Summary: In keto cohort, there's very strong evidence of no correlation between: - total plaque score and LDL particle count - total plaque score and small dense LDL - total plaque score and Lp(a) - total plaque score and OxPL Howerever, something quite interesting showed up: for both samples (keto and MiHeart), total non calcified plaque volume was almost the same, diverging on calcified plaque which was higher on the MiHeart sample. Both samples were of healthy people with median age of 50 who were not taking cholesterol lowering meds.
To my knowledge this is the first study to analyze a sub-population who, on the surface, appear to have optimal metabolic health as well as being in prime health overall and looking at how their diet and lipid markers differ from the general population that recent studies have confirmed have at minimum some level of metabolic dysfunction ( 92%) and record amounts of chronic disease, obesity, and mental disorders. I propose that we have much to learn by studying healthy people. For me it’s personal. Since adopting a mostly ketogenic and carnivore diet my health and well being has never been better, yet, for the most part the medical community, friends, and family have not only provided zero support for my journey to better health, but have tried to sabotage my efforts, albeit, generally having good intentions. I’m 75 year old, very low carb for 12 years and mostly carnivore for the last 4 years with LDL of 584.
@@DrTomMD Yes I am willing to have these tests repeated, however I cannot afford to pay for them and in BC medical insurance does not cover annual or bi annual testing; just the initial testing that were normal/optimal. Perhaps if I started to have symptoms they would do additional testing provided any positive tests would then inform a new treatment plan.
@@colinvankeith4814 if I were your physician, believe me, I could find the coding to get it covered. Your life is worth more than the cost of a carotid ultrasound
@@colinvankeith4814 The Best thing or governments can do is to provide easier access to all kinds of health tests. The situation is the same in all parts of the world. Only then we can hope, as population, to become healthier.
There is no such thing as Keto according to centenarians who don't have health problems. High carb centenarians. 2010 study title: "Discovery of Novel Sources of Vitamin B12 in Traditional Korean Foods from Nutritional Surveys of Centenarians." These Korean centenarians consume a high carb diet with 87% of plant foods and 13% from animal foods. They have almost no access to synthetic vitamins, supplements or fortified foods. Centenarian men take in about 1700 calories per day and about 300 grams of carbs per day. These people are set in their ways they do not play games with diets or experiment with any type of money making fad diet.
Er... Hope you guys ain't trying to jinx it unnecessarily. I wonder if we can really trust TPS and CPS 100%? To falsify statins and psk9i argument is only to measure preemptively if one is developing any soft plagues somewhere or not. I think I personally can't boldly pitch this theory to someone who already had heart attacks or strokes in the past without a proper scientific measurement. The pharma will *_ALWAYS_* have a standing ground on fear as long as we still don't have the "killing" (not to jinx) measurement.
I'd nominate Dave, Nick, and Adrian for a Nobel Prize if I could. The science they are doing regarding lipid metabolism is as pioneering as the work by Brown and Goldstein.
Phew! I'm so glad you had the Lp(a) data. Mine recently measured 187 after going carnivore for a few weeks for elimination reasons. The internet told me to worry! I'm so glad I decided to stay calm and wait for your study results. I suspected I might be an LMHR and my typical lipid panel changes after going carnivore responded accordingly. My hs-CRP is 0.6. I'm a fit/healthy 59 white male, no meds. I am considering getting a TPS, with AI-assist. Thanks for all the hard work guys!
@@nicknorwitzPhD Are you making a little poo joke, Nick? 😂 Otherwise of course he means "as an elimination diet to pinpoint the bad guy/s as foods are reintroduced". 😊 PS comment directed not at Nick but at the denizens of the internet.
Here is the longitudinal data for over a century. High carb centenarians. 2010 study title: "Discovery of Novel Sources of Vitamin B12 in Traditional Korean Foods from Nutritional Surveys of Centenarians." These Korean centenarians consume a high carb diet with 87% of plant foods and 13% from animal foods. They have almost no access to synthetic vitamins, supplements or fortified foods. Centenarian men take in about 1700 calories per day and about 300 grams of carbs per day. These people are set in their ways they do not play games with diets or experiment with any type of money making fad diet. Get your CIMT test and then you learn.
@@JennyMitich Don't pay any attention to fake studies just stick to real humans long term track record as you can't fool real people for over a century but anyone can write bought and paid for studies to fool the gullible.
@@StanDupp6371 There's a survivalship bias built into these studies. Many factors play into being a centenarian around the turn of the century. I suspect the fact that they survived famine, war, and disease, without reliable access to modern medicine attests to their superior genetic makeup compared to the average population. For all we know, they would've lived longer eating an animal based diet.
Absolutely amazing work. Keep it up. This work has repercussions to more than just the LMHR phenotype, as I believe it will lead to the finding of better markers of CVD risk. Likely composite markers.
"... it will lead to the finding of better markers ..." Not without great resistance from drug companies that are making so much money selling drugs to treat current markers -- unless they can find new drugs to treat the better newer markers.
Thank you Dave! 😊 I am a LMHR. I am 52 years old and my resting heart rate is 53. Just feel really good and have lots of energy on this diet ( as long as I avoid all of my allergens). Pretty much eating what I can eat. Which puts me on a meat based diet. Very low carb high fat. Ken Berry says that's the Proper Human Diet. If I had a bunch of that calcified stuff that clogs arteries I seriously doubt if my resting heart rate would be 53! And it definitely goes into the 40s when i am asleep.
it's not the 'proper human diet' at all - it' ignores all the evidence that people ate a huge variety of foods and were in good health. Study indigenous Australians, and Kitavan islanders and so on. Humans ate whatever they could find in the area they were.... including tubers, insects, (forrest dwellers) snakes, fish etc. Yes we ate meat, but we also ate nuts, berries, and tubers, bark, fungi, and shellfish and reptiles and so on.
Dave, congratulations to you and your team. Exciting results to say the least. The level of advancing new knowledge you are responsible for is not to be ignored. Just awesome Dave.
Dave, I love these updates, but do you mind doing a summary at the end for "normal people" that by the end of the video forget what was discussed in the middle and what were the outcomes
It’s interesting to see doctors striving to improve health instead of practicing manipulating data to justify flawed models and engaging in double speak.
It's really great work that we hope will change medical practices, sometime in the distant future, probably. I have low triglycerides and high HDL, so I've always ignored LDL levels. But it would be nice to have doctors utilize better things than just LDL levels as their diagnostics, and the mandatory following statins prescriptions.
I’m married to a PhD, I never call her doctor or introduce her to someone as doctor, there is nothing magical about a PhD except being able to successfully defend a unique thesis to your expert peer group. It provides acknowledgment of expertise within a very narrow field of study, although I confess some PhDs seem to receive a subsequent letter in the post saying “you now know everything there is to know on all subjects.” Personally I fond those “experts” less trustworthy overall”
Didn't you notice Dave called me Nick (PhD) and Adrian "Dr Soto Mota" (MD PhD) ... tbh, I prefer Nick or "Oreo Kid" ... even when I'm an MD PhD, I think the formalities just create an intellectual power hierarchy that's not productive. In two words, I agree with you...
@@nicknorwitzPhDIn college, I always called my Professors, Dr So and so. But in a group of friends, using first names makes it more fun. Life should be fun.
One of the perpetual jokes in my town is the insistence that we're all Phd's. Some people fall for it until you tell them it means Park High Diploma. It does give us license to spout off on all possible subjects with the appropriate gravitas.
The fact we as patients even HAVE to argue with our doctors, even when we provide strong medical literature and meta analyses is ridiculous frankly… our state of healthcare is sad.
@@qui1766I'm not picking sides here, but the preponderance of existing evidence is not on the keto/carnivore side. Perhaps that will change over time, I don't care, but for now medical providers have to stick with the data with a higher degree of certainty with regard to long term health outcomes. If your doc went to the comment section before mainstream scientific consensus to inform their medical practice they would be getting sued all over the place.
@@rpearce25 I don’t disagree, but I’m saying in general docs don’t keep up with medical literature, and it’s not their fault they don’t. Docs have way too many patients and are overworked as is. As someone who has a special interest in hormones, the way that many doctors including endocrinologists prescribe hormones is based on info from the 1960s when we knew basically nothing. I’m not even talking cutting edge science like this, I’m talking things that were easily disproven from years ago being common practice with doctors. When I have talked with doctors about certain things, they often tell me about random things they read online rather than peer reviewed research. What is being taught in medical schools on hormones (which is barely taught for GPs) and nutrition (which also essentially has no classroom time) it’s all information that’s been disproven from the 60s that isn’t even based in serious science. The medical education system for general practitioners has been teaching a lot of really outdated information. And instead of being open minded when presented with a number of peer reviewed medical analyses, patients are told they don’t know anything because they don’t have an MD. This isn’t every doctor obviously, but it’s the experience I’ve had with 80% of the doctors on Medicaid, and countless others have had bad experiences with this. One of my testicles died, upon their examination and determination, and doctors wouldn’t even refer me to a urologist or endo. Refused to get my testosterone levels checked and I had to figure everything else out myself. Told me I was “too young to worry about it”.
Can't wait to see the influencers dealing with that lipid-lowering excluded comparison, who am I kidding they'll probably ignore it. Can't wait to see when it becomes so big they can't ignore it and have to grapple with what this data is suggesting. I can't get over those R and P values for ldl in LMHR, it's literally what Dave and others have been hypothesizing for years "Perhaps ldl in this very different cohort is behaving differently". Also, shame that Miami heart didn't have lipid particle information, also I really wish there was a 1 to 5 year followup on Miami heart to see what "normal" or perhaps not normal but quite healthy compared to general population but not quite lmhrs, what their plaque progression looks like to compare to the LMHR followup. Hopefully there will be little to no plaque development, but if there is it would be great to have something to compare it to
- Yes, I wish MiHeart had longitudinal data as well - Of course, I should level-set that I fully expect the LMHR cohort to have some degree of plaque progression at a population level, given the average age is 55. I've said this dozens of times across podcasts even before the second scans came given the age of our mean. That said, I like speculate it will be lower than most if not all other major longitudinal studies, but that won't say a lot given they are all high risk (and I think both supporters and detractors alike are in agreement our cohort is probably not "high risk" relative to those cohorts). This is why the MiHeart match data was likely to be as interesting - and for many, *more* interesting -- than the longitudinal data of our study without a clear comparator (so far).
This was an outstanding discussion. Question for you gentlemen-If the LDL and Lp(a) particles are actually "firefighters," and NOT fire/inflammation "accelerants" (i.e. "wood"), then doesn't it make sense that we would want as many of these "firefighter" particles floating around in our blood at all times? If my supposition is correct, then it seems that treatment with statins and/or PCSK9 inhibitors would be a really BAD idea for those people who are trying to fight the atherosclerosis process!
It's actually good for immunity and clearing out of toxins, incidence of sepsis goes down as LDL increases. Could be ldl are "firefighters" but become "wood" on standard american diet ie metabolic syndrome.
I would love to watch and learn from this video, however I do not have an hour to view it. Shorter formats would accommodate many. Keep up the great work!
Con la dieta cetogenica en cinco meses revertí la resistencia a la insulina, en ocho meses perdí 24 kilos: bajé de 78 kilos a 54 kilos, mi IMC es 20.4. mi insulina es 3.7 uU/ml en ayunas y 4.3 post prandial, glucosa en ambos casos menor de 85, mis triglicéridos bajaron a 80, mi HDL aumentó un 50 % subiendo a 62, mi presión arterial se redujo a 115/70, pero por LDL alto (223). La médica que visité y llamaré Doctora estatina, no entiende razones y me quiere formular estátinas.
@@Oscar_AHhello there, mine is 749 and probably rising. But my other labs are good. My Dr. Is concerned. wants me to take statins, and see a cardiologist. But I am not convinced that statins are beneficial. I asked her to check thyroid. I am mostly animal based. Less then 20 grams of vegetable carb a day. I am a senior woman. So if I got this far in life and feel healthy & active I will take my chances. We all die of something in the end.
Dr. Attia is not a lipid scientist, so there is no reason to bash him. Cholesterol is not causal for heart disease. Apob is causal. That is what world-leading lipidologists like Dr. Cromwell, Dave Feldman's friend and mentor and Dr. Sniderman have stated in their YT interviews and I don't believe they are wrong. I noted that in Dave's YT conversation with Dr. Cromwell, Dr. Cromwell identified some methodological issues with Dave's research. which he was unable to refute. I am going to review that conversation.
Yep, this data is a classic black swan scenario that disproves the apob hypothesis. I've never understood why Attia and friends want to stop at apob when it's clear there is a deeper issue and cause. Not knowing the true cause is harming patients.
@@richardb8267 No it isn't malpractice. And I don't understand the endless bashing of Dr. Attia. He is not a lipid scientist. All of his knowledge comes from the scientists who have done the research. That Apob causes heart disease is a conclusion derived from probably hundreds of studies of every kind including, genetic, with all reinforcing each other. You will hear this on YT from world-leading authorities on lipids like Dr. Cromwell, Dr. Sniderman and Dr. Dayspring.
Interested in this topic, but sorry, I can't watch a 58 minute discussion. I'm looking for the 10 minute summary. Thanks for alll your work in this area.
When this is all said and done (with both pre and post ctas) a separate analysis of looking at another AI analysis focused on arterial inflammation using caristo cariheart software (FAI) from Oxford would be potentially eye popping and further explain differences between lmhr with and without plaque. Their Lancet ORFAN study shows astronomical association between specific types of inflammation and events with a max of 29x hazard ratio for the most inflamed. I’m sure they would happily finance that study with free AI scans.
Here's a ChatGPT summary: - Preliminary data on high LDL keto diet presented at the symposium of metabolic health. - Emphasis on the preliminary nature of the data and the importance of consulting with a doctor. - Collaboration with Dr. Adrian Sodomota and Nick Norwitz on mechanistic publications. - Comparison between the Lean Mass Hyporesponder (Keto CTA) study and the Miami Heart (MI Heart) study. - Explanation of the Total Plaque score, which quantifies plaque in 15 segments of the heart. - Spearman correlations between lipid metrics and Total Plaque score show significant differences between the Keto cohort and Miami Heart. - LDL cholesterol in Miami Heart shows a near-significant correlation with Total Plaque score, unlike in the Keto cohort. - Different populations show different strengths of associations with biomarkers. - LDL cholesterol's association with plaque progression varies based on the etiology of high LDL. - Lean Mass Hyporesponder group shows no significant correlation between LDL cholesterol and Total Plaque score. - Total Plaque score versus lipid particle count (LDLP) in the Keto cohort shows no correlation. - Total Plaque score versus small dense LDL particles also shows no correlation. - Total Plaque score versus Lp(a) and oxidized phospholipid ApoB shows no correlation. - AI-guided analysis of CCTA scans reveals plaque in all participants, highlighting the importance of resolution. - Quantitative analysis shows similar total non-calcified plaque volume between the Keto group and Miami Heart. - Excluding participants on cholesterol-lowering medication still shows similar results between the two groups. - Main message: Preliminary data suggests that high LDL levels in a keto diet do not correlate with increased plaque volume, challenging traditional lipid hypotheses.
I absolutely love these discussions! Just fascinating. I am not a doctor or researcher (okay, I take that back ;-) I research and analyse everything. I’m pretty sure I was a doctor in a previous life.
Have you ever compared LMHR, FH and homozygous ApoE4 lipids? I’m a 4/4 and my lipids are very similar to these findings. I’ve been lowcarb 35 years. I’m very lean and muscular
Hi Dave we met briefly at the PHC conference earlier this year. I would be interested to see if there is any correlation between high levels of blood oxalates and hypertension with plaque formation? i.e. could oxalates under pressure be damaging epithellial tissue over time. Particularly where this scenario coincides with fluctuating blood sugar levels.
Great discussion and information. Thank you all. I've been ketovore for a few years now and CAC went down (177 on my old diet down to 143 on keto). Cheers
Faridi et al just came out with an analysis of Miami Heart that included a subgroup analysis of only those with "Optimal risk factors" (n= 184) This was defined as, "not on lipid-lowering therapy and without hypertension, diabetes, or active tobacco use, optimal risk factors were further defined as having all of the following: systolic blood pressure
I'd like to see keto calcified plaque compared against what's considered a truly healthy Mediterranean diet where people are eating 12 cups of vegetables and salad a day and doing all the things in the best food categories such as when eating grains, only eating them in their whole form from 3 grains only. Quinoa, buckwheat, and amaranth. Plus having mushrooms a few times a week, high polyphenols, etc. A modified super Mediterranean diet where starchy carbs are cooled after eating to create digestive resistant starch, Etc
This study is not compelling because they excluded people on keto who have lots of plaque from the study, so of course the results look good. This study doesn’t inform an average person who wants to do keto what their risk of developing plaque is because this average person could be like the selected participants and not develop much plaque, or they could be like the people who are excluded from the study who have a tendency to develop lots of plaque. The difference could be due to genetics. So in essence, the study can’t tell, for an average person, if their risk of developing plaque increases, decreases, or stays the same, if they switch from a mixed diet to keto.
This study is very compelling for science because it challenges the notion that ldl is always causal. It is a unique group of subjects. Like they repeatedly said, this is not medical advice and in your case, if you don’t fit lmhr profile, it isn’t necessarily applicable to you.
This study is beyond compelling for science. This study is challenging the hypothesis that exist for more than half a century telling people that high ldl is the main cause of CVD (Atherosclerosis). But the data in this study suggest that LDL is NOT causal.
They didn’t want people who already broke their bodies and then went keto to try to fix it. They wanted to see lean people and see how their numbers tracked over time with high LDL. This is very compelling to me to see how these people track through time. This is what heart researcher should be doing instead of accepting the old tired assumptions that just aren’t true.
If they had selected individuals with existing plaque burden (vs excluding them) it would’ve completely undermined the point of this prospective study given it’s a comparison of plaque progression among healthy individuals with a matched Miami heart cohort lol.
@@rmpennivLooks to me they compared the Median of each the n=80 LMHR to MiHeart n= 80. The Median of both was CAC= 0. Thus Median wise both groups had very low TPS total plaque score. Peoples below the Median had mainly Very Low CHD Arterial Disease or NO Arterial Disease. Peoples above the Median have low, moderste or very very serious arterial Disease. Above the Median Both Groups have tons of peoples with CHD heart disease.
On the clacified plaque difference.. is there any theory suggesting that inflammation, which is lower on keto, accelerates the calcification? At the "oldest" period of their plaque progression, the keto folks may not be converting to calcified form -- that would be very interesting to explore and may be shown in the 1year data.
Excellent work! I am a cardiologist in Brazil, and I practice ketogenic and carnivore strategies. This data raised a question for me: does the KETO population have the same amount of non-calcified plaques as the MiHeart population, right? Could this be due to a shorter exposure time to a risk factor (in this case, dyslipidemia/elevated LDL)? However, upon further reflection, LDL levels and other particles did not appear to be predictors of plaque in the MiHeart study either. I sincerely hope this is not the case. I am eagerly awaiting the developments in this story.
Part 2 of why the Lipid Energy Model is probably not correct. This is an addition to my comment earlier. The reason why lean people see a greater increase in LDL than fat people is because doing keto is like 1) fasting and 2) being in winter. Keto is similar to fasting because you burn fat while fasting. Keto is similar to being in winter because there are very few plant foods (if any) in winter; so not eating carbs is like being in winter. Both fasting and being in winter are difficult conditions for the body. Fasting is self-explanatory. Being in winter means needing more energy to stay warm while being in an environment with harsh weather conditions and scarcity of foods. So when someone is doing keto, the body thinks that it's fasting or it's in winter and responds by conserving energy as a protective measure. It does that by lowering thyroid hormones to lower BMR. This has a side effect of lowering LDL receptors as well, which results in increased LDL in the blood. Since fasting and being in winter are more dangerous for lean people than for fat people because they have less fat reserves, lean people's bodies have a greater protective response, which results in a higher increase in LDL. That's why there is a correlation between BMI and the increase in LDL for people on keto. Reintroduction of carbs to the diet, as in the Oreo experiment, sends a signal to the body that 1) fasting or 2) winter is over. So the body can now relax and raise the thyroid hormones and BMR. In doing so, LDL receptors are restored as well, lowering LDL in the blood.
I read this yesterday and re-read it now and it is such a clear and logical way to explain the high LDL increase for fit, healthy people doing IF and low-carb. Wouldn't it be great if so many other RU-vidrs that are deep into this topic and actually know the above had the capability of explaining this issue so clearly and in just a few paragraphs like @justsaying7065 has above: simple terms and so efficiently. Thank you for your contribution.
High LDL cholesterol in context: The study looked at people following a ketogenic diet who had high LDL cholesterol levels. Surprisingly, these high levels didn't seem to be linked to more plaque in their arteries, which is usually considered a risk for heart disease. Comparing groups: They compared the keto diet group to another group of people with normal LDL levels. Despite the big difference in LDL levels, both groups had similar amounts of plaque in their arteries. Different types of cholesterol particles: The researchers also looked at different types of cholesterol particles, including small dense LDL particles, which are often thought to be particularly harmful. However, they didn't find any connection between these particles and artery plaque in the keto group. Other markers: They examined other blood markers that are sometimes used to predict heart disease risk, like Lp(a) and oxidized phospholipids. Again, these didn't show any relationship with artery plaque in the keto group. Detailed artery scans: Using advanced imaging techniques, they measured the exact amount of plaque in people's arteries. This gave a more precise picture than traditional methods. Similar results without cholesterol medication: When they excluded people taking cholesterol-lowering medications from the comparison group, the results were still very similar. Challenging traditional views: These findings suggest that in the context of a ketogenic diet, LMHR's high LDL cholesterol might not be as risky as traditionally thought. However, this is still preliminary research and needs more investigation.
You can take all those factors in determine metabolic health. If you did not start with a Fasting Insulin you are missing a trick. Insulin is a leading indicator long before HBA1C , fasting glucose or any lipid panel results that show up as a problem.
Agree with Nick's observation that it would be good to look at a ratio of partical-count/SD count I'm not sure I agree with his expectation since I'd expect that the plaque score in LMHR is for life before keto, and hence, nothing in them now is really related to their TPS. the 1-year change maybe, but TPS not really. The most interesting there is Lp(a) since it does not change as much with diet (though more than was previously thought), so that there is no relation is more interesting there. Would be interesting to see if lp(a) was the "keto" version vs lp(a) prior to keto.
Dave____the LMHR n=100 observations LDL-P, smLDL-p graphs are very thought provoking. Do you have PARTICLE Count graphs for Large Diameter HDL vs TPS. Do you have PARTICLE Count graphs for small Diameter HDL vs TPS. There are literature indicating small diameter HDL's are mire Heart Artery Protective. I gather smHDL's job is to extract/remove cholestrols from the arterial wall
In addition to the fraudulent Ancel Keyes research, it’s also important to remind people of the history behind the original studies that link LDL elevations, saturated fat consumption, and CV disease were conducted during a time when many many people smoked manufactured cigarettes.
@@fitmillvalmennukset6808 What publication? If you're referring to Seven Countries then it's clear you've never read it because 1) he didn't study 21 populations and 2) for Seven Countries he studied sixteen cohorts individually.
"Manufactured" cigarettes? The problem with all tobacco products is not the manufacturing, but tobacco, itself. Tobacco is naturally radioactive, in that it concentrates both radioactive lead (Pb-210) and polonium (Po-210). Radioactivity is present in canned tobacco, cigarettes, cigars, snuff, in fact, in all forms of tobacco. All plants will concentrate radioactivity found in the soil and precipitation whenever present, and this is why ALL smoking, no matter the plant source, is pollution that is damaging to the face, mouth, throat and lungs. (For example, areas of trees within the US Northeast concentrated the precipitated radioactivity released from Three Mile Island [1979 ], to the point that fireplace ash from those trees reached the radioactivity levels of radioactive hospital waste.)
Greetings from Copenhagen at the annual ARDD (age related drug development) conference. Lipidologist and past president of the National Board of Physician Nutrition Specialists and current question writer for the American Board of Internal Medicine here. Starting to get my head wrapped around the LMHR phenotype. I’m skeptical of the level of ‘ASCVD resistance’ being hypothesized. But I’m a healthy skeptic so willing to be proven wrong. Nevertheless, initial observations and some questions: 10:30 - the result of ‘massive flux’ should still be a lower ApoB steady state. But maybe, just maybe, there’s a relative resistance to influx across the endothelial wall (whether between cells or through cells irrespectively) and enhanced efflux - problem in terms of plausibility not being so much the former as the latter (ie nothing about keto that is consistent with improved sub endothelial efflux - resistance to influx is more plausible to me, and maybe that’s all that’s necessary… Though I’m still skeptical that LMHR’s have “Teflon arteries“ Q1: What is the average “length of exposure”? Ie Subjects presumably we’re not on keto for life and therefore lifetime exposure to “stratospheric” levels of ApoB. ASCVD is a very slow process in terms of plaque progression (as opposed to plaque rupture). So far, what I believe is driving the extremely high ApoB is a combination of ultra high saturated fat intake resulting in hypersuppression of LDL particle receptor expression at surface of hepatocyte combined with supranormal dietary cholesterol intake. And the posit is that the endothelia arena is somehow resistant, net result anyway, to influx and potentiallysupranormal efflux. Whether keto is driving the slower progression towards detectable ASCVD w/ above average endothelial cell layer resistance to net LDL particle retention or if driven by genotype (eg I presume these subjects are largely more naturally lean vs lean as a result of keto, no?) and a resulting possibly very low inflammatory state is still in question or other factors, if this is real at all gentlemen because, with all due respect as you know, “great claims require great evidence“. And this level of claim is so great that we are nowhere near, in my professional opinion, the level of great evidence necessary to accept LMHR are “heroically” resistant to subendothelial ApoB particle accumulation. Were any correlations with hs-CRP, Lp-PLA2, MPO, IL-6, urine albumin/creatinine ratio sought?
Answer to question 1) 4.7 years. 2) I believe they would argue that saturated fat has very little to do with it, Sat fat perhaps explaining 5-10% of the effect, as they have some cases of extremely high ldl with quite low sat fat but very high mufa and pufa ldls of 500+. Look at Nick Norwitz' Oreo experiment, which was a demonstration of the lmhr model where he added a dozen Oreos a day (adding quite a bit more sat fat per day) but also adding more carbs which reversed the lmhr phenomenon and brought his ldl from I believe 500 down to the mid 100s. He also did a washout and comparison with a high strength statin and th le extra sat fat Oreos brought down his ldl more than Statin. He's the gentleman in the bottom on the presentation and you can find his presentation of the Oreo study online. Nick or the others can perhaps take up your questions where I can't or correct anything that I have gotten wrong.
Greetings back to you as well, @DrTomMD - "Starting to get my head wrapped around the LMHR phenotype" > Given your questions ahead, I'd love if you could visit the hub page for our published papers: CholesterolCode.com/papers -- it's a fantastic resource that also includes the video abstracts to better understand the Lipid Energy Model as well. - "Q1: What is the average “length of exposure”? Ie Subjects presumably we’re not on keto for life and therefore lifetime exposure to “stratospheric” levels of ApoB." > Please be sure to check out our PI's presentation on the prelim data here: ru-vid.com/video/%D0%B2%D0%B8%D0%B4%D0%B5%D0%BE-3ItQedMPnsY.html with abstract published here: linkinghub.elsevier.com/retrieve/pii/S0026049524000805 (full paper coming shortly) Avg LDL-C was 122 for Keto-CTA pre-keto, 272 for mean of 4.7 years after. Avg LDL-C for MiHeart was 123 to matched age of 55.5. So the back of the envelop delta for LDL-C exposure ("Cholesterol-years") is (272 - 123) * 4.7 = 700.3 mg/dL. Both populations would have 50.8 years at nearly the same LDL-C exposure before the keto group moved into the LMHR-like phenotype -- so a little over 5 decades before. - "ASCVD is a very slow process in terms of plaque progression (as opposed to plaque rupture). " > I reference Brown and Goldstein frequently in my presentations for this study, even before it began. It's been long considered the strongest indicator for high exposure resulting in extremely rapid plaque development to symptomatic ASCVD in just a few years. Most existing RCTS are < 4.7 years and are looking at changes that are far less than the 700.3 mg/dL delta mentioned above. This is why these data are extremely fascinating in light of the more simplistic consideration of the Lipid Hypothesis as context independent. (ie, any population, regardless of context, is higher risk if at higher levels of LDL/ApoB) "So far, what I believe is driving the extremely high ApoB is a combination of ultra high saturated fat intake resulting in hypersuppression of LDL particle receptor expression at surface of hepatocyte combined with supranormal dietary cholesterol intake. And the posit is that the endothelia arena is somehow resistant, net result anyway, to influx and potentiallysupranormal efflux. " --> I think you'll find our existing published meta-analysis as very compelling (www.sciencedirect.com/science/article/pii/S0002916524000091?via%3Dihub) . If high saturated fat alone drove the high LDL-C levels we see in LMHRs, we'd see it across body compositions, particularly those with higher BMI. Note these are 41 different RCTs that we could find where at least one arm was adopting LC/keto and the results are quite consistent. - "Whether keto is driving the slower progression towards detectable ASCVD w/ above average endothelial cell layer resistance to net LDL particle retention or if driven by genotype (eg I presume these subjects are largely more naturally lean vs lean as a result of keto, no?) and a resulting possibly very low inflammatory state is still in question or other factors, if this is real at all gentlemen because, with all due respect as you know, “great claims require great evidence“. And this level of claim is so great that we are nowhere near, in my professional opinion, the level of great evidence necessary to accept LMHR are “heroically” resistant to subendothelial ApoB particle accumulation." --> To be sure, we're not asserting LMHR are somehow immune from ASCVD -- in fact, I've quite literally speculated our cohort of average 55yr olds will likely show at least some population level increase in non-calc plaque (our longitudinal endpoint) -- but that's because I'm confident all populations of mostly male 55 year olds will develop ASCVD. In short, no population is immune, which is also why I stressed everyone work with their doctors for their individual context. With all this said, ours is the first prospective study on a population with extremely high LDL cholesterol that excludes those with molecular FH or any major risk factor for ASCVD - which is great as I think this provides us a scientific opportunity to better see the independent atherogenicity of LDL/ApoB at a population level in this group of people.
"Were any correlations with hs-CRP, Lp-PLA2, MPO, IL-6, urine albumin/creatinine ratio sought?" --> on this I cannot answer yet as I'm blinded to those data. But I believe those markers we do have will likely come forward in future papers. (Can't say more than that for reasons I'm sure you understand -- but feel free to reach out privately if interested in what our roadmap is atm)
Dave____ Time Stamp 50:37. Table 3. Thats great Match results for the Median of LMHR compared to Median of MiHeart. Great low Plaque volume in BOTH. Was'nt it reported that both cohorts at Median had CAC= 0. THUS when they are not proned to CHD, CVD you would expect great matching numbers. What happens when we get off the Median. Looking at both cohorts when they have concerning levels of CAC. How well do both cohorts compare then. Which group then will have the most soft plaque. Developed from their respective Diets.
In the cholesterol-lowering medications group, there were similar results of the non-calcified plaque. I thought that one of the statin's protective mechanisms was calcifying the plaque, so why was there any soft plaque?
Am I missing SOMETHING. At minute 55:35 we are comparing n=54 subjects. Apparently they these 54 have very little TPS plaque. But the earlier studies by Dave and Budoff on LMHR had n=80 subjects. With many many with TPS 40 to 80. A score of 50 is very serious!!! Why are we not Looking at these peoples. Guess theres 26 subjects of the n=80 thats Not Lucky with diet. Including LMHR peoples. What can these n=26 peoples with Lots Heart Plaque eat???? Do they need control Lipoproteins?
After thinking about this, I occurred to me that I don't know what these numbers represent. Are these data from a change in plaque over the year or is it simply a snapshot in time? If a snapshot, was it the preliminary blood draw or the one at the end of the 1 yr period?
This may have been stated before, but I'm noticing that most of the ppl with highest plaque are all on the left side of the graphs. (the lower end of the comparison markers.)
Ok, so basically other than glucose/insulin/A1c we don’t have any idea what to measure in the laboratory to determine someone’s cardiovascular risk. Great 👍the more we learn, the more we learn we don’t know anything.
The data make total sense, since we know that you need inflamation, insulin resitance and or peroxidation for plagues to occure. It´s like banning air because of storms, you need conditions for air to be harmfull.
Non-calcified plaque is 46.4 and calcified plaque is 4.9 in MI Heart group. Av age of the group is 54.8 years. That means calcified plaque is roughly 10% of the non-calcified plaque. Only Calcified plaque could be detected in CAC score test, whereas major portion of the plaque is non-calcified type which could not be detected in CAC score test. Thought provoking data.
From what I see LDL seems so far to have no impact on risk for LMHRs. However, LDL IS associated nwith plaque score in the "normal" pop in this study. The idea that while waiting for answers, LMHRs that aren't obligated to be on keto might want to eat ~100g of carbs to normalise their LDL (instead of reducing saturated fat) therefore seems weird. to me. Once you eat the 100g of carbs, you fall out of the LMHR criteria and LDL is associated with plaque in the pop he would now be. At that point, when he is no longer a LMHR, shouldn't he also try to reduce saturated fat to further reduce his LDL? From what I understand saturated fat does have an impact on LDL when you aren't a LMHR (as in you now eat carbs). Even in Nick "Low carb Data distortion", the study that claim that keto shortens lifespan, Nick points out that having carbs
Because they were studying the effects of LDL on Plaque. I agree though. BP would be interesting to see and I suspect it to have a bigger effect as well.
@@matthiaspriester2368 why study something that is totally debunked? Even big data says that LDL correlation is too noisy. There is zero reason to study it. Also, when they say percentage correlation they should also disclose noise percentage. If signal to noise ratio is too low or confounding factors are not clear they we just need to discard crap studies. Medical is mafia and only way to stop it is when "insurance" or "govt" stops paying for chronic illness. Chronic illness is not an insurance. It is pension.
The Lipid Engergy Model is probably not correct. I believe that the large amount of cholesterol in LDL in LMHR is not from VLDL, but from chylomicron remnants. People on keto eat a large amount of fat, which means they use a lot of chylomicrons to transport the dietary fat from the intestine to the blood. After the triglycerides are removed from the chylomicrons, they are left with cholesterol and become chylomicron remnants. The remnants go back to the liver. The liver will use some of the chylomicron remnants to make VLDL, but most of them will be used to make de novo LDL. So the liver secretes a large number of LDL directly because there are so many chylomicron remnants. The liver secrets a small number of VLDL, which is consistent with low fasting triglycerides in LMHR. There are other evidences that suggest that LMHR are likely not making a lot of VLDL as proposed in the Lipid Engergy Model. In addition, LMHR do not need a lot of VLDL to supply triglycerides to the muscles because chylomicrons have already delivered triglycerides from the meals to the muscles. The triglycerides from the meals are stored in intramuscular lipid droplets, which can be used later when the person is not eating. Further, LDL receptors in LMHR are down-regulated due to lower thyroid hormones. So a combination of increased de novo LDL secretion from so many chylomicron remnants and less uptake of LDL result in high LDL in the blood. Lastly, high HDL in LMHR is also not difficult to explain. HDL usually correlates with LDL (excluding people who have insulin resistance). Because when there's so much cholesterol in the system, you need a lot of HDL to do reverse cholesterol transport (RCT). Conversely, when LDL is not high, you just don't need that much HDL to do RCT. Therefore, high HDL in LHMR is not a marker of health, but rather that there’s too much cholesterol in the system.
Here's a question: what's the half-life of a chylomicron remn... how about for LDL? And what if you parsed ApoB48vsApoB100... what would you expect in an LMHR?
Interesting. But I think that for practical purposes if the total plaque volume doesn’t correlate with ldl (subject to final publication and others studies) then I’m not sure if the theory behind this phenomenon matters to the average person who fits this profile? Would love to know if others disagree? But it is an interesting academic question!
Why not look at the plaque versus age of participant? Of the LMHR, how about age before beginning keto diet? I would expect that to show a correlation.
@@nicknorwitzPhDObserving plaque progression would be revealing. The CAC and AI-CCTA are points in time but who knows when those plaques formed. Are they increasing or being cleared? Over time the CAC scores appear to increase, sometimes significantly with statins. But what about non-calcified plaque? Would it be cleared by the body before calcification? Are we preempting clearance by calcifying it?
P-value: The p-value is a measure of how likely it is that the results of a study happened by chance. It ranges from 0 to 1. A smaller p-value (typically less than 0.05) suggests that the results are less likely to be due to random chance. In simple terms: If p < 0.05: We say the result is "statistically significant." This means we're pretty confident the result isn't just a fluke. If p > 0.05: We can't be sure if the result is real or just happened by chance. Think of it like this: If you flip a coin 10 times and get heads 9 times, the p-value would tell you how likely it is that this happened by chance with a fair coin. R-value (correlation coefficient): The r-value measures how strongly two variables are related to each other. It ranges from -1 to +1. The closer r is to -1 or +1, the stronger the relationship. In simple terms: r = 1: Perfect positive relationship (as one goes up, the other goes up) r = -1: Perfect negative relationship (as one goes up, the other goes down) r = 0: No relationship Think of it like this: If you plotted two variables on a graph, the r-value tells you how closely the points follow a straight line. r close to 1: Points form a clear upward line r close to -1: Points form a clear downward line r close to 0: Points are scattered with no clear pattern In the context of this study, low r-values (close to 0) suggest that there isn't a strong relationship between the variables being studied (like LDL levels and plaque in arteries). The p-values help determine if these weak relationships are statistically significant or just due to chance.
51:20. You saying half a dacade like it's a long time for plaque build up. It can take decades. Plus LMHR are very health conscious, probably more exercise, less bad habits, less processed food. The fact that they are no better than the normal population it's what bothers me. I don't want to be at a 'no great risk that normal population', I want to see protective, reversal, better than the average population that is full of HD. You can have fun speculating but his has 0 value right now.
Your desire for things that lower ASCVD risk is valid, but assuming that something has 0 value because it doesn't lower risk is fallacious. You're missing the biggest point of this simply because it's not satisfying what you're personally looking for. The current narrative is that LDL is an independent risk factor for ASCVD - the higher the dose (cholesterol-years), the higher the rate of plaque progression. Studies like these are effectively providing counter-arguments to that narrative, which, although may not impress or be of value to you personally, is a MASSIVE finding that, along with more studies, improves our understanding of ASCVD and helps us prevent/treat it. People are finding life-changing benefits to keto diets, but are scared when they find their LDL goes up because they fear that it necessarily increases their ASCVD risk. They are perceiving a trade off between keto benefits and **increased** risk of ASCVD. Many people would be much, much more comfortable with keto if it was shown that there is little to no **increased** risk. These people are looking for relief from the chronic, debilitating physical and mental conditions they suffer from and desire that more than decreasing ASCVD risk.
@@saintwithatie I'm not sure where keto might be the only solution for some people. I've seen people heal on both sides, low fat and high fat. It's quick results, i'll give you that, but to potentially sacrifice long term health for something that could be fixed in other ways, it's a personal choice I guess. I did short term keto some years ago to fix my depression, it helped a lot, kinda change from depression to anger and with prolonged fasting also lost some serious weight but I slowly went off it and focused on longevity and the benefits remained. I've seen most people even in the group that think that being LMHR makes them immune and the authors don't do a good job warning people and they create a lot of hype. Especially Nick.
@@thehappyfellow5500 I'm glad you got relief from your depression! Mental conditions can be absolutely brutal. You're right that there are many avenues to health - there are conditions that can be satisfactorily treated with numerous treatments besides keto. When it comes to assesing actual risk of developing diseases, the thing to remember is to not get too fixated on a single or a few biomarkers and the statistics surrounding them. Biomarker statistics are merely one out of several tools used in the scientific process. Also, I'm sure we probably haven't seen the exact same videos of Nick's, but I disagree that Nick did a bad job of being nuanced and transparent. He's said over and over and over and over again what his positions are and what he limitations of his studies are. He spent so much time clarifying this on Simon Hill's podcast that commenters complained that too much of the episode was him being defensive. I also disagree that most commenters got the takeaway that LMHR are immune. If they did, then that was not due to a poor job of communicating on Nick's part, but due to confirmation bias, simple misunderstanding, a lack of intellect, or even intentional misrepresentation.
@@saintwithatie I'm not talking about this video but the channel as a whole. Most watch the short videos, and not the podcasts where he is not being as enthusiastic. Not very many of his videos have the same curb of enthusiasm but presents as fixed science and you can see it in the comments what people get from it. Dangers are almost never presented. The nuances Nick presents are also often shallow. Case and point: the video "The cause of High Cholesterol Matters". He presents this problem of 2 people in their 20s, we edit ones genes to have high cholesterol and another just get high cholesterol from diet. All else being equal. He then shows a graph where people with the same amount of cholesterol get CVD sooner if they have a genetic mutation that raises LDL. He uses this example to answer the question: do the guys in their 20s get CVD at the same time - implied answer: NO. Well he completely fails to comprehend the time of exposure. Of course in the presented graph those with a genetic mutation get CVD sooner because THEY HAVE HIGH LDL FROM INFANCY. A fact that Nicky completely ignored and thus presents a false dichotomy when presenting his example.
@@thehappyfellow5500 You have a fair point when referring to the short-form content. The problem is that short-form content creators have to play the time/attention game - there's just not enough time/attention to make completely nuanced takes in short-form content. You have to make a choice, and the ultimate goal is to funnel people from the short form video to the longer form videos for the entire nuance. The exposure time issue you mentioned is something that Nick has addressed in a few places (forgive me for not having videos and timestamps to back up this assertion, but please trust me that he has.) I keep seeing criticism like yours - that he doesn't talk about the dangers enough. It seems like what you guys want is for him to explicitly say "High LDL is dangerous" before everything he says. If so, that's unreasonable - he's stated numerous times that LDL is an ASCVD risk factor and that for many individuals higher LDL increases risk. He's even stated that he feels that keto may be contraindicated for certain individuals due to them already having high LDL or plaque without them having even started keto. He doesn't need to and doesn't have time to say this in every video. It's okay for him to just assume we're all on the same page with LDL being a risk factor and just move forward with asking questions of how the risk is modulated by other factors such as the cause of the "elevated" LDL. Additionally, his specific hypothesis, which he's clarified and emphasized as a hypothesis over and over again, is that LMHR have lower - not 0, but **LOWER** - ASCVD risk than other populations with similar LDL exposure. People keep insisting that he says or infers the risk for LMHR is 0 (aka, LMHR are immune), but he has NEVER said any such thing. Nick cannot make this any clearer. He has done his due diligence to explain this but, as I said before, people are hellbent on not listening to what he is actually saying and instead bringing up a bunch of stuff other idiots have said and holding him to unreasonable standards.
You folks jumped the gun on this one. Just 4 hours after you posted this Layne Norton declared that “the cholesterol hypothesis really isn’t a hypothesis anymore” based on the settled science. If only you had known you wouldn’t have spent so much time on this video explanation.
CAC of 0 is the best we have currently, outside of the CCTA dave is doing. Here's the current knowledge on CAC of 0: Very low risk: A CAC score of 0 indicates a very low risk of cardiovascular events (heart attack, stroke, or cardiovascular death) for the next 5-10 years. Better than risk calculators: A score of 0 can reclassify many patients who were considered "intermediate risk" by traditional risk calculators to "low risk." No benefit from statins: For patients with a CAC score of 0, studies showed no benefit from statin therapy over a 12-year follow-up period. The number needed to treat was "infinity," meaning there was no detectable benefit.
the mi heart cohort is overweight and the keto group is not.... seems not a good comparison.... Just by doing keto they are likely to be more health conscious.
None of these individuals have any credentials in lipidology. If their work was critiqued by some of the leading lipidologists, like Dr. Cromwell and Dr. Sniderman, we would likely find out about flaws in their methodology.
Nope. They tried to match the cohort. There is a slight difference in the BMI 22.5 (± 2.7) and 25.8 (± 3.6) for the LMHR and MiHeart cohort, respectively. I agree, it is not perfect, but no study ever will be. However it is not a huge difference. Also, they did a discussion with Bill Cromwell and he gave his thoughts to that matter. Matt Budoff is a researcher in Cardiology/Lipidology, so I would say there is some credentials there.
@@matthiaspriester2368 not a signficant difference? One is medically overweight and one isnt. the standard deviation puts many more participants in the mh cohort into overweight category.
