#335 - Carnivore MD vs Harvard Heart Doctor: Seed Oils are Actually GOOD For You | Paul Saladino & Nick Norwitz

Watch every episode ad-free & uncensored on Patreon: https://patreon.com/dannyjones Dr. Paul Saladino is a physician, nutrition specialist & leading expert in the science of the carnivore diet. Nick Norwitz MD PhD is an expert at Harvard in heart health, cholesterol, and obesity. SPONSORS https://whiterabbitenergy.com/?ref=DJP - Use code DJP for 20% off. PAUL SALADINO LINKS @Paulsaladinomd https://www.instagram.com/paulsaladinomd https://paulsaladinomd.com http://Heartandsoil.co http://Lineageprovisions.com NICK NORWITZ LINKS https://staycuriousmetabolism.com @nicknorwitzMDPhD https://www.instagram.com/nicknorwitz FOLLOW DANNY JONES https://www.instagram.com/dannyjones https://twitter.com/jonesdanny OUTLINE 00:00 - Flaws in medical research 12:46 - Who's funding nutrition studies 16:06 - Calories don't cause obesity 18:34 - GLP-1 drugs 23:32 - The truth about high LDL levels 36:27 - Is high LDL bad? 46:52 - Western medicine doesn't care about metabolism 54:43 - "Evidence-based" medicine is not the best medicine 01:02:59 - How gut health changes the brain 01:10:08 - Seed oils explained (omega 6 oils) 01:14:25 - History of seed oil consumption 01:27:30 - Linoleic acid's role in the body 01:42:54 - Seed oil studies are historically rigged 02:07:46 - The #1 cause of obesity in America 02:21:02 - Most dangerous ingredient in seed oils 02:30:54 - Blue zones are a myth 02:33:20 - Sunlight vs. blue light 02:50:09 - Are fish actually healthy to eat? 02:57:29 - what causes fat mass in obese people 03:03:22 - Mark Bell's sugar diet 03:11:07 - Is fruit actually unhealthy? 03:25:11 - Curiosity & the ambiguity of nutrition Learn more about your ad choices. Visit podcastchoices.com/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  At Humana, our Medicare Advantage plans are easy to understand and easy on your wallet. Like offering more benefits than you'd get from original Medicare alone, and including dental, vision, and hearing coverage in every plan. And the best part is, every plan has a $0 or low monthly plan premium, which makes it easier to save, too. So this Medicare planning season, plan well with Humana. Learn more at gethumana.com. Humana is a Medicare Advantage, HMO, and PPO organization with a Medicare contract. Enrollment in any Humana plan depends on contract renewal. At Humana, our Medicare Advantage plans are easy to understand and easy on your wallet. Like offering more benefits than you'd get from original Medicare alone, and including dental, vision, and hearing coverage in every plan.

• 0:42Speaker 00

  And the best part is, every plan has a $0 or low monthly plan premium, which makes it easier to save, too. So this Medicare planning season, plan well with Humana. Learn more at gethumana.com. Humana is a Medicare Advantage, HMO, and PPO organization with a Medicare contract. Enrollment in any Humana plan depends on contract renewal.

• 1:08Danny Jones?

  Breaking news, 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?

• 1:19Speaker 02

  You want to go first? 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

• 2:01Speaker 02

  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.

• 2:23Danny Jones?

  And you also did the famous Oreo versus statin thing we talked about.

• 2:26Speaker 02

  I'll never live that down.

• 2:27Danny Jones?

  You did an experiment on yourself where you took statins for 30 days and then Oreos for 30 days and Oreos dropped your cholesterol.

• 2:35Speaker 02

  So Oreos 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 incentive structures. So I was doing research in an area around lipids and cholesterol that I thought was fascinating. And I had this tool at my disposal, social media, which, you know, I don't have, you know, multi-million dollars to do large trials, but I do have some tools which are social media and then useful brands.

• 3:16Speaker 02

  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 going to be two weeks of Oreo cookies, then a washout period and then a high dose statin therapy, so 20 migs of Crestor. And I know how to dot my i's and cross my t's, so I got, you know, 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, help me to design the study and write the paper and then we executed it.

• 3:58Speaker 02

  And as predicted, a priori, the Oreos lowered my cholesterol by more than twice as much as the statin at about a third of 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.

• 4:40Speaker 02

  And I think in the world we live in now, where there is clearly an uncomfortable collision, uh, incursion event between like academia, conventional medicine and the general public because of access to information.

• 4:53Danny Jones?

  Right.

• 4:53Speaker 02

  Um, and social media, that's something we need to like, understand and play with practically, um, 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?

• 5:15Danny Jones?

  Right.

• 5:15Speaker 02

  Uh, and push forward research. I will tell you it's been a success. I, 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 a

• 5:24Danny Jones?

  Yeah, we'll definitely get, we'll definitely get back to it, but I want to hear, uh, Paul's background.

• 5:29Speaker 03

  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.

• 5:44Danny Jones?

  Why was that unfortunate?

• 5:46Speaker 03

  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. Um, I ended up going into psychiatry because I got really interested in human story, humanity, suicidality, neuroinflammation in the brain and connections with the, 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. Um, 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 are anachronisms and, you know, psychiatry is kind of like 50 years behind the rest of medicine.

• 6:30Speaker 03

  So it, 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 in four years of residency of nutrition or nutritional biochemistry or any sort of thinking about these things, nothing beyond like a gluten lecture for, you know, formal celiac disease

• 7:14Speaker 03

  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. Oh, wow. Yeah, yeah, really severe eczema. I had the whole atopic triad with asthma, eczema, and probably some allergic symptoms.

• 7:58Speaker 03

  I mean, I've seen people reverse depression and ocular autoimmune conditions, thyroid conditions, inflammatory bowel conditions, 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 that 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's been really eye opening for me and it's kind of cool to talk about.

• 8:43Speaker 03

  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. And 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.

• 8:59Danny Jones?

  There, 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 us for long stints and I always feel the best, like bar none compared to anything. That is the 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.

• 9:39Speaker 02

  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 like

• 9:57Danny Jones?

  Why was keto at the bottom of your to do list?

• 9:59Speaker 02

  I mean, think about the ecosystem in which I grew up. I had 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.

• 10:14Speaker 02

  That was, you know, what would be the harm about trying this next diet?

• 10:19Danny Jones?

  What was the first thing you tried?

• 10:21Speaker 02

  I went, what was it like, like standard Mediterranean? I did like low FODMAP, specific carbohydrate. Those are kind of the two that

• 10:28Danny Jones?

  Were there any drugs, pharmaceutical drugs that you tried at all?

• 10:30Speaker 02

  I was on various glucocorticoids. I was on some first line, first line therapies.

• 10:39Speaker 02

  Misalamine, some biologics.

• 10:43Speaker 02

  Yeah, no, it was, 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, my, my college commencement, 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 cushioned. Cause I was taking Stewart at the time. Nobody really knew that, but I was actually like in an active flair. So my life, on the surface, it was, it was nice. I had a lot of nice things on paper, but it was falling apart under the scenes. Actually, like leading up to that commencement, I was in a flair and I wanted to be the speaker because it's a fun opportunity, but I was

• 11:22Speaker 02

  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.

• 12:03Speaker 02

  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.

• 12:23Danny Jones?

  Wow.

• 12:24Speaker 02

  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 to 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 RCT?

• 13:09Danny Jones?

  Companies that have a ton, lots of money to make, right?

• 13:11Speaker 02

  Well, it's never been done. Pharmaceutical companies. Yeah. 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 sort of the types of studies that are needed to make them standard of care aren't gonna 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.

• 13:47Speaker 03

  Did you know that food, processed food companies spend $11 billion on research a year in NIH into nutrition? And that NIH, last I checked, spends about a billion, has about a billion dollar budget. The food industry, and 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 to 11x what the NIH budget for nutrition studies is. So it's, I mean, yeah.

• 14:16Danny Jones?

  Not only that, but they're hiring people from NIH and the FDA to work in their companies.

• 14:20Speaker 03

  And they have, yes, they do that after the people leave, right? There is a revolving door. And for 70, 80 years, industry has had its fingers in academia and in policymaking. 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, the, 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.

• 15:04Speaker 03

  It's very hard to erase that sort of programming that we've had since Ansel Keys, since the 1950s.

• 15:10Danny Jones?

  The 1950s, that's when RJ 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.

• 15:27Speaker 03

  And that pales in comparison to what private companies will spend. I mean, 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 or 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?

• 16:03Danny Jones?

  No.

• 16:04Speaker 03

  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,

• 16:17Speaker 03

  It doesn't matter what you eat, just get enough protein and be in energy balance. But the global energy, 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 I've interacted with personally or hundreds of thousands that I've 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.

• 16:51Danny Jones?

  Right.

• 16:52Speaker 03

  It's about the quality of those calories. But there's something sinister going on beneath the surface.

• 16:56Danny Jones?

  Right.

• 16:57Speaker 03

  Yeah, Global Energy Balance Network.

• 16:58Danny Jones?

  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.

• 17:04Speaker 02

  I would go a step further and say, oh, calories don't cause obesity.

• 17:10Speaker 03

  I agree with you.

• 17:11Speaker 02

  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'm 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 it's 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.

• 17:52Speaker 02

  Rather than thinking about the like complex multifactorial cascade of factors that goes into determining what is ultimately the dependent variable, not the eat independent variable, the dependent variable calories. It's easy to sweep it under the rug. I, 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 GLP one paper.

• 18:38Speaker 02

  So the two biggest, the two biggest drugs, um, probably in history or to be the biggest drug uh, is in history are statins. I think, you know, trillion dollar market over time, something like

• 18:50Danny Jones?

  When did statins first come on the market?

• 18:52Speaker 02

  Oh, I don't know. Mid 1900s, but probably.

• 18:55Danny Jones?

  Really?

• 18:56Speaker 03

  Yeah. What was the first one? Um, was it?

• 18:58Danny Jones?

  This might be a steep question.

• 18:59Speaker 02

  Not sure. Um, but definitely one of the biggest, most prescribed drugs. I think one in four people over 40 are taking it for like secondary. Yeah, something like that. So actually that was in the, the, the paper I can share the reference. But, um, so anyway, this paper came out in cell metabolism last year. Now let's be clear. Cell metabolism, cell metabolism is not a dinky journal. It's a highly regarded scientific journal.

• 19:22Danny Jones?

  1987.

• 19:23Speaker 03

  With low of statin, yeah.

• 19:24Speaker 02

  And, um, this was a human trial where they effectively showed that statins chop GLP-1 levels in humans in half.

• 19:34Danny Jones?

  Okay. What's, what's GLP?

• 19:36Speaker 02

  So GLP-1 is the hormone that drugs like Ozempic and Wegovy try to mimic. So now there's this huge drug market about not exactly biomimicking GLP-1 because they're given at super physiologic doses. That's true. But GLP-1 is a hormone that, um, is depleted in a lot of, um, metabolic health conditions. So, you know, insulin resistance related conditions, diabetes, obesity, PCOS, et cetera. There tends to be a GLP-1 deficiency, has to do with, uh, inflammation in the gut, um, decreased GLP-1 production in the gut. So the hormones produced in the gut, it's called incretin hormone, and also just inflammation, inflammatory cells in the gut have their own GLP-1 receptor. So they'll sop up the GLP-1 and make it more

• 20:16Speaker 02

  bio, uh, less bioavailable. So long story short, low GLP-1 levels are one of the markers for various metabolic diseases. Uh, right now we're treating a lot of people with GLP-1 receptor agonists, which are effective for weight loss. And I'm not against these drugs. Let's be clear, I'm not. However,

• 20:34Danny Jones?

  So Ozempic is a receptor agonist?

• 20:36Speaker 02

  For GLP-1, yeah. I find it interesting that there are human data in a prominent journal showing that statins, a very common drug, deplete levels of GLP-1, which is a hormone and related to a blockbuster group of drugs. It cuts the levels in half. Steve, if you can bring up, it was like, it'll be say statin GLP-1 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 20 mags of Torvastatin versus control, if it's popping up. Those are the results.

• 21:13Speaker 02

  The red lines are statin. That's not subtle. It's not subtle at all.

• 21:19Speaker 02

  And so-

• 21:19Danny Jones?

  What is the blue line?

• 21:20Speaker 02

  The blue line's the control group.

• 21:21Danny Jones?

  Okay, gotcha.

• 21:22Speaker 02

  So it was a placebo-controlled trial, and basically it's showing, you know, statins chopped GLP-1 levels in half. And this was also associated with worse glycemic control, so an increase in average blood sugar, HPA1C, increase in insulin, and increase in insulin resistance, which are all kind of known effects.

• 21:39Speaker 02

  But what bothers me about this graph is not the effect.

• 21:45Speaker 00

  At Humana, our Medicare Advantage plans are easy to understand and easy on your wallet, like offering more benefits than you'd get from original Medicare alone, and including dental, vision, and hearing coverage in every plan. And the best part is, every plan has a $0 or low monthly plan premium, which makes it easier to save, too. So this Medicare planning season, plan well with Humana. Learn more at gethumana.com. Humana is a Medicare Advantage HMO and PPO organization with a Medicare contract. Enrollment in any Humana plan depends on contract renewal. At Humana, our Medicare Advantage plans are easy to understand and easy on your wallet, like offering more benefits than you'd get from original Medicare alone, and including dental, vision, and hearing coverage in every plan.

• 22:27Speaker 00

  And the best part is, every plan has a $0 or low monthly plan premium, which makes it easier to save, too. So this Medicare planning season, plan well with Humana. Learn more at gethumana.com. Humana is a Medicare Advantage HMO and PPO organization with a Medicare contract. Enrollment in any Humana plan depends on contract renewal.

• 22:46Speaker 02

  I'm not concluding from this, no, you can't take statins, or you, you know, GLP-1s are, you know, a hack.

• 22:53Speaker 02

  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 GLP-1 levels in human by half should be a headline. I bet you if you replace 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,

• 23:35Speaker 02

  why isn't this even in the realm of awareness? I don't think that their physicians are hiding this information from people. But at the end of the day, if you're going to start a medication, you deserve to have some informed consent. Right. 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. You should at least know what's going on. 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

• 24:19Speaker 02

  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, you know, muscles, fat. And one is called UDCA. It actually can be prescribed as a drug. And what they found, in humans, again, is just giving back the UDCA, basically reversed the effect.

• 24:50Speaker 02

  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 GLP-1 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. Again,

• 25:21Speaker 03

  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. This is part of

• 25:33Speaker 02

  That happened to me, too. Yeah.

• 25:34Speaker 03

  Right. This is part of common, not, not always, but commonly in human physiology. It happened to me a lot when I was strict carnivore.

• 25:41Speaker 02

  Lean mass hyperresponder. I just interrupted you for a sec. I was listening to your pod with Gary Brecker this morning, and you said your LDL was 125, right?

• 25:49Speaker 03

  Now.

• 25:50Speaker 02

  And he's like, oh, that's high. And you're like, yeah, that's high. You know what mine is? Mine's like 250.

• 25:54Speaker 03

  Mine was as high as 500.

• 25:56Speaker 02

  Whoa. 574.

• 25:58Speaker 03

  Yeah. So

• 25:59Speaker 02

  This is my last.

• 26:00Speaker 03

  In the setting of

• 26:01Speaker 02

  I'm not, I'm not, but to be clear, I'm not saying this is fine for all people. Dick measuring our LDL levels. We can talk about it later. It's now open information. Actually, it was Mark Hyman and Andrew Huberman was talking about my cholesterol. I was paused. I'm like, all right, this is how you introduced me to the world.

• 26:14Speaker 03

  Yeah.

• 26:15Speaker 02

  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.

• 26:20Speaker 03

  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. I think we've all experienced this sort of lean mass hyperresponder 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.

• 27:02Speaker 02

  Right.

• 27:03Speaker 03

  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, Apo B containing lipoproteins are, that's a broader term for LDL and other lipoproteins, which are broadly felt to be atherogenic. These are sacrosanct in Western medicine, and anything that challenges that hypothesis, this lipid hypothesis, is just disregarded, or is not felt to be valid, and is kind of cast out to the side. So it's quite interesting, because that's a very central theme. If we talk about, we'll talk about seed oils in this podcast, and it comes back to that same idea in many ways. Apo

• 27:43Speaker 03

  B 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 Nyx. I mean, I eat carbohydrates now. I don't eat carbs. When you mentioned that you- Like fruit. I eat fruit and honey- Right. And milk. So, milk has lactose, but I don't do- You're not eating bowls of cereal. 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

• 28:26Speaker 03

  better, but my electrolytes did not stay within normal limits. Right. It turns out that there is a need for insulin signaling at the level of the kidney to resorb certain electrolyte molecules. Yes. And that a lot of people, not everyone, some people probably do better with long-term strict keto than others. 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- Interesting. I mean, this is what's interesting, and what I've kind of seen over the years, is that for people who have autoimmune conditions, inflammatory bowel diseases, eczema, skin

• 29:10Speaker 03

  conditions, psoriasis, there are some foods that are widely considered to be healthy that can be triggers for some people. And that's just 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 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. 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

• 29:52Speaker 03

  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, 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 Apo B 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, your LDL is sky high.

• 30:37Danny Jones?

  Yes, that's exactly what happened to me.

• 30:38Speaker 03

  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 Apo B 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 can I just?

• 30:52Danny Jones?

  I, well, I want to say, because it was 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 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 bad. 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

• 31:37Danny Jones?

  electrolytes and more salt in your system and drink way more water if you're not eating carbs.

• 31:43Speaker 02

  I just want to double click on something that Tom, Paul said, I don't know if I said Tom.

• 31:51Speaker 02

  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 piqued, or should be piqued, when you have a patient who has normal LDL, and then their LDL quintuples with the dietary shift. Like, this doesn't happen. This is not known to happen. In fact, familial hypercholesterolemia, which you can tell is a genetic disease, familial inherited, Right. is now, I believe, diagnosed based on just like a threshold blood lipid level.

• 32:33Speaker 02

  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 dollar drug industry? Right. And I said earlier that I think the Oreo versus 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

• 33:15Speaker 02

  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 versus statin paper, was like, very widely circulated. I think it had 15 times the, like, media attention score of your average New England Journal paper, which is the highest impact factor. Great marketing stunt. 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 that didn't understand before, and what did that allow them to do? Act on the physiology.

• 33:59Speaker 02

  So even before the Ori 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, costs your GLP-1 and a half, like that is better patient care.

• 34:43Speaker 02

  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 Apple B 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.

• 35:22Speaker 02

  But it was on like seed oils, and it's actually not a seed, corn oil versus a higher saturated fat diet. 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. Third one down in the top left.

• 36:03Danny Jones?

  Now, you were talking about titrating in carbs to a keto diet?

• 36:07Speaker 02

  Yeah. 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 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 healthful. I was doodling out, you know, how I think about this. Can you bring up steve oil, uh, sorry, seed oil map complex? It's in the top left. Uh, that's a simple one.

• 36:50Danny Jones?

  The one above that.

• 36:51Speaker 02

  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

• 37:37Speaker 02

  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 doodle 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.

• 37:49Danny Jones?

  Nuance doesn't get views. That's the problem.

• 37:51Speaker 02

  But it can. I think you can be provocatively reasonable.

• 37:55Danny Jones?

  Yes.

• 37:55Speaker 02

  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. But does the clickbait? Is it then followed by something with depth? So you do need to pay homage to the clickbait gods or whatever. But that doesn't mean you can't use that as a tool to really advance conversations and research.

• 38:21Danny Jones?

  Totally, totally agree with you.

• 38:23Speaker 02

  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.

• 38:29Danny Jones?

  So before we get to CDOS, I want to ask though, is LDL bad? If you have high LDL, is that bad?

• 38:33Speaker 03

  See, Nick sort of foreshadowed this. My perspective, Nick can add if he feels differently, is that it's contextual. And 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 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.

• 39:07Danny Jones?

  Yes.

• 39:08Speaker 03

  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.

• 39:20Speaker 03

  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, four to six X, right? 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 unfortunately, very few studies are done with fasting insulin. I think if studies were done with fasting insulin, that's probably the best marker.

• 40:05Danny Jones?

  Fasting insulin.

• 40:06Speaker 03

  That's an easily obtainable blood marker. 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, right? 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.

• 40:48Speaker 03

  And if you're saying LDL causes atherosclerosis, you're, the associated inference is that more LDL is always bad. And that's really, 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've become more metabolically healthy because you're getting rid of garbage foods, if you're getting rid of quote carbs, right? And you become more metabolically healthy with a higher LDL. 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, if you stratify the relationship between LDL and cardiovascular disease, there's a marked attenuation when people are insulin sensitive.

• 41:32Danny Jones?

  Interesting.

• 41:33Speaker 03

  Versus insulin resistant, so.

• 41:34Danny Jones?

  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 plaque you have.

• 41:47Speaker 03

  Probably the best imaging, yeah, that you could do is a CT angio. I mean, there's something called a CAC, but it's not as, it's not the same test.

• 41:53Danny Jones?

  Probably the CT angios, you gotta go in that frigging cancer machine, they radiate.

• 41:56Speaker 03

  It's a lot of radiation.

• 41:57Danny Jones?

  Right.

• 41:58Speaker 03

  Yeah, you don't want to do it.

• 41:59Speaker 02

  Above age 40, a CAC is pretty good in terms of, let's say a warranty on your heart.

• 42:05Danny Jones?

  I got a CAC and it said it was zero.

• 42:08Speaker 02

  Yeah.

• 42:09Danny Jones?

  But I also, I think it might've 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've 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.

• 42:24Speaker 03

  Yeah, depends what algorithm they use to interpret CT angio.

• 42:27Speaker 02

  You're, you're, you're getting dangerous and close to things that I'm not supposed to talk about.

• 42:33Speaker 03

  I could talk about it.

• 42:34Speaker 02

  Until Friday. I can talk about what you know. A couple of things I want to poke at. We can come back to the CAC thing later. I actually want to put on my Jade Tower academic prude hat for a minute, for a purpose.

• 42:48Speaker 03

  Iver Tower.

• 42:50Speaker 02

  Yeah, Iver Tower Harvard prude hat.

• 42:55Speaker 02

  So Paul, you effectively said ApoB is not causal. You've said that, right?

• 43:00Speaker 03

  I don't believe ApoB is causal. I don't believe there's enough evidence to suggest that ApoB is causal.

• 43:04Speaker 02

  Okay.

• 43:05Danny Jones?

  Which means what again?

• 43:06Speaker 02

  So.

• 43:06Speaker 03

  Necessary but not sufficient.

• 43:09Danny Jones?

  It's.

• 43:10Speaker 02

  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.

• 43:26Danny Jones?

  Hmm. And you're, when you say ApoB, you mean LDL.

• 43:30Speaker 02

  So just, we should probably define these. ApoB is, stands for apolipoprotein B.

• 43:35Danny Jones?

  Yes.

• 43:35Speaker 02

  It is an apolipoprotein on LDL particles. So there are more particles than just LDL.

• 43:40Danny Jones?

  It's a proxy of LDL.

• 43:41Speaker 02

  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.

• 43:50Danny Jones?

  Got it.

• 43:50Speaker 02

  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 it.

• 44:00Danny Jones?

  Okay. And Paul is saying that it's not causal.

• 44:03Speaker 02

  Right. And then, and then he's, he's trying to, you know, redefine what you mean by causal. And the reason I bring this up is because in these discussions, that little

• 44:18Speaker 02

  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 ApoB is causal. So again, it's interesting social dynamics. My position on ApoB 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.

• 44:56Speaker 02

  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?

• 45:06Danny Jones?

  Hmm.

• 45:07Speaker 02

  If it's super, super shallow, you know, because say you have a positive hormonal and metabolic milieu, then.

• 45:17Speaker 02

  That needs to be weighted when making decisions about what intervention you start or don't, or stay on 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 ApoB and LDL are through the roof. Those are two very different things. Yes. And the failure to wrap context around this individual marker, that's the issue. The issue is not that the marker doesn't have any value in and of itself. That's more

• 45:55Speaker 02

  or less my position. And it's also why I'm very comfortable giving, you know, recommendations, advice on like ways to lower your ApoB, if that's desired, while myself living with crazy high LDL. A pattern that arises in my, in 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 of my history of IBD, how it affects me personally. And what works for me shouldn't generalize to another person. Do you eat any fruit at all, like Paul does, or any carbs at all?

• 46:36Speaker 02

  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 ApoB substantially, which isolated probably would, all things being equal, be more likely to lower my risk specifically for CVD than other things. So you eat zero carbs? Basically. I'm always in ketosis.

• 47:05Speaker 03

  Carbohydrates.

• 47:06Speaker 02

  Carbohydrates.

• 47:07Speaker 03

  That word carbs is kind of like colloquialism, right? People hear carbs, they think like pasta bread.

• 47:12Speaker 02

  Yeah, yeah, yeah.

• 47:13Speaker 03

  It's a carbohydrate. I don't think you eat any carbohydrates because you definitely don't eat any carbs.

• 47:17Speaker 02

  Yeah. I like, I mean, I'll have a little bit, but nothing that will keep me out of ketosis for a prolonged period of time. What do you typically eat throughout the day? Um, now, uh, probably, so I eat two meals a day, um, probably in like a six to seven hour window. So breakfast and dinner. Yeah, breakfast and dinner, like 11 a.m., noon, I'll have a meal. Probably, um, eggs, cheese, salmon, uh, olive oil, um, maybe some academia nuts and then dinner can be, um, fish, chicken steak. Um, I'm pretty simple.

• 47:48Danny Jones?

  No sides, just the meat.

• 47:49Speaker 02

  Pretty much.

• 47:50Danny Jones?

  Wow.

• 47:51Speaker 02

  Pretty much. Um, and 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 people to be healthy. But no, no, it's just, it's not worth it for me. It makes me feel unwell.

• 48:08Danny Jones?

  I understand. Yeah.

• 48:09Speaker 02

  And there's, uh, so there's a lot of individual context. And so, uh, uh, seed oils is another good example. Um, well, actually.

• 48:18Danny Jones?

  And why do you, so, so there's like, uh, a lot of people don't like to eat breakfast. They think breakfast is bad.

• 48:24Speaker 02

  I mean, breakfast is fine.

• 48:25Danny Jones?

  You skip lunch.

• 48:26Speaker 02

  Well, uh, when I say breakfast, I mean, when I break my fast. So 11, 12, sometimes 1.

• 48:30Danny Jones?

  Okay, I got you.

• 48:31Speaker 02

  So, yeah. Lunch, dinner, if you want to say it.

• 48:33Danny Jones?

  I heard that, um, 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.

• 48:41Speaker 02

  I think that's kind of a fairy tale.

• 48:43Danny Jones?

  No.

• 48:44Speaker 03

  There's any evidence for that.

• 48:44Danny Jones?

  That's the Jack Cruz Kool-Aid I've been drinking, bro. Come on, don't break my.

• 48:48Speaker 03

  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 the proteins, 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.

• 49:32Speaker 03

  It's just sort of, maybe we're doing hand waving here. I, I think that that's not what I mean when I say causal. I, I think of causal as direct relationship, right? 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 or ApoB containing.

• 49:48Speaker 02

  Smoking caused lung cancer?

• 49:49Speaker 03

  Well, can I get to that? Yeah. The, you know, if your, 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 what 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.

• 50:33Speaker 03

  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 ratios, perhaps the most predictive, because those are changed in sort of metabolic dyslipidemia. But again, physicians don't do that.

• 51:16Speaker 03

  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. 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, right? What causes metabolic dysfunction? I think most people would agree.

• 51:59Speaker 03

  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 this 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? But 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 get back there, and what makes us less

• 52:44Speaker 03

  metabolically. That's the most interesting question to me.

• 52:46Danny Jones?

  How important is the LP little a marker?

• 52:50Speaker 03

  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 little a, 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, 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

• 53:29Speaker 03

  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 little a looks to be a mop, a sort of cleaning service for oxidized phospholipids. I think there are two scenarios for LP little a, and 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 little a, and that may not represent an

• 54:13Speaker 03

  increased cardiovascular risk. But if your LP little a 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?

• 54:29Danny Jones?

  Yes.

• 54:30Speaker 03

  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 little a and the plaque score.

• 54:40Danny Jones?

  Interesting.

• 54:41Speaker 03

  And that's interesting to me because Western medicine, again, says LP little a horrible 100% of the time, but I think there's more nuance here. So I think there's two scenarios for LP little a. 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 little a can be problematic. But I'm not convinced that a baseline high level of LP little a, which could be genetic, necessarily indicates that you have this burden of oxidized, that has damaged membrane components.

• 55:16Danny Jones?

  I've only got my LP little a measured once. I don't, because it's expensive.

• 55:19Speaker 02

  Yeah, and generally it's recommended to get it once because it's assumed to be static, which it is more resistant.

• 55:24Danny Jones?

  It's assumed to be static.

• 55:25Speaker 02

  It's more resistant to change generally than, say, LDL.

• 55:28Speaker 03

  You can lower it with more saturated fat.

• 55:30Danny Jones?

  So is a lower LP little a good genetically?

• 55:34Speaker 02

  Conventionally, I would say on balance, yeah. Like, I have a very high LP little a. I inherited it from my dad. It's known as what are called Kringle repeats. So basically, Paul was describing LP little a quite nicely. It's like an LDL, but it's got a little tail. It's called an apple little a tail. And the tail is determined by how many, what are called Kringle repeats, you inherit from, you know, one or 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.

• 56:14Speaker 02

  I'll get back to LP little a in a sec, but I just want to finish the conversation and thought around semantics. I don't want to beat a horse on this, but...

• 56:25Speaker 02

  Just from my position, I think causal and most important gets confused. It's like insulin sensitivity, metabolic health, I think it's most important.

• 56:36Danny Jones?

  Agreed.

• 56:36Speaker 02

  I still think Applebee's 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?

• 56:53Danny Jones?

  Of course.

• 56:53Speaker 02

  So like for evidence-based 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, it was a Nature letter in 2015 by Nicholas something I was reading today. It's, 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

• 57:34Speaker 02

  group of people and do what's considered a quote "gold standard," and then prescribe the outcome to everyone without looking at the individual context.

• 57:41Danny Jones?

  Right.

• 57:41Speaker 02

  So the theme that keeps coming up is context, context, context. Now, I will hit LP little like quickly, but I then want to...

• 57:48Danny Jones?

  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 like a custom...

• 58:09Speaker 02

  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 in multi-omics. They had a paper last year in Nature of Biomedical Engineering. How many types of type 2 diabetes are there, Paul? How many types of type 2 diabetes? Yeah. Are we back to linguistics? Okay, it's a, I 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, you know, in lab testing on a cohort of patients.

• 58:53Speaker 02

  And 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 pathophysiology. Right. Again, context nuanced. So you've got incretin dysfunction, liver dysfunction, muscle dysfunction, beta cell dysfunction in 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 two 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.

• 59:32Speaker 02

  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. Oh, wow. 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're 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.

• 1:00:17Speaker 02

  Hmm. And quickly on LP little a, 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 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 little a as basically a wound healing surrogate evolutionarily for vitamin C. You know about this Pauling work? A little bit. So Linus Pauling, who, uh, smart guy, two Nobel prizes. Um, in the nineties, him and his colleague, uh, Dr. Rath, developed this idea that, um, LP little a rose is a replacement for vitamin C. So most mammals can synthesize vitamin C.

• 1:00:59Speaker 02

  Humans can't. And a few other animals can't, like the European hedgehog. Um, and basically vitamin C has wound healing properties. LP little a also has wound healing properties. So if you have a cut, you want to like heal up quickly, evolutionarily scar, don't bleed to death, yada, yada, yada. Um, first, the evolutionary pattern is fascinating because LP little a like 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, um, high dose vitamin C and also L lysine, has to do with how the LP little a actually binds, called the lysine binding sites, you

• 1:01:39Speaker 02

  could effectively reduce the stickiness of the LP little a. So there might be ways, again, beyond the quote, gold standard evidence-based RCT, yada, yada, that you could potentially attenuate your LP little a risk. I think first and foremost, agree with Paul, being metabolically healthy. But beyond that, there's some really interesting physiology that, that we can talk about. The last thing I'll say about LP little a is, isn't it interesting that 10 years ago, nobody talked about it? And now everybody's talking about it. And it just so hap- yeah, yeah. It was, I was surprised. It was, um, my subject, the most popular newsletter I ever wrote. Really? On a pretty, would seem like an esoteric topic. I never hear anybody talk about it. So many people were fascinated by it. Um, the observation I'm making, again,

• 1:02:24Speaker 02

  incentive structures. 10 years ago, people didn't talk about it. Now there are New England Journal trials on five different medications targeting it. Interesting. So incentive structures is, is, is, 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 the debate. But should we get into seed oils?

• 1:02:51Speaker 03

  Can we get into metabolic health real quick?

• 1:02:52Danny Jones?

  Yeah.

• 1:02:53Speaker 03

  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

• 1:03:35Speaker 03

  is like nine micro IU per ml, but there are other metrics that suggest that 90% plus 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 nine. I think the best level is probably below five. Most of the time when I check mine, it's less than three. And again, fasting insulin is a $30 test. You can get it online. There are, although it's democratized lab companies now, if your doctor won't order it for you, you need a new doctor. 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?

• 1:04:21Speaker 03

  Not bad.

• 1:04:21Danny Jones?

  It should be below five what? What is the measurement?

• 1:04:23Speaker 03

  It's micro IU per ml.

• 1:04:27Speaker 02

  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.

• 1:04:37Speaker 02

  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 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 of examples, both out of like, top papers that came out

• 1:05:20Speaker 02

  this year in 2025. One was on autophagy in the brain, something really interesting. Which means what? Basically, it's a cellular recycling process. We like, break up and clean things. People often associate with fasting. There was a study, I think it was in Nature, again, I can send all the references after the fact, but basically what they showed is that in depression, autophagy is dysfunctional in a brain region called the lateral hybinaula, which, think about it, 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 like, the drugs we use to treat human beings, so SSRIs, selective serotonin reuptic inhibitors, ketamine,

• 1:06:05Speaker 02

  different classes of antidepressants, they converge on this pathway to like, alter this basic metabolic function. Or another example, again, this is all like, literally the Cell Science Nature Press 2025 data. There was another one, Paul, I'll have to share this one with you, you'll love it, but on a neurotransmitter called homovanilic 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. Homovanilic acid does. Interestingly, in humans...

• 1:06:40Speaker 02

  Homovanilic 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 homovanilic acid, or either of the gut bugs, is sufficient to reverse depression phenotypes.

• 1:07:10Danny Jones?

  Whoa.

• 1:07:11Speaker 02

  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 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

• 1:07:52Speaker 02

  the roots of the tree of metabolic diseases, and that manifests in all the metabolic diseases, obesity, cardiovascular disease, depression, Alzheimer's, you name it. Highlighting that importance is, I think, somewhere where we're unified.

• 1:08:05Speaker 03

  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 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?

• 1:08:48Speaker 03

  You didn't sleep enough, you ate crappy, you had a stressful event in your life, you got exposed to a toxin, like, these can probably be linked to most of the issues we have, because 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 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, many of the same things that affect inflammatory bowel disease, that's wild. And that's where Western medicine has completely lost the plot.

• 1:09:26Danny Jones?

  Yeah, it seems like it's all connected. And just trying to treat one thing is like playing whack a mole.

• 1:09:30Speaker 02

  Medicine is silo metabolism is unified. That is a fact.

• 1:09:33Speaker 03

  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.

• 1:09:44Danny Jones?

  Right. That's crazy.

• 1:09:46Speaker 03

  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-

• 1:09:58Danny Jones?

  Is medical intervention number three?

• 1:09:59Speaker 03

  I think it is.

• 1:10:00Danny Jones?

  Wow. That's crazy.

• 1:10:02Speaker 03

  You can fact check it, but I'm pretty sure-

• 1:10:03Danny Jones?

  What about, um, quick, quick little, so I don't want to spend too much time, but a quick question. What about, um, uh, what is the shit I'm taking again? Zetimib? Is that bad?

• 1:10:11Speaker 02

  I think it's most benign, in terms of side effects of the LDL lowering drugs. Basically-

• 1:10:15Danny Jones?

  It lowered my, it cut my LDL in half.

• 1:10:18Speaker 03

  I would, I think- Did it change your cardiovascular risk?

• 1:10:21Danny Jones?

  Right. I don't know.

• 1:10:22Speaker 03

  And why did you take it in the first place?

• 1:10:24Danny Jones?

  It lowered my LDL.

• 1:10:26Speaker 03

  And did they get a fasting insulin?

• 1:10:27Danny Jones?

  That's a good question. I haven't looked. I got my blood work.

• 1:10:29Speaker 02

  You think it would change fasting insulin?

• 1:10:31Speaker 03

  No, no. Whoever prescribed you Zetimib-

• 1:10:33Speaker 02

  Oh, you're just saying context.

• 1:10:34Speaker 03

  Whoever prescribed you Zetimib didn't look at your metabolic health. They, you were eating keto, presumably Danny, I'm telling you your own story here.

• 1:10:41Danny Jones?

  Yeah.

• 1:10:41Speaker 03

  You were eating keto, your LDL goes up, they give you a Zetimib to lower your LDL under the premise that it's increasing your cardiovascular risk. They did nothing to assay your cardiovascular metabolic health.

• 1:10:51Speaker 02

  It's, it's, medicine is-

• 1:10:53Danny Jones?

  I'm pulling out my blood work.

• 1:10:54Speaker 02

  The art of making decisions at an individual basis, given incomplete and imperfect data. So, again, down to the individual level-

• 1:11:04Speaker 02

  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.

• 1:11:14Danny Jones?

  Right.

• 1:11:15Speaker 02

  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 and humility. On the precautionary principle, I avoid them, defined as highly industrialized oils. But I think a lot of the claims 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.

• 1:11:56Speaker 02

  So if we bring back up the, uh, the complex, actually, you know, the complex or a simple version of the seed oil map, um, Steve, the simple version here. I think if we think about it like this, so linoleic acid's at the middle, uh, focus on the, the side and the bottom, how is it processed outside the body and how is it processed inside the body? Cause 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 would be fun.

• 1:12:32Speaker 03

  Do people understand what linoleic acid is? We might want to back up and do fats, I mean.

• 1:12:36Speaker 02

  Go ahead.

• 1:12:37Speaker 03

  Yeah. So we, we touched on this earlier.

• 1:12:42Danny Jones?

  Can you see if it's on there?

• 1:12:43Speaker 02

  Oh, your, your insulin?

• 1:12:46Speaker 03

  Um, I'm betting you a meat stick that I brought you.

• 1:12:50Speaker 02

  You already gave me the meat stick, so I'm not giving it back.

• 1:12:53Speaker 03

  I'm betting you're delicious. I'm taking one back if it's not on there.

• 1:12:56Speaker 02

  I'm South African, I will fight you for that drool.

• 1:12:59Speaker 03

  The, uh, so when we have fats, we have saturated fats, right? Which is a chain of carbons and all the carbons have hydrogens. Um, all of the positions of the carbon atom are occupied by hydrogen. When you have a monounsaturated fat, you have one double bond.

• 1:13:15Speaker 02

  You owe me meat stick.

• 1:13:16Speaker 03

  Oh.

• 1:13:16Danny Jones?

  It's on there?

• 1:13:17Speaker 03

  He gets a meat stick.

• 1:13:18Danny Jones?

  3.2.

• 1:13:18Speaker 03

  That's pretty good, right? Less than 5 micro IU per ml. So just to complete the discussion there.

• 1:13:24Danny Jones?

  If you didn't know who ordered this for me, you wouldn't have made that bet.

• 1:13:27Speaker 03

  Yeah, maybe they were listening. They were listening to 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 azetimibe to you. I'm not your physician.

• 1:13:44Danny Jones?

  Okay.

• 1:13:45Speaker 03

  So, anyway, that's the conversation there.

• 1:13:47Danny Jones?

  And cut it out.

• 1:13:48Speaker 03

  Well, don't take my advice. I'm not your doctor.

• 1:13:50Danny Jones?

  Oh, really? I take all my medical advice from the internet.

• 1:13:53Speaker 03

  You're a sovereign human. You're a sovereign human. 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...

• 1:14:07Danny Jones?

  Yes.

• 1:14:07Speaker 03

  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.

• 1:14:18Danny Jones?

  Right.

• 1:14:18Speaker 03

  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.

• 1:14:32Danny Jones?

  Okay.

• 1:14:32Speaker 03

  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.

• 1:14:42Danny Jones?

  Right.

• 1:14:42Speaker 03

  So...

• 1:14:43Danny Jones?

  And polyunsaturated fats, for the layman, are seed oils, right?

• 1:14:46Speaker 03

  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 soybean oil might be alpha-linolenic acid, which is an omega-3. 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, no, no seed oil

• 1:15:28Speaker 03

  is purely polyunsaturated fat, and no animal fat, butter is not purely saturated either, right?

• 1:15:35Danny Jones?

  Right.

• 1:15:35Speaker 03

  So, polyunsaturated fat is not synonymous with seed oils. Part of the concern for me with seed oils is that they do contain large amounts of polyunsaturated fats, right? Specifically omega-6

• 1:15:49Danny Jones?

  Yes.

• 1:15:49Speaker 03

  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.

• 1:16:07Danny Jones?

  Okay.

• 1:16:08Speaker 03

  Not even close to omega-3s, right? We're talking about, you know, a few, people who are supplementing with fish oil might have two grams, or a gram to two grams of omega-3. In 2025, the average American consumes five tablespoons of seed oils, which is

• 1:16:25Danny Jones?

  A day?

• 1:16:26Speaker 03

  A day.

• 1:16:26Speaker 02

  When you say seed oils, are you saying linoleic acid and omega-6, or are you saying, so the way-

• 1:16:32Danny Jones?

  So, let's break it down simple for people.

• 1:16:34Speaker 02

  Can people see this?

• 1:16:34Danny Jones?

  For people that don't know, for people that get all their information from 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?

• 1:16:49Speaker 03

  A little more complicated than that, but yeah.

• 1:16:50Danny Jones?

  It is a little bit more complicated, but if you want to break it down, make it binary, that's basically how most people understand it.

• 1:16:56Speaker 02

  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 monounsaturated, one double bond, or polyunsaturated. Within polyunsaturated, there's omega-3, so like fatty fish, fish oil, and then there's omega-6. And, 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.

• 1:17:38Speaker 02

  If omega-6 rich foods are like highly refined and processed to get the oil that is heated and has additives added to it, that is the highly industrialized seed oil.

• 1:17:49Speaker 03

  True.

• 1:17:50Speaker 02

  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 gonna have the biggest disagreement.

• 1:17:59Speaker 03

  Okay.

• 1:18:00Speaker 02

  About omega-6. So.

• 1:18:03Speaker 03

  Yeah, we can talk about.

• 1:18:04Speaker 02

  The physiologic impacts of omega-6 specifically, and then we'll talk about processing.

• 1:18:07Speaker 03

  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 five 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.

• 1:18:24Danny Jones?

  And where are they getting all of this from?

• 1:18:25Speaker 03

  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 also.

• 1:18:35Danny Jones?

  Just basic processed foods.

• 1:18:36Speaker 03

  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, right? 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.

• 1:19:22Speaker 03

  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. 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.

• 1:20:05Speaker 03

  French fries, obviously, it's in bread and all the fast food restaurants, processed foods. Yeah. In order to get five tablespoons of corn oil, you would have to eat 60 years 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, 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 will never use walnut oil,

• 1:20:48Speaker 03

  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. Sure. 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, 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. Right. 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

• 1:21:28Speaker 03

  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. Right. So there's a difference between saying linoleic acid is, you know,

• 1:21:53Speaker 03

  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 10x 1,000% higher than it ever has been historically. Because of our consumption.

• 1:22:15Danny Jones?

  Do we know when our consumption, this five tablespoons per day started? Like, how, when did this start? And like, how, how has it grown?

• 1:22:25Speaker 03

  The first seed oil was introduced in 1911. Procter 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.

• 1:22:44Danny Jones?

  Wow.

• 1:22:45Speaker 03

  Humans didn't have like chest pain, like this clinical syndrome is not defined until much later. Yeah. So.

• 1:22:53Danny Jones?

  Holy shit. Global production of vegetables. Is vegetable oil the same thing?

• 1:22:56Speaker 03

  Yeah. Vegetable oil is the euphemism, right? So seed oil is.

• 1:22:59Danny Jones?

  Oh, look, it shows all of them. Palm, soybean, canola. Wow.

• 1:23:02Speaker 03

  So 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. Right? Because animal fats, 1999% of what we eat is animal fat. And then Procter and Gamble makes Crisco.

• 1:23:48Speaker 03

  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 $100,000 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 Missola 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, Polly unsaturated her family tonight.

• 1:24:31Speaker 03

  So they're talking about cooking with this corn oil. There are these crazy ads. Yeah. So like, anyway, they, they become a part of the conversation and the cultural milieu over the last, let's say a hundred years, give or take, starting in 1911. Before that, essentially cottonseed oil was made in the 1860s, but not used in food until 1911. Previously, most people know this, but previously seed 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 slipperiness when they're wet.

• 1:24:59Danny Jones?

  Right. And when did this food pyramid get constructed? Do we know what year that happened?

• 1:25:04Speaker 03

  There's been a couple of them, but I think the first one, I was, I want to say the 80s.

• 1:25:07Danny Jones?

  With bread at the bottom.

• 1:25:09Speaker 03

  Yeah, I think it was the 70s or 80s, I'm guessing, but yeah.

• 1:25:11Danny Jones?

  And that, that had to do with, that was funded by some of these industries as well, right?

• 1:25:15Speaker 03

  There is, there is evidence of industry funding and yeah.

• 1:25:19Speaker 02

  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 and not in center structure.

• 1:25:39Danny Jones?

  It's super important.

• 1:25:40Speaker 02

  No, no, I, I'm really not trying to color the conversation.

• 1:25:42Danny Jones?

  We're trying to break down your ivory tower, Nick.

• 1:25:44Speaker 03

  It's important for context. It's important for context.

• 1:25:46Speaker 02

  I'm a slicker agent.

• 1:25:48Speaker 03

  We'll, we'll get to the science, but it's, it's important for context, I think.

• 1:25:51Speaker 02

  I appreciate that.

• 1:25:52Speaker 03

  And I, I apologize, I'm not trying to color the conversation. I just think that's, and Danny was curious, and I think that's a really interesting question because when, just, just intuitively, again, this is not, this is not double line randomized placebo controlled trial.

• 1:26:05Danny Jones?

  Right.

• 1:26:06Speaker 03

  When humans introduce new things into their diet and environment, we probably should be cautious.

• 1:26:11Danny Jones?

  Yes.

• 1:26:11Speaker 03

  So, and again, that's just, that's just philosophical, like we're not, you know, not everything that gets introduced is bad for us.

• 1:26:17Speaker 02

  I wanna, 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

• 1:26:37Speaker 02

  You know, the way these seed oils are introduced into our diet is evolutionarily unprecedented. It's coincident with a decline in metabolic health. Therefore, we should just-

• 1:26:49Speaker 03

  We didn't talk about the coincidence with metabolic health. But I don't like to draw those because I think there are so many things that do that. But yes, that's it.

• 1:26:55Speaker 02

  We agree on that. So, but so I see that as different. I see it is different saying, look, this could be a problematic compound. Here are the reasons and let's do some more research. Then 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 substantiated.

• 1:27:20Danny Jones?

  RFK said that?

• 1:27:21Speaker 02

  I'm pretty sure. Didn't he say something to that effect?

• 1:27:23Speaker 03

  I don't know.

• 1:27:23Speaker 02

  It's the most unhealthy-

• 1:27:24Speaker 03

  I don't know if he said that.

• 1:27:25Speaker 02

  We can, Steve, you can find it and people can fact check me. I'm 99% sure he said something.

• 1:27:29Danny Jones?

  He also said that EMFs cross the blood brain barrier.

• 1:27:32Speaker 02

  He did say something on Rogan about, anyway. So I don't think he's the best scientific resource. Not to talk about him as a human.

• 1:27:38Speaker 03

  He's a great human.

• 1:27:39Danny Jones?

  He's got good intentions.

• 1:27:39Speaker 03

  He's a great dude.

• 1:27:40Speaker 02

  Intentions count.

• 1:27:41Speaker 03

  I love him as a human.

• 1:27:42Speaker 02

  But I guess I want to challenge listeners to say like, yeah, this is important context. But now let's talk about like-

• 1:27:50Speaker 03

  Let's talk about the science.

• 1:27:51Speaker 02

  The 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? Is it bad in the body?

• 1:28:00Speaker 03

  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, and you can add your, add your correlative, 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, right? We have had an explosion of chronic disease in this country. Obesity, infertility, cancer, dementia, depression.

• 1:28:29Danny Jones?

  I think it has a lot to do with technology too, people being sedentary.

• 1:28:31Speaker 03

  Exactly. Choose your boogeyman. And I don't like those overlays. I think that Nick is right to 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 in pools, right? You know, like this, 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, right? 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

• 1:29:12Speaker 03

  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 try and figure this out. But yeah, the correlation is not terribly instructive. Do you want to start talking about linoleic acid physiology, or you want me to? Um, let me say a word and then I'll let you add to it. Yeah. Um, so from my perspective, I don't know exactly what Nick's gonna 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 essential, quote-unquote, for humans. Now, the levels which we need are questionable.

• 1:29:57Speaker 03

  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 oils. There's linoleic acid in steak. There's linoleic acid in... Fish? I agree. Yeah, fish and egg yolks. It's in all, it's in all whole foods, right? Yeah. Okay. Now, so it's considered to be an essential fatty acid because when you deprive rats or mice... Of linoleic acid? Yeah, they don't do well. You have to feed them a very specific diet. I don't think that many humans...

• 1:30:42Speaker 03

  In recent memory are deficient in linoleic acid. Okay. We could argue differently for omega threes 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, um, let's just say second messengers in the human body. And, um, 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. Right. When you, uh, when you work out, you need inflammation to repair and rebuild. Right. And if you abrogate or you 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?

• 1:31:24Speaker 03

  In the mitochondria, you generate reactive oxygen species, you generate superoxide species. These are essential for proper signaling, both at the level of insulin and, 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. Um, and so anti-inflammatory and inflammatory second messengers do come from both omega six and omega three 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 three or omega six, 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.

• 1:32:09Speaker 03

  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 Stefan Geyer, he did a great paper about this, I think in, uh, 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

• 1:32:52Speaker 03

  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 polyencyltrated fats stay in our membranes and that's just something to think about.

• 1:33:14Danny Jones?

  Interesting.

• 1:33:15Speaker 02

  Steve, can you bring up adipose tissue cardiovascular mortality?

• 1:33:22Danny Jones?

  The bottom one.

• 1:33:22Speaker 02

  The bottom one. So what do you make of this graph? It's from a meta. I think you actually shared it with me 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 six and specifically linoleic acid in human fat tissue. And it shows a favorable effect.

• 1:33:46Speaker 03

  It shows a favorable effect.

• 1:33:47Speaker 02

  So what do you make of that?

• 1:33:48Speaker 03

  There are other studies they didn't include that show an unfavorable effect.

• 1:33:52Speaker 02

  Of human adipose tissue?

• 1:33:53Speaker 03

  Yeah, I can show you one. Yeah.

• 1:33:56Danny Jones?

  So can you explain this? S H H E C 308?

• 1:33:59Speaker 02

  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.

• 1:34:18Danny Jones?

  Okay.

• 1:34:19Speaker 02

  And if it's to the right, it's unfavorable. So here it's showing a favorable effect. Now, here's my thing.

• 1:34:27Danny Jones?

  A favorable effect to cardiovascular mortality?

• 1:34:30Speaker 02

  Of having higher linoleic acid levels in the body. Now.

• 1:34:33Danny Jones?

  So having more seed oils is better for cardiovascular?

• 1:34:35Speaker 02

  First of all, linoleic acid, I wouldn't conflate with with seed oils.

• 1:34:39Danny Jones?

  Okay.

• 1:34:40Speaker 02

  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.

• 1:35:09Speaker 03

  It's tough. It's an interesting, this is, 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?

• 1:35:22Danny Jones?

  Yeah.

• 1:35:23Speaker 03

  But higher levels of linoleic acid in the blood do often correlate with better cardiovascular outcomes.

• 1:35:28Danny Jones?

  Interesting.

• 1:35:29Speaker 03

  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 the activity of an enzyme called D6D, delta 6D saturase, also known as fatty acid desaturase 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, right?

• 1:36:12Speaker 03

  That is consistently linked with worse cardiovascular outcomes, right? And D6D 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 D6D is causal for cardiovascular disease.

• 1:36:54Speaker 03

  And that's just saying if you look at a bunch of people with various levels of delta 6D saturase based on their genetics, the people that have higher levels of delta 6D saturase, an enzyme that moves linoleic acid down this synthetic pathway, tends 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, right?

• 1:37:21Danny Jones?

  Right.

• 1:37:22Speaker 03

  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 oxlam molecules.

• 1:37:32Danny Jones?

  Okay.

• 1:37:33Speaker 03

  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 difficult. Yeah. It's not the full deciding factor, but it's confusing for sure.

• 1:38:12Speaker 02

  I don't think you can disregard based on a...

• 1:38:15Danny Jones?

  One second, one second. Steve, what happened to our background, bro? What do you got going here? It disappeared. I can bring it back up. I didn't want to like distract everybody.

• 1:38:25Speaker 02

  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, but...

• 1:38:34Speaker 03

  The only reason I mention is because the other one I was going to show, I think, was similar size or a little bit bigger than one of them.

• 1:38:38Speaker 02

  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 Helm's Deep, you have the orcs that are outside the linoleic acid in circulation, and then those that get through the barrier, or say biotransformed 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.

• 1:39:23Speaker 02

  So in this case, you know, how much bioconversion 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 the health proxy? Is it delta six desaturase activity? We can measure that. Is it linoleic acid in adipose tissue? Is it circulating? Like, what are 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.

• 1:40:05Speaker 02

  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, 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 dihome. Oh, dihome. 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, it sounds kind of cool, so we'll say that.

• 1:40:49Speaker 02

  So interesting thing about 1213 dihome is it decreases with age and has really beneficial effects on the heart. So it can inhibit perivascular fibrosis, basically the hardening of vessels. So dihome keeps the arterial walls more flexible. Flexible, improves cardiovascular function, inhibits things that are bad metabolically, like ER stress. And again, this is an oxidized- And you lose this as you age. 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 1213 dihome levels by about 39% from a cold plunge. Really? Yeah, because this is something made in brown and beige fat. There were studies done that show this? Yeah, human studies.

• 1:41:34Speaker 02

  I have a YouTube video where I get input from, I think it was the first- Which study was it? I can find it while Paul is responding.

• 1:41:42Speaker 03

  Steve, can you show my screen? But yeah, this is the study I was mentioning.

• 1:41:47Danny Jones?

  Holy shit, that worked good.

• 1:41:49Speaker 03

  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.

• 1:42:04Danny Jones?

  And this is from what?

• 1:42:05Speaker 03

  This is just an independent study, right?

• 1:42:07Danny Jones?

  Okay.

• 1:42:08Speaker 03

  So we're just showing that when we're looking at adipose tissue, the results are conflicting and confusing.

• 1:42:13Danny Jones?

  Yeah.

• 1:42:14Speaker 03

  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?

• 1:42:21Danny Jones?

  Yeah.

• 1:42:21Speaker 03

  Or do we look at RCTs? Cause we can talk about randomized controlled trials like Minnesota and Sydney. Do we look at adipose levels in correlation with coronary artery disease? I think Nick is starting to talk about oxylipins. 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.

• 1:42:54Danny Jones?

  Sin, linoleic, linole, easy for you to say. Acid comes from seed oils though, right?

• 1:43:00Speaker 03

  Not exclusively, right? Because it's, it's found in things like an almond has a little bit, right? An egg yolk has a little bit. We talked about this, right?

• 1:43:07Danny Jones?

  Right, right, right.

• 1:43:08Speaker 03

  Steak has a little bit of linoleic acid.

• 1:43:10Danny Jones?

  But primarily it comes.

• 1:43:11Speaker 03

  I think that the major, the major source of exposure for humans to linoleic acid in the last 100 years is seed oils.

• 1:43:17Danny Jones?

  Yes, okay.

• 1:43:18Speaker 03

  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.

• 1:43:31Danny Jones?

  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?

• 1:43:51Speaker 03

  It depends on the quality of the trial, right? So at, on my X account, I pinned the 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.

• 1:44:14Speaker 02

  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 cardiometabolic profile, independent of brown adipose tissue. Cell Reports Medicine 2024, first author, Cuardo Fasoli.

• 1:44:29Danny Jones?

  And they gave, how many people were they putting in the cold plunge?

• 1:44:33Speaker 02

  And what was the, I have to look back at the, 64.

• 1:44:38Danny Jones?

  So I was only aware of one study that was like a, was on like Scandinavia, I forget who, Heuerman always talks about it.

• 1:44:47Speaker 02

  Was it the dopamine one? The one where dopamine increased peripherally? Anyway, we can get back to that.

• 1:44:53Danny Jones?

  I don't think so. I think this was a cardiovascular one.

• 1:44:55Speaker 02

  Go ahead, Paul.

• 1:44:56Speaker 03

  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?

• 1:45:08Danny Jones?

  Right.

• 1:45:09Speaker 03

  You look here, so I summarized about 11 of them, and there's Roast Corn Oil, there's Ozone Diet Heart, there's one called the Medical Research Council Trial, Los Angeles Veterans Trial, Sydney Diet Heart, Minnesota Coronary, Diet and Reinfarction, there's St. Thomas Atherosclerosis, National Diet Heart Study, the Finnish Mental Health Hospital Study, there's Houtsmuler, Diabetic Angiography or Angiopathy Trial. And so these are all done between, let's say, 1958 and 1980s.

• 1:45:38Danny Jones?

  Okay.

• 1:45:38Speaker 03

  We don't have any more recent trials on seed oils.

• 1:45:41Danny Jones?

  Wow.

• 1:45:42Speaker 03

  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 you have some trials which say seed oils don't increase the risk of cardiovascular disease, or potentially even lower it. And

• 1:46:07Danny Jones?

  So there are some that say it lowers it.

• 1:46:09Speaker 03

  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, you can basically pick something wrong with every single one of those trials. For instance, if you look at the Ozodiet Heart Study, we can double click on this.

• 1:46:30Danny Jones?

  Can we see who funds these trials too?

• 1:46:32Speaker 03

  They're, they're from so long ago. So here's Ozodiet 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

• 1:47:16Speaker 03

  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 at another one. What's a good one here? The Finnish mental hospital studies, another.

• 1:47:42Danny Jones?

  Why don't we do these studies anymore? If it's such, such a hot topic in society?

• 1:47:46Speaker 02

  I was reading the Minnesota coronary experiment study, which is done in a multi-center, multiple mental hospitals. And actually, I was, 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.

• 1:48:00Danny Jones?

  Ethics have changed.

• 1:48:01Speaker 03

  Millions of dollars also, and who funds 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 dollar study, over seven years plus potentially, right? The ethics are difficult. 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.

• 1:48:41Speaker 03

  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 seed 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, 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. So this is, um, this is pretty commonly included in meta-analyses, 1959 to 1971, 676 subjects. Controlled diet, which is often the saturated fat-rich diet versus the experimental diet.

• 1:49:26Speaker 03

  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, but to be high in poly-actricated fats from soybean oil. The other was served as a control with a normal hospital diet. After six years, the diets were reversed. Now, the use of the cholesterol lowering diet was associated with significantly reduced mortality from coronary heart disease. Okay? Now, there were significantly more trans fat in the controlled diets. The hospital K had 2% trans fat in the controlled diet versus zero 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 cardio-toxic medication, thyoridazine, which we don't use anymore,

• 1:50:11Speaker 03

  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. 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 thiarytizine. And that's going to make the 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 the 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, look at the combined.

• 1:50:55Speaker 03

  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 if you throw out the trials that are obviously poorly constructed, right? So then you have to

• 1:51:07Danny Jones?

  It's the foundation of all the new stuff we come up with is this these poorly done studies.

• 1:51:11Speaker 03

  These poorly done studies, which will probably never be repeated.

• 1:51:14Danny Jones?

  That's crazy.

• 1:51:15Speaker 03

  So it's this, we end up in this situation where we almost have to look at mechanisms. Because the randomized controlled trials and then, you know, you can look at stuff like we can look at

• 1:51:23Danny Jones?

  And who is the guy Huberman was talking about? 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.

• 1:51:39Speaker 03

  Bhattacharya has talked about that or no, it's John Ioannidis.

• 1:51:43Danny Jones?

  No, he had like a he had like an Asian last name, like a Chinese or Japanese or something like that.

• 1:51:49Speaker 02

  It's one thing to say

• 1:51:50Danny Jones?

  What was that guy's name?

• 1:51:51Speaker 02

  Incorrect, another thing to say incomplete.

• 1:51:54Danny Jones?

  He said either incorrect or new stuff has basically

• 1:51:59Speaker 03

  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 could always poke holes in a study. I think one that would be good to talk about that actually think.

• 1:52:20Speaker 02

  Is on balance, a pretty decent study that has gotten some heat is the Minnesota coronary experiment. If we're going to delve into one.

• 1:52:25Speaker 03

  We can talk about it.

• 1:52:26Speaker 02

  So, um, yeah, just to kind of give a high level breakdown of this, um, there were patients kept at mental hospitals and I think one nursing home and they were given a, a diet that was either, um, very elevated in linoleic acid. I think it was close to 14% of K-calc from linoleic acid.

• 1:52:45Speaker 03

  Eighteen to 20.

• 1:52:46Speaker 02

  Of calories from linoleic acid? Are you sure?

• 1:52:48Speaker 03

  Well, uh. Can you punch it on this, Steve? Our experimental diet goal was to provide 18 to 20% of calories from polyunsaturated fat while the control diet aimed for 18% of calories from saturated fat. Okay. There were 9,000, give or take, participants.

• 1:53:00Speaker 02

  I, I think it ended up being like 13 point, I actually have the primary paper up here. Um, something like 13 point, uh, anyway, that, that aside, there was a, 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, uh, linoleic acid in the form of corn oil versus a group that got a higher saturated fat diet relatively.

• 1:53:30Speaker 03

  Right.

• 1:53:31Speaker 02

  And then the results were a massive drop in LDL in the corn oil group.

• 1:53:35Speaker 03

  Right.

• 1:53:36Speaker 02

  But trending towards worse mortality. So more deaths and more cardiovascular disease, including on autopsy. So they had autopsies of these people.

• 1:53:46Speaker 03

  Especially in the older, the older age groups, over 65.

• 1:53:49Speaker 02

  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 and.

• 1:53:56Speaker 03

  There's a crazy story about this one.

• 1:53:57Speaker 02

  Yeah, Malcolm Gladwell, you should have.

• 1:53:58Speaker 03

  I was telling, Nick, Malcolm Gladwell did a, uh, did a podcast about this on his revisionist history called The Basement Tapes. Mm-hmm. The history of this is that Ansel Keys, so who is a kind of an infamous researcher. Yeah. Um, I didn't mean to interrupt you, Nick, but I'll just add this and then I'll let you run with it again. Um, infamous researcher 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, I mean, Ansel Keys-

• 1:54:40Danny Jones?

  And that's this stuff?

• 1:54:41Speaker 03

  That's this study.

• 1:54:43Danny Jones?

  Oh, wow.

• 1:54:43Speaker 03

  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, that's possible that he wasn't happy about this, who knows?

• 1:54:59Danny Jones?

  Whoa.

• 1:55:00Speaker 03

  Or they just got lost.

• 1:55:01Speaker 02

  Yeah, so I, I again come 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.

• 1:55:09Speaker 03

  Who knows?

• 1:55:09Speaker 02

  We can talk a little bit more about the study and the criticisms of it. Steve, can you go copy the PubMed ID and Paul's tweet and then go to figure six 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.

• 1:55:29Speaker 03

  Right.

• 1:55:30Speaker 02

  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 three quarters of the patients dropped out of the trial.

• 1:55:51Speaker 03

  It's complicated.

• 1:55:51Speaker 02

  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 Ansel Keys knew trans fats elevated saturated fats, so would have designed the diet in such a way-

• 1:56:12Speaker 03

  They elevated LDL. Trans fats elevated LDL.

• 1:56:14Speaker 02

  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 would be.

• 1:56:23Speaker 03

  Mm-hmm.

• 1:56:24Speaker 02

  Now, even if there was a difference, I really find it unlikely that it drove-

• 1:56:29Speaker 03

  You might go to my screen, Steve.

• 1:56:31Speaker 02

  Oh yeah. I have that. And you want figure? I was gonna show six in the panel on the bottom left. You'll know what I mean when I say it. Show it.

• 1:56:42Speaker 02

  I don't think that the trans fat difference, even if it exists, would drive the full effect. It's possible. Figure five or figure six? Six. Okay.

• 1:56:51Speaker 02

  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 end 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.

• 1:57:34Speaker 02

  So how do you account for findings like, are we seeing Paul's screen? If you go down to the, scroll down to 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 I'm 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. The lower the cholesterol goes, the more people die. 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.

• 1:58:17Speaker 02

  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.

• 1:58:49Danny Jones?

  Yeah.

• 1:58:50Speaker 02

  It's rebutting a claim, not necessarily making the extreme opposite claim. And I think that's super important.

• 1:58:57Speaker 03

  I mean, these might be interesting to look at, too.

• 1:58:59Danny Jones?

  The higher the cholesterol, the lower the mortality rate?

• 1:59:02Speaker 03

  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, cholesterol drops. When you give people polyunsaturated fats, 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-Meier survival curves we can talk about as well.

• 1:59:23Danny Jones?

  Okay.

• 1:59:24Speaker 03

  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's 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, in other saturated fat-rich margarins. As Nick has pointed out, both groups probably got trans fats.

• 2:00:09Speaker 03

  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.

• 2:00:27Danny Jones?

  Right.

• 2:00:27Speaker 03

  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, right? 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.

• 2:00:52Speaker 02

  Yeah, I think it's just a matter of, even if, even if.

• 2:00:58Speaker 02

  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 Apo便. It's like, well, lower is better with respect to what?

• 2:01:43Speaker 02

  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 60 saturation, 12, 13 dihomie, 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.

• 2:02:09Danny Jones?

  Right.

• 2:02:10Speaker 02

  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 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.

• 2:02:51Danny Jones?

  To dietary recommendations?

• 2:02:54Speaker 02

  It says no relevance.

• 2:02:55Danny Jones?

  Who's dietary recommendations?

• 2:02:56Speaker 02

  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 in 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. Okay, 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."

• 2:03:38Speaker 02

  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. And 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, which 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 guideline say, hey, don't get more than this much linoleic acid?

• 2:04:13Speaker 03

  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 Willet 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 nine 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.

• 2:04:47Danny Jones?

  I saw that video you did.

• 2:04:48Speaker 03

  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 calories from the... It's totally false what Willard is saying here. In distinction, they definitely tell you to limit your saturated fat.

• 2:05:08Speaker 02

  Right, and so it's a matter of like, double standards. I really like, I read it before, but I'm gonna read it again, how this paper ends. Ramsden and 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 provide 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.

• 2:05:44Speaker 03

  Right.

• 2:05:45Speaker 02

  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.

• 2:06:02Speaker 03

  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 weak. 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 experimental group, and the blue dotted line is the control group, and you know, the bottom right is women over age, actually, all participants over age 65. You can see a large divergence there. And what you see is that 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, right? So in a Kaplan-Meier curve, or maybe I mixed them up.

• 2:06:45Speaker 02

  No, you're right. So lower survival if the, the red line is lower than the blue line.

• 2:06:50Speaker 03

  Yeah.

• 2:06:50Speaker 02

  In the over-65 group, and so, I don't think...

• 2:06:53Speaker 03

  The diet group is the blue line, I'm sorry. So that, in this way, it's going up, so the people, the cumulative proportion of death, they kind of reversed it. The cumulative proportion of death, the blue line is the experimental group, the red line is the control group. Experimental group meaning what? 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, right, 450, 500 days. So right here, you see this clear divergence. 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. 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,

• 2:07:37Speaker 03

  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. None of it's perfect. If you look at the best trials, in my opinion, I would argue, they show things like this and the 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?

• 2:08:22Speaker 03

  Or should I be eating soybean oil? What do I do to be healthy?

• 2:08:26Danny Jones?

  Got it. Now, what is your current LDL? Is it still in the 500s?

• 2:08:31Speaker 02

  Last check was 574.

• 2:08:32Danny Jones?

  574. And you're letting it ride at 574?

• 2:08:34Speaker 02

  I'm monitoring my cardiovascular health by coronary C T injury.

• 2:08:41Danny Jones?

  Right, right, right.

• 2:08:42Speaker 02

  And last check, it was zero.

• 2:08:43Danny Jones?

  Zero.

• 2:08:44Speaker 02

  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 high LDL. But then she went keto and it went to like the well into the 400s. 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 um, we ended up talking about like, whoa, what should she do? Her lifetime exposure to LDL on Applebee's astronomical. Got a coronary CT and geography? Zero.

• 2:09:21Danny Jones?

  Zero.

• 2:09:22Speaker 02

  Zero.

• 2:09:22Danny Jones?

  Sixty-five.

• 2:09:23Speaker 02

  Sixty.

• 2:09:24Speaker 03

  So, yeah, how can LDL be causal, right?

• 2:09:26Speaker 02

  Well, again, we're getting back to. 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.

• 2:09:36Speaker 03

  Does she know her fasting insulin?

• 2:09:37Speaker 02

  It's low.

• 2:09:38Speaker 03

  Presumably.

• 2:09:39Speaker 02

  Yeah, I've seen it's probably like three years.

• 2:09:40Speaker 03

  She's metabolically healthy.

• 2:09:41Speaker 02

  She's very metabolically healthy.

• 2:09:42Speaker 03

  Wow.

• 2:09:43Speaker 02

  Typically or by blood work? Yeah, yeah.

• 2:09:45Speaker 03

  Yeah.

• 2:09:45Speaker 02

  She looks like she's like forty.

• 2:09:47Speaker 03

  Yeah, right.

• 2:09:48Danny Jones?

  What do you think the ultimate cau- I know there's probably multiple causes. But what do you think the ultimate cause is why so many people are obese in America?

• 2:09:55Speaker 03

  This is the big question, man.

• 2:09:57Speaker 02

  So, so actually, this is a good, a good place to talk about mechanisms. Do you think seed oils can cause obesity and so how?

• 2:10:04Speaker 03

  Okay, so let me pull up another study that I, I found this one in preparation for this podcast. I think you guys will find this interesting. So, um, there are a couple of things here.

• 2:10:16Speaker 03

  Could.

• 2:10:17Danny Jones?

  Endocannabinoids.

• 2:10:18Speaker 03

  Yeah. So, this one is interesting. This is a trial from twenty twenty. And it looked at levels of two AG and anandamide. These are endocannabinoids, similar to cannabinoids that you would get from like marijuana. In a hundred and eighty-three 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 two 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, right?

• 2:11:01Speaker 03

  And conversely, there's a drug called ramonabant, which is a, a CB1 antagonist. So cannabinoid receptor one antagonist is ramonabant. Ramonabant 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.

• 2:11:27Danny Jones?

  Oh, shit.

• 2:11:27Speaker 03

  So it, it's off the market in the United States. But when you block the CB1 receptor mechanistically with ramonabant, 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 things, but will include seed oils, also processed grains, processed sugars. Right. 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

• 2:12:09Speaker 03

  polymorphisms in D6D, right, so fatty acid desaturase 2, or who are predisposed, is it possible that consuming linoleic acid or Western foods increases the production of 2AG and AEA, leading to appetite dysregulation? It certainly happens in animal models. If you give mice or rats linoleic acid, you see levels of 2AG 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 2AG 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 punitive mechanism by which seed oils may affect satiety.

• 2:12:54Speaker 03

  Interesting. 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. Yes. And you're kind of done. Right. But something different happens when you add a potato chip or whatever, like It's like you can't stop. 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?

• 2:13:36Speaker 03

  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? 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,

• 2:14:20Speaker 03

  I was like, that's really interesting. Is it possible, again, this 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.

• 2:14:38Speaker 02

  I think it's an interesting hypothesis. I want to, you would agree, I don't mean this to be offensive, but that is stretching. Do you think?

• 2:14:49Speaker 03

  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 2AG and AEA. I think every piece is there. In studies where the levels of linoleic acid are decreased, you can see these also go down.

• 2:15:08Speaker 02

  Let me phrase this a different way.

• 2:15:09Speaker 03

  When people lose weight, these go down.

• 2:15:11Speaker 02

  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?

• 2:15:22Speaker 03

  Who knows? 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 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, right?

• 2:16:05Speaker 03

  We have these randomized controlled trials where we're looking at saturated fats versus seed oils specifically. But I think 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.

• 2:16:21Speaker 02

  Okay.

• 2:16:21Speaker 03

  Yeah.

• 2:16:22Speaker 02

  I want to ask a few, this is really helpful. I think people are going to appreciate hearing this from you. 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 zero to 10, how confident are you?

• 2:16:34Speaker 03

  Okay.

• 2:16:35Speaker 02

  So on a scale of zero to 10, how confident are you that linoleic acid can cause obesity in humans?

• 2:16:43Speaker 03

  Now, obesity wouldn't be 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.

• 2:17:00Speaker 02

  Okay.

• 2:17:00Speaker 03

  And downstream effects of ox lambs. And so, and then obesity is just more complex.

• 2:17:08Speaker 02

  All right. So we'll start with negative downstream effects on LDL oxidation and production of ox lambs, zero to 10, how confident?

• 2:17:14Speaker 03

  Those are two different outcomes.

• 2:17:16Speaker 02

  Oxidation of LDL.

• 2:17:17Speaker 03

  Pretty confident. There's more.

• 2:17:19Speaker 02

  Give me a number.

• 2:17:20Speaker 03

  Eight to nine, multiple randomized controlled trials showing that more linoleic acid leads to higher levels of oxidation of LDL.

• 2:17:26Speaker 02

  And how about obesity, out of curiosity? And if it's a two, then say two.

• 2:17:29Speaker 03

  Obesity is such a, it's just such a complicated thing, right? So is your question, what contribution to obesity do seed oils have?

• 2:17:36Speaker 02

  Omega six, and then I'm going to ask about seed oils. Those are two different questions.

• 2:17:40Speaker 03

  Oh, okay. So you're asking about omega six?

• 2:17:41Speaker 02

  Omega six.

• 2:17:42Speaker 03

  Well, I guess.

• 2:17:44Speaker 03

  I don't know that we can necessarily differentiate those because omega-6 don't occur like, are you talking about like walnuts?

• 2:17:50Speaker 02

  Yeah.

• 2:17:50Speaker 03

  No, I don't think walnuts cause obesity much.

• 2:17:52Speaker 02

  But to be clear, like, three ounces of walnuts is something like 31, 32,000 milligrams of omega-6. It is more, it's, there's a ton of omega-6.

• 2:18:03Speaker 03

  Let's, let's check that.

• 2:18:04Speaker 02

  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.

• 2:18:12Speaker 03

  Well, that's less than a tablespoon, but okay. I mean, you know, well, we're talking grams, right?

• 2:18:18Speaker 02

  Okay, 10 grams.

• 2:18:19Speaker 03

  10 grams, yeah, yeah.

• 2:18:22Speaker 02

  Of just linoleic acid.

• 2:18:23Speaker 03

  Yeah.

• 2:18:24Danny Jones?

  An ounce of walnuts contains roughly 10.8 grams of omega-6 fatty acids.

• 2:18:29Speaker 02

  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.

• 2:18:38Danny Jones?

  It also contains 2.5 grams of omega-3s.

• 2:18:41Speaker 02

  ALA. We can talk about that later. But, okay, so, so, you know, if somebody were to consume four ounces of walnuts, that's like, you know, on the order of 43, 44 grams of just linoleic acid.

• 2:18:56Speaker 03

  Right.

• 2:18:56Speaker 02

  So that's gonna be, you know, multiple, like, they're almost 400 calories from just linoleic acid. You're on a 2,000 calorie diet, that is 20% of your calories from linoleic acid. So could four ounces of walnuts be bad for you? Cause obesity?

• 2:19:10Speaker 03

  I think it depends on the context, yeah. I think that in general, if we're talking about walnuts specifically.

• 2:19:15Speaker 02

  Maybe. You're like, you're, you're a very unconfident, this is interesting, maybe, but we, we don't know.

• 2:19:20Speaker 03

  Yeah, we don't know.

• 2:19:21Speaker 02

  Okay. I think that's useful to hear. Now.

• 2:19:23Speaker 03

  And again, like, the walnuts conversation is very different than the seed oil conversation.

• 2:19:28Speaker 02

  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 creep 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 are unfrag, they're fragile and they're bad for you. I have literally had me say that like, Quest, have people tell me that Quest candy bars, non-ironically, are healthier than sardines because they're high in PUFA.

• 2:20:03Speaker 02

  And it's just like, but-

• 2:20:05Speaker 03

  Sardines are high in PUFA or Quest candy bars are high in PUFA?

• 2:20:07Speaker 02

  Uh, sardines, they have omega 3. So like-

• 2:20:09Speaker 03

  Oh, well, yeah.

• 2:20:09Speaker 02

  I'm just, I'm just saying, that is at the extreme end of the interpretation.

• 2:20:13Speaker 03

  Sure.

• 2:20:13Speaker 02

  But

• 2:20:16Speaker 02

  triage point one, if people get nothing out of it, um, is linoleic acid omega 6 in whole food is very different than the heated processed stuff, right?

• 2:20:26Speaker 03

  Certainly going to occur with, uh, many other cofactors, vitamin E, et cetera.

• 2:20:30Speaker 02

  Right, right. But also, there's gonna be, just to complete the, the, 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 metabolite, 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 measure, it's called myeloperoxidase, MPO. Myeloperoxidase is really interesting because it, um, increases cardiovascular risk in several ways. One way is, uh, increasing the oxidation of LDL from within the vessels. Interestingly, it's, uh, produced by fat, actually around blood vessels, it's called perivascular adipose tissue. It decreases

• 2:21:14Speaker 02

  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 out, I can boost my ketone levels with sesame oil over 20 hours to like 6 millimoles.

• 2:21:55Speaker 03

  Yeah, whether that has any clinical relevance is questionable.

• 2:21:57Speaker 02

  The, the point is, whether we're talking about 12, you know, 13 dihome, I guess we're calling it, um, oxidation by myeloperoxidase, generation of 4HNE, turning into ketones, this biomolecule has so many paths.

• 2:22:11Speaker 03

  Sure, linoleic acid can go a lot of different places.

• 2:22:13Speaker 02

  And the metabolic milieu, your, 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 oil. I can agree with you on that. Your lean, healthy keto are, you know, two ounces of walnuts bad for you? I don't think so.

• 2:22:45Speaker 03

  I don't think so.

• 2:22:46Speaker 02

  Yeah.

• 2:22:46Speaker 03

  I mean, it's a different situation.

• 2:22:47Speaker 02

  Oh, I agree. And I just, I think that's really, those are extreme examples.

• 2:22:51Speaker 03

  Yeah.

• 2:22:52Speaker 02

  But they highlight a very important point.

• 2:22:54Speaker 03

  Yeah, I think what, most of what I think is important about this conversation is the oxidized, well, presumably oxidized, refined, bleached and deodorized seed oils.

• 2:23:03Speaker 02

  Okay. So I want to ask you now, refined, bleached and deodorized, big $10 scary words.

• 2:23:09Speaker 03

  Right.

• 2:23:09Speaker 02

  Specifically, what's going on that you're concerned about in that? The refining, let's, the heating oxidation, we can table that, that's obvious. Refining, bleaching, deodorizing. What specifically in that chemical process is increasing risk?

• 2:23:23Danny Jones?

  What is the, isn't there something called hexane or something?

• 2:23:26Speaker 03

  There is hexane, yeah.

• 2:23:27Danny Jones?

  And that's neurotoxic?

• 2:23:29Speaker 03

  Benzene also.

• 2:23:30Speaker 02

  Hexane is neurotoxic. But again, it's a question of-

• 2:23:32Danny Jones?

  And hexane comes off of when you do the bleach and the oxidizing of these oils.

• 2:23:37Speaker 02

  It's used to extract the oil from something where-

• 2:23:39Danny Jones?

  Right, right, right.

• 2:23:40Speaker 02

  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 there's 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 it's very different from someone saying seed oils contain neurotoxins and implying that

• 2:24:18Speaker 02

  there's actually seed oil-associated neurotoxicity. Which, it's hard, it's hard because you wouldn't go off of like, what is required to cause acute toxicity? It's not like you're gonna have a tablespoon of corn oil and get neurotoxicity. So there's the, 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.

• 2:24:44Speaker 03

  There have been studies on this. Steve, will you show my screen real quick?

• 2:24:49Speaker 03

  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 tucking 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

• 2:25:16Danny Jones?

  looking at Acrylene's one?

• 2:25:19Speaker 03

  Acrylene is, is one, that's when you heat the oil. You can look at the presence of heavy metals in vegetable oils. That's been looked at. Now, I mentioned this early in the podcast, antimony is probably the biggest issue. It's migration from the polyethylene containers, edible vegetable oils. And then the third one to consider is that the vegetable oils are actually quite high in phthalates. We haven't talked about this at all. Phthalates are endocrine disrupting sort of

• 2:25:50Danny Jones?

  Phthalates are in vegetable oils?

• 2:25:51Speaker 03

  Yeah. And this is, they say it in the title, non-negligible exposure source to humans. And they actually give a, a relative amount here. In this paper, they do the calculated average estrogenic equivalents 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 equivalents from these phthalates. I mean, you know, we're talking like, there's 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

• 2:26:36Speaker 03

  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, for many, many

• 2:26:54Danny Jones?

  Yeah, 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?

• 2:27:10Speaker 03

  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 looked at the peroxide value in omega three and omega six oils, and they might've looked at acrylene 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, a deep fryer, but you put soybean oil into a deep fryer. If you go to Five Guys, if you go to In-N-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.

• 2:27:55Danny Jones?

  And they change the oil once a month?

• 2:27:56Speaker 03

  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.

• 2:28:03Danny Jones?

  Yeah.

• 2:28:04Speaker 02

  I just texted you the graph. Your computer's hooked up. You can pull it up.

• 2:28:08Speaker 03

  Yeah, well, if you look at what's in, um, so, um, some of these oils, these, these are the aldehydes, um, and, and some of these aldehydes are, they're quite high with heating. There's another graph in, um, in the paper where they talk about the amount of specific aldehydes and acrylene specifically. The amount of acrylene, um, in a large French fry at McDonald's is equivalent to the amount of acrylene in a pack of cigarettes. Now, this is just one compound. And when I've said this in the past in my content, uh, people like to say, Paul Saladino is saying that seed oils are worse than cigarettes, which is not what I just said.

• 2:28:49Speaker 03

  People can re-watch the tape, but, um, it's, it's basically saying that of this one compound, which is a carcinogen, um, which is very likely, it is, is pretty significant. So this is a quote from there. 154 gram potato chip serving, uh, aldehyde contents are not dissimilar to those arising, um, 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 oils.

• 2:29:18Danny Jones?

  Right.

• 2:29:19Speaker 03

  That looks to be very bad, but, um, at least in terms of that one compound. So there's, there's a, there's a, um, a spectrum here.

• 2:29:26Danny Jones?

  So what about like, uh, Steak and Shake down the road? They're advertising that they cook all their fries in tallow now.

• 2:29:32Speaker 03

  So my perspective is this doesn't solve the equation completely. If you actually, when you raid into that one, they, they never solved this problem where the fries were pre-soaked in seed oils.

• 2:29:41Danny Jones?

  Oh, no.

• 2:29:42Speaker 03

  So they, 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 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 clean, just a simple organic chemistry equation, like a peroxide value. The, 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

• 2:30:24Speaker 03

  is sort of a, an oil that is from beef fat, right? So people don't know tallow. It's a beef fat. 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, a lower degree of oxidation relative to a seed oil. Down, down the road we go. And so theoretically, Steak and Shake cooking in their fries in tallow decreases the amount of things like this acrylene, these aldehydes.

• 2:30:55Danny Jones?

  Yeah.

• 2:30:55Speaker 03

  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.

• 2:31:09Danny Jones?

  Yeah.

• 2:31:10Speaker 03

  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.

• 2:31:15Danny Jones?

  Right.

• 2:31:15Speaker 03

  Not have any oxidative liability in the human organism. So there's a lot.

• 2:31:20Danny Jones?

  This is like, it's just like we talked about. I mean, this is just like one siloed.

• 2:31:26Danny Jones?

  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 of 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 fucking 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 use or what it is.

• 2:32:07Speaker 03

  Environment, is this light energy magnetism?

• 2:32:09Danny Jones?

  Yeah, is that part of it? And then like another, 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.

• 2:32:23Speaker 03

  It's not true.

• 2:32:23Danny Jones?

  It's not true?

• 2:32:24Speaker 03

  It's only the Nicoya Peninsula. The blue zones are kind of a myth. Yeah.

• 2:32:27Danny Jones?

  Okay, but like, I don't know, if, 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,

• 2:32:38Speaker 03

  That's true.

• 2:32:38Danny Jones?

  Most of the people there, they wake up and 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 fuck they're doing.

• 2:32:55Speaker 03

  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.

• 2:33:04Speaker 03

  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 is a big deal. So these are all things that make a difference, purpose. And these are all things that haven't 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 Ikaria, 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.

• 2:33:47Speaker 03

  Icaria, 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.

• 2:34:13Danny Jones?

  And different values, different overall values. They don't value earning a huge salary as we do in America.

• 2:34:20Speaker 03

  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, 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 spending, and they're spending, they're generally spending that time at the beach with their family. It's just, it's families on the beach, all, at least where I live, right? And where you've visited it. These are coastal towns, but family's a big part of the ethos there. So these are, these are other pieces of the conversation that are not able to be ignored.

• 2:34:57Danny Jones?

  Yeah, there's definitely so many pieces too. And I think, and doesn't, um, 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, uh, if the sun, sun exposure can lower things like Alzheimer's, cholesterol, heart disease, this kind of, this kind of stuff.

• 2:35:21Speaker 02

  I think there's a small effect of like infrared light on PCSK9 and lowering LDL. I don't think it's going to be that tremendously.

• 2:35:28Speaker 03

  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 on the podcast. I mean, 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?

• 2:36:13Speaker 03

  Because outdoors, you're getting infrared. Does the infrared balance the UV? You have whole, I think of-

• 2:36:18Danny Jones?

  He brought a big incandescent light bulb and he shined it in our faces during the podcast.

• 2:36:22Speaker 03

  Oh, yeah, like his chicken light.

• 2:36:23Danny Jones?

  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. It's like-

• 2:36:32Speaker 02

  I lived for all my teenage years in a room with giant iguanas that had a big heat lamp.

• 2:36:36Speaker 03

  Oh, yeah.

• 2:36:36Speaker 02

  That did my medical- I mean, that's why, eating a standard American diet, I was resistant to waking.

• 2:36:41Speaker 03

  It's, it's-

• 2:36:41Speaker 02

  That was the secret, the iguana's lamp.

• 2:36:43Speaker 03

  Yeah, you think of, I think of sunlight-

• 2:36:45Speaker 02

  I'm joking everybody about that.

• 2:36:46Speaker 03

  I think of sunlight as like whole food, you know, and then indoor light is like processed food. They're very similar, you know. A 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 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 a light that you consume affects you in, in, in ways that are, that are not dissimilar from-

• 2:37:30Danny Jones?

  Yeah, not just by, you know, not just from like a biological perspective, but from a, a, 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 SeaWorld.

• 2:37:49Speaker 02

  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.

• 2:38:15Danny Jones?

  Hmm.

• 2:38:16Speaker 02

  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.

• 2:38:25Speaker 03

  I think I saw you talking about that.

• 2:38:27Speaker 02

  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 it has to do with a mitochondrial dance.

• 2:38:47Danny Jones?

  Is there any animal that doesn't sleep?

• 2:38:49Speaker 02

  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 damage mitochondrial components.

• 2:39:31Speaker 02

  So, like anything, biology, nature, they operate in cycles. And this fusion and fission 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 and fission, sort of 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 is going to be different

• 2:40:15Speaker 02

  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,

• 2:40:57Speaker 02

  I pity the people who can't be confused, awed and humbled 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 this data, Paul, I actually just texted you a picture of, it was a mouse study. You have to do, in my experience, to pluck their eyeballs out. But they showed that high blue light exposure caused mitochondrial fragmentation in the retina, a little of the mitochondria fracturing apart. A giant boost in oxidative stress.

• 2:41:41Speaker 02

  So the red here on this image is oxidative stress.

• 2:41:45Danny Jones?

  It's black.

• 2:41:45Speaker 02

  In the retina. So you can see blue light exposure, way more oxidative stress.

• 2:41:49Danny Jones?

  Wow.

• 2:41:50Speaker 02

  And what ends up happening is, if you check out the other picture, the retina thins. That is on the right, like the thinned retina from blue light exposure. And in humans, there's like risks of things like age related.

• 2:42:01Danny Jones?

  Well, it's crazy because there's a lot of, there's a couple that I'm aware of, like big time video gamers, competitive video gamers, who have, they play the games, but on the computer screen, right in front of them. And they've had retinal detachments and they've had surgeries because of that.

• 2:42:17Speaker 02

  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.

• 2:42:27Danny Jones?

  Yeah.

• 2:42:27Speaker 02

  So this is not saying like, you can't like, watch a movie with your partner at night, but like.

• 2:42:34Danny Jones?

  Get a big red light panel and blast it in your face while you're watching the movie.

• 2:42:37Speaker 03

  The retina is a really interesting thing. I mean, there's, we can circle this back to CDOs if we want, or we can just leave that, that dead horse.

• 2:42:43Speaker 02

  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 how a different fatty acid.

• 2:42:49Speaker 03

  Yeah. 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 stuff. 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.

• 2:43:15Speaker 02

  Wow. I mean, it's very physiologically possible. Combination of high blue light and things that it can oxidize.

• 2:43:22Speaker 03

  Yeah, the retina is so that's that's 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.

• 2:43:52Danny Jones?

  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 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.

• 2:44:25Speaker 03

  The cataracts, that's in the lens. So that's the front part of the eye, the retina is a little bit deeper.

• 2:44:30Danny Jones?

  Maybe it wasn't.

• 2:44:31Speaker 03

  But it's interesting.

• 2:44:32Danny Jones?

  Maybe it was a different surgery.

• 2:44:33Speaker 03

  It probably was, yeah. It's interesting. No, the red light in the cataracts is interesting.

• 2:44:36Danny Jones?

  All anecdotal stories are super interesting to me, you know?

• 2:44:39Speaker 02

  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.

• 2:44:52Danny Jones?

  Their what?

• 2:44:53Speaker 02

  Their N equals ones, their anecdotes, their stories.

• 2:44:54Danny Jones?

  Oh.

• 2:44:55Speaker 02

  Like as in like I cut out seed oils or, you know, X, Y, and Z. And then this happened.

• 2:44:59Danny Jones?

  Yeah.

• 2:45:00Speaker 02

  And there's a couple of 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. 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.

• 2:45:21Speaker 02

  The way we have done science historically has been studying populations of heterogeneous humans. There's always a lot of a 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 Lyver, Kapler Meyer 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",

• 2:46:06Speaker 02

  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 at an 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.

• 2:46:50Speaker 00

  Mm-hmm.

• 2:46:51Speaker 02

  And to me, that's so silly. 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 like 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.

• 2:47:35Speaker 02

  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 what we've talked through here, I think what we've hopefully risen is a lot of curiosity and uncertainty, because there's not definitive answers for a lot of the questions we want to ask. And that's okay.

• 2:48:00Speaker 03

  I think the similarities of how people get there are interesting as well, between divergent paths. It's always been interesting for me, because 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.

• 2:48:18Danny Jones?

  Really?

• 2:48:18Speaker 03

  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 psy-ops 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.

• 2:49:00Speaker 03

  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 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 equals one 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 unanimous,

• 2:49:45Speaker 03

  where 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.

• 2:49:55Danny Jones?

  Burn less?

• 2:49:56Speaker 03

  Burn in the sun. Yeah.

• 2:49:57Danny Jones?

  Oh, interesting.

• 2:49:58Speaker 03

  Yeah. Yeah. They don't, it's not that they burn their food less, it's that they burn, their skin burns less.

• 2:50:03Danny Jones?

  Interesting.

• 2:50:03Speaker 03

  So their human experiences. When you decrease the amount of polyunsaturated fats, again, this is just observation, sort of like

• 2:50:10Danny Jones?

  Yeah.

• 2:50:11Speaker 03

  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.

• 2:50:32Danny Jones?

  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 wear sunglasses, 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.

• 2:50:53Speaker 03

  Well, yeah, there's a connection there, I think, between the brain and the skin in terms of melanin connection, melanin

• 2:50:57Danny Jones?

  Yep.

• 2:50:58Speaker 03

  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.

• 2:51:16Danny Jones?

  Right.

• 2:51:17Speaker 03

  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, the 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 in 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,

• 2:51:59Speaker 03

  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.

• 2:52:10Danny Jones?

  Hmm. 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

• 2:52:22Danny Jones?

  Um, 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.

• 2:52:33Speaker 02

  You're not taking my sockeye salmon.

• 2:52:34Danny Jones?

  I should be eating fish that was caught in the Gulf of Mexico. Is there, is there any?

• 2:52:40Speaker 02

  I think that's a sustainability thing.

• 2:52:42Speaker 03

  Uh, not that I'm aware of. The problem I have with fish in general is it's just so full of heavy metals, microplastics.

• 2:52:48Danny Jones?

  Really?

• 2:52:49Speaker 03

  Yeah.

• 2:52:50Speaker 02

  More so farms.

• 2:52:52Speaker 03

  Uh, even the, even the wild stuff's pretty bad today.

• 2:52:55Speaker 02

  Do you have a, a test you suggest getting? I'll get it in a report, but I ate a ton of fish, like.

• 2:52:59Speaker 03

  Just check, you check your.

• 2:53:00Danny Jones?

  Yeah, I ate a ton of like snapper and grouper that's caught right out here.

• 2:53:03Speaker 03

  Check your serum heavy metals, just start with that.

• 2:53:05Speaker 02

  I have.

• 2:53:06Speaker 03

  Lead, mercury.

• 2:53:07Speaker 02

  Lead, mercury, cadmium are all fine.

• 2:53:09Speaker 03

  Arsenic?

• 2:53:09Speaker 02

  Um, I don't recall, but, um, I mean, the, the mercury is on the, it's like nine ish. It wasn't like low, low, but I also don't eat like, I try to avoid like swordfish and.

• 2:53:20Speaker 03

  Right.

• 2:53:21Speaker 02

  You know, like a big I two, uh, 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.

• 2:53:28Danny Jones?

  Sardines are really low mercury, right?

• 2:53:30Speaker 02

  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.

• 2:53:39Danny Jones?

  Mm hmm.

• 2:53:39Speaker 02

  Like the distribution across fish is massive.

• 2:53:42Speaker 03

  It's big.

• 2:53:43Speaker 02

  So.

• 2:53:43Danny Jones?

  Yes.

• 2:53:44Speaker 03

  There's no tests for microplastics and PFAs that are widely available.

• 2:53:48Speaker 02

  Yeah.

• 2:53:48Speaker 03

  Um, these are interesting to me.

• 2:53:50Speaker 02

  Um, I just think a thing we keep coming back to as you were speaking is like the context in the human body and the vilification of single components in food. So another example we were talking about, I think we're talking about with both of you off air was like salt. Like is salt bad? People say saturated fast bad and this, that 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.

• 2:54:35Speaker 02

  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, 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 F1 alpha, increase levels of a hormone called VEGF that makes vessels grow. So what they find, at least in animals, is that more, you know, 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,

• 2:55:17Speaker 02

  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 like the blue inset. Maybe I did, maybe I didn't. Yeah, blood-brain barrier image too. So like, 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 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 hormone system is changing. And this ends up changing things like nervous system tone.

• 2:56:01Speaker 02

  So that can increase blood pressure, including nervous system tone to the arteries and the kidneys. It also increases susceptibility to inflammation, which can drive up blood pressure. But interestingly, so, you know, you can't do these controlled experiments in humans, but you can look at like human genetic cases or interventional trials and see, you know, is there, you know, a lineup? So what do we see in human obesity? Increased blood pressure. Well, what will we predict to see if you had human obesity, but no leptin signaling?

• 2:56:33Danny Jones?

  No increase in hypertension?

• 2:56:34Speaker 02

  No, so you would expect in congenital leptin deficiency, which is 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 than 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

• 2:57:18Speaker 02

  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, adjusting sodium restriction. What is the effect of sodium restriction on blood pressure? Obesity, it drops it. And non-obese?

• 2:57:31Danny Jones?

  Doesn't affect it at all.

• 2:57:32Speaker 02

  Nothing at all. Which is fascinating, and actually, if you go, go to-

• 2:57:36Danny Jones?

  That's crazy.

• 2:57:37Speaker 02

  Go to NEJM dot plot. 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. They got a tiny salt diet versus a massive salt diet. As you drop the low-

• 2:58:00Danny Jones?

  The low body fat's on the far left.

• 2:58:01Speaker 02

  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 was a direct effect of leptin on the kidneys that caused 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.

• 2:58:45Speaker 02

  And then studies like this, New England Journal, there's no refining the message-

• 2:58:50Danny Jones?

  Right.

• 2:58:50Speaker 02

  -to account for various metabolic conditions, various metabolic factors. So when it comes to saturated fat, omega-6, salt, what we keep on seeing again and again, and this is the theme, is that like-

• 2:59:02Speaker 02

  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 macar diet and you're sedentary, should you be relatively more concerned about omega-6 and salt? Probably. If you're lean 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.

• 2:59:31Speaker 03

  When I read this one on your Substack, 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?

• 3:00:10Speaker 02

  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

• 3:00:54Speaker 02

  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

• 3:01:36Speaker 02

  insulin. Because I think, you know, one thing that will happen is the higher insulin levels cause partitioning of more energy to the fat cell.

• 3:01:43Speaker 03

  So you're saying insulin resistance?

• 3:01:45Speaker 02

  Yes.

• 3:01:46Speaker 03

  Which is kind of like metabolic dysfunction.

• 3:01:48Speaker 02

  Yeah, so it's, it's, it's a, it's a, it's a hand wavy, or it's, it's a wide umbrella, but intentionally.

• 3:01:56Speaker 03

  Sure.

• 3:01:56Speaker 02

  Because I think to get like, to say XYZ is the sole piece of the puzzle will be misleading.

• 3:02:01Speaker 03

  Do you think all carbohydrates cause that to the same extent? Because there are, there are lots of populations like the Tuukka Sinta 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...

• 3:02:17Speaker 02

  No, I don't.

• 3:02:18Speaker 03

  Yeah, I don't see excess carbohydrates as a major driver of insulin resistance.

• 3:02:22Speaker 02

  It's not sufficient.

• 3:02:23Speaker 03

  Right.

• 3:02:24Speaker 02

  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.

• 3:02:37Speaker 03

  I'm so interested in the seed, though.

• 3:02:39Speaker 02

  I, I agree, I agree. But, 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. And not only did 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, it was like coded as irritability, but that aside. Not only do the mice have more anxious behavior, and they're a valid test for that,

• 3:03:21Speaker 02

  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, it 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 rations changed, sugar intake skyrocketed, and then they followed people, followed babies,

• 3:04:03Speaker 02

  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.

• 3:04:16Speaker 03

  From a process of sugar.

• 3:04:16Speaker 02

  So when you're talking about the seed, I think it starts pre-birth. It 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 the 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 gonna have that RCT in humans, transgenerational

• 3:04:58Speaker 02

  RCT on diet coke and anxiety, like, it's not possible to do. So what are we left with? 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, this is interesting data, and...

• 3:05:24Danny Jones?

  What do you guys think? I'm sure you've seen Mark Bell's Sugar Diet. Have you seen this?

• 3:05:30Speaker 02

  I've covered it, yeah.

• 3:05:32Danny Jones?

  Yeah, you made a video about it.

• 3:05:33Speaker 02

  Yeah.

• 3:05:33Danny Jones?

  What is going on there?

• 3:05:36Speaker 02

  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, 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 et al. 2025, and they showed that protein restriction. So a 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.

• 3:06:17Speaker 02

  Protein restriction causes about, in the lean healthy men, a 600-ish increase in energy expenditure per day without any increase in activity. So it was, 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. It was very consistent when they went back to a higher protein diet. So the protein restriction was 9% of calories from protein. And then when they went back up to like 18% calories protein, their metabolic rate lowered. And what they were able to show is in these mice, sorry, in these people, it was an increasing

• 3:06:59Speaker 02

  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, I can find the study in a second, but, and they were able to show like a causal pathway, but by FGF21 changes fat cell metabolism, increases energy expenditure quite massively. Again, a 600 calorie effect. A couple of 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.

• 3:07:41Speaker 02

  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.

• 3:07:53Danny Jones?

  Okay.

• 3:07:54Speaker 02

  Same effect, same massive increase in energy expenditure and the participants, the way they, 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 four to one 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

• 3:08:36Speaker 02

  intake on average over to like the whole up titration by over 300 calories per day. I think a calculator is like, I should have been in a quote unquote 6,000 calorie surplus, but I lost 6.4 pounds.

• 3:08:45Danny Jones?

  So it's a low protein, which is the comment on there?

• 3:08:47Speaker 02

  Low protein. And people are gonna 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 FGF21 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

• 3:09:32Speaker 02

  because I think FGF21 signaling of fat cells is gonna 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 for our overall health. It was pretty cool.

• 3:09:53Speaker 03

  Wow. 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, right?

• 3:09:59Speaker 02

  Right.

• 3:10:00Speaker 03

  So it doesn't, it's not gonna do well long term. We don't know what the effects are long term with uncoupling this, this sort of metabolism to the 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

• 3:10:18Speaker 03

  Maybe it helps people jumpstart in their weight loss a little bit.

• 3:10:21Speaker 02

  Yeah.

• 3:10:21Speaker 03

  Problem is like, you need amino acids for other things, right? You need amino acids to make neurotransmitters. You need amino acids 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.

• 3:10:34Speaker 02

  No, right.

• 3:10:35Speaker 03

  It's an interesting illustration of metabolism.

• 3:10:38Speaker 02

  Yeah.

• 3:10:38Speaker 03

  Yeah.

• 3:10:39Speaker 02

  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 restriction diets, and that's how it works. But you can imagine in, in popular media, if you can do a sugar diet and can make it work, that's going to 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. So it's what gets amplified incentive structures become bad.

• 3:11:18Speaker 03

  You know, what else works is just eating good quality food.

• 3:11:22Speaker 02

  Yes, exactly.

• 3:11:23Speaker 03

  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, 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, right? Doesn't improve their fertility, doesn't improve their mental health and their sleep.

• 3:11:46Speaker 02

  Right.

• 3:11:46Speaker 03

  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.

• 3:11:53Speaker 02

  I wanted to ask you, when, is there a certain time you choose to eat fruit during the day?

• 3:11:58Speaker 03

  All day.

• 3:11:58Speaker 02

  All day you eat fruit?

• 3:11:59Speaker 03

  Yeah.

• 3:11:59Speaker 02

  So you're not necessarily in ketosis?

• 3:12:01Speaker 03

  Never.

• 3:12:02Speaker 02

  Really?

• 3:12:03Speaker 03

  Never.

• 3:12:03Speaker 02

  Only eating meat and fruit, so you're never, you're never in ketosis?

• 3:12:06Speaker 03

  Never.

• 3:12:06Speaker 02

  Interesting.

• 3:12:07Speaker 03

  No.

• 3:12:08Speaker 02

  And 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 huge difference to you adding the fruit in?

• 3:12:20Speaker 03

  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 lot of side effects, long-term keto. I had a lot. Heart 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's 2.3, right? So the fruit doesn't impair metabolic health in any way, shape or form for me. Interesting. Remain metabolically healthy.

• 3:12:50Speaker 02

  Yeah. Again, it's, there's complexity and nuance. So like with fruit as an example, um, I don't, you know, the, I think it was cell metabol- like how fructose gets processed in the small intestine. This is something that I think often gets overlooked.

• 3:13:02Speaker 03

  Yeah, but this one's, there's some nuance here that, that I want to talk to you about because, yeah.

• 3:13:06Speaker 02

  I'll say my bit and then.

• 3:13:07Speaker 03

  Yeah, go ahead.

• 3:13:07Speaker 02

  So 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 and 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, um, if you have like glucose, you can consume glucose, it'll go, get absorbed, go through the portal lane, hit the liver. The same thing won't happen with fructose. Fructose actually, it gets bio transformed by the small intestine, uh, into glucose and other organic acids. So when you say have like a handful of blueberries, the amount of fructose in those blueberries, negligible amount actually gets to the liver. It's bio transformed into other sugars and organic acids beforehand.

• 3:13:53Speaker 02

  So in this case is one of those things where like, when we're talking about exogenous intake, the dose makes the poison.

• 3:13:59Speaker 02

  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.

• 3:14:24Speaker 02

  I was asking somebody the other day, um, you know, do they think fructose is uniquely harmful? Someone with good physiology background, they said yes. And then I asked him, 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 is 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 than focusing on like, one component that it might be rich in. Anyway, Paul, what were you gonna say about the?

• 3:15:07Speaker 03

  No, that's a, that's a great segue to 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 the gut. There's SGLT1 and there's Glut2. Fructose is Glut5. But when glucose and fructose are administered together, glucose can use, uh, fructose can use Glut2 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.

• 3:15:50Danny Jones?

  Right.

• 3:15:51Speaker 03

  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

• 3:16:10Danny Jones?

  There's fiber, there's all kinds of things.

• 3:16:12Speaker 03

  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, and sugar handling, glucose handling in the body. And when you give extra quote sugar with watermelon juice, it actually improves

• 3:16:54Speaker 03

  the handling of that glucosa. So you can improve by giving extra sugar in a whole food form. Acutely. Yeah, cherry juice, blueberries, all these things, they have great effects in the short term when you're using them. So the 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 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

• 3:17:33Speaker 03

  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, 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, 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

• 3:18:17Speaker 03

  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

• 3:18:59Speaker 03

  is when you give honey, or when you give fruit, which contains sugar, you don't get that effect. You don't get LPS rising.

• 3:19:05Danny Jones?

  Interesting.

• 3:19:05Speaker 03

  You don't get endotoxemia because these compounds in the fruit probably prevent the overgrowth of the bacteria.

• 3:19:11Danny Jones?

  Right.

• 3:19:11Speaker 03

  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 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...

• 3:19:35Speaker 02

  You're like a little, like, not Nick, but he's thumping.

• 3:19:38Speaker 03

  Not this guy. 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 popular influencer saying that recently, Glucose Goddess was saying that, this French biochemist.

• 3:19:54Danny Jones?

  Glucose Goddess?

• 3:19:55Speaker 03

  Yeah.

• 3:19:55Danny Jones?

  Oh, wow.

• 3:19:55Speaker 03

  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 in 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, 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

• 3:20:39Speaker 03

  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 interindividual 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.

• 3:21:01Speaker 02

  I agree with Paul mostly. The thing I really agree with is, like, the package matters. Well, you're talking about compounds in blueberries, honey, or like we're talking about walnuts earlier, like the effect of like allogitanins on like, you know, is it, is it uralithin A or hippercasum? I think it's uralithin A 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 therein like fructose, you know, than we give it credit for. And other factors, actually, just a quick tangent, you're talking about like the, basically leaky gut and toxemia. There's also new data

• 3:21:42Speaker 02

  showing that you can manipulate your mucin lining and change the gut flora with stress. So stress activates, that changes signaling in a region called the amygdala and there's a signal to glands in the gut called Brunner's glands that change mucin production. So like, another way where like, all of 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.

• 3:22:28Speaker 02

  Cause it's like, oh hell, I'm not gonna say a mango is bad per se, but if you have metabolic syndrome and you choose choices, a mango, blueberries, or hard boiled legs for breakfast,

• 3:22:42Speaker 02

  I'm gonna go with first the hard boiled legs, then the blueberry. And I don't know, I'm like, I'm eating the mango.

• 3:22:46Speaker 03

  Yeah, yeah, makes sense. Can I add some context there?

• 3:22:48Speaker 02

  Yeah.

• 3:22:49Speaker 03

  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

• 3:23:34Speaker 03

  Seed oils and derivatives.

• 3:23:35Speaker 02

  Well, I mean.

• 3:23:36Speaker 03

  These are the two greatest movers that I see.

• 3:23:38Speaker 02

  In terms of the actual metabolite, 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 it can go kind of unchecked, deplete intercellular ATP. This has been shown, lead to activation of, I think it's NAPD, NAPDH oxidase four and cause mitochondrial dysfunction.

• 3:24:01Speaker 03

  But it's so small. You talked about this earlier, the amount of fructose that you absorb, it's so small.

• 3:24:06Speaker 02

  Well, depending on what you're eating.

• 3:24:08Speaker 03

  It's so, it's all just converted to different things, you know? Like I don't think all that mitochondrial.

• 3:24:11Speaker 02

  So a couple of blueberries couldn't do that.

• 3:24:14Speaker 03

  No.

• 3:24:14Speaker 02

  But could the fructose from, and this is, this is the difficult hypothetical, because I said like the bowl of Rice Krispie, you know, cereal and orange juice. There's gonna be too much fructose in that for the bio, the pathway is going to be saturated. So I'm saying.

• 3:24:31Speaker 03

  Yeah, I don't know about that. Because if you 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.

• 3:24:43Speaker 02

  I think.

• 3:24:44Speaker 03

  It's about 50% fructose. And granted, maybe it's not enough in one single bowl, but that actually improved glucose handling.

• 3:24:51Speaker 02

  Acutely.

• 3:24:52Speaker 03

  Yeah.

• 3:24:53Speaker 02

  Well, but I mean, like I can eat Oreo cookies acutely and drop in my LDL. Does that mean Oreo cookies are good for a long term?

• 3:24:57Speaker 03

  Well, I mean, you know, like it's just speculative, you know?

• 3:25:00Speaker 02

  I think a lot of this is speculative. I think.

• 3:25:03Speaker 03

  I think it was an eight week study.

• 3:25:05Speaker 02

  I think the human study, the saturation started to kick in around like half a gram per kilogram 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 like 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 and just energy. But the macronutrients, you know, the things that give you energy, the stearic acid, the palmitic acid, the maristic acid, short chain fatty acids, you know, fructose, sucrose, whatever. They're each unique biomolecules with unique effects.

• 3:25:46Speaker 03

  Of course.

• 3:25:47Speaker 02

  So stearic acid, you know, probably can improve mitochondrial function.

• 3:25:50Speaker 03

  We know it does.

• 3:25:50Speaker 02

  Yeah. So I mean, like. That's the broader concept I'm getting to. I guess coming back and probably bring it to the end because I'm not gonna miss my plane.

• 3:26:00Danny Jones?

  Yeah, you gotta leave soon.

• 3:26:02Speaker 02

  Is that context matters and what I mean by that is this is 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 macro new screen 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 that go into a system that processes it in many different ways. Does it get bio converted in the small intestines is the linoleic acid oxidized by myloperoxidase because you have excess fat tissue or is it converted to 4HNE

• 3:26:43Speaker 02

  or 12, 13 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, but are bad. It's comical.

• 3:27:01Speaker 03

  Yeah, I agree.

• 3:27:02Speaker 02

  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 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 it like I got all of this. You get 20% of it

• 3:27:41Speaker 02

  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 naive.

• 3:28:05Danny Jones?

  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.

• 3:28:11Speaker 02

  But it's fun, right? It's like, this is an interesting idea.

• 3:28:14Danny Jones?

  Yeah.

• 3:28:14Speaker 02

  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 zero 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 signaling about it, but I think we need more of that. And it's hard because I keep pulling it back to, but incentive structures.

• 3:28:56Speaker 02

  The incentive structure doesn't always favor saying, hey, let's sit down and have a nuanced conversation between people who have differing, differing ideas and 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.

• 3:29:16Danny Jones?

  Well, thank you guys for doing this, man.

• 3:29:18Speaker 02

  Thanks for having us.

• 3:29:19Danny Jones?

  This has been super fun. Paul, where can people find you online?

• 3:29:23Speaker 03

  It's Paul Saladino M D everywhere, all the socials, website. Yeah.

• 3:29:27Danny Jones?

  Amazing.

• 3:29:28Speaker 03

  Yeah.

• 3:29:29Danny Jones?

  Nick?

• 3:29:30Speaker 02

  My name, Nick Norwitz, N O R W Y T Z. I don't think there's another Nick Norwitz around and I'm really having fun with my Substack right now, StayCuriousMetabolism.com. So you can check it out there. And thanks for having us, Danny.

• 3:29:43Danny Jones?

  Beautiful.

• 3:29:43Speaker 03

  Thanks for having us. Can I just add one more thing?

• 3:29:45Danny Jones?

  Of course.

• 3:29:45Speaker 03

  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 kinds 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 like this, cakes, you feel much better. That's about all people need

• 3:30:29Speaker 03

  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 of their 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 whole foods, as, 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

• 3:31:12Speaker 03

  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.

• 3:31:22Speaker 02

  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, 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

• 3:32:05Speaker 02

  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.

• 3:32:33Danny Jones?

  What are you gonna eat for dinner tonight Danny? That's a good question. I'm thinking about probably a steak. That's a good choice. Safe, safe. No sides. But tomorrow, I think I'm doing a fruit bowl.

• 3:32:43Speaker 02

  You're good. I'll be snacking on some dried steak on the plane.

• 3:32:47Danny Jones?

  Eat some of that lineage on the plane, bro. Hell yeah. Oh dude, that stuff's amazing. That lineage, that lineage stuff, the, those, uh, those dried steak chips. It's good, right? Fantastic. They're dried steak, yeah. Yeah, thank you. Thank you for all that stuff, dude. I really appreciate that. I wanted Nick to have some for the plane too. Oh yeah. Alright, man. Thank you guys. Thank you for having us. Goodnight, everybody.

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