t think all plants are bad. I think that there’s no reason to go on an overly restricted diet for preventive ideas that are only speculative.

But I do think I would really like to advocate for is that we back off on our assumptions that it’s going to be bad for you. And that we acknowledge that a lot of the nutritional ideas that we have that would say that it’s bad for you, like the lack of fiber, for example, that we honestly don’t have the information to say that it would be bad for you. And what I would love to see is a lot more study that could help us tease those apart. I know that nutritional studies, there’s not a lot of incentive to do them. But that’s part of why I wanted to organize the conference is to bring together people to brainstorm about what are the easiest hypotheses to test and where can we go from here?

John: You mentioned the conference. So when’s the next conference coming up? Where can people find you online? What’s your website? All that good stuff.

Amber: Oh, yeah. Thanks for asking. So the next conference is going to be May, Memorial Day weekend, May 23rd and 24th, here in Boulder again. The tickets are not yet on sale, but the website is up, carnivorycon. And we’re now taking submissions because I really wanted to open it up to the community in the same way that the Ancestral Health Symposium does in order to bring more voices into the science. So if you have an idea for a research idea that you’d like to present, that’s where you should go now.

John: Okay.

Amber: And I have a couple of different websites, I should probably unify them at some point. But I have one that I originally made to just talk about very carefully scientifically-backed ideas about the ketogenic diet. And that’s called ketotic.org.

John: Okay.

Amber: And then I finally got up the courage to talk about this crazy all-meat thing that I was doing. And so it’s obviously I couldn’t back up things that I was talking about in the same scientific way, I could only give ideas. And so I made that site be called empirica, like empirical but without the L, and it’s a “.ca” because I’m Canadian.

John: Okay. So we’ll link to both of those.

Amber: I’m very active on Twitter. Far too active, probably, I need to give that up. It’s such time constraint.

John: Twitter is so scary. Talk about YouTube being scary. God, I just don’t even go to Twitter. Oh, I applaud your ability to get in on that.

Amber: Well, there are some really interesting conversations there. So that’s why I’m there.

John: That’s true. Well, we really appreciate you coming on and being such a good sport and chatting with us for so long. And we’ll look forward to seeing you at the Carnivore Conference in May and hopefully before then, and just really appreciate your time and your expertise. And thank you for coming on and sharing your story, Amber.

Amber: Thank you so much for having me. I likewise really appreciate, deeply appreciate that you’re willing to talk to someone who has some different views from you and some the same and try to find these points of commonality so that we can move forward together and stop all this senseless he said-she said kind of nonsense.

John: Couldn’t agree more. Very well said. That’s what we’re trying to do here, we’re trying to kind of highlight individual stories. So, but thank you so much.

Amber: Bye.

John: Bye-bye. The “Gene Food” podcast is our attempt to synthesize the latest developments in the fields of genetics, nutrition, and medicine, and offer you practical tips and stories you can use in your own unique health journey. If you enjoyed this podcast, you can find more information online at mygenefood.com.

John O'Connor

John O'Connor is the founder of Gene Food, host of the Gene Food Podcast and a health coach trained at Duke's Integrative Medicine Program. Read his full bio here.

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