@@nicknorwitzPhD, I listened to all of it though it was 2.5hrs using 2x speed ;-). Great job; I'm still curious. And Nick.. you need to try cheesecake or other baking made with Allulose or using RX sugar chocolate syrup, works out very well.
@@TheProofWithSimonHill being in a chronic state of ketosis drives Cortisol up, which in turns makes the body want to store fat, ut you're in Ketosis so now you're about to blow out your thyroid and drive down body temp Proven over and Over - in less than 5 years IN CHRONIC KETOSIS, not low carbish
As a 70 something LMHR, like Nick I have weighed the pros and cons of introducing drugs to lower my sky high LDL. Here’s what I know: All of my bio-markers with the exception of LDL is considered optimal, I have never felt better in my life both mentally and physically, plenty of energy, stamina, sleep well, enjoy hiking and occasional very strenuous exercise and I like the image when I look in a mirror naked. At my age I know that I am an outlier; one of the less than 1% of people my age that does not have any metabolic dysfunction. I don’t know the amount of benefit if any I would have by taking a drug to lower LDL but I am aware of adverse side effects. Also all of the experts that recommend lower LDL also criticize my diet that is the opposite of their recommendations; no fruit, veggies, grains whole or otherwise, instead mostly red meat with the accompanying fat. Am I stupid to not tamper with what has worked wonders for me?
@@colinvankeith4814 - here's my take on this. Yes, with a high fat, protein rich diet you'll feel more energized and your so called stamina will be high, but the human body has its limitations. High LDL will make you feel good, better healing etc, but in the long run isn't beneficial for cardiovascular risk. To live long and to be healthy in the long run is not to maximize your highs. Look at it as a gas burner. If you go full flame, you'll shine strong but limits your time. Gandhi is another analogy......
@@acke26 A study of the oldest of the old taken from NHANES data found that only the elderly with highest LDL survived to over 100 years of age. Luckily for them they didn’t burn out.
Curious pushups! As a clinician this podcast reflects a lot of how I practice. 99.9% of my patients are getting statins, zetia, or repatha, (not much BA yet) if indicated and informed of benefits and risks. A CT A really helps people to clarify their decisions too. As of now I have 3 patients in my practice w LDL> 200 and a clean CTA. One in their 50s,60s, and 70s. I now require also getting a carotid ultrasound as CT A is not perfect. If both are clean and the patients, after being informed of this gray area in medicine wants to continue w surveillance then I am ok with this. I will stress that this is
Absolutely. Especially when people deny high blood cholesterol is one if the main factors that cause atherosclerosis or think sky high cholesterol is ok for everyone if they eat a specific diet or that they should pour seed oil down the drain while there's an overwhelming amount of quality scientific evidence to back up positive health outcomes with eating seed oils and negative health outcomes with high blood cholesterol. These false messages do so much harm itjust makes my blood boil.
Beautifully done Simon and Nick!! Truly how one ought to have a discussion instead of a throw down. Putting the health of a patient as the ultimate goal instead of feeding personal ego or just regurgitation of old papers without accounting for new developments making them less relevant. Great job!
"Truly how one ought to have a discussion instead of a throw down" -- agreed! Simon kept his position (a normal concern for misinterpretations of this study) while also premising its new information for listeners. Nick's actual curiosity for nutrition science and how to get public attention to give a deeper look at how health anomalies can inform us, was refreshing. The 5 hours flew by....Can't wait to hear more on LDLs. Many diverse body types (esp. ageing parents) suffer w/ this. Thanks so much.
Pushups! 👍🙂. Asiide from that I have a great deal of admiration and respect for Nick. I love that he is willing to think “outside the box” despite any negative pushback. That takes a lot of courage. Many Thanks Simon for hosting Nick, and being open minded enough to hear him out.
An interesting discussion (and nice that it’s not in an echo chamber). I too have noticed a correlation between BMI and LDL. Like most, my medical ‘history’ started with diagnosis of a condition (T2D). On diagnosis, my LDL was on the high side (above recommended levels). I was I’d say slightly overweight but not obese (79kg and 178cm). I lowered carbs considerably (long before I had even heard of low carb, keto or anything - just that it seemed to be logical if my body didn’t metabolize glucose very well, then eat less of it). My A1C dropped down to 5 (from 12.8) and my LDL fell quite quickly to well under the recommended max). Over time (2 or so years) I lost about 5kg (without actually trying) and my LDL started to creep up ever so slightly towards the high end of normal. Thus, I think that my case seems to converge with the inverse relationship between LDL and BMI. Therefore, I hesitate with respect to lowering LDL pharmacologically when it appears to be an outlying bio marker going in the wrong direction. It’s probably worth pointing out that on T2D diagnosis all my liver enzymes were high (which I just assumed was excess alcohol) yet these too just dropped to normal levels after going low carb (without any reduction in alcohol). I have regular full blood work done and everything else also looks fine. I’m far away from LMHR criteria (TG and HDL meet the levels but my LDL is too low [even though it might be considered high]). Looking forward to further advances in understanding what might be going on.
In my opinion, LDL receptor down-regulation likely contributes to elevated LDL in people on a keto diet. My guess is that the down-regulation could be from increased saturated fat intake, increased cholesterol intake/absorption, and decreased thyroid hormones. How much these 3 factors impact the LDL receptor depends on individual genetics. The reason why adding carbs back to a keto diet lowers LDL is because carbs increase thyroid hormones, which upregulates LDL receptors, thus increasing LDL clearance from blood. In the study below, the low-carbohydrate group demonstrated a 30% decrease in LDL receptor gene expression. Retterstøl K., Svendsen M., Narverud I., Holven K.B. Effect of low carbohydrate high fat diet on LDL cholesterol and gene expression in normal-weight, young adults: a randomized controlled study. Atherosclerosis. 2018;279:52-61.
Curious pushups! This was an amazing podcast. Like Simon mentions at the beginning, understanding each other as the goal was accomplished, as a listener. No attacks and curiosities raised. Both humble. Great discussion.
I’m still listening and the entire podcast was fabulous. A former LMHR who added carbs back successfully. I love listening to all sides which is why I subscribe to this channel.
Yes, go for push ups! This chat clarified a lot for me, I didn't expect to make it all the way through but it kept my attention and I will be interested to see how the conversations evolve out of this.
An absolute great discussion. I am impressed Simon that you really focused on listening and learning rather than trying to rebuttal all of Nick’s points. I think about 2 hours could have been cut out and still made the same impact but definitely worth the watch!
About halfway through and I'm learning so much. Very grateful for Norwitz' transparency about his own disease, his reasons, and how he personally weighs the pros and cons of choosing medication for him. I feel it's very nuanced and helps me look at my own situation through a more informed lens. Great interview. I make the (granted arbitrary) cut for an LMHR, as my LDL is 445 mg/dL (which made my doctor quite concerned) HDL 60, TG 30 (being 14 hours fasted, as Dave Feldman recommends). Been eating mostly carnivore with some carbs over the last 7-8 months. Also because of stomach issues, like Norwitz - plus food-induced eczema on my scalp.
Nick, have a chat with Mantzoros in Harvard. He said in this podcast that the root cause of CVD is insulin resistance and metabolically-illed arteries. And Simon seemed to agree!
Curious push-ups. Definitely moved the conversation forward regarding this important and fascinating area. It’s very pertinent and impactful to those of us in specific risk and phenotype categories trying to make critical decisions on how to approach health challenges. Thank you!
I really enjoyed hearing what Nick had to say. I also eat a keto diet after trying so many others with no success. This is the only one to resolve all my health issues. If I could eat differently I probably would, but the consequences are just not worth it. Forgot to add curious and pushups.
Curious pushups! 😂 I listened to this whole episode on a podcast and I can’t thank you enough for asking all the questions I have in my head. And not just with this video either. I was vegan for seven years then back to standard American diet and then last year plus I was carnivore until I got my ApoB number and particle size back! I had made the jump that being in ketosis as a result of the fast mimicking diet, wouldn’t that be good long-term !?!? I did not qualify as a LMHR and unlike other carnivores am not willing to take the risk of high ldl and ApoB despite feeling great. I am tired of people telling me and others that cholesterol does not matter! Nick was the perfect guest for this back and forth!💜
The question was asked "If you could bring down your ApoB to 60, without side effects, would you do it?" I understand the question. Simon really wants Nick to say that it's better to have a low ApoB. 🙂 And that's fine. Simon still operates on the belief that high ApoB is bad by definition. But in the context of the LEM, this is impossible. Because the high LDL-C / ApoB is a direct result from the high levels of fat transport. As is shown by the use of Statins in Nick's Oreo experiment. It went down a bit, but couldn't bring it down any further. And if I remember correctly, the dose was quite high. So it's a nice idea, but not practical. I'm mentioning this because I think it's important in relation to understanding the LEM.
“The belief that apoB is bad”? When did that become a belief? It’s probably one of the most established fact in medicine. Is it not applicable to keto dieters subgroup or what?
@@peterfaber7124 I agree. In the average population ApoB may have more weight in causing disease... but not necessarily in those healthy, active and have an efficient fat metabolism. Statins were clearly shown to have very little effect on CVD. David Diamond has gone over this ad nauseum.
Pushups! Great conversation, kept me company on my 2 hour drive down to work, then home again, with some to spare. It is so interesting to me that curiosity doesn't get the better of some folks to want to understand what is happening with this phenotype. 😊
I've done experiments on myself since my 20's. In my 20's, no matter how many vegetables I ate I was still bloated, constipated and straining. I put myself on probiotics for 2 years until my symptoms resolved. Knowing what i know now, I also would've removed dairy from my diet. My latest experiment was trying to use diet to get my cholesterol lower. I went from flexitarian (since my 20's) to vegetarian to vegan/WFPB. OMG. my cholesterol didn't budge! I then followed McDougall and Esselstyn's dietary addition of oat bran and high nitrate plants, specifically, arugula, and drastically reduced my consumption of oil and processed plant-based foods. That did the trick. I dropped my LDL from 144 to 82. Dropped total from 211 to 166. Dropped HDL from 65 to 57. Trigs went up from 145 to 160. HS-CRP was tested when my cholesterol was 211 and it was 0.3. BMI dropped from 23 to 21. My next experiment is getting adequate sunshine and seeing how high I can get my Vitamin D levels to go.
"Broken lipid metabolism" in FH doesn't really hold at all; the only reason why we would see individuals with FH-levels of LDL-C in the absence of any identified genetic condition is because similar pathways are being overwhelmed, e.g., LDL-R. We presented case studies at the Heart UK conference in the past two years of people with LDLs of >15mmol/L, in some cases ~21mmol/L...to suggest the absence of "broken" LDL-R implies this is perfectly normal lipid metabolism is a gross stretch, particularly given that these levels are reversible (to an extent) with diet.
Fascinating and thought provoking conversation, and I will be curious (see how I did that) to see the outcome of further studies researching this model.
Way to model mutual respect and civil discourse here, Simon and Nick. Thank you for providing clarity and nuance concerning both the LHMR phenotype and Nick’s views (both his hypotheses and his own personal approach). From what I had initially seen elsewhere, I still had so many questions (most of which you addressed). I think two of the biggest take-home points are that (1) LMHRs are a rare and unique phenotype, recommendations for whom are likely not to be generalizable to the “gen pop” level, AND (perhaps more importantly) (2) Nick’s own unique medical history makes his personal dietary choices even more specific and less generalizable to the “gen pop” level (or even to other LMHRs). I hope listeners heard loud and clear that Nick doesn’t eat carbs because he would have an IBD flare-up. This is not a prescription for others; thank you for stating that. I hope folks listen through the whole thing to really get the nitty gritty nuance and the many ways you gents helped bring clarity about what you each ARE and ARE NOT saying (and what you say boldly but hold loosely). The most valuable timestamps for me (after all the preceding context, of course), were ~3:50:00 to 4:02:00 and ~4:15:30. [I listened to the podcast version in case that impacts timing] Would love to hear more about pushups in future, gentlemen. Thanks for the great chat. Thanks for inspiring curiosity. (By the way, I can spell supercalifragilisticexpialidocious too.) 😉 Cheers!
The only one thing I hate of Norwitz is that he never acknowledges that the most important self experiments on LMHRs were done by Feldman. The white bread experiments of Feldman were first and basically identical to the Oreo experiment. And he should be acknowledging those fundamental experiments (but he never does).
@@sharkair2839 Yes, of course, he always mention him. But never acknowledges that the Oreo experiment is a copy of the white bread experiments of Feldman.
Curious/ push ups. Also, Nick can make a keto burned-Basque cheese cake. It's super easy (basically just cream cheese) and he might even be able to eat some himself. Thanks for the amazing conversation to both!
Thanks Simon another great episode….although I always listen to the pod rather than watch on UA-cam. I didn’t hear you say how many pushups you could do…I’m curious to know if you feel like sharing?😜
I listened carefully to half of this. I stopped listening because i thought the weight of the discussion was more about him than the issue he was trying to raise. I'm not sure exactly what this guy's message is (??) after listening for 2 hours (!!) In one way, he is saying... the results of my experiment are striking enough to provoke a debate about them (-because they could be relevant to more people than just me)... but then, in another way, he is ALSO trying to stress, that because the results are only linked to him (an "n" of 1) he is not suggesting that they are applicable to the general population... (-and therefore the results may not be significant at all). He strkes me as both a guy who is trying hard to be "objective" and a guy who is totally self-absorbed in himself. I started to care less, and less, about his results and potential "significance" of his experiment as his level of self-absorption started to irritate me. Your podcast Simon, is one of the best in the business, but on this 1 occasion, you gave your guest too much time and space to make a "word-salad" out of his 1 big opportunity to bring his message to the world. The guy focused too much on himself and not the data. 😕
Nick would LOVE to just talk about the data. However, he is having to talk about things other than the data because others who are misrepresenting him are muddling his message, which requires him to spend, as you stated, valuable time simply defending himself. I know it's a lot to sort through, and maybe simon will release an edit that makes things more clear. But if not, I encourage you to give it another go and see if things are more clear by the end.
@@saintwithatie yes, he came across as a guy on the defensive alright. He does seem to be very conscientious and meticulous about how he conducts his research. And he does seem to be rattled by others who have muddled his message. Perhaps I will finish the podcast then to see where it leads. Thank you
Let us know what you think by the end! I appreciate not all my episodes are for everyone and that's perfectly ok. I enjoy getting a little deeper into the weeds than other shows ... I find the more surface level conversations are less likely to challenge the ideas I hold. That said, I am rolling out some shorter solo episodes to help consolidate some of my views/learnings :) So stay tuned for those! Thanks for taking time to submit feedback!
Great podcast! HUGE fan of @nicknorwitzphd! Pushups Curious. BTW, would love to have a conversation, Nick. I am also a LMHR with Crohn's disease. I believe I was also one of the first ones to hear Dave Feldman speak at a Ketogains conference in Las Vegas several years ago. He was explaining to me and Robb Wolf what his talk would be about in the back of the conference room,. Crazy how far he (and your group) has come! Appreciate all you do!
In relation to the low-carb community not believing in lipid-lowering drugs,... It may be a factor that these opinions are held by people in the low-carb community who don't have CVD. From the point of these people, taking a statin for high(ish) cholesterol doesn't make a lot of sense. But the message of the cardiologists often is: "You should be on a statin." So it's not so strange there is resistance against that message in the low-carb community.
I wonder why the message is that (for a specific phenotype) adding carbs (no matter the source) to a keto diet can lower LDL dramatically, and not that removing all carbs (no matter the source) from a balanced diet will raise LDL dramatically. And it’s obvious to anyone following the carni crowd, that they would try to suggest that statins are as bad as Oreos after Nick’s experiment. To expect anything different would naive.
All net carbs. Fiber can irritate my IBS, but not IBD as far as I'm aware. I just get bloated and farty. I've yet to find a good protocol to prevent this response. Maybe one day. I've to routinely eat Brussels with walnuts bacon. Too good.
@@nicknorwitzPhD Sounds like you have dysbiosis. You need to pack down 100g of fiber today with some probiotics and after 6 weeks to 2 months the farting should subside. I had a similar issue at first as well, I was waking up at night to huge farts.
Hi Great podcast Nick. I have a question, hopefully you see it :) When you were on the Oreo diet you said you took a ketone supplement to help with your gut. So, why don’t you take the ketone supplement and eat a more standard healthy Mediterranean diet? Also, have you considered doing a plant based keto diet for the animals and the planet?
The one thing that makes me wonder is why we are always talking about LDL particles being atherogenic, while atherosclerosis occurs only in very specific places of the arteries. Would it not make more sense to say that those places of the arteries are atherogenic?
Shear stress/blood pressure is an important factor in the development of atherosclerosis - it influences the expression of caveolin-1. And no, atherosclerosis occurs everywhere. But not equally fast.
@@EVanDoren Everywhere? Not really. Mostly in places where there's mechanical stress and/or endothelial damage. These things are not caused by LDL, but LDL is drawn to it like a moth to a flame.
@@EVanDoren I attempted to tag you in a top-level comment but I'm not sure the tag worked. I'm confused about your positions and wanted to understand better. You should see the comment easily by sorting by new comments.
Excellent discussion, Simon you always impress me with the choice of guests and curiosity you have. With regard of LMHR phenotype on carnivore diet and the question of risk of CVD: I think in about 20 years we may see retrospective observational data in this regard given so many are on a carnivore diet nowadays. As much as I would love a good RCT, I am sure it will never happen. But who knows...after all carnivores out there are now running their own experiment in life and, indeed, they may give us an answer in the future.
Thanks yes will be interesting to see what happens. However, the pessimistic part of me suggests we won't learn unless there's good clinical data. We're likely to only hear of the success stories - not the people who gave up due to side effects or died earlier than they otherwise would have on another diet. At the very least someone should start collecting proper data on a keto cohort, and monitor them prospectively over decades to come.
Please strive to equalize the audio quality and level between the interviewer and the guest. In ths case the guest is speaking further from their microphone.
I speak a lot... Simon is presumably trying to equalize the audio input AUC. It's said that Nick Noise Exposure, in decibel-minutes, is causally and in a dose-dependent manner associated accumulation of 'mind-blown-ness.' Please listen with caution. You don't want to have a Major Awesome Curiosity Event.
Australian health professional here - The 3 things that combine to cause plaque build-up in my opinion are - 1. High APO B 2. Endothelial dysfunction, lack of natural VIT C. 3. Mild insulin resistance. God speed to you all.
Andy, question: thoughts on Peter Attia's statement high ApoB is "necessary but not sufficient." Is this true entirely? Or do you expect a threshold effect whereby high above a certain level ApoB - irrespective of etiology - will always 100% of the time drive ASCVD?
@@nicknorwitzPhD I'd agree with the necessary but not sufficient statement, I think the main driver is endothelial dysfunction caused by mild or worse insulin resistance and low VIT C, high oxidative stress. Have you had a CTCA with your high levels of ApoB?
Wrong. The cause is the accumulation of cholesterol in foam cells. To get there, LDL particles have to be transported across the endothelial layer via transcytosis. LDL transcytosis is the main limiting factor in the development of atherosclerosis. And it is dependent on the following factors: 1. By far the most important: LDL cholesterol 2. Inflammation accelerates transcytosis 3. High blood glucose accelerates transcytosis 4. High blood pressure accelerates transcytosis 5. Some hormones can be protective (estrogen). Otherwise, some plant foods contain active compounds that can increase cholesterol efflux from foam cells. Others can block cholesterol absorption in the gut. Third can block or increase bile acids formation, which decreases cholesterol in the blood. Finally, we can decrease cholesterol synthesis in the liver. Summary: eat plant-based, minimize animal products, saturated and trans fats. Certain plant foods can farther improve the outcome, but that's too much for a UA-cam comment.
I don't understand why the enfasis of LMHR being a very rare phenotype. I really have a question. Of all people who go on a ketogenic diet and are consider lean, what percentage does not transforms into a LMHR?
Because they don't have genetics driving their cholesterol up (unlike those with Familial Hypercholesterolemia, FH), studying them long enough could definitively determine if high cholesterol causes cardiovascular disease (CVD). However, no one wants to fund this research due to fear of the potential result: that high cholesterol in a healthy metabolic state might be protective against CVD and all-cause mortality. I predict this will be the finding of the crowdfunding study on Lean Mass Hyper-Responders (LMHR), which has already completed initial tests with results that seem to support this hypothesis.
@@fadiyt8816 I just ask this: "Of all people who go on a ketogenic diet and are consider lean, what percentage does not transforms into a LMHR?" this has notthing to do with risk. Is just, puting lean people on a KD and checking their LDL, HDL and, TG every day or week for a month or two. Is not that difficult to access.
I'm enjoying listening to this episode in bite sized chunks as I get time. It's a pleasure to listen to people with somewhat different views have an intelligent and constructive conversation. @Simon, hopefully you can line up a session with Anthony Chaffee, Shawn Baker or Paul Saladino. I would love to see where the conversation goes and where the common ground is. @Nick, I would love to see you debate Dr Alo on your channel - it would be comedy gold 🙂
@@TheProofWithSimonHill that would be great if you could sit with Shawn Baker. He has been very level headed and honest in the interviews I've seen him in. If he doesn't know, he's quite happy to say "I don't know". I can see it being a really constructive discussion.
I have been taking high dose statins for the past three years with ezetemibe and combine this with a vegan diet. Maybe the discussion for statins should now focus on its potent antioxidant benefits particularly at the endothelium and its protective effect! Perhaps this settles the fact on both sides that LDL itself isn't causative and the lipid lowering benefits of statins are overstated. However statins provide both benefits! Unfortunately tolerance to statins will always be an issue in a population. My advice is: be the N=1.
@@TheProofWithSimonHill to be lean - get your cholesterol above 300 get your at rest mid day body temp up to 98,6 and your pulse to 80 check the data from 1940s -
This is so interesting but I'm not sure if I'm considered an LMHR. I'm NOT on a keto diet but a lower (100-200g/day) carb, 80% whole foods plant based diet. Recent lipid testing showed HDL 117, Triglycerides 59 and LDL 174. Female 63 yrs, 125 lbs. Not on any lipid lowering drugs due to low overall risk but considering using. Not sure if advice for LMHR applies to me. Am I a separate phenotype? I haven't seen my situation addressed before?
You could easily find out if you are an LMHR by cutting back on your carbs further for a while and then testing. If you are hyper responder, you will most likely always be a hyper responder no matter what your diet is. Your (lipid testing) response will just be different when not eating a very low carb diet.
The problem with the inquisitive researcher is that he always finds marginalization at the beginning until the specialists first understand his work, then the rest of the people who are subordinate to the specialists and have nothing! ..This puts Nick in line with society, and I tell him to continue!
I am so excited to listen to this podcast! In April, my partner (meat eater) had bloodwork done and found out his cholesterol was 331! So as an experiment, he started eating my plant-based, vegan meals with one cheat week in the middle where he ate seafood because we were on vacation at the beach. He just had bloodwork done yesterday and his cholesterol came back as 230. This was amazing and so validating for me that a whole-foods plant based diet DOES help with cholesterol.
Somewhere along the line, the "necessary and sufficient" definition of causality seemed to get lost from its original intention, per Rothman, and now gets wielded about with the seeming intent of providing some robust epistemic test to the evidence, but in ways that are probably less useful than they appear. Rothman's original concept of adding "sufficient" to "necessary" was to improve on merely considering causes as "necessary" because that was unsatisfactory. For example, cigarette smoking causes cancer; but smoking cigarettes is not "necessary" for someone to develop cancer. Yet based on the evidence, smoking is certainly a cause of cancer. Adding "sufficient" was in Rothman's formulation a "sufficient-component cause" model, because to apply a strict "sufficient" test would be to apply a deterministic definition, that the guest himself applied, which isn't suitable for biological processes. In fact, we could apply the "necessary and sufficient" definition to argue that smoking does not cause cancer, because in the strictest sense, smoking is neither necessary nor deterministically "sufficient" to cause cancer. One particular limitation of the limits of "sufficient" and its deterministic implications is that it can't account for dose-response relationships, which is crucial to determinations of biological processes and related causality, because if a cause is "sufficient", it is considered fully sufficient (as articulated by the guest), i.e., its mere presence should bring about the effect. But this is not the cause, as LDL/ApoB exhibit dose responses (that are linear), i.e., as the cause increases this changes the corresponding effect. "Sufficient" can't account for this, in the crude deterministic definition that is applied to it. Tl;dr, the "necessary/sufficient" definitions are not a useful framework for thinking about causality in the context of biological processes and multifactorial diseases. It is a distraction, more hindrance than help.
35:00:00 in. Good for you on bringing up the Shawn Baker quote. Shawn is literally the one who promoted this study on a large scale, and what he took away from the study is what many in the low carb community did. If bad Oreos lower cholesterol, then lowering cholesterol must be bad.
I'm sure they can't make that connection, doesn't sound like Shawn he's not that stupid. lowering cholesterol with Oreos is a mechanistic action to energy provision. seperate to lowering by blocking production at the liver.
@@Petunia-fl9lu “If eating pure absolute garbage junk lowers your LDL cholesterol more so than even satin drugs what does it say what does it say about the act of lowering cholesterol?” Shawn Baker
@EVanDoren Making a standalone comment so we don't blow up others' comments. I'm confused what your position is. 1. What is your issue with Nick? I'm very familiar with his work, his position, and his communication, and I have seen nothing unsavory or fraudulent coming from him. Every criticism of him I've encountered has been a misunderstanding or a straw man. What are your specific reasons for dismissing him and his work? 2. What is your position on LDL and ASCVD risk/development? I ask because you are commenting what seems to me to be refutations of other comments, but you're essentially saying the same thing the comment said. Do you agree with the following?: - The thing we are trying to avoid is the excessive buildup of plaque. I say "excessive" because it appears that plaque will form to some degree throughout the lifetime, but we want that buildup to be as slow as possible so that buildup isn't the thing that eventually causes an event that leads to injury or death. - There are several steps that lead to excessive plaque buildup. LDL must exist in the lumen (obviously) -> LDL must pass through the endothelium via passive or active transport into the intima -> LDL must get "trapped" in the intima via incorporation into foam cells -> foam cells become a plaque that can build up over time - All of the above outlined steps are mediated by factors such as inflammation, blood sugar, etc. that 1) result in the transformation of certain compounds into versions of themselves that are more atherogenic and 2) interact with receptors and other cellular machinery in a way that makes it more likely for the LDL to end up in the intima and trapped in foam cells. If you DO agree with all of the above, then why does it seem like you disagree with statements made such as (and I'm paraphrasing here) "LDL is simply a biomarker." "ASCVD is driven by several factors." "The mere presence of "elevated" LDL isn't sufficient to spontaneously induce all of the steps required to form plaque." "High Apob, inflammation, endothelial dysfunction, nutrient deficiencies, and metabolic/insulin dysfunctions are all risk factors for ASCVD"
"it appears that plaque will form to some degree throughout the lifetime" - not necessarily. If LDL-C is low enough, then cholesterol efflux into HDL can negate or even reverse the build-up. "LDL must pass through the endothelium via passive or active transport into the intima" - the transport is always active, it's called transcytosis. It's basically caveolae turned into vesicles, which are transported along the microtubules by the motor proteins. It's like a molecular elevator. "LDL must get "trapped" in the intima via incorporation into foam cells" - it's called fluid phase pinocytosis, the cell basically gulps down a bit of intercellular fluid together with lipoproteins. The cell cannot metabolize cholesterol, thus the accumulation. "All of the above outlined steps are mediated by factors such as inflammation, blood sugar" - those factors simply change the expression of caveolin-1 and other proteins needed for transcytosis. Estrogen blocks SR-BI, which is the docking protein inside caveolae. "interact with receptors and other cellular machinery in a way that makes it more likely for the LDL to end up in the intima and trapped in foam cells." - more likely for LDL to be transported across the endothelium "LDL is simply a biomarker." - LDL is the cause. No atherosclerosis without LDL. There are primitive African tribes where almost everyone heavily smokes, inflammation is sky-high, but they have total cholesterol around 100 mg/dl, and zero atherosclerosis. "ASCVD has several factors." - there is one factor. Cholesterol inside of LDL. The others are merely modifiers. They can accelerate or decelerate the process. They cannot initiate it. "The mere presence of LDL doesn't spontaneously induce transcytosis." - the mere presence of LDL is sufficient. "inflammation, endothelial dysfunction, nutrient deficiencies, and metabolic/insulin dysfunctions are all risk factors for ASCVD" - they are merely accelerators.
@@EVanDoren Thanks for the reply! This is really helpful and I think I now realize something. It sounds like the disconnect is that you are focusing solely on the cholesterol in the LDL that gets consumed by macrophages as the initiator of the transformation of macrophages into foam cells and thus initiating plaque formation, while others like myself and Nick would focus on the entire chain of events and modulating factors thereof that happen up to the point of foam cell formation. If that is what is going on, I would mostly agree that cholesterol in foam cells is the most direct cause of plaque formation/buildup. I say mostly because there are still known and unknown factors modulating the transformation of cholesterol-containing macrophages into foam cells. I would say "Under the right conditions, cholesterol in macrophages causes plaque formation" Would you agree about this disconnect, and if so do you think it lends into the reason you don't like Nick?
@@saintwithatie 1. Not only macrophages can become foam cells. 2. There is no chain of events. No endothelial injury, nothing. 1-2-year-old babies already have fatty streak in their arteries, especially if mother's nutrition is rich in saturated fat. Transcytosis is a normal process. Pinocytosis is a normal process. Cholesterol getting into the artery wall cells walls is a normal process. What follows is a race between LDL delivering cholesterol and HDL getting cholesterol out via efflux. I'm not speaking about the latest stages of the process - we have all the means to not getting there in the first place. There is a disconnect between claimed ideals and Nick's actions, I also think that his actions kill people. Therefore, I don't like him. He claims he is not like other keto-shills, but he acts exactly like one of them.
@@EVanDoren I think we're still disconnecting. It seems like you're interpreting "chain of events" as having a negative denotation. The phrase just means that one thing must happen before the next thing. LDL gets transported across the endothelium before the foam cell precursors (macrophages are one, but there are others, as you pointed out) consume it, and the foam cell precursors consume LDL before turning into foam cells. These are events that are chained together chronologically - a chain of events. Saying that something is modulated doesn't mean that it is not "normal." Every single "normal" process in the body is modulated by a variety of factors. The speed of LDL delivering cholesterol and the speed of HDL getting cholesterol out are both "normal" yet modulated processes. I'd be interested to know where you are from and how you became interested in this topic. I see you have a playlist with a Russian title, so with your name and the title I'm guessing you are Russian or at least from a Russian-speaking area. I am wondering if there is a disconnect stemming from differences between Russian English and American English. I befriended a Russian woman during a trip to Korea and I've noticed such between us. Can you elaborate on how any of Nick's actions are killing people? Not the actions of others or the misrepresentations of his words by others, but his words and actions alone, taking into account all of his transparency and all of the clarifying that he does (which is so much that commenters are saying made this video too long). I am interpreting "shill" to mean that he is being fraudulent in his stated positions and is only promoting (or rather, not demonizing) keto for personal gain. Do you really think that he does not believe what he is saying? Do you really believe that he does not have a passion for metabolic health and a desire to advance that field? I've only seen him behave in a vastly more transparent, professional, and scientific manner than most other scientists regardless of field or communication channel. What exactly are the actions of his - again, not the actions of others or misrepresentations of his actions by others, but his actual actions - that you disagree with? What did he do vs. what do you think he should have done?
ApoB, which is predominantly LDL, is arguably the most important risk factor for atherosclerosis. The correlation found between ApoB and atherosclerotic cvd occurance suggest that “elevated” apoB is the only factor necessary to form plaques. While other risk factors increase atherosclerosis, they are not necessary at all. High presence of inhibitory factors as suggested by mechanism studies might be able to stop oxidation and modification process but they do not have causal relationship with the factors you’ve mentioned and do not correlate well with them either. It’s not like good results from crp or homa-ir will prevent you from developing plaque with elevated apoB. That’s never been shown. No data exist to my knowledge that suggest that, you might want to do subgroup analyses which will probably tell you that you still have atherosclerosis with high apoB and everything else normal
@Simon, OmegaQuant founder posted a 1m:37 sec video on the OmegaQuantLab channel a month. It says that "improving" your n~3 numbers reduces your CV risk, regardless of your cholesterol level. I wonder if it would be interesting to have him on to discuss this and related topics. I can't include the link because then yt won't post my comment.)
Really enjoying it so far, but commenting midway to say I didn’t realize Dr. Alo was a quack. I appreciate it when you tell your audience you don’t necessarily agree with things your guests put forth.
Mostly PUFA fat. PUFA destabilises LDL so I suspect there's a feedback mechanism which makes the liver produce less. Not necessarily a healthy change in that biomarker.
I'm half way through, and I still don't understand why he thinks he needs different data for this sub population. I don't see a reduction on TGL and an increase in HDL and LDL cholesterol as such a distinct group. It is what most meta analysis show that happen when going keto or low carb. The reason for not believing general population data would not apply to this sub population is still unknown to me. For all I see, I could believe LDL-c over 100 wasn't a problem for me because I haven't seen specific LDL-c x CVD studies with a population of Brazilian men, father of one, left handed, brown haired, former smoker but currently athlete, engineer and nutritionist and that are called Cadu.
The first thing is that we can never assume that population-level statistics necessarily play out in sub-populations, especially the smallest sub-population of the individual. This is done all the time but it is logically fallacious. It is always a valid question to wonder how things play out when factors relevant to the outcome change even slightly. This applies to ASCVD risk as a function of LDL exposure, risk of deficiency as a result of a particular level of nutrient consumption (nutritional RDAs), etc. The second thing is that, in this case, we actually already have evidence suggesting that there are factors related to the specific cause of "hyperlipidemia" that affect ASCVD risk. I don't have the timestamp, but Nick cites a study suggesting that certain populations with similar levels of "hyperlipidemia" but different causes for it have different ASCVD risk.
As far as I'm concerned, you can't assume a result from a sub population would apply to another, or to the whole population, but a study that comprised many subpopulations has a far greater chance to apply to the subpopulations it covered. Of course there's a chance it does not, in which case the effect on the other subpopulations must be greater than the average result if the study showed a overall statistic significant result. But when we are talking about something that's been showed over and over for many populations, it is irresponsible to assume there is no risk for a specific population. If we were talking about improvements of something, we could take the conservative approach and say perhaps this benefit doesn't apply. But we're talking about a causal factor of the #1 killer disease in the world, we MUST assume the risk also applies while doing further studies. I've past the part of mentioned, and although bit different risk profiles, all of the differnwyr causes for high Ldl-c showed a HIGHER risk than regular ldl-c level.
@@cadupradoo "It is irresponsible to assume there is no risk for a specific population." Is this what you think Nick is saying - that there is no risk for LMHRs?
No, I don't. He says he doesn't know what the risk is, but the set of these actions, as Simon very kindly suggests with his questions, is that the information that is passed when this discussions happens is mostly that "since I'm not sure what the value is, I don't take action, even though it is highly unlike that the value is 0". And I don't think the scientific question isn't there, I just think that the whole community acts like there is nothing on the subject to make decisions on. Also, about the study you mentioned, it compares monogenic, polygenic (which also has an environmental factor) and non determined causes for high LDL at recruitment. It is expected that the results are different, since the monogenic people have had high LDL-c since birth. The polygenic have had a combination of genes since birth with environmental factors, and the other group have had high LDL-c more recently. It has come back to cholesterol-years like many would expect.
@@cadupradoo What actions are you referring to when you say "the set of these actions"? Also, yes, it may indeed come back to cholesterol-years. If that happens, then that's great - we've learned something. It's stil possible that it might not be, so it's worth investigating, and doing that requires data from populations such as LMHR, which is why Nick wants that data (going back to your original question.)
3:46:00 in, Nick just finished talking about being upset with Peter Attia’s statement that he’s tried to understand the other side, but Nick thinks this is disingenuous. I’m a little confused by Nick thinking this because they also talked about Peter having Dave Feldman on his podcast, who does have the scientific chops to speak on this subject. I admit I haven’t listen to that podcast, I plan to after this one. I realize it was four years ago, per UA-cam. However, is that not an example of Peter trying to understand the other side?
There is a difference between merely having someone on your podcast and having the best-possible-faith, hungry-for-understanding engagement with what someone is saying. What Nick highlights is Attia's misrepresentation of certain points by focusing on the words of people OTHER than the study authors (what Nick refers to as "the words of rando extremists off social media") instead of focusing on the actual words and positions of the study authors. Would you not agree that this behavior is inconsistent with really trying to understand something? If you want to understand something via discussing it with others, it behooves you to represent the thing accurately, yes? Otherwise, you're discussing and trying to understand a strawman, not the actual thing.
1:04:51 Regarding lab grown meat, the thing is we cant make lab grown mest that is cell for cell, nutrient for nutrient, identical to real meat. If you could prove that we could create lab grown meat, identical with every molecule. That’s a different story
My problem with blaming LDL levels for the cause of heart disease is we are not taking into account what the person is consuming for food. I believe it’s the diet that driving poor health. Most Americans have a poor diet aka S.A.D. If the familial cholesterol population ate a whole food diet I believe they would have better health and less heart disease. I don’t really hear anyone talking about changing their dietary patterns. It’s always only about lowering LDL.
I wrote an entire booking on changing dietary pattern. No only to improve LDL-C but also body weight, blood pressure, fasting glucose, muscle mass, bone density etc
I just got my blood test 3.5 months ago and then again 2 weeks ago, they are looking at whether I am familial cholesterol. I am a 7 year vegan, eat a whole food diet fresh fruit, plants, and nuts I weigh 171 pounds and run 10 to 12km 5-7 days a week, go to the gym twice a week (54 years old). I have just discovered I have high LDL so diet does not change high LDL if familial cholesterol. Not that I can figure out because when I first got my results back 3.5 months ago, I thought it would be the oat milk cream I take for my coffee so I gave it up and it didn't change anything. I take supplements where I need them like B12 and protein powder in my shakes, do not drink any kind of plantbased milk, water only and electrolytes when I run. Basically, my point is to your quote about familial cholesterol population eating a whole food diet to change LDL, I do and it hasn't changed my LDL.
It’s curious that while dayspring and nick have different views on the science they have similar speaking styles- kinda long winded and they don’t let Simon get a word in edgewise. After all the pushups I still get the feeling that nick is a troll, and given the obesity epidemic, focusing on lmhr people isn’t the best use of scientific funding
@@sethboviper Their funding is mainly private. So, no tax payers money goes into it. People who want to know, pay for the research. And I think that is a good way to go.
How curious, push ups? ...💤 🛌 😅 I thought I was curious, Nick takes it to a whole new level, which I think will make him an excellent researcher. It's just too bad the animals and the planet pays for it. So to Nick, if humans stopped eating animals, more specifically ruminants, the climate emergency wouldn't be so much of an emergency. The pebble analogy to both the complexities of human physiology and the amount of information presented felt like a breaking wave when the pebbles was a motivation looking for solid answers. I don't think Nick will have to worry about having too many people unfollow him on X Twitter for not being a sugar Nazi, I not convinced those kind of people would have made it to the "baking cheesecake" bit. As for 10 hours, please don't. That said, the lean mass high responders, interesting but, the lipid model way more so. Imagine being able to look at genetics and physiology and predict health outcomes. One more point, all cause mortality, absolutely agree not a the best indicator, living majorly incapacitated or entirely incapacitated or as a vegetable definitely needs inclusion. Last thing I need to say, Yes it was too long! 😅
@@YaYippieYeah observational only. No data. I'm in a group of 11 people - direct friends. We share our eating habits and I recently went on a nine day fishing trip with three of them. All four of us are in our 60's and ate the same keto diet the entire trip. We all have similar panels, except one had a grossly higher LDL-c, and another had a TG/HDL ratio higher than 1.0 (rest were below 1.0). Of the entire 11 group of friends, seven are LMHRs per the definition. I am also a member of two FB groups (70K members) that follow keto and carnivor diets. The stated prevalence of LMHR is very high. I'm not special. Daily home workouts plus three resistance training gym visits per week, 5'8", 155lbs. Before keto, four years ago, I was 175lbs. Bloods: Before K: HDL=64, LDL=145, TG=74 After K: HDL84, LDL=191, TG=48. These are just facts. I have no idea of whether I'm killing myself or not, but CAC score one year ago was zero, which is why I support these studies and believe they are worth while. I assume you don't need data on the growing prevalence of keto consumption.
@@YaYippieYeah lack of evidence is not evidence of lack....just because a group hasn't been studied doesnt mean they dont exist. Many clinics are finding this phenotype who work with people who are LCHF/Keto - Dr. Berg, Dr. Ovadia, Dr. Nadir Ali, Dr. Cromwell and the growing database that Dave/Nick have in their cohort.
Yo Simon have your ever heard of Dr. Peter Rogers? He's an absolute riot. Go check out one of his talk on chef AJ if you haven't already. He is in the low fat McDougall camp and he explains everything in an extremely interesting way via mechanistic and observational data.
@@TheProofWithSimonHill got a lot out of it but - try many different N=1 exps on ourselves to see how we respond and keep doing what makes us feel good. Referencing the take on his IBS and fiber management. It seems to have opposite effects on different people. - LA is burned in priority when consumed, therefore the argument that it is easily oxydized is probably not a problem for oxLDL. BUT I am still curious: if not in keto, will LA still be prioritized? If yess, we don't have 'access' to our carbs? If not, would it not accumulate in our fat tissue? - the risk profile for LMHRs is not known but does not seem to be that risky. In that pop, saturated fat doesn't have a big impact on LDL. So a person on keto might fully thrive and tell you that butter is good, but it's probably wise not to consume vast quantities of saturated fat if not on keto, because for THAT SEGMENT of the population, it is linked to LDL. If we're not on keto and not sure about our metabolic health, it would be wise to be more conservative. I would like to ask on the advice for LMHR that will add the sweet potato: if in that case, they are not longer on keto, their LDL would drop and therefore NOT be LMHR anymore? In that case, wouldn't ALSO limiting saturated fat also have a substantial impact on LDL? Learned a lot but still have lots of questions 😅. It's my first Podcast I listened from you, will definitely subscribe!
By not having access to our carbs, I was saying are we storing the carbs in order to burn LA or if both stay in the blood and burned simultaneously or if LA will go into tissues while we burn sugar
@@TheProofWithSimonHill the double Oreo gift? haha But in all seriousness it's tough to pick a certain part of the conversation I found most interesting because it was more about that the conversation was happening at all. You challenged things Nick has said in the past in a polite way, and it led to him responding in a polite way. There were no interruptions, no heated character attacks, etc. I applaud you both for taking the time to do this, even having a double episode of sorts. If these conversations don't happen, we'll never get anywhere, and people will remain in their tribal echo chambers. Looking forward to the next one.
2:03:30 in. Simon is asking why Nick doesn’t use the precautionary approach and lower his LDL. I think this is the biggest rub on Nick. Nick uses the precautionary approach to a higher degree than most in other circumstances, like staying away from certain artificial sweeteners, but not in the case of lower ldl? Seems like a contradiction to me. He starts talking about trade offs on if lower LDL is actually better, but the reality is, Nick’s LDL is 95 on a mixed diet. So does Nick really think there is a longevity trade off of something like dementia in bringing his LDL back to what it is naturally on a mixed diet?
So, LDLc is just a marker. The actual risk is plaque. He clarifies that he is monitoring plaque (soft and hard), and will pivot his treatment if things change and as new data comes out. He also recommends monitoring and pivoting as necessary to others.
@@nicknorwitzPhD You are keto because of your Ulcerative Colitis, but can’t you still be keto while adding a “healthy” carb source to lower your LDL? Can’t you still be keto and take a medication to lower your LDL back to your mixed diet normal? Do you think getting you back to 95 would be a trade off?
@@worldnomad2301 I can't add sufficient carbs to have any large impact on my LDL because that would prevent the therapeutic endogenous ketosis. I've tried ezetimibe and Crestor and am intolerant to both. Considering the benefits of pharmacotherapy are not clear in my phenotype/case, that I have no evidence of plaque on CCTA (now 5 years on this WOE), no family history of MACE associated with high cholesterol, that the medication have known potential side effects and unknown long-term safety profiles in the case of PSCK9i (esp in metabolically healthy persons; and there are 'curious' findings such as increased Alzheimer's HR in MR studies), then the calculus of pro vs con of treatment sits with lots of unknowns. I reserve the right to change my personal choice at any time and do not extrapolate from my choice to suggest others should do the same. Is that fair?
Great talk, I understand Nicks frustration, people tend to argue out of emotion rather than engaging with the science when it comes to this as they’re potentially triggered by the what they perceive as a dangerous idea
5 Hrs what a absolute treat
Also can't wait for the comments on this one 🤣
Ditto...
Glad you enjoyed it!
@@nicknorwitzPhD, I listened to all of it though it was 2.5hrs using 2x speed ;-). Great job; I'm still curious. And Nick.. you need to try cheesecake or other baking made with Allulose or using RX sugar chocolate syrup, works out very well.
@@TheProofWithSimonHill being in a chronic state of ketosis drives Cortisol up, which in turns makes the body want to store fat, ut you're in Ketosis so now you're about to blow out your thyroid and drive down body temp Proven over and Over - in less than 5 years IN CHRONIC KETOSIS, not low carbish
As a 70 something LMHR, like Nick I have weighed the pros and cons of introducing drugs to lower my sky high LDL. Here’s what I know: All of my bio-markers with the exception of LDL is considered optimal, I have never felt better in my life both mentally and physically, plenty of energy, stamina, sleep well, enjoy hiking and occasional very strenuous exercise and I like the image when I look in a mirror naked. At my age I know that I am an outlier; one of the less than 1% of people my age that does not have any metabolic dysfunction. I don’t know the amount of benefit if any I would have by taking a drug to lower LDL but I am aware of adverse side effects. Also all of the experts that recommend lower LDL also criticize my diet that is the opposite of their recommendations; no fruit, veggies, grains whole or otherwise, instead mostly red meat with the accompanying fat. Am I stupid to not tamper with what has worked wonders for me?
@@colinvankeith4814 all.i have to say is we will see. Sure seams like playing russian roulette. And why??
No.
@@colinvankeith4814 - here's my take on this.
Yes, with a high fat, protein rich diet you'll feel more energized and your so called stamina will be high, but the human body has its limitations.
High LDL will make you feel good, better healing etc, but in the long run isn't beneficial for cardiovascular risk.
To live long and to be healthy in the long run is not to maximize your highs.
Look at it as a gas burner. If you go full flame, you'll shine strong but limits your time.
Gandhi is another analogy......
@@acke26 A study of the oldest of the old taken from NHANES data found that only the elderly with highest LDL survived to over 100 years of age. Luckily for them they didn’t burn out.
@@colinvankeith4814 this can easily be explained by reverse causation.
Curious pushups! As a clinician this podcast reflects a lot of how I practice. 99.9% of my patients are getting statins, zetia, or repatha, (not much BA yet) if indicated and informed of benefits and risks. A CT A really helps people to clarify their decisions too. As of now I have 3 patients in my practice w LDL> 200 and a clean CTA. One in their 50s,60s, and 70s. I now require also getting a carotid ultrasound as CT A is not perfect. If both are clean and the patients, after being informed of this gray area in medicine wants to continue w surveillance then I am ok with this. I will stress that this is
Plant-based diet is superior to statins
Soooo much medical and nutritional misinformation out there, it's very refreshing to hear a discussion like this! Thank you Simon Hill.
Absolutely. Especially when people deny high blood cholesterol is one if the main factors that cause atherosclerosis or think sky high cholesterol is ok for everyone if they eat a specific diet or that they should pour seed oil down the drain while there's an overwhelming amount of quality scientific evidence to back up positive health outcomes with eating seed oils and negative health outcomes with high blood cholesterol. These false messages do so much harm itjust makes my blood boil.
@@demonfedor3748you know what seed oil Is right?
You said bacon is a superfood. It clearly causes colon cancer and cardiovascular disease. Check yourself, Dr. Berry.
You said bacon is a superfood. It clearly causes colon cancer and cardiovascular disease. Check yourself, Dr. Berry.
@@demonfedor3748 positive health outcomes to consuming seed oils, ???
Beautifully done Simon and Nick!! Truly how one ought to have a discussion instead of a throw down. Putting the health of a patient as the ultimate goal instead of feeding personal ego or just regurgitation of old papers without accounting for new developments making them less relevant. Great job!
Thanks for the feedback!
"Truly how one ought to have a discussion instead of a throw down" -- agreed! Simon kept his position (a normal concern for misinterpretations of this study) while also premising its new information for listeners. Nick's actual curiosity for nutrition science and how to get public attention to give a deeper look at how health anomalies can inform us, was refreshing. The 5 hours flew by....Can't wait to hear more on LDLs. Many diverse body types (esp. ageing parents) suffer w/ this. Thanks so much.
Pushups! 👍🙂. Asiide from that I have a great deal of admiration and respect for Nick. I love that he is willing to think “outside the box” despite any negative pushback. That takes a lot of courage. Many Thanks Simon for hosting Nick, and being open minded enough to hear him out.
An interesting discussion (and nice that it’s not in an echo chamber). I too have noticed a correlation between BMI and LDL. Like most, my medical ‘history’ started with diagnosis of a condition (T2D). On diagnosis, my LDL was on the high side (above recommended levels). I was I’d say slightly overweight but not obese (79kg and 178cm). I lowered carbs considerably (long before I had even heard of low carb, keto or anything - just that it seemed to be logical if my body didn’t metabolize glucose very well, then eat less of it). My A1C dropped down to 5 (from 12.8) and my LDL fell quite quickly to well under the recommended max). Over time (2 or so years) I lost about 5kg (without actually trying) and my LDL started to creep up ever so slightly towards the high end of normal. Thus, I think that my case seems to converge with the inverse relationship between LDL and BMI. Therefore, I hesitate with respect to lowering LDL pharmacologically when it appears to be an outlying bio marker going in the wrong direction. It’s probably worth pointing out that on T2D diagnosis all my liver enzymes were high (which I just assumed was excess alcohol) yet these too just dropped to normal levels after going low carb (without any reduction in alcohol). I have regular full blood work done and everything else also looks fine. I’m far away from LMHR criteria (TG and HDL meet the levels but my LDL is too low [even though it might be considered high]). Looking forward to further advances in understanding what might be going on.
In my opinion, LDL receptor down-regulation likely contributes to elevated LDL in people on a keto diet. My guess is that the down-regulation could be from increased saturated fat intake, increased cholesterol intake/absorption, and decreased thyroid hormones. How much these 3 factors impact the LDL receptor depends on individual genetics.
The reason why adding carbs back to a keto diet lowers LDL is because carbs increase thyroid hormones, which upregulates LDL receptors, thus increasing LDL clearance from blood.
In the study below, the low-carbohydrate group demonstrated a 30% decrease in LDL receptor gene expression.
Retterstøl K., Svendsen M., Narverud I., Holven K.B. Effect of low carbohydrate high fat diet on LDL cholesterol and gene expression in normal-weight, young adults: a randomized controlled study. Atherosclerosis. 2018;279:52-61.
Been waiting for this one Simon! Appreciate you having Dave, Nick and Cromwell on
You're welcome. Enjoy
Curious pushups! This was an amazing podcast. Like Simon mentions at the beginning, understanding each other as the goal was accomplished, as a listener. No attacks and curiosities raised. Both humble. Great discussion.
I’m still listening and the entire podcast was fabulous. A former LMHR who added carbs back successfully. I love listening to all sides which is why I subscribe to this channel.
Glad to have you on board!
Brilliant, glad to see you together Simon and Nick. Congratulations. 🎊
Enjoy Phil! Thanks for all you do!
Enjoy
Really appreciate the dialogue and treating, the patient, as intelligent consumers of nuanced information. Push up and curious 😊
Yes, go for push ups! This chat clarified a lot for me, I didn't expect to make it all the way through but it kept my attention and I will be interested to see how the conversations evolve out of this.
Glad it was helpful!
Two of my favorite people!!! Thank you for joining minds! 5 hours!!!! 🎉❤😊
An absolute great discussion. I am impressed Simon that you really focused on listening and learning rather than trying to rebuttal all of Nick’s points. I think about 2 hours could have been cut out and still made the same impact but definitely worth the watch!
About halfway through and I'm learning so much. Very grateful for Norwitz' transparency about his own disease, his reasons, and how he personally weighs the pros and cons of choosing medication for him. I feel it's very nuanced and helps me look at my own situation through a more informed lens. Great interview.
I make the (granted arbitrary) cut for an LMHR, as my LDL is 445 mg/dL (which made my doctor quite concerned) HDL 60, TG 30 (being 14 hours fasted, as Dave Feldman recommends). Been eating mostly carnivore with some carbs over the last 7-8 months. Also because of stomach issues, like Norwitz - plus food-induced eczema on my scalp.
Nick, have a chat with Mantzoros in Harvard. He said in this podcast that the root cause of CVD is insulin resistance and metabolically-illed arteries. And Simon seemed to agree!
I’m scared to listen since it’s nearly 5 hours, but going for it :) !!
Jump in! Let us know what you think
Curious push-ups. Definitely moved the conversation forward regarding this important and fascinating area. It’s very pertinent and impactful to those of us in specific risk and phenotype categories trying to make critical decisions on how to approach health challenges. Thank you!
I really enjoyed hearing what Nick had to say. I also eat a keto diet after trying so many others with no success. This is the only one to resolve all my health issues. If I could eat differently I probably would, but the consequences are just not worth it. Forgot to add curious and pushups.
curious pushups! we need another Nick podcast, thanks subbed :)
Thanks for the sub!
Been looking forward to this one, boys!
Hope you enjoy Dr Grapeftuit (how do you feel about this inside joke nick-name?)
@@nicknorwitzPhD loving it
Enjoy mate
It’s finally out! 🎉
That's the spirit!
Enjoy!
Curious pushups! 😂
I listened to this whole episode on a podcast and I can’t thank you enough for asking all the questions I have in my head. And not just with this video either. I was vegan for seven years then back to standard American diet and then last year plus I was carnivore until I got my ApoB number and particle size back! I had made the jump that being in ketosis as a result of the fast mimicking diet, wouldn’t that be good long-term !?!? I did not qualify as a LMHR and unlike other carnivores am not willing to take the risk of high ldl and ApoB despite feeling great. I am tired of people telling me and others that cholesterol does not matter! Nick was the perfect guest for this back and forth!💜
Best 5 hours !!!! Exceptional educational podcast. Love and respect you both!!!!
The question was asked "If you could bring down your ApoB to 60, without side effects, would you do it?"
I understand the question. Simon really wants Nick to say that it's better to have a low ApoB. 🙂
And that's fine. Simon still operates on the belief that high ApoB is bad by definition.
But in the context of the LEM, this is impossible. Because the high LDL-C / ApoB is a direct result from the high levels of fat transport. As is shown by the use of Statins in Nick's Oreo experiment. It went down a bit, but couldn't bring it down any further. And if I remember correctly, the dose was quite high.
So it's a nice idea, but not practical.
I'm mentioning this because I think it's important in relation to understanding the LEM.
LEM is bullshit
“The belief that apoB is bad”? When did that become a belief? It’s probably one of the most established fact in medicine. Is it not applicable to keto dieters subgroup or what?
@@peterfaber7124 I agree. In the average population ApoB may have more weight in causing disease... but not necessarily in those healthy, active and have an efficient fat metabolism.
Statins were clearly shown to have very little effect on CVD. David Diamond has gone over this ad nauseum.
Pushups!
Great conversation, kept me company on my 2 hour drive down to work, then home again, with some to spare.
It is so interesting to me that curiosity doesn't get the better of some folks to want to understand what is happening with this phenotype. 😊
I've done experiments on myself since my 20's. In my 20's, no matter how many vegetables I ate I was still bloated, constipated and straining. I put myself on probiotics for 2 years until my symptoms resolved. Knowing what i know now, I also would've removed dairy from my diet. My latest experiment was trying to use diet to get my cholesterol lower. I went from flexitarian (since my 20's) to vegetarian to vegan/WFPB. OMG. my cholesterol didn't budge! I then followed McDougall and Esselstyn's dietary addition of oat bran and high nitrate plants, specifically, arugula, and drastically reduced my consumption of oil and processed plant-based foods. That did the trick. I dropped my LDL from 144 to 82. Dropped total from 211 to 166. Dropped HDL from 65 to 57. Trigs went up from 145 to 160. HS-CRP was tested when my cholesterol was 211 and it was 0.3. BMI dropped from 23 to 21. My next experiment is getting adequate sunshine and seeing how high I can get my Vitamin D levels to go.
"Broken lipid metabolism" in FH doesn't really hold at all; the only reason why we would see individuals with FH-levels of LDL-C in the absence of any identified genetic condition is because similar pathways are being overwhelmed, e.g., LDL-R. We presented case studies at the Heart UK conference in the past two years of people with LDLs of >15mmol/L, in some cases ~21mmol/L...to suggest the absence of "broken" LDL-R implies this is perfectly normal lipid metabolism is a gross stretch, particularly given that these levels are reversible (to an extent) with diet.
A very wonderful and rich meeting
That's kind. Thank you.
Thanks
Fascinating and thought provoking conversation, and I will be curious (see how I did that) to see the outcome of further studies researching this model.
Way to model mutual respect and civil discourse here, Simon and Nick. Thank you for providing clarity and nuance concerning both the LHMR phenotype and Nick’s views (both his hypotheses and his own personal approach). From what I had initially seen elsewhere, I still had so many questions (most of which you addressed). I think two of the biggest take-home points are that (1) LMHRs are a rare and unique phenotype, recommendations for whom are likely not to be generalizable to the “gen pop” level, AND (perhaps more importantly) (2) Nick’s own unique medical history makes his personal dietary choices even more specific and less generalizable to the “gen pop” level (or even to other LMHRs). I hope listeners heard loud and clear that Nick doesn’t eat carbs because he would have an IBD flare-up. This is not a prescription for others; thank you for stating that.
I hope folks listen through the whole thing to really get the nitty gritty nuance and the many ways you gents helped bring clarity about what you each ARE and ARE NOT saying (and what you say boldly but hold loosely).
The most valuable timestamps for me (after all the preceding context, of course), were ~3:50:00 to 4:02:00 and ~4:15:30. [I listened to the podcast version in case that impacts timing]
Would love to hear more about pushups in future, gentlemen. Thanks for the great chat. Thanks for inspiring curiosity. (By the way, I can spell supercalifragilisticexpialidocious too.) 😉
Cheers!
The only one thing I hate of Norwitz is that he never acknowledges that the most important self experiments on LMHRs were done by Feldman. The white bread experiments of Feldman were first and basically identical to the Oreo experiment. And he should be acknowledging those fundamental experiments (but he never does).
if i"m not mistaken, he mentioned him early in the podcast as his mentor.
@@sharkair2839 Yes, of course, he always mention him. But never acknowledges that the Oreo experiment is a copy of the white bread experiments of Feldman.
Curious/ push ups. Also, Nick can make a keto burned-Basque cheese cake. It's super easy (basically just cream cheese) and he might even be able to eat some himself. Thanks for the amazing conversation to both!
I’ve been waiting for this one!
Enjoy!
Here until the end- "Stay Curious" indeed...thanks, gentlemen!
Thanks Simon another great episode….although I always listen to the pod rather than watch on UA-cam. I didn’t hear you say how many pushups you could do…I’m curious to know if you feel like sharing?😜
I listened carefully to half of this.
I stopped listening because i thought the weight of the discussion was more about him than the issue he was trying to raise.
I'm not sure exactly what this guy's message is (??) after listening for 2 hours (!!)
In one way, he is saying... the results of my experiment are striking enough to provoke a debate about them (-because they could be relevant to more people than just me)... but then, in another way, he is ALSO trying to stress, that because the results are only linked to him (an "n" of 1) he is not suggesting that they are applicable to the general population... (-and therefore the results may not be significant at all).
He strkes me as both a guy who is trying hard to be "objective" and a guy who is totally self-absorbed in himself. I started to care less, and less, about his results and potential "significance" of his experiment as his level of self-absorption started to irritate me.
Your podcast Simon, is one of the best in the business, but on this 1 occasion, you gave your guest too much time and space to make a "word-salad" out of his 1 big opportunity to bring his message to the world. The guy focused too much on himself and not the data.
😕
Nick would LOVE to just talk about the data. However, he is having to talk about things other than the data because others who are misrepresenting him are muddling his message, which requires him to spend, as you stated, valuable time simply defending himself.
I know it's a lot to sort through, and maybe simon will release an edit that makes things more clear. But if not, I encourage you to give it another go and see if things are more clear by the end.
@@saintwithatie yes, he came across as a guy on the defensive alright. He does seem to be very conscientious and meticulous about how he conducts his research. And he does seem to be rattled by others who have muddled his message. Perhaps I will finish the podcast then to see where it leads. Thank you
Let us know what you think by the end! I appreciate not all my episodes are for everyone and that's perfectly ok. I enjoy getting a little deeper into the weeds than other shows ... I find the more surface level conversations are less likely to challenge the ideas I hold.
That said, I am rolling out some shorter solo episodes to help consolidate some of my views/learnings :) So stay tuned for those!
Thanks for taking time to submit feedback!
@@TheProofWithSimonHill I like the longer format. I agree, it gives enough time to get into the weeds and do a topic justice
@@TheProofWithSimonHill lol, five hours of ramblings... I can tell all the atherosclerosis theory and practice in 45 minutes.
Great podcast! HUGE fan of @nicknorwitzphd!
Pushups
Curious.
BTW, would love to have a conversation, Nick. I am also a LMHR with Crohn's disease. I believe I was also one of the first ones to hear Dave Feldman speak at a Ketogains conference in Las Vegas several years ago. He was explaining to me and Robb Wolf what his talk would be about in the back of the conference room,. Crazy how far he (and your group) has come! Appreciate all you do!
Curious. Not only was I listening, I plan to make a response vid to something Nick says at 4hrs5mins. Great stuff both.
In relation to the low-carb community not believing in lipid-lowering drugs,... It may be a factor that these opinions are held by people in the low-carb community who don't have CVD.
From the point of these people, taking a statin for high(ish) cholesterol doesn't make a lot of sense. But the message of the cardiologists often is: "You should be on a statin."
So it's not so strange there is resistance against that message in the low-carb community.
I wonder why the message is that (for a specific phenotype) adding carbs (no matter the source) to a keto diet can lower LDL dramatically, and not that removing all carbs (no matter the source) from a balanced diet will raise LDL dramatically. And it’s obvious to anyone following the carni crowd, that they would try to suggest that statins are as bad as Oreos after Nick’s experiment. To expect anything different would naive.
Nick, Do all forms of carbs give you flareups? Which form of carbs triggers your flareups: glucose, fructose, galactose, or fiber?
All net carbs. Fiber can irritate my IBS, but not IBD as far as I'm aware. I just get bloated and farty. I've yet to find a good protocol to prevent this response. Maybe one day. I've to routinely eat Brussels with walnuts bacon. Too good.
@@nicknorwitzPhD Did Oreos give you flareups? What about dextrose? I don’t know if dextrose is feasible as it may give you a glucose spike.
@@nicknorwitzPhD Sounds like you have dysbiosis. You need to pack down 100g of fiber today with some probiotics and after 6 weeks to 2 months the farting should subside. I had a similar issue at first as well, I was waking up at night to huge farts.
Just had to say I really enjoyed this episode. Stayed for the whole thing curious push ups!!!
Glad you enjoyed it!
Hi Great podcast Nick. I have a question, hopefully you see it :)
When you were on the Oreo diet you said you took a ketone supplement to help with your gut. So, why don’t you take the ketone supplement and eat a more standard healthy Mediterranean diet?
Also, have you considered doing a plant based keto diet for the animals and the planet?
The one thing that makes me wonder is why we are always talking about LDL particles being atherogenic, while atherosclerosis occurs only in very specific places of the arteries. Would it not make more sense to say that those places of the arteries are atherogenic?
Shear stress/blood pressure is an important factor in the development of atherosclerosis - it influences the expression of caveolin-1. And no, atherosclerosis occurs everywhere. But not equally fast.
@@EVanDoren Everywhere?
Not really. Mostly in places where there's mechanical stress and/or endothelial damage. These things are not caused by LDL, but LDL is drawn to it like a moth to a flame.
@@EVanDoren I attempted to tag you in a top-level comment but I'm not sure the tag worked.
I'm confused about your positions and wanted to understand better.
You should see the comment easily by sorting by new comments.
@@saintwithatie UA-cam stopped notifying me about the new comments. Just saw it.
Excellent discussion, Simon you always impress me with the choice of guests and curiosity you have. With regard of LMHR phenotype on carnivore diet and the question of risk of CVD: I think in about 20 years we may see retrospective observational data in this regard given so many are on a carnivore diet nowadays. As much as I would love a good RCT, I am sure it will never happen. But who knows...after all carnivores out there are now running their own experiment in life and, indeed, they may give us an answer in the future.
Thanks yes will be interesting to see what happens. However, the pessimistic part of me suggests we won't learn unless there's good clinical data. We're likely to only hear of the success stories - not the people who gave up due to side effects or died earlier than they otherwise would have on another diet. At the very least someone should start collecting proper data on a keto cohort, and monitor them prospectively over decades to come.
Please strive to equalize the audio quality and level between the interviewer and the guest. In ths case the guest is speaking further from their microphone.
I speak a lot... Simon is presumably trying to equalize the audio input AUC. It's said that Nick Noise Exposure, in decibel-minutes, is causally and in a dose-dependent manner associated accumulation of 'mind-blown-ness.' Please listen with caution. You don't want to have a Major Awesome Curiosity Event.
Thanks for your feedback
Australian health professional here - The 3 things that combine to cause plaque build-up in my opinion are -
1. High APO B
2. Endothelial dysfunction, lack of natural VIT C.
3. Mild insulin resistance.
God speed to you all.
Andy, question: thoughts on Peter Attia's statement high ApoB is "necessary but not sufficient." Is this true entirely? Or do you expect a threshold effect whereby high above a certain level ApoB - irrespective of etiology - will always 100% of the time drive ASCVD?
@@nicknorwitzPhD I'd agree with the necessary but not sufficient statement, I think the main driver is endothelial dysfunction caused by mild or worse insulin resistance and low VIT C, high oxidative stress. Have you had a CTCA with your high levels of ApoB?
@@andynater1885 then by this statement, ApoB is NOT causative
Wrong. The cause is the accumulation of cholesterol in foam cells. To get there, LDL particles have to be transported across the endothelial layer via transcytosis. LDL transcytosis is the main limiting factor in the development of atherosclerosis. And it is dependent on the following factors:
1. By far the most important: LDL cholesterol
2. Inflammation accelerates transcytosis
3. High blood glucose accelerates transcytosis
4. High blood pressure accelerates transcytosis
5. Some hormones can be protective (estrogen).
Otherwise, some plant foods contain active compounds that can increase cholesterol efflux from foam cells. Others can block cholesterol absorption in the gut. Third can block or increase bile acids formation, which decreases cholesterol in the blood. Finally, we can decrease cholesterol synthesis in the liver.
Summary: eat plant-based, minimize animal products, saturated and trans fats. Certain plant foods can farther improve the outcome, but that's too much for a UA-cam comment.
A very nice and interesting podcast- those 5hrs went fast 😊
Hoping for a follow up with the same fabulous content!
Glad you enjoyed it!
I don't understand why the enfasis of LMHR being a very rare phenotype. I really have a question. Of all people who go on a ketogenic diet and are consider lean, what percentage does not transforms into a LMHR?
Because they don't have genetics driving their cholesterol up (unlike those with Familial Hypercholesterolemia, FH), studying them long enough could definitively determine if high cholesterol causes cardiovascular disease (CVD). However, no one wants to fund this research due to fear of the potential result: that high cholesterol in a healthy metabolic state might be protective against CVD and all-cause mortality. I predict this will be the finding of the crowdfunding study on Lean Mass Hyper-Responders (LMHR), which has already completed initial tests with results that seem to support this hypothesis.
@@fadiyt8816 I just ask this: "Of all people who go on a ketogenic diet and are consider lean, what percentage does not transforms into a LMHR?" this has notthing to do with risk. Is just, puting lean people on a KD and checking their LDL, HDL and, TG every day or week for a month or two. Is not that difficult to access.
I'm enjoying listening to this episode in bite sized chunks as I get time. It's a pleasure to listen to people with somewhat different views have an intelligent and constructive conversation. @Simon, hopefully you can line up a session with Anthony Chaffee, Shawn Baker or Paul Saladino. I would love to see where the conversation goes and where the common ground is. @Nick, I would love to see you debate Dr Alo on your channel - it would be comedy gold 🙂
Out of those three, I'd be most inclined to sit with Shawn Baker. Anthony Chaffee has proven to be very disingenuous.
@@TheProofWithSimonHill that would be great if you could sit with Shawn Baker. He has been very level headed and honest in the interviews I've seen him in. If he doesn't know, he's quite happy to say "I don't know". I can see it being a really constructive discussion.
I have been taking high dose statins for the past three years with ezetemibe and combine this with a vegan diet. Maybe the discussion for statins should now focus on its potent antioxidant benefits particularly at the endothelium and its protective effect! Perhaps this settles the fact on both sides that LDL itself isn't causative and the lipid lowering benefits of statins are overstated. However statins provide both benefits! Unfortunately tolerance to statins will always be an issue in a population. My advice is: be the N=1.
"My advice is: be the N=1." Love this. And if you're feeling well and doing well, I applaud you :). Live your best life!
Simon - for those who don't have 5 hours, is there anywhere we can see a writeup of your views on the issues discussed?
I’ll cover in a shorter solo ep soon!
Great discussion.
Glad you thought so!
Thanks for the deep dive!
My triglycerides went from 7.2 mmol to 0.7 mmol after 3 months on carnivore.
What happened to your ApoB? And fasting blood glucose?
yes, never blame the saturated fat for what the sugar and inflammation and cortisol did
@@TheProofWithSimonHill to be lean - get your cholesterol above 300 get your at rest mid day body temp up to 98,6 and your pulse to 80 check the data from 1940s -
The timestamps are a major W, thanks man.
you're welcome!
This is so interesting but I'm not sure if I'm considered an LMHR. I'm NOT on a keto diet but a lower (100-200g/day) carb, 80% whole foods plant based diet. Recent lipid testing showed HDL 117, Triglycerides 59 and LDL 174. Female 63 yrs, 125 lbs. Not on any lipid lowering drugs due to low overall risk but considering using. Not sure if advice for LMHR applies to me. Am I a separate phenotype? I haven't seen my situation addressed before?
@@karenberube3646 The cut points chosen to characterize this phenotype included LDL-C ≥ 200, HDL-C ≥ 80, and TG ≤ 70 mg/dl
You could easily find out if you are an LMHR by cutting back on your carbs further for a while and then testing. If you are hyper responder, you will most likely always be a hyper responder no matter what your diet is. Your (lipid testing) response will just be different when not eating a very low carb diet.
I wonder what the other 20% of the diet looks like.
Such a brilliant topics thank u 🙌🏻
You're so welcome!
The problem with the inquisitive researcher is that he always finds marginalization at the beginning until the specialists first understand his work, then the rest of the people who are subordinate to the specialists and have nothing! ..This puts Nick in line with society, and I tell him to continue!
worth the watch! what a treat.
Glad you enjoyed it!
I am so excited to listen to this podcast! In April, my partner (meat eater) had bloodwork done and found out his cholesterol was 331! So as an experiment, he started eating my plant-based, vegan meals with one cheat week in the middle where he ate seafood because we were on vacation at the beach. He just had bloodwork done yesterday and his cholesterol came back as 230. This was amazing and so validating for me that a whole-foods plant based diet DOES help with cholesterol.
You obviously didn't listen to this episode or understand Nicks position.... lowering LDL only and not considering overall health is myopic
@@evolved.healthso he made a universal statement and not for a specific phenotype after all?
What about HDL and triglycerides?
This is excellent 🎉🎉🎉
Thank you. Three confetti trumpets. Wow! (idk what else to call those)
@@nicknorwitzPhD 😁😊😊
Glad you are enjoying it
Somewhere along the line, the "necessary and sufficient" definition of causality seemed to get lost from its original intention, per Rothman, and now gets wielded about with the seeming intent of providing some robust epistemic test to the evidence, but in ways that are probably less useful than they appear.
Rothman's original concept of adding "sufficient" to "necessary" was to improve on merely considering causes as "necessary" because that was unsatisfactory. For example, cigarette smoking causes cancer; but smoking cigarettes is not "necessary" for someone to develop cancer. Yet based on the evidence, smoking is certainly a cause of cancer.
Adding "sufficient" was in Rothman's formulation a "sufficient-component cause" model, because to apply a strict "sufficient" test would be to apply a deterministic definition, that the guest himself applied, which isn't suitable for biological processes. In fact, we could apply the "necessary and sufficient" definition to argue that smoking does not cause cancer, because in the strictest sense, smoking is neither necessary nor deterministically "sufficient" to cause cancer.
One particular limitation of the limits of "sufficient" and its deterministic implications is that it can't account for dose-response relationships, which is crucial to determinations of biological processes and related causality, because if a cause is "sufficient", it is considered fully sufficient (as articulated by the guest), i.e., its mere presence should bring about the effect. But this is not the cause, as LDL/ApoB exhibit dose responses (that are linear), i.e., as the cause increases this changes the corresponding effect. "Sufficient" can't account for this, in the crude deterministic definition that is applied to it.
Tl;dr, the "necessary/sufficient" definitions are not a useful framework for thinking about causality in the context of biological processes and multifactorial diseases. It is a distraction, more hindrance than help.
CURIOUS PUSH UPS. Almost at the end.....😮
Sorry shallow comment but...🔥🔥 I did listen to every minute though! X
The algorithm appreciates your contribution. And fire emojis are always a welcome reply.
Ty glad you enjoyed it!
great conversation! curious!
Thanks for listening
35:00:00 in. Good for you on bringing up the Shawn Baker quote. Shawn is literally the one who promoted this study on a large scale, and what he took away from the study is what many in the low carb community did. If bad Oreos lower cholesterol, then lowering cholesterol must be bad.
Speaking for myself, do you feel I provided a fair representation?
I'm sure they can't make that connection, doesn't sound like Shawn he's not that stupid. lowering cholesterol with Oreos is a mechanistic action to energy provision. seperate to lowering by blocking production at the liver.
@@Petunia-fl9lu “If eating pure absolute garbage junk lowers your LDL cholesterol more so than even satin drugs what does it say what does it say about the act of lowering cholesterol?” Shawn Baker
@@nicknorwitzPhD You put in caveats, but the provocativeness of the study, right or wrong, pushed that narrative to some extent.
Mondelez is very influential, of course! 😜
@EVanDoren Making a standalone comment so we don't blow up others' comments.
I'm confused what your position is.
1. What is your issue with Nick? I'm very familiar with his work, his position, and his communication, and I have seen nothing unsavory or fraudulent coming from him. Every criticism of him I've encountered has been a misunderstanding or a straw man. What are your specific reasons for dismissing him and his work?
2. What is your position on LDL and ASCVD risk/development? I ask because you are commenting what seems to me to be refutations of other comments, but you're essentially saying the same thing the comment said.
Do you agree with the following?:
- The thing we are trying to avoid is the excessive buildup of plaque. I say "excessive" because it appears that plaque will form to some degree throughout the lifetime, but we want that buildup to be as slow as possible so that buildup isn't the thing that eventually causes an event that leads to injury or death.
- There are several steps that lead to excessive plaque buildup.
LDL must exist in the lumen (obviously) -> LDL must pass through the endothelium via passive or active transport into the intima -> LDL must get "trapped" in the intima via incorporation into foam cells -> foam cells become a plaque that can build up over time
- All of the above outlined steps are mediated by factors such as inflammation, blood sugar, etc. that 1) result in the transformation of certain compounds into versions of themselves that are more atherogenic and 2) interact with receptors and other cellular machinery in a way that makes it more likely for the LDL to end up in the intima and trapped in foam cells.
If you DO agree with all of the above, then why does it seem like you disagree with statements made such as (and I'm paraphrasing here)
"LDL is simply a biomarker."
"ASCVD is driven by several factors."
"The mere presence of "elevated" LDL isn't sufficient to spontaneously induce all of the steps required to form plaque."
"High Apob, inflammation, endothelial dysfunction, nutrient deficiencies, and metabolic/insulin dysfunctions are all risk factors for ASCVD"
"it appears that plaque will form to some degree throughout the lifetime" - not necessarily. If LDL-C is low enough, then cholesterol efflux into HDL can negate or even reverse the build-up.
"LDL must pass through the endothelium via passive or active transport into the intima" - the transport is always active, it's called transcytosis. It's basically caveolae turned into vesicles, which are transported along the microtubules by the motor proteins. It's like a molecular elevator.
"LDL must get "trapped" in the intima via incorporation into foam cells" - it's called fluid phase pinocytosis, the cell basically gulps down a bit of intercellular fluid together with lipoproteins. The cell cannot metabolize cholesterol, thus the accumulation.
"All of the above outlined steps are mediated by factors such as inflammation, blood sugar" - those factors simply change the expression of caveolin-1 and other proteins needed for transcytosis. Estrogen blocks SR-BI, which is the docking protein inside caveolae.
"interact with receptors and other cellular machinery in a way that makes it more likely for the LDL to end up in the intima and trapped in foam cells." - more likely for LDL to be transported across the endothelium
"LDL is simply a biomarker." - LDL is the cause. No atherosclerosis without LDL. There are primitive African tribes where almost everyone heavily smokes, inflammation is sky-high, but they have total cholesterol around 100 mg/dl, and zero atherosclerosis.
"ASCVD has several factors." - there is one factor. Cholesterol inside of LDL. The others are merely modifiers. They can accelerate or decelerate the process. They cannot initiate it.
"The mere presence of LDL doesn't spontaneously induce transcytosis." - the mere presence of LDL is sufficient.
"inflammation, endothelial dysfunction, nutrient deficiencies, and metabolic/insulin dysfunctions are all risk factors for ASCVD" - they are merely accelerators.
@@EVanDoren Thanks for the reply! This is really helpful and I think I now realize something.
It sounds like the disconnect is that you are focusing solely on the cholesterol in the LDL that gets consumed by macrophages as the initiator of the transformation of macrophages into foam cells and thus initiating plaque formation, while others like myself and Nick would focus on the entire chain of events and modulating factors thereof that happen up to the point of foam cell formation.
If that is what is going on, I would mostly agree that cholesterol in foam cells is the most direct cause of plaque formation/buildup. I say mostly because there are still known and unknown factors modulating the transformation of cholesterol-containing macrophages into foam cells. I would say "Under the right conditions, cholesterol in macrophages causes plaque formation"
Would you agree about this disconnect, and if so do you think it lends into the reason you don't like Nick?
@@saintwithatie
1. Not only macrophages can become foam cells.
2. There is no chain of events. No endothelial injury, nothing. 1-2-year-old babies already have fatty streak in their arteries, especially if mother's nutrition is rich in saturated fat. Transcytosis is a normal process. Pinocytosis is a normal process. Cholesterol getting into the artery wall cells walls is a normal process.
What follows is a race between LDL delivering cholesterol and HDL getting cholesterol out via efflux.
I'm not speaking about the latest stages of the process - we have all the means to not getting there in the first place.
There is a disconnect between claimed ideals and Nick's actions, I also think that his actions kill people. Therefore, I don't like him. He claims he is not like other keto-shills, but he acts exactly like one of them.
@@EVanDoren I think we're still disconnecting.
It seems like you're interpreting "chain of events" as having a negative denotation. The phrase just means that one thing must happen before the next thing. LDL gets transported across the endothelium before the foam cell precursors (macrophages are one, but there are others, as you pointed out) consume it, and the foam cell precursors consume LDL before turning into foam cells. These are events that are chained together chronologically - a chain of events.
Saying that something is modulated doesn't mean that it is not "normal." Every single "normal" process in the body is modulated by a variety of factors. The speed of LDL delivering cholesterol and the speed of HDL getting cholesterol out are both "normal" yet modulated processes.
I'd be interested to know where you are from and how you became interested in this topic. I see you have a playlist with a Russian title, so with your name and the title I'm guessing you are Russian or at least from a Russian-speaking area. I am wondering if there is a disconnect stemming from differences between Russian English and American English. I befriended a Russian woman during a trip to Korea and I've noticed such between us.
Can you elaborate on how any of Nick's actions are killing people? Not the actions of others or the misrepresentations of his words by others, but his words and actions alone, taking into account all of his transparency and all of the clarifying that he does (which is so much that commenters are saying made this video too long).
I am interpreting "shill" to mean that he is being fraudulent in his stated positions and is only promoting (or rather, not demonizing) keto for personal gain. Do you really think that he does not believe what he is saying? Do you really believe that he does not have a passion for metabolic health and a desire to advance that field?
I've only seen him behave in a vastly more transparent, professional, and scientific manner than most other scientists regardless of field or communication channel. What exactly are the actions of his - again, not the actions of others or misrepresentations of his actions by others, but his actual actions - that you disagree with? What did he do vs. what do you think he should have done?
ApoB, which is predominantly LDL, is arguably the most important risk factor for atherosclerosis. The correlation found between ApoB and atherosclerotic cvd occurance suggest that “elevated” apoB is the only factor necessary to form plaques. While other risk factors increase atherosclerosis, they are not necessary at all. High presence of inhibitory factors as suggested by mechanism studies might be able to stop oxidation and modification process but they do not have causal relationship with the factors you’ve mentioned and do not correlate well with them either. It’s not like good results from crp or homa-ir will prevent you from developing plaque with elevated apoB. That’s never been shown. No data exist to my knowledge that suggest that, you might want to do subgroup analyses which will probably tell you that you still have atherosclerosis with high apoB and everything else normal
@Simon, OmegaQuant founder posted a 1m:37 sec video on the OmegaQuantLab channel a month. It says that "improving" your n~3 numbers reduces your CV risk, regardless of your cholesterol level. I wonder if it would be interesting to have him on to discuss this and related topics. I can't include the link because then yt won't post my comment.)
episode on Omega 3s and Omega Quant coming out in 2 weeks.
Really enjoying it so far, but commenting midway to say I didn’t realize Dr. Alo was a quack. I appreciate it when you tell your audience you don’t necessarily agree with things your guests put forth.
He’s not. It was obvious that he was extrapolating from LDL lowering data and suggesting that PCSK-9 inhibitors would probably have the same effect.
What actually is the macronutrient breakdown of Oreo's? Are they a split between fat and carbohydrate?
40% energy from fat
Mostly PUFA fat. PUFA destabilises LDL so I suspect there's a feedback mechanism which makes the liver produce less. Not necessarily a healthy change in that biomarker.
Saturated Fat 6g
29%
Total Carbohydrate 74g
27%
Protein 3g
Mercifully, we have chapters/topic labels....thank you!
Fair. Very fair.
You're very welcome!
I'm half way through, and I still don't understand why he thinks he needs different data for this sub population. I don't see a reduction on TGL and an increase in HDL and LDL cholesterol as such a distinct group. It is what most meta analysis show that happen when going keto or low carb. The reason for not believing general population data would not apply to this sub population is still unknown to me. For all I see, I could believe LDL-c over 100 wasn't a problem for me because I haven't seen specific LDL-c x CVD studies with a population of Brazilian men, father of one, left handed, brown haired, former smoker but currently athlete, engineer and nutritionist and that are called Cadu.
The first thing is that we can never assume that population-level statistics necessarily play out in sub-populations, especially the smallest sub-population of the individual.
This is done all the time but it is logically fallacious. It is always a valid question to wonder how things play out when factors relevant to the outcome change even slightly.
This applies to ASCVD risk as a function of LDL exposure, risk of deficiency as a result of a particular level of nutrient consumption (nutritional RDAs), etc.
The second thing is that, in this case, we actually already have evidence suggesting that there are factors related to the specific cause of "hyperlipidemia" that affect ASCVD risk.
I don't have the timestamp, but Nick cites a study suggesting that certain populations with similar levels of "hyperlipidemia" but different causes for it have different ASCVD risk.
As far as I'm concerned, you can't assume a result from a sub population would apply to another, or to the whole population, but a study that comprised many subpopulations has a far greater chance to apply to the subpopulations it covered. Of course there's a chance it does not, in which case the effect on the other subpopulations must be greater than the average result if the study showed a overall statistic significant result. But when we are talking about something that's been showed over and over for many populations, it is irresponsible to assume there is no risk for a specific population. If we were talking about improvements of something, we could take the conservative approach and say perhaps this benefit doesn't apply. But we're talking about a causal factor of the #1 killer disease in the world, we MUST assume the risk also applies while doing further studies.
I've past the part of mentioned, and although bit different risk profiles, all of the differnwyr causes for high Ldl-c showed a HIGHER risk than regular ldl-c level.
@@cadupradoo "It is irresponsible to assume there is no risk for a specific population."
Is this what you think Nick is saying - that there is no risk for LMHRs?
No, I don't. He says he doesn't know what the risk is, but the set of these actions, as Simon very kindly suggests with his questions, is that the information that is passed when this discussions happens is mostly that "since I'm not sure what the value is, I don't take action, even though it is highly unlike that the value is 0".
And I don't think the scientific question isn't there, I just think that the whole community acts like there is nothing on the subject to make decisions on.
Also, about the study you mentioned, it compares monogenic, polygenic (which also has an environmental factor) and non determined causes for high LDL at recruitment. It is expected that the results are different, since the monogenic people have had high LDL-c since birth. The polygenic have had a combination of genes since birth with environmental factors, and the other group have had high LDL-c more recently. It has come back to cholesterol-years like many would expect.
@@cadupradoo What actions are you referring to when you say "the set of these actions"?
Also, yes, it may indeed come back to cholesterol-years. If that happens, then that's great - we've learned something. It's stil possible that it might not be, so it's worth investigating, and doing that requires data from populations such as LMHR, which is why Nick wants that data (going back to your original question.)
Stay curious! Pushups! Lets gooo!!!
3:46:00 in, Nick just finished talking about being upset with Peter Attia’s statement that he’s tried to understand the other side, but Nick thinks this is disingenuous. I’m a little confused by Nick thinking this because they also talked about Peter having Dave Feldman on his podcast, who does have the scientific chops to speak on this subject. I admit I haven’t listen to that podcast, I plan to after this one. I realize it was four years ago, per UA-cam. However, is that not an example of Peter trying to understand the other side?
There is a difference between merely having someone on your podcast and having the best-possible-faith, hungry-for-understanding engagement with what someone is saying.
What Nick highlights is Attia's misrepresentation of certain points by focusing on the words of people OTHER than the study authors (what Nick refers to as "the words of rando extremists off social media") instead of focusing on the actual words and positions of the study authors.
Would you not agree that this behavior is inconsistent with really trying to understand something? If you want to understand something via discussing it with others, it behooves you to represent the thing accurately, yes? Otherwise, you're discussing and trying to understand a strawman, not the actual thing.
CURIOUS!!!
you made it all the way to the end!! well done
@@TheProofWithSimonHill Would not have missed a moment. Thanks for adding Part 2 and the MVX discussion. Fascinating stuff!
1:04:51 Regarding lab grown meat, the thing is we cant make lab grown mest that is cell for cell, nutrient for nutrient, identical to real meat.
If you could prove that we could create lab grown meat, identical with every molecule. That’s a different story
Hey, the verification word is curious. Also, push-ups.
You made it to the end!! Well done
My problem with blaming LDL levels for the cause of heart disease is we are not taking into account what the person is consuming for food. I believe it’s the diet that driving poor health. Most Americans have a poor diet aka S.A.D. If the familial cholesterol population ate a whole food diet I believe they would have better health and less heart disease. I don’t really hear anyone talking about changing their dietary patterns. It’s always only about lowering LDL.
I wrote an entire booking on changing dietary pattern. No only to improve LDL-C but also body weight, blood pressure, fasting glucose, muscle mass, bone density etc
I just got my blood test 3.5 months ago and then again 2 weeks ago, they are looking at whether I am familial cholesterol. I am a 7 year vegan, eat a whole food diet fresh fruit, plants, and nuts I weigh 171 pounds and run 10 to 12km 5-7 days a week, go to the gym twice a week (54 years old). I have just discovered I have high LDL so diet does not change high LDL if familial cholesterol. Not that I can figure out because when I first got my results back 3.5 months ago, I thought it would be the oat milk cream I take for my coffee so I gave it up and it didn't change anything. I take supplements where I need them like B12 and protein powder in my shakes, do not drink any kind of plantbased milk, water only and electrolytes when I run. Basically, my point is to your quote about familial cholesterol population eating a whole food diet to change LDL, I do and it hasn't changed my LDL.
You misunderstood my statement. My statement was to address their health. I could have been more clear. Good luck with your journey.
@@DouglashansenCa could be the nuts and or tropical oil intake.
Thank you ❤️❤️
What's with the Oreo commercial 👀
It’s curious that while dayspring and nick have different views on the science they have similar speaking styles- kinda long winded and they don’t let Simon get a word in edgewise. After all the pushups I still get the feeling that nick is a troll, and given the obesity epidemic, focusing on lmhr people isn’t the best use of scientific funding
@@sethboviper Their funding is mainly private. So, no tax payers money goes into it. People who want to know, pay for the research. And I think that is a good way to go.
CURIOUS!!! 🙂
Push-ups? I like sit-ups better but still curious!
How curious, push ups? ...💤 🛌 😅 I thought I was curious, Nick takes it to a whole new level, which I think will make him an excellent researcher. It's just too bad the animals and the planet pays for it. So to Nick, if humans stopped eating animals, more specifically ruminants, the climate emergency wouldn't be so much of an emergency. The pebble analogy to both the complexities of human physiology and the amount of information presented felt like a breaking wave when the pebbles was a motivation looking for solid answers. I don't think Nick will have to worry about having too many people unfollow him on X Twitter for not being a sugar Nazi, I not convinced those kind of people would have made it to the "baking cheesecake" bit. As for 10 hours, please don't. That said, the lean mass high responders, interesting but, the lipid model way more so. Imagine being able to look at genetics and physiology and predict health outcomes. One more point, all cause mortality, absolutely agree not a the best indicator, living majorly incapacitated or entirely incapacitated or as a vegetable definitely needs inclusion. Last thing I need to say, Yes it was too long! 😅
LMHR is not a rare phenotype. It's becoming more and more prevalent in the growing ketovore community.
"LMHR is not a rare phenotype." Can you tell me where i can find that data?
@@YaYippieYeah observational only. No data. I'm in a group of 11 people - direct friends. We share our eating habits and I recently went on a nine day fishing trip with three of them. All four of us are in our 60's and ate the same keto diet the entire trip. We all have similar panels, except one had a grossly higher LDL-c, and another had a TG/HDL ratio higher than 1.0 (rest were below 1.0). Of the entire 11 group of friends, seven are LMHRs per the definition. I am also a member of two FB groups (70K members) that follow keto and carnivor diets. The stated prevalence of LMHR is very high. I'm not special. Daily home workouts plus three resistance training gym visits per week, 5'8", 155lbs. Before keto, four years ago, I was 175lbs. Bloods: Before K: HDL=64, LDL=145, TG=74 After K: HDL84, LDL=191, TG=48. These are just facts. I have no idea of whether I'm killing myself or not, but CAC score one year ago was zero, which is why I support these studies and believe they are worth while. I assume you don't need data on the growing prevalence of keto consumption.
Rare in the general population. Not rare among lean persons on ketogenic diets.
Like to see this defined
@@YaYippieYeah lack of evidence is not evidence of lack....just because a group hasn't been studied doesnt mean they dont exist. Many clinics are finding this phenotype who work with people who are LCHF/Keto - Dr. Berg, Dr. Ovadia, Dr. Nadir Ali, Dr. Cromwell and the growing database that Dave/Nick have in their cohort.
I couldn't continue beyond 60 minutes. I was expecting a scientific debate . For new listeners I recommend skip the first 60 minutes minimum
If you’re interested I would keep listening. We cover a lot. First 60 mins sets the stage
Good interview. lots of interesting information, but way too long. should have been posted in two or even three episodes
Thanks for the feedback. Curious as to why you’d like it broken up given there’s timestamps and you can come back whenever you want?
Curious (pushups). Thanks fot the episode =)
My pleasure!
Yo Simon have your ever heard of Dr. Peter Rogers? He's an absolute riot. Go check out one of his talk on chef AJ if you haven't already. He is in the low fat McDougall camp and he explains everything in an extremely interesting way via mechanistic and observational data.
McDougall really declined in his late 60’s until the time he died. Maybe his diet had something to do with it
@@michaelcarter3004 Nah, he had a massive stroke when he was 18. It's incredible he was so high functioning and vital for another 60 years.
Curious. With push ups
Get after them! Nice work listening to the end. What did you find most interesting?
@@TheProofWithSimonHill got a lot out of it but
- try many different N=1 exps on ourselves to see how we respond and keep doing what makes us feel good. Referencing the take on his IBS and fiber management. It seems to have opposite effects on different people.
- LA is burned in priority when consumed, therefore the argument that it is easily oxydized is probably not a problem for oxLDL. BUT I am still curious: if not in keto, will LA still be prioritized? If yess, we don't have 'access' to our carbs? If not, would it not accumulate in our fat tissue?
- the risk profile for LMHRs is not known but does not seem to be that risky. In that pop, saturated fat doesn't have a big impact on LDL. So a person on keto might fully thrive and tell you that butter is good, but it's probably wise not to consume vast quantities of saturated fat if not on keto, because for THAT SEGMENT of the population, it is linked to LDL. If we're not on keto and not sure about our metabolic health, it would be wise to be more conservative.
I would like to ask on the advice for LMHR that will add the sweet potato: if in that case, they are not longer on keto, their LDL would drop and therefore NOT be LMHR anymore? In that case, wouldn't ALSO limiting saturated fat also have a substantial impact on LDL?
Learned a lot but still have lots of questions 😅. It's my first Podcast I listened from you, will definitely subscribe!
By not having access to our carbs, I was saying are we storing the carbs in order to burn LA or if both stay in the blood and burned simultaneously or if LA will go into tissues while we burn sugar
PUSH-UPS
Good chat, guys.
Get after them! Nice job listening to the end. What did you find most interesting?
@@TheProofWithSimonHill the double Oreo gift? haha But in all seriousness it's tough to pick a certain part of the conversation I found most interesting because it was more about that the conversation was happening at all. You challenged things Nick has said in the past in a polite way, and it led to him responding in a polite way. There were no interruptions, no heated character attacks, etc.
I applaud you both for taking the time to do this, even having a double episode of sorts. If these conversations don't happen, we'll never get anywhere, and people will remain in their tribal echo chambers.
Looking forward to the next one.
2:03:30 in. Simon is asking why Nick doesn’t use the precautionary approach and lower his LDL. I think this is the biggest rub on Nick. Nick uses the precautionary approach to a higher degree than most in other circumstances, like staying away from certain artificial sweeteners, but not in the case of lower ldl? Seems like a contradiction to me. He starts talking about trade offs on if lower LDL is actually better, but the reality is, Nick’s LDL is 95 on a mixed diet. So does Nick really think there is a longevity trade off of something like dementia in bringing his LDL back to what it is naturally on a mixed diet?
So, LDLc is just a marker. The actual risk is plaque. He clarifies that he is monitoring plaque (soft and hard), and will pivot his treatment if things change and as new data comes out. He also recommends monitoring and pivoting as necessary to others.
Sincere response: do you think your reply is missing the bloody elephant in the room? Why am I keto in the first place?
@@nicknorwitzPhD You are keto because of your Ulcerative Colitis, but can’t you still be keto while adding a “healthy” carb source to lower your LDL? Can’t you still be keto and take a medication to lower your LDL back to your mixed diet normal? Do you think getting you back to 95 would be a trade off?
@@worldnomad2301 I can't add sufficient carbs to have any large impact on my LDL because that would prevent the therapeutic endogenous ketosis. I've tried ezetimibe and Crestor and am intolerant to both. Considering the benefits of pharmacotherapy are not clear in my phenotype/case, that I have no evidence of plaque on CCTA (now 5 years on this WOE), no family history of MACE associated with high cholesterol, that the medication have known potential side effects and unknown long-term safety profiles in the case of PSCK9i (esp in metabolically healthy persons; and there are 'curious' findings such as increased Alzheimer's HR in MR studies), then the calculus of pro vs con of treatment sits with lots of unknowns. I reserve the right to change my personal choice at any time and do not extrapolate from my choice to suggest others should do the same. Is that fair?
@@saintwithatie LDL-C is the main driver of the endothelial LDL transcytosis and thus cholesterol accumulation in the foam cells.
Curious
Curious!
Made it to the end! Well done
Great talk, I understand Nicks frustration, people tend to argue out of emotion rather than engaging with the science when it comes to this as they’re potentially triggered by the what they perceive as a dangerous idea