The $10M Gap: Why Metabolic Health Research is Failing Us | Nick Norwitz DSH #908

This is interesting

because I think that interest from the general public actually has a lot of value.

We'll talk about the citizen sciences movement later, but to cut to the story, I envisioned this experiment where I could use my understanding of new physiology, new metabolism,

to lower my cholesterol, which a lot of people see as bad, with Oreo cookies.

All right, guys, we got Nick Norowitz here today.

He's working on some very interesting studies.

Could you tell everyone what you're working on right now?

Sure.

I mean, I have my foots in a lot of different puddles, but a lot of my research broadly right now is in metabolism.

So cholesterol, lipid metabolism, particularly in low-carb diet context.

That's my area of interest.

Things like carnivore diet, inflammatory bowel disease.

We got a lot going on, so we can start wherever you want.

We'll start with the one that made you break out in the space, which was the Oreo one, right?

Yeah.

So

me and my friends had been studying cholesterol cholesterol dynamics, particularly in a low-carb context, for some time.

To give a little bit of framework to this,

one of my areas of interest is in therapeutic carbohydrate restriction, so low-carb diets, including ketogenic diets, which now are becoming very popular for far beyond things like diabetes and obesity.

People may or may not know they had, or ketogenic diets have been used for about 100 years for epilepsy, but now they're being used for mental health disorders, inflammatory and autoimmune disorders, and the literature is picking up steam really fast.

But a major obstacle to clinical implementation of ketogenic diets is cholesterol levels.

Because some people see their cholesterol levels shoot through the roof, like not just blip up, but go to levels that are so high that if a doctor sees it, they either think it was a lab error or that you have a one in one million genetic condition, like homozygous familial, hypercholesterolemia.

So, my history is I adopted a ketogenic diet back in 2019 for inflammatory bowel disease.

It happened to work for me, but I was surprised to find, you know, I had this response and my cholesterol shot through the roof.

And so using myself as a case in point, you get caught between a rock and a heart place, right?

It's like my levels are so high that some people think I might, you know, get a heart attack in a few years and die in my 20s of heart disease.

At the same time, this dietary intervention is working wonders for something that basically had me in palliative care in the ICU.

So there's a lot of patients, different conditions, that are caught between this rock and a hard place.

And so the reason this is an area of interest is I kind of want to address this cholesterol boogeyman, particularly in that context, and start to unravel some of the really interesting metabolic mysteries that I think are going on.

in what we've termed the lean mass hyper responders.

That term isn't really important right now.

We can break it down.

But getting to your question about the Oreos,

you know, I'm a total dork.

Like, I haven't introduced myself, but like my background is I did cell bio and bio cam at Dartmouth.

I graduated valedictorian there.

I then went to Oxford to do my PhD in metabolism.

Now I'm finishing up my MD at Harvard Medical School.

Like I've done the most conventional of conventional trainings.

My head has been stuck in books and academia and it's been fun.

Like I love engaging in that environment.

But we're living now in a time where academia and the general public are colliding because the the general public has

access to information, which I think is awesome.

Right.

We can have conversations like this and disseminate it to a bunch of people.

But then you ask the question, like,

how do you bridge that gap and get people interested in?

I've thrown out some terms now, talked about cholesterol, I've talked about lean mass hyper responders.

Maybe I'm losing people.

The point is, like, how do I get people to turn to this and say, wow, this is interesting?

Because I think that interest in the general public actually has a lot of value.

We're going to talk about the citizen scientist movement later, but cut to the story, I envisioned this experiment where I could use my understanding of new physiology, new metabolism,

to lower my cholesterol, which a lot of people see as bad, with Oreo cookies.

And that wasn't enough for me.

I wanted to do it quite rigorously.

So I wanted a comparison.

The obvious comparison is the most common medication used for Oreo cookies, statins.

So I used high-dose statins.

and

I actually had a lipidologist consulting, a professor named William Cromwell, who's highly respected in academia.

I went through the Harvard IRB, got the appropriate exemptions,

dotted my I's, crossed my T's, and then ran this protocol that we ended up publishing the data.

So you can go look Oreo versus statin on PubMed, you will find it.

And basically the intervention was I just, you did a run-in of my normal ketogenic diet,

and then I added on Oreo cookies, one sleeve per per day.

So that's 12 cookies, about 100 grams of carbs, and did that for about two weeks.

Wow.

Then did a washout period of three months to kind of return to my baseline status, and then did high-dose statin therapy for six weeks.

The results were that in my particular metabolic context, which I engineered to kind of do this metabolic demonstration, the Oreos lowered my LDL cholesterol.

Some people call that the bad cholesterol.

They lowered it by 71%

in two weeks.

Wow.

And this is not something I'm faking.

Like, this is going straight into my

health record online in Epic to my PCP.

You know, I'm getting the labs done standard through.

There's no faking that result.

In fact, actually, the funny thing is, if you look at the paper, it's a 16-day

quote, two-week block.

The reason it was 16 days, not 14, is because at 14 days, which was the second blood draw after the intervention started, the drop was so profound, me and my team decided, let's replicate this on two sequential days, so triplicate, just to make sure this isn't a lab fluke.

And actually at that point, my cholesterol was still going down.

So it dropped 71%, and then a statin had the expected effect a statin would have, which is actually about, in my case, it was 32.5%.

But the punchline was, the headlines ran, Harvard scientists, Harvard medical student, lowers cholesterol with Oreo cookies and they outperform a statin.

This was an interesting thing for me.

We can delve into the metabolism a little bit, but

there was the one element of it, which was I wanted to do a metabolic demonstration for the metabolic demonstration's sake.

There was the other element of it, which was a social experiment for me.

Because

I feel like we're living in a really exciting time.

I alluded to it already, where like academia, general public, social media, they're colliding.

And I get to kind of like work at that interface.

So what would the result be if I threw out a social media grenade like that?

And would it facilitate productive discussion or just put everybody into an unproductive frenzy?

And truth be told, I didn't know what the answer was, to be honest with myself.

So there was always a gamble this could do more harm than good.

And I was going to try to be honest and audit the effects.

I would say I'm pretty confident it's had a positive effect.

Really?

Yeah, we can break that down, but I'll pause right now to just like kind of get questions high level and explain why this happened.

Or anyway, go ahead.

Yeah, so it helped with the cholesterol, but I would argue Oreos are pretty unhealthy for you.

Agreed.

I agree.

So that's the thing, right?

Is your visceral emotional response or anybody that's listening is

trying to put a value judgment on this?

Because what you have here is an apparent paradox.

Quote, bad intervention.

Do we agree Oreos?

Adding, look, this wasn't a swap, so I wasn't like swapping out fats.

I was adding Oreos.

Do we agree that adding Oreos to the diet is probably an unhealthy intervention?

And then people would think you're lowering your LDL, quote, bad cholesterol is a good thing, especially if you have exceptionally high levels to begin with.

So what do we have here?

Bad intervention coupled with good outcome.

Even if that's in only one patient, you have to grapple with that and say,

how do we reconcile this?

And I think the interesting thing and the reason, among others, that I knew this would go viral was that people are uncomfortable with that cognitive dissonance.

When I say bad intervention, good outcome, I show that.

They want to put a value judgment.

They want to layer a value judgment.

Like, oh, this proves LDL isn't a problem.

I didn't say that.

This proves statins are poison.

I definitely didn't say that.

This proves Oreos are a healthy question mark.

I definitely didn't say that.

I said none of those things.

And so my whole shtick, you'll hear me say it again and again, is stay curious.

I think curiosity is really what lets us fully manifest our humanity.

And so

I invite people, I do a lot of now weird demonstration, put out provocative content, but not one that is actually like in any way dogmatic.

It's just like, here's a curiosity, and I want to invite you to investigate this with me

rather than reflexively jumping to a value statement.

And then when people do jump to that value statement, kind of investigating, well, why did we do that?

And how can we

attenuate that response to actually have more productive dialogue?

And I will tell you, you know, I was saying that I think the Oreo versus Statin Study had positive effect.

It's been really funny.

I mean, I've talked about this in academic circles, at Harvard, at conferences, universally in academia, people are like, wow, this is fascinating.

And I get emails from clinicians, cardiologists, like, I read this study and I was provoked to go down the rabbit hole of your literature because we have a lot more studies on it.

This was just kind of like a provocation to get people to look at those studies.

And they're now saying, I understand the physiology of your model.

It's called the lipid energy model.

And now I have patients in the metabolic state you're in.

But rather than jumping to medications, we're trying like carbohydrate, quote, titration protocols.

So we're using bananas, sweet potatoes, and we're lowering LDL more than medications ever would.

And so then the patient's happy, the doctor's happy.

And I don't know, you know, what the absolute benefit of that intervention is, but if we're set in an area of unknown and you have patients in those places like me, where they're between a rock and a hard place, the more options we have and the better we understand the physiology, I mean, the better.

So the fact that this is already being leveraged, our understanding of the mechanisms by clinicians, I think is pretty exciting.

And I can't name names, but

well, I should say, the reason I did the Oreo versus Tatin experiment is because I'm, I was at this time 27, I'm now a 28-year-old, PhD and medical student with no money.

If you gave me $10 million to do a study, I would never have needed to do this.

But

But this is a way to get attention to then generate partnerships to get those funds.

So So right now we're designing a study with a really prestigious lab.

I don't want to throw them under the bus in case this podcast goes sideways, but where we're probably going to try to do like a $1.2 to $3 million multi-omic study.

Wow.

And this arose because the conversations I got to have because of

doing something crazy like Oreo versus Staten.

So

it's been a little bit of a ride, but it's been fun.

That's interesting.

So as an entrepreneur, what's the business side of these studies?

Because you're spending millions to fund them then.

Ah,

that

is a critical question.

And I'm going to reframe it, which is,

I would say the reason metabolic health studies don't get done is because there's not a clear business model.

There's a very clear business model for pharmaceuticals, cellulose drugs.

Metabolic health interventions don't immediately make people money, which actually sets up a really unfair comparator.

Because when you go into medicine people want quote evidence-based medicine and that sounds sexy it's great virtue signaling right we want the high-grade RCTs to prove this intervention works

however if you have millions of dollars

not billions of dollars really going into funding pharmaceutical trials

procedural trials you're gonna have a larger body of literature on that than on something that actually doesn't have a clear business model.

So I was actually talking with one of my professors at Harvard who added this

project he wanted to do.

It would be about a $10 million project,

$10 million.

Oh, million.

Which actually sounds like a lot.

But then I'm like, let's quantify this and do a comparison to see like, you know, what is, this is hard money to get for a metabolic health intervention that actually isn't easily monetizable.

How does that compare to say Novo Nordisk market cap?

Just name one company.

And it ended up being that is the same as the mass comparisons of a Cairo spiny mouse versus two adult hippopotamuses.

Like the pools of money are enormously different.

Then you layer on to metabolic health interventions, which are like, you know, lifestyle diet interventions, do them rigorously.

It's expensive.

It's hard to recruit, get ethics.

And what you end up with is a research infrastructure that is biased wildly against these sort of interventions.

So how do they get done?

This is a really sad reality, is there are now studies getting done.

But I think a lot of it is not coming from,

you know, NIH funding.

NIH doesn't have a ton of funding to throw at this compared to, say, pharma.

But often philanthropists who are funding these trials because they've, or their family has suffered.

And so

I'm only in this space because I suffered terribly with inflammatory bowel disease.

I'll make an example of like the bazooki group.

I don't know if you've heard of them.

They're funding a lot of trials in metabolic psychiatry at Stanford, at Harvard.

They gave a friend and colleague of mine, Chris Palmer, I think several million dollars to start up like a metabolic psychiatry clinic at McLean.

I don't know if they've branded it that exactly, but the only reason they're pouring money into this is because one of the members of the family suffered terribly with bipolar disorder and ended up going into remission only with metabolic therapy, in this case a ketogenic diet.

And so then they became passionate about this as something that is worth doing

to help people.

But you see kind of like the disconnect there.

You have a business model for pharmaceuticals and on the other end you have a research environment that is being built on the backs of passionate people who have suffered and people with different resources, which is really unfortunate at the one level.

It doesn't seem fair that it's happening that way.

However, the silver lining I put there is that like

that motivation and that purpose-driven

energy, I think

is going to win the day in the end because the data will win the day in the end.

And

once you get enough people and there's more and more of us who are suffering and you have the right people suffering come together, then trauma bonding.

Yeah, then you're going to get the studies done.

And that's not to discount like, you know, the New England journal trials that prove a pharmaceutical is beneficial or say that

pharmaceuticals aren't beneficial.

It's just saying we have a chronic disease, a metabolic disease pandemic, really, that's rising.

And to treat chronic metabolic diseases at their root requires metabolic interventions, you know?

And and that really, the fundamentals there are lifestyle,

which

I can tell you from being in academia that

nutrition science, and actually the general public probably get this as well, like it's conceptualized as kind of hooey or soft science.

And I get why that is,

because it's probably the scientific field more than any other that is diluted with terrible studies.

And I thought that too, like before I went into metabolism science.

And I say metabolism science to avoid the brand of nutrition science, like, I'm like, I know what's healthy, you know, my plate five-a-day, quote, balanced diets, these platitudes we hear all the time.

The fact of the matter is, I don't consider that true hard science.

But when you start to delve into

the metabolism

and, you know, the

fundamental physiology that really is kind of coming out in the preclinical literature mostly.

So, journals like Nature Metabolism, Cell Metabolism, that's my pleasure reading.

You read things

that

just make you stop and blow your mind.

And I can come up with, you know, a myriad of examples because these things come out all the time, like how the bile acids that we think, oh, they just digest fat, they can circulate in your body, go to your brain, bind to TGR5 receptors, and affect depression.

And this is like in like top tier level scientific journals.

Now it is pre-clinical.

You know, they're doing these mechanistic studies in mice and then people like to brush that away.

But I want to like recognize that disconnect of like, what does it take to take that preclinical and make it clinical?

It requires

the sort of research that is really hard to do unless there's a clear business plan.

And

it's kind of the heart of your question, there isn't.

What do we do that?

So then it just never gets studied.

Yeah, I think we need to reshape the way, you know,

medicine is very dysfunctional.

That is not even a controversial statement to say.

People like think of medicine and hospitals as this like a giant entity that is all aligned.

Like you go into a hospital, you're training in medicine, like the doctors, the nurses, the healthcare workers, they will say, they will shout, this is a dysfunctional system.

And we're just trying to do the best by our patients within it, which I fully believe.

Like the vast majority of physicians I've met are.

tirelessly hardworking and always trying to put their patients first and often martyring themselves in a system that is broken.

Wow.

Which is why I feel kind of like bad you hear a lot of doctor bashing because people get frustrated and they don't realize that the doctors are just as frustrated, if not more frustrated.

And so you have these two parties that appear on social media to be warring when they could not be more aligned.

It's just the broader incentive structures, which only a little bit we've talked about, the economics, say, with respect to the research in pharmaceuticals.

They're the things that are messed up.

And so, like, how do we restructure the incentive structure?

How do we like reshape medicine to be metabolic and foundational, like health-focused, preventative medicine, all of of that, all the nice terms you hear.

If I had

a solve for you, if I had an answer for you, everybody listening should say I'm crazy.

Because everybody's trying to solve, not everybody, but a lot of people are trying to solve this problem.

I'm here talking to you.

I'm a 28-year-old medical student.

I'm not pretending to be super wise.

I can identify the problem.

But to fix it requires, I mean, a multi-pronged approach with,

I have confidence, but the pathway isn't clear to me.

Right.

It'd be tough to fix, I think, with big pharma as the enemy.

Right.

So well, how do you restructure

the incentive structures?

I don't think we cast it as like enemy and

like, you know, virtue and vice, good and bad, like a battle between good and evil.

Like we can think about it that way.

I don't think we're ever going to, quote, win

if it's that way.

There's always going to be like layered incentive structures.

We have to find a way to align the incentives.

So eventually you're going to have to create, I think, in a capitalist society, a business model that favors metabolic health intervention.

It just might be that the studies and the research that are built on the back of these suffering individuals, myself included, might just be the catalyst to jump us to that point.

Along with things like advances in technology,

wearable technology, monitoring technology, if we get more data on ourselves, I've had a provocative statement that I think like, you know, medicine's going to flip in terms of what we see as the gold standard from like the RCTs, the randomized control trials, which we now herald, to

N equals one medicine, which now has a dirty wrap.

Oh, it's the anecdote.

Oh, it's just the case report.

That's nothing compared to the randomized control trials.

But the thing that the top tier of evidence, what we consider the top tier of evidence, now misses.

is you take these randomized controlled trials.

Yes, if you're testing a drug versus a placebo, you can get a group difference in an RCT and say, at a population level, this is efficacious, this monotherapy.

But what you miss there is the specificity, the heterogeneity, because those two groups you were comparing are composed of massively heterogeneous people.

So a drug can prove statistically significantly beneficial.

It doesn't mean that every patient that takes it is going to benefit.

And so

I think where we're moving towards is a form of medicine that is going to focus on the fundamentals of physiology and metabolism, the root cause.

But to get there, what we need is to start collecting lots more data on individuals in like multi-omic profiles.

No, big words.

Sorry for throwing jargon.

But like, you've heard of your genome.

Yeah.

Your proteome, your microbiome, all these things that make you you, which are beyond just you.

If you had the microbiome, you could conceive of yourself as a meta-organism.

We now have technology where we can start to not only take pictures of your

multi-ohm, all the things that make you you, but take multiple pictures over time and end up with this cool video of like you as a physical biological metabolism individual.

And once we understand that and compare, you know, use machine learning, AI, to start to like

see that network, see that video of metabolism, then we can see what's going wrong in it for any individual and build empiric protocols to address the root cause of disease

in a manner that is highly specific and takes into account

the person, the individual at an unprecedented level.

I'm completely making up numbers here, but I think like 15-20 years is that's where we'll be.

Wow.

Which will be a, I think, a real transformation.

That's exciting.

And how we treat people.

I mean, that's maybe me just like pie in the sky, but it's a cool idea, right?

No, that's super exciting.

I just can't see that being affordable to everyone.

It's tricky.

I mean, again, that's the question: is is like, how do you make it economically viable?

I think in any circumstance with new technology, often like it might start in a more privileged population.

We can do things to try to make it more broadly available.

I don't think that necessarily should retard the introduction of the technology.

But the question of how do we make this a viable business model?

I would say broadly, at a large scale, like,

economic level, the multiple metabolic health epidemics, obesity, diabetes, Alzheimer's, like you look at their collective toll on the economy, it's trillions.

Or it will be trillions, say, by mid-century.

Like, it's not sustainable.

So, the only solution is find a way to fix them.

And I don't think we're going to pharma our way out of the metabolic health epidemic, which means

logically,

the only economically viable option is to address the root cause.

The only thing is that requires a long perspective rather than an acute perspective because we're not per se selling a product.

We're looking at the economic toll of poor metabolic health on this country and on this world.

And how we shifted that short perspective to the long perspective, again, that's just beyond my expertise.

It's something I'm grappling with as I'm entering my career.

But again, I would be

arrogant and crazy to tell you I had an answer right now.

So that's why you did this recent study, then the carnivore study.

So

I would say we have a study coming out at the time we record this in about a week or so where it was just, it was a case series of 10 patients used a carnivore diet to treat inflammatory bowel disease, which sounds kind of heretical.

Anything carnivore diet sounds heretical.

And

I would say

that

there

is no funding right now to do, say, the study I want to do, which should say be a rigorous randomized control trial.

I say this in the video abstract that hopefully will be released by the time this podcast drops, of, say, a carnivore diet versus a whole food, plant-based vegan diet in the context of inflammatory bowel disease.

The rigorous, high-grade, randomized control trial that everybody wants to see.

I don't have the funds to do that.

I don't think anybody has the funds or will to do that.

And so, what you're left with is what can we do with the resources available to us?

And so, this is kind of like a first-step provocation of, look, there's biological plausibility for why a carnivore diet or animal-based ketogenic diet could help in inflammatory bowel disease.

That's ulcerative colitis and Crohn's disease, including in treatment-resistant cases where like biologics aren't working, there's these like immunomodulators, all these drugs that people aren't being on and like they're suffering.

You know, at death's door, some of them have parts of their intestines removed.

And I will tell you from direct personal experience, now I'm not carnivore, but from direct personal experience, suffering from ulcerative colitis,

where I had gone in the span of two years from being like a sub-3 marathon runner, high-performing academic to being like in a hospital bed, barely able to like, you know, walk to labs in days that I wasn't on the hospital with brain fog.

Like you get so desperate, you'll try anything, which is actually what got me to try a ketogenic diet.

Now, I wasn't a carnivore diet, but that changed my life.

And,

you know,

it not only made me feel better, but my inflammatory markers dropped.

And I went to eventually biopsy-proven remission.

And I'd been there off medications for a long period of time.

Now,

I won't extrapolate my experience to the general public.

I'm not going to say this will work for every case of IVD and Crohn's.

I don't know that.

But that event for me was enough to get me curious and start to immerse myself in communities and find that, and I say this all the time, but the most remarkable thing about my personal story is that it's not at all unique.

I know so many people who have suffered with chronic metabolic diseases, and conventional medicine just hasn't served them to the point that they get desperate and and try something that seems extreme and fringe and isn't evidence-based, and then it works.

And what do you get when you have these cumulative, you know, clinical narratives?

It's quite compelling, especially when

you can show this to clinicians.

So what we do in this case series of tempatic is we go through people who had severe Crohn's

or ulcerative colitis.

who self-adopted animal-based ketogenic diets.

And all of of them had remarkable, astonishing clinical improvements.

So we go through each of the cases, which I mean, we had lab values, we had biopsy documentation of their disease.

We kind of quantified their improvement on a clinical grade.

And then we just present this as like, here are 10 people's stories.

There are many more, there are hundreds more, but let's start here.

and see if this is compelling enough to then front further research, include patient quotes.

It's like really moving since I interviewed at least nine of the 10 of these patients.

my my colleague also interviewed some

and to talk about how you know some of them say like how like their their life with inflammatory bowel disease was a different lifetime and they just feel like completely a new person

it is it is touching and it just emphasizes the importance of getting this research done

but

It's just even heretical to raise the topic of say like a carnivore diet because of the narratives that a lot of us have internalized.

And so like the question is, how do you open up this discussion and do it in a thoughtful and nuanced manner?

Because

it's easy to get typecast.

You know, like

if I say I'm interested in a carnivore diet, not even that I eat a carnivore diet, which I mostly don't.

that I'm interested in it from a physiologic metabolic level for this use case intervention.

Immediately, people come

to

generate assumptions.

They might not verbalize them, but they'd be like, oh, you must be a climate denier, or you must be like conservative, this, the other things.

Or you must be someone who argues carnivore diet is the best for every person.

You just had Anthony, actually know Anthony right before me.

Right.

And he might have a more staunch position on a carnivore diet than I do.

I would not argue, say, a carnivore diet is the best for longevity or any of that.

What I'm saying is,

here's a particular medical use case where we have a combination of incredible clinical stories, loads of them, along with biological plausibility.

We know that ketones can help with stem cells in the gut, that there is an inverse association between ketone levels in the gut and IBD activity in clinical cross-sections, or that fibrid elimination can be therapeutic in Crohn's disease by changing microbiome metabolism, actually having gut bugs like mucos beryllium migrate around in the gut.

So like I can explain to you the physiology, present to you the biological plausibility, combined with really powerful, true clinical narratives.

And what we're left with there is I think people should be like, well, maybe there's something here.

How do we find a way to invest in future research so that this can be an option, not obligatory, but an option for people who are suffering like you couldn't imagine if you haven't lived it.

Yeah, you might have to hit up Joe Rogan.

I got named up from one of his episodes, actually.

Yeah, I think it was 2069 with Sean Baker.

Oh, okay.

And

actually,

I probably shouldn't confess this, but I'm going to confess this.

It was after that episode, because Joe was talking about the carnivore diet with Sean.

And I know Sean.

We're friendly.

And I'm like, hey, Sean,

like,

why don't we just do a case series on like what use case?

Because there's a bunch of use cases potentially for carnivore diets and autoimmune inflammatory conditions.

I have a soft spot for IBD because I've suffered from it.

And so he helped us recruit some of the cases.

And

it was actually with a mind to be like, you know, Joe might find this interesting.

So we'll see if he comments.

It's a pretty easy read.

It's one of these things where, like, look, this is a bunch of clinical stories.

There might be some medical jargon, but it's going to be open access, published probably on September 2nd, if not before.

And people can just give it a read, see if they find it compelling.

We present in the discussion section, you know, our arguments for biological plausibility.

And bear in mind,

while people like to, again, you know, generate camps, like I mentioned Anthony, I mentioned Sean, I mentioned Joe.

You might put me in a box, therefore.

I also am very friendly with Simon Hill, who's prominent in the plant-based community.

He's great.

We're friends with him.

I've had him on.

Yeah.

He's a wonderful guy, very thoughtful, and I appreciate his challenges.

We just had a five-hour podcast, actually.

It's totally pleasant.

And

I've been to like, you know, probably the most, the most cited,

one of the most cited nutrition researchers is Walter Willett at Harvard.

Maybe you know that name.

I haven't.

Listeners might know the name name if they know the space, but like I've been to his house and chatted with him on like prominent vegans channels.

So like I'm very comfortable talking about different diets for different interventions and keeping an open mind about the literature.

And it's really actually hard to get people to meet you at that place of like, let's just have a reasonable discussion about the physiology and the possibilities without necessarily having the topic at hand bleed into other topics.

So if I say, let's talk about why I don't think it's sensical that red meat causes diabetes, which the headlines have been blowing up over right now since the most recent studies.

And I did a dissection of the studies.

And then people try to like, well, I'm going to try to defend this paper because I have other issues with red meat, say with respect to climate change.

I'm like, that's a different topic.

I'm super happy to talk to you about that topic.

But that is separate from, does red meat cause diabetes?

Like, that's the question at hand.

It's the same.

Can a carnivore diet treat inflammatory bowel disease in treatment-resistant patients?

It's a different question than does carnivore diet improve longevity as compared to a vegan diet?

Those are separate issues.

And I just think

in the social space, we really fail to parse those issues.

Right.

Well, I think in general, when people feel like they're losing an argument, they will just defer to another point.

Right.

Yeah.

Ducking and dodging.

And it's like, in short form, it's really hard to catch people out on that.

Right.

Right.

So that's why I appreciate long form.

No, I appreciate it, man.

Social media needs people like you and Huberman because the average person won't read these research papers.

Yeah.

I guess that's another question.

And I'll throw this out to you because I don't have a superb answer, but it's like,

how do you find the influencer you're going to trust?

Do you have a good answer for that?

No, I don't because there's so many options on social media.

Yeah, but like, what are the criteria?

Like, are you going to go with degrees or like brands?

I don't think those are great criteria.

But like,

if people don't have scientific chops, and that's not slowing shade, that's just the reality.

Like, how do you actually evaluate the individual who you're going to listen to and audit when you're in an echo chamber?

And, like, I don't have a good answer for that, but I think it's just like something for people to contemplate.

Like, how do you define the criteria by which you're going to follow and trust somebody?

Yeah, no, that's a great question because there's so many health influencers these days blowing up, and it's easy to follow Brian Johnson or Lane Norton or whoever you want to follow.

I have interesting thoughts about both those gentlemen.

But yeah, I know.

I have to say, I do appreciate Brian's sense of humor.

So anyway,

but yeah.

Another thing you've said that you've gone viral for is you say calories aren't the cause of obesity.

What did you mean by that?

Yeah.

So here's another thing where

you say something and people immediately hear something different.

So if I say calories don't cause obesity, that is not saying calories don't matter.

Nor is it saying, you know, well, let's dissect this idea of calorie balance.

Calories in minus calories out equals, you know, weight stored.

That is a physiologic equation, an expression of thermodynamics that can hold true without being a causal explanation.

That word cause, and I apologize if I'm over-intellectualizing this for people, but this is truly how I see it.

That word cause is very important because it's speaking to physiology.

What is the physiological driver of obesity?

And even if thermodynamics holds in humans, it does not mean calories cause obesity.

So let me reframe this.

Let me say, what if we envision, and this isn't my original idea, this has been put forward by others, including in a recent paper in obesity called Trap Fat, I did a video on it, but the idea that what if we conceive of obesity as a disorder of fuel partitioning?

So we're all gonna eat, right?

We're all gonna get energy.

You can quantify that energy as calories.

The question is then, well,

what does your body do with those calories?

Because it has options.

It can build lean tissue.

It can expend that energy as heat or, quote, non-exercise activity thermogenesis, neat.

Or it can store it in fat.

Now, if you start from that start point,

then what you can see is that if your body maladaptively partitions fuel, say, into fat, then what can happen downstream, not as a driving force, but as a consequence of maladaptive fuel partitioning is

more hunger and decreased energy expenditure.

And so your body over the long term can solve that calorie equation, but the causality is flipped, whereby your hormones and your metabolic milieu determine how your body partitions the energy, and then downstream of it over time, energy intake and energy expenditure are adjusted.

in order to

result in chronic obesity or healthy weight.

The reason I think this is really important and not just some sort of academic exercise is

because people,

it's helpful then to change, what are you focusing on?

What are the levers you're trying to pull in order to

help manage your weight?

And I would say it's much more beneficial to focus on levers that, quote, optimize fuel partitioning, which is a whole different topic.

We can dive down if you want to spend another two hours

Versus what might impact the scale the next morning.

Because what I'm not saying is if you eat 10,000 calories for a week, you won't gain weight.

I'm saying that isn't that pertinent to what actually causes obesity chronically.

Wow.

And what keeps you, you know, at your people say set point.

But like, you know, what determines how your body is going to adjust for you in terms of energy intake and energy output in order to get you to a certain weight set point.

And if calories are your focus, are your metric, you're almost, well, you have a much lower chance of success than if we reframe the conversation of saying, look, calories are not irrelevant, but what really matters is fuel partitioning, where you put the calories.

And you can show this.

I mean, it's easily, most easily shown in animal models who also obey the laws of physics, but like you can take animals, right?

and manipulate one group so they store more fat, even pair matched for feeding.

So you have two groups, say say, of rats, and you feed them the same calories, but the one group gains way more weight and may end up way heavier.

You can even feed that group fewer calories, and it'll end up with more fat and end up being heavier.

And so, you know,

animals, they also obey thermodynamics, but just the fact that you can engineer these circumstances tells you there's more to the physiological story.

And then, if you want to layer in calories on top of that, what you could say is that, like, look,

now let's take, okay, you have the group X and group Y.

The group X rat gets fed the same number of calories or fewer calories, and they end up fatter than the group Y rat.

But now let's focus just on the group X rat and say, if I gave that rat a calorie-restricted diet versus gave that rat access to all the food they want, ad libidum feeding, they call it, which rat now in that X group is going to end up fatter?

The one with access to more food access?

So access to calories can allow one to fully manifest the obesity phenotype.

But again, the core of the problem is, I think broadly speaking, maladaptive fuel partitioning, what your body does with that energy.

Interesting.

And I just think framing that as a more functional way to think about how we go about living our lives.

Now,

the interesting thing, I would think, and this is kind of to cut through

the fighting and the vitriol and the confusing messaging because people might be confused now is

I just had this vision, a paper just came out and it was trying to reconcile two warring models of obesity, carbohydrate, insulin, energy balance.

And I read it and I'm like, this is interesting.

It seems kind of political and handy wavy.

And then I was thinking about like, well, what are the clinical implementation?

What are the clinical like takeaways from these two different models both taken in their steel man?

And I imagined it as a Venn diagram, right?

So you have the one model is the one circle, the other model is the other circle.

Then what is the degree of overlap?

You know, if we layer these, like what's in the center where both would agree?

And the center is way, much bigger than the margins.

Oh, really?

I would say so, because, like, what is the advice that you hear over and over again, no matter what camp you're hearing it from?

Eat whole, unprocessed foods, right?

Right?

Probably prioritize protein.

And you're eating, like, whole single-ingredient foods, you know, eating enough protein.

You know, we can...

Get into the nitty-gritty about like, you know, I would argue that there's probably an advantage to carbohydrate restriction if you're insulin resistant.

I think the literature backs that up.

I don't need to sell you on that.

Like the big first step for everybody is focusing on what I think we could agree are the fundamentals, which are like, if you eat a real whole foods diet,

I can intellectualize why that might be, but I pretty much guarantee you're going to be trending in a positive direction if your starting point is a conventional diet.

Do you know what I mean?

So like, I realize I have a tendency to analyze, intellectualize.

I'm an academic.

I apologize.

That's what what I do.

You can already get a flavor of that.

If you want the nitty-gritty metabolism, we can talk about towering conjugated bile acids and all that.

I'm more than happy to do it.

But like at a high level, if you want the simple, like, what do I do, Nick?

I'm confused.

I would say, yeah, start with acknowledging like what we kind of all agree on, which, like, you know, whole foods, diet, whether you prefer animal-based, plant-based, that's, like, basically an opinion thing.

And then from there, trying to cultivate curiosity in your own metabolic health journey.

Because like when I work with people kind of as like a, I don't know what you want to call me, a nutritional coach, metabolism coach, whatever.

Like the moment I know they're going to be successful for the rest of their life is when I see that light go on in their eye when they realize, wait, this isn't a chore to engage in my metabolic health.

Like this is the coolest experiment that I get to do forever, where my body is the lab and I get to empirically tweak things on me and as a result, learn more about how my body operates and then feel and function better in all elements of my life.

Like, that's a true joy.

Do you know who Dave Dana is, by the way?

I don't.

Who is that?

Dave Dana is a, everybody should check him out.

He's, um, I think mostly on Twitter X, but else is on

other platforms.

Dave E.

Dana.

He's a guy that I met, I think it was early 2023.

At the time I met him, he's around 400 pounds

and I think in a pretty dark place.

Yeah.

And he just, he had this mindset of curiosity and interest and engagement.

Bear in mind, he has no academic background in metabolism

or nutrition, but

he adopted that mindset.

And as a result, he's now lost, I don't know, he's lost so much weight.

I'm not going to tell you what my weight is, but he's definitely lost more than I weigh.

Whoa.

He has done an MBA.

He got married.

His mental health is better.

His finances are now in order.

And actually, he's become a little bit of a social media celebrity.

I think most of his followings, at least on Twitter, are bigger than mine.

He, I mean, not that I was ever his formal coach, but I joke that

I got upstaged and booted as a coach because now he's posting selfies with Arnold Schwarzenegger.

Like Arnold Schwarzenegger is having him as a spokes guy for his app and like going to like Muscle Beach with Arnold, taking pictures.

So it's like,

I mean, this is an extreme example.

Not everybody's going to be taking selfies with the Terminator, but of someone who started from like the lowest of low points with, you don't need the academic background, it's just like I'm curious in metabolism and I want to engage in communities where I can learn more about this,

have support, and kind of just like iterate along the way, find what works for me.

And he ends up going, you know, from being over 400 pounds in financial debt and kind of depressed to being married with an MBA, hitting up with a Schwarzenegger to like happy, fit, just smiling like

with infinite energy and positivity.

That, I think, is just emblematic of the power of what I consider like metabolic medicine.

Absolutely.

And that was from a ketogenic diet or what else did he do?

He, I mean, again, it's one of these things where putting labels on it sometimes puts people off.

So I think he would define it as like a

lower carb animal-based diet.

I mean, he's tested ketones and he's been a ketosis and he eats mostly like, you know, he's been on a ketogenic diet.

Yes.

The answer is yes.

However, he's not religious to it.

Sometimes he's traveling and like he'll post an accountability photo of like, look, I had this half roast beef sandwich, you know, just normally, or I was with like my, you know, mother-in-law in the hospital was being treated for cancer.

And like, we got this thing at the cafeteria and it wasn't perfect, but I'm still on the bandwagon.

Now, everybody has their own approaches to things.

Like me, I'm like, you know, an all-or-nothing guy.

So that approach doesn't really work for me.

But some people do better, you know, with a little bit of personal liberty, and that's fine.

Like, you don't need to say, I'm part of this tribe, and I am sticking to this approach because it's the rules of the label.

You can flex out of that

for sure.

But that's the cool thing about

metabolic health and

envisaging yourself as your lab and your test subject is you can see how you respond.

to those things.

So if you have, you know, that one lint truffle, do you then go off the bandwagon?

Are you someone who can actually have one lint truffle and just enjoy that moment and have it every like month I'm not that person

some people very well might be so it's about knowing yourself and introspecting yeah you know and then combining that with I think interest in physiology metabolism well I guess you don't have to go down that rabbit hole but I do find it's so fun I love yeah I mean you're strict with your diet but you're willing to do these crazy tests like you ate four and a half pounds of butter in a week that's pretty crazy yeah it was I mean again like all these are all like demonstrations that was again a metabolic demonstration to break with expectations.

The Oreo thing, I lowered my cholesterol with Oreo cookies.

Again, metabolic demonstration.

Not generalizing, Oreos will not lower cholesterol for everybody.

It's a very particular case.

But the fact that I can engineer that metabolic case, predict this is going to work, get an IRB exemption from a study, announce I'm going to do the study, then carry out the study and be right.

That tells me that.

Oh, so you knew beforehand that it would be.

I mean,

i understood the physiology and i boldly made a public hypothesis people can go look it was on plant chomper's uh he's a prominent vegan youtuber he was on his podcast friend of mine and i said i'm gonna do this we'll see what the results are based on what had been done before i guessed that i would be right but this isn't something where i like you know tried to hide the data then it came out the way i liked then i released it no right no i'm like look as an intellectually honest person and a scientist i like to be out there about my hypotheses I'm not afraid of being wrong and falling on my face.

Like that's what science is.

Take a bold hypothesis, put it out there.

The data will show what the data will show.

There shouldn't be shame.

I know there is.

But there shouldn't be shame about being wrong.

It's just about the process of science, asking the question with integrity, having your model, and then trying to actually break your model.

Not tweak things and massage things and go through like statistical gymnastics to fit.

to your worldview, but try to break it.

So with our lipid energy model, I thought, like, what is the most extreme way I can test this on myself?

And it's like, well, based on my understanding of the physiology, Oreos should lower my cholesterol.

What should I do?

I should test this.

Like, that is a way to try to break the model because it doesn't really make sense, right?

Or

let's say it's a very extreme way to test it in a way where you could see that this would fail or not produce results based on our model.

And if that were the case, then I need to reevaluate the model, act the butter as it did work.

So the butter thing was another example of

in my my circumstance, that should have lowered my LDL cholesterol.

The lab screwed up and didn't get my final lab measures.

So I did a repeat later on.

And actually, that was the case.

People can look up on my YouTube channel.

It's like 600, 6,384 calories or whatever, like that's the thumbnail where I did that experiment.

And you'll see me say, I was wrong.

Not like, here's a platitude.

Let me tell you how I'm awoken wrong.

I'm like, no, I was 100% wrong.

And here's my new understanding based on the results that happened to me.

I made this prediction and I was dead wrong.

And I'm not afraid to say that.

I think that's the funnest part about science.

My dad used to tell me, my dad's an academician and

scientist as well.

And even from a young age, he'd say, you know, Nick, with science, like, it's cool when you're right.

Your hypothesis is right.

But.

It's even cooler

when you're completely and entirely wrong.

Because then you have to go, wait, what?

What's going on here?

And that's when you really start to learn.

So

that's where all my learning has taken place,

the bulk of it with my cholesterol response.

Like when I'm on keto, I was doing it the way I thought was healthy at the time.

That meant I really wasn't eating any red meat.

I wasn't having any butter, very low dairy.

I was eating lots of leafy greens and avocado and salmon and olive oil.

That's what my ketogenic diet looked like.

In fact, for those who think I'm a carnivore, look up Nick Norwit's new Mediterranean diet keto cookbook.

It's like, you can look on the front, like that's what I used to eat like.

And nevertheless, point being, nevertheless, I had this weird response with my cholesterol where it broke with expectations.

How am I eating tons of fiber and plant foods?

And my cholesterol has gone from where it was on a mixed diet where I was eating like fudge and ice cream at like 90.

to when I was on my first ketogenic diet, it was in the high 300s.

That doesn't make any sense based on what I understood at the time about physiology and medicine.

And so it provoked me to get curious and start to understand what might be going on to explain the phenomenon that I didn't understand.

I love that, man.

Nick, it's been really fascinating.

I can't wait to see what you do next.

And hopefully, you get some funding one day, man.

Yeah, it's on the horizon.

I think

this is kind of like my, I guess, quote, coming out period.

Like, I've spent the last 11 years in academia, really only the last, I mean, since the turn of the new year, did I think, huh, like engaging in these public social spaces is something that I could really enjoy.

And while it might seem silly with titles like Ori versus Datin, et cetera, an area that could add value because it's like

people might disagree.

I know about some academicians I would disagree, but I think it is a freaking awesome thing that now there is this incursion of these social media, general public, and academic worlds where they're forced to interact.

And like it or not, they're forced to interact.

And I get to be that a person, I say that person, not the only one, but a person who's like coming up in a time, you know, where I'm doing my academic training, conventional centers in medicine and science.

So I see that aspect.

I am engaged in social media, so I see that aspect.

I'm doing like medical training, so I see the medical perspective.

I've been the patient, so I see that perspective.

And so I kind of get to sit and see all these different perspectives and think about like, how can I bridge them?

And I just find that loads of fun.

And figuring out how to evolve as a communicator is, I always like learning new skills, is something that I find really exciting.

So, you know, what I'd offer to people that are listening, if they found this at all interesting and follow along, is like,

I think often influencers are kind of, especially let's say influencers in medicine, physiology, nutrition have their shtick and are cemented in their thing.

They might say they evolve to some degree and many do, but like I am so tremendously undifferentiated in this space that while I do love to nerd out and educate,

I'm really excited about, like I say, growing as a communicator and I'm considering everybody who's quote, an early adopter of me, their feedback as my data on how to evolve and grow.

I love it.

So anyway, it's a tremendously fun time.

Sorry, I took up like 99% of the airspace here.

No, you're good.

That's how it should be, man.

Spotlights on you.

Where can people find you, man?

At Nick Norwitz, N-I-C-K, N-O-R-W-I-T-Z on basically all social platforms.

My biggest at the moment is Twitter, trying to build that Instagram.

And I really enjoy doing YouTube breakdowns on my YouTube channel, again, Nick Norwitz, where I my bread and butter is breaking down the metabolism.

So I might tell you about like, you know,

metabolic bypasses of genetics and cancer metabolism and tell it through the lens of, say, Harry Potter or something with fun, goofy analogies.

And

it's, it's fun because I just, I read this stuff and I sit there with awe and excitement over like, you know, a nature metabolism paper at 3 a.m.

And then I just think like, how can I bring this joy and awe to other people?

Realizing that like it needs to be communicated in some sort of fun way with analogies.

And so you want to learn about gut health, anti-aging science, you know, diets, obesity calories, whatever.

I love hitting on all this stuff.

And there's always new and exciting stuff.

More content that I could ever fill in a lifetime.

Yeah.

We'll link below.

Thanks for coming on, man.

Thanks, man.

Yup.

Thanks for watching, guys.

See you next time.