Mark Bell's Power Project - The Ketogenic Diet Is Powerful (Don’t Let PHd’s fool you) - Nick Norwitz || MBPP Ep. 1091

Episode Date: August 7, 2024

In episode 1091, Nick Norwitz, Mark Bell, Nsima Inyang, and Andrew Zaragoza talk about how Nick was able to massively drop his LDL Cholesterol by eating 12 Oreo Cookies a day. Follow Nick on IG: https://www.instagram.com/nicknorwitz/   Official Power Project Website: https://powerproject.live Join The Power Project Discord: https://discord.gg/yYzthQX5qN Subscribe to the Power Project Clips Channel: https://youtube.com/channel/UC5Df31rlDXm0EJAcKsq1SUw   Special perks for our listeners below!   🥜 Protect Your Nuts With Organic Underwear 🥜 ➢https://nadsunder.com/ Use code: POWERPROJECT to save 15% off your order!   🍆  Natural Sexual Performance Booster 🍆 ➢https://usejoymode.com/discount/POWERPROJECT Use code: POWERPROJECT to save 20% off your order!   🚨 The Best Red Light Therapy Devices and Blue Blocking Glasses On The Market! 😎 ➢https://emr-tek.com/ Use code: POWERPROJECT to save 20% off your order!   👟 BEST LOOKING AND FUNCTIONING BAREFOOT SHOES 🦶 ➢https://vivobarefoot.com/powerproject   🥩 HIGH QUALITY PROTEIN! 🍖 ➢ https://goodlifeproteins.com/ Code POWER to save 20% off site wide, or code POWERPROJECT to save an additional 5% off your Build a Box Subscription!   🩸 Get your BLOODWORK Done! 🩸 ➢ https://marekhealth.com/PowerProject to receive 10% off our Panel, Check Up Panel or any custom panel, and use code POWERPROJECT for 10% off any lab!   Sleep Better and TAPE YOUR MOUTH (Comfortable Mouth Tape) 🤐 ➢ https://hostagetape.com/powerproject to receive a year supply of Hostage Tape and Nose Strips for less than $1 a night!   🥶 The Best Cold Plunge Money Can Buy 🥶 ➢ https://thecoldplunge.com/ Code POWERPROJECT to save $150!!   Self Explanatory 🍆 ➢ Enlarging Pumps (This really works): https://bit.ly/powerproject1 Pumps explained:      ➢ https://withinyoubrand.com/ Code POWERPROJECT to save 15% off supplements!   ➢ https://markbellslingshot.com/ Code POWERPROJECT to save 15% off all gear and apparel!   Follow Mark Bell's Power Project Podcast ➢ https://www.PowerProject.live ➢ https://lnk.to/PowerProjectPodcast ➢ Insta: https://www.instagram.com/markbellspowerproject ➢ YouTube: https://www.youtube.com/markbellspowerproject   FOLLOW Mark Bell ➢ Instagram: https://www.instagram.com/marksmellybell ➢https://www.tiktok.com/@marksmellybell ➢ Facebook: https://www.facebook.com/MarkBellSuperTraining ➢ Twitter: https://twitter.com/marksmellybell   Follow Nsima Inyang ➢ Become a Stronger Human - https://thestrongerhuman.store ➢ UNTAPPED Program - https://shor.by/JoinUNTAPPED ➢YouTube: https://www.youtube.com/c/NsimaInyang ➢Instagram: https://www.instagram.com/nsimainyang/?hl=en ➢TikTok: https://www.tiktok.com/@nsimayinyang?lang=en   Follow Andrew Zaragoza ➢ Podcast Courses and Free Guides: https://pursuepodcasting.com/iamandrewz ➢ Instagram: https://www.instagram.com/iamandrewz/ ➢ TikTok: https://www.tiktok.com/@iamandrewz   #PowerProject #Podcast #MarkBell #FitnessPodcast #markbellspowerproject

I imagine the Oreo cookie cholesterol drop where I lower my LDL massively with Oreo cookies. They tanked my LDL by 71%. Of course I know Lane's gonna jump on it. We published the meta analysis of 41 randomized control trials. What does Lane love? The randomized controlled trials.

What does he decide to do? He completely ignores the meta analysis of RCTs despite flexing he loves to talk about RCTs And then you get your feelings hurt because I said you did a poor job Well, guess what dude data over feelings read your own shirt But when it comes to the topic of cholesterol like should people pay attention and watch out for how much saturated fat they're eating But I would say it needs to be for the person that's listening and wants to kind of interpret their own blood work What if they do have high LDL they see that and there's a bit of concern.

Were you born with high LDL? Or were you like me and your LDL was low and then skyrocketed on keto? What are we missing when it comes to artificial sweeteners? I'm not arguing that just taking a little bit of sucralose and putting it in your black coffee and that's all you have is gonna cause insulin resistance.

But sucralose can, in the context of carbohydrates, will induce insulin resistance. Thanks for coming on the show, Nick. Can you explain to our audience a little bit about yourself and how you got into just really having a great YouTube channel that's giving out great information, but also trying to keep it entertaining because this stuff can get really stiff and really sciency real quick. Yeah. No, thanks so much.

And definitely will caveat this. I'm at the very beginning of my, let's say social media journey, but my background is largely typical academic. I grew up in a very academic household. Both my parents are physicians. Went to school, went to Dartmouth, studied biology, biochemistry,

then went to Oxford University in the UK to do a PhD in metabolism before jumping back across the pond to Boston to do my medical degree at Harvard. So I'm in the very last stretch of the whole MD-PhD marathon. But along that journey, I had a parallel struggle with personal health issues, really ulcerative colitis and inflammatory bowel disease was the thing that hit me quite hard at the end of college. And I was struggling with it through the end of college

and then really at the beginning of grad school where things got really severe, shit hit the fan, pardon the pun, and I ended up in and out of intensive care. To give people a picture, sorry if this is TMI, but bloody diarrhea 20 times a day, losing 20% of my body weight in months during flares, ending up in hospital beds, bradycardic,

which means low heart rate too, even in the 20s, which is like, that's not like you're a good marathon runner, you're a triathlete, that's like, there's something wrong with you. So I was really incapacitated and it had been like, going from high performing academic athlete, marathon runner, triathlete, to I barely could roll out of bed.

I couldn't really perform in lab and even though I had everything, you know, my future seemed really nice on paper, gonna finish my PhD at Oxford, go to Harvard, get my other doctorate, and then pursue yada, yada, yada. I really, like day in and day out, was struggling to just stay afloat with respect to my studies,

let alone things like a social life. I mean, I was in my early 20s at that point. Romantic life was completely out the table. I had no quality of life whatsoever. And so, long story short, out of desperation when standard things weren't working, I just started throwing spaghetti at the wall and trying different things. I eventually tried a ketogenic diet and it was the only thing that put me in remission, which I define as feeling better, also having a

massive drop in inflammatory markers to totally normal levels. And then when I eventually got my next colonoscopy, I was in biopsy-proven remission. My disease was for all purposes gone. And I've been in remission now for five years. I finished up my PhD at Oxford in metabolism and am now in my last year at HMS, Harvard Medical School, as I mentioned. So I'm really at this interesting cusp in my life. I'm 28. I'm living in a really cool time where academia, the Jade Tower academia that I've been a part

of my entire upbringing, which used to be very isolated, is now forced to interact with the general public because we're living in the information age. So you end up with these interesting tensions between academia, the general public because we're living in the information age. So you end up with these interesting tensions between academia, the general public, and I find myself having a lot of fun in the education, public education sphere, while also finishing up my clinical work and continuing to pursue research,

just figuring out what I want to do with my future, how I want to, as I say, make metabolic health mainstream, which are four words that really encapsulate what I see as my career and life mission for the next, hopefully, 70, 80 years. There's a lot of people that are embarking on ketogenic diets, low carb style diets, carnivore diets. What should people be aware of in the case of maybe like heart disease?

Like, it seems to be kind of confusing. I've seen a lot of your videos on cholesterol. I've seen you debunking some stuff that was said by Lane Norton and things of that nature. But when it comes to the topic of cholesterol, like should people pay attention and watch out for how much saturated fat they're eating, how much cholesterol? Because there are cases it does seem like there's a percentage of the population that can have adverse side effects, maybe if they're eating too much saturated fat,

even if they're just, I guess, in a caloric surplus on a carnivore diet, or even if they're just having, they're doing the carnivore diet and maybe their adherence isn't 95%. Yeah. So what I'm gonna do is prime people. This is going to be a very long, drawn-out answer.

But what I would say it needs to be, because what I really don't like and what I see a lot of is oversimplification by people who think listeners aren't intelligent enough to digest the nuanced message, which is why you get comments like, lower LDL is better. Lower Applebee is better. People are afraid of giving the nuanced message because they think people will interpret it

inappropriately and so they end up giving what I think are oversimplified message and that leads to a lot of infighting. So what I'm going to say is, you're not going to get easy yes, no's out of me, you're going to get a lot of we don't know here or where the limits of the literature are.

And I think that's the fair and appropriate thing to do. So I'll say it's not black and white. Should people worry at all? Yes. Are there unknowns that we need to unpack? Yes. And so starting high level, you're right. I see high cholesterol as kind of the boogeyman of ketogenic diets.

We have all these expanding use cases from starting off with epilepsy. Now we have inflammatory and autoimmune disorders, ulcerative colitis, rheumatoid arthritis, mental health disorders, schizophrenia, bipolar, depression, and a whole host of therapeutic applications that are expanding for ketogenic diets. However, you're not going to be able to make this standard of care while this remains kind of the boogeyman, the high cholesterol, because heart disease remains a leading killer. And despite innovations in pharmacotherapy, which we have more and more of, it's still a leading killer.

We're not beating it. So people are understandably scared of heart disease. And one of the one risk factor for heart disease is LDL cholesterol, or more specifically, the LDL particles. So the LDL cholesterol is the cholesterol fraction in the spherical particles that are LDL. If you've heard the term APO-B, APO-B is a proxy for the LDL particle counts since there's one APO-B lipoprotein per LDL particle.

I'd show you on my hand crocheted Applebee particle sphere that Dave Feldman's mom gave me, but I re-gifted it to Simon Hill with permission. So he has it, unfortunately. But that aside, this is a known risk factor. It has a causal relationship within the cascade of cardiovascular disease, but the nature of the relationship isn't so simple as, oh, it's causal, oh, it's necessary, therefore lower is better. And I think an important thing that we're trying to do is understand why. Why might LDL go up in people who go low carb? Because it doesn't go up in most people.

So that's a really interesting thing. Your average person, they go low carb, their LDL doesn't go up. It actually tends to stay the same. And their APO-B, their LDL particle count, might actually go down. You might end up with a much healthier LDL profile and overall lower APO-B levels.

But in some people, LDL and Apple B can go up, and they can go up to astronomical levels. Which begs the question, well, why? What's driving that? And for the longest time, it's been easy to scapegoat, saturated fat, no, be like people are just butter-guzzling. Or say, oh, throw your hands in the air, it's something with the genetics. I think it's a little bit intellectually lazy, doesn't really answer the question with any degree of precision, and also doesn't explain

some really interesting patterns we see, some that are seemingly paradoxical with respect to who presents with these high LDL levels. So if I ask you guys, you know, if you have someone, if we assume that a high LDL is unhealthy, right, so that will be an unhealthy response, which population going low carb would you expect to have the unhealthy response of high LDL, presuming we think it is? The people with obesity and metabolic dysfunction who are unhealthy at baseline, or the generally insulin sensitive, lean people who are healthy at baseline? Do you think the healthy people or the unhealthy people are going to have the unhealthy response?

What do you think? The unhealthy people. Right. One would think. But what we find is actually it's the lean insulin-sensitive people who have the jumps in LDL cholesterol and in a dose-dependent manner by which the leaner you are, the higher LDL tends to go. And we've now codified this in the literature in multiple studies, including a meta-analysis

of 41 randomized controlled trials where we took the WHO BMI classifications. So normal BMI being 18.5 to 25 kilograms per meter squared and then overweight 25 to 30, class 1 obesity 30 to 35, class 2 obesity 35 to 40. And we asked the question, if we did meta-analyses for each of these categories, what do we see with respect to LDL change? What we saw was the only category with increases in LDL was the lean people. People with overweight or class one obesity, no increase. People with class two obesity actually see a decrease.

And if you look at individual participant level data, you do see a dose response effect, whereby the leaner you are, the higher your LDL tends to go. And that is a meta of RCTs. I'll also say, via clinical observation, I've had lots of people report, clinicians report to me via email saying, I had a patient whose BMI was like 43, and I put him on a ketogenic diet.

When they started, their LDL was like 80. And it stayed around 80 as they were losing weight until they hit like a BMI of 25, 24. Then it shot up to 250. So this seems to be something that is specific to lean insulin sensitive people generally. Hence the term that was coined by Dave Feldman way back in 2017 when he just kind of observed this empirically and said, Oh, this is quirky, the lean mass hyper responder. Now lean mass hyper responder, there's a lot of confusion about the terminology, which is now historic because it just caught on.

The lean mass part refers to the association between this phenotype and being leaner, although there's actually no lean criteria. But I've never seen a lean mass hyper responder like with class II obesity. Now the definition of the phenotype is very high LDL, above 200 milligrams per deciliter, along with high HDL above 80 milligrams per deciliter and low triglycerides below 70 milligrams per deciliter. And that triad, LDL 200 or above, HDL 80 or above, triglycerides 70 or below, is incredibly

rare in the general population. And is actually pretty common among people who go low-carbon or lean. But if you look at like, say, a population database like NHANES, say like 90,000 subjects, you might find like three lean mass hyporesponders. So the union of these lipids is incredibly rare, but we think constitutes a metabolic signature that suggests some really interesting underlying physiology that occurs when lean insulin-sensitive people go low carb. So that is a very different understanding than, oh, they're just eating

a lot of butter. And I'll pause because I've been monologuing a little bit. So let me ask you this. Like for those lean mass hyper responders with high HDL, high LDL, is, are there any health risks there for those individuals seeing those types of numbers? Like, do they actually, is there anything that they would be worrying about? Because initially you would assume, or if somebody looks at that blood work, they'd be like, oh, this doesn't look very good. Yeah. That's the response of basically everybody who first manifests with the phenotype. It was Dave Feldman's response. That's why he got involved in this. It was my response.

And just for like actually context, when I went keto, I was eating very little meat, very little dairy, very low saturated fat, actually pretty high fiber, about 35 grams per day. My LDL went from 90 to 350 like immediately. This isn't a saturated fat fiber elimination phenomenon. Those can modify, but they're not necessary for the phenotype to emerge. Now your question, well, what's the risk? And the only appropriate answer to that, and I will stand by this, is we don't know. We simply don't know because this population is incredibly unique, not like anything we've

ever seen before, and they've never been studied with respect to what is the risk profile. Now I will distinguish we don't know the answer to what should be done on a one individual clinical basis. I think I've articulated this position, my colleagues have as well. It's like we can be intellectually honest to what the limitations of the science are and say, look, this is a unique population. We have reason to believe their risk profile will be very different.

We can go over some of those data than other people with similarly high LDLs. At the same time, the bulk of the literature, the quote preponderance of evidence, that's a term you'll hear bandied about by clinicians. The preponderance of evidence meaning like the general body of literature would say LDL levels that high are dangerous. So all things being equal,

the conservative thing to do would be to lower them if you can. Unfortunately, it's never so simple as that on the individual level. People might be medication intolerant, the medications would come with side effects, and you know, individuals might need a ketogenic diet therapeutically. If they don't, if somebody is just toying with it, they're a lean insulin sensitive athlete, their LDL goes to 500, if I were them, I'd probably just say, I'm going to eat a sweet potato and some honey and not gamble on my heart health. I think that's a pretty reasonable thing to do. But it's not so simple for everybody because it might be a kid with epilepsy.

They increase the carbs. Maybe they're presumably reducing their heart risk, but they're having seizures. Or for me, I go into a colitis flare. And then of course, there are medications on the table, we can talk about what options those are, but the answer to your question is we don't know, and what we want to do is study why this occurs, and also what the risk associated is with this profile

so people can make more informed decisions. So it's a scientifically legitimate question to ask, what is the absolute risk profile in this population because we do not know what it is. At the same time, without those data, on an individual level, I think the conservative thing to do is lower if you can where you can, but with a consideration of other things with respect to your personal picture. Did you do the Oreo cookie study kind of on your own or is this something you brought to Harvard?

Oh yeah, so. Picture what they said about it. Should I give background on this cookie experiment? Yeah, absolutely. So people might know about this already, but we had had papers rolling out on this interesting phenotype that I think really could teach us a lot about general human metabolism.

But there's a lot of dogmatism and resistance to talking about it. So even after the meta-analysis of RCTs that I mentioned was published, which was like our eighth paper or something, There was still very little chatter. And me, being anybody who knows me knows, I'm very passionate. I'm a hard worker. And the flip side of that is I'm incredibly impatient. I'm like, this conversation isn't happening fast enough. I want to accelerate things. And I want to force a conversation

that people don't want to have. So I tried to conceive within the constraints of the resources available to me, because I'm not a professor emeritus with multi-million dollar grants or whatever. At the time I was a 27 year old, now I'm a 28 year old medical student with a little social media following and a little creativity. So I thought, hmm, what can I do to really poke people and force heads to turn towards this phenotype. So I imagined the Oreo cookie cholesterol drop, which based on my understanding, our understanding of the physiology of this phenotype, I said, I can present this apparent paradox where

I lower my LDL massively with Oreo cookies by adding Oreo cookies to my diet. But I decided, yeah, that's not enough. We need to go big or go home. So I said, let's make it a crossover trial. So I have a comparator. I decided to compare it to high intensity statin therapy because that's standard of care. So I went with 20 milligrams of resubastatin.

Crestor is the brand name, which is like gorilla dose of statin. And I know how to dot my I's and cross my T's. That's what a life in academia will teach you. So I got Harvard Medical School to grant me the IRB exemption that makes it quite above board. I have my PCP ordering all my labs, which went straight into my Electronical Medical Record.

Could not fake that. And I wanted to have another reputable name, not another reputable name, a reputable name in lipidology on the paper. So I approached William Cromwell, who is a highly esteemed lipidologist, over 30 years experience, national lipid fellow. And just as a little extra fun fact, one of the reasons I approached him, the main reason I approached him is I knew him to be a very open-minded intellectual who would come to the table humbly,

but also give me critical feedback on the approach and make it as rigorous as possible. And let legitimacy, but also, we can unpack this a little bit. I think there's definitely some tension between certain people in social media, their opinions on cholesterol, and people like Peter Atiyah and even more so the guy who trained him, Thomas Dayspring.

Let's just say I have had tensions with my colleagues. Now the thing about William Cromwell is he actually trained Thomas Dayspring who trained Peter Atiyah. So it was in part for me a shielding because it makes it more difficult to criticize if you have him on the paper and also given his particular relationships and what has been said before. So anyway it was me and Professor Cromwell designed the study and then I announced it a priori saying I'm going to do this. I haven't done it yet, but I'm going to do this.

I told the world I was going to do it on Chris McCaskill Plant Chompers YouTube channel. So, went on a platform that would not be favorable to what I might discover, although I know Chris to be a pretty honest guy. Said, I'm going to do this, we'll find out what happens. So, I again, dot my i's, cross my t's, and then I executed. And the protocol was, I was going to eat 12 Oreo cookies per day, standard Oreo cookies, which that's 100 grams of carbs, and it was a pure addition to my diet. So I locked in my standard ketogenic diet for two weeks as a run-in phase, then added

the Oreo cookies to my diet for an intended two weeks, then did a washout period of three months to return to my normal weight and cholesterol levels, then did the 20 mgs of Crestor for six weeks. The Crestor was six weeks because that's what's needed to give the statin a quote fair trial. Whereas the Oreo trial was shorter because well you try to eat a sleeve of Oreos on top of your diet every day consistently. Trust me it's not as easy as it sounds. Anyway, the results were, drum roll, that the, sorry I shook the camera there, the Oreo cookies were twice as potent as the statin that lowering my cholesterol in one third of the time frame.

They tanked my LDL by 71%. My starting LDL in the Oreo phase was 384, dropped it to 111 in 16 days. The reason it was 16 days and not 14, I did say two weeks, is because we were getting lipid tests weekly, right? So week two was only the second follow-up lipid test beyond baseline and the drop was so massive that me and the team decided, look, we need to actually replicate this. Let's make it a triplicate on sequential days.

So after day 14, 15, then 16, just to show this isn't a fluke of the test. Like this is something. And actually days 15 and 16, it was still down trending. So it might have gone even lower. It might have broken below 100 with continued Oreo therapy. But I was done by that point. I had demonstrated the points.

Then I did the washout, did the statin, and it lowered my LDL by what you'd expect a statin to lower your LDL by by 32.5%. But was not as powerful as the Oreos. So that was the finding. And it had its intended effect. It stirred conversation about a really interesting phenomenon. I'll pause there. We can dig into some of the response.

But that was a project. At the bottom of the study in tiny letters, it says Nabisco. Ha ha ha. Bought and paid for, just like every other piece of science. How do you think I'm paying for my tuition? Expensive, man. Yeah, no. Oreo has not given me any money.

They wouldn't even give me the pleasure of retweeting me. But in all seriousness, the metabolic demonstration which this was intended to be, really did spark up conversation. It got a lot of media coverage. There's something called an altmetric score, which tracks media attention. It's in the top 0.02 percent, not 2 percent, 0.02 percent of all 26 million papers ever

tracked and has a score about 19.1 times that of your average nature paper. So it hit and it hit hard and we've had some really stimulating conversations around it within academia and within social media. I think it's provoked people. Like I said, I want to force a conversation and it has. That said, I was always aware throwing out this grenade, that there was going to be mixed responses, with a lot of people jumping to the conclusion, oh, this guy is trolling us.

Like, this can't possibly be real. With all the bogus headlines out there, how do you separate the Harvard medical student lowers his cholesterol with Oreo cookies headline, which I consider to legit bait from other nonsense headlines. Right? So there was always going to be a little barrier to entry where people had to dig down a little bit. But I think overall, the response has been incredibly positive. People might have seen some discussions on social media. I think I've been even more taken by those in academia, like the number of clinicians,

cardiologists who have reached out to me who was like, wow, I went down the rabbit hole on this and this is stunning. To the point that a lot of people are now aware of the research we're doing and are applying the physiological principles in their practices. So people might be worried, oh, what was the effect of this? Were you having a negative effect? Were you tricking people into having Oreo cookies? I would strongly argue actually the net effect clinically, if anything, was positive because

one, I don't think any adult's seriously going to believe Oreo cookies are health food after reading that headline. And if I made this joke before, so I've already kind of dug my grave if this is an inappropriate joke, but I say, look, if I trick you that Oreo cookies are a health food, then honestly, natural selection should just thank me. Because... No, but in seriousness, I don't think anybody's like, people might play with this with their confirmation bias,

saying something about statins that I'm not, fine. Those people have already made their decision, and they're just using me to fuel a fire. I don't really care about those people. What I'm more interested in is the people that dig a level deeper and those clinicians that said, wow, this was a really interesting phenomenon. Something clearly happened here and I went down the rabbit hole. There's actually a lot of literature on this, including interventional trials that play

into the same principle where you use sweet potatoes or fruit to lower cholesterol. And now, you know what? I actually had these patients in my clinic. I didn't know what to do with them. They were medication intolerant. And now we're treating them with carbohydrate titration. They're eating a sweet potato per day. They like bananas.

They're having some bananas and papaya. And their LDL is cut from 400 to 100. And they're comfortable with that. And I'm comfortable with that. And they're not on a prescription pill. So the only person that's upset now is Pfizer, which I think the patient and clinician are generally okay with.

So it was an N equals one metabolic demonstration meant to provoke attention to what is legitimate science and legitimate scientists asking, what are legitimate questions? I believe Peter Itea kind of says something to the effect of, he's a proponent of some of these medications, APOB medications and things like that. And I believe he was kind of referencing that he just doesn't think that people can eat

enough or I'm sorry, they can't eat low enough amounts of saturated fat in order to get their APOB low enough via diet, exercise and whatever. What are some of your thoughts on that? What is maybe someone like Peter Aetia in your opinion, what do you feel that someone like that is maybe missing? I think Peter, like a lot of people, has a tendency to make blanket statements.

And I say that because he does. Like I posted the other day a clip of him saying, and this is if not an exact quote, a very close paraphrase, he was going through a list of unequivocally true things. He's like, these are unequivocally true things in medicine. He said, lower LDL in Apple B is better than higher. I'd push back on that.

I'd say you have to define the context better. You have to say, with respect first, to what outcome? Are you speaking only about cardiovascular disease or overall health, health span and longevity? Because if you're talking about the latter, you actually don't have great data to support that. We can dig into the weeds on Applebee and all-cause mortality if you want, but that's a quite nuanced conversation. You also have to

consider the fact that you can't lower a biomarker in isolation like snap your fingers. An intervention is required, and that intervention modifies other things and can come with other downsides. So I don't like the oversimplification of lower is better. And we also know that there's enormous heterogeneity with respect to how people with, you know, a given LDL level will manifest in coronary plaque. So some people might have very high LDL levels for a while and develop no plaque even though they're older people. Now for those people, does the literature say if

you do a scan, say you do a CAC, we can talk about CCTAs later, but a CAC even, and somebody who is like 55, 60, they have no plaque despite higher LDL levels, do you have evidence to say that lowering that is actually going to improve outcomes? The data tend to say no. So I think it's taking population data and trying to apply it, a blanket statement to it that should be practiced by individuals. And I'm personally against that because I don't think every person, because the way you expressed it, it sounds like he was advocating for

every person being on lipid lowering therapy. To be clear, I don't know if he said that, but I don't think we have data to say that is necessary or helpful. Now with respect to the effects of saturated fat on LDL cholesterol, different people respond differently. Again, getting to the idea of heterogeneity. For me, saturated fat is basically meaningless. In fact, here's a fun fact. The highest my LDL ever was,

which was 545 milligrams per deciliter, which would give a cardiologist a heart attack. Most cardiologists have never even seen levels that high. It was actually when I was eating a diet that was one gram of saturated fat for every 5.67 grams of unsaturated fat. The fatty acid composition of my diet was like olive oil but with more PUFA. And the reason my LDL got that high is because this was early on in my learnings and I'm

like, oh my God, my LDL is high. I want to lower it by cutting out saturated fat and cholesterol in case I'm a hyper absorber or something with respect to the cholesterol. So I cut out all butter, all dairy, all high saturated foods, all coconut, and high cholesterol foods. So I even transitioned to eating egg whites, which I would never do otherwise. And my cholesterol intake went from something like 2,000 milligrams to like basically zero. It was very, very low.

But as a function of cutting out all those foods, I ended up losing a little bit of weight acutely. Now, what does our model now say what happens when you get leaner? Your LDL goes up. So actually, accidentally, by cutting out cholesterol and saturated fat in me, I ended up inadvertently skyrocketing my LDL to the highest it's ever been. I bring this up because, again, to make the point, like the physiology, the underlying physiology that's affecting these lipid phenotypes really does matter and has implications on

how you address lipid phenotype. So part of it has to do with just understanding the physiology for curiosity's sake, but there are direct clinical applications whereby in your average Joe, person on a standard diet with metabolic syndrome, yeah, lowering saturated fat will probably lower LDL a little bit. But for a lean mass hyper responder, saturated fat might not have a big impact and adding freaking Oreo cookies, which actually add saturated fat to the diet, might lower LDL.

Now I'm not recommending that as a health intervention, but I'm just trying to highlight the fact that everybody's physiology is so unique, particularly in the context of a ketogenic diet. So the levers we have to pull are manifold and different levers have different bang for their buck for different individuals. And then you get to the question,

well, is it necessary to lower LDL? If so, to what level? What are the benefits and what are the risks of various interventions? I said at the beginning, I was gonna be long-winded on this because it requires long-winded discussions because frankly, lower is better is an inappropriate and insufficient overly

simplistic statement. And if Peter wants to challenge me on that, I'm happy to have a conversation with him thus far. He has not responded to my solicitations. And if we go to like the end game, which is like, I guess people are trying to prevent plaque, the buildup of plaque, right? There's no current information. I don't believe that there's anything we can do to reverse plaque. Now, I guess we can use common sense and say, hey, you know, a

good nutritional intervention and exercise is always great. But we don't really, it doesn't seem like there's randomized controlled trials with anything that can go in there and just kind of nuke some of that plaque out of there. Is there? No, I think there are some suggestions that with multimodal lifestyle intervention, including like stress reduction, improved sleep,

dietary changes, exercise, that you might get a little bit of reversal, but for practical purposes, I would say, don't assume you can reverse it, and try to prevent it from accumulating in the first place. But even the new, like some of the new drugs, the PCSK9 inhibitors, things like that, they don't actually get rid of plaque, do they?

I'm not aware of literature, there could be. There very well could be, and I could not be aware of it. So I'm actually just not gonna comment on that. But no, I'm not aware of it. If you're someone that's taking supplements or vitamins or anything to help move the needle in terms of your health, how do you know you really need them?

And the reason why I'm asking you how do you know is because many people don't know their levels of their testosterone, their vitamin D, all these other labs like their thyroid, and they're taking these supplements to help them function at peak performance. But that's why we've partnered with Merrick Health for such a long time now, because you can get yourself different lab panels like the Power Project Panel, which is a comprehensive set of labs to help you figure out what your

different levels are. And when you do figure out what your levels are, you'll be able to work with a patient care coordinator that will give you suggestions as far as nutrition optimization, supplementation, or if you're someone who's a candidate and it's necessary, hormonal optimization to help move you in the right direction so you're not playing guesswork with your body. Also, if you've already gotten your lab work done, but you just wanna get a checkup, we also have a checkup panel that's made

so that you can check up and make sure that everything is moving in the right direction if you've already gotten comprehensive lab work done. This is something super important that I've done for myself. I've had my mom work with Merrick. We've all worked with Merrick, just to make sure that we're all moving in the right direction and we're not playing guesswork with our body.

Andrew, how can they get it? Yes, that's over at MerrickHealth.com slash power project and at checkout enter promo code power project to save 10% off any one of these panels or any lab on the entire website. Links in the description as well as the podcast show notes. For the person that's listening is like this is this is amazing stuff, but for the person that's listening and wants to kind of interpret their own blood, what if they do have high LDL, they're trying to drop body fat, they're trying to get healthier and it's something that they see that and there's a bit of concern even though they're heading in the right direction

as far as their body composition is concerned. How do they interpret that for themselves? If they should figure out if they should try to lower their LDL or not? Right. First things first, don't take advice off of social media or podcasts. I think there's a lot of anti-doctor stigma. I really do encourage people to have conversations with their doctor. Now, your doctor should be open-minded.

So one thing you can do is determine what bucket you think you fit into with respect to your risk profile. Highlight your concerns and bring those to your doctor. So, if you do feel you fit the lean mass hyper responder phenotype, then see if your doctor is aware of this phenotype and is willing to work with you, given your priorities, to get to a place where you're both comfortable. It's not my place to tell you your risk profile because that goes so far beyond an individual marker and includes things like your personal baseline risk. Do you have any plaque?

Have you had a scan? I think functional tests are very functional. If you're of a certain age especially, you can get scans now, a coronary artery calcium scan or a CCTA, coronary CT angiography, which sees not just calcified plaques but also soft plaques. Do you have any plaque at baseline? And that kind of gives you some sense first of, like, the buffer room you have. If you have advanced cardiac disease, you're probably going to want to take a more conservative stance than if you have no plaque whatsoever. So that's

thing one. And then things like what is your family history? You know, if you had, you know, two parents or a parent and a grandparent who died of heart attacks, that's a different profile than, oh, you have no family history of cardiovascular disease. So there are a lot of pieces to this puzzle, which does make it complex. So there's not a simple answer I can give. I would say, yeah, I mean, but take the number seriously. Like, I'm not flipping, I've had lots of conversations about my lipid levels.

And we can talk what I have and haven't done with respect to my lipid levels, but it's not something I see and just brush off. It's something that I'm carefully monitoring and thinking about the pros and cons of any intervention. And I have the luxury of not really having a very strong family history of cardiac disease and having completely clean coronaries,

you know, at this point in time. So like from my perspective, you know, I've tried different things I can modify, but I let's say have quote buffer room and a lot of people might not. So first thing is take it seriously and talk with your doctor along that path to try to figure out, well, ask why is the LDL high? Do you have a family history of high LDL all the time? So were you born with high LDL? Or were you like me and your LDL was low and then skyrocketed on keto? Because those are two very different things.

If you've always had high LDL, if you've always had an LDL of 200, then you might have familial hypercholesterolemia. So, this might be a genetic phenotype. If you're very lean and insulin sensitive and you manifest a lean mass hyperrespondo phenotype, then, you know, you might be having this metabolic response to carbohydrate restriction, which can be treated with carbohydrate reintroduction. If you're neither of those things, and say you have obesity and you have low LDL at baseline,

but you went keto and your LDL went up, and maybe your triglycerides went up really high too, then it might be something entirely different. Maybe you do have a gene that interacts with your diet, or you're getting your lipid tests at the wrong time or not fasted, or you're really sensitive to saturated fat. That could be the case. The point is there are a lot of different things that can change that number. And you can't look at that number in isolation.

You need to look at it in the fuller picture of your overall lipid phenotype, which can give you like, I'd like to call it like a metabolic signature. It's like a thumbprint or a signature of like, what is the underlying physiology that might be driving this up? And then take into account other factors in your history that can help you assess your risk profile and what interventions are on the table for you based on what drugs you're tolerant of, what dietary adaptations you can make, and even things like what insurance will cover because some of these drugs might be very expensive. So medicine really is an art on an individual level.

You can kind of see why I really am resistant to statements like lower is better because it's just not that simple and it doesn't injustice to the individual case to pretend that it is. What's going on over there Andrew? Yeah, so I have become, I'll admit it, a bit of an ask-hole when it comes to cholesterol and all this and this subject because the main thing that I always bring up is I've had high cholesterol for as long as I've been doing blood work. Whether I've been on a, you know, following a really strict diet or not, it's kind of always been high. My dad had triple heart bypass surgery

because of high cholesterol. So ding, okay, cool. Maybe I am not okay, cool. But I have something to put on the wall that can potentially make sense of all this. Maybe it's hereditary or there's a genetic thing there. However, when I'm thinking about the way my dad grew up, the way he ate, the way he currently eats, he's never been overweight. But he's also never ever followed a diet of any kind. He just kind of eats whatever.

So my diet in comparison to his are very different. I can't think of a time where he ate a lot of meat, right? Like I definitely eat way more higher cholesterol foods than he does. I crush a ton of eggs every single day, although recently this year I have introduced egg whites to try to see if I can just manipulate that number through dietary cholesterol interventions of my own and unfortunately they haven't moved at all. If anything, they've gotten higher. I don't know what my numbers are exactly, but they are over 200. When it comes to the genetic or the hereditary component of all of this, how much of the

habit factor plays into all of this? Because again, my dad had high cholesterol, probably still does, but now he's on statins and he's got at least one good valve in there running and working very well. Although I have high cholesterol as well, but again, my lifestyle is completely different than his, but do I still need to be concerned with that part of the equation even though our lives are completely different? I would say lifestyle-wise, it sounds like you're doing all you can to reduce your risk. But you can consider these, I think, by and large, independent factors.

So if you want my simple answers like, should you be concerned at all, should it be on your mind, or should you just not worry about it? Well, yeah, you should be appropriately concerned. It doesn't mean, per se, that you need to go along and treat it, but you should take it seriously. Because Apple B and LDL, it is an independent risk factor, but it's one among many. Just because it is a risk factor and we presume it confers some degree of risk, it doesn't actually tell you about the absolute amount. So you can think about it like,

you have a, say like a simple line graph, y-axis versus x-axis. And along the x-axis is your LDL level, right, or your LDL exposure you could say. Along the y-axis is how much plaque you accumulate, you know. Even if we say the slope is always going to be positive to some extent, right? A very, very shallow slope is very different than a very, very steep slope. So even if we say it confers, quote, risk, well, how much risk? Is it going to get you when you're 60 or when you're 400? You know what I mean?

So I think that's a question that needs to be asked in this particular context. It's like, well, what is the absolute amount of risk conferred? Especially pertinent to, say, lean mass hyper responders, where something we do know with respect to cholesterol levels is that, well, let's say, I shouldn't say no, something that the data would support to date, is that the etiology, the driving cause of the high LDL, as well as the other metabolic context, will affect that relationship between

LDL level exposure and plaque accumulation. We do need a measure of what the absolute risk is if we're going to intervene, because we want to do a cost-benefit analysis. So if there are costs to an intervention, which there often are some costs, they might not be big, we can quibble over that, but there often are costs, what is the benefit you're going to be reaping?

Another way to phrase this, I did a video on it, and I used the goofy analogy of Godzilla versus the Geico Gecko. That was just a goofy analogy for the idea that we need to understand absolute risk. We can't just say this is a risk. We just say, well, how big a risk is it? Because in an individual setting, we want to do a cost-benefit analysis for any given intervention. That's the short of it.

And with respect to lean mass hyper responders as a phenotype, the interesting thing about it is it's really the first phenotype that really isolates this variable that we've been talking about all this time of high LDL. In the general population, you have maybe some high LDL, but it's not that high and it's against a backdrop of metabolic dysfunction because our population is metabolically unhealthy. And the only other comparison group that we know of with LDL levels that we're seeing, the levels of 300, 400, 500, is familial hypercholesterolemia. And in the more extreme cases like LDLs like mine, homozygous familial hypercholesterolemia, which is a one in one million genetic disorder, which does manifest in severe heart disease very early on in life, but the

driving cause is different. There's a broken lipid receptor, whereas in lean mass hyper responders, basically lipid physiology appears to be quite normal. We don't have any evidence of causative genes and it is not a congenital phenotype. I'm not born with high LDL. My baseline LDL on a standard diet, even like a standard American diet, if I ate McDonald's every day, my LDL will be about 90. But with carbohydrate restriction that goes up, it appears to be a metabolic response. And that etiology, that cause, that physiology, we have no reason to assume that it would confer the same risk as familial hypercholesterolemia. Because

in medicine and physiology, the cause always matters. You can't take one marker in isolation and make something of it. Another analogy that I've been using for that is like take that example of height. You can be 6'5". I'm not, as you can tell, but you can be 6'5 for various reasons. You could have tall parents, then you're 6'5 because you have tall parents, or you could have as a child a, you know, pituitary, a brain tumor screening growth hormone. You're gonna end up at 6'5 in both cases, but you're actually gonna have very different underlying physiology, and the consequences are going to be very different. So, returning back to lean mass hyper-responders,

what we have here is an unprecedented phenotype representing really interesting physiology that is an outlier in its extremeness, but probably represents underlying human physiology, that provides a natural experiment for asking a really provocative question. What is the risk of this phenotype? How does it occur, you know, underlying physiology, and then separately, what is the risk? And it is a question that I think every single scientist with interest in this field of cardiology and lipidology should be interested in because it provides the strongest ever

test of the lipid-hard hypothesis. If high LDL levels are truly sufficient at a certain threshold, above a certain threshold, above a certain threshold, to drive cardiovascular disease just by bulk flow, we should see lean mass hyper responders manifesting with profound heart disease. And so, you know, there's a natural experiment here, an opportunity to study this phenotype. And we're only starting to get a peek at what the profile might be based on very preliminary data that are coming out of the Lump List Institute.

There's actually a question I wanted to ask you, kind of shifting a little bit on other applications of the ketogenic diet and as it actually pertains to mental health. Because we had Dr. Chris Palmer on a few weeks ago and he was talking about some of the things he does with his patients that have bipolar, schizophrenia, other types of disorders and how beneficial he's actually found it in practice. There's a video I actually want to see if we can pull up and if we can, we will. If we can't, it's alright. But it's of Lane Norton actually talking about how he mentioned influencers are really putting

forward the ketogenic diet right now and talking about how great it can be for those types of individuals. And one of the things he mentioned is that we shouldn't be rushing to conclusions about the ketogenic diet and its benefits in this specific sense because we haven't compared it to just carbohydrate, we're not carbohydrate, but caloric restriction in the same sense. I think he referenced a study and he mentioned like all of these individuals ended up losing a certain amount of weight. We should see what caloric restriction would do if they were to lose the same amount of

weight to see if the ketogenic diet would actually show the same types of benefits. But one of the things I noticed when Lane was talking about it is he seems to not just have this idea of the caloric restriction aspect of things, but he also seems to just really actually just be against the ketogenic diet in general because of this.

So I'm just curious of your thoughts on this specific thing because I think you've made a video on some of the idea of the ketogenic diet and mental health disorders. Yeah, for sure. I'll start with the mental health disorders question, and then I will happily directly address Lane as an influencer himself and his anti-keto stance. Maybe just try to speak a little louder.

Okay. Thank you. Yeah, so with respect to the mental health study, this was a... It was a trial, an uncontrolled trial using a ketogenic diet for severe mental health disorder, bipolar and schizophrenia. And there were across the board improvements in mental health, and these severe mental health disorders consistent with other literature, other clinical trials including retrospective case series and actually ongoing RCTs or some ongoing. We can actually talk about what's happening down in Maryland, which is a whole different

kettle of fish. But the results were quite remarkable and there were broad improvements in mental health in these patients. And yes, they also lost weight. So it's true from this trial alone, you can't dissect the contribution of improved overall metabolic health, including or associated with weight loss and improve mental health features. But I'd add a few things. One is that, well, don't you think considering the amount of time and effort and resources and money that have gone into other weight loss trials, resources and money that have gone into other weight loss trials, including drug trials, we would have seen some signal of this somewhere else, right? Like think

about all the millions and billions probably of dollars that have gone into you know looking at GLP-1 receptor agonists and their evolutions. Don't you think if there was a mental health benefit signal someone would have reported on it or someone would have reported on it? Or someone would have reported on this with another diet? So I think, you know, while absence of evidence is an evidence of absence, the fact that this stands out, ketogenic diets stand out for improving mental health with underlying biological plausibility, and I won't unwrap that now in this whole podcast, but Lane can go ahead and read Chris's book to start or watch some of my coverage on brain

metabolism. As Lane likes to remind people he has a PhD, well, I have one in neuro metabolism. And so first thing is, well, why isn't there signal in other conditions? And then the second thing is, and I have seen Lane's coverage, he talks about jumping to conclusions like this shouldn't be used as intervention. But here's the thing. Those patients often are, well, they always are suffering. Schizophrenia and bipolar disorder are no joke.

And a lot of them are sufferingering with treatment resistant disorders. So I think that study was funded by the bazooka group the bazooka group Family of billionaires the father of the family David bazooka I think got his money from starting roblox the reason they're funding these kind of trials is because their son who was on five drug therapy, by the way, there's no randomized controlled trials on five drug combination therapy that is empirically derived based on people trying to see what works, and we still do it, he ended up getting treated by Chris Palmer for treatment resistant bipolar disorder and it saved his life. It changed his life. So yes, these data are to some degree in the early stages of the development.

But that doesn't mean we should throw them out the window and suggest they aren't important or that we're just, quote, jumping to conclusions about the potential benefit because right now there are real people in the world suffering with treatment-resistant mental health disorders, and if a dietary change that you even just trial for a month could save their life, why aren't you covering that in a positive respect with some degree of curiosity? Why are you jumping on the bandwagon of this is just a keto cult? Which he likes to do. And he honestly likes to play the strong man. And I'm going to frame this because I'm now going to go on a further monologue about Lane Norton and just say I've tried to have conversations with Lane repeatedly.

I don't like to go after people in absentia, but the fact that he's misrepresented our work and the physiology underneath it after having exchanges with us in private streams and refusing the opportunity to engage in discussions, which have been put forth by multiple people, including Simon Hill, Dom Dagostino, Thomas DeLauer, if he's not willing to come to the table and he wants to take the opportunity to do independent coverage of our work with respect to this lipid phenotype, and then botch the physiology, then yes, I'm going to punch back Lane. So, you know, what I'm going to say is what I'm going to say, if he wants to have a discussion with me, I am very open to burying the hatchet, I'll say that upfront. But Lane tried to cover the our literature before specifically the Oreo versus statin study. It was, there's some background there. So I know Lane. I don't know that well personally, but he's a pretty easy guy to read at some level. Like, you know, he's gonna clout chase if something is trendy. That's fine. That's actually

no shade on that. That makes sense. He's an influencer. So I'm doing this project, put yourself in my shoes, Oreo versus statin study, thinking about, oh, who might jump on it? Of course I know Lane's gonna jump on it, of course. So to prophylax against negative feedback, because I know Lane is anti-keto, what would you do if you're in my position? You're gonna try to reach out and make some sort of bridge.

Because honestly, I'd rather have everybody as an ally. I try to bridge build before I bridge burn, but if you poke at me I will yell Dracarys and come after you for the Game of Thrones past the dragon, you'll get that one. But anyway, so I reach out to Lane privately before I submit the Oreo vs. Staten paper and say, hey, I'm submitting this thing. Do you want to look at the discussion section? I will give you the opportunity to see it before it goes to submission and even comment on the discussion section and then I will acknowledge you in the comments. So if you want to add caveats, let me know. Oh, and by the way, I'm going to highlight one prior report we've published a bunch but here's

a Journal of Clinical Lipidology consensus statement that I wrote with other with leading lipidologist like Ronald Krauss, who was recommended to me by Peter Rettia, you should read this so if you do end up representing this, you at least represent our stance that this is scientifically interesting but deserves clinical caution. Now time went by. Then we published the meta-analysis of 41 randomized controlled trials. What does Lane love? The randomized controlled trials, the human randomized control, right? So we opened this discussion group,

this DM group on Twitter, and he's asking us questions about this meta-analysis of randomized controlled trials. And we're answering all his questions. My friend Adrian Sotomota, who's an MD, PhD and professor down in Mexico, is taking time out of his busy clinical and research schedule to answer all of Lane's questions.

We're answering questions about the physiology of Oreo versus statin, and we're offering to have a discussion with him. Or, if he doesn't want to have us on for any reason, William Cromwell, that respected lipidologist who trained Thomas Dayspring, who trained Peter Atiyah, is willing to have a conversation with him. So Lane has had every opportunity to have an intellectually honest exchange and present a nuanced point of view. What does he decide to do? He decides to do a hatchet job coverage where he's talking about the Oreo versus

Staten is just an n equals one and the keto zealots are blowing it out of proportion and here are some randos making commentary about it, rather than representing what the researchers are saying, he completely ignores the meta analysis of RCTs despite flexing he loves to talk about RCTs, and then screws up on the physiology, pulling a point from a paper about triglycerides in saying that it contradicted our underlying model, even though he asked that question in the DM, and I have screenshots of me explaining it to him, the answer, and it's in the paper. So it just seems quite honestly disingenuous

when you put everything, every opportunity here to have a nuanced conversation, spread nuanced messaging, and you go and do a hatchet job while trying to sell your data over feelings t-shirt. And then you get your feelings hurt. Because I said you did a poor job. Well, guess what, dude, data over feelings, read your own shirt. So yeah, right now I'm in Dracarys mode.

But I'll say again, dude, I've heard from people that he's a pretty thoughtful guy in real life. If he wants to bury the hatchet and grow out and like, you know, move forward, I'm fine. I'm very willing to be his friend. I'm also willing to punch back if I think he's misrepresenting our data in a harmful way. And quite honestly, I think the issue surrounding our literature is less so how we and my colleagues represent the literature, but how it gets characterized by people like Lane.

And then what happens is his followers have a misrepresentation of what we're trying to articulate and the dialogue degenerates, and there's infighting. But not because I said something I didn't say, but because he said something or implied something that I didn't say or wasn't willing to actually amplify the voice of the researchers who were trying to push forward what is interesting, legitimate science. So yeah, I do have a bone to pick with Laine.

You're probably wondering why am I wearing these glasses. Well, it's because I'm being bathed in blue light. And blue light isn't necessarily bad. There's blue light in the sun. But if you're in your office, if you're indoors, if you're in front of a screen during the daytime, it's not a great idea to have your eyes being bathed by blue light all day long. That's why EMR Tech, a company that we've partnered with, has blue light daytime glasses and blue light blocking evening glasses. These glasses right here are meant for you to wear during the daytime when you're in front of screens, etc. But if you're outside, take the glasses off and get the natural sunlight. And if you're at home in the evening when sun sets and you need to be in front of the TV

or you need to be in front of your computer or on your phone, these glasses are the ones to get. They also have the best red light therapy devices on the market. If you stand in front of any of EMR Tech's red light therapy devices, you will actually feel how much stronger the output of the red light is on those devices versus any of the competitors. They also stronger the output of the red light is on those devices

versus any of the competitors. They also have some of their smaller red light devices like their Firewave, Fire Dragon, and Fire Storm. And then if you want to get some of their bigger panels they have their Firehawk, which is their biggest panel, and the Inferno panel. These are literally the best red light therapy devices on the market. And if you want to save on them, Andrew, how can they do that? Yes, you got to head over to EMRtech.com. That's E-M-R-Tech-T-E-K.com. And at checkout, enter promo code power project to save 20% off your entire order. Again, that's EMRtech.com promo code power project. Links in the description as well as the podcast show notes. Something that may not have been on people's radar years ago. It may have been on some people's radar, I guess,

but it wasn't really much on my radar. I didn't really hear a lot of people talking about it, but you're hearing more and more about it all the time. And I did mention, we did talk a little bit about plaque, and I actually think that there is some evidence, maybe not super substantial evidence, but there's some evidence that the Sun can be a powerful mechanism to potentially help with heart health and

things like that. So what are some things you've learned over the years and what are some things you're seeing in terms of the sunlight and metabolism? metabolism. Wow, that's so to be perfectly transparent, like my Bostonian skin. Being a medical student in Boston, I have been deprived of sunlight. And so I've been kind of selectively ignoring that sect of literature, because it would only make me depressed since I have no possibility of getting sunlight during most of the year since I'm cooped up inside a hospital. That said, I'm transitioning to a different phase of life where I may have more exposure. I've read very little. What I'd say is that little that I have read has really struck me about just how powerful

light exposure can be as a metabolic manipulator. So just to give kind of some examples, I used to think or I think a lot of people think that the Sun entrains your circadian rhythm and has most of its effect via, you know, passing through your eyes. Some people might even know that there are special photoreceptors, these retinal ganglion cells that are, you know, not conscious vision, but then they feed into this area of the brain, the suprachiasmatic nucleus, and it regulates your whole rhythm, right? Well, there's actually a lot more data now that there are like alternative paths from

the eye to different parts of the brain, or even receptors that are non-optic, like receptors in various areas of the brain that will receive light because, you know, light wavelengths can penetrate through like, you know, tissue. So there are receptors actually all over the body that can respond differentially to light, affect things like glucose homeostasis in pretty profound ways. So what I would say is I would not underestimate light, but I like to delineate what I actually know a lot about and what I don't know a lot about. And my short answer is what I've read is really cool, but I'm not a light expert. And so I don't have really that well informed commentary at this moment on light and metabolism, even more specifically light and lipidology. But maybe for around two, I'll read up on that.

I have a series of things I wanna become more expert in, and I can put that on the list. Sorry, I don't have a more satisfactory answer. We're also starting to hear more about leptin, and it was talked about maybe a couple years ago. I guess people were sort of linking it to obesity in some ways, and then I guess more recently, I've heard the term leptin resistance.

Can you inform us on some of that and what are things to look out for? How do we just make ourselves healthier via some of this knowledge from leptin? Yeah, so leptin is an interesting hormone. It is primarily in adipokine, which means it's a hormone released from fat tissue, adipo meaning fat. It's released from other tissues actually as well, but primarily fat tissue. And its discovery is interesting because they had discovered these mice that were really fat and what they discovered is, oh, these mice, they have leptin deficiency.

When you give these leptin deficient mice back leptin, then they lose a bunch of weight. And at that early point in time, it was the moment where people were like, oh, we figured out obesity, yes. If we give people leptin, they'll lose weight. Turned out, didn't work like that. So in most cases of obesity, what'll happen

is there's a degree of leptin resistance. So just like with insulin resistance, where actually in insulin resistance, you end up with high insulin levels, because your body's trying to compensate, it's similar in metabolic dysfunction and obesity, where leptin levels will rise, but you're actually kind of resistant to the signal of leptin. Now, there's new literature on how that's mediated. It actually has to do with histone deacetylases, probably primarily in the brain, whereby these proteins, HDACs, histone deacetylases, which basically put acetyl groups, which are functional groups onto and off of proteins, can toggle the sensitivity

of the leptin receptor, or the leptin pathway via the leptin receptor, which can be adaptive because during fasting periods you might have changes in leptin and might want to change the receptor sensitivity such that you're actually hungry. Because if you have less leptin signaling, you tend to be more hungry with reduced energy expenditure and vice versa. So all I can say is what we know about leptin resistance is it tends to occur in parallel with insulin resistance. If you have insulin resistance, you probably have some degree of leptin resistance. And the mechanisms may have something to do with modifications of the leptin receptor. What to do about that? I mean, my guess, since these new basic science data were only discovered now in 2024, they're probably going to be followed with pharmacotherapy

trying to target that pathway. Maybe HDAC6 inhibitors, which seem to work in mice to sensitize the leptin. So a combination like leptin and HDAC6 inhibitor therapy might have some interesting potential. But at this point in time, it's really under the umbrella of this probably should self-correct if you address the root cause of the metabolic dysfunction. So if you overall improve your metabolic health, your leptin sensitivities should improve. So it's not really like a hormone that I think is super actionable to like measure in yourself. It's not something I think like, oh, I should get leptin every month to see what's happening to that.

But it is an interesting hormone among many. I'm curious about this because I've seen a few videos on your channel where you've talked about the topic of bone density. You mentioned L-citrulline in increasing bone density and curious if you can go in on that or potentially I just saw that in the title of one of your videos. But we know there are many ways weight training, even running to an extent can help increase bone density, at least if you don't do it a crazy amount. But what are some ways that people can truly do that?

Because I think one reason it's getting super popular is Peter Atiyah. He talked about that in his book and his podcast and people are getting DEXA scans right and left to try to figure out how they can increase their bone density. So how can we really focus on that? Yeah. I mean, this is one of the, the basic answer for like the majority of the population is the boring bread and butter stuff, which is get enough calcium, get enough vitamin D. A lot of people, especially in Northern latitudes, are vitamin D insufficient, so probably should be supplementing with D3, and then getting

sufficient calcium. I personally take 4,000 IU, which is pretty high, 2,000 is probably enough for most people, of vitamin D3, and then getting calcium, probably 1,000 milligrams per day, up to maybe 1,200 milligrams per day, up to maybe 1200 milligrams per day, ideally through whole food sources always. And in addition to that, weight bearing activity. But the thing is weight bearing activity affects people's bones differently. It's similar to muscle, right? So if you load bones, they should get stronger.

If you load muscle, they should get stronger. But we all know that there are those people that can hit the gym and do like, you know, tons of reps and sets and will put on muscle very slowly. And the other people who can like do 10 pushups and they just like bulk up immediately. My brother is the latter group. I am the former group, unfortunately. I remember one year we started, I brought him to the gym, we started benching together and he could only bench like 90 to start, then a year later he's benching like 250.

I'm like, Sammy, what happened? He's like, I'm just going to go in and just lift a little bit. So anyway, yeah, no, I'm the smaller brother now. Anyway, so it's the same with bones where there's a variation in how bones will remodel in response to mechanical stress. I actually one of my quirky element of my health history is I have a defect in one of the pathways that mediates that response. So normally what should happen is you load bone up and there's a cascade of

events so that your bones remodeled to get stronger. There's one pathway that's important to that, the molecular pathways called the Wnt. I have a defect in the receptor for Wnt or one of the receptors. So I had this really crappy thing happen to me when I was a teenager where I had no like, you know, I was a healthy young guy for my entire teenage years. Like, basically never even had to go to the hospital. And I started running marathons. And I was pretty good. Like, I was running sub-three marathons before I was 18.

And my first year I could run, like, a 3,000 mile a year, no problem. But then what happened is I started getting all these fractures. And I got more and more and more and more. And then I ended up getting a DE dexa scan at one point after some Really weird breaks were like bones in my foot were just like snapping in half and it turned out I had like full-blown osteoporosis

It took a couple years to figure out what was going on But what we eventually ended up figuring out was I have a defect in this pathway That prevents my bones from remodeling properly to mechanical stress such that when I was highly loading them They actually ended up getting weaker over time. That will not affect 99.999% of people. I'm like one in a billion that has this particular mutation. That aside, there is still variation in how bones respond to mechanical stress. So that brings me to the citrulline paper, which was really interesting.

I think it was a nature metabolism, but they were looking at what mediates variation in a mouse model of bones responding to mechanical loading. So they would take mice and kind of do mechanical loading exercises. So they could like load one leg and not the other so that the other leg served as a control or they could do treadmill tests. And they saw, yeah, some of these mice are high responders where like you put them on a treadmill and they run their bones get way stronger for how much they ran and other bone other mice that run and they're low responders, their bones don't get stronger. So they asked the question,

well, why? What's mediating that effect? Ended up finding out it was a particular gut bug in the microbiome. But as a general rule of thumb when it comes from microbiome, it's a pretty messy area. And we care generally less about the bug, but what metabolites are the bugs generating that are mediating in the effect?

And what they ended up finding was that L-citrulline, which is a supplemental or a supplemental bull amino acid, was mediating the effect, that it was signaling to osteocytes, which are kind of like the conductors in the bone. So you have your osteoclasts, osteoclasts with a C for cutting down bone, and osteoblasts for building up bone.

And their balance is coordinated by the osteocyte. And they found that citrulline signals to osteocytes indirectly. It actually had to be turned into arginine. Arginine is made in the kidneys and then there is nitric oxide, yada, yada, yada. But let's say indirectly it signals downstream in osteocytes to help enhance bones response to mechanical stress. So it was just an example, you know, on my channel I like to break down new science

in my favorite journals, cell metabolism, cell and nature, nature metabolism, that kind of thing. And talk about, you know, the preclinical data, the mechanisms that we're really just beginning to understand, which you need to do in animal models. Some of these tests, you really just, you can only dissect the mechanism in animal models. And then talk about the underlying physiology and what this could mean. So to be clear, there are no data in humans, no randomized control trials

showing citrulline improves bone density. That would be a kind of difficult trial to do, it would be a long term trial, bone turns over slowly. But the underlying physiology is there, whereby now we understand this mechanism by which there's variation in how bones respond to mechanical loading, and one element of the puzzle, one thing that could give a boost so you get more exercise bang for your bone buck, albeit speculative, is altering your metabolism in the form of boosting your citrulline levels and getting sufficient levels.

So again, speculation, but I think it's pretty interesting speculation. So yeah, I think that's pretty. Nick, do you lift or not? I do, I do. I'm not very good, but I enjoy exercise. I've always been an endurance athlete. And so I do more pushups than all of us combined and that once like what I've

seen him bang. You can do more pushups than all of us combined in this room. Yeah, that's weird. I, um, I, I don't know what's up with me. I that started in high school where it was my freshman year of high school. You can Google Nick Norwood's the body achieves what the mind believes and see a 13 year old me where it was like my freshman year of high school, you can Google Nick Norwood's The Body Achieves What The Mind Believes and see a 13 year old me, where it was like my freshman year of high school, we had these, you know, they used to have fitness tests, I guess they're not like wow, you have fitness tests, but we had this push up test. And I'm like, I want to be the best in the class at all the tests, but I want to break one school record. So I asked them, what's the push up record? It's three to second military style cadence, it's

monitored like it's 72. I'm like, I think I can do that. So I train, I ended up my freshman year doing 240. And then it became a thing where I would do pushup athons annually and train my senior year. I did 427 in a straight set, which was my peak of all time. But yeah, I have weird muscular endurance. Like I'm just wired for my muscles

not getting tired. But the flip side of that is like I'm not a power athlete. So, you know, I mean, I'm small, so I have good bang for my buck. I benched like 185% body weight at a one rep max. But I'm also very small. So I'm not going to tell you my weight because the actual weight is just given to us in percentages. We're not smart enough to calculate over here. Why I'm like, Oh wow. Nick's really impressive in the same way. Carry the one carry the one anyway, but no, I've always, I mean, I, people ask what sport I do now. And I kind of joke like, you know, the sport in medical school is just trying not to become a couch potato. So just keeping up you know some consistent routine but I

just want to point out that I think it's great I think it's great that you lift because you had all those breaks you were an endurance athlete previously then you kind of find out that you know when you lift you don't maybe get the same response as other people and a lot of people I think a lot of people would give up a lot of people would stop but there's so many benefits to just exercising and resistance training in general I'm glad that you still engage in it. Well I can gain like I mean like I can gain skills and I can gain power I can't make advancements I'm just slower and so I do different things I mean I do like I can make advancements, I'm just slower. And so I do different things. I mean, I do like, I can't bench a very high low, but I can do 10 muscle ups. Like I have my

skill set. And so it's like always just trying to find something new. And honestly, for me, and I think for a lot of people, I mostly do it for the like the mental health benefits, I am so much more productive, so much more on point. And it's at this point in time, and I'm sure it is for you guys as well. It's where it's like, if you don't work out, you're just off. Your day is just off. You just don't feel like good as a person. So it's not necessarily about like, I need to have my best day and hit PRs every day. I acknowledge that there are going to be ebbs and flows right now. This week, my workouts suck because of this burn I got. I don't actually think we were online when we were talking, but I

got a pretty bad burn along my right side, so I'm all bandaged up. So I'm waddling around the gym, I'm doing a bit, but you show up and you don't kick yourself for not having your best day, but you just have this consistency, this habit, this routine, and I think it just lifts all elements of life. So I genuinely enjoy activity. And it's something that I want to enjoy throughout my life. I do want to get more targeted about it now that I'm kind of coming out of what I consider the worst of my training at this time. Academically speaking, I might have more flexibility.

So there might be some, you know, I haven't done like a lot of cardio in a while. Maybe I'll get into rucking, maybe I can do that. Maybe I'll try to pick up some new skill or try to hit a new target. It's just like it's fun. It's a fun part of life. I think in general, people think about taking care of yourself as a chore. But I also think everybody's capable of getting to that point where they have a mind shift, be it physical exercise, or learning about your metabolic metabolic health where they're like, hey, this is kind of a privilege. This

is kind of fun. Like doing experiments myself for metabolic health, like always titrating and tweaking. And when you can actually find pleasure in that, like that's when you unlock health span for life or your best chance of having it. And I'm there. And I actually just like, it does dovetail with my interests. Because you know, when I'm reading these like, some metabolism papers about, oh, this quirky thing with L-Citraline, like, what is the relevance to me? And then I can tie it to like my osteoporosis history. It makes it really fun and relevant. And I guess my mission in part of a few, but it's like, to try to highlight that nerve enthusiasm for other

people where it's like, taking care of your metabolic health, learning about metabolic health, and then engaging in your metabolic health every day is such a cool privilege, because it's like your body is the system, your body is the lab. So when you learn about these things through listening to conversations,

whatever form you want to ingest media, and then you can apply it on yourself. I mean, maybe it's just like different ideologies, but I find that so cool and exciting. I don't know. Do you feel like you're on a diet? Like does it, you know, is it annoying? Is it hard?

Is it inconvenient? Not at all. I mean, well, the only extent to which it is, is for social reasons. I think everybody can kind of get that. Any sort of dietary restriction, be you vegan or keto, whatever. In social settings, it can be a little bit difficult. I would say that's the hardest element of it. I don't feel deprived of anything. Like I have no sweet tooth. But you know, if I go out say, you know, on a group date with my girlfriend and some new friends, and we go out to dinner. It is, is it still somewhat awkward to be like, I'm just gonna get a plain steak and nothing else? Everybody else is indulging in the bread rolls and gets the desserts and gets the drinks.

Yeah, a little bit. And it's not like every time you're gonna delve into, let me tell you my history of bloody diarrhea, blah, blah, blah, blah, blah, like nobody needs to hear that. They can inquire if they want, but you don't always unpack your rationale. So I think it's totally fair to acknowledge there can be peer pressure and awkwardness given our social norms. And in fact, I think it's really necessary to acknowledge that if you want to embark on lasting lifestyle change, because the fact of the necessary to acknowledge that if you want to embark on lasting lifestyle change. Because the fact of the matter is, that's something you're going to have to deal with and you're going to have to make an adult decision in a moment about what you want to do.

And so if you want to prioritize your health, then that creates an awkward moment for you, then that is an adult decision that I think people have to make. I will say that people that like know you and love you will become accustomed to it very very quickly and I think the negative apparent social stigma or discomfort often for a lot of people flips into a positive when people around them who are also suffering because most of us have friends and loved ones suffering with some metabolic illness see how well that person is doing and then you become the change maker within your social group.

I've seen that again and again. If you're the person that can start in your social group and stick it out, other people will follow you. The gravity of that is it ripples on metabolic health that are beyond yourself. If you're listening here and you're in the process of making a change or you have made a change or you want to make a change, realize that, like, you don't have to just be the listener and learner. You can be the leader within your own social sphere

in a really, really powerful way. For years on this podcast, we've been talking about the benefit of barefoot shoes. And these are the shoes I used to use back in like 2017, 2018, my old Metcons. They are flat, but they're not very wide and they're very stiff and they don't move. That's why we've been partnering with and we've been using Vivo barefoot shoes. These are the Modus Strength shoe, because not only are they wide, I have wide ass feet and so do we here on the podcast, especially as our feet have gotten stronger, but they're flexible So when you're doing certain movements like let's say you're doing jumping or you're doing split squats

You're doing movements where your toes need to flex and move Your feet are able to do that and perform in this shoe allowing them to get stronger over time and obviously they're flexible So your foot's allowed to be a foot and when you're doing all types of exercise your feet will get stronger Improving your ability to move Andrew. How can they get the hands on these? Yes head to vivo barefoot.com slash power project and enter the code that you see on screen to save 20% off your entire order Again, that's at vivo barefoot.com slash power project links in the description as well as the podcast show notes I think that the healthy habits tend to promote other healthy habits and it gives you momentum. You know, the walk that you didn't really feel like going on, as soon as you're done

with it, it might pep you up a little bit and then maybe you end up lifting or you're just more kind of energized for the day. I think that we have a tendency to kind of think that our energy is going to come from like a cup of coffee, but you can kind of like almost spin up your own energy. What I thought was really interesting video that you did was the midnight cake video. And I think that would be interesting if you could explain that because it sounds to me a little bit like the rich get richer and the poor get poorer situation of someone who's leaner and in better shape kind of always has an advantage.

You know, someone who's lean and in shape goes on a walk, they're gonna burn a lot of calories. Someone that maybe has more body fat, obviously they're gonna burn a lot of calories as well, carrying their weight around and stuff like that, but they're not gonna burn the same way as somebody with more muscle mass. So maybe you can explain a little bit

of this midnight cake situation. So it was a paper review video covering a paper published in Obesity recently entitled Trapped Fat, talking about the fuel partitioning model of obesity. And the thesis of the paper is that obesity is primarily a disorder of quote fuel partitioning. So where your body puts your energy, you eat food, you eat let's say calories or you eat food that contains energy that can be measured as calories, your body's gonna do something with that energy right? It can put it into building lean tissue, it can expend it or it can store it in fat. And while thermodynamics is, let's say, a rule,

a law of physics that has some relevance to biology, people incorrectly assume that calories are causal for obesity. And the fuel partitioning model really tries to reframe that by saying, what obesity, chronic obesity is, and we can dig into all the nuances and nitty gritty and counter arguments, but what it primarily is, is metabolic dysfunction, such that your body preferentially is biasing fuel towards fat storage. And then downstream of that, downstream as a consequence of it, you have compensatory mechanisms whereby you get hungrier, so you will increase energy intake over time, eat that midnight cake,

and or you will reduce energy output. So there is the calories in calories out element, but it's placed downstream, not upstream, not causally. And so that's the idea, that there's, you know, fuel partitioning that energy is trapped in fat and then downstream that causes increased hunger and decreased energy output. So the whole midnight cake thing was alluding to something I said in the video, which was what if it's not the binge that causes obesity, but obesity that causes a binge. By that what I really mean is what if you know,, we, well, let me frame it. Yeah, we'll use it as like this willpower element, right? You open the fridge. It's

midnight, you're hungry. You look there and there's the cake. And you're fighting yourself in your mind. You're like, All right, I want this, but I have willpower. I'm going to exert that willpower and I am not going to grab the cake. That's the framework we have, and to some extent there's truth to that. But I'd like to layer in another element, which is you're not just fighting your abstract mind, but you're fighting your physiology. Starting at the fat cell, which has no brain, has no mind, is operating independently. And so if you have dysfunctional metabolism where you're partitioning fuel into fat, you are fighting physiology

that maybe you can win the midnight cake battle once, but you will lose the war. That's the idea of it. And I want to, again, reemphasize this is entirely consistent with thermodynamics, calories in, calories out. But it places it downstream. Because I think what people, the conclusion they tend to jump to is that calories in,

calories out is an explanatory and causal model of obesity. When it's not, it's just a description of what happened post-hoc. So we talk about things like calorie deficit and calorie surplus. And people will often be like, well, don't you need to be in a calorie deficit to lose weight? To that I'd say, no. If you lost weight, it means you were in a calorie deficit. But if we're thinking prospectively and like calculating out surpluses and deficits, so

if I calculate my basal metabolic needs using Harris Benedict, tack on an activity factor, tack on 500 calories above that and then eat that I'm eating at a surplus. What if I lose weight? Then what do you say? You're like, Oh, well, your body compensated, maybe it didn't absorb yada, yada, yada. The actual definition of a deficit or surplus is defined post hoc. It's not a pathophysiological model. It's a post hoc description of what happened. It's not that interesting. It doesn't actually speak to the biology or the physiology. An additional layer to that is the whole acute doesn't equal chronic thing.

Because it's true. If you shove 10,000 calories down someone's throat for a week, yeah, they're going to gain some weight. But that doesn't actually represent the underlying pathophysiology that's causing chronic obesity. Because the body does shift and adjust to your input. So what we're really concerned about is what is driving like chronic weight balance, not necessarily what will happen over one week if you try to shove calories down somebody's throat. To caloric intake changes and to macronutrient changes, there are these metabolic shifts that take weeks to implement. So what you end up with if you try to, you know, make conclusions from these short-term studies,

even the short-term metabolic award studies, is misleading findings with respect to the pathophysiology of obesity and how different intake profiles affect our body composition and weight. is misleading findings with respect to the pathophysiology of obesity and how different intake profiles affect our body composition and weight. Quite honestly, it's misleading. I had an interview with Walter Willett at his house where we were talking about one study that had kind of become gossipal and we did a reanalysis and he agreed with our reanalysis and basically he called this one study which was, you know, with respect to calories inysis and basically he called this one study which was, you know, with respect to calories in calories out, he called it worse than useless and misleading.

Which is interesting coming from him, if you don't know who he is, he's a very prominent nutritional epidemiologist at Harvard. I won't dig into it, but let's just say people would probably presume we have different perspectives on nutrition broadly. But at least on this, we had a consensus that the short-term feeding trials can be incredibly misleading. But they also the bulk of the literature that are apparently in support of calories out, calories in calories out being causal. So that was a lot. Let me pause, because I hope you have questions on all of that.

It was kind of a shotgun approach to trying to explain. Yeah, one of the things that you said in the video that I thought was great was just this idea of that perhaps, you know, rather than somebody, you know, putting more logs on the fire, they're throwing their logs in the basement. You know, someone that doesn't have a metabolism that's working correctly.

Yeah, so that's fuel partitioning. It's like, your body's receiving energy. Is it gonna be the one that throws into the fire? Are you someone, like, say I overfeed. I go, quote, surplus, or try to go surplus. What happens? My body temperature goes up, I get incredibly jittery, I'm bouncing around all the time.

My body's throwing those logs straight onto the fireplace. Other people, like my dad, will take those logs and throw them into the fire. Sorry, not in the fire, into the garage. Put them in storage and gain body fat. So if we each overfeed, I won't gain weight. We're all gained very little weight Whereas he'll gain a lot of weight now We both went into the same or we could go into the same calculated surplus

But we might have a variation of I gain no weight and he gains 10 pounds In fact, they did an overfeeding experiment recently. It was a lipid experiment where I fed 6,000 calories per day actually more like 6300. Every day, and my calculated surplus was something like 27000 calories, which should amount to something like 7 pounds, and I gained 0.7 pounds. So I gained a little bit of weight. But again, like, what is the value of the model? If it predicts you're going to gain 7 pounds, and you gain 0.7 pounds. it predicts you're going to gain seven pounds and you gain point seven pounds? And also, does that translate to chronic outcomes? No.

And why did I have that response? Because me as an individual, I have different fuel partitioning, which is why in part, I'm resistant to obesity. So I think framing it that way is a lot more functional. And it helps people, I think, make decisions that are more practical. Because if you start to envision obesity like that, then you make decisions to optimize for metabolic health, which will favor fuel partitioning, which will lead to success in the long run, versus trying to engage in interventions that will impact the scale tomorrow morning, but might

then end up leading to poor fuel partitioning. So then over time, your body's going to be fighting itself. Right? What's an example of that? What happens when you're, so let's say you're trying to restrict calories and you get really hungry and you're in that midnight, like the whole midnight cake thing is alluding to The idea that like when you're hungry and you binge Are you binging on hard-boiled eggs? No, you're binging on that chocolate cake and the function of that

Because a high sugar food will say spike insulin spike glucose spike insulin and actually cause more fuel partitioning into fat You end up with this vicious cycle where the fattening actually cause more fuel partitioning into fat, you end up with this vicious cycle where the fattening and the poor fuel partitioning ended up making you hungry and making you binge and then you binged on something that caused more bad fuel partitioning and then you're hungry again and you end up in this vicious cycle. So figuring out how to eat in a way that favors fuel partitioning and people that are insulin resistant that will be helping to keep insulin levels low by eating a low glycemic low diet, you can start to break that cycle, but that does mean

breaking the mindset of choosing things based on a calories in calories out model. You might end up eating foods like avocado, extra virgin olive oil, macadamia nuts, whatever, or other nuts that, you calorie but they actually don't associate with weight gain over the long term. Why is that? Well, high level favorable fuel partitioning. So maybe go for the higher fat satiating whole foods that are promoting favorable fuel partitioning than trying to cut calories with a light and fit yogurt, which I have a bone to pick with for a whole different reason. Quick question about, you said you were eating 6,300 calories per day for a certain period and you only gained how much weight?

0.7 pounds. 0.7 pounds. 0.7 pounds. Now, when it comes to you and kind of how your reaction was to that, do you naturally move, fidget a little bit more? So a question I have for you is, a simple thing that we suggest people to do is after you eat, try to take a walk. Because you'll see some people, they'll eat a specific meal. And obviously, there's other nutritional recommendations, eating whole foods, etc. But some people, when they eat a big meal, they'll go and sit down and relax.

And that's what they do with every single meal. But the simple change of eating and then trying to just have a little bit of movement long-term can have a very big change in how people respond to the way they partition nutrients. So how big of a change do you think somebody can make to that aspect of their metabolism? Because that's not neat. Going out and walking after a meal isn't like you're neat increasing. But maybe that small change can lead to other changes

that have a favorable impact on the metabolism. You ready to have your mind blown? Yeah, let's go for it. Alright, because it actually might be neat. So I'm going to give you the element that your listeners won't know and you will know. And then I'm going to give you the element that you don't know. Okay. Which is, so you alluded to the idea that walking after eating, especially if you ate

carbs, can have some benefits. One of the reasons being is contracting your muscles, which you'll do when you walk, will help move the glucose transporters, they're called GLUT4, from inside muscle cells to the surface. So then your muscles become a better sink for glucose. And this is because there's a pathway whereby insulin causes the glucose receptors to move to the surface, but there's an independent pathway, whereby muscle contractions independent of insulin will help the muscle, these transporters move to the cell surface. And then you'll slink more glucose, it might help stabilize your blood sugar. So there's that element, so you'll have more stable blood sugar and that can have metabolic benefits. I think there's also the element Mark alluded to earlier, whereby like healthy habits beget other

healthy habits. So if this one little intervention makes you feel better, and you feel encouraged by it, then you might end up actually just eating healthier to begin with, which will have even you know, the bigger impact. So that's what I would say high level. Now for the fun part, where I talk about need a little bit, this is getting into the nitty gritty, so I apologize for the people I lose. But you actually know I was wrong. It's not neat.

It's thermic effective food. I got ahead of myself. I was excited, but I'm going to talk about it anyway. Which was, this is another element where it's like, it's something that we talk about, but gets oversimplified. So you know, people talk about the thermocaffective food, whereby if you say eat protein, you burn more calories digesting protein.

So your quote, thermocaffective food, the amount of energy you spend digesting it is higher. So then you extract fewer calories from the same quote calories measured that you eat of protein, say versus carbs. But there are other things that affect the thermocaffective food as well. And so the tie-in to what I was talking about here

is really interestingly, there is this phenomenon whereby better, more efficient insulin signaling in muscles can actually affect the thermocaffective food. Because what happens? Remember I was talking about those glucose transporters getting transported? Well, there, these glucose transporters, they're kind of tied down inside the muscle cell membrane

in these little vesicles. They need to get transported to the top of the muscle cell membrane so they can sync that glucose. How are they tied into the muscle? There's an anchor, a molecular anchor. The molecular anchor is called tug. And in order to get the glucose transporter to the muscle cell surface,

you need to cut the tug anchor. Now, one could think, oh, you cut the tug anchor, the glucose transporter moves, end of story. But biology usually repurposes things. And so what happens is that the tug anchor is broken into two halves, and the one half actually ends up going into the nucleus, activating PPAR alpha, I think it is, not gamma, I'm pretty sure it's alpha, and promoting thermogenesis. So the implication of this is that if you have good insulin signaling, you're going

to have more thermic effect of food after eating. That is the extrapolation. It is an extrapolation indeed, but one that I think continues to add other layers about just... Well as Mark was saying, the lean people get leaner, the people with obesity get more obese because you have these vicious cycles. This is another element in which once you start to fix your metabolic health, you get advantages off of that in pretty profound forms that you wouldn't really even possibly think about, like the fact that you'll have

more efficient insulin signaling so you get better glucose sink. And on top of getting that better glucose sink, you get more thermogenesis after eating, because that C-terminal end of the tug anchor is going to your nucleus and increasing thermogenesis. Which you know, I realize this is nitty gritty, but if nothing else, just take a pause and listen if you want and think about the elegance, the beauty, even the messiness to some extent of these systems and how much more complicated it is than calories in calories out or a bomb calorimeter, which is why these oversimplified heuristics of just eat less, move more, never end up working.

Because your physiology is really complicated, and so you need to find a way to work with it, improve, say, fuel partitioning, rather than trying to work against it, because you might win one midnight cake battle, but again, you will lose the obesity war, until you kind of internalize this truth about metabolic complexity, but it's We learn so much from just like mere exposure in society that sometimes those lessons are really hard to unlearn Like it's hard to get out of calories mindset So one of the really fun things about doing this podcast is that we get to speak with and learn from so many people in different walks of life and

get to speak with and learn from so many people in different walks of life. And one thing that we tell listeners is like, hey, if somebody has some good information, take what you can. And if there's something that you disagree with, don't throw everything out. Just ignore that side of things. As we started talking to more and more people, I started getting very picky and choosy with the information that I would take. One of those things being artificial sweeteners. Now, I didn't really know much about them, but then you talk to a couple of people and, you know, of course, Elaine Norton will point

to a lot of studies and say how like they are, you know, we're not a Petri dish, therefore they're totally safe for us. But you had put out some information recently and it really caught my attention. So with some of those studies, or maybe you can take this where it was somewhere different, but with those studies, like what are they missing and why should we just not completely ignore the fact that, hey, maybe there actually is some detriment to taking in so many artificial sweeteners? Yeah. So first things first, I'll play Lane's game, and we can talk about randomized control trials,

because there are randomized control trials showing artificial sweeteners can be harmful. But there's nuance there. So before I even get into that, I want to frame this as people love simple. People love, oh, lower is better. Oh, artificial sweeteners are bad. Artificial sweeteners are OK, benign. It's not that simple. People love, oh lower is better. Oh artificial sweeteners are bad, artificial sweeteners are okay, benign. It's not that simple. Non caloric sweeteners, people sometimes think you know, oh they're either a free lunch or there's no such thing as a free lunch. Zero calories, they're benign, no free lunch.

That's one kind of heuristic that people fall into. Another is there's natural like stevia and then there's unnatural like aspartame or sucralose and they go on the natural unnatural heuristic. These are heuristics that are imperfect and the fact of the matter is non-neutral sweeteners are a very heterogeneous group of biomolecules with different effects. It's like saying all fat sources or all fats have the same metabolic effect, but we know stearic acid and like linoleic acid are gonna have different metabolic effects or if you want to say even protein sources like you know peanuts, peanut butter is not the same protein as an egg. Now that's getting a little bit far afield with respect to the analogy, but you get my point. These

are heterogeneous molecules with heterogeneous effects. And metabolic context matters. So really we just have to break it down sweetener by sweetener, context by context, and say what does the data actually show us and what is there to be concerned about? Starting with randomized control trials. There are randomized control trials showing harm in humans. So one example would be a study out of Dana Small's lab, Cell Metabolism 2020, it was the one I covered recently, where what it did was it,

it was actually investigating this uncoupling hypothesis whereby the idea is, oh, if your body gets sweet, but doesn't get the energy that it should associate with sweet, then it's gonna get all out of whack and have metabolic dysfunction. So they ended up doing a randomized controlled trial where they compared a pure sugar, regular sugar drink, that was 120 calories. And I think the intervention was, I'm trying to pull this out of memory, I'm pretty sure

it was something like, I forget what the age range was, but it was generally healthy adults, and I think there were 40-ish of them, maybe 45, and they had seven sweetened drinks over two weeks. So not crazy doses, pretty reasonable doses of either sucralose, regular sugar, or sucralose combined with carbohydrates in a calorie-matched manner with the regular sugar. And what they ended up finding was actually was the combination group, weirdly enough, which went contrary to their hypothesis, but that had insulin resistance induced by these, by the artificial sweetener combined with the carbohydrates, which is relevant in a real world context, because you know, that light and fit yogurt I mentioned, like that is sucralose mixed into carbs.

Or if you have like, you know, a sucralose in a dessert, or you have it in your coffee, with you know, a mixed meal, and you have a bagel, generally people are taking this in, in the context of carbohydrates, and often high glycemic load carbohydrates. So this is actually the real world, probably use case. And what they found was one, two weeks of consuming it in this randomized controlled trial in the context of carbohydrates did indeed induce insulin resistance. And along with that changed dopaminergic circuitry activity in the mesolimbic system, the reward system in the brain on functional magnetic resonance imaging. So we're seeing a strong signal here whereby sucralose can indeed, in the context of additional carbohydrates, but not when having those

carbohydrates alone, or not when having the sucralose alone, can induce insulin resistance and changes in brain circuitry. And in fact, they did a sub-study on teenagers where the effect was so profound, 13 to 17 year old, they had to terminate the study for ethical reasons. Because the HOMA IR jumped so much. I think it was like 2 out of 3 went from below 3.5 to above 12.9. And I know somebody's gonna say, oh, it was only a few people. I'm like, yeah, because they terminated it early because the response was so profound and consistent with the larger adult randomized control trial. And so, one, there's a few lessons to take away from this. One, RCT data, yes. Concerning, yes.

Context, doesn't matter, yes. Now, this is just one study, but the interesting thing you can take away about it is like, based on these data alone, you know, I'm not arguing that just taking a little bit of sucralose and putting it in your black coffee and that's all you have is going to cause insulin resistance. The data actually don't support that. But sucralose can, in the context of carbohydrates, again in a calorie controlled fashion to just having sugar, will induce insulin resistance. We don't know exactly why that is, but it is a clear signal.

And what are the consequences of that? Well, one, insulin resistance is kind of crappy, but there are other possibilities, and I emphasize the word possibilities, that arise since we don't know exactly how the effect is mediated. So take the brain changing findings. One reason this really scared me in something I presented in the video was,

what if, and this is a possibility, the effects of insulin resistance were mediated in a top-down manner, such that somehow the dopaminergic circuitry was being affected by the sucralose combined with the multidextrin, and that that was causing insulin resistance in a top-down fashion. If that's the case, could it be possible that, you know, the teenagers who have this profound response and are having their neurodevelopment go through a critical period, could their brain be rewired in a fashion that could set them up for metabolic dysfunction for life? It's a possibility. It's a possibility we need to entertain and then take that in the context of the choices we're making every single day.

So, what I want to emphasize here is there are data of concern, and there are also things that make us think about maybe we should be concerned about this, and even if we don't have the randomized controlled trial data for every finding, you know, it's not, it doesn't mean we should discard the data. Actually, I'm going to pause because I know it took for a long time, answer any questions you have. And then I want to talk about another sweetener, aspartame and anxiety in sperm. Very interesting study out of PNAS. So I guess, you know, so then my next question then is because like whenever I'm asked for like, you know, hey, like I want to lose a couple pounds here and there.

I always recommend like, all right, just stop drinking your calories, right? Like, you know, they'll have coffee with all of the fixings. They'll have dinner with the high sugar soda. And again, just more calories that aren't really going to help them feel fuller. They're not really going to do anything for them. But after seeing what you just talked about right now, it seems like if I'm telling somebody that's going to go to like In-N-Out and they're going to have hamburger fries, I've been telling them, okay, well then have the diet Coke. Don't have the high sugary Coke. It seems like potentially that is leading them to insulin resistance, whereas having

the regular... If this person's active, they are trying to manage their weight and they are exercising, it seems like the diet could then lead them to insulin resistance, I guess, faster than the full sugar soda. Am I understanding that correctly? So again, this comes down to the heterogeneity of different biomolecules. A diet coke, for example, is aspartame, not sucralose. And, you know, just because I'm saying, you know,

artificial sweeteners can have problems, isn't saying they're worse than a coke. So you end up in this difficult calculus where it's like, you know, if you're giving me this binary, this person is getting this meal and they have to have a Coke or a Diet Coke, based on what I've seen in the literature, which should they choose? I'm still going to lean towards the Diet Coke. But that is a different framing than what we were talking about. We're talking about, could the diet version and the artificial sweeteners be harmful as compared to something that's more neutral? And I would say the answer is yes. So I mean, the question I'd pose to that person is, can you have some sparkling water

maybe? And, and I know I said that with a little bit of tone, but in all seriousness, I think acknowledging what the risks or the potential harms of having something are, and then deciding, is this worth it for me, given the considerations at hand? And if the person really loves Diet Coke, nobody's going to be perfect with their diet. So like, fine, if that's your guilty pleasure, that's your guilty pleasure. As long as you're informed about what the consequences might be, and you make an informed decision as an adult, I don't care what your decision is. I just want you to have the information to make an informed decision.

On the topic of diet coke, there was a really interesting mouse study where they showed a diet coke at dose equivalent, or not diet coke, aspartame. Aspartame, which is the sweetener in diet coke, at dose equivalents of two to four diet cokes per day in mice not only promoted anxiety, but promoted anxiety in subsequent generations. It was inheritable, even though future generations did not get exposed to the aspartame. It could even be found at the four diet coke dose in the F2 generation, the grandsiders of these mice, which is super crazy. Now I want to frame this with a couple other things. Biological plausibility for anxiety induction, yes, aspartame is broken up into various compounds.

Some can affect transport of different amino acids through the blood-brain barrier, change neurotransmitter balance. There's actually one RCT that I know of on aspartame and irritability slash anxiety. We're leaving that aside for now because that's not the point. There's biological plausibility there for inducing anxiety that it can also change epigenetic marks, say on sperm, so it could be inherited. And so you're left with, we have these interesting mouse data, published in actually a pretty good journal, that even low doses of aspartame, equivalent to what people drink,

can induce anxiety and that can be inherited. What do you do with that? Now you could be like some people we know and say it's not a human trial, it's a mouse trial and throw it in the bin. Or you could say, you know, thinking practically as a scientist, we're never going to have a randomized control trial looking at diet coke at two to four diet coke doses as an isolated intervention that's followed for two generations. Nobody's done that study. Nobody's going to do that study. So given the literature we have, even with its caveats, let me take that and as an informed consumer decide, is that concerning enough for me not to have the Diet Coke and maybe try something else in its place? That's all I'm saying. I'm

not saying that I have proven for sure Diet Coke will cause your grandchildren to have anxiety. I'm saying there are signals in the literature that are quite legit that cause me to pause. And quite honestly, for me, not speaking about people listening, but for me, I don't care enough to risk it by having Diet Coke in my diet. So I'll find something else. And the nice thing is, because non-chloric sweeteners are such a huge heterogeneous group of compounds, you might be able to find things that are more benign. I think stevia tends to be more benign, as does monk fruit. Allulose might even have metabolic benefits. So again, it doesn't fall into the easy heuristic of,

if it has very low calories or zero calories, it's good or bad. You know, it's benign, or there's no such thing as a free lunch. It's complicated because these molecules are complicated. Are artificial sweeteners harmful? To some degree, yes. The answer is yes.

There's clear data, even in the RCTs like we went over, they can be harmful. Doesn't mean that having a diet coke is going to cause a massive glial blastoma multiform to like explode in your brain, you're going to die. No. I'm not saying that, but like we just need to pause and take a nuanced dissection of the literature, acknowledge that there are downsides, present people with those data. It can cause insulin resistance. There might be effects on mental health.

Even if the signal is only in mice, there might be transgenerational effects. And then have people walk away with those data as informed consumers of nuanced information, and then decide, do I want the Coke diet Coke, or am I motivated enough to try the sparkling water or still water? I want to have a serious conversation with you about your balls. And I'm being serious here. On this podcast, we talked about a lot of things to help men improve the health of

their penis, because it's important. And your balls have very thin skin. This is true, you can touch them right now. And you know, it's pretty thin. Women do a lot of things to take care of their vaginal health and men, we don't really think about the things that we put right directly on our balls, like our boxers. A lot of popular brands out there have chemicals that are literally touching your balls. Think about this. When you're in the gym sweating, when you're at work sitting, when you're doing all these things, these things could be permeating into your scrotum. Things like BPA, phthalates, pesticides, incesticides, toxic dyes, toxic fertilizers, formaldehyde, all of which could lead to and could exacerbate lower testosterone, erectile dysfunction,

and potential infertility. That's why I've partnered with NADS. And NADS is made with 100% organic cotton and no toxic dyes. So instead of putting just anything on your manhood, it's a good idea to get your hands on some NADS. And Andrew, how can they get it? Yes, that's over at NADSunder.com. That's N-A-D-S-under.com. And at checkout, enter promo code powerproject

to save 15% off your entire order. Again, that's at NADSunder.com. Links in the description as well as the podcast show notes. Damn. That's some heavy shit. That gets rid of one of my favorite diet sodas, the Diet Ginger Ale Splash. Yeah, but you like Zevias, right? No, no, I don't like Zevias.

There's this Diet Ginger Ale Splash that's so good. It has five calories. I love that shit. Which one? What sweetener is in it? Aspartame. I just looked it up right now. I just looked it up right now.

Here's the nice thing, is you do make something on the order of presumably like 10,000 sperm a second. So I guess as long as you're not planning on reproducing right now, you might get a little bit of sperm turnover. Just don't like... What I'm trying to have a kid, maybe don't you might get a little bit of sperm turnover. Just don't like... When I'm trying to have a kid, maybe don't have it for a little bit. Yeah. Yeah. Anyway. No, again, it's like, I...

It's difficult. Let me reveal a struggle internally I really do have, which is, on my channel, I really like to break down the basic science, just for curiosity's sake. I love physiology, I love metabolism, I get excited about it and want to teach about it. But if you're talking about the frontier of metabolism, it's always going to be mechanistic basic science where the extrapolations to human are going to be speculation. To some degree, we can speculate and to some degree that's fair. But there's always a little bit of a reach. And one thing you know about social media is people want the actionable items. People want the like, I do this and I get this benefit and it's

assured. People love the confidence. And you see this all the time, even in thumbnails or statements like, I'm trying not to talk about people in their absence, so I'm actually not gonna name names, but things like, do this one thing and it's the best intervention for longevity, or like, this model of obesity is the be-all end-all. It explains all phenomena in the diet space. These are hyperbolic claims.

They are not substantiable, but they're actually really good if your main objective is to get engagement. So I'm caught, like I think a lot of us are, in this tension of I want to be intellectually honest and represent the data for what it is. I want to give people actionable takeaways while remaining honest. So that's going to require a little bit of stretching and speculation. And I also, and this is a criticism I get quite a bit, is like people say, oh, you waffle, you're not clear. Like, what should I do?

Because they want that prescription. They want the like simple message. And I'm pretty resistant to giving it because you can see with all these topics, there is no honest, simple message. And if you resist giving that honest, simple message that takeaway is necessarily going to, you know, hurt engagement to some extent. So it's a balance. There's no perfect balance with respect to, you know, like giving people instructions, not instructions, but like this is the the takeaway, the

one-liner. This is what you need to do to get the benefits. Being perfectly honest to every nuance and caveat, like you can't really do either thing. On the one end, you just become a sellout. On the other end, you're an ideologist and a purist who while it sounds nice, you end up posting YouTube videos that get 300 views. So how do you find that balance is something that I'm posing because I just want to say like, it's something I think we all struggle with. And we're all just trying to find the balance and how to navigate that at any given time. So I think it's something just for people to keep in their head because there is an incentive structure built for people to give these confident, simple messages, but they will never represent the scientific reality,

the scientific full picture. Is there anything you're working on or poking around with now that's kind of new that you're getting fired up and excited about? Oh, so many things. A lot of them I can't talk about, but I would say keep your eyes peeled for the first publication, like full form publication

of the Lean Mass Hyper Responder LUNQUIST study. So we did a study where we were looking at the relative levels of plaque in a Lean Mass Hyper Responder group with mean LDL levels of 272 for 4.7 years as compared to a matched control group. Now I can talk about the data because they've already been presented, which was in the lean mass hyper-responder group, there was no increase in plaque and actually trending towards decreased plaque and no association between LDL

and plaque levels. But that paper is going to come out in its full form shortly. I've already seen and sent back the author's proofs. So that's kind of exciting. We have a few collaborations. We're spinning up with pretty major labs at... I probably shouldn't name the institutions, but including like starting to look at the multi-omic profile of lean mass hyper responders, maybe finally trying to test this hypothesis of like, can you take lean people and a priori convert them into lean mass hyper responders, and

then look at, you know, what is the multi-omic profile that predicts that conversion? I should explain multi-omic means all the ohms. So your microbiome, your proteome, your genome, your metabolome, and then you integrate that into like one huge picture of what the physiology is. And you can actually take that over time, hence longitudinal. So you get this super high resolution video of everything that's going on in the body plus microbiome. So we're going to be doing that since now we're accumulating more resources and partners. That'll be probably a one point two million dollar study.

So we got to get the funds for that. I'm really excited about just having a little bit of free time this year to start to explore storytelling and social media a little bit more. Like I said at the beginning, I'm at this interesting pivot point in my life where I want to figure out how I have an impact. Until 2024, I really didn't do much in terms of like long form content production. My YouTube was just like, I'm going to talk about a paper on my phone that I just saw. Now I've got a nice camera. I have a teleprompter below me.

You can't see it, but I'm going to start using that, like nice lightings. I'm going to be traveling around for podcasts. I was going to come see you guys in Davis. Stupidly got injured, ended up canceling that trip. But there's a lot of fun partnerships that I will be spinning up. And it's just going to be exciting time to like explore scientific communication because it's something I just, you can tell I love to talk. I'm going to be having a lot more conversations, doing a lot more digest, you're going to be seeing a lot more of me. So I invite you to engage.

I invite you to engage. I think one thing I'd like to offer very genuinely is there are a lot of influencers, gurus, whatever you want to call them out in the space. I think a lot of people are quite entrenched. There are others that are very dynamic and willing to evolve. What I'll say is I'm young, I don't pretend to be wise, I'm at the very beginning of this process and excited about that in such a way that like I know I'm going to be growing and evolving very dynamically over the next several years. And what I'd offer to my audience is like, look, I want to come here, I want to teach you

what metabolism, but I want you to be my teachers as well in the most authentic way whereby your feedback is genuinely my data. I look at as many comments as I possibly can, interact with people, see what's resonating, see what's not resonating, where I step in it, where I really hit home with something. And feedback and engagement is like how I'm going to grow and evolve. So like, I love to teach, but I'm also looking for, you know, teachers and then together assemble assembling like what I kind of consider a metabolic health army because one thing I have learned from my years in research and even more so in medical school is the medical and research infrastructures we have are pretty screwed

up and biased against metabolic health. The way this research moves forward is grassroots bottom up metabolic health army. Like the you know, it's not going to change another way. It's really sad to say. but that's the fact of the matter. That's the conclusion that I think anybody who's spent serious time in this space will come to. And so on the one hand, it's a little bit sad and pessimistic. On the other hand, it's pretty exciting because by virtue of the era we're living in with all this access to information and interactions you know, interactions between academia,

social media, the general public. The public actually gets a really powerful say in how this ship that is our country's metabolic health, the world's metabolic health is steered. And I think that's pretty cool. So you have a lot of power. Metabolic health army with a soldier, Lane Norton. I'll recruit him. I'll whip him in shape. Hey, thank you so much for your time. Where can people check out some more information on you websites, YouTube, stuff like that?

Yeah. I will be spinning up a website nicknorwitz.com, although it's shut right now as it's being geared up. I'm on YouTube at Nick Norwitz, on Instagram at Nick Norwitz, on Twitter at Nick Norwitz. There's only one Nick Norwitz in the world as far as I'm aware, so I'm an easy guy to find. I have a newsletter that I'm having pretty fun with, Stay Curious Metabolism, that's via Stubstack.

So choose your preferred forms of media, follow along, engage, give me feedback, let me know what you want to hear about what messages resonate, which don't. And yeah, I'm just, I just feel very lucky to be here now with you guys and in this space, learning, evolving, talking, and hopefully teaching along the way. Strength is never weakness, weakness is never strength. Catch you guys later, bye.