Hey everybody. This is Dr. Chris Masterjohn of Chris MasterJohnphd.com,
and this is a special episode of Mastering Nutrition where Dr. Paul Saladino, Carnivore
MD came on my podcast, Mastering Nutrition, to talk more about the carnivore diet. So stay tuned for carnivore diet part two. This is Mastering Nutrition with Chris Masterjohn,
take control of your health, master the science, and apply it like a pro. Are you ready? Welcome to part two of the carnivore debate. This is a friendly debate between me and Dr.
Paul Saladino, carnivore MD. In this episode, we talk conceptually about
the carnivore diet. What is a carnivore diet? Is it a 100% all animal diet? Is a 90% meat diet, a carnivore diet, a carnivore-ish
diet, or a carnivore diet that you cheat on? And we talk about why it’s important to clearly
define the carnivore diet. Then we talk about whether a carnivore diet
is ancestral. Did we evolve eating a carnivorous diet or
an omnivorous diet? And so if we go on a carnivore diet now, are
we returning to our ancestral diet? Or is the carnivore diet a modern innovation
that has been invented because it has practical or medical utility. And what is that utility? Who is a carnivore diet for? Is it for everyone because we should all return
to our ancestral diet? Is it for ancestral diet enthusiasts, or is
it for people who have specific health conditions that the carnivore diet can be used as a therapeutic
strategy? And then we talk about keto. To what extent do keto and carnivore overlap? Why talk about keto in the context of carnivore? Is a carnivore diet intrinsically keto? At mildly keto? Is it intensely keto, or can it be both? And then we just transition into talking about
keto specifically. So who is a keto diet for? What is the clinical utility of a keto diet? And then we talk about whether a keto diet
is dangerous. Not in the context of whether it’s intrinsically
dangerous, but what are the potential risks for some people. And there, we talk about hormones, we talk
about sports performance, we talk about antioxidant defense and glycation, and we talk about acid
base balance. And because we talk about acid base balance,
we must return to the question of whether the Inuit have the metabolic disorder of a
CPT-1A deficiency nearly permanently fixed in their population. Whether they have this apparent positive adaptation
to, and genetic impairment in the ability to make ketones, whether they had that as
a protection against acidosis as I argue, or whether they have it for some other reasons
such as to promote warmth in a cold environment, which is Peter from Hyperlipid’s view. Make sure by the end, you check out my free
guide to getting your vitamins and minerals on a carnivore diet at Chrismasterjohnphd.com/carnivore,
and check out Dr. Paul Saladino, his work at carnivoremd.com, and his podcast Fundamental
Health. And without further adieu, let’s hear a word
from my sponsors, and then get right into the carnivore debate part two. This episode is brought to you by Ancestral
Supplement’s grass fed beef brain. Our Native American ancestors believed that
eating the organs from a healthy animal would support the health of the corresponding organ
of the individual. Ancestral supplements has a nose to tail product
line of grass-fed liver, organs, bone marrow, brain, and more. All in the convenience of the capsule. For more information or to buy any of their
products, go to ancestralsupplements.com This episode is brought to you by Ample. Ample is a meal in a bottle that takes a total
of two minutes to prepare, consume, and cleanup. It provides a balance of fat, protein, and
carbs, plus all the vitamins and minerals you need in a single meal, all from a blend
of natural ingredients. It’s available in original, vegan and keto
versions, portioned as either 400 or 600 calories per meal. I’m an advisor to Ample, and I use it to save
time when I’m working on major projects on a tight schedule. It keeps my brain going while I power through
the day, never letting food prep get in the way of my productivity. Head to amplemeal.com and enter the promo
code Chris15 at checkout for a 15% discount off your first order. Paul Saladino, Doctor, welcome back to the,
oh, actually I was on your show. Welcome to my show. It’s good to see you again. It’s good to be on your show, It’s good to
be on your show, Chris. It’s good to be here. So I think we should continue this friendly
carnivore debate. I think the way my mind works is to start
from the very basic level and build up on it or go down into detail. I think we should start at, what is a carnivore
diet? So I could see someone saying, a carnivore
diet is a meat heavy diet. A carnivore diet is a meat only diet. In your view, what does the word carnivore,
and when we talk about a carnivore diet, what exactly do we mean by that? Yeah, that’s a great question, man. It’s been defined a lot of different ways
over the course of history. There are some people who say a carnivore
is an animal of any sort that eats a large amount, and that number is kind of arbitrary,
more than 75% of their foods is animals. Colloquially, I think the carnivore diet is
defined as people who eat the vast majority of their diet as animal foods, and I think
technically, I mean, it’s not something that we’re really dogmatic about, but it’s basically
excluding all plants from the diet. Though in my book, I give space for this thing
called a carnivore- ish diet. Mostly animal foods with a few plant foods,
perhaps with attention to a spectrum of plant toxicity, and individual sort of sensitivities
to various plants. I think that perhaps one of the more interesting
parts of thinking about a carnivore diet for me is that it challenges the notion, I don’t
think you hold this notion, but I think this notion is held within functional medicine
circles. It challenges the notion that plants are invariably
good for humans, and starts to introduce this underlying idea that plants may have variable
levels of toxicity on an individual basis, and individual plants may be more toxic than
others based on the things that they harbor within them. I think that most people will not find the
concept that plants have toxins to be too strange. Though once we dig down into the details and
trying to find which things are toxins and which things not, there’s definitely some
disagreement about that. But I think most people, if they’ve heard
of lectins or oxalates or other frank neurotoxins in plants, they’ll say, “Oh yeah, plants have
toxins.” I go a little further in some of my work and
call into question a lot of the plant nutrients as perhaps toxic, and that’s where it gets
kind of granular. But at a high level, the carnivore diet is
just a fully animal-based diet. And some people have said whole foods animal
base, and I like that. It’s just like, “Hey”- It’s the answer to whole foods plant based. Whole foods plant based, right? Hopefully explaining this right. And I think that I don’t advocate for a carnivore
diet, that’s just me. Our first conversation is perhaps relevant
at this point to bring up. Our first podcast was kind of a drill-down
into the nutrients that we need as humans, and where they are in plants versus animals. And I think that one of the interesting things
that I learned as I dug more into that, was that you can get a lot of nutrients from animals,
nose to tail. And that was one of the things that I think
came out of our first meeting, and you can let me know if you agree with that. But when we’re talking about a ketogenic diet,
which we’re going to talk about today, people like Volek and Phinney have said a well constructed
ketogenic diet, quote unquote. And so I think you could adapt it to a carnivore
diet and say, “Hey, there’s a way to do a well-constructed carnivore diet with attention
to certain micronutrients. Rather than just eating a rib eye at every
meal.” These are things like iodine or calcium or
boron or biotin or riboflavin or folate, which may not always be adequate for humans in a
steak. So- Right. This is sort of like the phrase that the American
Dietetic Association wrote a position paper on vegan diets a few years ago, actually a
decade ago, where they talked about well-planned vegan diets. I think that’s kind of what you’re getting
at with the nose to tail thing, is a well-planned or well-formulated carnivore diet is, and
I think you and I agree on, I would say 80% to 90% that you can mostly prevent frank overt
nutrient deficiencies by eating nose to tail animal product. And we talked about this in detail on part
one, so we don’t need to completely go over it. But I mean, I basically feel that I’m skeptical
that you can get optimal amounts of everything even on a well-formulated carnivore diet,
but then again, what is optimal for each person is different. And so could very well be that some people
get what’s optimal on a carnivore diet. But back to the definition. Let’s pause there for a moment. And then we bring up questions around like
how do we measure optimal, right.? Yep. And if we’re saying optimal, we have to have
some sort of a metric. I think that the main point of contention
for most people, and what came out of the first discussion was vitamin C, which we don’t
have to really recapitulate here now. No, but that would be a great example. Yeah, I mean, that’s the one that stands out
for me. I didn’t take away, I mean, you can let me
know if there were other nutrients you felt like might not be optimal on a well-constructed
or intentional carnivore diet other than vitamin C. but I mean, vitamin C’s a whole rabbit
hole that we can go down or we talked about in the first podcast, but in the instance
of vitamin C, it’s like, how do we measure that? How do we really know what’s optimal? And I think that any discussions of optimal
have to have a metric, right? And in the case of vitamin C, we talked about,
do you measure 8-hydroxy-2-deoxyguanosine? Do you measure the peroxides? Do you have to do something really esoteric,
like measure oxidized to reduced glutathione? How do you know what optimal is? It’s quite an interesting discussion because
the carnivore diet certainly provides enough vitamin C to prevents scurvy, but then the
subsequent question becomes- A well formulated one, yeah. Yes. Yeah. Do we need more than that? So those are really interesting questions. Yeah. So coming back to this definition, I mean,
you don’t eat 25% of your diet as plant foods, right? No. And do you eat any plants? No. Okay. So I mean, if you’re sitting down at the,
I don’t know what kind of drink you’d have on a carnivore diet. Okay. You’re sitting down at the steak bar, right? With some guy who says- Topo Chico, [crosstalk 00:11:48]. Mineral water, yeah. Yeah, yeah. Sharing mineral water. And someone says, “Yeah, I’m carnivore. I eat 90% of my diet animal products.” I mean, do you go, “Oh, cool man.” Or do you go, “No, you’re carnivore-ish, I’m
carnivore.” No, no, I’m not going to be, no, no. No, I don’t literally mean next to that guy. I know you’re a polite guy, but in your sort
of intellectual definition, is a 90% animal diet a carnivore diet, or a carnivore-ish
diet? I don’t know that it really matters, to tell
you the truth. [crosstalk 00:12:20]. Yeah, I think it’s, go ahead. I think probably a 90% carnivore diet is carnivore-ish. Okay. If we’re getting right down to it, it’s probably
carnivore-ish, and just for the sake of simplicity. But I don’t think that’s not pejorative in
any way because- No, no, no. I mean- Because I think that people can, one of the
things that I think that we all rebel against is this dogma, and I mean, this is actually
kind of interesting because without being too judgmental, this is what happens in plant-based
circles or vegan circles as people will say. You aren’t really a vegan because you ate,
and that’s not what I do, or people tend to do within carnivores circles. It’s not like we’re going to say to somebody,
you’re not really a carnivore. Like I said, it’s more of this perspective,
where do we get most of the nutrients or where do we get the most nutrients? Where do we get nutrients to be optimal humans? Do plants have toxicity? Let’s think about that. Okay. And for some people, [crosstalk] plants, go
ahead. But there’s a pejorative way to define something
and a gentle intellectual way of doing it. Sure. I’m big on definitions, because I think that
semantics are super important and how we talk about things greatly impacts how we think
about them. And you brought up what vegans do, yes, there’s
vegans who might be dismissive of other vegans because they have the occasional animal product,
but I see the opposite problem. I see, for example, T. Colin Campbell says
in the China study that the ideal thing would be to restrict your animal products to no
more than 2% of your diet. And he says, “2% of your diet is so inconsequential
that you might as well just eat 100% plant foods.” Then Joel Fuhrman does something more moderate
in Eat to Live. He says that most people can live within what
he calls a 10% junk food diet. All animal foods fit into his 10% allotment
of junk food. And he says about 10% of people need more
animal foods than that, because they have digestive problems. Now, putting aside their actual claims, what
I want to point out is what they’re doing with the language there is they are dismissing
what could be extreme importance of minor components of the diet. So for example, in T. Colin Campbell’s 2%
of the diet plant food, you could have two oysters and a clam for breakfast every single
day on Campbell’s 2% of your diet- That’s animals. And yeah, and fit within the 2% of your diet
as animals. And that could prevent a zinc deficiency,
that could prevent a B12 deficiency, the 2% of your diet, you could sit down and eat four
grams of liver every day, or two grams of liver, one clam, one oyster for breakfast,
every single- Two ounces? Or two grams? No, two grams. Two grams of liver? Chris. Yeah, but listen, that’s not my point. If you eat two grams of liver, a clam and
an oyster every day, you are doing a great deal to prevent frank deficiencies of nutrients- Sure. That are primarily found in animal products,
because you’ve used that 2% very wisely. Joel Fuhrman’s 10%, you know how many nutrients
you can fit into your diet by eating 10% of your diet as the most nutrient dense animal
products? If you take all the organ meats and shellfish
and whatever else that you eat, and you make that 10% of the diet, you have completely
turned around the nutrition around zinc, around B12, around a lot of nutrients that are very
important to get from animal products. So when I look at that, I say, I’m not going
to call someone vegan if they’re eating a 98% plant-based diet, and then they’re deliberately
sitting down- Sure. To get 2% of their diet as the most nutrient
dense animal foods. Why? Because it’s not about the relative bulk,
it’s about the importance of that thing in a diet. In other words, if the contribution of your
animal products to your mostly vegan diet is the difference between irreversible neurological
degeneration having it and not, then that 2% was so profoundly important that you have
to call that diet, not vegan, right? So I think there’s a difference between a
carnivore who only cares about 100% animal foods, but occasionally cheats for the hell
of it, versus, if you sat down, you made a diet that was 90% meat, but then you said,
okay, the most nutrient dense plant foods that are rich in vitamin C and folate and
magnesium and manganese, I’m going to deliberately include 10% of my diet to cover all those
bases. Then I think, okay, carnivore-ish is an okay
term, but to call that carnivore I think would be misleading, because the plant foods are
so important in changing what the nutrition is. So the way that I would think about a fair
term for carnivore would be if everything that is important to your nutrition is coming
from your animal foods, and you’re only eating animal foods except when you occasionally
eat something that you don’t care about, that wasn’t important in any way to your health,
then that’s a carnivore diet that you sometimes cheat on. Whereas, a 90% animal diet and 10% really
important plant products that are making a really important nutritional contribution
to that diet, that’s a meat-heavy diet, not a carnivore diet. That’s how I see it. Yeah. No, I think that’s totally reasonable. And those discussions are super fascinating,
and we kind of went through that in the first talk because as we’re thinking about this
and we’re trying to see if the concept of an entirely animal-based diet is even viable,
and that’s again, that’s the first podcast or parts of it. Is there anything we’re really missing on
that type of diet? That’s a fascinating question. So going forward from there, I think one of
the things we should kind of try to reconstruct here is are we viewing a carnivore diet as
a return to the ancestral diet? Or are we viewing a carnivore diet as an idea
that’s developed in the last couple of decades? Or correct me on the timing if you want to
trace the history better than I can, but a new idea as a health hack or a medical treatment
for diseases. So, in other words, is this a new dietary
approach based on trying to achieve a certain effect? I guess they’re not mutually exclusive, or
is this the way we’ve always eaten until we messed things up and we’re going back to that? Which of those do you place more emphasis
on? I think they’re both important, Chris. And it’s impossible to really know how we
ate. And we’ll talk about some studies that might
give us some perspective, but as we talked about before the podcast, neither of us is
paleoanthropologists. So- Right. And I think there’s an interesting hypothesis
here. And ancestrally, the question is, if our ancestors
could access big fatty animals and eat them in their entirety, did they eat plants? Did they have a need for plants? Or, this is something that I’ve kind of asked
in my books and my writings and it’s just the hypothesis that I’ve suggested. Is it possible that given an abundant supply
of delicious wooly mammoth fat meat, organs, tendons, brain, eyeballs, whatever, we didn’t
really have a need for plants. And I have suggested that perhaps plants were
survival foods. That plants might have been selected by our
ancestors during times of scarcity. If anyone here has ever hunted, they know
that it’s pretty hard to always get something good. Maybe 80,000 years ago or a hundred thousand
years ago when there were tons of megafauna, we could, we could have an abundant supply
of animals all the time. And again, these are imperfect numbers, at
least within the last 20 to 30,000 years depending on the [condom] we’re looking at, there’s
been megafaunal extinctions. So I don’t think we know. But I think it’s an interesting question. If animals can provide us with everything
we need to function as humans, and again, that’s sort of an ongoing conversation, then
if we had access to animals, is there a need for plants? And the downside to plants is something I’ve
talked about a lot, though we haven’t talked about it a lot here. They have anti nutrients, they’re not always
benign. They’re not just totally friendly species. And throughout our history, at least recent
history, anthropology and ethnography, we can see that at least recent hunter-gatherers
went to great lengths to detoxify a lot of those plants in those situations. And so the corollary question is, so they
had a lot of animals, would they have even bothered to eat those plants? Maybe, maybe not. It’s an interesting- So, well, I mean, what do you make of the
correlation between latitude and animal product consumption? The data that I’ve seen indicate that basically
the further you go from the equator, the greater the animal and lower the plant consumption. You get up into the Arctic, and plants are
equal to, or less than 5% of calories. You get down to the equator and animal foods
bottom out at 36% of calories. So what I see when I look at that is that
first of all, no one’s carnivore or vegan. But it seems as though plant foods are becoming
more and more limited as you get into the Arctic, and the more plant foods are available,
the higher the plant food consumption is. And it does make sense to me that to some
degree, obviously, if there’s a giant animal that you can hunt and you get all your calories
from that, you probably won’t go looking for plant foods. But at the same time, it seems like at the
equator there are big animals, and people do hunt them and they do eat mostly those
animals for an extended period of time. But they also feast rather heavily on the
calorie and protein dense plant foods that are there. And there’s this famous story from one of
the Kyungsung, where an anthropologist asked them, and this is contrary more to agriculture
than to carnivory. But they asked them, “You see everyone has
developed agriculture around you, why don’t you develop agriculture?” And the guy said, “Why would we develop agriculture
when we have all these mongongo nuts?” But it seems like you could infer into what
they’re saying that by their behavior, they also say, why hunt another giraffe when I
just hunted a giraffe two weeks ago, just got done eating a bunch of giraffe, and there’s
a bunch of mongongo nuts right here. And that’s what their behavior plays out. So I mean, if plants are the choice that you
make when you don’t have animals, why are equatorial hunter-gatherer diets so high in
plant foods? The mongongo nut story is pretty interesting
actually, because the only reason they have access to that many mongongo nuts is because
the elephants can’t be hunted anymore. And they’ve changed the [crosstalk 00:23:39]. by the law? Yeah. By the law. And so I think that it’s a great question. The corollary question or the follow up question
in my mind is, are there really that many big animals left? Maybe they can hunt giraffes, I didn’t know
Kyungsung could still hunt giraffes. They certainly can’t still hunt elephants. I don’t know if they can anymore. I don’t think they can. There’s not a whole lot of big animals left. And I think about this all the time when I’m
out in the woods hunting as well. The animals we have on the earth now are not
very fatty. And as you know, the fat is pretty important. Well, either fat or carbohydrates are pretty
important to human nutrition. And I think of those nutrients is kind of,
one or the other or both are pretty essential. We can’t just eat protein. [inaudible] starvation and it doesn’t work. And so when I go out hunting, there’s nothing,
unless I’m going to get a buffalo on a special range, there’s not even big animals anymore. So there’s not a whole lot of availability
to get animal sources of fat. And perhaps there are big animals in equatorial
regions, but I’m not aware of them much anymore. I think that they can’t hunt elephants anymore. And in speaking with my friend, Miki [Vendor
00:00:24:51], he’s a paleoanthropologist, he was telling me that because they can’t
hunt the elephants, the elephants are overrunning the savanna, and they’re actually destroying
the baobab trees. They’ll break them down, they’ll crush them. So the elephants are changing the landscape
in certain ways. And- Do you know how old this phenomenon is? Because when I read Ethnography on the Hadza,
I don’t have the papers on hand, so I don’t remember how old it was. They were eating 20% of their diet as baobab. Right. [crosstalk 00:25:19]. Are the elephants overrunning them in the
last 20 years? Or is this like a century- I’d have to look, I’m not sure. Yeah. I think it’s just they can’t hunt the elephants,
they’re going to eat the baobab or the mongongo or whatever’s available, because they don’t
have the big animals. I mean, if they don’t have fat, this is the
question. So in the ethnography that I’ve read of the
Hadza, they consider baobab a food group. And I got the sense that like they say, “We
have to get enough of this, we have to get enough of this, we have to get enough of this.” And baobab’s in one of those things where
they say, “We have to get enough of this.” Yeah. And it seems like it’s extremely rich in calcium. And so my impression has been that the Hadza
used baobab as, sort of Americans use milk. The American government says, “Okay, where
are we getting these things?” And and you can criticize the industrial contribution
to the food pyramid slash my plate or whatever, but research indicates that we should try
to get, I think, about 1000 to 1200 milligrams of calcium a day. Americans are doing that from milk. It seems to me like cattle herders did that
for milk. Inuit did that from fish bones. Hadza did that from baobab. But so I mean, you’re thinking of, I guess
this is one of the problems that we have in general, is that we don’t actually have any
ethnographic data from a time when there was no contact with Westerners, because by definition,
Westerners made the ethnographic data. So, and I think we probably have a better
glimpse if we look at a survey of, the older we go back, the less and less the colonial
governments impacted hunter-gatherer and cattle herding diets and stuff like that. But we don’t actually have anything pure to
go on. And many people feel that, or I think it’s
a compelling suggestion that the landscape for these hunter-gatherers is different than
it might have been. So who knows? Yeah. One random point on that is, paleo people
often point to how historically when we transitioned from a hunter-gatherer to an agricultural
lifestyle, we got shorter. But the extant hunter-gatherers are shorter
than everyone else- Living now. Yeah. And so I asked Stephen [Geanne] about this
once, and his speculation was that the extent hunter-gatherers had been pushed into such
marginal environments that they’re basically on the border of food insecurity. Whereas, if you look back at the archeological
record, we’re looking at hunter-gatherers that have very robust supplies and nutrients. Although I have my own spin on that. When I read a collection of paleoanthropological
work, my impression has been that hunting and gathering was never able to sustain the
resource stress that occurred as hunter-gatherers multiplied. And it was actually pressure to centralize
and adopt agriculture to counter that that, Jared Diamond said that agriculture was the
biggest mistake we ever made. I feel like that’s kind of the wrong spin
on it. We were basically forced into agriculture. I mean, even you said, hunters made the megafauna
extinct. Well, you can only hunt something extinct
so long before it’s not a source of calories anymore. And so hunting, it works for awhile, but if
you increase your population density enough, you’re kind of forced into a more efficient
means of producing things. But- Yeah. That’s very interesting what you point out
about the living hunter-gatherers, and I do think it mirrors the suggestion that their
environments are maybe not what they used to be. I think there’s pretty good data that at the
agricultural transition at the time of the neolithic revolution around 10,000 to 12,000
years ago, depending on where we look on the earth, skeletons got much shorter, and we
can see this at the Dixon Mounds, there’s been a lot sort of published about the increased
incidence of parodic hydro restenosis and tuberculous lesions and shortening of femurs
and other long bones. So I do think that, at least from what I’ve
seen, we did get shorter with the agricultural transition, but the fact that the hunter gatherers- Well, we’re tall now. Well, we’re about back to where we were, right? So the average I think was like 5’9, 5’10,
and that’s about where it is now. 5’8. So… What an interesting point that you’ve pointed
out about the hunter-gatherers, that yeah, that does suggest that their environment is
probably not what it was, and we have sort of marginalized them and perhaps it was different. And then I’ll just say one more thing. The neolithic transition, I don’t think anybody
really knows why that happened. There’s a compelling hypothesis that you’re
referring to that perhaps we over hunted the megafauna. And the other one is meteoric events like
the Younger Dryas event or something creating mass extinctions. But probably, it was a major change in the
availability of foodstuffs that had been uniquely valuable for us. And we kind of referred to it earlier, at
least within the US, if we’re talking about the Dickson Mounds, which are in Illinois
or Ohio, there’s tons of buffalo, and I mean, that’s a big animal. But you can imagine, a wooly mammoth is three
times the size of elephant and a huge amount of fat. Well you said before, why would you eat plants
if you had big megafauna around? I mean, similarly, if having mongongo nuts
is a sufficient reason not to develop agriculture for the Hadza, then certainly having megafauna
is a sufficient reason not to develop agriculture. And I think that kind of, I mean, I don’t
have a doubt on hand anymore, but I did do a lot of reading on it, and I based my impression
that we were forced into agriculture on the basis that there was evidence for declines
in bone health prior to the development of agriculture. And then everything got worse, and then everything
got better. I view that as technology development. I mean I think if we look around us now, and
I mean, I don’t know who originally made this observation. Peter Thiel has pointed this out. We developed technology and then technology
causes problems, and then we develop new technologies to solve the problems caused by the old technology. But even though we always make problems, things
tend to get better as we go on. I mean, you could debate the net betterment
in agriculture. But I think what happened was, actually, I
think there’s a very good parallel with the Industrial Revolution. So in the Agricultural Revolution, you say,
“Oh, we can efficiently produce this grain.” And you’re like, “Well, this provides calories.” And you don’t know jack about the nutrients
in that grain. So you eat a diet that’s 90% wheat, or 90%
corn or something like that, and you wind up with profound nutrient deficiencies, because
you had no idea how to properly construct a grain-based diet. And you can debate whether a grain based diet
can be as good as an animal based diet, but it’s certainly the case that one of the worst
grain-based diet you can have, is when 90% of your diet’s just one grain. We did something similar, in the Industrial
Revolution. We started refining bread before we knew what
the vitamins were. So we produced this source of calories that
had no nutrition in it whatsoever. Things are better now that we fortify bread,
you can debate- … whatsoever. Things are better now that we fortify bread. You can debate the value of fortified bread,
but it’s still classical nutrient deficiencies were rampant at the time of the early industrial
revolution and industrializing food that are not now because we figured out how to live
with white bread. Maybe we don’t live as well as we would without
white bread but we figured out how to coexist with white bread in a way that we did not
figure out in 1925. And so I think that’s what we’re seeing there. I mean, we’re kind of agreed that the ethnographic
record is complicated to interpret because of the effects of Westernization throughout
the period where it’s been developed. So, I think that’s a good segue to go back
into some of the data on what we might be able to infer from prehistoric remains. So when I look at the prehistoric record,
I think one of the most compelling things, which we’ve talked a little bit about this
as we were preparing, one of the most compelling things is that the salivary amylase gene,
which functions to produce an enzyme in the saliva called amylase, which breaks starch
into glucose and it’s main function as far as we can tell is to allow when you eat starch
to allow a better glycemic response to it because you start breaking a little bit of
that starch into sugar. You activate taste receptors on the tongue
and that activates a preparatory phase insulin response. It allows a smoother glycemic response. So the higher your salivary amylase, the better
your glycemic response to starch. It’s a very starch specific adaptation because
its function is to digest starch and the data from multiple modern Western societies including
Japan, America, and Europe and from multiple hunter gather and non westernized societies,
whether those groups are starch eaters or not, the data indicates that about 99% of
all humans measured have duplications in the salivary amylase gene at least one duplication,
if not, five, six, seven duplications. The more there’s a history of starch eating
in that group, the more duplications there are. But even when there’s no known historic contribution
of starch to the diet, those duplications are still there. They’re not found in any of the other apes
except Bonobos, but theirs is inactivated and they’re not found in Neanderthals and
our falls are not found in Denisovans. So my impression from that is no one knows
when the salivary amylase gene was duplicated, but I think that data indicates that if it’s
so almost universal among all humans from very disparate ancestry… For example, like when was the last time that
a European had common ancestry with like a Hadza? I think this is back towards our most recent
common ancestor in that area. It’s clearly after we split off from the other
apes. It’s clearly after we split off from Neanderthals
and Denisovans. But it’s clearly before the most recent common
ancestor of all humans that have been measured. And since the humans that have been measured
are so disparate as to include European Americans and very highly isolated hunter gatherers
from Equatorial regions. This is indicating to me that it is way, way
back towards our most recent common modern human ancestor. And that doesn’t mean that we need to eat
starch, but it means to me that however high the amount of animal foods in our past diet
was, the contribution of starch to the diet must have been… If it was significant to derive a nearly complete
selective sweep for the duplication of a starch specific gene, it must’ve been meaningful
enough to say that that diet was not purely carnivorous. That’s how I see it. This is really fascinating, Chris. I was thinking about this. So the point that you make is really important
to note about the non presence of salivary amylase duplications in Neanderthal and Denisovans. And just so people understand, this is human
lineage and evolution. The way that I’ve learned this, and again,
I’m not a paleo anthropologist, is that probably we diverged from apes about 6 million years
ago. I did a podcast with Bill Von Hippel about
this, and there was this East African rift Valley, perhaps half of the rift valley moved
up when there was this glacial or this tectonic plate shift and the rift valley raised. The forest essentially changed to Savannah
and our ancestors moved out of the trees 6 million years ago as Australopithecus. Then we went through a series of increasingly
human looking people with homo habilis, homo erectus, homo heidelbergensis. And the way that I’ve understood this is that
many people believe that homo erectus, which is around about 1.8 million years ago, was
probably the precursor for the Denisovans and the Neanderthals and that that’s the precursor. And that homosapiens only showed up 500,000
years ago, 350,000 years ago. And so we share a common ancestor with Neanderthals
and Denisovans, but it’s not believed now that Neanderthals and Denisovans evolved from
homo sapiens. And I think that’s fairly interesting. And then our ancestors, homo sapiens, evolved
somewhere in Africa, this fertile Eastern part of Northern Africa. And then the stuff that I’ve suggests that
our homo sapien ancestors left Africa about 70 to 80,000 years ago, maybe even sooner,
50 to 60,000 years ago, moved up into Europe and at that point encountered Neanderthals
who were there as homo erectus descendants who’d been there from before and then moving
east encountered Denisovans and other races of people who are also descended from homo
erectus. And so what we’re doing when we encounter
those people 50 to 60,000 years ago, is coming back into contact with homo erectus lineages. And so I think you’re right. I think it is interesting to note that we
all have the salivary amylase duplication and somewhere in that homo sapien lineage,
we probably got it. Now the key question for me is when did we
get it? And I don’t think we know when we got it,
but they left Africa for some reason. I think this makes sense almost in the context
of what we were talking about before. Was it a scarcity of large animals, and an
increased reliance on tuberous vegetables or need for starches that led us to move out. That would make sense to me. But the other really interesting thing about
the salivary amylase duplication is that for the vast majority of our evolution as humans,
we didn’t have it. Neanderthals don’t have it, Denisovans don’t
have it. Homo erectus doesn’t have it. Homo habilis didn’t have it. Homo heidelbergensis doesn’t have it. And to me that suggests that we were not eating
many starches up until sixty to seventy thousand years ago, or if they were, why would you
get a salivary amylase duplication if you are eating… 70,000 years ago, if you start eating a lot
of starches, that makes sense. That’s a selective pressure to have a little
bit more of an advantageous genetic polymorphism. But the three, 6 million years before that,
it’s an interesting question. We probably were not eating a whole lot of
starch because we didn’t get a salivary amylase duplication. To me, it brings up this interesting question. If Neanderthals and Denisovans had a salivary
amylase duplication, you could argue much more strongly that those individuals and homo
erectus and even further back we were eating starches. But the fact that they don’t, to me is probably
the most interesting part of the story saying… Yeah, I don’t know. That to me suggests we were not eating starches
until 60 to 70,000 years ago at the latest, and then maybe even more recently than that. So we don’t know. The papers that we shared, the furthest back
we see it is 12,000 years ago. And that’s in the time of the Neolithic Revolution. Yeah, but whoa, hold on. That’s true. But that’s from archeological remains. I don’t know that it’s been looked at in many
archeological remains. What’s also true is that the first paper that
came out with it, and I don’t remember if this is complete or not, but looked at Japanese,
Hadza, European Americans, Baka, Mbuti, [Gokug] and Yakut. I don’t know when European Americans, Japanese
and Mbutis had the last common ancestor, but it’s got to be way older than that archeological
remain. I mean, the inference has to be about who
has and who doesn’t. So I think I completely agree with you that
that indicates that all the other lineages that we sprouted off from, didn’t have it. But I think the fact that it’s shared across
all these different hunter gatherers that we… I don’t know when our most recent common ancestor
with them is, but I’m guessing it’s got to be almost as old as the most recent common
ancestor of all humanity because Mbuti did not recently give birth to any European Americans. You know what I mean? Like we diverged from them a long time ago. When you’re saying a long time, we can say
like, I mean, I don’t know, I’m just guessing, but to me it seems like the most common or
the most recent common ancestor would be 70, 60, 70,000 years ago as we move out of Africa. That’s homo sapians moving out of Africa. That’s the most common ancestor. And from there we move across the planet. So whether or not it was present for 500,000
or 70,000 years, I don’t know. But I think it’s possible that at least the
hypothesis or one hypothesis would that we move out of Africa. Mickey Van Dora has shown this really well,
that as humans move to different continents, we cause megafauna, extinction in all those
continents. So you’ve got a wonder, was it a megafaunal
extinction in over hunting in Africa that caused us to move out of Africa? And you could imagine that a megafaunal extinction
could have a need for starchy vegetables and the salivary amylase duplication. So it’s interesting. That strikes me as very plausible that megafaunal
extinction could have underlied the initial adoption of starch, but this has to predate
the Mike… So I actually, I have to be very frank. I am not as well versed on the research on
the migrations and Neanderthals and Denisovans. It’s been a very long while since I’ve followed
anyone on this. My understanding is that it’s debated whether
we migrated out of Africa 50, 70,000 years ago, 200,000 years ago, or whether there was
like three different migrations out of Africa that wound up converging. I think that’s very controversial. I think the most recent common ancestors also
somewhat controversial, but let’s say it’s 70,000 or 200,000. Like the Wikipedia page for it has it pegged
at 200,000. I don’t think it matters. So, like some time that was prior to the splitting
off of basically everyone that’s alive, right? I mean if isolated hunter gatherers in Africa
right now have these duplications, then it’s not just traced to the migration out of Africa. It’s traced to the most recent common ancestor
of the people who stayed in Africa and evolved there and the people who migrated out of Africa. But the exact date I don’t think matters that
much. I think we’re largely agreeing on this was
at least as recent as humans split off from Neanderthals, Denisovans, other apes, et cetera,
and did not have our ancestors up there. I think what I think we’re disagreeing is
where to put the emphasis. So why would we not be putting the emphasis
on the evolution that shaped present humans? If we evolved from the ancestors of homo habilis
and erectus to move to what has become the ancestors of everyone alive today, why wouldn’t
the changes to the genome of the ancestors of all living humans be the primary thing
to look at rather than the… Let’s say megafaunal extinction drove a starch
rich diet at a certain point and we are all descendants from those people. I mean, wouldn’t it be fair to point out that
the shaping of our genome has come from that inclusion of starch in the diet? Well, I think, but then the question becomes
how much is the genome shaped by that? Right? I think that there’s a little bit of an inference
there around like, “Oh, it had a huge impact or it affected us profoundly.” I can’t come up with a schema by which I could
quantify that. And my perspective is because we developed
this adaptation, does that mean it’s ideal for us or does it mean we had the ability
to have perhaps a little more efficiency with a fallback food. Look, how nutritious is a sweet potato really? And what kind of starches are these people
eating? These tubers pale in comparison to animal
meat and organs. And I think that, I don’t know how you would
feel about that statement, but look, I mean you can get complex carbohydrates, but you’re
primarily looking at a calorie source. You can get a decent amount of potassium and
maybe some beta carotene, but I don’t honestly know what ancestral tubers were like. My suspicion is that they were pretty horrible
and not very much like what we see today. I wouldn’t want to eat them. I don’t think I’d want to eat them. We actually have pretty good data on even
very recent evolution in potatoes. So in the Andes, potatoes were domesticated. And even in living and ethnography, it’s been
documented that they have many varieties of potatoes and the ancestral varieties of potatoes,
they will freeze dry and they will stomp with their bare feet in water and then they will
pass running water through them for three days to detoxify the bitter alkaloids that
are poisonous. And they always peel the potatoes and they
also have bred whiter, less bitter potatoes that are less toxic. And in America, I believe the last case of
potato poisoning was in the 1940s. There hasn’t been a potato poisoning case
largely because we’ve further bred them to be even less toxic. So I mean, clearly inclusion of plants in
the diet has at various points… Well, I mean it depends, right? Because some plants are more toxic than others
clearly. But we can say in general, I think, the other
thing is this is also reflecting like specialists in certain foods. So if you’re going to gather tubers and you’re
going to eat like 90 different plant foods and one of them is a moderately poisonous
potato and you never get the dose of that that does much to you, it’s not that big a
deal. But if you’re going to specialize in potato
consumption, then all of a sudden the bitter alkaloids and their toxic effects become very
meaningful. And so you have to specialize cultural adaptations
of how to process those things. Not that much different from the way that
cattle herders developed cultural specializations around consuming milk, such as fermenting
it to reduce lactose content and not that much different from the way we developed cultural
adaptations around tool use and the ability to hunt animals better. So, I mean I think it’s totally true that
plants can be toxic, that there are cultural adaptations to that, but cultural adaptations
and innovations around food sources has been a constant feature of human evolution since
we developed fire and tools. But yeah, I mean if you develop the fire and
the tool and you cook the meat, generally you don’t have toxins that you need to leach
out with running water. So you have a point there. But, okay. I mean, but the point that I’m making about
these duplications, it’s not that this shows we need to eat starch, you don’t need to eat
starch. We’ll live without starch. What it shows, it’s an evolution of an ability
to handle starch well. And what I think it shows is not that we all
need to eat starch, it’s that starch was… I mean, we talked about was how important
was start eating. I think it was so overwhelmingly important
that the selective sweep to duplicate the amylase gene was nearly 100% fixed. 1% of people from all the population studied
don’t have the duplication. So it’s 100% in some cultures. Some cultures have one or two people in them
that have been measured that don’t have it. And I just, all that I think that means is
that it’s one really compelling example that plant foods had been consumed in our ancestral
diet and that those shaped our genome. I guess to turn this around, we’ve focused
more so far on the ancestral part, less about the utility part. But what I was asking was to what degree is
this a return to the ancestral diet versus an innovation in what we can use to make people
healthier in a contextual way. And so when I look at this, what I see is
this is not a return to the ancestral diet. Yes, the ancestral diet definitely had more
animal products than what many people are advocating in modern society as a healthy
diet. But I believe the ancestral diet was omnivorous
and at times higher in plants, at times higher in animals, but generally omnivorous. And that I see carnivore as a way to yes,
get inspiration from the fact that we come from hunters, but it’s really in terms of
involving a 100% carnivore diet or a diet that does not have very meaningful nutritional
contribution from plant foods, I see that as taking inspiration from the past, but really
being the development of a new idea that has some medical application. And we’ll talk about keto in a little bit. I see keto as the same thing, but it was a
very hypothesis driven way to treat a specific disorder of epilepsy and has evolved from
that to generalize to other things. Carnivore I see it got put in place more at
the grassroots level and now it’s in search of a scientific definition. It’s like many people are doing carnivore
and saying, “It helped me lose weight and help clear up my eczema. It helped cure this autoimmune disease.” But why it works and what the boundaries of
its utility are is something where we need to reverse engineer from what people are doing
at an anecdotal level. Whereas keto, we developed it with inspiration
from fasting physiology. We developed and said it treats this thing,
and then other people broadened it on an anecdotal level to say maybe it can work for these other
things. So I mean, that’s my perspective on ancestral
versus modern tool. I mean, I think the salivary amylase duplication
could be seen in another light. Like I said, I mean, what’s the common ancestor? The fact that it didn’t happen until who knows
to 70,000 years ago suggests that for the majority of our evolution, we were probably
not eating a whole lot of tubers. So in that sense, it could be very ancestral
and this is the salivary amylase duplication is a recent modification or adaptation to
a changing landscape. I agree with you. I do think that we’re probably all descended
from a people that were forced to eat these foods. But as you’ve noted, tubers are not the best
foods on the planet. I mean, I’m obviously making a non-scientific
qualification there, but I mean, cassava… Value judgments are okay. Yeah. Cassava ancestral potatoes, these things are
toxic man. A lot of the plant foods we eat today have
an ancestral form that was very toxic. Almonds, I mean these are cyanogenic glycosides
and a lot of these things are quite toxic and we’ve made them into more palatable and
less poisonous things. But I mean, cassava is just like what you’re
saying. When people in South America use cassava to
get rid of the hydrocyanic acid, they have to do the same sorts of things, crush it,
bake it in the sun off gas, et cetera. I didn’t mean to interrupt you. Sorry. I’m open to the fact that these shaped us. I just don’t think that… I see it in a different light. I see it as like, wow, the majority of the
time we were probably not eating a lot of tubers and if we weren’t eating a lot of tubers,
we were probably eating a lot of animals and that shaped us for millions of years. As we talked about before the podcast, 70,000
years is plenty of time for us to change, but it’s quite interesting. I think from an ancestral perspective you
could argue with a salivary amylase duplication from the complete opposite perspective and
say, “Hey, this is really ancestral.” And then with regard to the modern therapeutic
intervention, I think you’re right about that in some sense. I think it’s a very possible plausible modern
therapeutic intervention. And we’ve sort of been looking at this from
two different perspectives that are disparate. One of them is a nutrient perspective and
the other one is we haven’t really talked on this is the toxins and immunologic perspective,
which is much less well defined, but at least clinically and mostly anecdotally at this
point. What we see for some people is that removal
of plant foods seems to ameliorate some degree of immune activation. The hypothesis that I’ve generated personally
for that is just that, “Hey, these plant foods could be triggering immune activity via a
variety of mechanisms.” And when we think about it from that perspective,
yeah that’s a whole different spin on it and very much of a medical therapeutic intervention
of this type of eating to say, “Hey, if you don’t need plants foods in your diet, you’re
distant ancestors were eating mostly animal foods, and you construct a carnivore diet
well, the removal of plant foods could be a really powerful intervention for people
who are not finding health or wellness or their goals, are not finding relief from their
suffering in other ways. Especially if we can define that it’s, and
doable and sustainable from a nutritional, clinical perspective. So I was talking to Chris Kresser earlier
today. Earlier in the morning I recorded a gut focused
panel with Chris Kresser and a couple of other people and he had mentioned this on Joe Rogan
in the past too. His hypothesis is that a carnivore diet is
basically excluding most of the fermentable carbohydrates and by removing a lot of things
that feed… You take someone who’s microbiome is messed
up, removing the source of food for the negative parts of the microbiome, the bad bugs, could
produce relief from symptoms that way. I think that’s an interesting hypothesis. I think the plant toxin is interesting hypothesis. I’d like to make two points. One is, so the thing is there could be a variety
of problems that people have with plant foods and it just happens to be on a probability
based level, it happens to be the case that even if it weren’t… So just to play a completely made up numbers
game. Even if it were the case that half of people
with autoimmune conditions have some plant top compound as a trigger for them and half
have some animal compound as a trigger for them. Not saying that’s the case. I’m just saying as a thought experiment. Then what you would still expect to see is
that as people play around, people self select for their diets, they don’t talk about it
that much usually if the diet doesn’t work for them or if it’s not appealing to them,
some people find success, they find other people who find success, they congregate and
form the community. So you would expect that some people who are
drawn to the idea of a carnivore diet, they basically have a 50 50 chance of eliminating
their trigger. And if they have success, they’re going to
aggregate form a community. That community is going to have a greater
voice and it’s going to create a sense that all over the place, people are curing their
auto immune conditions. It might be that one person had to take out
rice, one person to take out wheat, one person had to take out oxalates, one person to take
out cyanogenic glycosides or something like that. Could be a very heterogeneous pool of people. In the same way where if I had like a beef
allergy and I went vegan, and I had no idea that I had beef allergy, I would experience
profound benefit from going vegan, but that’s not because veganism was the cure for my condition. It’s because I just happened to cut out half
of my foods and I cut out the one that had the trigger in it. So I think that what we have is we have a
collection of people that may or may not be homogeneous. It could be the case that for most or all
or some of them, they needed to remove all plant foods. But it could also be that 20% of these people
needed to eliminate X type of plant food. 20% needed to eliminate Y type of plant food. And so I think that studying the mechanism
of how people are benefiting is where there’s really going to be game changing ability to
like really tailor the diets to the people that need them. I agree. I agree with you, Chris. You know what happens clinically in medicine
though, is that mainstream Western medicine doesn’t acknowledge that food of any sort
is triggering illness. And I think that elimination diets are one
of the most powerful tools we have in medicine. And 99% of physicians in the world are not
using them because they’re not taught to us in medical school. And so I think that the paradigm shifting
concept here is that food can trigger immunologic reactions and connected with that is a broadened
spectrum of autoimmunity. I think a lot of diseases that we have, a
lot of illness that we have as modern humans is autoimmune in nature and it isn’t thought
about that way necessarily. And I think that if mainstream Western medicine
realized that food could trigger disease, then we would begin to actually make headway
with this. And I think that regardless of the type of
elimination diet that people choose to do, an elimination diet is very powerful. I think the carnivore diet is a particularly
appealing elimination diet to me because of the nutritional adequacy of that diet and
the ability of a carnivore diet to provide so many nutrients in such a small package,
right? If you are going to do a vegan diet, it’s,
in my opinion, basically impossible to get all the nutrients you need without extreme
attention to detail and large amounts of food. And I think that more often than not, plant
based diets result in longterm nutritional insufficiency. So I worry about the sustainability of vegan
diets, but I do think that they can help some people if they eliminate the thing that they
are reacting to. Now, how common is beef allergy? Great question. That’s the question that I should be asking. You know? I don’t know. I don’t know how many people. Does the carnivore diet fix everyone? Nope. Does it fix a whole heck of a lot of people? It’s pretty powerful, man. I mean, I was talking to Michael Ruscio on
his podcast and he also uses a carnivore diet in his practice, people with gut issues. And he said he thought maybe 70% of people
got better on the carnivore diet. That’s still 30% of people didn’t get better
from gut issues and I thought, ” Michael, 70% man, show me another thing in Western
medicine that can do that. They’re pretty rare.” And I think that elimination diets are efficacious. Now there’s more to understand here. I think the cases where people don’t seem
to do well on a carnivore diet are fascinating. It’s like what’s missing there? Are they allergic to beef? Is there something in beef that’s triggering
them? I don’t know. Or is there something else? Something that a carnivore diet is not going
to remove? Clinically, what I’ve seen is that if somebody
has an overgrowth of certain types of bacteria, Clostridium difficile, other things, switching
to a meat-based side isn’t necessarily going to allow the gut flora to eliminate a very
pathogenic organism. Switching to an animal based diet isn’t going
to allow people to get rid of a huge burden of toxic heavy metals. And I think that there may be some people
that react to animal foods, but I’m not convinced of that yet. So I think it’s a really powerful elimination
diet. And part of my message is just bringing some
sanity to the current environment that’s demonizing meat because I think that it’s, in my opinion,
I have a strong belief that it’s a much better elimination diet than a vegan diet is for
many reasons. And I do have concerns that many plant toxins
can trigger the immune system. And at least clinically, my sense is that
animal foods do it a whole heck of a lot less. Yeah. So I think that, I mean we clearly have clinical
experience from different people showing benefits to carnivore, showing benefits to vegan, showing
benefits to semi versions of each. I mean, and then also there are standard therapies
in gut circles like low FODMAP diets that carnivore diets are. Right? Like a carnivore diet is a zero FODMAP diet. So I think when we’re talking about clinical
experience, clinical experience can provide a set of possibilities of what exists, but
it really can’t attach numbers to the percentages because every clinician has a non-random sample
of people that come to them. And if you have a popular internet or book
presence, then that becomes a very non-random sample. Oh, yeah. Absolutely. I don’t think Joel Fuhrman is lying when he
says that his clinical experience is that only 10% of people need more than 10% animal
products in their diet. It’s just that no one goes to see Joel Ferman
if his book isn’t appealing to them. And if they try his diet and they feel like
crap, they’re probably not going to go back to him. So what we really need, I think, is where
we probably make some headway would be if you take a low FODMAP diet and you take a
standard IVs treatment and you take a carnivore diet, how do they compare head to head in
studies. But I want to give you the last word on this
topic of who is this for? Because you’re the one with clinical experience
of people on a carnivore diet and I don’t have any. So, how would you give a general guideline
to who should try a carnivore diet? I mean, apart from just saying everyone should,
are there certain types of things that you could look for that would make someone more
likely to benefit from a carnivore diet? I mean, this is what we were just talking
about. There’s very little that I’ve seen to disqualify
someone from a carnivore diet. And can I say with 100% certainty that a carnivore
diet is going to fix everyone? No. But I’ve seen some pretty amazing things that
really shook me throughout my medical education. Things I’d never seen with mainstream- It took me throughout my medical education,
things I’ve never seen with mainstream medications or things that were pretty profound, and patients
who were previously recalcitrant to many therapies and many diets who got better with the exclusion
of plants. And so I’m pretty darn convinced that it’s
a valuable adjunct. Is this the only medication? “Is it the only therapy?” No, absolutely not. Is it the only dietary prescription? No, absolutely not. But it’s a really powerful one. I think that the question is not who should
try a carnivore diet, but maybe who should not try a carnivore diet. I think that the common questions I get are,
“I have heart disease. Can I do a carnivore diet? I have gout, can I do a carnivore diet? I have fatty liver disease, can I do a carnivore
diet?” And for all of those, I would say unequivocally,
“Absolutely you can do a carnivore diet.” The only situation that I’ve run into where
I’m pausing for a moment is chronic kidney disease. And I think that the data there is not entirely
clear, but if somebody already has pre-existing kidney dysfunction, we’d want to have some
attention to macros and follow the kidney function pretty carefully. There’s also some interesting data, I believe
it’s in rats, to suggest that a ketogenic diet could be helpful for polycystic kidney
disease, which is not an acquired thing. It’s a genetic cyst formation in the kidneys. And I have seen examples of people having
clinical improvement at a level of humans with a ketogenic diet or a carnivore diet
for polycystic kidney disease. In that kidney disease, I have seen improvement,
but if people have pre-existing chronic kidney disease related to hypertension or other things,
diabetes, I think it’s fine to try. You just have to be careful of the protein
macros and make sure that the kidney function doesn’t decline and there’s lots of nuance
there. But I think the question is who should and
who should not try a carnivore diet? And that’s the only situation I’m aware of
at this point off the top of my head. The rest of the situations I think are completely
fine and that people could give it a try. As we’ve said throughout this podcast, it’s
important to educate yourself about it and to be aware of how to construct it intentionally. Speaking of keto, we decided one of the things
that we have loose threads from our part one was we mentioned we wanted to talk about keto
and we never really got there, so now we can. Let’s start by what do keto and carnivore
have to do with each other? Are they two different things, or is there
some overlap here that helps us segue into keto? There’s definitely some overlap here. I think that for the majority of people, when
you eliminate carbohydrates almost entirely from your diet, you’re going to get some level
of ketogenesis. It’s difficult to quantify that. We usually use serum levels of beta-hydroxybutyrate,
which as you know are not the only ketone in the bloodstream, and it’s in flux so it’s
not perfect. We certainly can’t measure levels of citrate,
Acetyl CoA, or enzymes of gluconeogenesis at a clinical level, so we don’t have a great
sense, or enzymes of beta oxidation at a clinical level. We don’t really know. But generally speaking, the amount of carbohydrates
that we consume on a carnivore diet is extremely low. Now, the amount of protein and fat percentages
can vary widely in the way- [crosstalk 01:09:12]. What are we having people go on for protein? What I recommended for people as protein is
about 0.8 to 1 gram per pound of meat … per pound of lean body weight or per pound of
volume. Somewhere in that sense. I’m 170 pounds, I probably eat about 150 to
170 grams of protein per day. I interviewed Stan Efferding on my podcast
the other day, and it’s always a question, I think. I had Rob Olf on, I said, “How much protein,
how much protein? I just, I’m curious what people think.” And I think a gram per pound of body weight
is probably a pretty safe place to be. I think that more than that, there’s limited
evidence that more than that is beneficial. And I don’t think that- What’s your BHB? It depends on how much fat I’m getting. It’s usually between 0.7 and 1.5 or 2 for
me [ crosstalk 00:04:00]. I think you and I would probably agree on
this. Carnivore diet from carbohydrate restriction
is going to tend to increase ketone levels and the relative amount of fat and protein. The diet’s going to determine how much more
fat, less protein, more ketones, more protein, less fat, less ketones. Would you agree with that? Yeah, but I think there will always be some
level of ketones, even if people are [crosstalk 01:10:22]. Yeah, just from not eating any carbs. Yeah. You’re going to get some. It’s trace, and I’ve always wanted to ask
Dom if there’s really … I don’t know that there’s any real clinical, magical thing that
happens at 0.5 millimolar, but … I agree with that. We talked about who is a carnivore diet for. Let’s talk about who a keto diet is for. Where do you see the difference in the clinical
utility? Would you put some people on a keto diet that
you wouldn’t carnivore, or vice versa? Or would you tend to emphasize that the carnivore
diet be keto, or more keto for certain people? And generally, for people who don’t care about
the carnivore diet who are listening in any way, would you, in any context, tell those
people they should be on a plant-inclusive keto diet? My clinical experience, and again, this is
a confirmation bias or a bit of a selection bias, but is that a lot of people find a carnivore
diet to be easier to stick to with less cravings than a ketogenic diet. And so, when given the option of a ketogenic
diet or a carnivore diet, if somebody is willing to do a full elimination of plant foods, I
think it’s a better option. I always frame it in the perspective, “Let’s
see if we can do 30 days of carnivore, and then we can add plant foods back if you’d
like or see how you feel and go from there.” But generally speaking, I think that ketogenic
diets often include a lot of foods that I’m not super excited about. They often include a lot of nuts, which are
high in oxalates or lectins and I think can be triggering for a lot of. They can include a lot of leafy green vegetables,
which, from my perspective, maybe don’t have the best things in them. More oxalates, isothiocyanates, which I don’t
think are great. It’s a whole separate podcast. We’d have to do- More folate, more potassium. Right. And then I also think that there’s nuance
around sweet taste and incretins like GLP-1. When we put anything sweet in our mouth, whether
it’s sorbitol, or erythritol, or glycine, even things that don’t … are not carbohydrates
and that don’t trigger insulin classically, we can get GLP and other incretins being released. And I think that people end up with a lot
of cravings or difficulty maintaining a ketogenic diet to a greater extent than they do a carnivore
diet. I’ve heard people say that. Again, there’s a lot of bias here, but people
tend to feel like they can stick to a carnivore diet more easily, probably because it’s all
savory flavors and the sweet is not changing satiety signaling or incretins. Given the option, I would opt for a carnivore
diet for those reasons, less plant toxins. A higher protein carnivore diet. Why do you say that? Well, how are you distinguishing them? Or do you mean carnivore … Carnivore over keto. Carnivore versus keto. Yes. We said before, any carnivore diet’s going
to be at least a little bit ketogenic. Right, right. When you say carnivore versus keto, you mean
a carnivore diet that’s lower fat, higher protein? No, no. I mean plants versus no plants. Oh, I see. Yeah. I’m saying plant [crosstalk 01:13:33]. Oh, I see. Yeah, so you’re saying that even the little
bit of sugars in low carb, low calorie vegetables, that would be included on a plant inclusive
keto diet, you think even those tend to be problematic from a satiety perspective? I think they can be problematic and not even
… those and the sweeteners used in “Processed ketogenic foods.” Right? The sugar alcohols, glycine, things like this. So yeah. And it’s the exclusion of plants. Now, if we’re talking about macros on a carnivore
diet, which perhaps is your corollary question … Like I said, I generally look for about
0.8 to 1 gram of protein per pound of body weight and then either … from anywhere from
1:1 to 2:1 in terms of fat to protein ratio based on what people feel like works for them. I think that’s [crosstalk 01:14:24]. You don’t really pursue a treatment effect
of having more fat, less protein for the deliberate purpose of raising ketone levels? No, I don’t. Okay. I don’t. The way that I look at keto is much in the
way that I look at carnivore. I don’t think that a consistent, sustained
ketogenic diet is ancestral. I see a keto diet as a mimic of fasting physiology
developed by the Mayo Clinic in the 1920s for the specific purpose of treating epilepsy. I think the evidence around that is very supportive
of the idea that increasing GABA activity and/or decreasing glutamate activity is the
primary way that keto diets treat epilepsy. I know there’s a lot of other hypotheses,
but I think not only is that … is there a very robust evidence that they do that,
but it’s also the case that almost every single drug that’s used to treat epilepsy targets
GABA activity. I think a single exception is a drug that’s
used to target low voltage calcium ion channels that treats absence epilepsy, which is a very
specific type of epilepsy. I think there’s a very clean story across
the glutamate GABA balance effect of keto and all the drugs used to treat epilepsy. And I think that keto is a very hypothesis
driven way to replace the drugs that were available at that time. I now see that as generalizing very much. I think that many of the things that it’s
promoted for are, it can be an effective tool for it, but it’s not a very specific tool
for it, so a lot of people use it for weight loss, for example. Yes, of course keto is going to work for weight
loss. There’s a lot of other ways to treat weight
loss. It’s a debatable issue but of how sustainable
are different approaches, how effective are different approaches, but I’m in the school
of thought that the sustainability of the behavior change is the main thing that drives
whether weight loss is successful over time. And if people want to use keto for that, and
they find it to be useful for that, more power to them. But I think where keto is going to have the
highest likelihood of generalizing as a very specific treatment is going to be a diseases
that are psychiatric and/or neurological in origin that are related to glutamate GABA
balance. Many psychiatric disorders are included in
that, many neurodegenerative disorders are included in that, even things like chronic
pain and asthma are included in that. My hypothesis is that the glutamate GABA effect
is so central to the effect of the keto diet that it is … that’s where we’re going to
see the most bang for the buck in terms of showing strong results clinically. Insulin resistance and things like that, sure
I believe it can be used for those, I just don’t think it’s very specific like most diets
that create sustained improvements in nutrition combined with improvements in body composition
are going to help with metabolic disorders like that. That’s the way that I see the keto diet. I would expand on a little bit from the neurotransmitter
perspective. And again this is just nuance, but I think
that sodium channels are in there, I think chloride channels are in there. I guess the chloride channels are [crosstalk
00:11:52]. Chloride channels are all related to glutamate
GABA balance, but … Yeah, yeah. Yeah. I think it’s certainly been used in psychiatric
illness with interesting effect. Chris Palmer at MGH McClain is using it for
schizophrenia and bipolar with good effect. There’s some efficacy there in terms of the
way that it changes things in the brain. I think that’s one potential therapeutic option. I also think that a lot of ketogenetic diets
are elimination diets of some sense because you’re eliminating some foods. People could have immunologic benefit from
a ketogenic diet as well if they’re eliminating triggering foods. I think that there is a glutamate gala thing
going on in the brain. I think there is … there are changes in
the brain architecture that we can talk about, or at least in terms of the energy metabolism
in the brain with ketogenic diet. I think that- If you want to add something there, feel free
to go into it. We can maybe get into it later if we decide
to talk about the mechanisms and the benefits of it like a molecular level. But yeah, I think they’re beneficial there. The one nuance that I would bring up here
is that … and this is interesting, people often say that ketogenic diets mimic fasting
physiology, but I’m not sure they mimic fasting physiology completely because we are getting
calories. We are getting calories, right. Mm-hmm (affirmative). We’ll probably get into this a little bit,
but it’s … I did a podcast with David Sinclair. It was really interesting. I talked to him about this. He’s a big NAD guy and interested in the mechanisms
of NAD and NADH ratios, and triggering of certain genes, which we’ll probably get into,
the sirtuins, PARP, FOXO, MT2, metallothionein-2, et cetera. But he thought that ketogenic diets were tricking
the body into thinking that it was fasting. But yeah, it’s probably like that. But because we’re getting calories, we’re
not totally fascinating. What’s interesting, and you can let me know
how you think of this, or what you think about this. In a fasting state, the ATP to ADP ratio and
ADP to AMP ratios are going to be lower because we have low calories. Agreed. NAD to NADH ratios change in favor of NAD
so that NAD tends to go up, at least in the cytosol, it’ll pool NAD with fasting. But in a ketogenic state, with calories, it
seems to be a little different. It’s like you get the increased NAD to NADH
ratio, but you don’t have low ATP to ADP because you have calories and you don’t get ADP to
AMP, so [crosstalk 00:14:30]. Wait a second. Can you say that one more time? How are you distinguishing between the effect
on NADH versus ATP? Because you have adequate calories, so only- In the ketogenic state. In the ketogenic diet … Ketogenic diet. Yeah. … if you’re feeding someone as opposed to
fasting. Yes. I think we’ve seen that, that there are times. Can you run over one more time what you said
about NADH. Oh, just that in a ketogenic diet there’s
good evidence that NAD to NADH ratio is increased, and that’s been documented. We can go over that data if you’d like to
review that. Where? Are you talking about in the liver? Are you talking about in the brain. Both. I think that’s mostly been studied in the
brain. But I think it would happen in both because
I think that the mechanism would be the same with the metabolism of beta-hydroxybutyrate
versus glucose. But I don’t think that ATP to ADP ratios would
change in the same way that you do when you’re fasting because you’re not necessarily in
a caloric deficit, right? We have energy, we’re doing metabolism, but
… In that way, I think it’s uniquely different than fasting, right? Because in the fasting, you’re getting all
these signals, you’re getting ADP … ATP to ADP ratios going down, ADP to AMP ratios
going down, and in ketogenic diets because you’re feeding someone, I think there’s going
to be a discordance there, right? NAD to NADH ratios. I’m 95% agreeing with you. I would need to look more at the research
on the NAD, NADH stuff to understand it better. But I agree with you that with the principle
that there’s a partial replication of the fasting physiology, that’s not in the calories
in the ATP. Yeah, and I think that’s really interesting
that it’s only partial and the [crosstalk 00:16:14]. That’s why it doesn’t kill you. Well, yeah, exactly. That’s why it doesn’t kill you. Do you want to review some of the NAD, NADH
stuff? It’s quite interesting. There’s a great paper. We can. There’s a great paper on this. It gets into the weeds in terms of some of
the biochemistry, but we can talk about it. This. Can you chat me a link to it so I can look
at it. Yeah. [inaudible 00:16:45]. Do you want to pause the video for a moment
so we can get this. We can edit it out later if it’s … do you
have it on hand if it’s quick? I’ll send it to you. (Silence). Did you get it? Did you put it in the chatbox or … I emailed it to you. Oh, okay. I’m still waiting on it, but you can explain
it. It’s really interesting, and I had to puzzle
over this myself, but the idea … The paper is called beta-hydroxybutyrate as a signaling
metabolite. Is that fewer NAD molecules are consumed per
Acetyl CoA when beta-hydroxybutyrate is used versus when glucose is used. And the cellular compartment in which NAD
is consumed is different. This is why the NAD- NADH ratio changes during
ketogenic physiology rather than glucose based state physiology. And this has been documented in the brain
and multiple other studies, both with MRI and other methods, I believe both in humans
and … definitely both in humans and in animal models. But in the paper they say that metabolism
of one molecule of glucose, two molecules of Acetyl CoA involves the conversion of four
molecules of NAD to NADH. Two of these molecules are converted in the
cytosol during glycolysis. The other two are converted in the mitochondrion
by pyruvate decarboxylase, the cytosol in NADH is shuttled into the mitochondria, essentially
depleting the cytoplasmic NAD pool with high glucose utilization. In contrast, when you use beta-hydroxybutyrate
and the same two molecules as Acetyl CoA, only two molecules of NAD to NADH are used,
and both … in the mitochondria, and both are using the mitochondria by an enzyme called
BDH1 preserving the cytoplasmic NAD pool. The cytoplasmic and mitochondrial NAD pools
are distinct and the preservation of cytoplasmic NAD by beta-hydroxybutyrate appears to have
important cellular effects, which is getting ahead of what we were going to be in this
discussion as NAD as a co-factor for the sirtuins PARPs… Ok, ok, so they’re saying beta-hydroxybutyrate
is going to reduce NAD to NADH, but because it can be done in the mitochondria it can
preserve the cytosolic NAD pool. Yeah, it uses less [crosstalk 01:25:40]. And that’s analogous to why you would make
lactate in the cytosol. Yeah. You just restore the NAD levels in the cytosol. Yeah. Real quick, the way that I would view that
is that ketones in a ketogenic state, you’re preserving cytosolic NAD with beta-hydroxybutyrate
in a normal glucose based state on a mixed diet, you’re primarily preserving cytosolic
NAD by lactate production. Although lactate production is largely happening
in astrocytes, so I guess if beta-hydroxybutyrate is being metabolized in the neuron, that would
perhaps create a more effective NAD rescuing effect in the cytosol of the neuron. That makes sense. Yeah. The two studies, ketogenic diet, modulates
NAD dependent enzymes and reduces DNA damage in the hippocampus. We can talk about that one eventually. And then the other one is … What’s the sales point here, that the NAD
is used for NAD hydrolyzing enzymes? [crosstalk 00:20:46]. Metallothionein enzymes and others. And this has been documented as well, that
those enzymes do get turned on by ketosis and beta-hydroxybutyrate. It’s an epigenetic mechanism. And turning on longevity genes FOXO3 or sirtuins,
et cetera. It’s pretty interesting and … That’s a fair point. Yeah. And I think what’s interesting about that
is that you have enough energy so you have ATP to ADP ratios that are maintained because
you have energy, but in a way you’re tricking the body into thinking that you’re in a fasting
state and turning on these longevity genes. That’s getting ahead of our conversation where
we are at this point. But that’s [crosstalk 01:27:33]. No, I think it can segue into one of the points
that I wanted to talk about here. And so I think that makes sense. And I think it makes sense specifically that
you’d be doing that in ketone utilizing tissues. And so specifically you’re talking about doing
that in the brain. Maybe to a lesser extent, you’re talking about
doing that in muscle, but you’re not talking about doing that in the liver, which is on
a ketogenic diet, the livers bearing the brunt of metabolism to a greater degree than otherwise
because the liver is making all the ketones from fatty acids, and the liver physiology,
because beta oxidation is taking place there and because ketones are being produced rather
than utilized basically as the opposite physiology of the brain and other ketone utilizing tissues. And actually, this is very interesting because
one of the groups that was showing how oxidative stress is prevented in the hippocampus on
a ketogenic diet showed that antioxidant status was worse than the liver. And so, to a very large degree, the liver
is bearing the brunt of transferring beneficial effects to other tissues such as these effects
that you’re talking about in ketone utilizing tissues. In that study, what was the length of time? Because I think that as we get into this discussion
of ketogenesis, one of the themes that I seem to see as we were reviewing studies in tandem
was that the acute phase of transition into a ketogenic diet, and we … I think we need
to be very careful, like you said, with semantics and differentiate a ketogenic diet from fasting
physiology. But as we transitioned into a ketogenic diet,
there are changes, and this is the foreshadowing of the things we’re going to talk about. There are changes in hormones and pH levels,
which based on what I was looking at, the studies you may disagree with this, tend to
be transient and resolved within a few weeks going back to normal levels. And so interestingly, as you’ve pointed out
… And even in the brain, this has been shown in the hippocampus of rats. When we shift to a ketogenic diet, we are
pushing more metabolism through the mitochondria electron transfer chain, and there are more
reactive oxygen species created. And this is in terms of mitohormesis, the
increase in reactive oxygen species in the mitochondria in the brain, and perhaps other
places in the body result in activation of mitochondrial biogenesis, PGC-1 alpha pathways,
FOXO3, and glutathione peroxidase, and increased enzymes to make more glutathione. And so after time, so there’s that increase
that bumped in reactive oxygen formation with the first transition into ketogenic physiology
as more of the mitochondrial electron transport chain is used, and then the body corrects
it, and there’s more of these antioxidant mechanisms, these endogenous antioxidant mechanisms
turned on. And so the timeframe of that is very important. If we look at the response to ketogenic physiology
… I can answer your question about the timeframe. Unfortunately, my Chrome browser that held
these tabs open quit and I’m restoring it now. But this group showed that there was a time
course where signs of oxidative stress in the hippocampus increased up to I believe
the three day point, and after three weeks they looked better. Exactly. However, what they showed in their study was
essentially that the hormetic stress was yielding low … If we consider it three weeks long-term
… and it’s a rat study so we can’t go that long. Over the course of those three weeks, the
short term effect on the hippocampus was more oxidative stress that then activated the endogenous
responses to that oxidative stress produced a hormetic effect that led to protection from
oxidative stress. However, in the liver, the glutathione remained
depleted through the three-week time point. It wasn’t statistically significantly different
that three weeks versus two weeks, but it looked to me like it was even lower, no sign
of it reversing course and their measures of oxidative damage were actually conflicting
in those tissues. But the general image that I get there is
that the hippocampus benefited at the expense of the liver, and the hippocampus benefited
specifically through hormetic stress. This ketogenic diet is essentially mildly
pro oxidant in terms of the balance between oxidative stress and antioxidant protection. In the hippocampus, the ketogenic diet is
a mild oxidative stress that induces protective responses that we can call pro medic because
the protective response exceeds any harm done by the mild stress. In the liver, that was not the case. I could share these data if the … [inaudible]
loads, but in any case, the glutathione remained depleted and the [inaudible 00:26:49], which
is a marker of oxidative damage remained elevated in the liver. [crosstalk 00:26:54]. That’s interesting. I think the oxidative stress is coming from
increased utilization of the electron transport chain. And I think that the long-term effects are
that it no longer is an oxidative stress because of the way that the reactive oxygen species
are managed long-term. In the short-term, I think there’s an increase,
but long-term, there’s no increase in reactive oxygen species, and there’s actually usually
a decrease in reactive oxygen species, at least in the brain. And I would love to see people check this
in the liver [crosstalk 00:27:30]. The liver is in many ways different from the
brain in the case of ketogenic diet. One of the benefits of ketones that is cited
by Veech is that ketones increase … they increase the amount of NADH in the mitochondrion
versus the amount of FADH2. And so the way that works in the electron
transport chain favors less generation of reactive oxygen species. But Veech also points out that in fatty acid
oxidation, you’re doing the opposite. Fatty acid oxidation is occurring in the liver,
not the brain, primarily in a ketogenic diet. In the liver fatty acid is actually generating
more FADH2 then you would have … less NADH than you would have if you were burning glucose. And so you’re essentially transferring the
mitochondrial NADH to FADH2 ratio. You’re basically giving that benefit to the
brain, but the liver is bearing responsibility to create that benefit. The liver has to balance the accounts. Liver does this all the time, like the muscle
makes lactate, liver takes it, turns it back to glucose, sends it back there like the … When
the liver is handling metabolism in the rest of the body, if you got a benefit one place,
the liver suffering. Like in the Cori cycle, muscles are making
glucose, the liver is getting depleted of ATP to make that glucose and send it back
to the muscle. In ketogenesis, the liver is bearing the brunt
of dealing with all the fatty acid oxidation. The fatty acid oxidation is going to be up-regulating
uncoupling proteins in the liver, which decreased mitochondrial efficiency. Ketones are going to be increasing mitochondrial
efficiency in the brain at the expense of the liver. Fatty acid oxidation is generating NADH, reducing
FADH2, ketones get sent to the brain taking NADH reduction from the liver, giving it to
the brain, reversing that metabolism in the brain. The brain is benefiting, but it is that at
the expense of the stress put on the liver. What’s interesting, I think that then we have
to look and say, “What’s the net?” Right? Is there a way that we can clinically look
at the liver? And what’s interesting is that from that perspective,
we do not see evidence of oxidative stress in the liver on a ketogenic diet. In theory, this is what’s happening, and I
don’t see elevated GGT, AST, ALT, or other markers of oxidative stress in the liver,
in humans on ketogenic diet long-term, we have to say what’s going on. And then as we’ve seen in animal models, we
obviously can’t study this very well in humans, the ketogenic diets is lifespan extended. It’s mimicking caloric restriction and turning
on these longevity genes. I want to dwell on that point because I want
to … you brought it up before and I’ll let you finish your thought, but I want to hover
there for a minute because I do want to talk about that. The ketogenic seems to mimic the caloric restriction
physiology its epigenetic effects. beta-hydroxybutyrate has direct effects on
the histone deacetylase, HDAC 1 and 2, and the NAD to NADH ratios can affect the differential
transcription of genes FOXO3, sirtuins, MT2, the PARPs], and appears to have a life standing
… life span extending effect in animal models, much like interventions, which affects sirtuins
do. This is the work of David Sinclair and others
with resveratrol and other molecules that affect the NAD to NADH ratio. Clinical evidence that the liver is stressed
by a ketogenic diet are … I’ve not seen it in humans. Well, look, I’m not saying that the liver
is being acutely damaged by a ketogenic diet, but we’re talking about oxidative stress benefits
in the hippocampus and we’re relying on animal experiments to talk about those things. You’re not also measuring oxidative stress
in the hippocampus of your patients either, right? [crosstalk 00:31:36]. We only understand these mechanistic details
from animal experiments and the hippo … the people who did the hippocampus paper are the
people that I’m citing for this. After they published their paper in 19 … or
in 2008, I believe it was, they published another paper in 2010, Acute Oxidative Stress
and Systemic Nrf2 Activation by the Ketogenic Diet. And that’s where they mapped out the time
course of reactive oxygen species. H2O2 was increased that one day in the … by
the ketogenic diet, declined thereafter, and was significantly lower than baseline at three
weeks. The 4-HNE, which is a marker of oxidative
damage, was elevated at three days, and it wasn’t statistically significantly elevated
at one and three weeks, but it actually looks pretty much just as high. That didn’t seem to benefit in the same way. Maybe that was early damage from those day
one or three that persisted, but in the liver, [crosstalk 01:38:36].That’s in hippocampus. And then in the liver, the glutathione was
cut in half in the liver at three days, stayed cut in half at one week and three weeks. In fact, at three weeks, it looks even worse
than it did at three days. We’re not measuring hepatic glutathione in
anyone’s patients. We’re not measuring hippocampal 4-HNE, we’re
not measuring hippocampal H2O2, right? Both 4-HNE, we’re not measuring hippocampal
H2O2 right. So I mean I think it’s very clear that there’s
neurological and psychiatric benefit. My personal way of seeing that is that that’s
mainly from the glutamate GABA balance. I think these things on oxidative stress are
not fully mapped out yet. But I think if we’re going to go into details
about affecting NAD FADH2 and all these different things, I think it’s necessary to point out
that in proportion to the benefits that incur at the brain, you’re directly proportionally
having the reverse effect in the liver. And I think that then we, as people who work
with people, humans, we can sort of say that’s an interesting. Okay, how do we measure that in the liver? How do we test that? And the best proxy that I have for that is
AST, ALT, GGT, systemic markers of inflammation, things like this. And I haven’t seen an issue with it, but it’s
interesting it’s like, huh. Certainly we know there are cognitive benefits
to a ketogenic diet. But your patients aren’t also, they’re not
that ketogenic. Right? For the most part. I mean, what’s the typical millimolar ketones? I think it’s probably 0.5 to 1.5. Yeah, whatever I usually eat, I don’t eat
keto at all, but mine are 0.2 on a typical afternoon. But, I want to hover on the concept of longevity
effects here. So, I’ll say at the outset that I’m generally,
no matter what, whether it’s fasting, keto, resveratrol or whatever, I’m not too big on
looking at net lifespan in animals on the basis that, certainly in worms, just think
their physiology is so much different from ours. Even in mice, I don’t think that looking at,
if you put a mouse in a dark protected environment and let it live off its natural life protected
from germs, protected from nutrient deficiencies, protected from trauma. I don’t think that has much of a parallel
to the typical American dying of getting sarcopenia, osteoporosis, hip fractures, cardiovascular
disease and stroke. I do think that the average rats winds up
getting testicular cancer or something like that. I think that it just makes much more sense
to look at disease specific models rather than that longevity. But I want to take this back to a more conceptual
level. So we agree that ketones are partial replication
of the fasting state physiology and it’s one that allows us to continue the fasting state
physiology for a much longer period of time and fasting. I’ll agree with you on the point that you
made about the NAD plus conservation and cytosolic ketone utilizing tissues. And I agree that’s going to be beneficial
from the perspective of PARPs and sirtuins, which are involved in DNA repair and telomere
lengthening and other factors related to longevity. However, the fasting state physiology in my
view is something that you want to cycle in and out of. It’s not something that you want to remain
in perpetually all the time. And the reason is that there are many aspects
of health protective factors that are primarily happening in fed state physiology and we alternate
between different ones. So for example, autophagy is generally associated
with fasting state physiology, but antioxidant protection and repair processes, glycation
protection are generally energy intensive processes that are more regulated by the fed
state. And there’s multiple pathways regulating this. One of them is that citrate increases in the
cytosol in the fed state, particularly in a robust carbohydrate fed state and increases
acetylation in the nucleus, which turns on genes related to antioxidant defense. But also insulin has direct effects in glutathione
synthesis and has direct effects in regulating enzymes involved in particularly glycation
defense. But through glutathione synthesis is also
extremely important to antioxidant protection. If you look at that hippocampus paper, the
depletion of glutathione that occurs in the liver is a significant example of that and
glutathione depletion, I looked for papers and could not find any on ketogenic diets
and humans and hepatic glutathione or even plasma glutathione and could not find any. But it’s generally known and non-controversial
that glutathione cycles down in the fasting state and up in the fed state. And that’s basically for two reasons. One is that protein provides all the precursors,
so the influx of amino acids from protein is high and the fed state low in the fasting
state. And the other is that the synthesis of glutathione
requires insulin, magnesium and ATP. So insulin is a direct positive regulator
of glutathione synthesis. The insulin to glucagon ratio is what drives
that and that partly reflects, that it is ATP intensive. So on a ketogenic diet with adequate protein
you are providing amino acids, you are providing ATP levels, you’re not providing the insulin
response. That’s why glutathione levels are lower as,
for an example, in the livers of those mice or rats rather. So that’s an important thing to distinguish
here and maybe that’s why I wanted to say that in the beginning that a ketogenic diet
is not the same physiology as a fasted state, right? Because you do have influx of amino acids
and you do have ATP. And I think that that is going to change the
overall signaling and that’s as you say, I don’t know if that’s fully been studied and
I think that a ketogenic diet represents a unique physiology. I agree with you. When we are completely fasting for a week,
things are going to be different, right? And antioxidant status could decline with
all those mechanisms, but in a ketogenic diet, it’s kind of this unique thing that we need
to study a little more, because of the discordance between ATP levels and NAD levels. One of them mimics fasting, one of them doesn’t,
and I think that’s going to affect things differently. The other, just part that I would suggest
here is that absolute levels of insulin do not directly translate into levels of insulin
signaling. And I think that glucagon to insulin ratio
is important, but the absolute level of insulin tells us nothing about insulin signaling. We know this from cases of insulin resistance. And post prandial insulin levels on any diet,
even a diet that involves protein in a carnivore diet will rise, so there are insulin signals. Fasting insulin levels are much lower. I was actually looking at a paper the other
day with a friend and we were comparing postprandial levels of insulin signaling on a number of
people who are eating a carnivore diet. And then we were looking at another paper
of I think they were non-diabetic subjects and postprandial insulin signaling. But there’s not a whole lot of evidence that
I’ve seen about levels of postprandial insulin, but insulin does rise after a meal of protein
and fat. It still does. We know that protein is insulinogenic to some
extent. It’s not completely flat. So I don’t think we disagree on this at all
and a ketogenic diet is going to provide signals of being in the fed state, but they’re not
going to be as robust as signals from a carbohydrate inclusive diet and I think it’s misleading
to point to insulin resistance in pointing out why more insulin is not necessarily going
to make more insulin signaling. I mean it’s true that in an insulin resistant
person, they’re going to have higher insulin levels and less insulin signaling. That’s completely true. But it is also true that if you take anyone
with a given level of insulin resistance and you feed them carbohydrate, you’re going to
have more insulin and given the current state of resistance or sensitivity of their cells,
they’re going to have more insulin signaling because of that. I think that’s completely non-controversial. Also, if you look at diabetics, and I can
link this paper in the show notes, I can send it to you later. I believe I say this in my doctoral dissertation,
which I sent you. There was a study on diabetics showing that
they have low glutathione status, including an oxidized glutathione status in the blood
and that you could normalize that by putting them on a euglycemic hyperinsulinemic clamp. This is a model where they took human diabetics,
looked at their bad glutathione status and they pumped glucose and insulin simultaneously
in their blood. And did so in a way that allowed them to pump
just enough glucose to prevent hypoglycemia while simultaneously putting in very large
loads of insulin and what that did was normalize their glutathione status. So there is human evidence that insulin, even
in the context of being pumped full of glucose, even in the context of diabetes, insulin does
positively regulate glutathione in a way that increases it, which is consistent with the
livers of the rats that were fed the ketogenic diet as well. I think we’re in complete agreement that you
do not have a full replication of fasting physiology and a ketogenic diet. You do get fed state signals. Ketogenic diets were explicitly designed by
the Mayo Clinic for the purpose of creating a sustainable mimic of fasting state physiology
for the purpose of treating seizures because it was known that seizures could be treated
by fasting, but it was also known that you can’t fast perpetually or you die. Yes, they provide fed state signals but they
were literally designed to try to maximize the fasting state physiology that you could
get out of a diet that would keep you alive over time. I think a good model for understanding the
concept of cycling is basically when you fast, you primarily do things that break things
down and that are energy generating and that allows you to clean house. When you get fed, you do a lot of building
up, you do a lot of repairing and you do a lot of energy intensive protection. We need to harness both of those to optimize
our physiology for longterm protection. That’s my view. I think that’s a compelling thesis, that’s
a compelling premise and I think that it’s not totally clear that we can’t do that with
ketogenic diets. And I think that with ketogenic diets, what
I’m saying now is the other nuance we should say is that a four to one fat to protein ketogenic
diet developed by the Mayo Clinic for epilepsy is perhaps different physiologically than
a 150 to 170 gram of protein one-to-one or two-to-one fat to protein ratio that we would
be getting on a diet like this. I think that extreme dietary ketosis may have
different signals. And I appreciate what you’re saying. I think that we do want to make sure that
no matter how we’re eating, whatever sort of macronutrient composition we are consuming,
we are still getting anabolic signals. And I think it’s fascinating and there’s a
good amount of data to suggest that we can still get that on a diet that is ketogenic. It’s maybe not the classical ketogenic diet,
but we could still get that on something like a carnivore diet. With regards to the oxidative stress stuff,
I think that we talked about this a little bit in the first podcast. We need more studies on this, but I haven’t
seen clinically any change in lipid peroxides, 8-hydroxy2-deoxyguanosine, levels of glutathione
in myself or my patients on carnivore diets. The actual rubber meets the road translation
of all this to me suggests that people can have quite good, at least the best metrics
that I’m aware of, of oxidative stress even on this way of eating. It’s hard to know how those two things connect. We don’t observe it or at least I have not
observed that in my patients, but it’s something we could test for it and I wonder about that. It would be something great to do a study
on when the first carnivores studies are done. I know, right? I’ve got a feeling that will not be in the
first carnivore study. Maybe the third. No? I’m pretty sure the first carnivore study- I’ll lobby for it. We’ll just be looking at like blood pressure
and A1C or something basic, making sure it doesn’t kill people when they’re in the hospital. Okay. Study number two on the carnivore diet, look
at oxidative stress. Oxidative stress, hepatic glutathione, serum
levels of glutathione- In a study like we talked about before in
the, in a research study would be we’d be able to get the best measures because you’ll,
it’d be able to look at the redox status and find out how oxidized it was in the blood. Yeah, oxidized to reduced glutathione and
F2-isoprostanes, whatever we think is going to be valuable. So. Sorry, I didn’t mean to cut you off. Maybe we could circle, I know we’ve gone almost
two hours already, as an illustration of some of these concepts about ketogenic diets, perhaps
we should talk a little bit about the hormones. I think that the studies from [Volek] and
[Zajack] that we talked about previously that did not show significantly different changes
in sex hormones might argue that there’s still plenty of anabolic going on. If a ketogenic diet, now of course these people
are doing slightly different ketogenic diets not using a carnivore diet, it doesn’t seem
to mimic fasting physiology in terms of hormones either. From what I’ve observed in people who are
doing long fasts, the testosterone plummets, all of the things associated with anabolic
signals plummet. You can see IGF1 plummet and we don’t see
this in many of the ketogenic studies that we reviewed. In a number of those studies, IGF1 didn’t
change, testosterone didn’t change, other sex hormones didn’t change. Leptin seems to be sometimes goes down, sometimes
it’s the same depending on the study you look at, but I see that as an argument that, hey
look, there’s still anabolic signals and I think that that’s the question is, or at least
the hypothesis that eating a ketogenic diet doesn’t mimic fasting completely. I agree with you completely with regard to
fasting. When you fast, there’s all these low energy
signals, but I’m fascinated by this, this discordance in the ketogenic diet between
the ATP energy signal, NAD, and the hormonal data to me suggests we’re not fully fascinating
physiology, we’re not strapping everything off the face of the planet. I think part of the issue here is, first of
all, I’m thinking of this more from the perspective of possibilities rather than mean effects
and some of these studies are looking at mean effects. Another part of it is that there’s so many
different permutations of how ketogenic a ketogenic diet is and how low in carbohydrate
is a low carbohydrate diet. I’ve talked to, for example, I talked to a
type one diabetic who was managing his type one diabetes by eating a zero carb diet. His testosterone sex hormones just completely
tanked. When I look at that, I’m like, well that’s
pretty predictable. Insulin has positive regulation, thyroid hormone
has positive regulation of sex hormones. If there are other people whose sex hormones
are fine, well it can happen to them, that’s fine. I think you’re pretty well getting at the
key point, which is to what degree are you mimicking the fasting state physiology to
be taking a mild version of something that was designed to very largely mimic fasting
state physiology. You do a mild diversion that maybe 20% approximates
fasting state physiology. You’re probably at that point, rescuing yourself
from the fasting physiology effects of that. The negative fasting physiology effects what
I guess- Well, all fasting physiology is 100% negative
if carried out indefinitely. I mean, no one fasts forever and doesn’t die. Right? Fasting state physiology is intrinsically
lethal to carry out in perpetuity. And so the question is, to what degree are
you mimicking that? Well, I think if you’re keeping thyroid hormones
and sex hormones normal, then whether it’s because of the saturated fat or the protein
or other animal based nutrients or the calories or however you’re doing it, there’s something
that you’re doing that is providing enough anabolic signal to maintain fed state physiology. My perspective isn’t really to come here and
to say don’t to keto because it will tank your testosterone and it’ll throw your cortisol
through the roof. But I would come and say, I’ve had people
call me up who say I eat 60 grams of carbs a day, I do CrossFit, I wake up in the middle
of the night at 4:00 AM every day and my heart’s pounding through the roof, I feel hypoglycemic. My instinct is to say maybe with your lifestyle,
you need to eat more carbs and maybe you would have a different approach to that, but I do
think that in fasting state physiology, in glycogen depletion, you do hit a point and
this is natural, textbook physiology. You do get a point where you’ll raise cortisol. You do hit a point where you’ll raise adrenaline
at some point and so on a case-by-case basis, there should be an awareness that it’s a potential
product of excessive fasting-state physiology to spike cortisol, to spike adrenaline, to
tank testosterone, to tank thyroid hormone, and maybe if you do carnivore, mild keto perfectly
in a very well planned diet, maybe no one gets that effect, but we don’t really know. When we take a random sample of people who
weren’t specifically following that and we put them on that diet, then we’ll know, you
know what in what percentage does this happen. A lot of the studies that we’re looking at
are looking at means and if you take the mild version of the diet, you put some people on
it, the average cortisol isn’t significantly different, but it doesn’t rule out that there
are some people because of their constitution, their lifestyle, and the rest of their diet
where if you activate too much fasting state physiology, you will get negative effects. And I think that that is perhaps the tipping
point. When I see people and they’re calorie restricting
on the ketogenic diet, you can see the hormones change, but you can also see that change on
a non-ketogenic diet. If you’re calorie restricting, and my hypothesis
is that that is a function of calorie restriction more than it is a function of a ketogenic
diet and that if you mimic fasting physiology with caloric restriction, you will get the
effects of fasting physiology. You will get changes in the sex hormones and
if you see that, then you’ve crossed over the edge and it’s temporary. It’s okay if you want to fast, it will come
back. But if people are seeing that on a ketogenic
diet, I do not think that is a feature that is intrinsic to a ketogenic diet because there
are many studies would show that after the period of keto adaptation, three to six weeks
that most of the hormones look the same. You mentioned cortisol and adrenaline and
the studies with that would suggest the same thing. If you look at people who are keto adapted
and we probably don’t want to get in the weeds with all the studies that we were talking
about before this podcast, but the way that I saw those studies that once people were
keto-adapted, there was no clear data that cortisol, either at rest or with exercise,
was higher or lower on a ketogenic diet. In the short term, yes, as you deplete liver
glycogen, which is the signal for ketosis, there’s going to be hormonal changes, but
as we keto-adapt as we carnivore-adapt, maybe is what I should call it from now on, we’re
going to carnivore-adapt, it looks like those things are normal. Whether we’re looking at pH on- Glycogen? Well, no, I’m not talking about glycogen. Right now I’m talking about hormones and indicators,
so I’m talking about… I said, that hormones, it was like I said
it in French. I’m talking about sex hormones, testosterone,
cortisol, those types of things, pH. It seems to normalize once we become carnivore,
keto-adapted. In the short term, yeah, there are changes,
but I think people get misled by this concept that cortisol goes up on a ketogenic diet
because it doesn’t long term in many of the studies that I’ve seen. In fact, the majority of the studies we looked
at, it did not seem to be statistically significantly elevated on a low carbohydrate diet, long
term. In the short term, yes. In the first few days, and it’s because of
the depletion of liver glycogen, there are changes and then the body adapts and the same
thing with pH. We talked about that a little bit as preparing
for this podcast. The pH goes down a little bit in the beginning,
but then the body buffers and it looks to be about the same, it looks to be the same
long term. So in terms of studies that have looked at
people who are keto-adapted, I didn’t see any that showed that there were real differences
in hormones. I think that you bring up the good nuance
here, which is there’s, they’re looking at beans and if you mimic fasting physiology
you will get changes in these things and the way to get physiology is to calorie restrict. If you are getting out of the calories, I
am not convinced that a ketogenic diet or kitchen physiology, perhaps I’m referring
to low-level ketogenic physiology and a carnivore diet is intrinsically going to create hormonal
abnormalities. So I didn’t comprehensively review the literature,
but I looked at a few studies and we shared a few studies, we can post all the studies
that we shared in the show notes and people can take a look at these. My impression was not so much that there was
a time adaptation and cortisol. I thought it was more context dependent. So in people on a ketogenic diet where they
had an extreme therapeutic ketogenic diet for epilepsy, where they obviously had health
problems to begin with, and then people with rheumatoid arthritis, there were statistically
significant increases in cortisol- But those are the only two, three to seven
days. I don’t see the time course effect in the
[Volek] 2002 paper. The cortisol was like twice as high at baseline
in one group than the other and I just thought the cortisol data were too variable to be
useful. There was an exercise paper that we looked
at, and it was, if I recall correctly, cortisol wasn’t elevated at baseline, but it was elevated
during the first 90 minutes of the exercise program. So to me it looked like- No, that one was really quite misleading,
Chris. We’d have to really dig into that paper. There wasn’t a statistically significant difference
in cortisol at any of the time points with the exercise in that paper. Okay, well we can put the paper in the show
notes and then we can talk about it later, answer questions about it or go back and forth
later. But anyway, my impression is that it’s more
context dependent than time dependent. If there’s time adaptation data, I don’t know,
maybe it’s out there, but I didn’t get that impression. The time adaptation. I’ll just add that what I saw was that in
some of the studies you’ve said there were short term studies, right? Three to seven days. There were some increases in cortisol, but
in many of those in the kids with ketogenic diets, the increase in cortisol was still
within the normal range and it wasn’t- Oh, I agree with that. Yeah, there was a bump, but it was still within
the normal range. And again, this was only at seven days. And then if you look at the studies by [Volek
00:02:04:40], this is part of the group that’s in a lot of centers and ketogenic diets. They often do them in a setting of people
being keto-adapted and giving them two to three to four to five, six weeks. And those studies did not consistently show
any difference. So your interpretation may be equally valid
as mine, but the other hypothesis is that there’s part of a keto adaptation effect here. [crosstalk] I think there might be a keto
adaptation period, but most of the time is when people are claiming keto-adaptation,
there’s not very rigorously designed studies to test the idea. One point I do want to make about glycogen,
so many people look at [Volek’s] FASTER study as showing that when people are on ketogenic
diets for seven, eight months in athletes, glycogen metabolism is not any different than
glycogen contents, not any different than muscles. But [Phinney] Published a paper in 1983 showing
that muscle glycogen was cut in half on a ketogenic diet and [Phinney’s] Study was shorter. It was a few weeks long, but [Volek’s] keto
dieters were also eating four times as much carbohydrate as [Phinney’s] were. If you just think about the physiology, it
makes more sense to me that it’s going to be context dependent rather than… Yeah, there’ll be adaptations of course, but
context has to be a powerful modulator. Cortisol is part of a stress response and
so the other stressors are going to be part of the calculation of how the body is going
to respond. Hypoglycemia or not having a not being fed
well enough is a stress, hypo-caloric diets are a stress, so are many disease states,
so are psychosocial stress. My suspicion is that if we’re able, and we’re
getting to suspicion, my suspicion is that if we were able to test out all the variables
in a very rigorous way, we would eventually create a picture where, yeah, there are adaptation
periods, but there’s also big contextual modifiers where if someone has a cumulative stress threshold. I mean there’s a lot of people out there who
are dieting or doing keto at the same time or doing CrossFit who have a lot of psychosocial
emotional stress. I think some people are just way overloaded
on the stress fasting state physiology underfed side of things and just way out of balance
with the degree of rest and recovery that they have. The way that I think about it is look, carbohydrates
provide a more robust fed state signal than other macronutrients do. All macronutrients provide a fed state signal. So your body’s going to be looking at stress
signals of how much energy do I need and then fed state signals of how much energy do I
have and the relative balance of being under stressed or overstressed in my view is going
to be nourished by an amount of carbohydrate that provides a more robust fed state signal
but doesn’t induce hyperglycemic stress, which I think we would probably agree is itself
a stressor. There’s evidence for that as well. There’s evidence in carbohydrate-based diet
over feeding that that creates inflammation and evidence of oxidative stress. So we don’t want to be overfed in the carbohydrates
either. I think that my counterpoint to you is that
carbohydrates are, as you said, are not the only fed state signal and I do not think the
data clearly points to the notion that we need carbohydrates to get an adequate fed
state signal. I like that we’re talking about the fed state
signal’s important and the fed state signal is easily measured. It’s your testosterone, it’s your cortisol,
it’s your estrogen, it’s your- Insulin-to-glucagon ratio. I don’t know about insulin-to-glucagon ratio
necessarily. Maybe. I mean it’s going to be close to- That’s the single most classical textbook
index of the fed state versus fasting state is the insulin-to-glucagon ratio. The postprandial insulin glucagon ratio or
a fasting insulin glucagon ratio? Postprandial. Yeah. Yeah. I mean the postprandial is the fed state,
fasting is the fasting state. Yeah. [crosstalk] those things. I think you can see those things change when
people limit calories too much on these type of diets. I do not think carbohydrates are a unique
fed state signal. I don’t think we can need them to be in the
fed state. I agree. Sorry, I didn’t mean to cut you off. Yeah, and I mean maybe we should talk, I wanted
to comment a little bit about the FASTER study as well, but- Well, let me just state that I think we’re
in a complete agreement that carbohydrates are not a unique fed state signal. My position is simply that they’re a more
robust fed state signal and anecdotally, I think you make a compelling case that you
can have adequate fed state physiology on a carnivore mild keto diet. It’s worthy of study where that threshold
is and what are the contextual things that modify that and it’s worth keeping in mind
that when we come across someone who maybe doesn’t do that well on carbohydrate restriction
that less robust fed state signal might be why. It’s not to say that there aren’t other contextual
things to look at, like are you getting enough calories? I just think carbohydrates are one of the
things to look at in that calculation. Absolutely, absolutely. You want to talk about the FASTER study. I do want to talk about… You also want to talk about last time, so
I want to make sure we do talk about the acidosis issue and then let’s wrap up with final thoughts. This is going to be a long one, Chris. We’ll go quickly through these last- The FASTER study, they had 10% carbohydrate
in the diet and it was… And it’s an intriguing study that I would
encourage you to look at, its metabolic characteristics and keto adapted ultra endurance runners and
there was equivalent glycogen storage and utilization on this diet when they were at
10% carbohydrates for a period of keto adaptation. It was [crosstalk] It was a very low carbohydrate diet. It was just four times higher in carbohydrates
than the [Phinney] 1983 studies showing that glycogen in the muscles was cut in half. I just dispute that you can say that’s keto-adaptation
over months rather than less extreme carbohydrate restriction. You got to wonder. Yeah, we’ve got to compare the study and we
got to wait. We got to look at my muscle glycogen. There are a couple of quite interesting studies
looking at performance in ketogenic diets. I can send these to you. Keto-adaptation enhances exercise performance
and body composition responses to training and endurance athletes is the first one. I got to look and see how ketogenic this one
was. This was a 12 week ketogenic diets and the
low carbohydrate ketogenic diet group had significantly greater decrease in body mass
and body fat percentage and they had no change in the 100 kilometer time trial between that
group. And the high carb group, no change in the
six second sprint peak power are actually the ketogenic group. The low carbohydrate ketogenic diet increased
their six second peak power by eight Watts per kilogram body weight and the high carbohydrate
group dropped a negative 0.1 wa- A carbohydrate group trapped, -0.1 watt per
kilogram, and then the last measure was the critical power test. The peak power decreased by 0.7 watts per
kilogram and the high carb group increased by 1.4 watts per kilogram in the low carb
ketogenic group. Again, it was 12 weeks of keto adaptation
and this group had 6% carbohydrates, 17% protein, 77% fat. I mean, pretty interesting in terms of performance. There’s another one, Effects of four-week,
very low carbohydrate diet on high intensity interval training responses. This one was eight plus or minus 3% carbohydrates
in the low carb ketogenic diet group, and they performed great at high intensity exercises
and basically in summary there was no difference between those groups after a period of two
to four weeks of keto adaptation. In terms of performance, those studies are
intriguing for ketogenic diets. People always say, “Oh, you can’t do these
things on a ketogenic diet,” and I really think it’s fascinating. This question of muscle glycogen stores on
a ketogenic diet are fascinating. Again, I just did a podcast with Stan Efferding
and I’m curious. If I’m carnivore macros, what if you’re doing
zero carbohydrate or you’re getting a robust amount of protein will that increase glycogen
stores in the muscle? Who knows? But at least there’s some evidence that with
6% and 9% carbohydrates, the performance was equivalent after keto adaptation. Yeah, I think protein is super important here. I mean, so you recommend what is a higher
than average amount of protein in the diet. Oh, yes. I don’t want to go into all the details of
the studies because I did and we can post this in the show note. I did a review of the, of the evidence in
a Masterclass with Masterjohn Energy Metabolism Episode that took me over an hour to go through
the details of the studies. I think that I just don’t want to go into
that level of detail on the topic. I think we’re in agreement that you can get
good sports performance on a ketogenic diet. I don’t think that’s very questionable, I
think in principle you must have saturated muscular glycogen stores to be able to go
at peak intensity for the longest. You raised an important question here and
I made this point to before, that the degree of carbohydrate restriction and the amount
of protein in the diet are going to be key in determining how much muscle glycogen is
depleted. I think if we really want to answer this,
we have to ferret out the methods in measuring whether you’re getting to the highest intensity
and people have used different methods around that. You have to ferret out this idea around keto
adaptation. I mean, you and I still can’t come to agreement
precisely because there’s not enough data on it, whether Phinney 1983 and Volek’s FASTER
study are different muscle glycogen because of time of adaptation versus amount of carbohydrate
in the diet. I think that the evidence indicates that you
can get good sports performance on a ketogenic diet. I think the physiology indicates that you
cannot get maximum intensity unless your diet in some way is maximizing your muscle glycogen
stores. It’s just physiological fact that peak intensity
will require that you use anaerobic glycolysis. It’s hard to measure peak intensity in a study
because you have to provide adequate incentive to out compete the other person in order to
get there. That’s hard but we also have to look at things
like muscular glycogen content. What’s the threshold of carbohydrate restriction/how
does protein compensate when determining that? I just think that the studies are right now
kind of a mess. I think they vaguely support the idea that
if you do the model right, peak intensity requires carbohydrate, but there’s just too
many unanswered questions and none of them are … if you fall into the camp of it takes
a couple months to keto adapt, then no one has done those kinds of studies, unless you
count Volek’s observational study, the FASTER study. I’m going to leave my position at that. Yeah, and I mean it’s not … I think that
right now it’s just an academic question. I don’t have a bias against carbohydrates
per se. I just personally have found that I feel mentally
much more clear when I exclude them, and I don’t see a necessity for them in my diet. A nose to tail carnivore diet doesn’t have
carbohydrates so we have these types of academic curious meanderings together but I don’t have
a problem with carbohydrates. If people are kicking ass and loving their
carbohydrates and using carbohydrates as a [inaudible] signal to increase their muscle
glycogen. I think that’s awesome and I also want people
to know that there appears to be some compelling evidence that we may not need them to achieve
these levels of muscle glycogen and peak performance should we construct the diet well. But I appreciate so much that you’re putting
the contextual perspective on this because I do think that if we don’t get enough protein,
it’s likely we won’t have enough muscle glycogen, and- Yeah. That’s how I- I agree with that on protein for sure. Speaking of academic curiosities, one of the
things that you wanted to talk about in part one that we never got to, and we’re still
saving for last now, is the Inuit and why they have their genetics chairmen in ketogenesis. Can we tackle this? I think we can do it in five or 10 minutes. I don’t think we need to debate every detail,
but I think we can lay out the basic positions. I did this video back in 2017 I think, where
I argued that the Intuit have a CPT1A defect which specifically prevents fatty acids from
entering the mitochondria in the liver but not in other tissues and thereby specifically
prevents ketogenesis. I argued that that was the reason why, and
this by the way, is a metabolic disorder. It causes … it can in some infants cause,
and children, seizures in response to fasting. It is associated with infant mortality in
terms of homozygosity and it does when homozygous, it does dramatically increase the risk of
hypoketotic hypoglycemia during fasting, which is where you don’t produce ketones or enough
blood sugar, and so the brain starves, which can lead to hypoglycemic symptoms including
seizures, coma and death. The presence of this allele that blocks hepatic
beta oxidation therefore, ketone production basically achieved nearly universal prevalence
in the Arctic. My rationale for this was that ketogenesis
provides acid stress that when there are enough other stressors can lead to clinical acidosis. A few things to go along with that, there
are case reports of people developing and I know you have some criticisms to these. There are case reports of people developing
ketoacidosis from fasting during lactation, a couple of people on low carbohydrate diets
and of course there’s well known alcoholic ketoacidosis. In the case of the Arctic, the Arctic environment
appears to have created what we would expect to be other problems in dealing with acid-base
balance in the Inuit. In particular, most humans will spare their
nervous system at the expense of their bones by leeching calcium out of their bones to
provide calcium to the brain. The Inuit appear to have a adaptations that
lower parathyroid hormone to prevent bone resorption and have much better bones and
teeth as a result of this, but are much more vulnerable to hypocalcemic tetany. One argument for why this occurred was that
the Arctic environment is so physically demanding and harsh that the Inuit would benefit by
sparing their bones even at the expense of hypocalcemic tetany. It happens to be the case that one of the
key responses to acidosis is to take bicarbonate out of the bones. That’s part of the acidosis … a part of
compensation for acidosis. Part of it is to pee out the acids, part of
it is to breathe out carbon dioxide, part of it is to take bicarbonate out of the bone
to buffer the acids. It’s also the case that cold environments
are themselves compromising to acid-base balance. Cold environments decrease gas exchange across
the lungs. In hypothermia, this becomes a cause of acidosis
because you can’t exhale carbon dioxide as effectively. Cold environments also slow the excretion
of acid by the kidneys. In hypothermia, this becomes extreme enough
that the pH of the blood can drop as low as six and part of the cardiac arrest that can
occur in hyperthermia is from acidosis. There was a study, I think it was done in
Norway where they looked at a 10-year follow up of people who were admitted to the hospital
for primary hypothermia that caused cardiac arrest and the 10-year survival, one of the
main predictors, was the pH of the blood at the time of admission to the hospital. If the hypothermia had led to a pH of 6.0
they were likely to have died within the 10-year followup and the mean pH of the blood at time
of admission and the people who were survived after 10 years was 6.6. Hypothermia itself is a major impairment in
acid-base balance. When you’re on a ketogenic diet, you have
a 20-fold increase in the amount of acid in terms of the energy molecules carried in your
blood. Normally the only energy molecule, yes, there’s
other acids but the only energy molecule that you carry in your blood, it’s acidic usually
is fatty acids. If you get into a prolonged fasting or a very
therapeutic level ketogenic diet, you’re going to 20-fold increase the amount of circulating
acids carried by the ketones. Yes, I will definitely say that almost no
one who self selects a ketogenic diet develops ketoacidosis. No mistake about that. But in an environment where you have multiple
stressors placed on you including genetic adaptations to the cold or to the harsh environment
that prevent bicarbonate buffering, and the fact that the cold environment slows the adaptations
to acid-base balance, and also increases the risk of hypothermia where you can cause acidosis
in and of itself, then I think that being in a perpetual state of ketosis would create
an additional liability and that protecting the body from ever having 20-fold increases
in metabolic circulating acids is going to limit that degree of risk imposed by the other
aspects of the environment. That’s the updated version of my hypothesis. I know, I believe you favor Peter’s hypothesis
about warming or you can take whatever position you want. Yeah, so lot of parts to that. I think that the notion that dietary … the
ketogenic diets could lead to clinical ketoacidosis has not been demonstrated in the literature. The theory that you’re suggesting is pretty
much based on that possibility that that ketones could lead to ketoacidosis and therefore the
prevention of ketosis with the CPT1A mutation would prevent that. Now, I think that that rests on the premise
that people can get ketoacidosis from the ketogenic diet, which I said this has not
been demonstrated in the literature. There were four, as you’ve noted, there are
thousands, perhaps tens of thousands of people who are doing ketogenic diets with levels
of beta-hydroxybutyrate that are much higher than mine a lot of the time and people that
do episodes of fasting that last five to 10 days getting levels of beta-hydroxybutyrate
up to five, six, seven that do not develop clinical ketoacidosis in any way, shape or
form. There were a number of cases in the literature,
there were four cases in the literature- Because of acid-base buffering. Would you agree with that? Yeah, I believe that the body’s going to buffer
it. Yeah. There were four cases in the literature that
you found, and unfortunately in only two of those was the level of beta-hydroxybutyrate
actually measured in the blood. My feeling is that, and in one of those cases,
the level of beta-hydroxybutyrate was only 3.7 millimolar. You and I went back and forth a little bit
about potential situations in which you could have more acetoacetate relative to beta-hydroxybutyrate. That doesn’t seem terribly plausible to me
based on the fact that those two ketoacids equilibrate primarily based on the ratio of
NAD to NADH and you would have to have a largely imbalanced ratio to have a huge amount of
acetoacetate. When we see people on the hospital, if ketones
are even measured in the blood, it’s almost never acetoacetate. None of these measured acetoacetate. Only two of them, like I said, measured beta-hydroxybutyrate
and one of those was 3.3 which is not a high enough beta-hydroxybutyrate- But, I gave you a paper that showed that the
range of a acetoacetate to beta-hydroxybutyrate ratios in kids up to age 14 and I don’t have
data for older people, the mean is around one but the range goes up to 25. It seems like I don’t see any problem with
the possibility that her acetoacetate could’ve been great … her acetoacetate could have
been enough to bring that to 10 millimolar. Well, I think we’d have to look at that kids
and kinesiology. Why would it be so imbalanced in kids? Usually it equilibrates to one-to-one? Why would it … Well there’s almost no studies that show the
range of the ratios. Almost every study just tells the mean of
the ratio. Yeah, it would be … It’s very unusual. It would be very unusual to have a ketoacidosis
for the beta- hydroxybutyrate of 3.3 unless there’s something completely- I had my assistant completely scavenge the
literature looking for this and we compiled all the papers on the ratios and only one
of them had the range of ratios. That one is the one that showed that the range
was really broad and could have a acetoacetate to beta-hydroxybutyrate ratio of up to 25
in one of those people. And in order for that to happen, you’d have
to have a profoundly disordered NAD to NADH ratio to push it in that direction, and it’s
like, why would that happen? I think it’s very unusual, in my opinion,
in the other paper where beta-hydroxybutyrate was measured, that one we really can’t even
pay attention to because that person has chronic pancreatitis and an alcoholic. I mean chronic alcoholism. That one is not, in my opinion, the case of- Well the chronic alcoholism is the alcoholic
ketoacidosis paper, isn’t it? Yeah, there’s a ketoacidosis paper. No, I was just collecting the papers at a
non-diabetic ketoacidosis. Alcoholic ketoacidosis is one of the models
for that. Yeah, different, totally different situation. In that situation, her blood glucose had been
as high as 500 in the past, so she clearly had pancreatic dysfunction. In the other case reports that are in the
literature, the beta-hydroxybutyrate is not measured, and so we can’t really say that
this happens. I think there could be metabolic abnormalities
in these people, but these are unique, perhaps unique metabolic dysfunction that do not represent
the large population of people. So unless, in addition to CPT1A polymorphisms,
unless there’s a large metabolic dysfunction or a large predisposition to developing ketoacidosis
on a ketogenic diet, in the Inuit that goes along with CPT1A or if unless CPT1A also predisposes
them to gets ketoacidosis on a ketogenic diet, I have a real problem with the notion that
a ketogenic diet is really going to put them at risk. Do you find- Of ketoacidosis. Do you find it implausible that during the
migration to the Arctic there was some period where hypothermia was common? I mean- I mean it’s really cold up there and requires
cultural adaptations in any genetic adaptations to handle the cold. Yeah, I don’t think that there … I mean
if you look at how low people have to get in terms of hypothermia to affect their acid-base
status, it’s incredibly low. It’s in the level of the blood body temperature- Well what if- Well wait, wait, wait. The body’s temperature has to get into the
eighties Fahrenheit to affect acid-base status. I definitely do not think that the Inuit are
walking around right now with body temperatures in the eighties. They’re not clinical possible. Well I don’t think so either but I wouldn’t
be surprised if a number of people at some point in the history fell into a lake or something
like that. I mean it’s a freezing cold environment and
so it has to be the case that during a period of genetic adaptations and cultural adaptation
that exists today, there has to have been … and they have other signs of adaptation
to the cold. Those have to be driven by a period of greater
cold exposure than they have now because of whatever forced the selective sweeps to favor
that. It seems very plausible to me that flat out
hyperthermia would be a major risk of the Arctic environment. But, also, I’m not so sure that it’s fair
to say that you have to reach a threshold to affect acid-base balance. I mean generally the mediation is driven by
temperature which slows molecular transfers so everything slows down at cold temperatures. I think one of the issues here is that I’m
not saying that classical ketoacidosis that comes in diabetes would be the feature that
you would see. I’m just saying that the combined acidosis
from multiple factors including impairments in being able to handle acid-base stress could
combine to produce acidosis. Of course it’s going to look different in
that picture if it’s partly mediated by lower bicarbonate from lower bone resorption, partly
mediated by colder temperature, partly mediated by ketone production, et cetera. I mean if you take … you can have a mixed
acidosis, you know? Well the other thing that we haven’t discussed
is that I think that the data on ketogenic diets doesn’t support the fact that there’s
any change in blood pH. There were a number of studies that we- Because of acid-base buffering. Well sure. But clinically, it’s not observed. There’s no significant change in pH status
in three or four of those studies that we looked at together, Chris. It doesn’t really … It seems like the body
can adapt to this. We certainly don’t absorb or change the bicarbonate- Yeah, by taking bicarbonate out of the bone,
by exhaling carbon dioxide in the breath, and by peeing out ketones. Yeah, and there may be other mechanisms by
which we buffer it, but clinically we don’t observe changes in pH. And so the idea that CPT1A … The other thing
about CPT1A which Peter has noted in his blog is that the mutation is not pervasive in the
Arctic, that it’s concentrated in the coastal areas. The theory that he advanced was that it may
have something to do with omega-3 fatty consumption, but in the inland areas, it’s less common
to have a CPT1A mutation. It’s not 100% of the people. The coastal regions is more common, which
suggests that doesn’t make a whole lot of sense because that suggests another factor. He also talks, I think it’s also interesting,
his theory is that- Well he made the point that omega-3 from marine
fats upregulates CPT1A. Or, that it allows increased utilization of
fatty acids. Right, but his explanation for why it’s more
common in the coast was more marine fat, more omega-3s would upregulate CPT1A. It does make sense that if the, if CPT1A is
a risk of course factors- How would it? … that would increase its expression. How would it increase the expression? It’s like epigenetic modifier with omega-3s. I thought it had something to do with fatty
acids moving across the membrane than … Well omega-3 fatty acids are burned at a higher
rate for beta-oxidation. I’d have to look up those mechanisms. I’m quite sure that was his rationale though. I thought he had different rationale. Oh. Then he suggested that perhaps with increased
free fatty acids there was more of an uncoupling effect and it was probably a thermic effect,
but I don’t know. I do you want to say one thing about that. I wouldn’t be surprised if there’s a thermic
effect of it. I just don’t see the rationale for having
a specific impairment in ketone production, highly specific impairment in hepatic beta-oxidation
that causes the risk of hypoketotic hypoglycemia seizures and infant mortality in order to
achieve warming that we already have a sophisticated system for involving the hypothalamus, norepinephrine,
free fatty acid and lipolysis and UCP1. There are so many polymorphisms that could
be selected for in terms of brown fat production in terms of the hypothalamic response to cold
and in terms of UCP1 expression that I just don’t see why we wouldn’t see the changes
aimed at warming targeted all in those pathways and there are changes there, but why leverage
something that has such a specific effect on ketone production simply to get more warming
out of that rather than creating higher leverage in the system of warming as it’s designed? I don’t know why it would go one way and not
the other, but I think that the idea that they are trying to avoid ketosis for reasons
of acidosis, I just don’t think it … I don’t think there’s enough data to support that
with all the things we’ve talked about initially. Okay, fair enough. Do you want to add any final thoughts? I think we can take our break at least until
part three for now. Oh, Jesus. It’s been a long time. It was great having you on. I think we’re largely in agreement that keto
and carnivore can be tools to used. We’re largely in agreement that we need more
study. I think we’ve fallen a little bit different
places in terms of the probability that these things are going to offer, complete protection
from all the possible negative effects that we talked about. But certainly context is super important and
you’ve done amazing work in lining out how to properly plan a mildly, ketogenic, carnivore
diet, and if you’re going to do mildly keto carnivores, certainly do it the way that Dr.
Saladino has designed it. Oh, thanks. Yeah, so thanks for having me on. People can find more of my stuff at my website,
which is carnivoremd.com. I mentioned my podcast a bunch. It’s Fundamental Health with Paul Saladino
MD. I got a book coming out in February called
The Carnivore Code. Interestingly the subtitle is Unlocking the
secrets to optimal health by returning to our ancestral diet because you didn’t have
the amylase is what I’m going to put back in that subtitle with it. It’s going to be on the cover. No amylase. Awesome and so we’ll cross-post this. You can find me at chrismasterjohnphd.com
and check out my vitamins and minerals course set at chrismasterjohnphd.com/101. All right. All right. Thanks, Chris. Take care, Paul. This is great. Thanks. This episode is brought to you by Ample. Ample is a meal in a bottle that takes a total
of two minutes to prepare, consume, and cleanup. It provides a balance of fat, protein, and
carbs, plus all the vitamins and minerals you need in a single meal all from a blend
of natural ingredients. It’s available in original, vegan and keto
versions. Portion is either 400 or 600 calories per
meal. I’m an advisor to Ample and I use it to save
time when I’m working on major projects on a tight schedule. It gives my brain going while I power through
the day, never letting food prep get in the way of my productivity. Head to amplemeal.com and enter the promo
code: Chris15 at checkout for a 15% discount off your first order. This episode is brought to you by Ancestral
Supplements, grass-fed beef brain. Our Native American ancestors believed that
eating the organs from a healthy animal would support the health of the corresponding organ
of the individual. Ancestral Supplements has a nose to tail product
line of grass-fed liver organs, bone marrow, brain, and more all in the convenience on
a capsule. For more information or to buy any of their
products go to ancestralsupplements.com. All right, everybody. I hope you enjoyed that. This has been the Carnivore Debate Part Two
with Dr. Paul Saladino, Carnivore MD and yours truly, Dr. Chris Masterjohn, PhD. You can find my work at chrismasterjohnphd.com
and you can my free guide to getting your vitamins and minerals on a carnivore diet
at chrismasterjohnphd.com/carnivore. You can find Dr. Paul Saladino’s work at carnivoremd.com
and you can find his podcast in your favorite podcast app as Fundamental Health with Dr.
Paul Saladino. I hope you enjoyed this and I’ll see you out
on the interwebs.

Tagged : # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # #

Methew Wade

8 thoughts on “The Carnivore Debate Part 2 | Mastering Nutrition #70”

  1. 00:42 Cliff Notes
    05:18 Introductions
    05:28 What is a carnivore diet?
    18:15 Is the ancestral human diet carnivore or omnivore?
    50:40 Who is a carnivore diet for?
    01:08:03 To what extent do carnivore and keto overlap?
    01:10:34 Who is a keto diet for?
    01:18:50 Ketogenic diets are only a partial mimic of fasting physiology
    01:23:46 Ketones effect on the NAD/NADH ratio
    01:27:31 Ketogenesis has opposite effects in the liver as in the ketone-utilizing tissue.
    01:29:31 Ketogenic diets and oxidative stress
    01:40:18 Longevity: why you want to cycle between the fasting state and the fed state
    01:45:04 Can the ketogenic diet provide a sufficiently robust fed-state signal?
    01:53:11 The keto diet and thyroid, stress, and sex hormones
    02:10:05 Keto and sports performance
    02:18:05 Why do the Inuit have a genetic impairment in making ketones, to protect against acidosis, or to stay warm?
    02:35:48 Wrapping up

  2. There is no debate! Stop misleading the people! WFPBD is the only diet proven to reverse disease and help longevity! It's the best diet for humans.

  3. Getting shorter was good…in what longevity is concerned… shorter live longer than bigger..there are scientific proof of that.

  4. What were the mega fauna eating? Maybe, after they were over hunted, people ate the food that their food was eating

  5. Regarding the salivary amylase discussion around minute 50, from wikipedia:
    "However, not all humans possess the same number of copies of the AMY1 gene. Populations known to rely more on saccharides have a higher number of AMY1 copies than human populations that, by comparison, consume little starch. The number of AMY1 gene copies in humans can range from six copies in agricultural groups such as European-American and Japanese (two high starch populations) to only 2–3 copies in hunter-gatherer societies such as the Biaka, Datog, and Yakuts."

  6. Chris, re Potatoes: When I was eating a Plant Based diet for health reasons, I developed an allergic reaction to potatoes. After a few bites I would start sneezing violently, my nose would become itchy, my throat would close off, and I would gag. Red, white, russet, gold. Any potatoes. Now, I ate potatoes all my life with no problem. Since I went back to eating animal foods I occasionally eat a little, with no reactions. It must be all the plant poisons like Oxalates that did it? Also, yams made feel bad and gave me horrible IBS symptoms. I will eat a few bites at Thanksgiving this year, but usually avoid it.

Leave a Reply

Your email address will not be published. Required fields are marked *