Hello Mr Feldman . Have been following your work and I am very impressed . Here is my take on lipid maths . VLDL production will be high if we take excess calories in form of carbs and protein. With statin only difference will be that those VLDls will have low cholesterol and will have more TG. If VLDL production is decreased what will liver do with all the excess fat. Since VLDL, IDL and LDL all have same apoprotein B I dont think statins have much effect on LDL number , but statins make these LDL smaller and denser. Since labs measure concentration, it will be low but apo B particle count will be high . Did not find study where any statin showed sig reduction of particle count . Did not find any study where statins decreased VLDL . With LDL lowering we are just making LDLs smaller because of less cholesterol content
Dave, aren’t you being a little disingenuous? A number of participants were excluded from your study solely because they had positive CAC scores. Let that sink in. Excluded because of their CAC scores. You know this and never seem to mention this. And then you have the temerity to draw positive conclusions from the fact that the people you did enroll had low plaque scores.
As a medico, I think that this is a great example of the kind of respectful, sincere and open minded conversation that I think should be encouraged in the public domain to underpin the search for evidence and truth. Truth should always be able to stand up to inquiry and debate so I applaud the professionalism of everyone involved.
As a lean mass high LDL person , this provided few answers. All my other numbers are very good. If I change my diet to solely focus on cholesterol it will affect my other numbers. My diet of high saturated fat and protein has alleviated my peri menopausal symptoms. I’m not changing my diet for one factor. But I appreciate The discussion and I do feel as though these doctors are willing to challenge the current paradigm. So I thank you for that. People like me are in no mans land. Especially peri menopausal and menopausal women. Very little research on us. And there could be a marked difference between women and men. Most people who have dementia and Alzheimer’s are women. The driver for that appears to be insulin resistance. I’m more fearful of those than clogged arteries. I also have the genetic marker for BRCA. Again, I appreciate that this issue is being looked at with greater nuance.
@@Elusive.magick Sonagrams will not do the job. The plaque is simply too soft and close to the lumen (the lumen is the interior surface of a pipe, a straw, or an artery) of the artery which is very irregular within a specific range. Irregular enough to give a blurry sonogram image, even in the most modern digital expensive ones. Thats why Dave focused on him and Nick doing cardiac imaging along with CAC data. Settle for CAC data unless ya got more bucks than I. The cardiac imaging varies with region, but averages around 1500 bucks. So no go for me! But CAC is much cheaper, and very important to know, so yes for sure.
@@carriersailor2474The cac test only measures calcified plaque , though .Soft plaque (more likely to break up /dangerous plaque )may still exist when cac score is zero . (although , not necessarily).
As a boarded lipidologist (Bill Cromwell involved in education at the NLA and who graced our internist clinic for n 2015) I was mesmerized by the high level of sophistication of all three participants. Simon, I listen/watch to all your podcasts - your 10 hrs with Dayspring (who motivated my lipidology training was superb - I 1:46:52 watched it twice - and your understanding of this very nuanced
This is one of the best nuanced discussions of the competing lipid frameworks I've ever heard. The stand-off is typically between the high LDL metabolically healthy camp and the "establishment" that asserts high LDL/apoB is univocally bad. I've never heard before the more nuanced view that BOTH views are relevant factors. Having the Feldman/Cromwell group assert that high LDL/ApoB is in itself bad, while metabolic health is simply an additional vector that moderates its impact offered me a total new way to see this issue. Thanks so much!
Only 1 hour in, but this is the best podcast episode on the topic. Both Dave and Bill are incredibly consistent and excellent communicators (and great hosting, Simon!). Also laughed when Dave got excited about trancytosis and not being as bullish on the statistical analyses. Exactly what he told me. :)
@@realDaveFeldman Dave, coming from a guy with ASCVD, I like the deep dive. This transcytosis talk is fascinating to me. Thanks for the 100 down under.... I learn from it.
You need to take down your video on cancer as a metabolic disease. It’s clearly metabolic and not genetic. Thomas Seyfried’s work is crystal clear on this.
Very happy to see you conduct this because it feels to me the takeaway message many people are taking from Dave and Nick's efforts are LDL doesn't matter. I did get tripped up on the idea that preventing heart attacks doesn't increase life expectancy because inflammation, however. 🤷
People may me getting that message that LDL doesn't matter but they say they don't know if it matters. Honestly, do you feel this is a question that will ever be definitively answered? I think not.
Brilliant discussion with brilliant guests. I could listen to Dave and Dr Cromwell all day. First time watching your show and I must say the moderation was excellent. Really honed in on the right questions at the right times, and let the guests flow when that was needed. Great job.
Thanks for your comment and feedback. Welcome to the channel. I suspect you'll enjoy the 7 hour deep dive I did with Dr Thomas Dayspring over 3 episodes. You can find that in the archives. And Nick Norwitz is on in a few weeks to continue this discussion.
Good that Cromwell finally accepted himself that FH is a totally different framework than LMH. As Dave said, that is exactly what he was trying to explain. We cannot conclude the effects of high LDL on LMHs from FH studies.
I'm a simple man, I see Dr. Cromwell and cholesterol in the title and I'm avidly watching! I'll likely edit this comment with any takeaways after viewing. Thanks for the episode Simon!
@@TheProofWithSimonHill Dayspring calls Dave an LDL denier. I wouldn't put Cromwell in the same group. He is open-minded and interested in learning new things, like you are.
I’m so glad Dave Feldman and William Cromwell rise above any hint of dogmatic, group / tribal thinking in relation to the tiresome Keto / Carnivore-type diets versus Plant-based diets debates. This is what the public deserves, as opposed to the childish “My Gang” v “Your Gang” nonsense. They’re focusing intently on their subject, with open minds…and pushing forward the knowledge / science…for all of us. Hooray!
@@stevelanghorn1407 That Nick is young, makes his behavior even worse. Most young scientists are humble because they realize they do not have the knowledge of an expert with 40 years of experience. Healthy skepticism requires people to doubt their own beliefs, whether right or wrong. Good scientists practice this, naturally. It's part of their epistemology. Young scientists typically doubt their own beliefs more than older scientists because they realize there is so much they don't know. It's also more professional not to personally attack your peers over understandable disagreements. If Nick comes out and says he's been diagnosed with ASPD and tries to correct these behaviors, I will have empathy and "give him time."
Love this quote by William Cromwell, "people share one thing; it is their metabolic vulnerability and inflammation which significantly distinguishes who lives and who dies"
Why then put so much emphasis on one bio-marker like ldl?. Why not, instead, tackle hba1c, bmi, trigs, hdl, IR, waist size ,blood pressure ?....all bio-markers that low carb /keto diets manage to improve and even optimise .
@@kenadams5504 Precisely this. Statin drugs are one of the highest selling drugs of all time. And here Dr. Cromwell calmy states that lowering apoB does not necessarily improve all-cause mortality. It is hypocritical IMO. No patient would take an LDL-lowering drug if he thought it would not extend his life at all, and instead of a quick heart attack he would die at aound the same time from cancer or CKD. A GP prescribing these drugs absolutely believes he is prolonging the patient’s life, and so does the patient taking them.
@@kenadams5504 that’s exactly the work Dr. Cromwell has put into the model we use at Precision Health Reports. We do not focus on one biomarker (and especially not LDL-C) because cardiometabolic disease is an evaluation of many parts that include multiple highly predictive biomarkers, relevant clinical history, and the harmonization of many clinical-trial based guidelines.
I love listening to your interviews, Simon. You are so open-minded, fair-minded, patient, and polite that it's a joy. I feel that having access to leading edge information is crucial for those of us who have taken control of directing our own health care when modern medicine has failed us. Thank you so much for what you do.
Amazing episode! It was super interesting! This is state of the art knowledge. So much inside that's amazing at the edge of knowledge. I have found it hard to understand sometimes when they geek out on it. I'd love to read more about what they've mentioned, their views and arguments. If you could give ressources that'd be great! I think a bit more of an introduction with the basics is quite necessary to understand the depth of this. I wonder if you recommend it like a beginner's knowledge video (maybe by you). Thanks a lot!
My HDL-C is always above 75-80. My triglycerides are always below 50. True for my entire life. I have normal BP (less than 120/80). No pre-diabetes. My LP-IR was 30. Not perfect but less than 45. Always lean. Not a smoker. Waist to hip ratio is .85. But I always had high LDL-C. My first ApoB was 120. My CAC was zero until it wasn’t. Anyone who thinks that LMHR is cardioprotective is deluding themselves. Now I am on a statin and PCSK9i. I wish I had started sooner.
@@TheAnimalBasedCure the statin and the PCSK9 inhibitor. it’s always better to start before you have a positive CAC score which is more representative of end-stage cardiovascular disease.
This was a great discussion. I very recently got interested in this topic when I just got back my blood work. I eat a pescatarian diet - but very high on nuts (raw/natural - unsalted - almonds, pistachios, cashews, walnuts) which likely make up half my caloric intake in a day. I also eat no refined grains or added sugars (though dairy, veggies and fruits are pretty much consumed daily). I am lean and do exercise pretty much every day and walking is my main form of transportation. I've been the same size since I was 20 - and am now in my late 40's. Thus I anticipated that my cholesterol would be low, and it wasn't. It was surprisingly high, but triglycerides and fasting blood glucose were both at the lower end of normal. My LDL wasn't as ridiculously high as those deemed to fit the LMHR phenotype have (it was around 118 mg/L), but I was surprised it was as high as it was given everything. There is definitely much to be learnt here about lipid balance and what it means to be fat adapted from a health perspective. I also think understanding the type of dietary fat and protein consume tip the balance at all and how. My more plant-based fats may be why my LDL is still considered "healthy" and my TG/HDL ratio so favourable.
No Simon, Dave was talking about epilepsy medications not working at all or as good as the ketogenic diet. Take into account that these ketogenic diets for epilepsy survived the decades of "marketing atacks" of big pharma because for many they work much better than medications. Also take into account that these ketogenic diets for epilepsy are pretty extreme and cannot allow the incorporation of sweet potatoes. Same for bipolar disorders.
I'm a lean mass hyper responder with the elevated ldl , and do cardiovascular exercise every day ,so a sweet potatoe won't significantly affect my ketone production .I understand why an epileptic may not be able to exercise ,but why can't someone with bi-polar do light exercise (e- biking etc) to burn off any carbs in a sweet potatoe ?.
Interesting. I remember my dad(non keto) had high sky LDL to the point when I took him to the doctor to review his blood work, his doctor was genuinely concerned and was questioning him on whether he was short of breath or had breathing problems. The doctor told him he had never had any patient he had ever seen with such a high LDL level. He immediately prescribed him statins and told him to return in two weeks after another blood test to review. Just for context, my dad had T2D, was a chain smoker, had a poor diet and lived a sedentaryy lifesyle. Being old school, he did not take tge meds, he consumed a whole head(yes whole head not a few cloves) of chopped up garlic he swallowed with water. He did not change anything else. When he went for a follow up and had my dad go for blood tests again as he did not believe test results and felt the lab had erred. Finallly as puzzling as the results were, his doctor had no choice but to accept the results. His doctor asked him if he had done anything else but taken the meds. My dad lied and said no, just meds, why? The doctor said that he had never in all his many years of practice come across anyone whose LDL had dropped so low and normalized in two weeks of the prescribed meds. He said it often takes years for him with the meds prescribed to see LDL drop to that level in his patients. Again my dad did not take up exercise, put his T2D in remission, adopt exercise or healthier diet. In fact he remained a sugar addict during that period and remained a chain smoker. The only change was consumption of a head of garlic a day for the two weeks. No keto, no consumption of 12 oreos daily
@@tsebosei1285 It is no miracle I acknowlege. I believe had he stopped smoking, becone more active via walking instead of sleeping so much, better watched his diet and adopted healthier diet or at least given up his heavy consumption of sugar laden junk food, I am sure he would have neen even healthier. Instead he opted to consume garlic to the point of becoming a social outcast. Sadly with all the bad practices, the garlic only bought him more time before T2D cought up to him in the form of congestive heart faiilure from which he passed away at age 67. Interestingly though and I believe owing to his heavy garlic consumption even when he developed congestive heart failure, his blood pressure was always optimal. And that was another shocker for the doctor as he had never come across any other patient that developed congestive heart failure with developing accompanying high blood pressure. My dad also wasn’t on any blood pressure meds ever. Go figure. Garlic or placebo only God knows
Super interesting topic and exactly what is needed for the "regular" person to get a better understanding of lipids and Co. Thanks a lot for this podcast!
It’s more so the mechanisms of action in regards to this phenotype that may illuminate some currently overlooked aspect of atherosclerosis in the future. This is at least what I find interesting about it.
A friend of mine introduced me to your longevity plan, I have started cooking your plant-based recipes & now I am diving more into your podcasts, too. Excellent content! I am happily shifting the hours I used to dedicate to Hubermanlab to you. Wish you all the best!
This discussion shines some light for me on how people make broad statements about things that are intensely complex. People say, "high LDL is not a problem" etc when it is so complex. I don't know what to think.
Perfect example of how counterpoint views provide illuminating discussion. Respectful, amicable and expertly guided. Thank you. P. S. None of this is to takeaway from my first comment: After listening to the entire conversation, my takeaway is that (1) a negative bio marker (higher LDL) for those on Keto is not being accepted as a negative (given the current study environment) with potential negative health outcomes in the future; (2) there is a desire to isolate an individual probability from the population probability which strikes me as Russian roulette being played with one's health (and ignoring that the house nearly always wins in the health casino; (3) any competent testing (one not engineered to steer toward the desired outcome (all will be well) and which will take some length of time to substantiated (increasing risk to a population risk); and finally, (4) this potentially deadly game is being played due to an unwillingness to accept a sweet potato (or carb du juor) that might mitigate the risk in accord with current data in order not to impugn the efficacy of a Ketogenic diet. For my money, I'd like to see a study that addressed the atypical lipid profile, inflammation as well as long term effects of Keto and carnivore diets on kidney function. Such a study would at least put a pin in the debate....but at what cost to the health of many? (No horse in the race, but remember my disease management days when metabolic syndrome was but a nascent buzzword)
Great convo! You did well, Simon, listening & open-minded! Kudos for this one! The guests, of course, made it interesting and pleasant watching. Thankful for @realDaveFeldman with his perseverance, dilgence and passion to keep digging in spite of the discouragement. Will be staying tuned & wish him well! 🙏🏼
One issue with Feldman and Cromwell, in a majority of their talks, is their failing to highlight just how rare LMHRs actually are. I was unaware of how rare they are until I saw Feldman and his collaborator Nick Norowitz talk together on Plant Chompers channel. Norowitz explains early on in that interview that only about 3 people out of 90,000 people they examined fell into that category. People online are getting overly excited about this research as though it applies to everyone adopting a ketogenic diet, when that is so far from the truth according to Feldman's lead author, Norowitz.
I think at the end of the day everything is going to circle back to what Cromwell stated. Your reason for death will be based on your metabolic health and lifestyle. If you live a dangerous lifestyle, you are likely to die younger. If you have poor metabolic health, you are likely to die younger. There are many ways to damage the body, drug use, poor diet, poor sleep, etc. There are pillars to optimal health, the opposite of the harmful mentioned. Don’t do drugs, eat well, get proper sleep and live a safe life. You are likely to live longer barring any accidents.
I am a LMHR LDL522 HDL84 Triglycerides 42 Happened when I transitioned from keto to carnivore. I feel better @55 than I did in my 30’s and 40’s. Carmen
I'm 48 a feel better than I did in 20s and 30s. So the question is does living a lifestyle that makes you feel better than ever kill you sooner? Common sense says no. I felt like dying before I went keto/carnivore. It was a new beginning at life for me.
@@GoneCarnivore idk about that, Massai tribe eat meat 99% they are healthy not having any disease but it seems they live shorter, that mTOR activation seem as main driver for faster aging.
Great esp the stuff from William about the limits of benefits of lower ApoB via eg pcsk9 and esp Dave’s follow up question about all cause mortality vs just focussing on cv events (56:20) which is almost never properly addressed by those pushing ApoB / ldl maximal lowering esp given that from memory there is long known research identifying this J/U curve phenomenon. Fortunately, unlike Dayspring, Cromwell is not a propagandist for conventional medical science and is able to see some of its limitations as well as its strengths “It is ApoB but its certainly not just ApoB, other things are obviously going on that we dont quite understand yet”. Such a refreshing change from the flat earth conventional cholesterol lowering fixated medical specialists that dominate the cardio field. I havent finished listening but so far this is the best video on these topics I have seen. Having said all that, suddenly his hypothesis that eg pcsk9 lowering ApoB should not be expected to make a difference in all cause mortality because its individuals metabolic constitution that determines that simply doesn’t ring true. If pcsk9 lowers cv events it must eg lower the incidence of pretty well instantaneous complete blockages that kill instantly and individuals metabolic constitution would have nothing to do with whether they survived a complete blockage particularly if there was no immediate intervention.
Great conversation! As a likely LMHR with a non-zero CAC score (BMI 21.0, 130 LDL before LCHF and 350 after, HDL 40 before and 80 after, Trigs 300 before and 70 after), I would ask that the advice to "reintroduce some carbs to lower LDL" consider the fact that some of us are no longer considered metabolically healthy if we do so (trigs shoot back up and HDL goes down). Add to this that increasing carbs brings back chronic migraines for me and I feel forced to select a pharmacotherapy.
selective carbs are ok. go listen to the keto and low carb ultrarunners. i'm over the keto limit with carbs but my tg was 55 two months ago. and that was the day after I downed a bunch of energy gels of pure sugar for a half marathon race
@@carinaekstrom1 I'm not metabolically "flexible", but the health markers under LCHF indicate metabolic "health": A1C 5.2, Insulin 3.4, HDL 80, Trig 70, hsCRP 0.2
@@carinaekstrom1I don’t know if the desire or “ability” to eat carbs is a metric for good metabolic health. Choosing to not eat them is a choice made by people who have made a correlation between carbs and some ailment. I don’t feel at my peak health when I consume sugar so I don’t eat it. That doesn’t mean that I’m metabolically unhealthy. My numbers prove that I’m healthy.
@@Elusive.magick Numbers don't tell you everything. There are things in whole food plants that support immunity and all kinds of important functions that you don't see in numbers. Other than a higher number of healthy years lived.
I am a LMHR phenotype, and I am in ketosis around 10 hours per day, but I eat enough carbs to not stay in ketosis 24hrs a day. I achieve ketosis via 18/6 TRE, and my LDL is 196 my trig is 100 and my HDL is 60 (so I *would* be classic LMHR if I was in ketosis 24hrs per day, but I have attenuated response by consuming around 50g of carbs per day). This is my cautious approach for the time being. I am not giving up my 0.9 hsCRP nor my 2.9 fasting insulin, nor my 18 ALT nor my 5.2A1C nor my 100/70 BP, but at the same time, since I can achieve all of these great numbers while moderating my triad, I am going to do that. That's my risk management strategy given the current state of the data. I am absolutely *not* going to take any medication, *especially* not a statin. I am 60yrs and not taking any meds and committed to never taking any meds (sorry big pharma).
Why do people with high cholesterol live longer? I posit that if the other markers are ok, high cholesterol guarantees better health, which means longer life!
Excellent podcast and at the cutting edge of science on this specific topic. I am keen to see a "easy to understand summary / takeaways" from this podcast if its available anywhere (please point me there).
All I can say is, 66 years old, was told over 27 years ago, go on statins, never did, Iam still here no issues. In the gym 5 to 6 days a week, sauna 5 days a week, do plenty of cardio, either in the gym or in the yard. Changed diet even further 3 years ago, I use to eat lentils and quinoa for lunch everyday, oatmeal for breakfast. Doctor says your anemic, so I changed diet to include more whole eggs, meat and fish, stopped the lentils, quinoa, no processed anything, no sugar, the only sugar is small amount of fruit on weekends only. Fast more then 16 hours everyday, last cholesterol test after 22 hours no food and gym, was over Tc- 300, triglycerides-49. Doctor said was to high, I said, I can reduce it back to 200 if I go back to ice cream, bread and pasta, and by the way, checked the glucose 2 hours after eating organic sprouted oatmeal, glucose shot up to 205, after 2 hours, it should be below 140, I usually range in the 80 to 90s. Could I have plaque, I dont know, but then again, at 66, I can hit the bag 5 days a week, a thousand times, and do 8 sets of 100 push ups straight, once a week and never out of breath.
FWIW, I make fermented oats and they don’t seem to increase my bloos glucose more than 30-40 points (normal ~90 depending on exercise and time of day) and it peaks at 30-45 minutes post meal and drops to baseline or lower post feeding. I’m 65 and a LMHR with >400 LDL.
Looking forward to Dave's documentary. I'm a LMHR, CAC is 0, not interested in changing my diet. Dave is not the only one comfortable, there are many doctors that are not freaked out about the LDL levels in healthy people.
This was a great episode as I have been following interviews of Dave and Dr. Cromwell since adopting a low carb (but not necessarily keto diet) due to rising A1C levels. So glad to see them both on your podcast in particular as you are a great interviewer. I am curious if @realDaveFeldman or you have seen discordance between ApoB and LDL levels (e.g. dropping ApoB but high LDL levels) and why that occurs. Also curious if @realDaveFeldman has tested whether he is still insulin resistant and whether one needs to be on a Keto/low carb diet long-term if their previous pre-diabetic condition seems to be in remission.
I think that if you have a small number of large particles (volume) LDLc (and therefore small number apoB ) versus a large number of small (volume) particle LDLc (and therefore large number of apoB) as would occur with oxidized damaged LDLc then the ratios would be quite different. Listened to this from Dr Eckberg.
1:05:25 Cromwell seems to be implying that the only benefit of ApoB reduction is improved quality of life because of reduced number of CV events, not improved life span. Mathematically, that sounds no different from saying that CV events are uncorrelated with mortality, which doesn’t make common sense.
@@TheProofWithSimonHill This has and continues to be a point I'm bringing forward -- and exactly as @aroundandround points out, the math doesn't make sense here. ASCVD is the number killer worldwide, and thus PCSK9 LOF -- which does indeed reduce mortality and morbidity of ASCVD - should show reduce All Cause Mortality if there are no trade offs in non-ASCVD outcomes. I'm discussing this in the documentary as the original and still burning question that has yet to be answered.
I wonder how useful of a statistic all-cause mortality is in a population of 75%+ prevalence of overweight / obesity with many of the remaining 25% being technically not overweight but sedentary, high trigs, smokers, drinkers, yo-yo dieters...
@@TheProofWithSimonHill Please have him on alone. I would love to hear more about what the latest research is saying especially in regards to those of us with elevated Lp(a).
Yes this is a common problem with many researchers focus on specific and not consider the implications and bigger picture. Also why does the body create Apo B and what are the implications if lowered - lower CV but ??? eg higher cancer !!! Not a desirable outcome.
I found unsatisfying Cromwell’s response to the question of why, if you take away ApoB-induced atherosclerotic risk, mortality does not reduce. If you reduce the risk of myocardial infarctions (that can be fatal), all else being equal, you would expect increase in longevity unless the ApoB reducing drug has an underlying tradeoff, ie all else is not equal.
Me too, but I think he was making a point that was simply going way over my head, I felt I was glimpsing a truth but then it disappeared. My base assumption is that he’s been doing this for 30 years and I watch RU-vid’s.
Population life expectancy in western countries has been increasing for many decades (until a recent blip)- that is based on all cause mortality. Premature mortality from coronary heart disease (CHD) started rising from the late 1940's, peaking early 1970's. After concerted public health campaigns to reduce CVD (lifestyle changes, medical advances, etc), from the late 1960's onwards, premature CHD deaths dramatically dropped. By around 2007 pCHD mortality rates were lower than the 1940's. Then it plateaued, slight increase, but still lower than 1940's (despite the dramatic increase in obesity, metabolic disorders & sedentary lifestyles in the past few decades). So where is that signal that efforts to lower CVD mortality rates by lowering LDL-c / ApoB has lead to an increase in premature cancer/ all cause mortality? Wouldn't that show up in population life expectancy, death certificates & excess deaths data?
Another aspect of comparing the children FH. Why is everyone assuming the children’s diet is not affecting their health? Many children are bottle fed, infant formula is far from ideal and full of many of the ingredients we see in ultra processed food.
Hurray for Dave Feldman , I await The Data! Dr. Cromwell's speaking to stating use and intolerance was very interesting. I wish my cardiologist had started me off with a low dose statin. The high dose statin plus ezetamibe gave me several very bad reactions which he considered nocebo reactions, and I know were quality of life canceling reactions. Would I try a statin again? I don't think so.
I would like to see Dr Cromwell and Dr Philip Ovadia *together* on a podcast discussing CV and metabolic issues. Bouncing off their ideas and research off each other. With Simon as the emcee. They have different approaches on how to tackle metabolic issues / CV events.
@realdavefeldman Insipired by your research me and my husband did TC scan last year and again this year, one year later. My husband last year had the score of 143, this year - 109. How would doctor Cromwell explain this… Please let me add that he is very thin, 76 years old and has LDL of 270. I thought it was KNOWN that calcium score never regresses, and certainly not with such high LDL count. I truly wonder what will the trial show for the cohort of LMHR.
What is the study that Dr. Cromwell discusses (he calls it "Penn heart study") at 2:27:00? I have been searching for an hour and cannot find it. He states that it examines the predictive independence of ApoB vs HOMA-IR on MACE as measured by CAC. I cannot find any studies that compare these metrics, only studies that examine one or the other.
It would be neat to see what happens if a person ate a crappy diet for many years and had imaging done that showed a high CAC score and then needed bypass surgery due to blocked arteries, and then after the bypass surgery that same person switched to a low-carb animal based diet for 5 years, discovered he was a lean mass hyper-responder with cholesterol that had now skyrocketed upwards (i.e. LDL of 200 - 280 mg/dL), and got a follow-up CT angiogram to see if the bypasses were clogging up. Well, I just described my personal situation and it turned out all my bypass grafts were clear (i.e. no plaque).
Very difficult to draw conclusions from this. You’d have to compare to someone in the same position who didn’t adopt a keto diet post surgery and took statins. It may be that there’s no difference at 5 years but there is at 10-15. To me that seems like dangerous territory to be playing around with elevated ApoB. I would be consulting a reputable cardiologist.
@@TheProofWithSimonHill Since 2008 I have met with quite a few "reputable" cardiologists. They all have the statin mentality. That's all they know. I'm willing to play around with introducing some "healthy" carbs to help lower my cholesterol and LDL, but that's about it. But I'll be watching my blood sugar and insulin closely as I go.
@@Malcolm-AchtmanYour experience is brilliant! (Well, not a brilliant experience for you when you were suffering!) But from a scientific standpoint!! Long may you experience your great results!
Ok… my mother did the same exact thing after a crappy western diet then she went keto, ended up having a quintuple bypass, then went keto/low carb AGAIN because she “doesn’t believe in cholesterol”. She lost a lot of weight in total (about 45 pounds), but had to have stints to open the bypass arteries back up (she has a pacemaker too). Her cardiologist says there’s nothing else surgically than can be done… She can’t speak more than a few words because of the post-bypass strokes. She’s only 69 now. All this started when she was 61; she’s miserable and a walking dead woman, but still believes the keto hype because of comments like yours I hope someday the promoters of keto/low carb using animal fats can be prosecuted for mis and disinformation
@@seitanbeatsyourmeat666 Sorry to hear about your mother. In her case, like mine, you have to take into account all the heart disease that we developed in all those years we were eating junk food. I would say her weight loss on keto was beneficial. But so many other factors play into it. Was she diabetic or prediabetic? Did she exercise regularly? How was her sleep? How well did she manage stress? Was her thyroid health optimized? Did she get exposed to toxins (e.g. mold, pollution, smoke, personal care products)? Did she have micronutrient deficiencies, including low vitamin D3, low magnesium, etc? There's lots to consider before pinning the blame solely on keto/low carb animal-based diets.
There is cardiologist interview on “No Carb Life” channel who talk about his heart attack where he has perfect bio markers in lipids all life, training regularly, avoiding fat and red meat, having apoB around 30, doing regular heart stress check all was good and he have massive heart attack one day in the gym. He is now advocating for keto-carnivore lifestyle which he is practicing now and talking from his view why ppl should avoid carbs and seed oils. ApoB is not well understood in my opinion.
A great interview. It is fascinating watching the leading lipidologists change their viewpoints after working with Dave. Both Bill and Matthew (Budoff) were both firmly planted in the lipid hypothesis of ApoB being the main driver for ASCVD. Now Bill is pushing metabolic syndrome as the main initiator of ASCVD (and while still feeling high LDL is a driver, he also indirectly implies that LDL may not be a primary driver, although due to it's involvement, still an important modifiable factor to control rate of calcification) while Matt now suggests that someone with LDL over 200 mg/dL should get a CAC (or CCTA) scan done before deciding if Statins are needed. Treat patients as individuals, despite high LDL. These major shifts, which to the uninitiated may seem small, show that the there is finally a desire to determine and describe the reasons for the initiation of CVD as opposed to modifying a piece (ApoB particles) of the causal pathway. More open discussions on evolving science with open minded experts who acknowledge the limitations on their own understandings are desired.
Great interview, thank you. The only thing harder to get than a fasting insulin from my doctor is imaging for plaque!! I can buy the blood tests, but other than a CAC I can’t get advanced imaging without a doc. Frustrating. 65 yo F, keto/LMHR for 6 years, otherwise metabolically healthy, no inflammation, CAC 0 for past 5 years, worried about what I can’t see and don’t know.
Maybe, just maybe my food choices (zero carb, zero fiber, adequate protein, no fear of fat) that yields excellent metabolic function, optimal mental health and balance, great libido, a strong good looking body, lots of energy, and restful sleep likely results in the the perfect amount of LDL for me.
@@TheProofWithSimonHill The best indicator of future health is one’s present health. Now in my 8th decade of life my overall health is better than when in my 6th and 7th decades.
I am so confused now! Been doing carnivore 5 months. My CAC score was 7. I’m 56 and have had high cholesterol my entire life and never used meds. I smoked and was around secondhand smoke (nana smoked). Triglycerides were 116 and HDL 50.7 LDL was 245.1 and that was the first week of starting diet. I’m going back in a month to check bloodwork. My A1C was 5.8 so I hope that went down. Total cholesterol was 319. Now I’m freaking out. I’ve heard people who have been carnivore their entire lives and are perfectly fine 🤷🏼♀️. BP is always perfect 100% O2 great HR as well. Had a hysterectomy in 2019 for uterine cancer no chemo or drugs.
Great conversation and all three guys kept the conversation flowing but Dave is doing mental gymnastics and changing goal posts every 2 minutes every time Simon asks him a direct question he answers with another question
All I know is that the SAD was killing me with IBS, joint pain, chest pain, chronic fatigue, high blood pressure and that the carnivore diet got rid of all those problems. Now with cholesterol going up the suggestion is to eat carbs to bring LDL down? Ive raten some fruit and potatoes here and there so now the question is... Is sporadically eating carbs to lower that cholesterol number going to kill me sooner? I dont think so.
The way Peter Attia treated Dave on his podcast was memorable for its hostility and ambush-like quality. I’m hoping a big fat slice of Humble Pie and a side of Crow is publicly served to Attia and Dayspring when Dave wins a Noble Prize.
I lost all respect for Attia as a result of his hostile treatment of Feldman. I am patiently waiting for Attia’s admission of error for his severe reduction of APOB through the extreme use of PCKS9 inhibitors. And his latest rant concerning biohackers gives us another clue to his self induced superiority over influencers without medical or doctoral degrees.
Who funded the research to determine the safety and efficacy of statins? BIG PHARMACY!! Now, they wouldn’t have any reason to mislead people-would they ?????? After all it is only a multi BILLION DOLLAR industry!!!
Why our family doctors don’t check ApoB levels on annual exams when they check the lipids? How do we know if they were in the normal ranges.. only now we hear that they need to be checked as well.
What a fabulous discussion. Is there any data comparing raised ApoB levels in people who eat a standard type diet that is loaded with seed oils and grains against raised ApoB levels in people who eat only meat, dairy, eggs and vegetables? My point is if LDL particles are only taken up by macrophages when LDL is oxidised (which I think Dr Cromwell said) then what is the plaque progression on people with low levels of LDL oxidation but still high levels of overall LDL?
When you look at huge population data across countries and LDL and All cause mortality, the U-shaped curve makes it obvious that its not a good idea to ask all asymptomatic humans to lower LDL with statins once their LDL is above 100, without considering a whole bunch of other factors (presence of plaque, metabolic syndrome, etc.) It's irresponsible but that's whats happening in the U.S.
1:08:37 this is exactly what I have been saying- it is statistical chicanery. You can control the effects of confounders through stats. The effects are real and no amount statistical manipulation removes their effects within the body.
As a family doctor I was very impressed by this open minded type discussion format with very competent professionals. That said, I’m curious to know if there was a particular reason why Lipoprotein (a) was left out of the equation
Thanks Simon for bringing Feldman and the LMH conversation to your show. It's great to see that you are taking steps to move out of your strong echo chamber. I hope you keep moving out and bring in Dominic D'agostino and Nina Teicholtz (she's now a PhD, so you don't have to worry about her credentials anymore), Volek, Finney and, of course, Paul Saladino (he eats lots of carbs on these days as fruit and honey!).
Very complicated discussion...seems to me we need a detailed discussion of how to measure an individuals uptake and down reg of cholesterol. It seems I can't rely on my lipid panel, APOB and LP(a) numbers without knowing how my liver regulates those things. Are there any available tests that tell you how those markers interact at the individual level?
Interesting that several biohackers, mainly those sponsored by meat/food delivery services (e.g. Butcherbox) and animal protein-based supplements are now aggressively against a 1-day fast, which they promoted until recently, and in favor of high cholesterol levels.
When these lean mass hyper responders aren't consuming a ketogenic diet are their lipids abnormal? Such as is their hdl still higher than 80 and their trigs low? Thanks for the podcast!
Interesting study would be to take some LMHrs and look at historical labs. Although it’s all based on historical (and voluntary) dietary data…. So it’s not controlled in that sense
It might depend how good versus crappy their diet was before going keto. I would bet their total cholesterol and LDL were lower before keto, and that their HDL wasn't as high (maybe 50 - 60 or so), and their trigs were likely higher (say 70 - 100 or thereabouts).
From all the videos I’ve watched, and I am not sure of each persons details, they all seem to demonstrate, higher ldl, higher hdl, and lower triglycerides. They seem to believe the ratio of hdl and triglycerides has improved so they like those results. But most all of them have higher ldl as a result of more meats and less carbs. I’m on the fence about all this but im certainly seeing positive results in keeping the carbs down and seeing seed oil and sugar as poison.
@@softballbryan Your comment is accurate. The people who see the highest increases in LDL tend to be lean and metabolically healthy. A lean mass hyper-responder is defined as person whose LDL is above 200 mg/dL, HDL is above 80 mg/dL, and Trigs are below 70 mg/dL. But I consider myself to be a lean mass hyper-responder even though my HDL is only about 55 - 60, and my Trigs are a little higher (e.g. 75 mg/dL). My LDL is well above 200, more like 250 mg/dL.
As Dave says in this video (2:41:30), one of the criteria for inclusion in the LMHR study they conducted (where the cohort was compared against a group from Miami heart) was a documented history pre-keto of normal LDL levels. he doesn't specifically mention their HLD or trig levels, but those metrics and that ratio almost universally improve in response to carb restriction -- LDL is the one that varies, mostly depending on BMI or specifically lean mass. so it is probably reasonable to infer the LMHR cohort were normal before.
FH is phenotype with different mechanisms and genotypes. There are FH people with high LDL and no plaque during their whole life and FH people with devlopping plaque during their childhood. High LDL can be associated with plaque formation but is it always causal ? or can it be a symptom of a dysfunctionnal ApoB/receptor problem ?
My LDL has been high or really high for over 40 years or since I started getting tested.. my recent test is 676 with a 451. High LDL and medium triglycerides. But getting retested because of triglycerides in a few weeks. I am Carnivore. I don't do meds.
I’m 5’7 , 150 lbs. was all aboard the ketovore diet for 2 months - then had a heart attack !!! Got a stent- home recovering now . I’m beginning to question a diet so high in cholesterol !
Don't listen to the ketodiots. They tend to blame attacks and strokes on the sweet potato eaten 4 years ago. For patients at risk of heart disease, keto is extremely dangerous. For those with clean arteries and no family risk, maybe keto of 10 years won't do much harm initially.
What about if people are trying to lose weight (lower BMI), reverse pre diabetes, or get off the BP meds but they are resistant to losing weight and have to stay in ketosis? Those are 3 risk factors compared to apoB. Right?
there isn't a specific crowdsourced statin study that I am aware of so statin studies have ties to government or Pharma companies so it boils down to trusting those entities that have often proved untrustworthy.
I hope you're going to point out that risk is just a number. One based on the general population. It has nothing to do with the cause of disease or with the individual patient. When you have the individual present, you can simply check to see if they're healthy. There is no need for speculation. And if you are that patient, you pretty much know if you're healthy without any tests. You don't need a doctor to tell you whether or not your diet is healthy.
agreed that risk is only a number. It actually tells you nothing. For example, what is the difference between tomorrow have a 20% chance to rain to 80% chance to rain? it tells nothing, we still do not know if it will rain tomorrow or not. We can only know till tomorrow! same as risk, 20% to 80% risk cannot tell you if you will or will not have a plaque! you can only know it once you got the plaque formed. So we need to know the cause and effect in order to predict.
Can I ask when you mention surveillance are you just looking at CTCA only ? what about plaque in other areas ? , I ask because I had a CTCA and had a zero score but then had a head to hip angio and had early plaque formation in the iliac artery
If I understood correctly, Dr Cromwell believes that it is not the Apo-b per se that is problematic. Rather it is oxidized Apo-b that is unable to transcytose back out of the arterial wall? Thus, one should conclude that it is whatever causes this oxidation to be actually the causal factor rather than the apo-b particle? Sure, lowering apo-b should, by the law of averages, result in less trapped, oxidized particles. However, unless we seriously believe the body is actively trying to damage itself when it is purposefully producing whatever level of apo-b it deems required for the environment in which it finds itself, pharmacological remedies would logically seem to be contra-indicated unless we believe science is smarter than nature. Rather we should focus on finding the root cause of that oxidation and seek to prevent it perhaps??
Nature is concerned about survival not longevity. So yes, science having the potential to be smarter than nature when it comes to longevity is a perfectly acceptable/logical position to hold.
@@TheProofWithSimonHill Just strikes me that nearly every time we’ve tried it, disaster ensues. Even if this time we might be right, why would nature increase apo-b as a survival mechanism if there wasn’t something else trying to kill it? Whatever it is doing this as a response to has not been understood and so in our ‘smartness’ we might be reducing the risk of a heart attack yet upping the risk of cancer etc etc There are many analyses I have seen where the actual benefit of lipid lowering therapy on mortality is almost null. Of course, different commentators will skew data and language to suit their narrative but there are enough credible people who hold this view for me to give it credence.
Just gone onto serious keto with very little carbs, LDL has shot through the roof! 10 stone good BMI but t2 diabetes, 5 stents! Everyone is afraid as I am not ‘healthy’. Do not take statins. This talk is very interesting but really refers to healthy people. Am I being silly not taking statins?
Simon, you should get Bob Harper on, on the outside he was a super fit looking paleo guy before he had his massive heart attack, I don't think he was keto though.
I don't think he has ever said that LDL-cholesterol (LDL-C) is the problem. He would definitely say that atherogenic Low Density Lipoprotein (LDL) particles are a big piece of the problem. He regularly says that LDL-C is a poor, hamfisted estimation of actual LDL.
This was a really interesting episode and great that Dave has done so much research. However, it worries me that as someone who doesn't have a good grounding in how the human body works and how all systems interact with each other, has the potential to influence the general public to make very consequential choices about their health. We will only see in years to come the impact of a ketogenic diet! An issue that's important on a population basis is the massive change in diet in the Western world with highly processed foods, refined carbohydrate and frequent consumption of high sugar/high fat foods .They have influenced the huge increase in heart disease, insulin resistance, inflammatory and metabolic conditions. It would be interesting to see the impact of a high fibre diet including carbohydrates such as brown rice, quinoa, freekah, bulghar wheat, potatoes with skins on, which contain protein, fibre and vitamins and minerals and are broken down slowly would have on ldl and plaque. As well as a range of protein and vegetables containing polyphenols. Excercise is another factor affecting metabolic disease. We have epidemic proportions of metabolic and inflammatory disease linked to poor quality diet and a sedentary life style, which is not present in tribes leading a hunter gatherer lifestyle.
if statins upregulate LDLc receptors on the liver thus taking them out the the bloodstream. but the oxidized LDL c cannot be cleared that way , how does that improve the situation?
I liked the information but made me think how complex it is to understand the multiple causes of the atherosclerosis that has caused me to have putting two stents last year. I have been doing low carb for the last three years, did keto after that for some time and lastly tried carnivore for the last three months. My LDL was elevated with low carb, managed with meds(no statins) but skyrocketed with carnivore. I am almost giving up of trying to understand the causes. Thanks anyway.
It's a pity that MGP wasn't mentioned as it plays a critical role in calcification of the arteries. It prevents the cacium forming on soft tissues and allowing calcium yo form on bones and teeth as part of the mineralisation of them. The gene expression gets suppresed when visceral fat toxins get involved. Vitamin k plays a role in it's activation. When the body immune function is compromised by inflammatory markers, oxidative stress then the allocation of vitamin k goes to immediate survival needs, like blood clotting. See Bruce Ames Triage Theory. A study was done in 1998 on knocking out the MGP gene in mice. All were healthy. 100% of them died early with calcified arteries. Not parts of their arteries, all of them. Both mice and humans have the MGP gene.
@davidzip8841 I quote "Dave, aren’t you being a little disingenuous? A number of participants were excluded from your study solely because they had positive CAC scores. Let that sink in. Excluded because of their CAC scores. You know this and never seem to mention this. And then you have the temerity to draw positive conclusions from the fact that the people you did enroll had low plaque scores" I hope I did catch the meaning of your comment. It's not an attack but I have to highlight that your comment is a prime example of why people on either side of the argument need to gain more clinical/scientific knowledge and understanding in this day and age where health information is so abundantly available. You have clearly missed the whole point of this study. I have yet to fully dive into the study myself, so I don't claim to fully understand all of it as of yet, But as a general rule, one of the reasons you want to remove people already presenting with the very conditions a study is addressing is so you can investigate one variable without interference from other pre-existing factors that already caused the condition such as previous lifestyle/eating habits that may be carried over a certain period of time in individuals (hence the importance of a "washout" period when assessing different diets using the same participants). It's like using a blank slate so you can see what ONE variable does on its own with as little interference as statistically/realistically possible. I hope that makes sense. I'll try and come back to this if I got anything wrong (happy to admit this should that be the case) upon further diving into that study.
So people were excluded from the Lean Mass Hyper Responder study because they had a positive CAC score? When Matthew Budoff (the primary in the study) presented the matched analysis of Hyper Responders vs. Miami Heart Study, both groups had approximately 50% of cohorts with positive CT angiogram scores upon entry in the studies, so not sure how it can be said they were excluded, when they apparently weren't.
@@reinerschafer1708 I am not sure what exactly the person meant to be honest. I haven't looked at the study in depth yet. I personally believe in the integrity of Dave Feldman, Dr. Budoff and their team so my response was to indicate that "if" anyone was excluded, it would have been for a valid reason rather than due to a lack of professional integrity (as the person I responded to was implying).
Any summary, take away? Particularly, if high LDL / apoB is independent (partially) mono-causal risk factor? And why Daves body responds differentenly to (saturated) fatty diet? (Am not able to listen all currently and found no summary at outro)
I'm not sure if you will get a chance to read this Simon, but thank you for hosting such an interesting conversation. It is nice to see balanced conversation around this topic. I have got two questions/points.. Firstly, the concept of 'metabolically healthy', as alluded to, is such a difficult thing to define. I do feel that simply the absence of a marker of metabolic ill health still leaves a lot on the table. Therefore within the 'lean mass hyper-responders' there is likely significant heterogeneity in their metabolism. I hope that exercise capacity and determinants of health beyond simply a normal BMI and normal glucose parameters are considered by Dave in future research. Secondly, while I recognise the end point in question has mainly been the presence or absence of atherosclerosis on non-invasive imaging. The hard endpoint on coronary events will at some point need to be considered more. In this regard I have for some time felt there is already evidence towards a more complex answer to the question of ASCVD. In as much as 1/3 of cases of ACS there is plaque erosion rather then plaque rupture. These plaques typically do not have rich lipid cores and are seen in patients without high lipids. Thus when we lump both ruptured and eroded plaques together we do run the risk of 'watering down' the strength of associations. Ultimately I would like to see more understanding in this area which maybe important to tease apart the lipid and inflammatory risk associated with ASCVD events.
no mention of IF in this presentation, both keto and no keto are doing IF, also what about letting - blood donations would think that refreshing the blood system would have some kind of effect, and would love to see a risk calculator and how to asess which risk matter most by the numbers, from what i can tell I have low risk with high ldl 132 not as high as you mention and have apob 1300, but my ir is was less than 25 after using statin for 2 week my ir rose to 32, none of my other numbers are high, but my dr wants me on statin. How do you find drs that are open to really work with diet changes and really discuss the numbers from nvr I wish dr like you would put up referral network for drs that don't want to make decision base to TC 212 alone. Also you guys use a little too much terminology that maybe a lot of us don't understand, providing links to your papers you discuss would also be beneficial.
Another interesting conversation ! I've never heard of either of them but I'm not in the keto camp either. Interesting subject matter though it seems like a very small percentage of the population - eating keto years on years and wondering what the CV impact is if you are otherwise metabolically healthy. I can see why someone would want to do it if it was to treat a very specific illness otherwise idk why someone would ever risk living their life on an elimination diet. From a nutritional standpoint and possible impact on the microbiome it seems- at least at this point with current research- to be unnecessary risk. It is entirely possible to be metabolically healthy eating carbohydrates so why go to such extremes? Just my own opinion. I know we all respond to foods, patterns, exercise differently. So many different factors at play and genetics a huge part of that as well as the composition of the microbiome. I hope they get some answers to their questions even if they are short term results. I have a good friend that has eaten high fat for years and has extremely high cholesterol so I hope they are right :/
I'm not sure I would call people choosing to eat a keto diet, choosing to eat an elimination diet. Aren't they just eating closer to how our humans would have eaten during the majority of our evolutionary past? For the most part it just seems they've "eliminated" modern grains, fruits and vegetables that hadn't been cultured yet for the vast majority of our past. Sure they could eat some primitive crab apples or plantains, but let's face it, they don't taste very good. Once you've chosen to consume the modern fruits, vegetables and grains found on supermarket shelves, you have chosen to eat very differently form what we ate during our evolutionary past. Not saying its necessarily bad to eat those modern foods, just saying someone is eating an elimination diet because they choose not to eat them, doesn't seem quite fair.
This was difficult to listen to. BMI for Simon is not surprising. He lifts and is fit. He has more muscle. A better question would be adipose % if he was looking for health info. Also it would have been helpful to spell out metabolic syndrome. I listened but nowhere did I hear why Mr Feldman was pre-diabetic. Did he have metabolic syndrome which includes obesity, high blood pressure, high abnormal lipid profile, and diabetic/diabetics. N=1 is not at all interesting to me. And no control with his study design. Now many lean mass hyper-responder are there out there? Why so they can eat a high fat diet? Also why risk it? What is the draw for a high fat diet? Is he unable to control his eating unless he limits it to low or no carb? Obviously I am not as mature as you Simon. “It’s a lottery bet.” Of course epilepsy is a different question all together. But what concerns me is the group of people going keto who has a family history of serious heart disease with family members dying in their 40 and 50s but a way for them to lose weight.
