Everything You Need To Know About SEED OILS (Including One Cool "Trick" To Make Them Less Damaging), With Dr. Nick Norwitz

My name is Ben Greenfield, and on this episode of the Boundless Life Podcast—

the punchline was the Oreo cookies slaughtered the statin for LDL lowering.

No way, really?

They were twice as powerful and they acted in one-third of the time. So the drop in LDL was a 71% reduction on the Oreo cookies in about 2 weeks. And then—

welcome to the Boundless Life with me, your host, Ben Greenfield. I'm a personal trainer, exercise physiologist, and nutritionist, and I'm passionate about about helping you discover unparalleled levels of health, fitness, longevity, and beyond.

Hey, just got done recording with Nick Norwitz, super smart researcher and public science/health educator. We primarily focused on seed oils, but we got into some other things too, including Oreos. You won't want to miss this one. Check out the show notes at bengreenfieldlife.com/nick. Norwitz. Here we go. Today's podcast guest is somebody who I've actually really been looking forward to interviewing. He's super smart. He's a researcher, he's an educator. You may have seen some of his fascinating videos on YouTube. And, his name is Nick Norwitz. He's an MD and a PhD, really good background in metabolism and in cell biology and biochemistry. So, He knows his stuff. I was going to say you're a smart cookie, Nick, in allusion to your self-inflicted Oreo test, but you've probably gotten that before.

Yeah. Not smart cookie per se before, but I'll never live down the Oreo cookie experiment.

Yeah. I mean, I know you've got some extensive podcasts about your Oreo cookie experiment, but it's my understanding that that kind of got you a little bit internet famous.

Yeah.

What's kind of like the 1 to 2-minute overview of that experiment? Well, let me go into the motivation.

Motivation behind that experiment. Yeah. Because the headline was, and to be clear, when I say headline, I mean like media, but also peer-reviewed literature that like Harvard scientist lowers his cholesterol with Oreo cookies. Now on the surface, that just seems like a complete troll and clickbait. And the reason is it's exactly what it is. It is clickbait, but it was clickbait with a purpose. So I did this experiment. I was, oh, I forget, second or third year medical student. And the motivation behind it was like, I have my toes in a lot of different ponds or puddles. A researcher, uh, I was trained to be a clinician, so I was in medical school, and also a young person like exploring this new thing that has not been accessible to any other prior generation of academics— social media. And to me, it's really fascinating, like, how you can use this tool to access people's imaginations, bring people to the table, and have difficult conversations. And part of that is just telling a story around science. So What I started to do is explore how could I take some of the more esoteric nerdy things that I love to study, be it like lean mass hyperresponders and cholesterol metabolism, intraorgan mitohormesis, whatever, and translate it into something that people go like, "Oh, that's interesting. I want to learn about that." So, I imagined and I engineered an experiment around something that we were studying. At the time, we had 9, 10 papers on this topic. On lean mass hyperresponders. So basically high level, when some people go very low carb, their cholesterol and in particular LDL goes through the roof.

When they go low carb. Yeah. So it'd be like low carb. I'm assuming that means slightly higher fat. Their LDL goes through the roof. Right. That seems like something you'd expect.

No, actually, no. So, well, really? Yes and no, because here's the caveat. One of the reasons we're interested in studying this is because ketogenic diets, they're exploding in terms of their different clinical utility. So, you know, epilepsy, diabetes, obesity, but not just diseases associated with, you know, having excess adiposity, but also mental health conditions, bipolar, depression. But there's a major clinical obstacle to like the broad acceptance, and that is this phenomenon that in a minority, not a majority, but in a minority, cholesterol goes up. And it's kind of like a boogeyman in medicine. If you don't know why it happens, it's just going to pop out in random patients, then you get this fearmongering around, well, we're not going to put this patient on low-carb because what if their cholesterol goes through the roof? God forbid, right?

Yeah. Yeah. And could I clarify? I don't want to rabbit hole too much here, but the reason I said obvious is I think a lot of people would just assume, well, if you're eating low carb, you're eating more fat. So you'd expect the cholesterol to go up if you're convinced that cholesterol responds like that acutely to dietary fat intake. But are you saying that cholesterol went way, way higher than what would be expected in a small group of individuals?

Two things. First, actually, if you look at the literature at the population level, if you put people on low carb diets, even if they're higher saturated fat, low carb diets, most people do not see an increase in LDL cholesterol.

Okay. Even, even that would surprise a lot of people.

And some people see a decrease. So here's something really fascinating and you can look this up. This was a paper in the American Journal of Clinical Nutrition. It was, if you want, like, you know, to appeal to the hierarchy of evidence, a meta-analysis of 41 human randomized controlled trials, not observational, meta of 41 human randomized controlled trials. What did we see? If you look at all the human randomized control trials for low-carb diets and you break them up by body mass index category, so lean category, like 18 point or like less than 25, then overweight, 25 to 30, and then obesity categories, what you see is if people have overweight or obesity, there's no change in LDL, no significant change. If they have class 2 obesity, so more obesity, when you go low-carb, LDL actually goes down at a population level. And it's specifically This is the weird thing. The lean and generally insulin-sensitive people who see the increase in LDL. So first, first paradox is, okay, if we assume LDL goes up and that's a bad thing, then why are we seeing this bad response in the lean, healthy people? That's the first paradox. And actually, dose-response. So if you take the individual participant-level data and you plot it out, the higher the BMI, the smaller the increase or even decrease you see in LDL. And I'll just add, I know I'm saying a lot, but we see this at the individual patient level. So, I've written many articles on this, but one case that I shared recently, it was a patient treated by my friend, Dr. Adrian Sotomayor, and he had a patient who had obesity, a BMI, I forget the starting BMI, let's say at around 40. It was quite substantial obesity and he put them on a ketogenic diet and the patient started losing weight. As he lost weight, he lost weight, he just got healthier and healthier, and his LDL and ApoB stayed low until he got to the BMI, like the healthy range, BMI 25, 24, and then his LDL did this hairpin turn and just shot through the roof, like more than doubled. And so what we're seeing here is that population levels and individual levels, there's a paradox number one, and that is LDL can go up, but it's only in a minority of people. What minority? The lean insulin-sensitive athletic healthy people. It's kind of weird, right?

Yeah. And it is kind of weird too that it happened to the guy whose cholesterol didn't start to go up until he got lean, indicating that maybe it's not purely driven by genetics. Or could it be that this person had the genetics but the adiposity was somehow protective, if you want to call it that, against the cholesterol increase?

Right. So here's a really important nuance is When people see LDL levels as high as we're talking, when I'm talking high, I mean my LDL is peaked at my LDL 574. If you tell a doctor that number, they think a few things. Either you have a lab error, you made an error, or this patient's going to die because those levels are so high. They're only seen based on common medical knowledge in a very rare condition known as homozygous familial hypercholesterolemia. Studying these rare patients, like a 1 in 1 million condition, actually ended up getting a Nobel Prize. But it's very rare. So most clinicians never see these levels in their career. And an important thing is that example, familial hypercholesterolemia, you're right, it's a genetic disorder. So you're born with these high levels. This is different. This is a metabolic response. So my levels, if I eat a mixed diet, including say Oreo cookies, my LDL is like 90. As soon as I restrict carbs, irrespective of saturated fat, my LDL goes through the roof. This happens at population levels. And individual levels. So, the question is why? And I'll just say at a very high level so I can finally answer your question, it probably has to do with fat fuel trafficking. So, when you're lean and you're insulin sensitive, when you go low carb, you switch into fat burning mode much better. And that trafficking of fat around the body requires a cholesterol carrying system. If people want the nitty-gritty, they can look up lipid energy model on PubMed and read that paper. But—

Okay.

Now, we're going to get back to Oreo. If we're right in this method, in this mechanism, then if you have someone who does have this response and it's being driven by a need for cholesterol-containing particles to traffic fat fuel, what if you just add back in carb fuel? That should reverse the effect.

Yeah, I'm tracking.

Okay. So I decided, you know, we actually already prior to Oreo study, had case series where patients did this or doctors did it with their patients and it was very effective, but it wasn't getting headlines. People didn't want to talk about it. So I'm like, I'm ticked off. People need to study this, learn about this because this is fascinating and very clinically relevant. So I'm like, how can I get attention on this? And I'm like, well, I bet you a Harvard med student lowering his cholesterol with Oreo cookies and comparing it to statins, probably would do the trick. So I went to Harvard's Institutional Review Board. I told them a priori I was going to do this, and then I announced the experiment before I did it. And then what I did is this experiment, and it was a crossover, which meant I did the Oreo intervention, which was I lock in a strict keto diet and then add on Oreo cookies. So not even a swap. I wasn't swapping out fat. In fact, since Oreo is half fat, I was adding fat, but I was also adding carbs and sugar. Then I did a washout period to kind of reset, and I did then high-intensity statin therapy. So 20 mg of rosuvastatin, Crestor, for 6 weeks. And the punchline was the Oreo cookies slaughtered the statin for LDL lowering.

No way. Really?

They were twice as powerful and they acted in one-third of the time. So the drop in LDL was a 71% reduction on the Oreo cookies in about 2 weeks, and then 32.5% for the statin. So the statin had the expected effect, The Oreos were just way more powerful. And the point was to highlight, hey, if we understand the physiology, we can get really fascinating results. And obviously it's a very provocative finding. Yes, you could call it clickbait, but it was also legitimate science. So that's the spiel on Oreo versus statin. But the lesson I want to highlight here is actually nothing about lipids. I mean, kind of, people can delve into that if they want. I have a ton of content, but I, as a young academic, somebody who's trained to be a doctor, somebody who's done a lot of academic science, spent many hours running clinical trials and in labs doing wet lab research. We right now are living at a fascinating time where academia and the general public are colliding violently because of social media. And one thing academia is terrible at is standing up and translating our results, our data, the science into stories around the science that actually attract people's attention and start discussions. So what ends up happening is quote unquote, this is how I'm going to put my like, you know, prudish academic hat on for a minute. The influencers take over the space, right? But that's in part because a lot of academics aren't standing up to translate themselves. So I find it interesting to engage in what you can call a game, but it's just like the ecosystem we now live in of engagement tactics. How can you attract people's attention, you know, with things that are flashy on the outside but actually lead them to much more deep nuance so we can start exploring these things together in a way that's motivated more by curiosity and a love of the science than just the incentive structures that be. And we can get into that. But what I'm referring to is right now the spotlight of medicine and science shines where there's a business model. So say where pharmacology can make money, that's just where the attention goes because there's a business model around it. So these are all complicated things, but The Oreo versus Statin study was my first attempt at saying, look, how can I raise the discussions that I think are important using the tools at my disposal? And it was quite successful.

So one of the questions about the Oreo thing, you know, speaking of helpful, how would that advise someone in terms of making dietary decisions, or how would that impact health in some way for someone to know the link between carbohydrate intake and cholesterol in these so-called lean mass hyperresponders?

That's an excellent question, Ben Greenfield. And I'll tell you why it's an excellent question is, you know, what made this study so provocative was we all agree Oreos are not a healthy food. I would say most of us at least. And most people would say that lowering LDL is a good outcome. So what was implicitly presented was unhealthy intervention, but good outcome. And that's a paradox. Now, I don't place any judgment value on statins, Oreo cookies, or LDL in the study, but in trying to resolve this paradox, people are very uncomfortable sitting with like a cognitive dissonance. So they pass their own value judgment. That's what made this provocative. But actually what I want to highlight and what I want to challenge people is there's actually a lot we don't know. We don't know, for example, if this LDL response in people like me is even dangerous. We are collecting those data, but we don't have it yet. So it brings us to really what the definition of medicine or what the art of medicine is. And it's sometimes making really difficult decisions in individual risk-benefit analyses with imperfect or incomplete information. And that's the situation we have here. And what we should do with that is chase the questions to get better information. So we're doing that currently, but I'll tell you how this unfolded from a clinical perspective, which was not that, as some people speculated, I turned Oreo cookies into a health food and now they're being sold for cholesterol lowering.

I mean, maybe if you made some kind of a cookie with shilajit coloring and a colostrum cream cheese filling or something like that.

I don't know. I mean, people joke around like, "You're tricking people into cookies being healthy." I'm like, "No real adult would believe that." But, hopefully. And if they do, then you can thank me and natural selection. But that aside, what ended up happening was the purpose of this was to amplify discussion around research. So I started getting a flood of emails and direct messages from clinicians who said, hey, actually, like, the science here is really interesting. I didn't know about this population of patients before this. Now it's on my radar and I'm using the physiology, my now new knowledge of the physiology, which I became aware of, I being the physician because of the Oreo versus Statin experiment to treat my patients. So, say patients who they're fine introducing say 50 to 100 grams of carbs, that's not necessarily metabolically challenging for them who have this response. And so, what they can do is basically drug-sparing approaches. So rather than having a patient say, oh, we're going to put you on statins for life, just give them a sweet potato. And in some patients, that is as or more effective and better tolerated. So it's just about acquiring knowledge to then make more informed and individualized decisions. So if anything, the irony here is this experiment ended up probably causing a lot more LDL and ApoB lowering because clinicians and patients who were interested in that then became aware of the physiology and used other carb sources to do so. Fruits, starches, whatever. It works with any carb. The reason I did Oreos is because I knew it would amplify the discussion around it because Oreos are just a sexy food.

Oh yeah, absolutely.

Absolutely.

It's a pattern interrupt. And actually, it makes me— I'm largely ketogenic. My cholesterol hovers around 200. It kind of makes me want to go out and try a little self-experiment myself, although I probably will go the sweet potato route.

Oh, if you actually want to collect data on yourself just for that purpose, do it with a quote-unquote healthier carb. I put my body on the line for science, so hopefully people don't have to. Although I will mention, after I did this, there were several doctors, including seniors to me at Harvard Medical School, who are also lean mass hyperresponders. There are quite a few who did replicate it with Oreos. So, it's been done more than once.

Ben Greenfield: You wrote something on Substack. I follow your Substack, by the way, and you wrote something that I wanted to ask you about today. This is actually one of the reasons I want to interview you today. It's about seed oils. And, you basically said that the general consensus on seed oils is that if seed oils, plant fats, and omega-6s are fragile, prone to oxidation and generate harmful carcinogenic products. They're bad. And then, the other quote is, "The elites have misled us. And as it turns out, animal fats like tallow are the health food, whereas omega-6s are unhealthy and to be avoided at all costs." So, my question for you is, what do you think about that consensus, and this is a kind of a big question, when you've also noted a large body of human evidence including observational and randomized controlled trial data suggests increasing polyunsaturated fatty acid intake is associated with and/or results in better cardiovascular disease outcomes. So, let's open that can of worms. Because I know you've written a lot about this and there's a lot of nuances. So, what's going on with seed oils right now?

So, first I'll just say I think at least one of those quotes was me intentionally being comedically hyperbolic as in I don't believe this, but this is the narrative. So, this is one of those terms as soon as people hear seed oils, their brain shuts off and they're like, I've decided what I'm going to think and I'm not going to listen anymore. And, if you're not saying the narrative I like, then I'm going to troll you. But let's start at the beginning. So step one is defining what we're even talking about, because seed oils is actually something with a really poor definition. Some people hear it and think we're talking specifically about hyper-industrialized processed vegetable oils, you know, the kind you see in the reels going on the conveyor belt in the plastic containers. That's one category. Then there's this logic creep, this domino chain where they're like, well, What's harmful about it? One thing that's harmful about it is the fragile omega-6. And so then omega-6 polyunsaturated fats. So just to define our terms, you have fats, they go into unsaturated and saturated. Among unsaturated, there's monounsaturated like olive oil type fats, then polyunsaturated, which includes omega-6, kind of like nuts and seeds, and then omega-3s like fatty fish. It's an oversimplified umbrella diagram, but there you go. So, people vilify this omega-6, which is found in the "seed oils." There's a little bit of rationale for that because, one, an imbalance in your omega-6 to omega-3 ratio, so very high omega-6 levels correlate with and may even cause inflammation.

Ben Greenfield: So, high omega-6 levels relative to omega-3s, like the ratio or just high omega-6 levels no matter what your omega-3 levels are at.

Good point. So the ratio, and this actually leads to another logical fallacy because if you look at the literature again and you look at not just circulating levels but also tissue levels, like in fat tissue, a lower omega-6 to 3 ratio associates with better outcomes. So from that, what you might conclude is, well, you want a lot of omega-3 and very little omega-6. But if you dig a little deeper, you actually find that both omega-3 and omega-6 levels when they're higher associated with better outcomes. One way we can explain that is it's not that omega-6 are bad per se, omega-3 are just better. So, the denominator drives that association. But taking a step back, I would say in general, those highly processed industrialized oils, I would put in the category of Generally harmful. You can do better. Omega-6s as a broad category. So now talking less processed, think about like walnuts. Walnuts have like 10,000 milligrams per ounce of omega-6. Is that harmful for you? I would argue no, not generally. And one huge nuance, this is, I think goes beyond just omega-6 and seed oils. And just think that needs to be emphasized is when we're talking about anything you ingest, it's not just an intrinsic property of the thing, let's say the omega-6, but also how it's interacting with the host, you. So let's take two extremes. If you're someone eating a westernized diet and you have obesity, let's say you ingest a bunch of omega-6, what happens? Your body has a very highly, like, say, oxidative environment. Literally, your fat cells are spitting out enzymes, like ones called myeloperoxidase, that oxidize fat. So you're in this state where you're actually prone to oxidize and damage the fat, which then can perpetuate poor outcomes. Let's take another extreme. Say you're lean and insulin sensitive and you're very low carb. Then what happens? Well, there are multiple things that can happen to that omega-6 that you ingested. It can actually be turned into compounds that are cardioprotective. So converted into hormone molecules. It can be converted into ketones. Actually, PUFAs and omega-6 are very ketogenic. So, as a health hack for me, if I want to boost my ketone levels, even keeping my carbs and protein the same, I can just swap saturated for polyunsaturated fats. Say swap butter for sesame seed oil or walnuts and my ketones will go through the roof.

Interesting. Okay. That's actually notable. That's a little like double-click bookmark, but sesame oil can be a ketogenic fatty That's interesting.

Very ketogenic. And again, there's more nuances because if you're eating like, say, sesame seeds, the whole product is inclusive of antioxidants that protect the natural omega-6. And you can do this if you actually look at the graphs. I can send you one of the graphs. If you look at just like the extracted omega-6 linoleic acid, it can get oxidized a lot. But then you add in the antioxidants that are present in sesame and they protect the fat against oxidation. So the oxidation levels go down. I know there's a lot of jargon here. What I'm really saying is like the interaction with the host and how you consume the fatty acid matter, eating it in a whole form, say sesame, oh, like walnuts, probably not harmful. If you're healthy metabolically, you're going to use that omega-6 very differently than somebody who's metabolically unhealthy. So omega-6 aren't bad. Highly processed industrialized oil, I think are quite harmful on balance and you can do better. But I think there is too much fear about omega-6 broadly because of the exaggerated perspective on quote-unquote seed oils.

Yeah, I think that is important from a definitive standpoint. Let's say someone hears that, that all too common headline nowadays, you know, avoid seed oils like the plague, ruthlessly avoid seed oils, seed oils are bad for you. And, they are a healthy host, right? They're a lean person. And, I know there's some other factors we can get into later. I think I even heard you mention cold plunging might be protective. And, they think, "Okay. Well, there's got to be some seed oils that I could consume." You've already mentioned that something like heavily fried foods like McDonald's french fries, probably there's better options than that. But, what are some seed oils or seed oil sources that you think are kind of unfairly vilified that people are currently cutting out of their diet and potentially missing out on the cardioprotective benefits of omega-6s?

I wouldn't even— let's even set aside making a claim about cardioprotectiveness. Let's just say things that might even be harmful. I see people cutting out nuts and seeds like walnuts and seeds, let's say walnuts, pecans, tahini. I love tahini. You can make a lot of nice dressings with that. I see people even getting very granular about things like, well, what is the exact poofa breakdown of my grain-fed versus grass-fed beef. Now, by all means, eat grass-fed beef, pasture-raised beef, maybe for ethical reasons more than anything else, but is there actually going to be a difference on your health based on a slight skew in omega-6 levels? Probably not. I even see people go so far as to avoid sardines or omega-3 rich sources. This is at the extreme end, but it does occur because they're like, well, this is a polyunsaturated fat and it's It's fragile, therefore I should avoid it. Which goes to tell you how far people have slipped down this logic creep chain of, "POOFAs are bad for you because they're fragile," which is a very sticky narrative. And I just want to fuck at that and think about all the sticky narratives. A big one was fat makes you fat. That was the whole low-fat era. Or saturated fat clogs your arteries. Polyunsaturated fats are fragile and prone to oxidation is actually in the same category. It's a sticky, easy concept that people adhere to, but it's a gross oversimplification. So my two cents, yeah, don't eat like hyper-processed oils in like plastic clear containers that have been like heated and reheated, but don't fear omega-6 as a category either. In fact, it can be used strategically for reasons I just mentioned.

Ben Greenfield: What if someone were going to start eating more seeds and nuts and be a little less fearful of omega-6s, but they're going through the airport, you've probably seen this, and they're buying the packaged seeds and nuts and it says something like vegetable oil, safflower oil, canola oil as an additive to the nuts? Do you get concerned at all about what you see in even some of these so-called healthy packaged foods as far as added oils?

I would say it's one of those categories where it's probably not the worst thing in the world, but it is suspicious and you can probably do better. So, when it comes to like nuts and seeds, I would say as best you can, get raw nuts and seeds. There's no health benefit to having like the coatings other than maybe they'll be delicious. I will like provide a disclaimer here. I almost exclusively eat raw nuts and seeds except there's one brand other like salt and vinegar pistachios that do have a little bit of sunflower oil on them and they're just so good. So, everybody has their guilty pleasure. It's not about being perfect. I would say if you're optimizing health, yeah, don't get the processed version.

Ben Greenfield: I want to know a little bit more about some of these host factors and some of the things that might make sources of omega-6 fatty acids more likely to be unhealthy. But, there's a term that I think might confuse a lot of people, linoleic acid, that's used a lot of times during the seed oil or omega-6 conversation. What is linoleic acid?

For our purposes, you can almost think of it as synonymous with omega-6. So to review our like fat hierarchy, you have fats as a category. And then you have unsaturated fats, which means they have double bonds and saturated fats. Each of these has actually a lot of things within them. Let's focus on unsaturated fats. Therein you have monounsaturated, so one double bond, like oleic acid and olive oil. And then you have polyunsaturated omega-3 and omega-6. The predominant omega-6, like the vast majority in the diet, is linoleic acid. So for simplicity purposes, omega-6, linoleic acid, kind of synonymous. There are other omega-6s, but they occur in much lower frequency.

All right, got it. I'm going to rapid fire a few at you then. Yeah. Related to omega-6 fatty acids and seed oils. Do it. Heating. You know, you go to this Whole Foods salad bar and says whatever, cold expeller pressed canola oil. I'm assuming there's a difference between that and whatever the fried oils that they're using at a fast food joint. But what do you think about when it comes to consuming seed oils that have been heated? Where do you draw the line?

I would not consume seed oils that have been heated. One thing that is true is that these are fragile fats. It doesn't mean they're bad, but it means you have to treat them with care. And the heating causes damage to the fats. It can cause the oxidation, the transformation into harmful byproducts. To give you just a case in point about how much variation there is, if you take two different nuts, so walnuts are super high in omega-6, about, like I said, 10,000 milligrams per ounce. Macadamia nuts are very high in monounsaturated fat, which is less fragile, still more fragile than saturated, but less fragile. So if you were to roast an equal amount of walnuts and macadamia, I think it's at 150 Celsius for like 20 minutes. You end up with 30 times the oxidized fats in the walnut. So, that just gives you an indication of how relatively fragile these fats are. So, I would say I would avoid high omega-6 fats that have been heated.

So, if I've got the sesame oil you talked about, that'd be maybe like an addition to a cold salad dressing, bottle of macadamia nut oil, I could use something like that for cooking probably.

Yeah. I will draw a little exception for toasted sesame oil. No, this is really getting into the weeds, but sesame is a weird outlier. Even people that are very anti-seed oil, say like Tucker Goodrich, admit sesame is kind of like an oddball. When you heat the sesame oil, there are actually antioxidants that the heat biotransforms them into even more protective forms, some of them. So you don't end up with that much oxidation. So a little toasted sesame oil as a dressing oil I think is fine with that exception. I wouldn't eat high omega-6 oils and I would preserve them for like omega-6 foods, kind of like toppings, dressings. You want to crumble some walnuts on like a salad with like some nice Roquefort cheese, which, and this is a fact, peer-reviewed fact, is the best cheese. Yes. Probably. Okay.

All right. Well, thank you for not ruining Asian food night for everyone. Okay. How about the additives? Like you hear a lot about, oh, there's these harsh chemicals that are used to extract the seed oils. So even if it doesn't have bad properties in the omega-6 itself. There's all these other chemicals that get added in during the extraction.

Yeah.

What's your take on the whole chemical extraction processing piece?

I would say precautionary principle. So, it's true. People were like, "Oh, well, it's processed with hexane until you end up with hexane in the oil and hexane is a neurotoxin." Those are each true, but I've never heard of a single case of hexane poisoning. From like a seed oil. So the question then becomes, what's the burden of proof? And what I mean by that is if you are holding someone to like claim, hey, this compound present in these doses is proven to be harmful, you might not get those data. However, if you're operating more on the precautionary principle and saying, hey, this isn't probably an ideal thing to have, not even just the hexane, but like as a composite, and it's easy enough to avoid without much risk, then I would say avoid it. So, there are additives that some of which either are additives or generated during the heating process that are thought to be carcinogenic, harmful. I would not go so far to say like this is going to cause neurotoxicity, but I would say what's the cost to avoiding it? And really the only cost I can possibly think of is that these hyper-processed oil's probably gonna be cheaper on balance. So if like you actually have a very limited food budget and you know, you're, you're in a situation of like poverty, then this would become an issue just because like, like buying a nice olive oil can be expensive. That's a whole nother kettle of fish. So I would say barring that limitation, I can't think of any single reason why you would ever choose this, you know, hyperprocessed heated oil that contains these potentially harmful additives, even if it's not proven without a shadow of a doubt.

Okay, okay, got it. That's clear. With omega-6 fatty acids, uh, you mentioned obesity, adiposity potentially being an endogenous factor that could contribute to oxidation and make them potentially more harmful. Yeah. Um, I've also heard something similar about like sunlight, particularly UVA and UVB radiation. Like if you have a high seed oil intake or high intake of omega-6 fatty acids that you get more skin damage if you go out in the sun. What's your take on that?

I'm not aware of literature that proves that's the case, but I wouldn't discount anecdotes. So I've heard the same people like, I cut out seed oils and now I don't sunburn. I think it's very plausible that at a high level these get incorporated into your skin and therefore you become more prone to like skin damage. It's interesting hypothesis. I haven't seen any definitive evidence on it. But I guess this is a good point to interject. When you're listening to someone and you're trying to evaluate if they're an expert, generally the best mark of an expert is not what they know, but how they can delineate, hey, these are the limits of knowledge and here's why. So there are certain ideas, and this is one of them, where it's like, hey, we don't have these data. At least that's the best of my awareness. But also, One of the reasons we don't have these data is because who is motivated to actually do the study? So this happens with food studies all the time, or like food research is like, I can't make certain definitive claims because the research is impractical or too expensive to do, and there's not a business model that is driving the research. There are a lot of questions I'd love to answer, but it might require a $20 million feeding study. Who's funding that? Basically nobody wants to. So it's difficult sometimes to talk about these topics because people are always shifting the burden of proof and not like clearly delineating like, well, what evidence do we have and what can we actually fairly conclude from that? So sorry, I went off on a tangent. Point being plausible, but I don't know of any evidence proving it's the case.

Okay. Now, now besides something like obesity or a high omega-6 to omega-3 ratio, Would there be other predisposing factors inside of somebody or as a part of their diet that might cause more oxidation of omega-6 fatty acids?

Yeah. I mean, I think the best way to go about it is to look at metabolic markers of poor metabolic health because obviously BMI is a very weak man's proxy. So, if you have elevated inflammation and hs-CRP or oxidative stress markers, that's probably a signal and that's also gonna correlate with dietary patterns like high sugar intake. So, you know, if you're having a high sugar, high omega-6 diet, that's probably not a, a good combination. To give kind of just an example of how like intricate this gets, I mentioned earlier that fat cells secrete certain compounds that oxidize fatty acids. So literally unhealthy enlarged fat cells, some of which sit around blood vessels, it's called peri, peri around vascular, perivascular, so around blood vessels. Adipose tissue fat. Let's go these enzymes, one's called myeloperoxidase. And it's really scary, but also fascinating because it exists outside the blood vessel and inside. So inside the blood vessel, one thing it's doing is, um, causing oxidation of lipids. So like you get oxidized LDL particles because this molecule's in the bloodstream, but then outside of blood vessels it's doing other things. So it decreases generation of healthy hormones. One's called adiponectin. It's kind of like yoga for blood vessels. So it makes your blood vessels stiffer. It also decreases like thermogenesis and brown fat activity. So what you're basically getting here, and I, I hope people get how cool this is, is like in obesity enzymes generating, that's creating like a metabolic pincer maneuver to leverage the omega-6 fats to harm blood vessels in that condition of ill health. Okay. And people don't need to understand everything I'm saying to take a step back and be like, wait, the narratives that we're told, oh, seed oils aren't harmful, there's no evidence of that, or seed oils are terrible, are grossly oversimplified. And you don't, you don't need to like understand all the biochemistry to just take a step back and be humbled by that biology because I, I think there's a lot of value in just doing that. Because I think it is a treatment for the frustration that arises from these simplified polar opposite narratives and trying to figure out— this is always what I'm trying to do, not necessarily successfully, but, but trying to figure out those quotes you presented at the beginning. How do we take contradictory and discordant data and try to make sense of it in a way that is nuanced?— and we can do this all day in journal clubs among academics, but in a way that the general public can start to understand. And it's not necessarily sexy and appealing, but I do get the sense, and I want to know if you get the same sense, Ben, that there is actually a lot of hunger for discussions like these where people are like, wow, that actually makes a lot of sense. Maybe I only got like 30% of it first round, but things are progressively clicking. I think people like being challenged with the details.

Yeah, a discussion slightly lower on the dogmatism scale for sure. Okay. So, what about cold exposure? I briefly mentioned it. I think it might play a role based on what I've seen you write. Is there any evidence that doing something like cold exposure could help with, I guess, less omega-6 oxidation?

Yeah. Well, this is another level of complexity. Not all oxidation is bad.

So, yeah, good point.

So basically what happens with cold exposure, and this has been shown in human controlled trials, is it causes some omega-6 to be converted into these signaling hormones. I think one's called 12,13-DiHOME that do things that are cardioprotective. So actually decrease One thing is called perivascular fibrosis. Terms aren't important. Basically, there are lifestyle interventions. Cold exposure is one of them, which can bias your metabolism to turn the substrates, the, you know, raw materials you're giving it, including omega-6, into healthy compounds that like are hormones that will help your heart. That's the high level. Just this idea that be it, you know, exercise or cold exposure or light, Exposure. All these things change your metabolism in ways to take the raw products you're ingesting and put them down different pathways because that's all what it's about. Like, how is your body partitioning what you're taking in? It's not what you eat, it's how your body uses what you eat. And so this is one example. Yes, cold exposure can cause some omega-6, I don't know what proportion, to be turned into hormones that help the heart.

Yeah. And, lest everyone rush out for their 20-minute 33-degree cold plunge, do you recall or do you know if there was any dose response or if there was anything in terms of temperature or time or anything like that? Yeah.

I'm trying to remember. So, the trial I covered over a year ago and I think it was a 39.4% increase in this compound. I forget the method. I think it was 2 hours but not in a cold plunge. I think it was near shivering threshold. Okay. If I recall, I always read hundreds of papers since then, but it was something like that.

Yeah, like a cold air exposure type of thing.

It could be that. Total sidebar, but I just did an experiment. Sardine dieting was kind of like popping off, and I did a sardine diet, which obviously very high in omega-3. And, one of the weirdest things that happened that I totally didn't expect was I became cold resistant. To a bizarre extent. I'm walking around in Boston in the winter, it's 30 degrees and I can just take my shirt off and I'm like, I'm not cold at all. And, it was so bizarre, I just needed to go on a little rabbit hole. Wow.

That's kind of cool. It's like the doctrine of signatures, eat a lot of fish and you start to develop thermoregulatory mechanisms like that of a fish.

There's actually literature that one of the omega-3 derivatives is called— I apologize for all these jargons, scientists aren't very creative, 12-HEPE is made by brown fat. It's an omega-3 derivative and it acts at brown fat kind of like is released and then signals back. It's called autocrine signaling, but also at muscles. It increases thermogenesis and it increases like glucose disposal into muscle tissue. So, I'm kind of piecing, I'm taking a leap of logic here because this is like basic science data that, oh, omega-3s can be turned into this hormone that increase thermogenesis. And I only found this though because I had this weird personal experience when I like hyperloaded on omega-3s. In fact, when I did omega-3 testing via OmegaQuant, my omega-3 levels broke the scale. I became like fatty acid levels of a dolphin. But it was just the most striking bizarre phenomenon where I just wouldn't get cold. Anyway, I have a letter on that as well. All this ends up in my newsletter generally, all these—

Okay. Yeah, your newsletter is great, by the way. And if you're listening, bengreenfieldlife.com/nicknorwitz, N-O-R-W-I-T-Z. WITZ. I'll link to Nick's newsletter and some other resources. Nick, speaking of fish, we talked about this ratio. Could someone theoretically, let's say they just don't have access to a lot of quality fish, they maybe don't like sardines, what about fish oil? Could someone just up their intake of fish oil to get their omega index, their percentage up and improve that ratio?

I would say in a word, yes. Omega-3 supplementation becomes a little bit complicated. I, I don't know that I want to go too far down the rabbit hole on this, but what I would say at a high level is it works, but there are still benefits to having actual fatty fish. So in terms of the forms of omega-3, and I don't just mean like EPA and DHA, the fatty acids have different carriers. So You know, sometimes they come in a triglyceride form. If you get like a fatty acid supplement like Nordic Naturals, which is great, that's going to be the form. It doesn't cross into the brain as well. It also isn't packaged with protective forms of, say, selenium. So there's a little bit of an oddity in the literature where there's good data on, you know, fish intake being protective, say, for the brain, and not as good literature for omega-3 supplementation. I wouldn't discount it. And I'll have an article coming up specifically on this because there are now particular forms of omega-3 that are being generated with this knowledge in mind. But I would say if you really don't like fish, yes, do an omega-3 supplement. And yeah, I'm, I'm not gonna go down the rabbit hole, but if you go to the, my newsletter, it'll have a little bit more information on the different forms of omega-3s, the different carriers and what you want for different outcomes. But generally, an omega-3 supplement will skew your peripheral ratio, so not in the brain towards a better omega-6 to 3 ratio.

Yes. Ben Greenfield: Okay. It's been a little bit one-sided in terms of the multisyllabic scientific term spewing, so I'll throw one in here. 4-hydroxynonenol. I don't know if I'm pronouncing that properly. 4-hydroxynonenol, I believe it's abbreviated 4-HNE. That's another one that you hear talked about in relation to seed oil intake as something that somehow contributes to chronic disease. Seed oils are chock-full of this stuff. What's the deal with 4-HNE?

Yeah, I would say it's one of these derivatives of processed seed oils for which there's a decent amount of literature that it's harmful, carcinogenic, genotoxic. Again, This isn't like you have a walnut and it's loaded with this stuff, but I would say, yeah, if you're eating like, you know, processed soybean oil or like oil that's been in a fryer, you're gonna get dosed up with this stuff. And all these things, I believe I'm correct on this, can just be made endogenously as well. So kind of speaking at a broader class, maybe people have heard of advanced glycation end products. You can quantify these like outside the body. So if I fry a bunch of bacon, It's loaded with AGEs. And if you have like a stack of pancakes with syrup, doesn't have much AGEs, but all that syrup and sugar is gonna make a lot of AGEs in the body. So again, your hormone, your hormonal metabolic milieu really matters. 4-HNE, probably harmful. No, it is harmful, but I wouldn't worry about like natural sources of omega-6 because of that.

Okay. So, don't go to IHOP frequently if you're concerned about 4-HNEs, in other words.

I just wouldn't go to IHOP frequently if you want to be healthy.

Alright, as much as we like whipped cream and strawberries. So, this is really interesting on seed oils. And obviously, there's a lot of nuances here. This is why I wanted to get you on the show. Everything from simple things like the amount of thermal stress that you might have to your level of adiposity to the nature of the seed oils and the processing and heating versus the more natural source such as say walnuts, the idea of your omega-6 to omega-3 ratio. One last thing regarding seed oils, any influence here, and this is kind of a little bit of a throwback to what you were saying about Oreos in terms of macros, anything in terms of in the literature carb percentage, protein percentage, fat percentages overall affecting any potential impact omega-6s might have on the body?

Not that I'm aware of, like direct literature. Again, if you're skewed towards a higher glycemic load diet, so like more sugary carbs, I would bet strongly that that would negatively affect how your metabolism is handling high omega-6 foods. That is my high-level perspective.

Okay. You, I think we're going to be a doctor at one point and then you kind of pivoted into public health education, into content production. Psychologically, is it weird for you not to be practicing medicine or is that something you didn't really see yourself doing originally?

Thank you for asking that question. So, I grew up always planning to be a clinician. Both my parents are physicians. Obviously, I went to medical school, I applied to medical school. So, Generally, when you do that, that's the intent you have. It wasn't until, you know, my last year or two of medical school that I even started contemplating doing something else. It's actually pretty taboo to not even apply to residency. So it was something that I thought a long time about, and I spoke with a lot of my advisors because in past generations, people haven't had the opportunities that were presenting themselves to me. And what I ultimately decided was, you know, medicine is evolving. And there's a niche, I think, that needs to be occupied with people who are medically trained and academics who position themselves as like communicators to the general public. And I was getting such amazing feedback from members of the community about how my education was helping them. That I thought, you know, this is what I love doing. Like, I would go— this is like in my last year of med school, I would be like, you know, rounding on patients and my mind would just be a little bit trapped elsewhere with the science. And then when I had like a day off, I'd be up at like 5:00 AM, like reading Cell Science and Nature, and I was all excited. And I realized I really wanted to want to have a calling for medicine. And I think it was something I convinced myself that I had because it's a profession that I have the deepest respect and admiration for. But as I went through the process, you know, and made friends where I could see like they got up every day excited about clinical care, I just, I didn't have that same passion for that practice. What I had was a passion for getting up, reading and learning and teaching about the science. So, I decided I think my skillset and where I can have the most impact is one, in science communication, and then two, in using that platform to empower people with information, empower people with their own data, go into the private sector, entrepreneurial sector, and also research. So, one thing I think most people can agree on is food, nutrition, metabolic health, they're underemphasized. When it comes to scientific research. And that's because we do not have a good business model around them. There's good business model around drugs, not around metabolic health research. And the fact of the matter is having a public presence and a profile and platform like I'm trying to build gives you the connections to help really get this research fired up. So now I'm talking with some very wealthy philanthropists, to get money, like we're talking $5-10 million for major projects that could change the course of medicine and healthcare. And it's not even that these are going to be governed by me in particular, but I feel like I can act as a bridge. I've identified some incredible labs and I'm like, hey, I can help design, ideate, but I can bring in resources to get the research done that will actually change clinical care. So I've decided to commit myself to this alternative path. It was a big risk, but now I honestly, I get up every day and I just, I couldn't be happier. And the way I would position it is not that I abandoned medicine or like quit the system to attack it from the outside, but that medicine is a team sport and you need to find your position on the team. I think I have a particular skillset that lends itself to something different. And then I'll leave, you know, the clinical care right now to my friends and colleagues who like thrive on that. So I'm exploring. I'm a young person just trying to figure out my life like, you know, anybody. But candidly, that is the process I've gone through. It was not an easy decision, but I definitely think it was the right decision for me.

Yeah, well, you're a great teacher. You know, phrases like adiponectin is yoga for the vasculature highlights that. And for those of you listening, Nick's content is great. Great follow on Instagram, YouTube, Substack. I'll link to all of his channels at bengreenfieldlife.com/nicknorwitz, N-O-R-W-I-T-Z. Twitter too or X. So, Nick, thank you so much for doing this. So, you're an incredible resource. I'm happy you're doing what you're doing. If that counts, you definitely help guys like me dig through the science a little bit better. So, I appreciate you, man.

I appreciate it. There's one more thing I have to say. It's been bothering me this entire time, but I've not noted it. Has anybody told you you look very much like Kit Harington? I don't know if it's the haircut and the beard right now. Like who? Kit Harington.

Jon Snow. I don't know who that is.

No?

I don't know who that is.

All right, look it up. Anyway.

All right, I'll Google it later.

All right. Everybody's like, watch the video version of this and just like look at your face. Look at it.

All right. All right. I'll check it out. Kent Harington. If you have comments, questions, feedback, or or want to pipe in on whether or not I look like Ken Tarrington, go to the shownotes at BenGreenfieldLife.com/NickNorwitz. And until next time, I'm Ben Greenfield and Nick Norwitz signing out. Have an incredible week.

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