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#335 - Carnivore MD vs Harvard Heart Doctor: Seed Oils are Actually GOOD For You | Paul Saladino & Nick Norwitz
03:36:33
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- [00:00]
Nick Norwitz
Foreign.
- [00:08]
Danny
Seed oils are good for you. And we're going to talk about that today. So first of all, why don't you guys, for people who haven't seen your interview and for people that aren't familiar with who you are, Paul, why don't you guys introduce yourselves, give yourself like a quick background.
- [00:20]
Paul Saladino
You want to go first?
- [00:21]
Nick Norwitz
Sure. My name is Nick Norwitz. I'm an MD, PhD, fresh out of med school. Actually like 10 weeks since graduation at Harvard Med. And my background is I got into speaking about metabolic health through a personal journey with inflammatory bowel disease at the end of college, in grad school and before med school. That really got me curious about the distinction between what we do in conventional medicine and what is, quote, evidence based care and what is actually the best care based on human physiology and how we can bridge the gap between metabolism, physiology, science, and what's working for people and modern medicine to actually just like help improve population metabolic health, which I don't think is controversial to say is not going in a positive direction right now.
- [01:23]
Danny
And you also did the famous Oreo versus statin thing we talked about.
- [01:26]
Nick Norwitz
I'll never live that down.
- [01:28]
Danny
You did an experiment on yourself where you took statins for 30 days and then Oreos for 30 days and Oreos dropped your cholesterol.
- [01:35]
Nick Norwitz
So Oreo, 16 days, statins for six weeks. This is actually like a good, a good case in point because one of the things that I find quite interesting is what gets talked about and what doesn't. We'll get into some examples of like research and what gets, I mean, suppressed is a strong word, but just what gets amplified and what doesn't based on the incentive structure. So I was doing research in an area around lipids and cholesterol that I thought was fascinating. And I had this new tool at my disposal, social media, which, you know, I don't have, you know, multimillion dollars to do large trials, but I do have some tools which are social media and then useful brands. So in order to amplify discussion around this area of research, we may or may not get into it. I basically formulated an experiment where I would test the cholesterol lowering potential of Oreo cookies versus standard of care statin therapy. So it was originally gonna be two weeks of Oreo cookies, then a washout period and then high dose statin therapy. So 20 mgs of Crestor and I know how to dot my I's and cross my T's. So I got an institutional review board letter exemption from Harvard, had my PCP ordering All my labs into my electronical medical record had a career. Lipidologist William Cromwell helped me to design the study and write the paper and then we executed it. And as predicted, a priori, the Oreos lowered my cholesterol by more than twice as much as the statin at about a third the time. And for me, that was. It was a social experiment more than anything because it was clearly engineered to be clickbait, obviously. And it's like, how can I use the tools provided by media and understand incentive structure of people's emotions to start a discussion around something that actually has a lot of nuance? So I think people in academia try to be idealistic and stay above, you know, engagement tactics and then end up kind of bitter and salty that they don't have a seat at the table and influence. And I think in the world we live in now, where there is clearly an uncomfortable collision, incursion event between like academia, conventional medicine and the general public because of access to information, right. And social media, that's something we need to like, understand and play with practically just because it's the ecosystem we now live in and we do it responsibly and draw our own lines. But that was me just kind of playing with like, what kind of reaction can I get and how can I actually leverage this to amplify nuanced discussions, right. And push forward research. I will tell you it's been a success. I want to get off this particular soapbox. We can return to it if you want, but I have reason to believe that it was.
- [04:24]
Danny
Yeah, we'll definitely get back to it, but I want to hear Paul's perspective. Background.
- [04:29]
Paul Saladino
I'm a traditionally trained medical doctor. I was a physician assistant in cardiology before medical school. Then I went to medical school at the University of Arizona. Did my residency, unfortunately, at the University of Washington. Not that the University of Washington is unfortunate, but the fact that I did a residency is unfortunate.
- [04:44]
Danny
Why was that unfortunate?
- [04:46]
Paul Saladino
You go. You go deeper down the rabbit hole and, you know, into a medical system that you realize is broken and doesn't really serve people. So when I was in medical school, I really liked internal medicine, but I didn't see it actually getting to the root cause of illness for humans. My dad is an internist. I didn't really want to repeat that. I ended up going into psychiatry because I got really interested in human story. Humanity, suicidality, neuroinflammation in the brain and connections with the things that we eat is very fascinating. And you know, you realize pretty quickly in your Residency in psychiatry, that it's all kind of a farce that the drugs we're using in psychiatry. I never practiced psychiatry. I've since left and don't consider myself in any way associated with psychiatry, but the drugs used in psychiatry or anachronisms and, you know, psychiatry is kind of like 50 years behind the rest of medicine. So it was an unfortunate thing that I did four years of that. But I suppose it shows you from the inside in, in some ways how medicine is broken with regard to that individual specialty and other specialties. So more broadly, what's interesting to me, similar to Nick, is human health, how we promote it and how we return to it when we lose it. And I've always been fascinated by food and environment as a really, really powerful lever that gets overlooked by western medicine. In medical school, I had perhaps 45 minutes in four years and then zero time and four years of residency of nutrition or wow, nutritional biochemistry or any sort of thinking about these things. Nothing beyond like a gluten lecture for, you know, formal celiac disease and maybe some nutritional biochemistry around the Krebs cycle. But beyond that, there's nothing taught in most medical schools that I'm aware of. And in my sort of life post medicine, in using my credentials to teach online through social media for the last six plus years, I've seen hundreds, if not thousands of people improve or reverse diseases that I was consistently shown or taught in Western medicine were incurable. Lots of autoimmune conditions. I mean, Nick had ulcerative colitis, I believe I've seen so many people reverse ulcerative colitis with dietary changes. Eczema that I had personally.
- [06:50]
Danny
Oh, wow.
- [06:50]
Paul Saladino
Yeah, yeah, really severe eczema. I had the whole atopic triad with asthma, eczema and probably some allergic symptoms. I mean, I've seen people reverse depression and ocular autoimmune conditions, thyroid conditions, inflammatory bowel conditions.
- [07:07]
Danny
Wow.
- [07:07]
Paul Saladino
Arthritides. All kinds of things improve when people do a variety of intentional dietary choices and lifestyle choices. That's powerful, right, that you can be taught in Western medicine, this very clear decision tree. If the patient has X, you give them Y medication. But it's really never this option you're given or you're never really challenged in medical school or residency to think like, what's at the root cause here? And could what someone is putting in their mouth or the way they're living with it from a circadian or light perspective or other lifestyle perspectives affect these things directly? And so that that's been really eye opening for Me and it's, it's kind of cool to talk about. I mean, I'm really fortunate that almost every day now when I'm in the United States, I get people that I just meet in life who tell me their story. Yeah, that means a lot. I mean, I was at the gym yesterday and you hear stories, you know, people come up and they say, oh, this just changing my diet really improve their life. That's cool.
- [07:59]
Danny
There hasn't been many things that I've experimented with in my life that have really moved the needle as much as being like really, really diligent about my diet and cutting out carbs and like being super keto. I've done it for, for long stance and I always feel the best, like, bar none, compared to anything that is like the thing that makes my body function the best. But like the problem for me is I have three kids and I gotta like take care of them. And I'm. It's almost like for me, it's just so hard to manage my life and maintain that diet and live in a house with my wife and three kids. So I gotta, I gotta make compromises somewhere. And then, you know, that's why I'm popping nicotine pouches all day.
- [08:39]
Nick Norwitz
I want to double click on something Paul said just to kind of give a little bit more form to something I said about incentive structures. So you mentioned I had ulcerative colitis. And I ended up trying a bunch of different diets for it. Ended up at the bottom of my to try list was keto. And then it worked like a charm.
- [08:56]
Danny
Like, why was keto at the bottom of your to do list?
- [08:59]
Nick Norwitz
I mean, think about the ecosystem in which I grew up. I had a pretty, a pretty conventional mindset about what keto was, let's just say a negative mindset. And when I tried it, it was more, I have nothing left to lose. That was, you know, what would be the harm about trying this next diet? So I went through.
- [09:19]
Danny
What was the first thing you tried?
- [09:21]
Nick Norwitz
I went what was like, like standard Mediterranean. I did like low fodmap specific carbohydrate. Those are kind of the two that.
- [09:28]
Danny
Were there any drugs, pharmaceutical drugs that you tried at all?
- [09:30]
Nick Norwitz
I was on various glucocorticoids. I was on some first line therapies, mesalamine, some biologics. Yeah, no, it was not fun. In fact, if you. One of my least favorite pictures, but it circulated quite a lot is at commencement. So my college commencement, I was the valedictory speaker, which was fun. But this Picture that goes around of, like, me at the podium in front of 11,000 people. And my face is actually Cushingoid because I was taking skewers at the time. Nobody really knew that, but I was actually, like, in an active flare. So my life, on the surface, it was nice. I had a lot of nice things on paper, but it was falling apart under the scenes actually leading up to that commencement. I was in a flare and I wanted to be the speaker because it's a fun opportunity, but. But I was, pardon the pun, shitting my pants, scared that I would actually shit my pants in front of 11,000 people. Because you're gonna get, like, an IBD flare. It's not something you can just, like, hold in. You will run red if the time strikes. So that, I think, was second to my colonoscopies. My first extended fast with now I'm gonna sound like an idiot, but a college cafeteria coffee enema to make sure I was emptied before the speech. So even then I had a little bit of grumble, but I was terrified, anxious. And I raised this because, like, if you were there, everybody says, like, that I was composed, that I didn't show it, but, like, underneath, my life was a wreck. And what I came to find after I tried XYZ with diet and something, you know, worked for me, and in this case, a ketogenic diet just to describe what that was like for me. About within a week of starting it, my energy was back, my flare symptoms had subsided, and then my next colonoscopy, there was no disease activity, like biopsy, proven remission, which was interesting. And what I came to learn, as Paul pointed out, is that, like, my story was not at all unique. There's this pattern motif of people struggling and becoming desperate and then trying something that is not within the mainstream and that it works. And then you're left doing a double take, like, well, what's up? So I still can't cite to you a randomized controlled trial explaining why a ketogenic diet would work or showing that it does work so it can't be recommended as standard of care. And you have the question, like, you know, what are the incentive structures that get certain studies done to allow them to become standard of care? It's not that people are being malicious. It's just that who's gonna fund the, like, super rigorous $10 million companies that.
- [12:10]
Danny
Have lots of money to make, right?
- [12:11]
Nick Norwitz
Well, it's never been done. And so that's just how our system is built. Again, not pointing fingers at doctors or even pharma it's just this is the business model. And if this is the business model, there are a lot of solutions that are physiology first and might actually work the best that are not getting explored. And the types of studies that are needed to make them standard of care aren't going to be done. And so what you could end up with hypothetically turns out to be the reality is a sick population that gets sicker. Because evidence based care does not mean best care.
- [12:47]
Paul Saladino
Did you know that food, processed food companies spend $11 billion on research a year and the NIH into nutrition. And the NIH, last I checked, spends about a billion, has about a billion dollar budgets. The food industry, this is not kale farmers of America or beef farmers of America or egg. This is not unprocessed food. This is processed food companies. 10-11x what the NIH budget for nutrition studies is. So it's. I mean, yeah, yeah, you go, not.
- [13:16]
Danny
Only that, but they're hiring people from the NIH and the FDA to work in their companies.
- [13:20]
Paul Saladino
And they have. Yes, they do that after the people leave. Right. There is a revolving door.
- [13:24]
Danny
Yeah.
- [13:25]
Paul Saladino
And for 70, 80 years industry has had its fingers in academia and in policy making. I mean, you know, the influence of what we think of as healthy or the food pyramid or the whole ethos, the whole zeitgeist of what we've thought of as healthy as westernized Americans, which is kind of the context that we all live in, has been influenced by companies for 80 years. I mean, this is why there is a almost indelible mark on our society now that meat and saturated fat things that Nick and I both eat, pretty moderate amounts of, pretty good amounts of, are harmful for you. It's very hard to erase that sort of programming that we've had since Ansel keys, since the 1950s.
- [14:10]
Danny
1950S. That's when R.J. reynolds bought all these food companies, right? Yeah, 1.9 billion. NIH spent approximately 1.9 billion on nutrition research in the fiscal year of 2019. That's insane.
- [14:27]
Paul Saladino
And that pales in comparison to what private companies will spend. I mean, right. Coca Cola itself, I believe between 2008, 2016, funded 379 give or take studies on sort of food. And those studies are generally aimed at advancing the narrative that weight loss is not about the quality of food you eat, it's about how much food you eat. So it's kind of advancing the calories narrative. It's okay to drink soda or eat candy as long as you exercise more, limit calories on the back end. In 2015, there was, I think, an expose in the New York Times about something called the Global Energy Balance Network. Have you heard of this?
- [15:03]
Danny
No.
- [15:04]
Paul Saladino
Oh, you've heard of it. It's. It was funded by Coca Cola. So this term energy balance gets thrown down around a lot today by very, I think, you know, preeminent people in the health and nutrition space. They'll say it doesn't matter what you eat, just get enough protein and be an energy balance. But the global energy, this, I think this is very misleading. It's kind of like food quality doesn't matter, right? Global Energy Balance Network is funded by Coca Cola. And they try and advance this notion. Again, it doesn't matter what you eat as long as you are in energy balance. It's again, calories forward without any attention to food quality. Nick's story, my story, the story of thousands of people that, that I've interacted with personally, or hundreds of thousands that have interacted with virtually tell a different story, right? It's all about food quality. You've seen this too, right? It's not just about how many calories you eat, Right. It's about the quality of those calories. But there's something sinister going on beneath the surface, right? Yeah. Global Energy Balance Network.
- [15:58]
Danny
Hey, guys, if you're not already subscribed, please hammer the subscribe button below and hit the like button on the video back to the show.
- [16:04]
Nick Norwitz
I would go a step further and say calories don't cause obesity.
- [16:10]
Paul Saladino
I agree with you.
- [16:11]
Nick Norwitz
And. And I want to unpack that a little bit because I know where people's minds go and they have a visceral reaction. But I'm not saying calories don't matter. I am not saying that when you take the energy balance equation, calories in minus calories out equals weight change. What is that? That is a post hoc description of what happened. It is not in any way shape or form a biological explanation for obesity. So I'm not saying calories in, calories out is a wrong model for obesity. I'm saying it's not a model at all. It doesn't give you a physiologic explanation. And the narrative around calories, I think, is one of those things where with enough exposure, just the mere exposure effect, you start to internalize a message and then thinking gets shut down. Rather than thinking about the like complex multifactorial cascade of factors that goes in to determining what is ultimately the dependent variable. Not the eat, an independent variable, the dependent variable, calories. It's Easy to sweep it under the rug. I try not to ascribe intention to these things. Maybe there is intention. I mean there are incentive structures, but I like to frame it as incentive structures as like, you know, why is or isn't something getting talked about without implying an individual person is sinister per se. A good example I'll bring up that really I found curious is this, I mentioned it to you earlier, the, the statins GLP1 paper. So yes, the two biggest drugs probably in history, or to be the biggest drug in history are statins. I think, you know, trillion dollar market over time, something like 20 billion first.
- [17:51]
Danny
Come on the market.
- [17:52]
Nick Norwitz
Oh, I don't know, mid-1900s, but probably.
- [17:55]
Danny
Really?
- [17:56]
Paul Saladino
Yeah. What was the first one? Was it low?
- [17:58]
Danny
That might be a Steve question, I'm.
- [17:59]
Nick Norwitz
Not sure, but definitely one of the biggest, most prescribed drugs. I think one in four people over 40 are taking it for less. Really? Yeah, something like that. So actually that was in the paper. I can share the reference, but so anyway, this paper came out in cell metabolism last year. Now let's be clear. Cell metabolism is not a dinky journal. It's a highly regarded scientific journal.
- [18:22]
Danny
1987 with Lova statin.
- [18:24]
Paul Saladino
Yeah.
- [18:24]
Nick Norwitz
And this was a human trial where they effectively showed that statins chop GLP1 levels in humans in half.
- [18:34]
Danny
Okay, what's GLP?
- [18:36]
Nick Norwitz
So GLP1 is the hormone that drugs like Ozempic and Wegovy try to mimic. So now there's this huge drug market about not exactly bio mimicking GLP1 because they're given at super physiologic doses. That's true. But GLP1 is a hormone that is depleted in a lot of metabolic health conditions. So you know, insulin resistance related conditions, diabetes, obesity, PCOS, et cetera. There tends to be a GLP1 deficiency. Has to do with inflammation in the gut, decreased GLP1 production in the gut. So the hormones produced in the gut, it's called incongruent hormone and also just inflammation. Inflammatory cells in the gut have their own GLP1 receptor. So they'll sop up the GLP1 and make it more bio. Less bioavailable. So long story short, low GLP1 levels are one of the markers for various metabolic diseases. Right now we're treating a lot of people with GLP1 receptor agonists which are effective for weight loss. And I'm not against these drugs, let's be clear. I'm not, however.
- [19:34]
Danny
So Ozempic is a receptor agonist for GLP1.
- [19:37]
Nick Norwitz
Yeah, I find it Interesting that there are human data in a prominent journal showing that statins, a very common drug, deplete levels of GLP1, which is a hormone and related to a blockbuster group of drugs. It cuts the levels in half. Steve, if you can bring up there was like it'll be say statin GLP1 is the image or figure 1h. It's a blue line and a red line. Yeah, that one. So this was from a human trial. 16 week human trial with I think it was 20mgs of torvastatin versus control. If it's popping up, those are the results. The red lines of statin. That's not subtle. It's not subtle at all. And so what is the blue line? The blue line is the control group.
- [20:21]
Danny
Okay, gotcha.
- [20:22]
Nick Norwitz
So it's a placebo controlled trial and basically it's showing, you know, statins chop GLP1 levels in half. And this was also associated with worse glycemic control. So an increase in average blood sugar, HbA1c, increase in insulin and increase in insulin resistance, which are all kind of known effects. But what bothers me about this graph is not the effect.
- [20:46]
Danny
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- [20:48]
Nick Norwitz
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- [20:53]
Danny
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- [21:15]
Nick Norwitz
I'm not concluding from this. No, you can't take statins or, you know, GLP1s are, you know, hack. I'm just perturbed that this comes out about a year and a half ago in a major journal and there is not only no headlines featuring it, which, you know, statins cut GLP1 levels in human by half. Should be a headline. I bet you if you replaced the word statin with steak, that would have been a headline everywhere. Do you agree? Or butter. I think there's selective reporting and then not only is it not presented in the media, but physicians don't talk about it. After I read this paper, the same day I polled 12 doctors in the area to ask them about this relationship. None of them knew about it. And this was in the Harvard area. Presumably some pretty well educated people who are like, why isn't this even in the realm of awareness? I don't think that they're, you know, physicians are hiding this information from people. But at the end of the day, if you're gonna start a medication, you deserve to have some informed consent.
- [22:17]
Danny
Right?
- [22:17]
Nick Norwitz
This is the kind of thing where it's like, I just think the patient should know in their decision making process. It doesn't mean don't take either medication. Heck, if it works best for you, take both.
- [22:26]
Danny
I'm not here to know what's going on.
- [22:28]
Nick Norwitz
This kind of information should be provided to patients or at least be in the awareness of their physicians. Again, not saying anybody's sinister, but major paper, human trial, this is the result. Like, how is this not talked about? Oh, and I'll add, the mechanism they found out, which is quite interesting, is that the statin altered the gut microbiome and altered levels of a bacteria that generates what are called secondary, certain secondary bile acids. So primary bile acids can be metabolized by bacteria into secondary bile acids. And these have numerous effects throughout the body. So they get into circulation, they can impact the brain muscles, fat. And one is called UDCA and actually can be prescribed as a drug. And what they found in humans, again is just giving back the udca, basically reverse the effect. So what I'm saying here is like, okay, there's a negative effect and actually there's a solution that has been demonstrated in humans in a major journal. So you could use this in your patient population to improve care, maybe attenuate some of the negative effects of statins on GLP1 and insulin resistance. But because we don't focus on metabolism and physiology, this gets entirely ignored. And that's just one small example about how I think dysfunctional norms and incentive structures lead to worse care.
- [23:50]
Paul Saladino
Again, there's a broader context here that I think we should talk about. You mentioned this in the beginning with your Oreo experiment, but I'm not sure everyone knows the whole story. Your LDL went up quite high when you went keto.
- [24:02]
Danny
This is part of that happened to me too. Yeah, right.
- [24:04]
Paul Saladino
This is part of common, not, not always, but commonly in human physiology. It happened to me a lot when I was strict carnivore.
- [24:12]
Nick Norwitz
For a sec. I was listening to your pod with Gary Brecker this morning and you said Your LDL was 125 right now. He's like, oh, that's high. And you're like, yeah, that's high. You know what mine is?
- [24:22]
Danny
Mine's like 250.
- [24:23]
Paul Saladino
Mine was as high as 500.
- [24:25]
Nick Norwitz
Whoa, 574.
- [24:26]
Paul Saladino
Yeah. So this is my Last in the setting of.
- [24:30]
Nick Norwitz
I'm not, I'm not. But to be clear, I'm not saying this is fine for all people.
- [24:33]
Danny
I'm just measuring our LDL levels.
- [24:35]
Nick Norwitz
We can talk about it later. It's now open information. Actually, it was Mark Hyman and Andrew Huberman was talking about my cholesterol and his pause. I'm like, all right, this is how you introduce me to the world. Yeah, but my cholesterol, we can talk about it. There's more nuance there. I'm not. Well, let me stop interrupting you. We'll go back to it. Go ahead.
- [24:49]
Paul Saladino
It's just interesting because in this context, and Nick has done a lot of research here, which is really interesting and we should talk about it later in the podcast. In the. I think we've all experienced this sort of lean mass hyper responder phenotype. And basically the idea as I see it, and Nick can add context to this as he sees fit, is that in some individuals, particularly individuals who are lean and fit, when you move over to fat based metabolism in a ketogenic type context, there are more energy moving molecules in the blood and that LDL actually moves triglycerides and cholesterol. And so it's not uncommon in human physiology to see LDL go up as a physiologic, perhaps not pathologic response in a ketogenic diet. Whether or not this represents an increase in cardiovascular disease risk is the main question.
- [25:31]
Danny
Right.
- [25:32]
Paul Saladino
And the central question here, which is something that I'm thinking of as you're describing this paper and the response to it, or lack of response to it in the general sort of media space, is that APOB and ldl, you know, apob containing lipoproteins are, that's a broader term for LDL and other lipoproteins, which are broadly felt to be atherogenic. These are sacrosant in Western medicine. And anything that challenges that hypothesis, this, this lipid hypothesis is, is just disregarded or is not felt to be valid and is kind of cast out to the side. So it's, it's quite interesting because those, that's a very central theme. If we talk about, talk about, we'll talk about seed oils in this podcast. And it comes back to that same idea in many ways. APOB I see as like a linchpin in Western medicine. And having my LDL go up super high and then having it. I had a similar response to Nick's. I mean, I eat carbohydrates now. I don't eat Carbs. When you mentioned that you like fruit. I eat fruit and honey.
- [26:27]
Danny
Right.
- [26:27]
Paul Saladino
And milk. So milk has lactose, but I don't do.
- [26:31]
Danny
You're not eating bowls of cereal.
- [26:32]
Paul Saladino
I don't eat bowls of cereal. Or rice or oats or pasta. And there's different responses to different grains, perhaps based on their processing. So. And processed carbohydrates, processed sugars probably react differently in the human gut than fruits and fruit juice, but. So I include carbohydrates in my diet now. I found for myself after a year and a half of long term strict carnivore, so meat and organs and fat, that my eczema got better, but my electrolytes did not stay within normal limits. It turns out that there is a need for insulin signaling at the level of the kidney to resorbitate certain electrolyte molecules.
- [27:06]
Danny
Yes.
- [27:07]
Paul Saladino
And that a lot of people, not everyone, some people probably do better with long term strict keto than others. I. I had massive electrolyte imbalances that were resolved when I added carbohydrates back. My immune conditions did not come back with the addition of fruit and squash and honey. But I know that for me, if I include things like tomato, for instance, which is technically a fruit, but within this nightshade family, that I will get a recurrence of eczema. So some things.
- [27:32]
Danny
Interesting, some.
- [27:33]
Paul Saladino
I mean, this is what's interesting. And what, What I've kind of seen over the years is that for people who have autoimmune conditions, inflammatory bowel diseases, eczema, skin conditions, psoriasis, there are some foods that are widely considered to be healthy that can be triggers for some people. And that's just a. That's something that I was never taught in medical school, and it's probably not something that everyone needs to worry about. But if people have unresolved autoimmune conditions, it's something to be aware of. More broadly, I think the. The LDL conversation is that in Nick's case, and again, I'll let him add context here if I'm leaving anything out. And in my case also, strict keto leads to a lean mass hyper responder quote, rise in ldl. Um, we can talk about cardiovascular implications for that later in the podcast. But the addition of carbohydrates, whether it's fruit and honey and squash or Oreos, then changes your physiology. You're no longer in ketosis and the LDL can come down. So that, that just so people understand that that's probably what happened to Nick with his Oreos in the beginning, which is this really sort of viral illustration of the fact that.
- [28:31]
Danny
That.
- [28:31]
Paul Saladino
That you can lower LDL just by changing your macronutrient ratios. And the bigger point that I'm just wanted to add here is that I see so many of these health discussions revolve around apob containing lipoproteins and ldl, and that that's often where they get stuck. Because a lot of people that I've experienced the stories of, they. They get healthier, right? They. They make changes. They do meat plus fruit and squash, or they do strict meat, or they do keto. Their autoimmune condition resolves, they feel better, less brain fog, better libido, fertility. And they go to their doctor, and the doctor says, oh, your LDL is sky high.
- [29:06]
Danny
Yes, that's exactly what happened to me.
- [29:08]
Paul Saladino
Whatever you're doing, stop it now. And you say, but wait, I just told you that I feel the best I ever have in my life. So this. This apob sort of linchpin is really critical to unpack. And what we know and don't know and what's been assumed about it is really interesting because.
- [29:21]
Nick Norwitz
Can I just.
- [29:21]
Danny
I. Well, I want to say, because it's interesting what you said about electrolytes, because the first time I ever did keto was under the guidance of Dom d'. Agostino. He was the one who kind of coached me through it all and. And introduced me to everything. And what I noticed was after, like, the first few weeks of doing it, I would. On a podcast, I would notice I'm, like, falling asleep an hour into it. Like, I had no energy. Like, I just couldn't. I just. I couldn't do it. And he was brought up to me. He's like. He's like, how much water and electrolytes are you drinking? I'm like, none. He's like, that's why. He's like, you just start pounding electrolytes. And I started doing that, and it, like, changed the game. I was, like, felt way, way back. Like, it was total night and day. So it's interesting. It's interesting that, like, I had no. I would have never known if it wasn't for Dom, that you had to get more electrolytes and more salt in your system and drink way more water if you're not eating carbs.
- [30:12]
Nick Norwitz
I just want to double click on something that Tom Paul said. I don't know, I said about this LDL and Applebee boogeyman, because I want to be very careful and say that I'm not condoning that my LDL is safe generally. In fact, in most people it's probably not. But there's the curiosity that gets peaked or should be peaked when you have a patient who has normal LDL and then their LDL quintuples with a dietary shift like this doesn't happen. This is not known to happen. In fact, familial hypercholesterolemia, which you can tell it's a genetic disease, familial, inherited, right. Is now, I believe, diagnosed based on just like a threshold blood lipid level. So an LDL above 190, they just assume it's genetic and familial and you can get, you know, diagnosed with FH and then, you know, treatments ensue. Anyway, point being, isn't it interesting just intellectually that I and other people like me can manipulate our LDL levels five fold with dietary shifts more than standard of care treatment, multi billion, maybe trillion dollar drug industry.
- [31:30]
Danny
Right.
- [31:31]
Nick Norwitz
And I said earlier that I think the Oreo vs. Statin had a positive impact. I think it had a positive scientific impact. Actually we've gotten, you know, funding to do more trials because of this, more partnerships. But even clinically, because it got the word out there. And in the weeks and months and now more than a year following that experiment, I have heard from dozens, if not hundreds of clinicians and cardiologists who are like, oh shit, I have these patients and I didn't know what they were until now. That paper ended up, the Oreo vs. Statin paper was like very widely circulated. I think it had 15 times the media attention score of your average New England journal paper, which is the highest impact factor.
- [32:12]
Danny
Great marketing stunt.
- [32:14]
Nick Norwitz
It was a marketing stunt. But to get a word out there and what the clinicians saw was now this new phenotype and this new reason for a patient presentation they didn't understand before. And what did that allow them to do? Act on the physiology. So even before the Oreo versus statin, we had worked with clinics where they had patients who had this phenotype but didn't need to be in therapeutic ketosis. So they just titrated back in carbs. And you can use a sweet potato. One patient like about a sweet potato worth of carbs addition per day lowered his LDL by 480. No medication can do that. So the point being is this wasn't, you know, I put no value judgment on LDL or statins in this. This was about interesting physiology that can actually serve people. Because if you can eat a sweet potato and get a more potent effect than taking, you know, a drug for the rest of your life. A drug that does that cuts your GLP one in half. Like, that is better patient care. So we need to understand the physiology of metabolism in order to advance care. And the fact that the field is so myopically focused on like a single marker, in this case LDL or Apple B, that is the problem. And so it's not that that doesn't matter. In fact, it's not even that. That's not, quote, causal. We might want to debate whether or not Applebee is causal, but it's that without further context, you are not serving people. So we'll go through a few studies. One that's been debated recently is a Minnesota coronary experiment. And the reason I bring that up is I was rereading it yesterday. It was a paper by Ramsden et al. Originally, this study was done decades ago, a long term randomized controlled trial. But it was on like seed oils and actually not a seed corn oil versus a higher saturated fat diet. It turns out the spoiler alert, the corn oil diet ended up doing quite poorly. But the conclusions, if you actually read the paper, weren't that Omega 6 is terrible, saturated fat is good. No, the researchers just said things like there are different physiological reasons for LDL to change. This matters, this context matters. And I think that the final lines of the paper. Steve, can you bring up there's like a Minnesota end quote. We can actually get into the study. It's the third one down in the top left.
- [34:34]
Danny
Now, you were talking about titrating in carbs to a keto diet.
- [34:37]
Paul Saladino
Yeah.
- [34:37]
Nick Norwitz
I just want to quickly read this quote because I think it's really important to frame our whole discussion and like, you know the angle I'm trying to take. This is what the paper ended on. Given the limitations of the current evidence, the best approach might be one of humility, highlighting limitations of current knowledge and setting a high bar for advising intakes beyond what we can provide it for natural diets. So I'll just frame up right now. We may end up debating this, but like I'm not against Omega 6. I don't think walnuts are terrible. But I think by the same token, like butter, saturated fat, rich whole foods are probably also very helpful. I was doodling out, you know how I think about this. Can you bring up. Steve, Steve, Oil, sorry, seed oil map complex. It's in the top left. That's a simple one. The one above that. The one above it. So I was drawing this doodle on the way to the airport about the way I think about seed oils. We might end up touching on a lot of this. People don't need to understand it. The point I want to make right now is I doodle out that and come to the conclusion, wow, there's so much we don't know about this. And I think one thing I want to do, this has been a long preamble to get to the seed oil topic. But my mission, I guess, is not to say good or bad, but to wrap context around this and give people, like, an awe and humility for how interesting and complex the biology is. Because right now we just hear, you know, clickbait taglines and people are very attracted to simplicity. But I really feel that there is a growing community of people who like, hunger for nuance and respond to it. So that little detail can be a framework we come back to. But I've been on my soapbox for too long. I'll pass it back to you.
- [36:19]
Danny
Nuance doesn't get views. That's the problem.
- [36:21]
Nick Norwitz
But it can, I think, if you can be provocatively reasonable.
- [36:24]
Danny
Yes.
- [36:25]
Nick Norwitz
That's what I try to play with. That's why I'm even like, playing with social media in the first place. Is like, oh, yeah, you need an engagement tactic. Harvard scientist eats Oreo cookies. Great clickbait. Yeah, but does the clickbait, is it then followed by something with depth? So you do need to pay homage to the, you know, the clickbait gods or whatever. But that doesn't mean you can't use that as a tool to really advance conversations and research.
- [36:51]
Danny
So totally agree with you.
- [36:53]
Nick Norwitz
I just challenge people to really hear the words that are going to be coming out of our mouths and the rest of this conversation.
- [36:58]
Danny
So before we get to see dolls, I want to ask though, is LDL bad? If you have high ldl, is that bad?
- [37:03]
Paul Saladino
See, Nick sort of foreshadowed this. My perspective, Nick can add if he feels differently, is that it's contextual. Yeah. And this is a, this is a really, really important question. It's a really important question. As Nick has suggested, the statin industry is potentially a trillion dollar industry. There are a lot of financial zeros on the line here. If, if, if LDL is not all it seems the mainstream medical perspective is that LDL and APOB containing the proteins are atherogenic. They are bad. They directly cause atherosclerosis.
- [37:36]
Danny
Yes.
- [37:37]
Paul Saladino
I don't agree with that. Based on what I've seen, I think it's much more nuanced. And contextual. Broadly, when I look at the evidence with APOB and ldl, we can just use one of those terms moving forward. In humans who demonstrate markers suggestive of insulin sensitivity, metabolic health, there is a different effect, cardiovascular sort of correlate for LDL levels than there is in people who are metabolically unwell. If you are a diabetic and you have a high ldl, that does seem to consistently represent a significantly increased risk of cardiovascular disease in some cases 4 to 6x.
- [38:18]
Nick Norwitz
Right.
- [38:19]
Paul Saladino
A low LDL if you are metabolically healthy, which is something that we can really only achieve proxies for whether it's an HDL or, or. Unfortunately, very few studies are done with fasting insulin. I think if studies were done with fasting insulin, that's probably the best marker, fasting insulin, that's an easily obtainable blood marker. I, I don't, I'm actually not familiar with a single study that's done with fasting insulin. But if you look at things that approximate insulin or you use that as sort of a third variable, anything that approximates insulin sensitivity, you see a markedly attenuated relationship between LDL levels and increased cardiovascular risk. And so I think that there's a question to me, if something is causal, you get into this sort of semantics of what is causality?
- [39:03]
Nick Norwitz
Right.
- [39:04]
Paul Saladino
Is. Is something consistently associated with a process enough to claim causality? I have a. My brain is simple in this respect. I think if something causes it, then LDL must be enough to initiate atherosclerosis on its own. And if you're saying LDL causes atherosclerosis, you're the associated inference is that more LDL is always bad. And that's really the, that's really the relevant clinical question is if you, Danny, go and eat a ketogenic diet and your LDL goes up, does that represent an increased risk of cardiovascular disease for you? Is that something we need to be aware of? Or if you become more metabolically healthy because you're getting rid of garbage foods, if you're getting rid of, quote, carbs. Right.
- [39:42]
Danny
Yeah.
- [39:42]
Paul Saladino
And you become more metabolically healthy with a higher ldl.
- [39:46]
Danny
Right.
- [39:47]
Paul Saladino
Is it possible that your cardiovascular risk is the same or lower now? So this is where the nuance comes in. I think it's very contextual. And like I said, if you stratify the relationship between LDL and cardiovascular disease, there's a marked attenuation when people are insulin sensitive, interesting versus insulin resistant.
- [40:04]
Danny
And the best way to determine whether or not you're getting the LDL is really affecting you is to get the CT angiograms where they can. Like, they basically put you inside of a CT scan with dye in your arteries and see how much black you have.
- [40:17]
Paul Saladino
Probably the best imaging. Yeah. You could do as a CT angio. I mean, there's something called a cac, but it's not as. Not the same problem with CT angios.
- [40:23]
Danny
You got to go in that fricking cancer machine. They radiate.
- [40:25]
Paul Saladino
It's a lot of radiation, right? Yeah. You don't want to do it.
- [40:28]
Nick Norwitz
Above age 40, a CAC is pretty good in terms of, let's say, a warranty on your heart.
- [40:35]
Danny
I got a cac and it said it was zero.
- [40:37]
Nick Norwitz
Yeah.
- [40:38]
Danny
But I also. I think it might have been Dom who told me this, that his parents got a CAC and it was zero. And then they also went and got a CT angio right after and it said they had, like. I don't know if it was. It might have been somebody else. And they said that the CT angio, they had, like, a high amount of plaque, but their CAC score was still zero.
- [40:53]
Nick Norwitz
Yeah.
- [40:54]
Paul Saladino
Depends what algorithm they used to interpret CT angio.
- [40:59]
Nick Norwitz
You're getting dangerous and close to things that I'm not supposed to talk about until Friday.
- [41:03]
Paul Saladino
I can talk about it.
- [41:04]
Nick Norwitz
I can talk about what? You know, a couple things I want to poke at. We can come back to the cat thing later. I actually want to put on my jade tower academic prude hat for a minute. For a purpose.
- [41:19]
Paul Saladino
Ivory tower.
- [41:19]
Nick Norwitz
Ivory.
- [41:20]
Paul Saladino
Yeah.
- [41:20]
Nick Norwitz
Ivory tower Harvard prude hat. So, Paul, you effectively said apob is not causal, and you've said that, Right.
- [41:30]
Paul Saladino
I don't believe APOB is cause. I don't believe there's enough evidence to suggest that APOB is causal.
- [41:34]
Nick Norwitz
Okay.
- [41:34]
Danny
Which means what, again?
- [41:35]
Nick Norwitz
So.
- [41:36]
Paul Saladino
So necessary but not sufficient.
- [41:39]
Nick Norwitz
It's. But you. The way you described it, seemed like you were talking about. So let me unpack these terms. Causal. Definitionally, and this is important. Definitionally means it is necessary and part of the causal cascade, effectively.
- [41:56]
Danny
And you say apob. You mean ldl.
- [42:00]
Nick Norwitz
So just. We should probably define these. APOB is stands for apple lipoprotein B. Yes, it is an apple lipoprotein on LDL particles. So there are more particles than just ldl.
- [42:10]
Danny
It's a proxy of ldl.
- [42:11]
Nick Norwitz
It's a proxy of, like, an LDL particle count. So it's a better marker for ldl. Whereas your standard LDL cholesterol is the cholesterol fraction generally calculated.
- [42:19]
Danny
Got it.
- [42:20]
Nick Norwitz
In all the LDL specific type apob containing lipoproteins. That doesn't make sense. They're proxies for one another as far as we're concerned. If there's a divergence we will highlight.
- [42:30]
Danny
Okay, and Paul is saying that it's not causal, right.
- [42:33]
Nick Norwitz
And then, and then he's trying to, you know, re define what you mean by causal. And the reason I bring this up is because in these discussions that little chink in the armor is all you need. And you know this for conventional academics to write you off and leverage that within academia to say this person doesn't know what he's talking about. Let's go through the evidence proving LDL is causal or Applebee is causal. So again, it's interesting social dynamics. My position on Applebee is it's causal insofar as it's necessary. But I agree with Paul. Context, context, context. So to think about this graphically, if you imagine like, you know, a simple like x, Y axis and on the Y axis is the amount of plaque you're accumulating in your heart. The X axis is your exposure to apob and let's say that there is a positive relationship. Is it a really steep line or is it super, super shallow? If it's super super shallow, you know, because say you have a positive hormonal and metabolic milieu, then that needs to be weighted when making decisions about what intervention you start or don't or stand or don't. So you know, if your absolute risk increase from having high apob is actually quite low on an individual basis, there's ways we can figure this out. That's different than I have already had a heart attack and I have metabolic syndrome and I had a standard American diet and my Apple B and LDL are through the roof. Those are two very different things.
- [44:12]
Danny
Yes.
- [44:12]
Nick Norwitz
And the failure to wrap context around this individual marker, this, that's the issue. The issue is not that the marker doesn't have any value in and of itself. That's more or less my position and it's also why I'm very comfortable giving you know, recommendations, advice on like ways to, to lower your app OB if that's desired. While myself living with crazy high ldl, a pattern that arises in my, my social media that I think confuses people is I'll often talk about things in a positive light that I don't adopt myself. So for example, particular fibers I think can be very beneficial. I eat basically a zero fiber diet because of my context, because my history of ibd, how it affects Me personally, and what works for me shouldn't generalize to another person.
- [45:02]
Danny
Do you eat any fruit at all like Paul does, or any carbs at all?
- [45:06]
Nick Norwitz
No, But I will add, were I not to need a ketogenic diet therapeutically for my ibd, I would happily eat a sweet potato or some fruit. I by no means think those are bad things. And guess what? It would lower my LDL and Applebee substantially, which isolated probably would, all things being equal, be more likely to lower my risk specifically for CVD than other things.
- [45:30]
Danny
So you eat zero carbs?
- [45:33]
Nick Norwitz
Basically, I'm always in ketosis.
- [45:34]
Paul Saladino
Carbohydrates. Carbohydrates. That word carbs is kind of like colloquialism, right? People hear carbs, they think like pasta, bread.
- [45:42]
Danny
Yeah, yeah, right.
- [45:43]
Paul Saladino
So carbohydrates. I don't think you eat any carbohydrates because you definitely don't eat any carbs.
- [45:46]
Nick Norwitz
Yeah, I like. I mean, I'll have a little bit, but nothing that will kick me out of ketosis for a problem.
- [45:51]
Danny
What do you typically eat throughout the day now?
- [45:55]
Paul Saladino
Probably.
- [45:56]
Nick Norwitz
So I eat two meals a day, probably in like, in a six to seven hour window. So breakfast. Yeah, breakfast. And dinner, like 11am Noon. I'll have a meal probably eggs, cheese, salmon, olive oil, maybe some macadamia nuts. And then dinner can be fish, chicken, steak. I'm pretty simple.
- [46:18]
Danny
No size, just the meat, pretty much. Wow.
- [46:20]
Nick Norwitz
Pretty much. The thing is, I like these foods. Like if I could, without gi. Upset or any consequences, have like a big dish of like Brussels sprouts with like dried cranberries and walnuts. That sounds delicious. And I think for a lot of salads, but no, no, it just. It's not worth it for me. It makes me feel unwell.
- [46:38]
Danny
I understand. Yeah.
- [46:39]
Nick Norwitz
And there's. There's a lot of individual context and so seed oils is another good example. Well, actually.
- [46:47]
Danny
And why do you so. So there's like a. A lot of people don't like to eat breakfast. I think breakfast is bad.
- [46:53]
Nick Norwitz
I mean, breakfast is fine.
- [46:54]
Danny
You skip lunch.
- [46:55]
Nick Norwitz
Well, when I say breakfast, I mean when I break my fast. So 11, 12, sometimes one.
- [47:00]
Danny
Okay, gotcha.
- [47:01]
Nick Norwitz
So yeah, lunch, dinner, if you want to say it.
- [47:03]
Danny
I heard that. I heard that the metabolism is working way harder in the morning, so it's better to eat in the morning and it slows down at high noon.
- [47:11]
Nick Norwitz
I think that's kind of a fairy tale. What do you think?
- [47:13]
Paul Saladino
No there's any evidence for that.
- [47:14]
Danny
That's the Jack Cruz Kool Aid. I've been drinking. Come on, don't break my.
- [47:17]
Paul Saladino
Can we go back to the lipid stuff? This is super interesting to me. I don't want to, I don't want to miss this point. I wanted to piggyback on something Nick was saying. The reason I think the conversation is so important is because it goes back to what we were talking about earlier. In Western medicine, as a doctor, when a patient comes to see you when someone is sick, it's important to try and understand what is actually at the root cause of their problem. Western medicine really points the finger at ldl. They have blockbuster drugs that lower LDL and they want to make LDL causal. I agree with Nick. LDL APOB containing lipoproteins, which include ldl, are necessary for atherosclerosis. If you do animal model knockout studies of apob, they don't get atherosclerosis. But I don't think that, that, that's just. Maybe I'm incorrectly defining the word causal. It's just sort of. Maybe we're doing hand waving here. I think that that's not what I mean when I say causal. I, I think of causal as direct relationship.
- [48:10]
Nick Norwitz
Right.
- [48:10]
Paul Saladino
So if your LDL goes up, your cardiovascular risk always goes up. Because if something causes atherosclerosis, ldl, you're sort of inferring that LDL are apoplexy.
- [48:17]
Nick Norwitz
Smoking cause lung cancer.
- [48:19]
Paul Saladino
Well, can I get to that? Yeah, the. You know, if you're, if your APOB goes up, you're sort of inferring that that LDL is directly damaging de novo to the endothelium or something. And I think that when Nick is saying, and I agree with this, is that it's all about context. That if the context is different, right. If someone is metabolically healthy versus not that APOB carries various risks. When I look at that equation, I think that what we should be focusing on is metabolic health and not ignoring ldl. But all of our myopic focus is on ldl. Never in all of my training, medical school, residency, even medicine rotations, surgery rotations, did anyone ask me to get a fasting insulin to assay someone's metabolic health. Within Western medicine, I think one of the greatest tragedies or greatest oversights is that physicians are not taught to think about metabolic health as the foundation upon which diseases manifest. And so if we're looking at metabolic health as the context in which we should interpret LDL and apob, why are we not assaying people's metabolic health? When people tell me about their stories. When I was working with patients previously, they would come to me with lipid panels and say, my doctor is concerned about my ldl. And I would say, what's your fasting insulin? And they would invariably say they didn't get one. There are ways to look at a traditional lipid panel that give you a sense of your metabolic health. Triglyceride to HDL ratio is perhaps the most predictive because those are changed in sort of metabolic dyslipidemia. But again, physicians don't do that. They myopically focus on LDL apob containing lipoproteins. So we're. We're forsaking patients by not appreciating the metabolic health. I would argue that it is insulin resistance, also known as metabolic dysfunction, that is the initiating event, that is the determining factor in atherosclerosis. So why are we not looking to treat that? Not necessarily with drugs, but let's ask the questions around what causes metabolic dysfunction in diet and lifestyle? That's where we need to go. That, for my money, that's where. That's where the return is. Right. That's the $64,000 question that very few in Western medicine are asking, and none in the traditional medicine world are being taught to ask.
- [50:25]
Nick Norwitz
Right.
- [50:25]
Paul Saladino
What causes metabolic dysfunction? I think most people would agree metabolic dysfunction, synonymous with insulin resistance, is at the root of so many chronic diseases that is reversible. Nick and I have seen that myriad times. You can reverse metabolic dysfunction. So why are we not thinking about that first? And if that determines the context in which your LDL levels should be interpreted, why is that not the first thing we're thinking of? And if. If the context of LDL determines its cardiovascular risk, then LDL is not really. Doesn't make sense. That doesn't make sense to me in terms of linguistics, for it to be causal. Yes, it's necessary, not causal. That's how I think about it. Again, we can get into, like, this splitting hairs. What does the word causal mean?
- [51:02]
Nick Norwitz
Yeah, but let.
- [51:03]
Paul Saladino
I think that this is a clarion call that we need to do a much better job in Western medicine understanding someone's baseline metabolic health, how to get there and how to. How to get back there and what makes us less metabolically? That's the most interesting question to me.
- [51:16]
Danny
How important is the lp? Little A marker.
- [51:20]
Nick Norwitz
Ooh.
- [51:20]
Paul Saladino
So this is an interesting one. I mean, Nick can speak to this also, because in the study that he recently did, they. They stratified this. Also the way that I see lp. This is lipoprotein little A. It's essentially an LDL molecule with an extra little protein on the outside called an apolipoprotein little A. And as I understand it, that is sort of a MOP for oxidized phospholipids in the human blood. Okay. Now oxidation, oxidation, okay, so oxidation is, is essentially loss of electrons. It's rusting, right? It's rancidity.
- [51:50]
Danny
Yes.
- [51:50]
Paul Saladino
It's damage of phospholipids. This is starting to sort of look toward the seed oils conversation, because when we get to the seed oils conversation, we will be talking about susceptibility or propensity for oxidation. Right. Which is loss of electrons. That's what we think of technically from an organic perspective, chemistry perspective, when we say oxidation. So phospholipids are these molecules that make up the membranes of your cells. And LDL is a membrane bound vesicle and it has phospholipids in the membrane. It also has proteins in the membrane, other compounds in the membrane. But LP looks to be a mop, a sort of cleaning service for oxidized phospholipids. I think there are two scenarios for lp. Nick can add if he disagrees with this or wants to add any more to this or he sees it differently. I think some people have genetically high LP and that may not represent an increased cardiovascular risk. But if your LP goes up acutely, that may suggest an increased burden of oxidation in your phospholipids, and that is suggesting an oxidative stress, and that is indicative of increased cardiovascular risk. Does that make sense?
- [52:58]
Danny
Yes.
- [52:59]
Paul Saladino
So in the study that Nick did, and again, Nick should talk about this because he'll be more equipped to do it, there actually was not a distinct correlation between the levels of LP and the plaque score.
- [53:10]
Danny
Interesting.
- [53:11]
Paul Saladino
And that's interesting to me because Western medicine again says LP horrible 100 of the time. But I think there's more nuance here. So I think there's two scenarios for lp. If you know your baseline and you see it acutely rise and you started smoking, or perhaps you started guzzling soybean oil and you're making your cells and your membranes more full of susceptible, fragile lipids, then, yeah, an increase in LP can be problematic. But I'm not convinced that a baseline high level of lp, which could be genetic, necessarily indicates that you have this burden of oxidized, that is damaged membrane components.
- [53:45]
Danny
I've only got my LP measured once. I don't. Because it's expensive.
- [53:48]
Nick Norwitz
Yeah. Generally it's recommended to get it once because it's assumed to be static, which.
- [53:52]
Danny
It is more assumed to be static.
- [53:54]
Nick Norwitz
It's more resistant to change generally than say ldl.
- [53:58]
Paul Saladino
You can lower it with more saturated.
- [54:00]
Danny
So is a lower LP good genetically?
- [54:04]
Nick Norwitz
Conventionally, I would say on balance, yeah, like I have a very high up delay I inherited from my dad. It's known as what are called Kringle repeats. So basically Paul was describing LP quite nicely. It's like an ldl, but it's got a little tail. It's called Apple a tail. And the tail is determined by how many what are called kringle repeats you inherit from, you know, one or two, both of your parents. And the longer tails get. The particle gets degraded or the precursor to the particle gets degraded earlier. So the shorter tails there tend to be higher levels and they actually tend to be more damaging on balance. I'll get back to L.P. lillay in a sec, but I just want to finish the conversation and thought around semantics. I don't want to beat it a horse on this, but just from my position I think causal and most important gets confused. So like insulin sensitivity, metabolic health, I think it's most important.
- [55:05]
Paul Saladino
Agreed.
- [55:06]
Nick Norwitz
I still think Applebee is causal, but that doesn't mean it's most important. It's the same with terms like evidence based, quote unquote and you know, best medicine. Evidence based medicine is not necessarily the best medicine. So these are things that people get caught in these buzzwords without thinking what do they really mean? So like medicine it's like, well do we have we checked the boxes on this type of intervention? Not actually does the intervention help the individual patient or the most people? Actually there was a nature letter in 2015 by Nicholas something I was reading the day is I think the top 10 highest grossing drugs help between 1 in 4 and 1 in 25 people who take them. The reason that's important is because you can run a double blind multimillion dollar rct, get statistically significant results and like sell a product and it can still not help most people. But what we do, and this is how medicine is built right now is like we take a heterogeneous group of people and do what's considered a quote gold standard and then prescribe the outcome to everyone without looking at the individual content. The theme that keeps coming up is context, context, context. Now I will hit LP quickly but I then want to.
- [56:17]
Danny
This is like the Human Genome Project was doing this thing where they basically take people's DNA and they come up with like custom tailored Treatments for them, like if you have a cancer or whatever, they take your DNA and they like figure out the exact type of drug or therapy to like target exactly what's in their body dependent on their biology. It's, it's like a custom.
- [56:38]
Nick Norwitz
The, the degree to which we're getting more resolution on not just the genome but the, on multi omics. So multi omics like transcriptome, proteome, you know, genome, microbiome. Actually, forgive me one more quick tangent, but this is super cool. One of my favorite labs is the Snyder lab at Stanford, who are like kings and multi omics. They had a paper last year in Nature Biomedical Engineering. How many types of type 2 diabetes are there? Paul?
- [57:06]
Paul Saladino
How many types of type 2 diabetes? Yeah, are we back to linguistics?
- [57:10]
Nick Norwitz
Okay, it's a, a read my mind question four. So what they did in this study, basically I'll try to make this short, but they did gold standard in lab testing on a cohort of patients and kind of dissected what was the main cause of type 2 diabetes. So insulin resistance, generally adult onset obesity in these patients because there's different pathophysiologies. Again, context nuance. So you can have incretin dysfunction, liver dysfunction, muscle dysfunction, beta cell dysfunction at your pancreas. Now the way we diagnose type 2 diabetes is like what is your average blood sugar? How do you respond after two hours on a glucose tolerance test? What they did in the study is basically show each patient individually had a dominant one of those four that was driving type 2 diabetes or 2 CO dominant. And then, and this is what was cool. You can't do this kind of experiment, those kind of lab tests clinically on patients, but they use machine learning and AI to then take the patients, put CGMs on them, and then the CGMs were able to decode from the shape of the CGM curve what the specific underlying pathology was driving type 2 diabetes in that individual patient.
- [58:21]
Danny
Oh, wow.
- [58:22]
Nick Norwitz
So as we evolve with AI, machine learning, biomonitoring tools, and the reason I'm going on this tangent is I think, and I want to see if Paul agrees, we are going to see a transformation in how medicine is practiced. Moving away from quote gold standards, RCTs which use heterogeneous groups of people, moving towards personalized medicine focused on physiology like that. Because now we're getting the tools to measure these things and act on them and quickly on lp. Because it's a fascinating story. I'm personally more concerned about it. I'll just give my high level opinion than LDL particles. But there's some really interesting work if you people want to go down a rabbit hole. I wrote a newsletter and did a video on it that I can share with you. So I don't go on too long right now. But about LP as basically a wound healing surrogate evolutionarily for vitamin C. You know about this Pauling work?
- [59:14]
Paul Saladino
Little bit.
- [59:14]
Nick Norwitz
So yeah, Linus Pauling, who? Smart guy. Two Nobel prizes in the 90s. Him and his colleague Dr. Rath developed this idea that LP arose is a replacement, replacement for vitamin C. So most mammals can synthesize vitamin C, humans can't and a few other animals can't, like the European hedgehog. And basically vitamin C has wound healing properties. LP also has wound healing properties. You want to like heal up quickly, evolutionarily, scar, don't bleed to death, yada yada yada. First, the evolutionary pattern is fascinating because LP arose independently in those organisms that lost the ability to synthesize vitamin C. And there's a lot of overlap. And the reason I bring this up is because some people think that if you take high dose vitamin C and also L lysine has to do with how the LP actually binds, called lysine binding sites, you could effectively reduce the stickiness of the lp. So there might be ways again beyond the quote, gold standard evidence based rct, yada yada, that you could potentially attenuate your LP risk. I think first and foremost agree with Paul being metabolically healthy. But beyond that, there's some really interesting physiology that we can talk about. The last thing I'll say about LP is isn't it interesting that 10 years ago nobody talked about it and now everybody's talking about it. L.P. just so. Yeah, really? I was surprised. It was on my sub stack, the most popular newsletter I ever wrote, really on a pretty. What would seem like an esoteric.
- [60:48]
Danny
I never hear anybody talk about it.
- [60:49]
Nick Norwitz
So many people were fascinated by it. The observation I'm making, again, incentive structures. Ten years ago people didn't talk about it. Now there are New England Journal trials on five different medications targeting it.
- [61:01]
Danny
Interesting.
- [61:02]
Nick Norwitz
So incentive structures is a point that I keep coming back to. Not people being sinister or corruption scandals, just simply incentive structures. I think we need to understand that, be it science, medicine, influencers talking in order to really understand the nuances of debate. But yeah, should we get into seed oils?
- [61:21]
Paul Saladino
Can we get into metabolic health real quick? Yeah, I just want people to understand because we touched on this a little bit. I think people are probably you and I clearly agree that the Most important thing is to be metabolically healthy. And I just want people to understand that. Most doctors do not test for this, but it's super easy. It's a fasting insulin test. It's you fast overnight, you get an insulin level in the morning. It's not perfect. If you pair a fasting insulin with a continuous glucose monitor. You mentioned those earlier. You have sort of a fasting insulin, and you have a proxy for a postprandial insulin with the postprandial glucose. So you can look at the shape of your CGM curve. And I think those two things, a fasting insulin will cost you $30 if you pay cash. And if you look at the distribution of fasting insulin, I think the average in the states is like 9.9micro IU per milliliter. But there are other metrics that suggest that 90/plus percent of the United States is metabolically unwell. So I think it's reasonable to suggest to people, just to give guidance, that you want your fasting insulin to be far below 9. I think the best level is probably below 5. Most of the time when I check mine, it's less than three. And again, fasting insulin is. It's a 30 test. You can get it online there. Although it's democratized lab companies now, if your doctor won't order it for you, you need a new doctor. Um, I think that if every doctor ordered a fasting insulin, you can immediately get a sense of where you are on some sort of a metabolic health curve. No test is perfect, but it's pretty darn good. Pop the hood, oil, check the dipstick. Okay, you're good. You got a fasting insulin of 4.5. Not bad.
- [62:51]
Danny
It should be below 5. What, what is the measurement?
- [62:53]
Paul Saladino
It's micro IU per milliliter.
- [62:57]
Nick Norwitz
I have to say one more thing before we get to seed oils around psychiatry. And I just think this is really important for people to hear because the diseases we battle with, when you don't have this metabolic, mechanistic picture, they become ephemeral and abstract. And nowhere is that a bigger problem than in psychiatry. Paul was talking about his training and, and the nature of the field is that every diagnosis is clinical. You don't really go with biomarkers. And, you know, because the brain is such a black box, it leads people to thinking that, like the brain and the mind, which is emergent from it, isn't just a metabolic organ and phenomenon. And so the emerging research, this is one of the areas I find most fascinating, is like, how brain metabolism influences the human mind. So I'll give a couple examples, both out of like top papers that came out this year in 2025. One was on autophagy in the brain. Something really interesting.
- [63:57]
Danny
Which means what?
- [63:58]
Nick Norwitz
Basically, it's a cellular recycling process. We like break up and clean. Things people often associate with, like fasting. There was a study, I think it was in Nature. Again, I can, I can send all the references after the fact, but basically what they showed is that in depression, autophagy is dysfunction, dystopian, dysfunctional in a brain region called the lateral habenula, which, think about at the depression center, leads to a buildup of the receptors for the excitatory neurotransmitter in the brain called glutamate. It basically dials up your quote, unquote, depression. And another interesting thing is the drugs we use to treat human beings. So SSRIs, selective serotonin, reuptake inhibitors, ketamine, different classes of antidepressants, they converge on this pathway to alter this basic metabolic function. Or another example. Again, this is all literally cell Science, Nature Press, 2025 data. There's another one, Paul. I'll have to share this one with you. You'll love it. But on a neurotransmitter called Homo vanillic acid, which is in the dopamine pathway. Now, a pet peeve of mine is when people say 90% of the serotonin is made for the gut, therefore it's good for your brain to make gut serotonin. Serotonin doesn't cross the blood brain barrier. Homo vinolic acid does. Interestingly, in humans, Homo vanilic acid levels are low in depression. And there's also decreased levels of the gut bugs that make this neurotransmitter. So this neurotransmitter is made in the gut, it goes to the brain and it can alter mental function. We know it's low in humans with depression. And in animal models where you can chop off heads, do brain staining, animal models of depression, just giving Homo vanilic acid or either of the gut bugs is sufficient to reverse depression phenotypes.
- [65:39]
Danny
Whoa.
- [65:40]
Nick Norwitz
So again, it can't be considered, quote, unquote, gold standard evidence based medicine because there hasn't been a human rct because nobody's funded and done that. But the fact, first of all, the physiology is incredible, that your diet, the way you live can change your gut bacteria. Those gut bacteria make a neurotransmitter that we know can cross the blood brain barrier and alter the mind what more link do you need to say? Yeah, what you do in your lifestyle, how you sleep, eat, live, affects the mind. And I think once we can, like, people can internalize just how much lifestyle impacts the roots of the tree of metabolic diseases. And that manifests in all the metabolic diseases. Obesity, cardiovascular disease, depression, depression, Alzheimer's, you name it.
- [66:31]
Danny
Right.
- [66:31]
Nick Norwitz
Highlighting that importance is, I think, somewhere where we're unified.
- [66:35]
Paul Saladino
It's really important for people to understand what you just said. I'll highlight that. That all those diseases which are taught to us in medical school as disparate conditions, they're all siloed, they're all connected, right? They're all sort of systemic metabolic dysfunction arising at the level of the mitochondria, the gut, it's all connected. But Nick said Alzheimer's, depression, cardiovascular disease, the list goes on. Autoimmune conditions in medicine, I think last time I checked, there were over 10,000 diagnoses, and there are probably 75,000 different drugs or maybe 25,000 different drugs. So medicine is, in my opinion, medicine is trying to make it more complicated. And when you think about it, like, from my perspective, the more I pulled back and this is really why I left traditional medicine, it's like, wait, wait, there's probably like five things going on in humans, right? You didn't sleep enough, you ate crappy, you had a stressful event in your life, you got exposed to a toxin like these. These can probably be linked to most of the issues we have because they. They affect us physiologically. But I wasn't taught about any of those diagnoses. In Western medicine, you're taught, you know, you're taught, you know, chronic myelogenous leukemia. You're, you know, you're taught these diagnoses, which are esoteric pigeonholes, silos, and they're not connected, but they're all connected. And to understand that depression physiology, neurochemistry in the brain may have at its root method many of the same things that affect inflammatory bowel disease. That's wild. And that's where Western medicine has completely lost the plot.
- [67:55]
Danny
Yeah, it seems like it's all connected. And just trying to treat one thing is like playing whack a mole.
- [67:59]
Nick Norwitz
Medicine is siloed, metabolism is unified. That is a fact.
- [68:03]
Paul Saladino
It's totally whack a mole. And then when you give things right, you give a statin, somebody comes in with elevated LDL and maybe they do have insulin resistance, you give them a statin, you just crush their glp, right? And you know, that's crazy. And then, you know, now you're playing whack a mole down the road. And this is why we get polypharmacy. And I think that this third leading cause of death is still medical intervention. You know, you have heart disease, cancer and then medical intervention. So we're clearly.
- [68:27]
Danny
Is medical intervention number three?
- [68:29]
Paul Saladino
I think it is.
- [68:30]
Danny
Wow, that's crazy.
- [68:31]
Paul Saladino
You can fact check it.
- [68:32]
Danny
But what about quick, quick little. So I don't want to spend too much time. But a quick question. What about what is the I'm taking again? Ezetimibe. Is that bad?
- [68:41]
Nick Norwitz
I think it's the most benign in terms of side effects of the LDL lowering drugs.
- [68:45]
Danny
Basically it lowered my, it cut my 80 my LDL in half.
- [68:47]
Nick Norwitz
I would, I think.
- [68:48]
Paul Saladino
Did it change your cardiovascular risk?
- [68:51]
Danny
Right. I don't know.
- [68:51]
Paul Saladino
And why did you take it in the first place?
- [68:54]
Danny
So it lowered my ldl.
- [68:55]
Paul Saladino
And did they get a fasting insulin?
- [68:57]
Danny
That's a good question. I haven't looked. I got my blood work.
- [68:59]
Nick Norwitz
You think it would change fasting insulin?
- [69:01]
Paul Saladino
No, no. Whoever prescribed context, whoever prescribed you Ezetimibe didn't look at your metabolic health. They. You were eating keto, presumably. Danny, I'm telling you your own story here. You were eating keto. Your LDL goes up. They give you Ezetimibe to lower your LDL under the premise that it's increasing your cardiovascular risk. They did nothing to assay your cardiovascular metabolic health.
- [69:21]
Nick Norwitz
It's. It's medicine is.
- [69:23]
Danny
I'm pulling up my.
- [69:24]
Nick Norwitz
The art of making decisions at an individual basis given incomplete and imperfect data. So again, down to the individual level, Danny, it might be a very reasonable thing for you to do, all things being equal, depending on like, you know, your individual cost benefit analysis to take that even if it doesn't necessarily have a positive effect and doesn't change your life course.
- [69:43]
Danny
Right.
- [69:45]
Nick Norwitz
So it's complicated and people want clear definitives. And now I really want to get into the seed oil debate, but I think broadly what you're going to find, my position is there's reason to be concerned. We need more studies in humility on the precautionary principle. I avoid them defined as highly industrialized oils, but I think a lot of the claims are are way overstepping and I don't like the leak into vilifying omega 6 fatty acids broadly. So I'd like to start the discussion. But I would like to be very clear and distinguish when we're talking about linoleic acid and omega 6 versus seed oil so if we bring back up the. The complex. Actually, you can do the complex or simple version of the seed oil map, Steve. The simple version here. I think if we think about it like this. So linoleic acids at the middle, focus on the side and the bottom. How is it processed outside the body and how is it processed inside the body? Because there are huge contextual factors here. So we can start wherever you want, I think, wrapping some context around all the things that can happen to Omega 6 inside the body, depending on individual factors. Be fun.
- [71:02]
Paul Saladino
People understand what linolic acid is. We might want to back up and do fats. I mean, go ahead. Yeah, so we, we touched on this earlier.
- [71:11]
Danny
Can you see if it's on there?
- [71:13]
Nick Norwitz
Oh, your. Your insulin.
- [71:14]
Paul Saladino
Yeah. I'm betting you a meat stick that I brought you.
- [71:19]
Nick Norwitz
You already gave me the meat stick.
- [71:21]
Paul Saladino
So I'm not giving it back.
- [71:23]
Nick Norwitz
I'm betting you they're delicious.
- [71:24]
Paul Saladino
I'm taking one back. If it's not on there, I'm so.
- [71:26]
Nick Norwitz
That African. I will fight you for that. Dr.
- [71:29]
Paul Saladino
The. So when we have fats, we have saturated fats, right? Which is a chain of carbons, and all the carbons have hydrogens. Um, all, all of the positions of the carbon atom are occupied by hydrogen. Um, when you have a monounsaturated fat, you have one double bond.
- [71:44]
Nick Norwitz
You owe me M. It's on there.
- [71:46]
Paul Saladino
He gets 3.2.
- [71:47]
Danny
3.2.
- [71:48]
Paul Saladino
That's pretty good, right? Less than 5 micro IU per ML. So just to complete the discussion there.
- [71:53]
Danny
If you didn't know who ordered this for me, you wouldn't have bet that. Made that bet.
- [71:56]
Paul Saladino
Yeah. Maybe they were listening. They were. Listen some of these conversations around this more broadly. So, you know, from my perspective there, I would say, okay, you're pretty metabolically healthy. Let's actually look at your risk with this ldl. I would not have recommended Ezetimibe to you. I'm not your physician.
- [72:13]
Danny
Okay?
- [72:14]
Paul Saladino
So anyway, that's. That's the conversation, and then.
- [72:17]
Danny
Cut it out.
- [72:17]
Paul Saladino
Well, don't, don't, don't take my advice. I'm not your doctor.
- [72:20]
Danny
Oh, really? I take all my medical advice from the Internet.
- [72:23]
Paul Saladino
You're a sovereign human. You're a sovereign human.
- [72:25]
Nick Norwitz
Yeah.
- [72:26]
Paul Saladino
So back to the fats. You have saturated fats, monounsaturated fats, and polyunsaturated fats. Saturated fats sound bad, but again, this is because of the zeitgeist. It's because we've been programmed to do. Saturated fats are. Yes, they're they're chains of carbons with a carboxylic acid on one end and they have no double bonds. Monounsaturated fats have one double bond. Polyunsaturated fats have two or more double bonds.
- [72:47]
Danny
Right.
- [72:48]
Paul Saladino
So linoleic acid is an 18 carbon omega 6 polyunsaturated fat with two double bonds. The omega 6 means the first double bond is at the carbon 6 positions from the end of the molecule. Okay, so that's just how we name fats, because we'll talk about omega 3s. We can talk about omega 3. First double bond is closer to the end of the molecule. That's all that means.
- [73:11]
Danny
Right? So and polyunsaturated fats, for the layman, are seed oils, right?
- [73:16]
Paul Saladino
Not necessarily. Right. Because a polyunsaturated fat technically just means it has two or more double bonds. Right. If let's take soybean oil, which is the most commonly consumed seed oil, as an example soybean oil, we can fact check this. I'd say it's around 50 plus percent linoleic acid. So 50 plus percent of what's in soybean oil is linoleic acid. But maybe 1 or 2% of what's in linoleic of what's in soybean oil might be alpha linolenic acid, which is an omega 3, three polyunsaturated fat. And then there's also going to be monounsaturated fats in soybean oil and a very small amount of saturated fats in a soybean oil. So.
- [73:56]
Danny
Right?
- [73:56]
Paul Saladino
No, no, seed oil is purely polyunsaturated fat and no animal fat. Butter is not purely saturated either.
- [74:04]
Nick Norwitz
Right, right.
- [74:05]
Paul Saladino
So polyunsaturated fat is not synonymous with seed oils. Part of the concern for me with seed oils is that they do contain lots of large amounts of polyunsaturated fats, right? Specifically omega 6.
- [74:18]
Danny
Yes.
- [74:19]
Paul Saladino
Polyunsaturated fat, that is linoleic acid. When you're talking about fish oil, you're talking about omega 3 predominant polyunsaturated fats. Our consumption of linoleic acid, linoleic acid is by far the single greatest polyunsaturated fat that we consume in our diets.
- [74:37]
Nick Norwitz
Okay?
- [74:38]
Paul Saladino
Not even close to omega 3s.
- [74:40]
Nick Norwitz
Right.
- [74:40]
Paul Saladino
We're talking about, you know, a few people who are supplementing with fish oil might have 2 grams or, you know, a gram to 2 grams of omega 3. In 2025, the average American consumes 5 tablespoons of seed oils, which is a day A day.
- [74:56]
Nick Norwitz
When you say seed oils, are you saying linoleic acid and omega 6 or are you saying so the way.
- [75:01]
Danny
So let's break it down simple. For people, for people that don't know, for people that get all their information from you, YouTube and from RFK. Seed oils are bad for you. And fish oils and things like avocado oil and olive oil and butter, these things are good for you, right?
- [75:18]
Paul Saladino
A little more complicated than that, but.
- [75:20]
Danny
It is a little more complicated. But if you want to break it down, make it binary. That's basically how most people understand it.
- [75:25]
Nick Norwitz
So I think the main confusion point is poly. So. So I'm holding up. I don't know if people can see a little diagram here of fatty acids. There's saturated and unsaturated. We can talk about saturated separately. A very complex group in and of itself. Within unsaturated, there's mono, unsaturated, one double bond or polyunsaturated. Within polyunsaturated, there's omega 3. So like fatty fish, fish oil, and then there's Omega 6. And this. Is this Omega 6 more or less synonymous with linoleic acid? Just because of the proportions that are consumed. The way I want to define seed oils and stick to these terms as best we can, because I think this, if nothing else, is the main confusion point. If omega 6 rich foods are like highly refined in process to get the oil that is heated and has additives added to it, that is the highly industrialized seed oil. And I think one of the big issues that arises is conflating omega 6 in seed oil. So let's start, because I think this is where we're going to have the biggest disagreement.
- [76:29]
Paul Saladino
Okay.
- [76:29]
Nick Norwitz
About Omega 6. So the physiologic impacts of Omega 6 specifically. And then we'll talk about processing.
- [76:37]
Paul Saladino
Well, we can talk about relative amounts because I think this is an interesting point. So what Nick is saying. So just back to what we were just saying. So the average American consumes 5 tablespoons of seed oils per day. The most commonly consumed seed oil is soybean, perhaps followed by canola. Soybean is approximately 50%, give or take, linoleic acid.
- [76:53]
Danny
And where are they getting all of this from?
- [76:55]
Paul Saladino
It could be in. It's probably french fries, it's in breads, it's in salad dressings. So the majority of seed oils people are consuming are heated. That's an important point.
- [77:04]
Danny
Also just basic processed foods.
- [77:06]
Paul Saladino
Processed foods. And so, and. And I think a lot of it is french fries. A lot of it is chips, Right. Those oils are boiled and heated. So there are. There's even nuance in. In the seed oil conversation that goes deeper.
- [77:17]
Nick Norwitz
Right.
- [77:17]
Paul Saladino
You can have a seed oil which, as Nick correctly points out, is industrially refined, bleached and deodorized oil, soybean oil, canola oil, peanut oil, sunflower oil, safflower oil. It's sitting on the shelf in a grocery store in a plastic container that can leach antimony into the oil. It's a transparent plastic container. So that is a fragile oil by nature of being polyunsaturated, that is being exposed to light and oxygen for months at a time. On the. This is just. And then you take those oils, and most of those oils that we consume today are then heated. Right. You're either frying with them in a pan or you're deep frying with them.
- [77:51]
Danny
Them.
- [77:51]
Paul Saladino
So there are levels to perhaps the potential harm of these oils. As you heat an unstable oil, it becomes more problematic, more inflammatory mediators are generated. So we can talk about heated seed oils, we can talk about unheated seed oils. And as Nick is pointing out, we should differentiate that from not even processed sources of Omega 6 things like walnuts. Right. That walnuts contain moderate amounts of omega 6. They also contain moderate amounts of omega 3. 3. But what I wanted to point out here is that. So let's just say corn. Corn oil is another commonly consumed oil. Seed oil, industrially refined, bleached and deodorized oil in our diet today. Again, chips, cakes, cookies, packaged foods. You look at labels, they're everywhere. French fries, obviously, it's in bread at all the fast food restaurants, processed foods.
- [78:40]
Danny
Yeah.
- [78:40]
Paul Saladino
In order to get 5 tablespoons of corn, you would have to eat 60 ears of corn. Right. Something that humans would never have done historically. Five tablespoons of soybean oil is two and a half pounds plus of soybeans. Five tablespoons of peanut oil, something the same. You know, you can look at these amounts. It's just in. In just to say, like a walnut. The amount of linoleic acid in a walnut pales in comparison to a tablespoon of. Nobody's doing. Walnut oil is not really a seed oil because it's so unstable, it has so much Omega 3. People never use walnut oil. It gets rancid so fast. But like a soybean is not the same as a tablespoon of soybean oil. Right. A tablespoon of soybean oil is the equivalent of, you know, hundreds of soybeans.
- [79:27]
Danny
Sure.
- [79:27]
Paul Saladino
And that's, that's not even the best example. You know, you have two and a half plus pounds of soybeans to get five tablespoons of oil. These are evolutionarily. And again, I'm sort of stacking the deck in my favor. I'll just. But I'm trying to say this as, as just in an unbiased way as possible. These are evolutionarily difficult amounts of oils to obtain from the actual parent foods. That's interesting. So we have those three differentiators we're talking about. Omega 6 linoleic acid occurs in most unprocessed foods that you or I eat today. There is Omega 6 linoleic acid in a grass fed steak. It's a small amount, right. It's perhaps 1%. 1% of the fat in a steak is linoleic acid. 50 of the fat in soybean oil is linoleic acid. So you see there's a spectrum, right. An egg yolk contains linoleic acid.
- [80:17]
Nick Norwitz
Right.
- [80:17]
Paul Saladino
So there's a difference between saying linoleic acid is, you know, per se harmful or is there a dose or is there a form factor here as well? So yeah, and we can differentiate all those things. But that's just something I wanted to differentiate for people. Like historically, our consumption of linoleic acid today is 10x1000% higher than it ever has been historically because of our consumption.
- [80:45]
Danny
Do we know when our consumption, this 5 tablespoons per day started? Like how, when did this start? And like how, how has it grown?
- [80:54]
Paul Saladino
The first seed oil was introduced in 1911. Proctor and Gamble made Crisco. Right. So before, so 1900, there were essentially 99% of the fat we ate was animal fat in 1900. And just to give context, again, record keeping, not the same. But the heart attack wasn't even a thing. There was no diagnosis of heart attack in 1900.
- [81:14]
Nick Norwitz
Wow.
- [81:14]
Paul Saladino
Humans didn't have like chest pain like that. This clinical syndrome is not defined until much later. Yeah.
- [81:21]
Danny
So holy. Global production of vegetables. Is vegetable oil the same thing?
- [81:25]
Paul Saladino
Yeah, vegetable oil is the euphemism. Right. So seed oil is.
- [81:28]
Danny
Oh look, it shows all of them. Palm, soybean, canola. Wow.
- [81:32]
Paul Saladino
1911 is Crisco. And then more and more become a part of it. There's interesting history from Procter and Gamble and the American Medical association that I can mention because we're on the topic. So the American Medical Association, I think was started in the 1850s, but it didn't really rise to prominence until the mid-1900s. And part of that was a major grant from Procter and Gamble to the ama. So there's a lot of speculation. Again, it's just purely speculation. But Procter and Gamble makes Crisco. Procter and Gamble was really behind the popularization of at that time, hydrogenated seed oils into the public sphere in place of butter and lard.
- [82:11]
Nick Norwitz
Right.
- [82:11]
Paul Saladino
Because animal fats 1900 99% of what we eat is animal fat. And then Procter and Gamble makes Crisco. They say it's cheaper, it's healthier, it's white, it's not going to raise your ldl. As we begin to understand lipoproteins, we can talk about saturated fats versus monounsaturated and poly and their effect on APOB and LDL. In 1939, I think give or take, Procter and Gamble makes the equivalent today of a hundred thousand dollar donation to the American Medical association for their sort of radio show. And then the American Medical association begins to sort of get more on this polyunsaturated fat bandwagon. You can find ads from, I would say the 1950s and 60s of these are incredible ads. I think they're from maybe Mazola corn oil. But you can see this becoming a part of the zeitgeist. And there's a great ad. Maybe you can find it, Steve. It's like Denise or whoever it is polyunsaturated her family tonight. So they're talking about cooking with this corn oil. There are these crazy ad. Yeah. So like anyway, they become a part of, of the conversation and the cultural milieu over the last, let's say 100 years, give or take, starting in 1911. Before that, essentially cotton seed oil was made in the 1860s but not used in food until 1911. Previously most people know this, but previously sea oils were used for lamp oils and for engine oils and they were used in World War II on submarines and ships because they retain their slippiness when they're wet.
- [83:29]
Danny
Right. And when did this food pyramid get constructed? We know what year that happened.
- [83:34]
Paul Saladino
There's been a couple of them. But I think the first one I.
- [83:36]
Danny
Was want to say the 80s bread at the bottom.
- [83:38]
Paul Saladino
I think it was the 70s or 80s, I'm guessing. But yeah.
- [83:41]
Danny
And that that had to do with that was funded by some of these industries as well. Right.
- [83:45]
Paul Saladino
There is, there is evidence of industry funding and yeah.
- [83:49]
Nick Norwitz
Can I make an imposition and a challenge which is I the way when I observe discussions around seed oils and just research in general, it does tend to devolve into history, talking about funding. It's not that. It's not important. Not incentive structure.
- [84:08]
Paul Saladino
I'm not trying to.
- [84:09]
Danny
Super important.
- [84:10]
Nick Norwitz
No, no.
- [84:10]
Paul Saladino
I'm really not trying to color the conversation. I just.
- [84:12]
Danny
We're trying to break down your ivory tower.
- [84:14]
Paul Saladino
It's important for context. It's important for context.
- [84:16]
Nick Norwitz
I'm a sleeper agent.
- [84:18]
Paul Saladino
We'll get to the science, but it's important for context. I think. I appreciate it and I, I, I apologize. I'm not trying to color the conversation. I just think, think that's, and Danny was curious and I think it's a really interesting question because when, just, just intuitively. Again, this is not, this is not double blind, randomized placebo controlled trial.
- [84:35]
Danny
Right?
- [84:35]
Paul Saladino
When humans introduce new things into their diet and environment, we probably should be cautious.
- [84:40]
Danny
Yes.
- [84:41]
Nick Norwitz
So.
- [84:41]
Paul Saladino
And again, that's just, that's just philosophical. Like, we're not, you know, not everything that gets introduced is bad for us.
- [84:47]
Nick Norwitz
I want to. One of the things I want to do is like, what? Draw out what I believe to be Paul's quite nuanced perspective as differentiated from the caricatures and memes that get propagated around each of us because of the way media works. And you know what I hear you saying, Paul, is the way these seed oils are introduced into our diet is evolutionarily unprecedented, is coincident with a decline in metabolic health. Therefore, we should.
- [85:19]
Paul Saladino
We didn't talk about the coincidence with metabolic health. I don't like to draw those because I think there are so many things that do that. But yes, that's it.
- [85:25]
Nick Norwitz
We agree on that. So I see that as different. I see it as different saying, look, this could be a problematic compound. Here are the reasons, and let's do some more research than people going on, you know, like, I'll just say it, Robert F. Kennedy Jr. Going on and saying, like, seed oils are. What was it? The most unhealthy thing in the human diet. That is a claim, that is a direct claim that I don't think could be substantial.
- [85:50]
Danny
RFK said that.
- [85:51]
Nick Norwitz
I'm pretty sure. Can you say something to that effect?
- [85:52]
Paul Saladino
I don't know.
- [85:53]
Nick Norwitz
It's the most unhealthy.
- [85:54]
Paul Saladino
I don't know if he said that.
- [85:54]
Nick Norwitz
We can. Steve, you can find it and people can fact check me. I'm 99% sure he said something.
- [85:59]
Danny
He almost said EMFs cross the blood brain barrier.
- [86:02]
Nick Norwitz
He did say something on Rogan anyway, so I don't think he's the best scientific resources. I talk about him as a human.
- [86:07]
Paul Saladino
He's A great human.
- [86:08]
Danny
He's got good intentions.
- [86:09]
Paul Saladino
He's a great dude.
- [86:10]
Nick Norwitz
Intentions count.
- [86:11]
Paul Saladino
I love intentions count.
- [86:12]
Nick Norwitz
But I guess I want to challenge listeners to say like, yeah, this is important context. But now let's talk about like, let's.
- [86:19]
Paul Saladino
Talk about the science.
- [86:20]
Nick Norwitz
Science and what we can claim, what we can't claim. So let's talk about not processed seed oils. Let's start with linoleic acid. Is it bad in the body?
- [86:30]
Paul Saladino
Well, okay, can I just back up? I appreciate what Nick is saying because a lot of times you will see, you see this graphical overlay and it's a correlation, right? And you can add your, add your cordial of cordial correlative element here, right? You see, because we know that in the last 100 years, coincident with the introduction of seed oils, glyphosate, vaccines. Choose your boogeyman.
- [86:51]
Danny
Right?
- [86:51]
Paul Saladino
Right. We have had an explosion of chronic disease in this country. Obesity, infertility, cancer, dementia, depression.
- [86:58]
Danny
Has a lot to do with technology too. People being sedentary.
- [87:01]
Paul Saladino
Exactly. Choose your bogeyman. And I don't like those overlays. I think that Nick is right to point point out that that correlation, you can make that correlation with a lot of things, right? You can correlate the number of movies Nicolas Cage appears in per year and the number, and the number of drownings and pools. Right. You know, like this, these are, these are, these are not the right way to do it. Now it is an interesting thing to say, like, okay, all of these things have become introduced into our society. Let's ask the questions around glyphosate. Let's ask the questions around vaccines. Let's ask the questions around ultra processed foods which are complex and are not simply containing seed oils. They contain many things.
- [87:34]
Nick Norwitz
Right?
- [87:35]
Paul Saladino
Let's ask the questions around other pesticides. Let's ask the questions around technology and devices and blue light and circadian rhythm disruption. There's a lot of things. I think that the interesting thing, the important thing is that we're asking the questions as physicians or as laypeople. We're trying to understand what is causing us to be so unhealthy as opposed to just, you know, like, let's just give us a medication, you know, you're sick, here's a med. No, no, let's, let's try and figure this out. But yeah, the correlation is not terribly instructive.
- [88:01]
Nick Norwitz
Do you want to start talking about linoleic acid physiology or you want me to.
- [88:05]
Paul Saladino
Let me say a word and then I'll let you add to It, Yeah. So from my perspective, I don't know exactly what Nick's going to say about linoleic acid physiology. The background that I have on it is that linoleic acid and omega 6 polyunsaturated 18 carbon is fatty acid, is, is essential, quote unquote, for humans. Now the levels which we need are questionable. We can talk about it in this conversation. But to become deficient in linoleic acid, you would essentially have to eat a diet of basically rice. I'm not even sure. You probably wouldn't even become deficient in linoleic acid if you ate only rice. If you ate purely like some sort of very. It'd be very, very difficult to become deficient in linoleic acid. No one becomes deficient in linoleic acid by avoiding seed oil. There's linoleic acid in steak. There's linoleic acid in fish.
- [88:54]
Nick Norwitz
I agree. Yeah.
- [88:55]
Paul Saladino
Fish and egg yolks. It's, it's in all whole foods, right?
- [88:59]
Nick Norwitz
Yeah.
- [88:59]
Danny
Okay.
- [89:00]
Paul Saladino
Now so it's considered to be an essential fatty acid because when you deprive rats or mice, yeah, they, they don't do well, but you have to feed them a very specific diet. I don't think that many humans in, in recent memory are deficient in linoleic acid.
- [89:14]
Danny
Okay.
- [89:14]
Paul Saladino
We could argue differently for omega 3s perhaps, but so, but linoleic acid does become incorporated into our cell membranes. It's an essential part of human physiology. It is a precursor for many, let's just say, second messengers in the human body, and those are, those generally have both inflammatory and anti inflammatory roles. And even framing it that way, let's just say inflammation is not always a bad thing.
- [89:37]
Nick Norwitz
Right.
- [89:38]
Paul Saladino
When you, when you work out, you need inflammation to repair and rebuild. And, and if you abrogate or you block blunt that inflammation, you don't become as strong. And so inflammation often gets billed as a horrible thing that you just want to completely annihilate from your body. That doesn't work. You need. We, we mentioned oxidation earlier today. You need oxidation, right? In the mitochondria, you generate reactive oxygen species, you generate superoxide species. These are essential for proper signaling, both the level of insulin and we can't complete. We're not trying to get rid of all oxidation in the human body. Right. We're not trying to get rid of all inflammation. And so anti inflammatory and inflammatory second messengers do come from both omega 6 and omega 3 fats. And so they're a part of our diets. The interesting thing for me about linoleic acid that I'll add is more context without trying to color it too much, is that the polyunsaturated fats, whether it's omega 3 or omega 6, are stored in the human body. The human body can make saturated fats, and we can interconvert those into monounsaturated fats, but we cannot make polyunsaturated fats, which is why they're essential. That also means that we store them. So the amount of, um, linoleic acid and other polyunsaturated fats, which could be omega threes, found in human cells, human membranes, human adipose tissue, um, and the tissue, the, the actual tissue you're looking at matters that is in many ways directly correlated to intake. Not always. Sometimes there are some nuances there. But we as a human species, and this has been done by Stephan Guy, did a great paper about this, I think, in the early 2000s, it's been shown that human adipose tissue has accumulated far more linoleic acid in the last 70 years. Because we eat more, we hold on to more. Whether or not that's good or bad, I'm trying not to pass judgment there. But we do hold on to fatty acids. The amount of omega threes and omega sixes in our body, specifically our adipose tissue and some other tissues, correlate pretty well with intake, so we don't get rid of them easily. The turnover of these fatty acids is slow. So it's just something to consider that if you eat saturated fat, right, that's going to have certain effects on your body. But your body can already make saturated fat, and your body can interconvert saturated fat with monounsaturated fats and vice versa. The polyunsaturated fats stay in our membranes, and that's just something to think about.
- [91:44]
Danny
Interesting.
- [91:45]
Nick Norwitz
Steve, can you bring up adipose tissue, cardiovascular mortality?
- [91:51]
Danny
The bottom one.
- [91:52]
Nick Norwitz
The bottom one. So what do you make of this graph is from a meta. I think you actually shared it with me and if I recall correctly, Paul, So this is what it's showing is the hazards ratio for cardiovascular related death, heart disease related death, as a function of omega 6 and specifically linoleic acid in human fat tissue. And it shows a favorable effect for Hylene. So what do you make of that?
- [92:18]
Paul Saladino
There are other studies they didn't include that show an unfavorable effect of human adipose tissue. Yeah, I can show you one. Yeah.
- [92:24]
Nick Norwitz
Do you know.
- [92:25]
Danny
So can you explain this? S H E C308.
- [92:29]
Nick Norwitz
Those are just the names of the studies, the cases is the number of patients. And basically, the way you read this is it's reported as a hazards ratio. Basically everything to the left of the vertical line, the 1.0 is a favorable effect in terms of linoleic acid concentrations.
- [92:48]
Danny
Okay.
- [92:48]
Nick Norwitz
And if it's to the right, it's unfavorable. So here it's showing a favorable effect. Now, here's my thing.
- [92:57]
Danny
A favorable effect to cardiovascular mortality of.
- [93:00]
Nick Norwitz
Having higher linoleic acid levels in the body.
- [93:02]
Danny
Now, so having more seed oils is better for cardiovascular.
- [93:05]
Nick Norwitz
First of all, linoleic acid, I wouldn't conflate with seed oils.
- [93:09]
Danny
Okay.
- [93:09]
Nick Norwitz
And also off of this, I'm not making the claim just to be clear. This shows linoleic acid reduces cardiovascular mortality. But if the claim is it increases it, then observations like this, it's just not consistent with that observation. So if we're talking about storage in the body and considering that, quote, bad, how does this effect even arise? Now? Maybe they omitted some studies. It's possible, but, like, still, it's tough.
- [93:39]
Paul Saladino
It's an interesting. This is an interesting one because. So one of the things that gets pointed out a lot is that if you look at linoleic acid levels in the blood, higher levels of linoleic acid in the blood, like we're looking at adipose here, right?
- [93:52]
Danny
Yeah.
- [93:52]
Paul Saladino
But higher levels of linoleic acid in the blood do often correlate with better cardiovascular outcomes.
- [93:58]
Danny
Interesting.
- [93:59]
Paul Saladino
Now, what's interesting about linoleic acid levels in the blood is that that is not a great proxy for linoleic acid intake. The best indicator of linoleic acid in the blood is a measure of. It serves as the best measure of an. The activity of an enzyme called D60 delta 60 saturates, also known as fatty acid desaturates. 2. So without getting too granular, like in the human body, linoleic acid gets broken down into intermediates. One of them is dgla, and then another one is arachidonic acid. And what we see pretty clearly is that if you have higher levels of this enzyme, D6D.
- [94:41]
Nick Norwitz
Right.
- [94:42]
Paul Saladino
That is consistently linked with worse cardiovascular outcomes.
- [94:45]
Nick Norwitz
Right.
- [94:45]
Paul Saladino
And D60 is acting on linoleic acid in the cascade to move it to downstream metabolites, specifically arachidonic acid. Downstream from arachidonic acid, you get things that are called ox lambs, so oxidative products of linoleic acid metabolism. And that's where things get quite complex, because those are myriad. The names are very esoteric, and they're linked to all Sorts of problematic things for humans. So there are. Actually, I want to come back to this, and I want to show you the study that. That actually looks at levels of linoleic acid in the fat tissue and shows different results than this. But specifically with regard to D6D, there are Mendelian randomizations which suggest that D60 is causal for cardiovascular disease. And that's just saying if you look at a bunch of people with various levels of Delta 60 Saturase, based on their genetics, the people that have higher levels of delta 60 saturase, an enzyme that moves linoleic acid down this synthetic pathway, tend to do worse from a cardiovascular perspective. And this is all part of this broader conversation around levels of linoleic acid in the blood and why that can be a little bit misleading for people. Because when you have higher linoleic acid in the blood, that's probably saying less of your linoleic acid is moving downstream.
- [95:50]
Danny
Right, right.
- [95:51]
Paul Saladino
And lower levels of linoleic acid, which are linked with worse cardiovascular outcomes, mean linoleic acid is moving down the pathway toward arachidonic acid and potentially these ox lam molecules. Okay, so that's interesting because that's the first piece to understand is that are you looking at D6D activity? Are you looking at linoleic acid being biotransformed into things in the human body? Or are you actually looking at linoleic acid levels? Adipose, as I said, is it's a decent marker of linoleic acid consumption. It's not perfect. And so when you look at this. This was interesting when Nick showed me this, but there are other studies, I need to find it for you, that look at linoleic acid in the fat and show different results in cardiovascular mortality. The problem with this, you look at the cases. So it's 308 cases, 110 cases for these two cohorts. It's like, it's. It's difficult. Yeah. It's not the full deciding factor, but it's. It's confusing for sure.
- [96:42]
Nick Norwitz
I don't think you can disregard, based on.
- [96:45]
Danny
Steve, what happened to our background, bro. What do you got going here?
- [96:51]
Paul Saladino
It disappeared.
- [96:52]
Nick Norwitz
I can bring it back up. I didn't want to, like, distract first, just in general, because this comes up again and again. The sample size of a study doesn't say much about its quality per se.
- [97:03]
Paul Saladino
But the only reason I mentioned is because the other one I was going to show, I think was similar size or a little bit bigger than one of them.
- [97:08]
Nick Norwitz
Oh, yeah. Well, I think I can put that As a sticky note for something I need to write independent content on, I can go through each of the three studies. But that aside, just to kind of reinforce what Paul is saying, because I think sometimes analogies pop into my mind and I want to share them. And I think it's a good point and an important point. So like, I've been seeing a lot of Lord of the Rings reels, girlfriend, boyfriend reels on Instagram. So now I'm thinking it's like if linoleic acid is orcs storming helms deep, you have the orcs that are outside the linoleic acid in circulation and then those that get through the barrier or say bio transformed into something more harmful. And so Paul is right that it can be misleading to look just at the orcs outside the wall. And what's important is how much your wall is broken down. So in this case, you know, how much bio conversion do you have into things that are harmful? I guess what I'd add here is a couple of things. One, we can't have a whack a mole game here. We need to be like, well, what is actually the health proxy? Is it delta 6 desaturates activity? We can measure that. Is it linoleic acid and adipose tissue? Is it circulating? Like one of these things are informative because if we're having a conversation where we're talking about one biological pathway, then people pull up contradictory data, then we jump off that marker onto another, we're never going to have a full conversation. So I think a lot of this is in the realm of curiosity and speculation. And I want to keep it there because Paul said, you know, it's complicated, the pathways even in just fat tissue, for what can happen to linoleic acid. And that is a context keeps coming up heavily contextual. So I'll give you an example of one good thing that can happen. I'm not saying this is the bulk pathway. I just want to kind of like broaden people's minds about like what happens to this once it's in the body. In fat tissue, in particular, brown and beige fat, it can be turned into a derivative, an Oxylipin called 1213 Di H O M E. Oh, dihomey. That's what, that's what I said to you, I think, like earlier, I don't actually know, I've never heard it said out loud. But yeah, 1213 dihome sounds kind of cool. So we'll say that. So interesting thing about 1213 dihomy is it decreases with age and it has really beneficial effects on the heart. So it can inhibit perivascular fibrosis, basically the hardening of vessels.
- [99:33]
Danny
So dihomy keeps the arterial walls more flexible.
- [99:37]
Nick Norwitz
Flexible improves cardiovascular function, inhibits things that are bad metabolically, like, er, stress. And again, this is an oxidized.
- [99:44]
Danny
You lose this as you age.
- [99:45]
Nick Norwitz
You lose this as you age. But interestingly, and then this is just a context mind opener, you can increase it with lifestyle intervention. So there are human trials showing you can increase 12, 13 dihomey levels by about 39% from a cold plunge.
- [99:59]
Danny
Really?
- [99:59]
Nick Norwitz
Yeah, because this song made in brown and beige fat.
- [100:01]
Danny
So there were studies done that show this.
- [100:03]
Nick Norwitz
Yeah, he went. Studies. I have a YouTube video where I get input from. I think it was the first.
- [100:07]
Danny
Which study was it?
- [100:08]
Nick Norwitz
I can find it while Paul is responding.
- [100:12]
Paul Saladino
Steve, can you show my screen? But yeah, this is the study I was mentioning.
- [100:17]
Danny
Holy shit, that worked.
- [100:18]
Nick Norwitz
Good.
- [100:19]
Paul Saladino
So you see there, I highlighted the platelet. Linoleic acid concentration was also positively associated with cad. This is adipose tissue. Concentration of linoleic acid positively associated with the degree of coronary artery disease in a cross sectional study of 226 patients undergoing coronary angiography.
- [100:33]
Danny
And this is from what?
- [100:35]
Paul Saladino
This is just an independent study. Right.
- [100:37]
Nick Norwitz
Okay.
- [100:37]
Paul Saladino
So we're just showing that when we're looking at adipose tissue, the results are conflicting and confusing.
- [100:43]
Danny
Yeah.
- [100:43]
Paul Saladino
I think that to Nick's earlier point, it's, it's, it's. We have to sort of decide like what markers do we care about the most with linoleic acid.
- [100:50]
Danny
Yeah.
- [100:51]
Paul Saladino
Or do we look at RCTs because we can talk about randomized controlled trials like Minnesota and Sydney. Do we look at adipose levels and correlation with coronary artery disease? I think lick is starting to talk about oxy lipins. I think it's useful to talk about ox lambs, which are these oxidative products of linoleic acid metabolism. And I think that we should probably talk some about oxidation of ldl, which is another problem. So broadly, the way that I see the seed oil conversation. Well, I guess we're sort of talking about linoleic acid versus seed oils now. But broadly, I think what we're looking at here is linole.
- [101:25]
Danny
Linoleasy for you to say acid comes from seed oils though, Right.
- [101:30]
Paul Saladino
Not exclusively. Right. Because it's. It's found in things like an almond has a little bit.
- [101:35]
Nick Norwitz
Right.
- [101:35]
Paul Saladino
An egg yolk has a little bit. We talked about this.
- [101:37]
Danny
Right, right, right, right.
- [101:37]
Paul Saladino
Steak has a little bit of linoleum linoleic acid.
- [101:39]
Danny
But primarily, I think that the major.
- [101:42]
Paul Saladino
The major source of exposure for humans to linoleic acid in the last 100 years is seed oil.
- [101:47]
Danny
Yes. Okay.
- [101:48]
Paul Saladino
If you look again, going back to the history historically, like indigenous groups, they're getting one to two, two and a half percent of their calories from linoleic acid because there's a small amount in meat and eggs and quail and birds.
- [102:00]
Danny
So how many do we know? How many of these, either independent studies or published studies, trials, whatever, do we have supporting the idea that linoleic acid increases cardiovascular disease? And then how many do we have that say that there's no effect or a better effect?
- [102:20]
Paul Saladino
It depends on the quality of the trial. Right. So at. On my X account, I pinned a thread that I did a few years ago and I looked at all 11 randomized controlled trials looking at saturated fat versus seed oils. And when you go through the thread, you can pull that one up. I don't know if you want to. I can pull that up here if you want. Steve.
- [102:44]
Nick Norwitz
Quickly, the name of the. Well, there's several papers, but the one about cold exposure. Cold induced changes in plasma signaling lipids are associated with healthier cardio Metabolic profile Independent Brown Adipose Tissue cell reports Medicine 2024 first author Juardo Fasoli.
- [102:59]
Danny
And they gave. How many people were they putting in the cold plunge?
- [103:02]
Nick Norwitz
And what was the. I have to look back at this.
- [103:07]
Danny
64, because I was only aware of one study that was like a. It was on like Scandinavia. I forget who Huberman always talks about it.
- [103:16]
Nick Norwitz
It was the dopamine one, the one where dopamine increased peripherally. Anyway, we can get back.
- [103:22]
Danny
I don't think so. I think this was a cardiovascular one.
- [103:24]
Nick Norwitz
Go ahead, Paul.
- [103:26]
Paul Saladino
So this is just one thing that you were asking about, Danny. It's like, okay, so when we're talking about seed oils, if we're just kind of in that realm and we're saying, okay, what are the randomized controlled trials that have been done with seed oils?
- [103:38]
Danny
Right.
- [103:38]
Paul Saladino
You look here. So I summarized about 11 of them. And there's roast corn oil, There's Ozo diet, heart. There's one called the Medical Research Council trial, Los Angeles Veterans Trial, Sydney Diet Heart, Minnesota Coronary. The diet and reinfarction. There's St. Thomas Atherosclerosis, National Diet heart study, the Finnish Mental Health Hospital study. There's Hauzmiller Diabetic Angio angiography or angiopathy trial. And so these are all done between, let's say, 1950, 8 and 1980s.
- [104:07]
Danny
Okay.
- [104:08]
Paul Saladino
We don't have any more recent trials on seed oils.
- [104:11]
Danny
Wow.
- [104:11]
Paul Saladino
And if you go through them, I mean, we can go through them individually if you'd like, or I can give you a high level. From what I think if you go through them, what you find is that the trials are consistently poorly constructed. We have some trials which say seed oils increase the risk of cardiovascular disease. And. And you have some trials which say seed oils don't increase the. Increase the risk of cardiovascular disease or potentially even lower it.
- [104:37]
Danny
And so there are some that say it lowers it.
- [104:38]
Paul Saladino
There are some that say it lowers it. But in my analysis, this is my analysis. Nick can look at these or he can give us his sense of what he thinks about the RCTs broadly as well. When you look at the ones that say seed oils are benign or beneficial, they're, they're, you can basically pick something wrong with every single one of those trials. For instance, if you look at the OZO Diet Heart study, we can double click on this.
- [105:00]
Danny
Can we see who funds these trials too?
- [105:02]
Paul Saladino
They're, they're from so long ago. So here's a diet heart 1958 to 1963. Right. Five year follow up, 412 participants. It's a control group and the experimental group is getting 76% of its calories from soybean oil. In the experimental group. Now, the experimental group had a significant reduction in serum cholesterol, which was associated with a reduced coronary heart disease relapse rate. And I said here, so they, they had more seed oils and they had decreased coronary heart disease relapse rate. Now, the potential flaws. The control group, right, had 9.6% of their calories from trans fat. This is the problem is that in the 1950s and 60s, we didn't really understand trans fat. So this is what I mean when I say these trials are poorly constructed. Right. The experimental group, which is the seed oil group, was also encouraged to eat more nuts, fruit and vegetables and to restrict their intake of refined grains and sugars. So this is a, this is a randomized controlled trial that gets included in a lot of meta analyses that will conclude, oh, seed oils are benign. But you see how poorly constructed the trial is. Like, okay, now you can go down here. We can look, look at another one. What's a good one here? The Finnish mental hospital studies. Another.
- [106:11]
Danny
Why don't we do these studies anymore if it's such a hot topic?
- [106:15]
Paul Saladino
I'm reading the Minnesota Coronary Experiment study.
- [106:17]
Nick Norwitz
Which is done in a multi center Multiple mental hospitals. And actually I was joking with someone because there's a section where they're like, and this is why we didn't get patient consents. Bottom line, ethics have changed around doing these sort of experiments.
- [106:30]
Paul Saladino
Millions of dollars also. And who funds it? It and the, I would argue, and this is just my perspective, the ultra processed food industry is comfortably ensconced, right? They are making billions of dollars on these foods. If a trial came out that said seed oils were harmful, someone stands to lose billions, if not trillions of dollars. Who pays for this? This is a 15 to 20 million dollars study over seven years plus potentially, right? The, the ethics are difficult and, and we're kind of stuck back to the apob thing also because it's probably difficult within western medicine to do any trial that could potentially raise your apob because we're stuck in this perspective that anything that raises your apob will increase your cardiovascular risk. And we know pretty clearly, as we'll see if we look at Minnesota coronary experiment, that and many of these like Sydney diet heart also giving someone sea oils lowers their ldl. But oftentimes, and I would say in the best constructed trials, not perfectly in the best constructed trials, that doesn't equate to a decrease in cardiovascular disease. So there are, so there are all sorts of problems in terms of our, our sort of paradigm today in terms of how we look at things. And there's this. Who funds it and why would it get done? Right, let's just look at the Finnish mental health Mental hospital study study. So this is, this is pretty commonly included in Meta Analysis 1959-1971. 676 subjects control diet, which is often the saturated fat rich diet versus the experimental diet. Uh, it was carried out in two mental hospitals near Helsinki. One of the hospitals received a cholesterol lowering diet, a diet low in saturated fat and cholesterol relatively high in poly saturated fats from soybean oil. The other was served as a control with a normal hospital diet. After six years, diets were reversed. Now the use of the cholesterol lowering diet was associated with significantly reduced mortality from coronary heart disease. Okay. Now there was significantly more trans fat in the control diets. The hospital K had 2% trans fat in the control diet versus 0 in the experimental group. And the hospital N had 0.6% trans fat versus 0.2. There were minor differences in baseline characteristics such as age, bmi, smoking and blood pressure between the two groups. And there was a cardiotoxic medication, thyroidazine which we don't use anymore. That was more commonly given to people in the control group. So there was inadequate randomization also between the two things. So you can see how, how like obfuscated these trials are. Like, how could you say, what's going on? You're giving a control group in hospital K and hospital N a diet with significantly more trans fat, which we know is cardiotoxic. And then there's more patients in the control group getting a cardiotoxic medication like thyroidazine. And that's going to make this saturated fat group look worse. So this is what happens with these trials, right? It's now you can go through all of them and look at these. But these. What's important to point out here is that meta analyses are written today and they have these trials in the meta analysis and they'll say, oh, look at the combined. Like if you just. If you do a forest plot with the results of all 11 of these trials, you might find a combined effect which favors seed oils. But what, what if you throw out the trials that are obviously poorly constructed?
- [109:35]
Danny
Right.
- [109:36]
Paul Saladino
So then you have.
- [109:36]
Danny
It's the foundation of all the new stuff we come up with is this. These poorly done studies.
- [109:40]
Paul Saladino
Yes, these poorly done studies which will probably never be repeated.
- [109:43]
Danny
That's crazy.
- [109:44]
Paul Saladino
So it's this. We end up in this situation where we almost have to look at mechanisms because the randomized control trials. And then, you know, you can look at stuff like we can look at.
- [109:52]
Danny
And who is the guy Huberman was talking about?
- [109:55]
Nick Norwitz
He.
- [109:55]
Danny
There's some guy at Stanford, a brain surgeon or something, who said. And Huberman said this. He said that this guy from Stanford, this brain Guy said like 60 to 80% of all the medical literature is either incorrect or outdated.
- [110:09]
Paul Saladino
Bhattachary has talked about that or. No, it's John Ionidas.
- [110:12]
Danny
No, I think he had like a. He had like an Asian last name, like a Chinese or Japanese or something like that.
- [110:19]
Nick Norwitz
Is one thing to say.
- [110:20]
Paul Saladino
What was that guy's name?
- [110:21]
Nick Norwitz
Correct. Another thing to say, incomplete.
- [110:24]
Danny
He said either incorrect or new. New stuff has basically.
- [110:29]
Nick Norwitz
Oh, yeah. I believe that you evolve models. That's what science is. It's never complete. It's always probabilistic and evolving. That's what's beautiful. I do want to get back into mechanism, but I think something to highlight. There is no perfect study. So you can always poke holes in a study. I think one that would be good to talk about that I actually think is on balance a pretty decent study that has gotten Some heat is the Minnesota Coronary experiment.
- [110:54]
Paul Saladino
If we're going to delve into one, talk about it.
- [110:56]
Nick Norwitz
So yeah, just to kind of give a high level breakdown of this, there were patients kept at mental hospitals and I think one nursing home. And they were given a diet that was either very elevated in linoleic acid. I think it was close to 14% of cacao from linoleic acid.
- [111:15]
Paul Saladino
18 to 20 of calories from linoleic acid. Are you sure?
- [111:18]
Danny
Well, can you punch it on this, Steve?
- [111:20]
Paul Saladino
Our experimental diet goal was to provide 18 to 20% of calories from punishment polyunsaturated fat by the control diet aimed for 18% of calories from saturated fat. There were 9,000 give or take participants.
- [111:30]
Nick Norwitz
I think it ended up being like 13 point. I actually have the primary paper up here, something like 13 point. Anyway, that aside, there was a larger 13.2% of calories versus 4.7. So there was a randomized controlled trial. In this case it was actually double blinded supposedly where there was a group that was given more linoleic acid in the form of corn oil versus a group that got a higher saturated fat diet relatively. And then the results were a massive drop in LDL in the corn oil group, but trending towards worse mortality. So more deaths and more cardiovascular disease, including on autopsy. So they had autopsy of these people.
- [112:16]
Paul Saladino
Especially in the older, the older age groups over 65.
- [112:18]
Nick Norwitz
It appeared to be the case. The fact is a lot of the data weren't available. They were like in the basement on like nine track tapes and they had to be recovered.
- [112:25]
Paul Saladino
There's a crazy story about this one.
- [112:27]
Nick Norwitz
Yeah. Malcolm Gladwell, you shared a post.
- [112:29]
Paul Saladino
Malcolm Gladwell did a, did a podcast about this on his revisionist history called the Basement Tapes. The history of this is that Ansel Keys, so who is kind of an infamous researcher. Yeah, I didn't mean to interrupt you, Nick, but I'll just add this and then I'll let you run with it again. Infamous research in the 1950s and 1960s was one of the primary authors of this paper and he and the main author did not publish the results for many, many years. And then Chris Ramsden, who's done a lot of interesting work in the space that we can talk about some other stuff that he's done, actually found the information in a one of these primary authors basements and redid the analysis many years later, 16 years later, I think. So that, that, I mean, Ansel Keys.
- [113:10]
Danny
That's this stuff.
- [113:11]
Paul Saladino
That's this study.
- [113:12]
Danny
Wow.
- [113:13]
Paul Saladino
Yeah. So it wasn't originally published, Ansel Keys obviously was in favor of the hypothesis that polyunsaturated fats were good for humans. He was kind of the beginning of this diet heart hypothesis and this didn't fit his results. So that it's possible that he wasn't happy about this. Who knows? Or they just got lost.
- [113:30]
Nick Norwitz
Yeah. So I, I again compare back to. It's interesting framing. Is it possibly suppressed? Maybe. I don't even know that that's a functional way to look at it. So we can talk a little bit more about the study and the criticisms of it. Steve, can you go copy the PubMed ID in Paul's tweet and then go to Figure 6 in the paper. It's going to become relevant in a second. But high level the criticisms as I understand them because again, there is no perfect study. It's been being talked about recently because I think Mark Hyman did a pretty viral reel on it where like you said in the other trials there was more trans fat in one group. It's being argued that the higher trans fat diet was the corn oil diet and that that accounted for the effect. And also about 3/4 of the patients dropped out of the trial.
- [114:20]
Paul Saladino
It's complicated.
- [114:21]
Nick Norwitz
My two cents on this is, okay, first of all, I don't know how much the trans fat difference between the groups actually was, if at all. It's interesting, Ramsden, and it'll actually talk about this in the paper. They talk about how Ancel keys new trans fats elevated saturated fat so would have designed the diet elevated ldl.
- [114:42]
Paul Saladino
Trans fats.
- [114:43]
Nick Norwitz
Elevated ldl, elevated ldl. So it would have been designed in a way to potentially minimize the trans fats. It's all speculative as to whether there was actually a difference in trans fats and what that difference will be. Now, even if there was a difference, I really find it unlikely that it drove.
- [114:59]
Paul Saladino
You might go to my screen, Steve.
- [115:01]
Nick Norwitz
Oh yeah, I have that.
- [115:02]
Paul Saladino
And you want figure I was going.
- [115:04]
Nick Norwitz
To show six in the panel on the bottom left. You'll know what I mean when I say it. Show it. I don't think that the trans fat difference, even if it exists, would drive the full effect. It's possible.
- [115:17]
Paul Saladino
Figure five or figure six.
- [115:18]
Nick Norwitz
Six.
- [115:18]
Paul Saladino
Okay.
- [115:20]
Nick Norwitz
You know, and then the other thing with the attrition, because this keeps on coming up, it's very easy to try to discredit studies like this by saying, oh, they lost 75% of their participants. But when you think about how it was constructed, the only way you get this sort of control is like hospitalized patients and guess what? Patients get discharged. So they selected to do the analysis on patients who had been in the study over a year and three quarters or more or less got discharged from the hospital. But there's no reason. And I was talking with another scientist about this study and I was making the point like, do you have any reason to believe that would actually bias the results? They still had over 2,000 people. Yes, the N value decreased, but I don't see any reason why the attrition would lead to bias. So I don't think that can account for the findings. So how do you account for findings? Like, are we seeing Paul's screen? If you go down to the. Scroll down a tiny bit, Paul, like the bottom left, you can read the caption. Death from any cause and change in cholesterol in the cohorts receiving the diets for one year or more. And what do you see? Like, there's actually a pretty clear dose response from cholesterol lowering and probability of death. That's what it's saying. The more right to you go, the lower the cholesterol drops as a result of the intervention and the higher the probability of death.
- [116:31]
Paul Saladino
The lower the cholesterol goes, the more people die.
- [116:33]
Nick Norwitz
And again, it's really important to be clear about what claims I am making and what claims I'm rebutting or not making. So I'm not saying Omega 6 linoleic acid kills. I'm not making that claim. What I'm saying, and actually if you read the Ramsden paper, they more or less make this point is this is highly inconsistent with the current diet heart hypothesis and that we need to be more humble about our knowledge based on the evidence and not make sweeping recommendations like chop saturated fat, increase unsaturated fat and LDL is bad, and if you lower it, it's good. It's again, the idea of the myopic focus on ldl, it's rebutting a claim, not necessarily making the extreme opposite claim. And I think that's super important.
- [117:26]
Paul Saladino
I mean these might be interesting.
- [117:28]
Danny
The higher the cholesterol, the, the lower the mortality rate.
- [117:32]
Paul Saladino
The as the cholesterol dropped, more people died. So as people in the. We talked about this earlier. As people got the seed oil group, they they cholesterol drops. When you give people polyunsaturated fats, you're. You will lower the ldl. We can talk about the potential mechanisms there. And so in the Minnesota coronary experiment, and these are the Kaplan Meyer survival curve we can talk about as well.
- [117:53]
Danny
Okay.
- [117:53]
Paul Saladino
Um, in the Minnesota coronary experiment, the people that had the highest degree of cholesterol lowering had the highest increased rate of death. Right, the most increased rate of death. And what Nick is saying is that this is in contradistinction to the mainstream recommendations that cholesterol lowering is always good. And this is why Minnesota has been talked about so much. It's the largest trial that we have. It was very rigorously conducted. Again, Ansel Keys, a proponent of the diet heart hypothesis, was one of the key investigators here. It was double blinded. So what that means is that the patients nor the doctors knew what was in these burger patties that they got. This is like the equivalent of beyond beef. In the 1950s and 60s, some people got burger patties that were enriched in corn oil, and some people got burger patties that were enriched in other saturated fat rich margarines. As Nick has pointed out, both groups probably got trans fats. And one of the criticisms of this study has been, well, did the experimental group get more trans fats? And then as Nick and I, I believe, are both arguing, what we know about trans fat is they raise ldl. Right. And in the experimental group, the LDL tended to go down.
- [118:56]
Danny
Right.
- [118:57]
Paul Saladino
So if the amount of trans fat in the experimental group were significant enough to skew the results, then why did the LDL go down so much in the experimental group? And why was it that the more the LDL went down, the higher there was the incidence of death?
- [119:12]
Nick Norwitz
Right.
- [119:12]
Paul Saladino
So you're, you're having worse outcomes, essentially, like it's trending toward worse outcomes when you give people more seed oils, potentially, which is different than what the experimenters expected.
- [119:22]
Nick Norwitz
Yeah. I think it's just a matter of even if, even if people are like, okay, well, there's a very potent specific trans fat that account for the effect. What I'm trying to say, and I think Paul's trying to say the same thing, is. Yeah, but practically in the zeitgeist and in medicine today, we still myopically focus on the biomarker ldl. Stuff like this proves that is a mistake. Even if there are other factors. I'm not actually attributing increased death to the change in ldl. I'm not. But it reinforces that the dogmatic blanket statements, reduce saturated fat, increase poly, get your LDL down, they're problematic. And you hear this again and again, these platitudes, lower is better with respect to LDL and Applebee. And it's like, well, lower is better with respect to what? Just cardiovascular risk. How did you lower it? What were the other effects of the interventions? Are you looking at other factors beyond just cardiovascular risk? There's so much context. And the reason people get pissed off is because even if you can't understand all the nuances of delta 6 desaturase 12, 13 dihomy, yada, yada, yada, people can tell when they're being patronized to. And I think what modern medicine has a problem with now is dumbing it down way too far right? And speaking down to people like, oh, lower is better. Don't worry about the details. We got that. And then we just end up speaking past each other. So it's important to entertain studies like this because they do have relevance to what recommendations we make. And I want to tap upon. Harvard School of Public Health did a rebuttal to it. Actually, one of the people said in the rebuttal is someone I'm, I'm quite close with and think, on balance, highly of. But they call the study an interesting historical footnote that has no relevance to current dietary recommendations. There's some interesting patterns in this rebuttal. I can send it to you, we can link it in the notes. But a few interesting things that I want to point out to dietary recommendations.
- [121:24]
Danny
Whose dietary recommendations.
- [121:25]
Nick Norwitz
It says no relevance. But the way they go about rebutting it again is like, it's interesting to see how when contradictory evidence comes up, people tend to divert. So they talk about, oh, well, omega 3s are important. I'm like, well, yeah, but I don't think that changed much from the study. And that's kind of like off point anyway. Or. And this was funny, I'm trying to find the exact line. Basically they say, well, in this study where people were eating 13.8% linoleic acid. Oh, yeah, here. The diet used in the Minnesota coronary experiment was never consumed by any appreciable number of Americans. And the level of linoleic acid was well above the range recommended by the American Heart association or any other group. So it sounds when you read that like a concession that too much linoleic acid could be bad. But it's, it's a diversion of what the, what the words actually mean is there is an RDA or like a target. So say, like, for vitamin D, I think it's 800 international units. Would you want to go that or above. The way it's reading here is like, well, we can disregard the study because they were eating so much linoleic acid. But have you ever heard any, like, media outlet that is associated with conventional medicine or doctor or guidelines say hey, don't get more than this much linoleic acid.
- [122:43]
Paul Saladino
But if you look at it, you're right. And if you look at it, I mean most Americans are eating that exactly that amount of linoleic acid today. 10 to 15% is the average linoleic acid in most of our diets today. So for Walter will it to say that 13 was far in excess of what is recommended or what is achieved by Americans. Like he's a little bit out of touch because it doesn't take much to get 13. I mean remember that fat traditionally is 9 calories per gram. And so if you're eating salad dressing with seed oils and you're going to McDonald's for fries or eating some processed food during the day and or even if you're going to Chipotle where they're cooking the chicken and the rice in seed oils, I mean they're pervasive.
- [123:16]
Danny
I saw that video you did.
- [123:17]
Paul Saladino
They're pervasive. Right. It's pretty easy to get 10 plus percent of your calories from linoleic acid. So it's an interesting criticism, but yeah, and as Nick is saying, I mean we certainly don't hear from the American Heart association like don't get more than 10 of your of your calories from the. It's totally false. What will it is saying here in distinction? They definitely tell you to limit your saturated fat.
- [123:38]
Nick Norwitz
Right. And so it's a matter of like double standards. I really like I read it before, but I'm going to read it again. How this paper ends, Ramsden at all say, given the limitations of current evidence, the best approach might be one of humility, highlighting the limitations of current knowledge. They don't say this but with respect to linoleic acid, omega 6 and saturated fat and setting a high bar for advising intakes beyond what we can provided by natural diets. So basically they boil it down to. And I love to get into the weeds but like you know, if you're eating this is how I read it, like steak, eggs, walnuts, whole foods. It's probably the most pragmatic approach.
- [124:14]
Danny
Right.
- [124:14]
Nick Norwitz
In the absence of high quality evidence saying, you know, these foods are bad and when I say these foods, I mean foods naturally rich in these components because yeah, like steak and butter get vilified based on much weaker evidence in my opinion than like this study.
- [124:32]
Paul Saladino
Oh well, we can talk about it but you know, I don't want to get, I want to finish talking about seed oils. But the evidence that Saturated fat is harmful for humans. Is. Is weak. We can. I mean, weaker than that. It's extremely weak. And you know, there's lots of evidence this is just a Kaplan Meier curve. So you can see on the bottom right, the red dotted line is the. The experimental group, and the blue dotted line is the control group. And you know, the bottom right is women over age. Actually all. All participants over age 65. You can see a large divergence there. And what you see is that the, the over age 65, the people who were getting the experimental diet that was rich in the seed oils, corn oil, in this case, had a much quicker death.
- [125:12]
Nick Norwitz
Right.
- [125:12]
Paul Saladino
So in a Kaplan Meier curve, or maybe I mixed them up.
- [125:16]
Nick Norwitz
You're right. So. So lower survival if the. The red line is lower than the blue line.
- [125:20]
Paul Saladino
Yeah.
- [125:20]
Nick Norwitz
In the over 65 group. And so I don't.
- [125:23]
Paul Saladino
The diet group is the blue line. I'm sorry. So that it's in this way, it's going up. So the people, the cumulative proportion of death, they. They kind of reversed it. The cumulative proportion of death. The blue line is the experimental group. The red line is the control group.
- [125:33]
Danny
Experimental group, meaning what?
- [125:35]
Paul Saladino
The seed oils. So the seed oil group was dying faster. You can see how much that blue line diverges from the red line in the bottom right at. Especially starting at 400 days, by 450, 500 days. So right here you see this clear divergence. And yes, it pretty much you can see that the experimental group, the blue line, is, is making up a larger cumulative proportion of the deaths than the experimental group getting the higher saturated fat. So this is, it's interesting, right? And this diverges from the mainstream guidelines at the time. And this is just one randomized controlled trial. We can look at some other ones. But this is what's tricky about the data. The RCT data on cereals versus saturated fat, as I said in the beginning, it's all done 30 to 40 years ago at best. Uh, none of it's perfect. If you look at the best trials, in my opinion, I would argue they show things like this and this trials that show different results. You have pretty major fatal flaws in the design of the study. This is what we're dealing with, though, and I think it's why, hopefully we'll get into this in a moment. We can also kind of step back, maybe look at some animal data and look at some mechanisms to try and guide us. And why I, I did kind of want to frame it for people from a historical perspective, because I think ultimately what we're dealing with here is the question. There are two major questions maybe to this podcast. Do I have to worry about my elevated ldl and should I be eating butter? I'm oversimplifying this obviously. Should I be eating butter or should I be eating soybean oil? What do I do to be healthy?
- [126:55]
Danny
Got it. Now, what is your current LDL?
- [126:59]
Nick Norwitz
Is it still in the 500 check was 574.
- [127:01]
Danny
574. And you're letting it ride at 574?
- [127:04]
Nick Norwitz
I'm monitoring my. Your cardiovascular health by coronary CT anger.
- [127:10]
Danny
Right. Right.
- [127:11]
Nick Norwitz
Last check, it was 00. I might also have. You know, there's a lot of context around this, including family history. My mom is actually in a similar boat, but she's 60. So her LDL, funnily enough, she probably has some sprinkling of a congenitally high ldl. So she's always had ildl, but then she went keto and it went to like the well into the four hundreds. So she's and given permission me to talk about this. And by the way, she's an MD. PhD as well. So like I'm not really. Yeah. So she can make her own medical decisions. But we ended up talking about like, well, what should she do? Her lifetime exposure to LDL and APOB is astronomical. Got a coronary CT angiography.
- [127:51]
Danny
000.
- [127:52]
Nick Norwitz
65. 60.
- [127:54]
Paul Saladino
So yeah. How can LDL be causal?
- [127:55]
Nick Norwitz
Right.
- [127:56]
Paul Saladino
Again, we're getting back.
- [127:57]
Nick Norwitz
It's, it's. There are better things to look at now than LDL and LDL I don't think should ever be looked at in isolation.
- [128:05]
Paul Saladino
Does she know her fasting insulin? It's low, presumably.
- [128:08]
Nick Norwitz
Yeah, I've seen. It's probably like three years.
- [128:10]
Paul Saladino
She's metabolically healthy.
- [128:11]
Nick Norwitz
She's very metabolically healthy.
- [128:12]
Paul Saladino
Phenotypically or by blood work.
- [128:14]
Nick Norwitz
Yeah, yeah, yeah. She looks like she's like 40.
- [128:17]
Paul Saladino
Yeah. Right.
- [128:18]
Danny
What do you think the ultimate cause? I know there's probably multiple causes, but what do you think the ultimate cause is? Why so many people are obese in America.
- [128:25]
Paul Saladino
This is the big question.
- [128:26]
Nick Norwitz
So. So actually this is a good, good place to talk about mechanisms. Do you think seed oils can cause obesity? And if so, how?
- [128:34]
Paul Saladino
Okay, so let me pull up another study that I found this one in preparation for this podcast. I think you guys will find this interesting. So there are a couple of things here could.
- [128:47]
Danny
Endocannabinoids.
- [128:48]
Paul Saladino
Yeah. So this one is interesting. This is a trial from 2020 and it looked at levels of 2Ag and Anandamide. These are endocannabinoids similar to cannabinoids that you would get from, like, marijuana in 183 obese females from Iran. And what they found was that there were three major dietary patterns, Western, healthy, and traditional. And the women, the obese women who had the Western dietary pattern had higher levels of 2 Ag and AEA. The reason this is interesting to me is because these can affect appetite and satiety in a negative way. Right. So you get the munchies from smoking weed.
- [129:30]
Nick Norwitz
Right.
- [129:31]
Paul Saladino
And conversely, there's a drug called Ramonabant, which is a CB1 antagonist. So cannabinoid receptor 1 antagonist is Ramona Bant. Ramona Bant works very well to reverse cardiovascular disease in trials. It reverses obesity in many ways. It. It minimizes appetite in a lot of ways. From a psychiatric level, it creates suicidality.
- [129:56]
Danny
Oh.
- [129:57]
Paul Saladino
So it. It's off the market in the United States. But when you block the CB1 receptor mechanistically with Ramona Band, you get positive metabolic outcomes. So it's interesting to me that in obese women who eat a Western dietary pattern, which of course encompasses many, many things, but will include seed oils, also processed grains, processed sugars.
- [130:18]
Danny
Right.
- [130:18]
Paul Saladino
They do. That does correlate with higher levels of endogenous cannabinoids. 2Ag and AEA. 2Ag and AEA are some of the breakdown downstream products from arachidonic acid, from linoleic acid. So it's possible, right, that in predisposed individuals, potentially individuals who have polymorphisms in D6D. Right. So fatty acid desaturates, too, or who are predisposed. Is it possible that consuming linoleic acid or Western foods increases the production of two AG and aea, leading to appetite dysregulation? It certainly happens in animal models. If you give mice or rats linoleic acid, you see levels of 2 Ag and AEA rise. I can show you that study, too. No one's actually done that study in humans. Nobody. Nobody has looked at levels of 2 Ag and AEA in humans when they give linoleic acid. But it's interesting that in obese females with a Western dietary pattern, you can correlate that with higher levels of these. So this is just one putative mechanism by which seed oils may affect satiety.
- [131:23]
Danny
Interesting.
- [131:24]
Paul Saladino
But when we're looking at. I'll say this, and then I'll pause Nick, and let you add whatever you want. When we're looking at obesity, I think that appetite and satiety are key, Right. Because, yeah, you probably know this Danny, it's. It's pretty hard to overeat unprocessed food. Like when you're eating steak and squash, you just get full.
- [131:44]
Danny
Yes.
- [131:45]
Paul Saladino
And you're kind of done.
- [131:46]
Danny
Right.
- [131:46]
Paul Saladino
But something different happens when you add a potato chip or whatever.
- [131:50]
Danny
Like, it's like you can't stop.
- [131:51]
Paul Saladino
It's like crack, a Coca Cola. Right. Something. And this may tie into leptin and fat and the hypothalamus. And Nick can talk to that as well if he wants. But, like, there is some saboteur to our satiety, I believe, within our food supply. Right. It's not. Nick said he doesn't believe it's calories that are making us obese. And I would agree with that. My take on that is it's the quality of the food you eat, not the amount of calories you eat. Because I sort of feel, and this is again just my perspective, that if you are eating generally high quality, unprocessed food, you will become a predominantly healthy human and your satiety mechanisms will be intact and you will be unlikely to overeat. If I put a gun to your head and force you to overeat, I could. Right. But generally speaking, in a free living human, you're not going to overeat. Steak, potato. Right, Right. Unprocessed food, you're going to overeat. Chips, Tostitos, Takis, brownies, Coca Cola. So there's something going on with satiety. So when I saw this, I was like, that's really interesting. Is it possible, again, just a possible putative mechanism that some people are more predisposed to this. Western dietary patterns affect the levels of these endogenous cannabinoids and make us hungrier. There are lots of other potential mechanisms by which seed oils may affect obesity, but that's just one of them that I thought was cool.
- [133:08]
Nick Norwitz
I think it's an interesting hypothesis. I want to you you would agree. I don't mean this to be offensive, but that is stretching, do you think?
- [133:18]
Paul Saladino
Well, I mean, you see higher levels of these in women with a Western dietary pattern. In animal models, giving linoleic acid leads to higher levels of 2 Ag and AEA. I think every piece is there in. In. In studies where the levels of linoleic acid are decreased. You can see these also go down.
- [133:38]
Nick Norwitz
Let me phrase this a different.
- [133:39]
Paul Saladino
When people lose weight, these go down.
- [133:42]
Nick Norwitz
Let me put it a different way then. Even if this is part of the puzzle, what percentage would you attribute the obesity epidemic to this mechanism? And then seed oils in general, who knows?
- [133:54]
Paul Saladino
Who knows? It's impossible to. I can't tease that out. Right. Because seed oils most of the time co. Occur with other things. Right. So broadly speaking, I think that we can take a step back and say we can all probably agree that a western dietary pattern is harmful for humans. A western dietary pattern is essentially, you can think of the, the epitome like a piece of, like a processed sweet roll of bread. Right. It's processed flour, processed sugar, processed seed oils, potentially some dyes, some dough conditioners, and some preservatives. We know that that is a metabolic nightmare for humans. And so if we try and tease it out, it's difficult to do that.
- [134:34]
Nick Norwitz
Right.
- [134:34]
Paul Saladino
We have these randomized controlled trials where we're looking at saturated fats versus seed oils specifically. But I think it's, it's, it's impossible for me to attribute specifically to seed oils. I think that when I look at the evidence on balance, seed oils look to be harmful for me. Okay. Yeah.
- [134:51]
Nick Norwitz
I want to ask a few. This is really helpful. I think people are going to appreciate hearing this from you, give a big following, a lot of clout that's easy to name. So I'm going to ask you some. Like, on a scale of 0 to 10, how confident are you. Okay, so on a scale of 0 to 10, how confident are you that linoleic acid can cause obesity in humans?
- [135:13]
Paul Saladino
Now, obesity wouldn't be the, the first outcome that I would think of. When I think of linoleic acid. The thing I'm most concerned about are the two things I'm most concerned about are propensity for LDL oxidation and incident coronary artery disease.
- [135:29]
Nick Norwitz
Okay.
- [135:30]
Paul Saladino
And downstream effects of ox lambs. And so, and then obesity is just more complex.
- [135:37]
Nick Norwitz
All right, so we'll start with negative downstream effects on LDL oxidation and production of ox lambs. 0 to 10. How confident?
- [135:44]
Paul Saladino
Those are two different outcomes.
- [135:46]
Nick Norwitz
Oxidation of LDL?
- [135:47]
Paul Saladino
Pretty confident. There's more. 8 to 9. Multiple randomized controlled trials showing that more linoleic acid leads to higher levels of oxidation of ldl.
- [135:56]
Nick Norwitz
And how about obesity? Out of curiosity. And if it's a 2, then say 2.
- [135:59]
Paul Saladino
Obesity is such a, it's just such a complicated thing. Right. So is your question, what contribution to obesity do seed oils have or omega 6?
- [136:07]
Nick Norwitz
And then I'm going to ask about seed oils. Those are two different questions.
- [136:09]
Paul Saladino
Oh, okay. So you're asking about Omega 6.
- [136:11]
Nick Norwitz
Omega 6?
- [136:11]
Paul Saladino
Well, I guess I don't know that we can necessarily differentiate those because Omega 6 don't occur. Like, are you talking about like, walnuts? Yeah, I don't think, I don't think walnuts cause obesity.
- [136:22]
Nick Norwitz
But, but to be clear, like, three ounces of walnuts is something like 31, 32,000 milligrams of omega 6. It is. More is. There's a ton of omega 6.
- [136:33]
Paul Saladino
Let's, let's check that.
- [136:34]
Nick Norwitz
Yeah. Steve, you want to check how much Omega 6 is in an ounce of walnuts? I think it's something like 10,000 plus milligrams.
- [136:42]
Paul Saladino
Well, that's less than a tablespoon, but. Okay. I mean, you know, well, well, if we're talking grams.
- [136:48]
Nick Norwitz
Right. Okay, 10 grams.
- [136:49]
Paul Saladino
10 grams? Yeah. Yeah.
- [136:51]
Nick Norwitz
Of just linoleic acid.
- [136:53]
Paul Saladino
Yeah.
- [136:53]
Danny
An ounce of walnuts contains roughly 10.8 grams of omega 6 fatty acids.
- [136:59]
Nick Norwitz
Sure. Okay, so. And, and I think I understand your position on this, but I don't think most people do. This is why I'm asking the question, not to be a dick, you know.
- [137:08]
Danny
It also contains 2.5 grams of omega 3s.
- [137:11]
Nick Norwitz
AoA. But okay, so, so, you know, if somebody were to consume 4 ounces of walnuts, that's like, you know, on the order of 43, 44 grams of just linoleic acid.
- [137:25]
Paul Saladino
Right.
- [137:26]
Nick Norwitz
So that's going to be, you know, multiple. Like they're almost 400 calories from just linoleic acid. You're on 2000 calorie diet. That is 20% of your calories from linoleic acid. So could 4 ounces of walnuts be bad for you? Cause obesity?
- [137:40]
Paul Saladino
I think it depends on the context. Yeah. I think that in general, if we're talking about walnuts specifically, maybe you're like.
- [137:46]
Nick Norwitz
You'Re, you're a very unconfident. This is interesting. Maybe, but we, we don't know.
- [137:50]
Paul Saladino
Yeah, we don't know.
- [137:51]
Nick Norwitz
Okay. I think that's a useful to hear now and again.
- [137:54]
Paul Saladino
Like, the walnuts conversation is very different than the seed oil conversation.
- [137:57]
Nick Norwitz
I agree, but I. The reason I'm asking these questions so explicitly again, not just to give you a hard time, but because I really, I think we understand the distinction in our minds. I just don't think it gets discussed. Like, I have literally the, the degree of domino chain logic group that you see is like, okay, highly oxidized processed seed oils are bad. Then it's Omega 6 are all bad. Then it's polyunsaturated fats. They're unfrag, they're fragile, and they're bad for you. I have literally had me say that, like, Quest has People tell me that Quest candy bars, non ironically, are healthier than sardines because they're high in PUFA and it's just like.
- [138:34]
Paul Saladino
But sardines are high in PUFA or Quest candy bars are high in PUFA.
- [138:37]
Nick Norwitz
Sardines, they have Omega 3. So like. Oh, well, I'm just, I'm just saying that is at the extreme end of the interpretation.
- [138:42]
Paul Saladino
Sure.
- [138:43]
Nick Norwitz
But triage point one, if people get nothing out of it is linoleic acid. Omega 6 in whole food is very different than the heated processed stuff. Right.
- [138:55]
Paul Saladino
It's certainly going to occur with many other cofactors, vitamin, et cetera.
- [139:00]
Nick Norwitz
Right, right. But also there's going to be just to complete the picture on what happens once it's in the body, even aside from outside. You mentioned obesity. One thing I think is really interesting as a hypothesis is could a certain metabolic state, let's call it obesity, make you more susceptible to omega 6? So you talked about LDL oxidation, one enzyme and a biomarker. You can go, you can go to Quest or LabCorp and get this measured. It's called myeloperoxidase. MPO. Myeloperoxidase is really interesting because it increases cardiovascular risk in several ways. One way is increasing the oxidation of LDL from within the vessels. Interestingly, it's produced by fat actually around blood vessels called perivascular adipose tissue. It decreases fat browning and decreases energy expenditure, at least in animals, and then decreases adiponectin, which is. Adiponectin is kind of like a yoga class for your arteries. So basically this fat produced hormone that does go up in obesity makes blood vessels stiffer, oxidizes ldl. So just the oxidation effect. If you have an environment where you're more susceptible to oxidation, have higher levels of this enzyme because you have more fat tissue secreting it, you might be more susceptible to damage from quote, unquote excess omega 6 versus say you're lean, healthy, on a ketogenic diet. Linoleic acid is incredibly ketogenic. Turns into. I can boost my ketone levels with sesame oil over 20 hours to like 6 millimoles.
- [140:24]
Paul Saladino
Yeah. Whether that has any clinical relevance is questionable.
- [140:27]
Nick Norwitz
The point is whether we're talking about 12, you know, 13 dihomy, I guess we're calling it oxidation by myeloproxidase. Generation of for Hne turning into ketones. This biomolecule has so many paths.
- [140:41]
Paul Saladino
Sure. Linoleic acids can go a lot of different places.
- [140:43]
Nick Norwitz
And the metabolic moleu, your metabolic status influences how you partition. I mean how you partition everything, how you partition calories, how you partition linoleic acid into different biomolecules. So I emphasize this because I want people to be thoughtful, just like applying it to their own life. What food are we talking about and what is my metabolic status? If you have pre existing obesity and you're eating a mixed macronutrient diet, maybe you shouldn't be cooking. I would think you shouldn't be cooking with corn. I can agree with you on that. Your lean healthy keto are, you know, 2 ounces of walnuts bad for you? I don't think so.
- [141:15]
Paul Saladino
I don't think so. Yeah, I mean it's a different situation.
- [141:17]
Nick Norwitz
Oh, I agree. And I just, I think that's really. Those are extreme examples.
- [141:21]
Paul Saladino
Yeah.
- [141:21]
Nick Norwitz
But they highlight a very important point.
- [141:24]
Paul Saladino
Yeah. I think what most of what I think is important about this conversation is the oxidized. Well, presumably oxidized refined bleach and deodorized seed oils.
- [141:32]
Nick Norwitz
Okay, so I want to ask you now refined, bleached and deodorized. Big $10 scary words. Specifically what's going on that you're concerned about in that. The refining. That's the heating oxidation. We can table that. That's obvious. Refining, bleaching, deodorizing. What specifically in that chemical process is increasing risk.
- [141:53]
Danny
What is the. Isn't there something called hexane or something?
- [141:56]
Paul Saladino
There is hexane. Yeah. Yeah, you can measure it.
- [141:58]
Nick Norwitz
Neurotoxic benzene also hexane is neurotoxic, but again it's a question of.
- [142:02]
Danny
And hexane comes off of when you do the bleach and the, and the oxidizing of these oils.
- [142:06]
Nick Norwitz
It's used to extract the oil from something where. Right, right, right. You can imagine it's hard to extract oil from corn. So it's used to like, you know, separate out the oil and then they try to remove the hexane. But some residual remains. I tried to look for how much residual remains and it does vary. I think it was like one study out of Iran or something like that, I found. But my question is again, this comes down to what do we know and what do we don't know. The fact that there is something that has neurotoxic potential used to treat food I think is eh. That concerns me. But that's very different from someone saying seed oils contain neurotoxins and implying that there's actually seed oil associated neurotoxicity, which it's hard because you wouldn't go off of like what is required to cause acute toxicity. It's like you're gonna have a tablespoon of corn oil and get neurotoxicity. So there's the argument of like, well, small cumulative doses are problematic. It's a reasonable hypothesis. The thing is, I don't think we'll ever really know know.
- [143:13]
Paul Saladino
There have been studies on this. Um, Steve, will you show my screen real quick? So we have, I mean, this is a study on the estimated of trace amounts of benzene and solvent extracted vegetable oils and seed oil cakes. I mean all, all seed oils are solvent extracted. So again, they're talking vegetable oils versus seed oils. But you can look in here and you can see if you read the paper that there are often trace amounts of benzene, which is a known carcinogen in, in seed oils. There are other potential contaminants also. So we have studies looking at go.
- [143:47]
Nick Norwitz
Crolian is one.
- [143:49]
Paul Saladino
Acroline is, is one. That's when you heat the oil. You can look at the presence of heavy metals and vegetable oils. That's been looked at. Now I mentioned this early in the podcast. Antimony is probably the biggest issue. Its migration from the polyethylene containers. Vegetable, edible vegetable oils. And then the third one to consider is that the vegetable oils are actually quite high in phalates. We haven't talked about this at all. Phthalates are endocrine disrupting sort of dates.
- [144:20]
Danny
Are in vegetable oils.
- [144:21]
Paul Saladino
Yeah. And this is, they say it in the title, non negligible exposure source to humans.
- [144:25]
Danny
Wow.
- [144:26]
Paul Saladino
And they actually give a, a, a relative amount here in this paper. They do the calculated average estrogenic equivalence of several major phthalates in edible oils. It falls into the range of 2.7 to 958.1 nanograms of estradiol per liter, 45 to 396 times those in bottled water. So this is a non, non negligible amount of estrogenic equivalence from these phthalates. I mean, you know, we're talking like there is a massive exposure to humans today cumulatively to these phthalates. So if I've never heard many people talk about this in seed oils and whether this is coming from the processing or the storage in the plastic containers. You could solve this by putting a soybean oil into a glass container. But that's never going to happen. Right. Most of these oils are in these polyethylene plastic containers on the shelf for many times. Times for many, many months. Yeah.
- [145:24]
Danny
It's interesting. I wasn't aware of buying the oils in glass. I knew glass bottles would probably be better, but I didn't. I wasn't aware of the importance of having a glass bottle that doesn't have exposure to UV light. The UV light has some sort of effect on, on the oil in the bottle.
- [145:40]
Paul Saladino
It's part of the oxidation process. Light, light, heat and oxygen are part of this, this process that breaks down the oils. Yeah. There's another study that I can find in a moment that actually looks, looked at the peroxide value in omega 3 and omega 6 oils and they might have looked at acrolein or other breakdown products. I know we talked about a study, Nick, where they heated oil. Right. And this is interesting. So you can take. We discussed this earlier in the podcast. Again, we're differentiating this from a handful of walnuts in, in function here. In practice, you don't put walnuts into a deep fryer, but you put soybean oil into a deep fryer. If you go to five guys, if you go to in and out, if you go to McDonald's, if you go anywhere, I've asked them what's in their fryer. It's usually some mix of soybean oil, corn and canola oils.
- [146:24]
Danny
And they change the oil once a.
- [146:26]
Paul Saladino
Month, once a week, probably, which is pretty crazy when you think about you're going 24 hours or, you know, 16 hours a day in the, in the fryer oil.
- [146:33]
Danny
Yeah.
- [146:33]
Nick Norwitz
I just texted you the graph. Your computer's hooked up. You can pull it up.
- [146:37]
Paul Saladino
Yeah, well, if you look at what's in. So, um, some of these oils, these, these are the aldehydes and, and some of these aldehydes are. They're quite high with heating. There's another graph in, in the paper or where they talk about the amount of specific aldehydes and acroline. Specifically, the amount of acroline in a large French fry at McDonald's is equivalent to the amount of acroline in a pack of cigarettes. Now, this is just one compound. And when I've said this in the past in my content, people like to say Paul Saladino is saying that seed oils are worse than cigarettes, which is not what I just said. People can rewatch the tape, but it's, it's basically saying that of this one compound, which is a carcinogen, which is very likely. It is, is pretty significant. So this is a quote from there. 154 gram potato chip Alda serving Aldehyde Contents are not dissimilar to those arising from a daily allocation of 25 tobacco cigarettes. So this is what we're talking. This is a specific use case of seed oils. Right. This is a heated fry. This is the, potentially the worst use case of seed oil.
- [147:47]
Danny
Right.
- [147:48]
Paul Saladino
That looks to be very bad, but at least in terms of that one compound. So there's, there's a, there's a spectrum here.
- [147:56]
Danny
So what about like steak and shake? Down the road they're advertising that they cook all their fries in tallow now.
- [148:01]
Paul Saladino
So my perspective is this doesn't solve the equation completely. If you actually, when you radiant to that one, they, they never solve this problem where the fries were pre soaked in seed oils, so they're cooking them in tallow. The tallow they're cooking them in has been altered. It's refined so it has less saturated fats and more monounsaturated fats so they can work with it more easily. So it's a, it's a liquid at room temperature. Tallow is not usually liquid. It in 73, 74 degrees. So the steak and shake tallow is a refined tallow that has more monounsaturated fats, less saturated fats just at a, at a clean. Just a simple organic chemistry equation like a peroxide value. The more unsaturated an oil is, the more quickly it's going to be damaged when you heat it. And so theoretically, if you had a higher saturated fat content, oil like a pure tallow, which is a refined, which is sort of a, an oil that is from beef fat.
- [148:57]
Nick Norwitz
Right.
- [148:57]
Paul Saladino
So people don't know tallow. It's a beef fat. Um, it's, it's solid, room temperature. If you were to heat that oil, it's going to have a lower degree of oxidation. Not zero, but a lower degree of oxidation relative to olive oil. Olive oil will have a higher degree of oxidation, you know, a lower degree of oxidation relative to a seed oil. Down, down the road we go, um, and so theoretically steak and shake cooking and their fries and tallow decreases the amount of things like this acrolein, these aldehydes. Yeah, somewhat. But I just think that for human health long term, look, we're all gonna, I've eaten french fries in my life. We're all gonna eat french fries. But if you have any significant amount of your diet that's from a deep fried food, no matter what it's cooked in, you're probably not optimizing.
- [149:39]
Danny
Yeah.
- [149:39]
Paul Saladino
And I don't think it completely absolves it. You can't just cook in tallow a deep fry, something in tallow and expect it to be right. Not have any oxidative liability in the human organism. So there's a lot.
- [149:49]
Danny
This is like we talked about. I mean this is just like one siloed part of this giant game of whack a mole that I feel like affects the human body. And like anecdotally I don't know what it is, but I'm sure you can attest to it. Like when you go to Costa Rica. I can go to Costa Rica for a couple weeks and just, I can eat pizzas, burgers, tacos, all the junk food they offer there. And I still feel way better than if I just eat something from, from Chipotle. Like if I eat a Chipotle burrito, I feel like I just ate a bag of concrete. But I can eat all the, all the garbage that they offer in Costa Rica and I still feel better than that. I don't know what that is about like how it's processed or about like the ingredients they used or what it is.
- [150:36]
Paul Saladino
Environment. Is this light or the environment, you know?
- [150:39]
Danny
Yeah. Is that part of it? And then like another part? Like I know, like, I don't know how legit it is, but I've heard that like Costa Rica is one of the countries that has the highest lifespan. It's like considered one of the blue zones or whatever.
- [150:52]
Paul Saladino
It's not true. It's not true. It's only the Nicoya Peninsula. The Blue Zones are kind of a myth.
- [150:56]
Danny
Yeah, okay. But like I, I don't know if it, maybe it's a myth, but I, I just always thought about that being like the people there, they don't live this rat race that people live in America. They just, most of people there, they wake up and they, they, they're just looking for waves, you know what I mean? They're enjoying the environment and they're not, they're not sitting in a cubicle all day in front of a screen trying to like optimize their return on investment for whatever the they're doing.
- [151:25]
Paul Saladino
There's something there. So I live, People may not know this, but I live in Costa Rica mostly full time now for the last four plus years. People in Costa Rica are pretty friendly. A lot of people work outdoors. They do some degree of moderate level activity in a outdoor context and family's a big deal. So these are all things that make a difference, purpose and these are all things that have been highlighted in the blue zones discussion. I think that the major failing of the blue zones paradigm is that the Blue Zones are Not prominently plant based. If you look at the blue zones, whether you're talking about Sardinia or Okinawa or you're talking about Iaria or you're talking about, I mean basically that's most of them. They, they eat significant amounts of meat. Meat is a central part of their diet. I mean there's a well known dish in Sardinia called Sarda pig Iaria, if anyone's been to that, that island in Greece. They, they're roasting lamb and other pig, you know, pigs on spits all the time. So to suggest that the blue zones are plant based is, is just falsification. But a good takeaway from the blue zones is. Yeah. Having moderate activity outdoors, not sitting in a cubicle, not looking at blue light all day, having family, having purpose. These things are valuable for humans and not inconsequential variables and different values, different overall value.
- [152:45]
Danny
They don't value earning a huge salary as we do in America.
- [152:50]
Paul Saladino
They don't. They take time off. And I know this because you see it, you know, these are very humble people. And when there is a holiday, everyone takes off. Yeah, right. They're not making any semblance of what we would make, you know, on a dollar per dollar basis in the United States. And they're on, they're taking every single day of vacation they can, they're spend there and they're spending, they're generally spending that time at the beach with their family.
- [153:15]
Nick Norwitz
Right.
- [153:16]
Paul Saladino
It's just, it's families on the beach all. At least where I live.
- [153:18]
Nick Norwitz
Right.
- [153:19]
Paul Saladino
And where you've visited it. These are coastal towns, but family is a big part of the ethos there. So these are, these are other pieces of the conversation that are not able to be ignored.
- [153:27]
Danny
Yeah, there's definitely so many pieces too. And I think. And doesn't. I know I've heard that UV light can also have a huge effect on things like cholesterol. Is that, is that right or is it vitamin D? Vitamin D levels can, if the sun exposure can lower things like Alzheimer's, cholesterol, heart disease, this kind of stuff. This kind of stuff.
- [153:51]
Nick Norwitz
I think there's a small effect of like infrared light on PCSK 9 and lowering LDL. I don't think it's going to be that tremendous though.
- [153:58]
Paul Saladino
I think when you're getting, when you're getting sunlight, you're doing a lot of things right. We know that sunlight affects sex hormones. Ultraviolet light has been associated with higher levels of testosterone in males. So that, that's been shown multiple times. UV light affects the gut microbiome actually increases diversity of the gut microbiome. Certainly from a circadian perspective, getting ultraviolet light is critical, and that is sort of the, the orchestration of all the hormones throughout the day. So there, there are many, many benefits to, I would say, full spectrum outdoor light with UV and IR and things you've talked about with other people in the podcast. I mean, yeah, you know, I had Tristan on my podcast too, and we talked about infrared. That was super fascinating to me that indoors you have no infrared light. Right. So are we as a species also deficient in infrared light? Because outdoors you're getting infrared. Does the infrared balance the uv? You have whole. I think of.
- [154:47]
Danny
He brought a big incandescent light bulb and he shined it in our faces during the podcast.
- [154:51]
Paul Saladino
Oh, yeah, like his chicken light.
- [154:53]
Danny
Like some people. Yeah, go. Go a little overboard with the stuff. I mean, maybe it's not overboard, but it's like, you know, you're bringing a light bulb with you everywhere you go.
- [155:01]
Nick Norwitz
It's like lived for all my teenage years in a room with giant iguanas that had a big heat lamp. Oh, yeah, that did my medical. I mean, that's why eating a standard American diet, I. Resistance awakening.
- [155:11]
Paul Saladino
It's a secret. Yeah, you think of, I think of sunlight.
- [155:15]
Nick Norwitz
I'm joking, everybody.
- [155:16]
Paul Saladino
I think of sunlight as like whole food, you know, and then indoor light is like processed food. They're very similar. You know, processed food has had certain components stripped away. We gave the example of the seed oils, the refining, the bleaching, the deodorization. Other processed foods are similar. And indoor light. I mean, these lights in here, right, this is blue light. It's flickering. It has no, it's not even the, the actual reproduction of the outdoor light light spectrum. It has no uv, has no ir. It's flickering. So there's. There's a lot of parallels there between. And people have done this, you know, far in advance of what I'm saying here. They've, you know, they've likened light to food in many ways. We talked about the light diet and things like this, and just the idea that the quality of light that you consume affects you in ways that are, that are not dissimilar from.
- [155:59]
Danny
Yeah, not just bio, you know, not just from like a biological perspective, but from a mental health perspective too. I think one of the best analogies I ever heard was Alexis Cowan explained, like, being inside all day in front of blue lights is the equivalent to orcas in a tank at Sea World.
- [156:18]
Nick Norwitz
So there's actually a study in nature, mental Health, day and night light exposure are associated with psychiatric disorders. It's an observational study in over 85,000 people. I'll just read from the abstract. Greater nighttime light exposure was associated with increased risk for major depressive disorder, general anxiety disorder, PTSD, psychosis, bipolar disorder and self harm behavior independent of nighttime light exposure. Greater daytime light exposure was associated with reduced risk of. And then all those terrible things. But did you. If you haven't, Paul, you'll love it. There was a paper out of Oxford in Nature on the mitochondrial origins of sleep pressure.
- [156:55]
Paul Saladino
I think I saw you talking about that.
- [156:56]
Nick Norwitz
Yeah, it was fascinating. So ironically, the first author happened to be at the department where I got my PhD at Oxford, so we ended up corresponding about this. But basically, why do we sleep? It's still kind of an open question, like why did we originally evolve to sleep? And this paper presents interesting data and I think rather compelling data that has to do with a mitochondrial dance.
- [157:16]
Danny
Is there any animal that doesn't sleep?
- [157:18]
Nick Norwitz
No, all animals. So this is very, very primordial. Basically like, you know, billions of years ago, one cell consumed another smaller cell. That smaller cell became our mitochondria. They developed a symbiotic relationship. Endosymbiosis, incidentally, actually might have to do with autoimmune disease. Another paper, another time. But mitochondria aren't just like static little engines, people say, powerhouse of the cell. They're not just like static. They, they dance together. And what I mean by that is they fuse together. Like different mitochondria will come and fuse together and then they will break apart. It's called fusion and fission. And this happens in cycles. So fusion helps with energetic efficiency, sharing components. Fission helps isolate out components for recycling. So damaged mitochondrial components. So like anything, biology, nature, they operate in cycles. And this fusion efficient cycle is really important and it corresponds with sleep. But really interestingly, what they were able to find in this study is you have to do this experiment in animals because you have to manipulate them. But you can change levels of the proteins that promote fusion efficient. So to bias the balance, fusion versus fission. And they could change sleep drive by altering the mitochondrial fusion, fission, balance. Long story short, like we think about the sun as the base of the food system, but I think it interacts with biology in so many more fundamental ways. As in like the light coming through the atmosphere at different times of day, which there's going to be different spectra go into your eyes, change mitochondrial dancing effectively in your brain. You know, the clinical implications of that can be intuited through like the study we just discussed about mental health. Now I don't have the exact domino chain of things that occur, but when we think about just how fundamental sun is to our biology, having studies showing that, you know, mitochondrial dynamics which interact with daytime light exposure can like literally change the dance of mitochondria, which can create like it's, it's not a clear picture, it's a complex, awe inspiring one. And I, that's always what I come back to. I said the other day when somebody left a comment, I forgot what the comment was. But like, I pity the people who can't be confused, odd and humble by physiology and metabolism. I find so much joy in life from like learning these things and be like, I don't fully see how this fits together. I like putting the puzzle together but it's never going to be complete. And that's what's so cool. And also just incidentally because we were talking about blue light in the newsletter I did on this, I looked at data separately on how blue light impacts mitochondrial fragmentation. So there's data. Paul actually just texted you a picture. Picture of. It was a mouse study you have to do in mice because you have to pluck their eyeballs out. But they showed that high blue light exposure caused mitochondrial fragmentation in the retina a little. The mitochondria fracturing apart. A giant boost in oxidative stress. So the red here on this image is oxidative stress.
- [160:14]
Danny
It's black.
- [160:15]
Nick Norwitz
Oh, there we go in the retina. So you can see blue light exposure. Way more oxidative stress.
- [160:19]
Danny
Wow.
- [160:19]
Nick Norwitz
And what ends up happening is if you check out the other picture, the, the retina thickness fins, that is, that's crazy. On the right, like the thinned retina from blue light exposure. And in humans there's like risks of things like age related.
- [160:31]
Danny
Well, it's crazy because there's a lot of big, there's a couple that I'm aware of, like big time video gamers, competitive video gamers who have, they played games but on the computer screen right in front of them and they've had retinal detachments and they've had to have surgeries because of that.
- [160:47]
Nick Norwitz
That's just like, that picture is just crazy to me. Like, and a mouse retina and a human retina and like, you know, chronobiology, it's pretty conserved.
- [160:56]
Danny
Yeah.
- [160:57]
Nick Norwitz
So this is not saying like you can't like watch a movie with your partner at night, but like get a.
- [161:04]
Danny
Big red light panel, blast it in your face while you're Watching the movie.
- [161:06]
Paul Saladino
The retina is a really interesting thing. I mean, there's. We can circle this back to seed oils if we want, or we can just leave that dead horse.
- [161:12]
Nick Norwitz
Well, because there's a lot of. There's a lot of just general oxidation in the retina. It's actually kind of a good model for different fatty acids. Yeah.
- [161:20]
Paul Saladino
And there's, there's very clear. Well, there's at least pretty strong associational evidence, I'll find. It's called the Blue Mountain study on the age related macular degeneration in seed oils. This is the Blue Mountains. I study evidence of protection against early AMD from eating fish. Greater consumption of omega 3 fatty acids, low intakes of foods rich in linoleic acid was protective for amd. Wow.
- [161:46]
Nick Norwitz
I mean, it's very physiologically possible combination of high blue light and things that it can oxidize.
- [161:52]
Paul Saladino
Yeah, the retina's. So that's, that's a, this is a great model system. I think that you have the blue light as an oxidant on a fragile tissue that is pretty close to being exposed to the environment. And then you see, at least this is again, just a, it's a, it's an observational study, but there was a pretty strong, pretty strong association here between lower consumption of linoleic acid and better outcomes and meaning less incidence of age related macular degeneration. That's striking. I mean, that, that makes sense mechanistically.
- [162:21]
Danny
Well, Jack Cruz told me a story, which was an anecdotal story on the podcast that somebody he knew who was older had to get cataract surgery. And I guess like six months leading up to his surgery, Jack told this gentleman to sit in front of his red light panel. He gave him a red light panel, told him to sit in front of it for an hour every day in like 20 minute increments. And he, the guy went in for his like pre op, like a week before the surgery and they like checked his eyes and they were like, you don't need cataract surgery anymore. Your eyes are fixed. And Jack attributes that to the red light, the cataracts.
- [162:56]
Paul Saladino
That's in the lens. So that's the front part of the eye. The retina is a little bit deeper.
- [162:59]
Danny
Maybe, maybe it wasn't.
- [163:01]
Paul Saladino
It's interesting.
- [163:01]
Danny
Maybe it was a different surgery.
- [163:02]
Paul Saladino
It probably was. Yeah, it's interesting. No, the red light and the cataracts is interesting.
- [163:05]
Danny
All the anecdotal stories are super interesting to me.
- [163:07]
Nick Norwitz
You know, it was funny. I was going through and Ranking the arguments for and against seed oils just out of. As an exercise and for something else I was doing, and I think an argument that often comes up is people talk about their N equals ones.
- [163:21]
Danny
Their what?
- [163:22]
Nick Norwitz
Their N equals ones, their anecdotes, their stories. Oh, like as in like I cut out seed oils or, you know, X, Y and Z and then this happened.
- [163:29]
Danny
Yeah.
- [163:29]
Nick Norwitz
There's a couple ways to rank that in terms of scientific rigor. Clearly it's not very strong. In terms of like, individual applicability, it's the strongest thing you can have. Mm. So I think we, we don't value it enough from a scientific perspective. It's great for hypothesis generation. Take Oreo versus Statin as an example. But at the individual level, it's like the way we have done science historically has been studying populations of heterogeneous humans. There's always a lot of cloud, a noise cloud of the data. And where you fall in it, you're not going to. Like when we plot out graphs we're looking at like Captain Meier survival curves, it's unlikely you're going to be right on the curve. You're going to be above or below it. And where you fall with respect to any given metric, you can only figure out by engaging in life as an N equals one experiment. Now, the more scientific training you have, the, you know, better resolution you can have and what conclusions you draw. But if someone makes a lifestyle intervention, say they quote, unquote, cut out seed oils, and then they say, I had this miraculous recovery from X, Y and Z, I'm inclined to give that more weight, actually a lot of weight in that individual context. And I think one problem we have is we all have our stories. So mine is ketogenic diet for ibd, yours is diet for eczema and other conditions. And I these form our interests and they're very valuable and individual level. And I think one area, one vulnerability that creates a lot of confusion is people get threatened by other people's stories or when their story doesn't match the data. Mm. And to me, that's so silly. Like, I kind of get it, it's confirmation bias. But at the same time, why should your story lose anything if a given paper or another person's journey is divergent? So if I say, and I believe this, I believe a ketogenic diet saved my life. If someone else does a low fat vegan diet and they get better results and they're healthier from where they were and they attribute their low fat vegan diet to their Improved health. I think generally there's an instinct to try to poke holes in that story and maybe there's a misattribution. I don't think it really matters. And the thing I love about metabolic health, and I hope we're unified on this, is in truth, it's approach agnostic, unlikely. If you're eating McDonald's and Oreos every day, you're going to be optimally, metabolically healthy. But like, if you get to a good place, that's awesome. And the what we've talked through here, I think what we've hopefully risen is a lot of curiosity and uncertainty because there's not like definitive answers for a lot of the questions we want to ask. And that's okay.
- [166:29]
Paul Saladino
I think the similarities of how people get there are interesting as well between divergent, you know, paths. Like, it's always been interesting for me, you know, cause I was a carnivore for a while, I was eating meat. And I've seen a lot of people improve autoimmune disease doing that. And there are many stories of people who improve autoimmune disease doing vegan diets. And so you think, okay, really? Yeah, yeah, definitely. I mean, some people's autoimmune conditions get worse on vegan diets, some people get worse things, but certainly people have improved ulcerative colitis doing vegan diets. And I think that there's the similarity that I see. There's, oh wow, they're cutting out processed food, right? That's great. That's super interesting. So there's, there's the similarity that we can kind of take away from that. Like, I think that if someone is suffering from an autoimmune condition, a chronic health illness, a chronic, a chronic, you know, health issue, then it's pretty clear that if you improve the quality of your food. If you kind of go back to the beginning of this conversation, if you put aside the idea of energy balance and all of these psyops that have been foist upon us. You don't think about calories, right? You think about food quality. There are a lot of ways to improve your health that may not look the same on the beginning. How well each of these is going to work. Work long term is probably bio, individual carnivore didn't work great for me because of electrolyte stuff. I've seen a lot of people do vegan diets and then end up with nutrient deficiencies long term, but at least in the short term, elimination of these ultra processed foods, which even can be equated on a caloric basis that that results in improved health in a lot of people. So that's fascinating to me. And we can kind of go back to that, that theme like, okay, this westernized diet comes containing all these ingredients, looks to be very harmful for humans. And so the similarities across those, those outcomes is really interesting to me. And then I mean speaking of n =1 Experiments with seed oils, I have to bring this one up because it's so strong. You can probably find a thread. I don't have a thread on my X account, but whenever I post about this, the, the, the community survey is, is unanimous or it's actually, I shouldn't say that it's very strong. The idea that like people who cut out seed oils, at least in terms of their personal experience, tend to burn less. And that's. I think this kind of mirrors the macular degeneration. Burn less, burn in the sun. Yeah.
- [168:27]
Danny
Oh, interesting.
- [168:28]
Paul Saladino
Yeah, they don't. It's not that they burn their food less, it's that they burn. Their skin burns less.
- [168:32]
Danny
Interesting.
- [168:33]
Paul Saladino
So their human experiences when you decrease the amount of polyunsaturated fats. Again this is just observation, sort of like community surveying, which is fascinating and as Nick says, hypothesis generating. You have less propensity, at least in these communities, to have UV susceptibility. That's interesting to me. And then if you look at the dermatology literature, there is backing for this. When you give animals higher linoleic acid diets and you expose them to UV light, they do tend to develop more aggressive cancers. When the cancers develop.
- [169:02]
Danny
Yeah, I heard the same thing about vitamin D. The lower your vitamin D, the more you'll burn and develop things like melanomas. And the same thing with. I think Alexis also said when you, you wear sun. I think this is also anecdotal, but sunglasses in the sun tend to. You tend to burn more when you're blocking your eyes and only exposing your skin or something like this.
- [169:22]
Paul Saladino
Well, yeah, there's a connection there, I think, between the brain and the skin in terms of melanin connection. Melanin Y production in the skin melanoma is a widely misunderstood cancer. It's the most aggressive skin cancer, but it's also not as sun associated as people think it is. Moderate level sun exposure across multiple populations. There was just a study published on this. I can pull it up. Moderate sun exposure is often protective against melanoma and melanoma. Your risk, I think in population studies is increased if you have multiple burns in Childhood. But across your life, if you have moderate level exposure, it's protective. So melanoma is interesting in terms of observational studies. There's another observational study that correlates the amount of seed oil consumption with increased rates of melanoma as well. If we're into this oxidative hypothesis around multiple. Yeah, pathologies here. So, yeah, sun stuff is fascinating and I think it definitely parallels these macular degeneration ideas in the retina too. If you're, you know, you think your skin and the retina on your eyes is, is very exposed to stressful circumstances from the uv and the way that you populate those cells, just like we talked about red blood cells, adipose tissue being composed of a representative amount of linoleic acid. Based on your diet, I think that the retina will be. And the skin will be as well.
- [170:40]
Danny
Another thing that's interesting too is I've heard people say that eating not just healthy meats, like fish, but eating fish that are native to the area you're in. Right. Instead of like eating fish that's imported from another part of the world, like Alaska. If we're living, if I'm here, living on the Gulf of Mexico, you're not.
- [171:02]
Nick Norwitz
Taking my sockeye salmon.
- [171:04]
Danny
I should be eating fish that was caught in the Gulf of Mexico. Is there, is there any.
- [171:09]
Nick Norwitz
I think it's a sustainability thing.
- [171:11]
Paul Saladino
Not that I'm aware of. The problem I have with fish in general is it's just so full of heavy metals. Microplastics. P.S. yeah.
- [171:20]
Nick Norwitz
More so farmed.
- [171:22]
Paul Saladino
Even the wild stuff's pretty bad today.
- [171:24]
Nick Norwitz
Do you have a test you suggest getting? I'll get it in report. But I ate a ton of fish.
- [171:28]
Paul Saladino
Like, just check yourself.
- [171:30]
Danny
Yeah, I ate a ton of like snapper and grouper that's caught right out here.
- [171:32]
Paul Saladino
Check your serum heavy metals. Just start with that.
- [171:34]
Nick Norwitz
I have lead, mercury, lead, mercury, cadmium, are all fine. Arson, I don't recall. But I mean, the, the mercury is on the. It was like 9ish. It wasn't like low, low. But I also don't eat like, I try to avoid like swordfish and you know, like big eye tuna. So like sockeye salmon, sardines. Actually you can go like online and just google the mercury content of these things. And you need to eat like, sardines.
- [171:58]
Danny
Are really low mercury, right?
- [172:00]
Nick Norwitz
Like sockeye salmon or, or sardines. You need to eat it like every day for 40 days to equate to like one, you know, mass equivalent of swordfish. So like the distribution across fish is massive, it's big.
- [172:12]
Paul Saladino
So there's no tests for microplastics and pfas. There are, are widely available. Yeah, these are interesting to me.
- [172:20]
Nick Norwitz
I just think a thing we keep going back to as you were speaking is like context in the human body and the vilification of single components in food. So another example we were talking about, I think we were talking about with both of you off air was like salt. Like, is salt bad? People say saturated, fast bad. And the other salt, I was down a rabbit hole the other day. And again, interacting with individual biology, there's some data suggesting if you have pre existing obesity, it could increase your blood pressure and actually make you more salt sensitive. So the mechanism appears to be, and I'm basing the mechanism off rodent studies, but there are human studies, including in the 80s and 90s in the New England Journal that I think makes the case pretty compellingly. But basically your fat releases leptin. The more fat you have, the more leptin you have circulating around. And one of the things leptin does is it acts on brain cells at the blood brain barrier. Their supportive cells to neurons are called astrocytes. So leptin can bind to receptors on astrocytes and do all sorts of things. One thing it'll do, activate a protein called HIF1alpha, increase levels of a hormone called VEGF that makes vessels grow. So what they find, at least in animals is, is that more an obesogenic diet that increases fat mass. The diet doesn't directly increase blood pressure immediately, but as the fat mass goes up and the leptin goes up, the blood vessels around the hypothalamus, basically the master control center of the body's endocrine system, they thicken. I actually think, Steve, I think I sent an image. It might be the one with the blue inset. Maybe I did, maybe I didn't. Yeah. Blood brain barrier image 2. So this is an image of the basal membrane at the blood brain barrier. And so what you see on the left is the control and on the right you can see it highlighted in blue is like the thickening of the membrane after, in an obesogenic context. So in obesity, the point here is like literally the vascular around the brain's master controller of the whole body's hormones is the, is changing. And this ends up changing things like nervous system tone. So that can increase blood pressure, including nervous system tone, to the arteries and the kidneys, and also increases susceptibility to inflammation, which can drive up blood pressure. But interestingly, so you can't do these controlled experiments in humans, but you can look at human genetic cases or interventional trials and see is there a lineup. So what do we see in human obesity? Increased blood pressure. What would we predict to see if you had human obesity but no leptin signaling?
- [175:02]
Paul Saladino
No increase in hypertension?
- [175:04]
Nick Norwitz
No. So you would expect in congenital leptin deficiency for people to be massive, have massive obesity because you don't have leptin signaling to suppress appetite, but you would actually expect, weirdly, the blood pressure to be lower, normal. That's exactly what we see. And people have argued that, well, if you give back leptin, it doesn't increase blood pressure, but you're not like super physiologically dosing it. So it's complicated, but there's that. And then if you look at studies done in like, I think it was 1989 in the New England Journal. Can you bring up Steve? New England Journal bar graph. This was a trial, a few up. This was a one down, one down. There we go. Oh yeah, this was a trial done, published in the New England Journal with lean people or people with obesity where they gave them a very high salt diet. It was something like 15 grams of salt versus a very low salt diet. They're testing sodium restriction. What is the effect of sodium restriction on blood pressure? Obesity. It drops it. And non obese doesn't affect it at all? Nothing at all. Which is fascinating. And actually if you go, go to.
- [176:06]
Danny
That's incredible. It's crazy.
- [176:07]
Nick Norwitz
Go to any jam dot plot lot. It's messy. There's a lot of variability. Of course humans have heterogeneity, but this is the association between percent body fat and change in blood pressure with salt restriction. So what you see is as your body fat drops, the drop in blood pressure you get from restricting salt, again, it was an astronomical drop in salt. Like had a tiny salt diet versus a massive salt diet as you drop.
- [176:29]
Danny
Below the low body fats on the far left.
- [176:31]
Nick Norwitz
Yeah. So as you drop, you know, at 30% body fat and below, the change basically drops to zero. So again, context the story I'm telling here, which I'm not 100% definitive, and I don't think this is the whole answer in humans, but it's a pretty compelling mechanistic story where leptin from fat tissue can remodel vasculature around the brain and change the way your body's hormones function and actually how your kidneys function. So it's a direct effect of leptin on the kidneys that cause it to retain salt. So this is a scenario, again, where, you know, you go up and look at, like, the AHA recommendations for salt, like, everybody should eat less than 2.3 grams. And it's just like you have studies like, even from the Framingham cohort showing that very low salt can associate with higher blood pressure. And then studies like this, the New England Journal, there's no refining the message to account for various metabolic conditions, various metabolic factors. So when it comes to saturated fat, omega 6, salt, salt, what we keep on seeing again and again, and this is the theme, is that, like, there is metabolic context that we can understand and use that to inform what the individual should be concerned about. So if you have obesity and you're eating a mixed macro diet and you're sedentary, should you be relatively more concerned about Omega 6 and salt? Probably. If you're leaning and keto, should you be concerned about, like, omega 6 from Whole Foods and salt? I don't think the data support that. So it's context, context, context.
- [178:00]
Paul Saladino
When I read this one on your sub stack, Nick, I wanted to ask you this, so I'm curious for your perspective, because we see this a lot, right? When you have the fat mass, the fat mass talks, right? The fat mass is secreting these adipokines, leptin, which can be problematic when there's leptin resistance. What do you think is the main driver of the fat mass? Because, I mean, I just, in my mind, I always want to pull it back to, like, what caused it, what caused it, what caused it. And I think Western medicine never challenged us to do this in medical school. So in your perspective, what are the major drivers of the obesity and the fat mass in these people? Because you can say, okay, you have more fat mass, more leptin. This is driving hypertension. Where did the fat mass come from?
- [178:41]
Nick Norwitz
So when I think about this, depending on what portion of the web, the network I want to talk about, I kind of think about it as, like, there's always an upstream driver and then some places in the network where various things converge. So we can talk about, like, circadian disruption and how that alters hunger hormones. We can talk about high insulin levels and how that directs energy to fat cells and causes them to expand. So I want to point out there's lots of different things converging on the fat. And then as the fat expands, it can cause downstream metabolic damage from, you know, harming the brain barrier, et cetera, et cetera. So in this mental image, I kind of see the fat Mass as one convergent point in the mechanism with respect to what causes the fat to expand. I would analogize this somewhat to the study I talked about earlier about the four types of type 2 diabetes, where I think there are lots of different causes that are going to carry different weight in different people. If I were to identify what I think the biggest lever is for someone struggling with obesity in this day and age, I think it's high insulin, insulin resistance and excess of dietary carbohydrates that are going to boost the insulin. Because I think one thing that will happen is the higher insulin levels cause partitioning of more energy to the fat cell.
- [180:13]
Paul Saladino
So you're saying insulin resistance.
- [180:15]
Nick Norwitz
Yes.
- [180:16]
Paul Saladino
Which is kind of like metabolic dysfunction.
- [180:18]
Nick Norwitz
Yeah. So it's a hand wavy or it's a wide umbrella, but intentionally.
- [180:25]
Paul Saladino
Sure, yeah.
- [180:26]
Nick Norwitz
Because I think to get like to say XYZ is the sole piece of the puzzle will be misleading.
- [180:31]
Paul Saladino
Do you think all carbohydrates cause that to the same extent? Because there are, there are lots of populations like the Tuka Cinta in the highlands of Papua New guinea who have 90% of their diet is carbohydrates from sweet potatoes. So maybe this is akin to the seed oil conversation. So I don't see, No, I, I don't, I, I, Yeah, I don't see excess carbohydrates as a major driver of insulin resistance.
- [180:52]
Nick Norwitz
It's not sufficient.
- [180:53]
Paul Saladino
Right?
- [180:54]
Nick Norwitz
It's not sufficient. But I think when you're in an environment where, let's say you already have a creeping degree of insulin resistance, there's a difference between the seed and what helps the seed grow.
- [181:07]
Paul Saladino
I'm so interested in the seed, though.
- [181:09]
Nick Norwitz
I agree, I agree. But it could start at like we were talking, for example, I think before we recorded about like artificial sweeteners. And there was a study out in the Proceedings of the National Academy of Science, this isn't obesity per se, but it was showing that even very low dose aspartame can cause transgenerational inheritance of anxiety. So if you give male mice it was the equivalent of two to four Diet Cokes or diet sodas, they literally say it in the paper that that's the dose equivalent. Not only do the mice have more anxiety and there's mechanisms to explain this. I think there's even one human randomized controlled trial where they did different doses of aspartame was like coded as irritability. But that aside, not only do the mice have more anxious behavior and there are validated tests for that, but the kids of the mice and even the grandkids of the mice have more anxious behavior. And then we also have data from like I think it's the. What was. It wasn't the Dutch hunger winter, but there was another natural experiment. I think after World War II was like 1953 where sugar rations changed in Europe and like isolated massive increase in sugar intake. I can find the study. It was like 100 days of life exposure. It was in science, I think last year was a big story. But basically there was a natural experiment where sugar rats and exchanged sugar intake skyrocketed and then they followed people follow babies based on where they were pre in gestation or afterwards and basically found a hint of what appears to be like epigenetic remodeling that predisposes to metabolic disease from a process. So when you're talking about the seed, I think it starts pre birth that develops your susceptibility and it ends up being the hand you're dealt. So another reason I bring these things up is, and this is a general truth, like what you do with your lifestyle doesn't just affect you. And I don't mean to be telling pregnant women you know how to live their life. That 29 year old white cis male saying you should do this in pregnancy is not a great look, but I'm wise enough not to mansplain that one. But just talking about the data, the fact is we'll never. You want, oh, the gold standard evidence, randomized control trial. We're never going to have that RCT in humans. Transgenerational RCT on diet coke and anxiety like it's not possible to do. So what are we left with? We, we're left with the evidence we actually can collect and what we can conclude from that, which is, I think this actually could be a concern then at the individual level, how much does it cost you to do an intervention in this case drinking water or seltzer instead of that coke. And that's not for me to tell you, it's just like this is interesting data.
- [183:53]
Danny
And what do you guys think? I'm sure you've seen Mark Bell's sugar diet. Have you seen this?
- [183:59]
Paul Saladino
I've covered it, yeah.
- [184:01]
Danny
Yeah. You made a video about it?
- [184:03]
Nick Norwitz
Yeah.
- [184:03]
Danny
What is going on there?
- [184:05]
Nick Norwitz
I'm fascinated by it. So, so this is one of those things where you know, to be honest, when it comes up, there are certain things where like you have your own mental heuristics and I'm like, I'm triaging this to the junk pile. But coincidentally a Paper came out in nature metabolism right around the same time. This did not actually influence, this is just a coincidence, it didn't influence Mark's decision to do it. But it was an experiment, actually. Three controlled studies, separate three controlled studies in nature metabolism. I think it was like Nicholson at all 2025. And they showed that protein restriction, so sugar diet's one type of protein restriction diet. If you're eating just fruit and fruit juice and candy, you're going to protein restrict. Protein restriction causes about, in the lean healthy men, a 600ish increase in energy expenditure per day without any increase in activity. So it was a 19 to 21% increase in total energy expenditure without changes in activity. No changes in thyroid hormone or other hormones generally associated with changes in energy expenditure was very consistent when they went back to a higher protein diet. So the protein restriction was 9% of calories from protein protein. And then when they went back up to like 18% calories protein, their, their metabolic rate lowered. And what they were able to show is in these mice, sorry, in these people, it was an increasing level of this hormone called FGF21, mostly made from the liver, which appeared to be signaling to fat cells to make the fat cells expend more energy. So then they did mouse models, because you can manipulate mouse models to kind of prove causality. Yeah, I can find the study in a second, but. And they were able to show like a causal pathway whereby FGF 21 changes fat cell metabolism, increases energy expenditure quite massively. Again, a 600 calorie effect. A couple interesting things about this study. First of all, they tested first a high carb, low protein diet, so 70% carb, 9% protein. That wasn't the only one they did. They replicated that. And then in the third study they did high carb and high fat, 9% protein, 41% carb, 50% fat, if I recall. So you could engineer this with ice cream. Basically. Okay, same effect, same massive increase in energy expenditure. And the participants, the way they do it is they also have the participants increase their energy intake to try to not lose weight. And I think in most of the studies they needed to increase their energy intake by quite a lot and then they still lost a little bit of weight. So they did high carb and high carb, high fat. I then actually I did another video where I replicated this using a ketogenic diet. So a 4 to 1 ketogenic diet which is 90% fat. So also low protein, same effect. I literally could not eat enough to keep the weight On I was just up titrating the calories and in like three weeks I lost over six pounds. And by the end I was, I had increased my caloric intake on average over to like the whole up type traction by over 300 calories per day. I think I calculated as like I should have been in a quote unquote, 6,000 calorie surplus, but I lost 6.4 pounds.
- [187:14]
Danny
So it's the low protein, which is the low protein.
- [187:17]
Nick Norwitz
And people are going to ask about the whole muscle thing. There wasn't significant effects on muscle loss and there was a change in nitrogen balance. There was a trend towards decreasing muscle mass or lean mass, but that's also coupled with a decrease in overall body mass. So it's not clear how this would affect physiology in the long term. And then just to add one more very interesting nuance is subsequent to that, another paper came out in cell metabolism where they genetically manipulated mice to increase FGF 21 just at the fat cells. And then this happened. The mice lived longer in an obesogenic context, but they lived longer with same or increased energy expenditure and improvements in body composition. The reason I find this really interesting is not because I think FGF21 signaling of fat cells is going to increase human lifespan substantially, but the mere fact that in mammals you can change fat cell metabolism with one hormone and change a mammal's lifespan speaks to how incredibly important fat cell metabolism is, is for our overall health.
- [188:22]
Paul Saladino
It was pretty, I think the problems with the honey diet or the sugar diet or that it doesn't really work, that it's not sustainable long term.
- [188:29]
Nick Norwitz
Right, right.
- [188:29]
Paul Saladino
So it doesn't, it's not going to do well long term. We don't know what the effects are long term with uncoupling this, at this sort of metabolism level of mitochondria with FGF21. I think that it's, it's interesting. Like Nick is saying, it's instructive. It's like a human petri dish. Yeah. But I think that maybe it helps people jumpstart, you know, their weight loss a little bit. But the problem is like you need amino acids for other things.
- [188:54]
Nick Norwitz
Right.
- [188:54]
Paul Saladino
You need amino acids to make neurotransmitters, you need amidst to, you know, to build and repair things in your human body. So yeah, this doesn't, doesn't work great long term. It's not the panacea.
- [189:04]
Nick Norwitz
No.
- [189:04]
Danny
Right.
- [189:05]
Paul Saladino
It's an interesting illustration of metabolism. Yeah, yeah.
- [189:08]
Nick Norwitz
I'm not condoning it by any means, but it's one of These things where sometimes BS is bs, other times you can pick at the BS and there's something fascinating underneath. As a teaching point, I put the sugar diet in that category. Do I think it's a good idea? No. You can even get the same effects by eating a non sugar diet that's protein restricted. So this is like a subset of protein restricted diets. And that's how it works. But you can imagine in popular media if you can do a sugar diet and can make it work, that's gonna be the thing that takes off. It's the same reason that my Oreo versus statin study took off. When we did this before with like sweet potatoes and fruit, it didn't. Mm. So it's, it's what gets amplified. Incentive structures.
- [189:47]
Paul Saladino
We come back, you know what else works is just eating good quality food.
- [189:51]
Danny
Yes, exactly.
- [189:52]
Paul Saladino
You know, and not restricting protein because we know that. I mean, there's so many good variables or so many good effects of protein in the human body. So I think people, it's, I think like Nick is saying, it's an illustration of human metabolism as a teaching point. Point. But man, like, show me the person that, and Mark Bell's done this in the past, that eats a high quality ketogenic diet and doesn't lose weight.
- [190:12]
Nick Norwitz
Right.
- [190:13]
Paul Saladino
Doesn't improve their fertility, doesn't improve their mental health and their sleep.
- [190:15]
Danny
Right.
- [190:16]
Paul Saladino
Show me the person that eats an animal based diet with meat and fruit and unprocessed food and doesn't have the same effects. It's like. Okay, there's. Yeah.
- [190:22]
Danny
I wanted to ask you, wind. Is there a certain time you choose to eat fruit during the day or all day? All day you eat fruit.
- [190:28]
Nick Norwitz
Yeah.
- [190:29]
Danny
So you're not necessarily in ketosis?
- [190:31]
Nick Norwitz
Never.
- [190:31]
Danny
Really?
- [190:32]
Paul Saladino
Never.
- [190:33]
Danny
Only eating meat and fruit. So you're never, you're never in ketosis?
- [190:35]
Nick Norwitz
Never.
- [190:36]
Danny
Interesting.
- [190:37]
Paul Saladino
No.
- [190:37]
Danny
And do you, do you experience the same. The same. Do you feel the same. Same energy levels, that is, if you didn't have the fruit added in. Or, or is there like a, a huge difference to you adding the fruit in?
- [190:49]
Paul Saladino
Personally, I feel better with the carbohydrates from fruit. Things like honey or fruit or squash, I feel better with that. So my energy is more steady. I don't have the electrolyte insufficiency, My testosterone's higher. I sleep better. I had a, I had a lot of side effects. Long term keto. I had a lot hard palpitations at night. Yeah. And interestingly, you know, if you look at my labs, I just got my Blood work. You know, my fasting insulin is 2.3. Right. So the fruit doesn't impair metabolic health in any way, shape or form for me.
- [191:18]
Danny
Interesting.
- [191:18]
Paul Saladino
Remain metabolically healthy.
- [191:20]
Nick Norwitz
Yeah. Again, it's. There's complexity and nuance. So, like with fruit. Fruit is an example. I don't. You know, the. I think it was a cell metabol, like how fructose gets processed in the small intestine. This is something that I think often gets overlooked.
- [191:31]
Paul Saladino
Yeah. But this one's. There's some nuance here that I want to talk to you about because.
- [191:35]
Nick Norwitz
Yeah, I'll say my bit and then.
- [191:36]
Paul Saladino
Yeah, yeah, go ahead. Yeah, yeah.
- [191:37]
Nick Norwitz
Like, I. I do not think fruit is bad. I do think fructose as a biomolecule is. Can be uniquely harmful when it's in the wrong place. So, like, you know, at the liver, there's a lot of things we can get into the biochemistry if we want, that it can do, but that's not the point. The point is rather that. I don't love this phrase, but the body is smart. So if you have, like, glucose, you can consume glucose, it'll go. Get absorbed, go through the portal vein, hit the liver. The same thing won't happen with fructose. Fructose actually gets biotransformed by the small intestine into glucose and other organic acids. So when you say, have, like, a handful of blueberries, the amount of fructose in the blueberries, negligible amount, actually gets to the liver. It's biotransformed into other sugars and organic acids beforehand. So in this case, it's one of those things where, like, when we're talking about exogenous intake, the dose makes the poison. I think that kind of thing often gets overlooked. And it can also reconcile why, like, potentially fructose, from saying, having a bowl of cereal with a glass of orange juice, which will saturate this mechanism, it'll overflow, and then you will get more of a fructose assault on your liver is different and not just, like, linearly associated with saying having some blueberries. And it's the same thing with, like. I was asking somebody the other day, you know, do they think fructose is uniquely harmful? Someone with good physiology background, they said yes. And then I asked them, like, do you think blueberries are harmful? Like, well, no, there's a lot that is in a blueberry that's not just fructose. And what I find interesting is the double standard, because when we talk about saturated fat, a lot of people say well, saturated fat is bad. And then extend that logic to dairy's bad, butter is bad, steak is bad. And I just want to show that those leaps of logic are actually very similar. So, like, from the whole human perspective, generally, there's more to the whole food in terms of how it impacts your body and focusing on like one component that it might be rich in anyway. Paul, what were you gonna say about the.
- [193:37]
Paul Saladino
No, that's a. That's a great segue, that point. So if you look at the research on fructose, I think fructose is a molecule we've been sort of told to fear incorrectly. If you look at the research in fructose, whether in animal models or in humans, it's almost always given isolation. Glucose has two transporters in, in the gut. There's SGLT1 and there's glute 2. Fructose is glute 5. But when glucose and fructose are administered together, glucose can use fructose can use gluten to with glucose. So what you get when you administer fructose by itself is you get fructose malabsorption, and fructose malabsorption leads to overgrowth of dysbiotic bacteria in the gut. But that doesn't happen with human food. There's no food that humans consume in a whole food form that does has isolated fructose.
- [194:20]
Danny
Right.
- [194:20]
Paul Saladino
But if you look at the literature with animals or humans, a lot of times people will be given IV fructose, right. Or they'll given pure fructose. These don't. It goes back to kind of what we were saying, the difference between an isolated component of a food and the whole food. So if you look at the studies on fruit, they're invariably healthy for humans. I mean, you look at even fiber.
- [194:40]
Danny
There's all kinds of things.
- [194:41]
Paul Saladino
Well, even without fiber, even looking at fruit juices. So orange juice, pomegranate juice, cherry juice, grape juice, watermelon juice, the list goes on and on. These all improve outcomes, whether it's DNA damage, whether it's oxidative stress, whether it's LDL oxidation, endothelial function. You can give someone watermelon juice with a glucose tolerance test, and it improves insulin sensitivity during the glucose tolerance test. So a glucose tolerance test, you give someone isolated processed sugar, it's called a glucola. It's basically like a sugar drink. And you look to see how well the body disposes of that with insulin handling and sugar handling, glucose handling in the body. And when you give extra sugar with watermelon Juice, it actually improves, improves the handling of that glucola. So you can improve by giving extra sugar in a whole food form.
- [195:29]
Nick Norwitz
Cherry juice, acutely.
- [195:31]
Paul Saladino
Yeah, cherry juice, blueberries, all these things, they, they have great effects in the, in the short term when you're using them. So fruit, I'm not familiar, maybe Nick knows one. I haven't seen a single study with whole fruit that suggests there's a harm to humans or even a fruit juice that's not like a super like sunny D, like a fake fruit juice. So I think that a lot of it is, is conflating studies that are misrepresenting fructose by itself as opposed to glucose and fructose co administration. And so I don't see fructose as a harmful molecule when we're eating it in that package. And then this is an interesting kind of also perspective gaze to the difference between fruit and processed sugar. Because if you look at the data, at least observationally and in terms of populations, pop. Processed sugar, which is just technically speaking, it's a disaccharide of glucose and fructose that looks harmful for humans. But when you give a glucose and fructose together in a fruit or a honey, these have different effects on humans. They just don't look to be harmful. I mean, honey has many, many trials showing improvements in metabolic health with honey, right? Something people think of as pure sugar, right. And they forget that honey has probably 300 to 300, 350 bioactive components along with the sugar. So I think what's going on here is at the level of the gut flora that when you give isolated fructose, you get fructose malabsorption, you get dysbiosis. If you give isolated sucrose, which is this disaccharide of glucose and fructose, you also cause dysbiosis, you cause overgrowth of the wrong type of bacteria in the gut. And that can lead to increased levels of a molecule in the human body called LPS lipopolysaccharide. And you see this, it's also known as endotoxin. You can give humans sugar and see endotoxin levels rise. Now endotoxin is another really negative signaling molecule in the human body. It actually tells the mitochondria like, hey, you're broken. It's a component of the gram negative cell wall, gram negative bacteria. So you don't want acute endotoxemia when you are eating a processed sugar. And what's interesting is when you give honey or when you give fruit which contains Sugar, you don't get that effect. You don't get LPS rise.
- [197:34]
Danny
Interesting.
- [197:35]
Paul Saladino
You don't get endotoxemia because these compounds in the fruit probably prevent the overgrowth of the bacteria. A lot of the bioactives or these compounds in the whole foods actually affect the gut bacteria by preventing overgrowth. It's incredibly complex, right, that the food we eat affects this delicate balance, this symphony of gut microbial populations in our. In our intestines. And that has effects on the human body. So people will say the same thing to me. And I see this from a lot of the keto influencers. Not Nick. Nick doesn't say this, but you're like.
- [198:06]
Nick Norwitz
A little like, not Nick, but he's not this guy.
- [198:09]
Paul Saladino
No, but like other keto influencers will say honey is the same as Coca Cola. Or, you know, orange juice is the same as Coca Cola. I mean, there was a, a popular influencer saying that recently. Glucose goddess was saying that. This, this, this French biochemist, Glucose goddess.
- [198:25]
Danny
Oh, wow.
- [198:25]
Paul Saladino
She was saying this. And you think like, well, that's not true. Like, you look at the actual effects on human physiology at multiple levels, you get completely different effects. I mean, orange juice improves endothelial function, sugar worsens endothelial function, which is sort of the reactivity. Yeah. And I think that it. One of the main parts of the mechanism here has to do with the overgrowth of bacteria in the gut and then this attendant increase in these molecules in the human body, lps, also known as endotoxin, and the negative effects those have. So the idea here is just like an. And Nick mentioned this, in this sort of population study, when sugar rations changed, you saw an increase in sugar potentially affect the epigenome. Right. The way that humans are programmed. And I think that, like, an increase in fruit rations probably wouldn't have the same effect. So when we're talking about carbohydrates and humans, the quality of the carbohydrate, like we've talked about throughout this podcast, matters massively. I don't think humans need to feel fruit. There's probably some inter. Individual variation, but these foods look to be delicate in the way that they affect the human body and the microbiome and the way it all connects. It's really interesting stuff.
- [199:31]
Nick Norwitz
I agree with Paul. Mostly the thing I really agree with is, like, the package matters. Talking about compounds in blueberries, honey, or like, we're talking about walnuts earlier, like, the effect of, like, ellagitannins on, like, you know, is it urolithinae or hypercaccum I think it's ur is the downstream product, but basically, like your microbiome will interact with components that are in your food and generate compounds that can have more powerful metabolic effects than the macronutrients or subgroups they're in, like fructose, you know, then we give it credit for and other factors. Actually, just quick tangent. You're talking about like the basically leaky gut endotoxemia. There's also new data showing that you can manipulate your mucin lining and change the gut flora with stress. So stress activates, it changes signaling in a region called the amygdala. And there's a signal to glands in the gut called Bruner's glands that change mucin production. So, like, another way where like all these things converge, we're talking about, like psychosocial things. They're not isolated, they converge on these metabolic pathways. But getting back to my point on fruit, I totally agree. Like a soda and like a honeycomb are two entirely different things. Fruit is not bad. Fruit requires context. But to that end, one of the things I really hate, and I think you probably feel the same way, is platitudes. So I hate the things of like, get your five a day, eat the rainbow. Fruit is always good because it's like. Well, I'm not gonna say a mango is bad per se, but if you have metabolic syndrome and your choice is a mango, blueberries or hard boiled eggs for breakfast. I'm gonna go with first the hard boiled eggs, then the blueberry. And I don't know, I'm like, I'm. If you. On the mango.
- [201:16]
Paul Saladino
Yeah, makes sense. Can I add some context there?
- [201:18]
Nick Norwitz
Yeah.
- [201:18]
Paul Saladino
So I think that in the setting of metabolic syndrome, my perspective is that you have essentially broken mitochondria, right? You have broken energy partitioning, you have broken, broken signaling in the cell that's creating this insulin resistance signal. And so in the setting of metabolic dysfunction, you don't process carbohydrates well, but the carbohydrates didn't cause the problem per se. So I don't think a mango, if you have metabolic syndrome, you're not going to handle the mango well, but the mango didn't get you there. I don't think you, I don't think you became metabolically unwell or insulin resistant eating mangoes. I think you became metabolically unwell. This is my hypothesis, eating processed sugar, affecting your gut flora negatively and potentially packing the membranes of your cells and mitochondria with too many seed oils and the derivatives. Well, I Mean, these are the two greatest movers that I see in terms.
- [202:08]
Nick Norwitz
Of the actual metabolism. I mean like fructose does have unique metabolism. So like in the early stages of glycolysis, that is a unique enzyme from glucose. And this enzyme actually doesn't have a positive feedback loop, sorry, a negative feedback loop. So you can go kind of unchecked, deplete intracellular ATP. This has been shown lead to activation of. I think it's NAPD, NAPDH oxidase 4 and cause mitochondrial dysfunction.
- [202:31]
Paul Saladino
But it's so small. You talked about this earlier. The amount of fructose that you absorb, it's so small.
- [202:36]
Nick Norwitz
Well, depending on what you're eating, it's.
- [202:37]
Paul Saladino
So it's all just converted to different things, you know, like I don't think all that mitochondrial.
- [202:41]
Nick Norwitz
So a couple blueberries couldn't do that. No, but could the fructose from. And this is, this is the difficult hypothetical because I said like the bowl of Rice Krispies, you know, cereal and orange juice, there's going to be too much fructose in that for the bio. The pathway is going to be saturated. So I'm saying component because if you.
- [203:03]
Paul Saladino
Look at it, I mean in diabetics there was a study where they had increasing amounts of honey and they went up to 125 grams a day. 125 grams a day of honey. In a diabetic, I think it's about 50% fructose. And granted maybe it's not enough in one single bolus, but that actually improved glucose handling acutely.
- [203:22]
Nick Norwitz
Yeah, well, but I mean like I can eat Oreo cookies acutely and drop my ldl. Does that mean Oreo cookies are good for long term?
- [203:27]
Paul Saladino
Well, I mean, it's just speculative.
- [203:29]
Nick Norwitz
You know, I think a lot of this is speculative.
- [203:31]
Paul Saladino
I think, I think it was an eight week study.
- [203:34]
Nick Norwitz
I think in a human study the saturation started to kick in around like half a gram per kg or something, which you can, you can saturate in a meal. I'm not being definitive on this, I just don't like the idea. How's another way to put this? People say like empty calories. This is something that we can probably agree on is. I think the term empty calories is stupid because it suggests that like the macronutrient cargo, like the carrier is itself inert in just energy. But the macronutrients, you know, the things that give you energy, the steric acid, the, the palmitic acid, the myristic acid, short chain fatty acids, you know, fructose Sucrose, whatever. They're each unique biomolecules with unique effects, of course. So stearic acid, you know, probably can improve mitochondrial function.
- [204:19]
Paul Saladino
We know it does, yeah.
- [204:21]
Nick Norwitz
So like, I mean, like, that's the broader concept I'm getting to, I guess, coming back and probably bringing it to the end because I want to not miss my plane.
- [204:30]
Danny
Yeah, you gotta leave soon.
- [204:32]
Nick Norwitz
Is that context matters. And what I mean by that is this is. It's difficult to explain without just coming off as this is so hand wavy to be useless, but I think it's useful and I'll try to explain why. When we're talking about like say macronutrient groups, this is a complete, like a very diverse set of molecules that is then packaged in foods that have been processed differently and have different bioactive effects. They go into a system that processes it in many different ways. Does it get bioconverted in the small intestines? Is the linoleic acid, you know, oxidized by myeloperoxidase because you have, you know, excess fat tissue or is it converted to 4H&E or 1213 DIhome, etc, etc. Etc. It gets so complicated that when you look at the platitudes that we hear bandied about, get your LDL down, eat less saturated fat, good or bad. It's comical. Yeah, I agree, it's comical. It's useless. And it is the basis for why nutrition is so frustrating and confusing for people. So I've thought about this a lot and what my solution is to that problem. Because people gravitate towards, they want simple, they want the to do. I think there's a way I want to see if you agree that you can, we can inspire curiosity and awe in the physiology of all of this. It's not about understanding. Like, I don't need to write a post and somebody reads and like, I got all of this. You get 20% of it. Great. Provided you went through the process and enjoyed it. Like, finding the awe in learning about science, metabolism, physiology is a gift that I think we can give to people. And with that humility and the curiosity that I honestly think curiosity can save lives. It's a difficult task, but I think it's one that can be accomplished. Maybe I'm just not.
- [206:35]
Danny
The more I know, I realize the more I don't know, after the last three and a half hours, I realize I don't know jack shit about any of this stuff.
- [206:41]
Nick Norwitz
But it's fun, right? It's like, this is interesting idea.
- [206:43]
Danny
Yeah.
- [206:44]
Nick Norwitz
And Then you grapple with it. And you know what, what I want to applaud Paul for not just here, but like offline is you're someone who I feel like I can have a genuine open intellectual conversation with and where we can start like a public conversation. And we didn't actually get to like nailing down the numbers. But like if I said what is your opinion on a 0 to 10 scale and you're start at X point, you'd be fine saying, hey, I kind of shifted on this in a very non defensive matter manner. And I think genuinely some people are like virtue signally about it, but I think we need more of that. And it's hard because pulling it back to. But incentive structures, the incentive structure doesn't always favor saying, hey, let's sit down and have a nuanced conversation between people who have differing ideas and see, see like what evolves from this conversation. We can both think of examples of people who might be a little bit negative on having open discussions or representing things honestly.
- [207:45]
Danny
Well, thank you guys for doing this, man.
- [207:48]
Paul Saladino
Thanks for having us.
- [207:48]
Danny
This has been super fun. Paul, where can people find you online?
- [207:52]
Paul Saladino
It's Paul Saladino MD Everywhere. All the socials website.
- [207:57]
Danny
Yeah, amazing.
- [207:57]
Paul Saladino
Yeah.
- [207:58]
Nick Norwitz
Nick, My name Nick Norwitz. Norwytz. I don't think there's another ignore what's around and I'm really having fun with my substack right now. Staycurious metabolism.com so you can check it out there. And thanks for having us, Danny.
- [208:13]
Danny
Beautiful.
- [208:13]
Paul Saladino
Thanks for having us. Can I just add one more thing?
- [208:15]
Nick Norwitz
Of course.
- [208:15]
Paul Saladino
I think that we've talked about a lot today and I appreciate Nick, you know, having this conversation. It's fun to talk to somebody as smart as he is about all these kind of ideas and share things and learn from each other. I think that a lot of this probably is overwhelming for people. You know, maybe you felt a little overwhelmed at times, but in my mind, this is just how I conceptualize it. If you, if you just take a step, if you can move one step beyond a calories model and start to think about a theme that we came to a lot of times in this podcast around food quality and the difference between food components and whole foods, you're. You're going to be light years ahead. You know, it's like, look, you said at the beginning of the podcast, when you don't eat carbs, quote unquote, which I'm imagining is processed breads and things, things like this cakes, you feel much better. That's about all people need to know, you know, like, if you just, if you move away from energy balance, which is probably a psyop started by Global Energy Balance and Coca Cola, along with many other nutritional psyops, I just think that there's actually potentially an active movement to confuse the consumer. And then we throw our hands up and we think, oh, calories is the simplest model. I'm just not going to eat too much. And I think that's exactly the wrong decision. Right. I think that if, if human, if, if humans just focus on food quality and, and, and whole foods, as overused as that word is from animal and plant origins, you are going to do better, you're going to get healthier, and that's really all you need to know. And it doesn't need to be overly complicated. You can dive into little things that, that we, we went down the rabbit hole on this podcast. But I think that if you move away from calories and you've moved toward the idea of food quality, you're on the right track. Just keep following your nose from there and you'll do good.
- [209:51]
Nick Norwitz
I also want to just add, you use the word overwhelmed, and I love that because I hope people feel that. I hope people feel that. And the reason being is like, like, if you go to the gym, you want to be, you know, have a good workout, feel exhausted, and then. What's the term? Progressively overload. Why should learning be any different? So, yeah, we're not going to go gentle on you because the, this, this conversation had a lot of chapters, and I think we went into the weeds and then pulled back. You don't need to get everything. But if you're willing to engage with these conversations and progressively overload your learning, just, like, going to the gym, like, that is awesome. Like, that is the journey. And yes, the big picture of, like, if you just kind of like, go back to basic principles, eat whole foods, that's great. But I do feel that learning about it gives you the insight and excitement to, like, engage in that, you know, be quote, unquote compliant with that, and then evolve and tweak the way you live indefinitely and enjoy that process. That's how I live. I think that's how Paul lives, how you have evolved your diet so many times. And that will make your nutrition journey not a chore, but a hell of a lot of fun, and you'll inevitably end up in a good place.
- [211:02]
Paul Saladino
What are you gonna eat for dinner tonight, Danny?
- [211:04]
Danny
That's a good question. I'm thinking about probably a steak.
- [211:06]
Paul Saladino
That's a good choice. Safe, safe.
- [211:09]
Danny
No sides. But tomorrow I think I'm doing a fruit bowl.
- [211:13]
Paul Saladino
You're good.
- [211:13]
Nick Norwitz
I'll be snacking on some dried steak on the plane.
- [211:17]
Paul Saladino
Eat some of that lineage on the plane, bro.
- [211:18]
Danny
Hell, yeah. Oh, dude, that stuff's amazing. That lineage. That lineage stuff, the. Those. Those dried steak chips.
- [211:25]
Paul Saladino
It's good, right?
- [211:25]
Danny
Fantastic.
- [211:26]
Paul Saladino
Dried steak. Yeah, yeah. Thank you.
- [211:27]
Danny
Thank you for all that stuff.
- [211:29]
Paul Saladino
Some for the plane, too. Yeah, yeah.
- [211:31]
Danny
All right, man. Thank you, guys.
- [211:32]
Paul Saladino
Thank you for having us, everybody. Thank you.