Yeah, the biggest issue I have with the entire medical field (coming from the perspective of a software engineer who's worked on large scale systems) is their propensity to try and derive mechanism from statistical analysis. Any of us engineers who've worked on large scale systems use statistical analysis to derive hypothesis for potential mechanisms, but we *never* view data teased out statistically as deterministic of mechanism. The medical field assigns causality to a single measurement in ways that are unquestionably unscientific and without sound basis. Make no mistake, if you assign causality to an element you are making a statement about the mechanics of the system. Deriving mechanism from statistical analysis is to put it frankly, asinine.
Totally agree. Statistics is just statistics. It may show correlation, and that in itself may be of some use (e.g. for public policies, trends etc.), but it is far from showing causation. For that you also need a mechnism that explains HOW a certain feature DRIVES a certain outcome.
@@NimrodGilAd to be fair, Nick seems to mostly agree with this, and I personally *want* to have low apob, because it does have a correlation, but if I don't have a low apob, I have seen zero evidence that the apob measurement by itself means that I have a problem. If all my other labs are absolutely perfect, I have zero reason to believe that the apob teat is correlating with disease in my case (clearly it does correlate with disease in many cases).
@@homomorphic I share your frustration - regarding the lack of refined data in these studies mentioned (most of them conclude "further research is needed"). But, the type of broad statistical study quoted is not what was used in determining the mechanistic drivers & processes of ASCVD. There's over 100 years of research. It's the totality of animal studies, metabolic ward studies, genetics, lab tracer studies, pharmacological studies, nutritional research & so on with the epidemiological studies that lead to the consensus that a high concentration of LDL particles (ApoB) over years of exposure is causal, necessary & sufficient in the development of ASCVD. And the totality of these studies DO find on average that the lowering of ApoB / LDL particles significantly reduces the risk of ASCVD deaths AND all cause mortality.
@@kazoz3520 while pointing to one factor as causal is a statement *about* mechanism. It isn't a mechanism. What is the exact mechanism of action? Surely after 100 years of statistical analysis this would be known (if statistical analysis could lead to understanding of mechanism which it can't, which is why you can't explain the precise mechanism). We have insights that apob is involved in the mechanism, but stating that it is *solely* causal in arterial disease, is to make an absolutely fraudulent statement that can not be backed by any evidence at all. To reiterate how science works, it goes like this: 1. Ask a question (thats done: "what causes arterial disease") 2. Do background research to provide the necessary material to develop a hypothesis about mechanism (this is where we've been for the last 80 years) 3. Construct a hypothesis of mechanism (many of these exist) 4. Test the hypothesis with tests deaigned to establish the hypothetical mechanism is viable (which means that not a single test can show the hypothetical mechanism is not a viable mechanism) - note here that in a complex system there can be multiple mechanisms of action. 5. Test the test to ensure that the test itself isn't flawed and producing bad data (this is where medical research falls down badly with far too high a frequency) 6. Once the test has been established as producing good data, then analyze that data and rule in or out the hypothetical mechanism (this is where the medical field is widely engaged in fraud, because step 5 was not properly done so the data being analyzed is just meaningless statistical data because either the hypothesis has been ruled out in which case the process is *over* for the current hypothesis, or the test Itself is demonstrably invalid)
Very well put. Causality implies the mechanism and the role something plays, and one only might need to add a primary driver to finish the topic. Keeping in mind of course the many things that might also cause the issue at hand.
I acutally love that you are differing slightly in your opinions. That makes the research-context more healthy :-D . With regard to the statistical adjustments used, I think many people (I don't think Nick and William are included here) do not realise, what assumptions go into them and that it less a question of if they are violated but more so how bad the effects of a violation are.
I might be wrong here, but I think that 99% of all statistics on LDL, ApoB and whatever, is done on populations where refined carbs are as natural as breathing. Once your HBA1c starts creeping up then, I believe, should you worry about lipoprotein and cholesterol. Or you could just work on lowering HBA1c? This is what I hope (and think) the LMHR study will end up showing.
"is done on populations where refined carbs are as natural as breathing." That is something that Dr Ken Berry points out about blood test ranges and also blood pressure numbers. I went to see a GP who has an interest in low carb and he ordered a fasting insulin test; no other doctor had requested this. I had been low carb for about 14 months at the time. The test says that it should be under 10. Mine was 7. He said he likes it to be between 2 and 5. My next test was 5; I was over the moon! I also agree with @stevemc2626 who mentioned seed oils.
There's something no one talks about. You sort of stumbled on it. When blood sugars creep up on a1c, it does affect lipids...this is called the synergistic effect. It's like adding ammonia and bleech together....by themselves they are stable. The synergistic effect of different foods can lead to mitochondrial dysfunction. The foods I'm referring to are carbs and simple sugar combined synergistically with different foods creates a BOMB....metabolic syndrome.
I love love that you and Nick are really shedding new light on Cholesterol and lipoproteins. Dave, you are correct to pause and reflect on statistical methods used to model something.. this can be so problematic across so many areas of science. Keep pausing and reflecting. An observation I would like to make is that using isolated particles or molecules as measures/biomarkers/causes of mortality all cause or heart disease is super problematic in the absence of systemic view of the roles these particles play. C27H46O is a molecule of mammalian life that has so so so many roles in our bodies that it is extremely difficult to tease things apart. You know all these roles very well, I'm sure as they stretch from repair, to building blocks for cell membranes, to precursors for much of our hormones, to the essential building block of Vit D. If we then look at Lipoproteins it is even more amazing since they themselves have complex functions with in our bodies as carriers essential to enabling everything. ApoB is a marker on the lipoprotein that allows it to be recognized by cells in the body that want something from the lipoprotein carrier. What is missing in this type of analysis is an appreciation of how lipoproteins rise and fall for so many reasons it is hard to even keep track of them. This is like trying to hit a moving target in a system so complex that it rivals our own galaxy. I wish you guys would take a step back and follow the path of Dr. Nadir Ali (Cardiologist) who spends so much time teasing out the actual functions and behavior of these essential molecules of life, rather than constant analysis of associative or correlative relationships with Disease X. Take a step back look at the bigger picture and that will provide the important answers we are all seeking. THe body makes all these molecules for a reason. There is no way that they are causal. Insulin does damage to the human body when in excess, but ultimately it is not causal. The root cause is something else. Nick takes about ApoB in a causal chain.. and already I know that he has lost sight of human evolution and is now following the path of allopathic medicine which cannot ever see the big picture.
Points we can agree on being the use of LDLc & APOB as bio makers of metabolic dis-regulation. However the more I look at it, the more LDLc and APOB look like markers not drivers. Very low LDL,and it seems APOB, associates with higher ACM until other cofounders are accounted for. In an earlier study low serum albumin (marking clinical malnutrition) needed to be factored to quench the rapidly increase in mortality as LDL was lowered. Consist with your lipid energy model, interrupting LDL metabolism will result in increased ACM through clinical malnutrition unless energy transport can be supported by other pathways!
"Points we can agree on being the use of LDLc & APOB as bio makers of metabolic dis-regulation." High LDL-C/ApoB can have various causes. The most important one in the general population is mitochondrial dysfunction. If mitochondria is unable to burn all the substrate for energy it will convert AcetylCoa into the citrate and push it out into the cytosol (via the citrate shuttle). In order to get rid of this AcetylCoa the cell will convert it either into fatty acids / triglycerides or it will convert AcetylCoa into HMGCoa and down all the way to cholesterol. If this happens in the liver, both TG and cholesterol will get released into the blood stream (to prevent accumulation and damage to the hepatocytes) in a (V)LDL particle. This is exactly what happens in the so called "atherogenic dyslipidaemia". But it is just a consequence of dysfunctional mitochondria and that is caused by chronically elevated insulin. AND chronically elevated insulin is the primary cause of atherosclerosis, not cholesterol/LDL/ApoB !!!
I listened very carefully and although he talked about MVX score as a measure of the overall risk, they did not use that to adjust the apob graph, they used undefined "nutritional factors" so the graph is next to USELESS, without these nutritional factors being explained, which he completed failed to do so. At the least the apob graph was based on real data and not some "mythical" nutritional model. By describing apob as a "peddle" he is causes me to dismiss it as a major risk factor, even if it is accepted as such. As Dave mentioned it goes back to the terminology I know about of pattern A and pattern B LDL . Too much pattern B, remnants, is the bad sign., mainly pattern A and hence high HDL and low triglycerides is good . I will stick with this.
Dave thank you for speaking at a moderate pace - I’m no expert so it takes a moment or two to follow some of Nick’ s points but then I find I’ve been run over by the next flood of expert knowledge
@vickilahtinen7254 When I listen to Nick's videos, I usually slow the playback speed so I can understand him. Even then I must regularly pause. Nick talks so fast that when playback is slowed, he just slurs his words and sounds drunk - haha!
Meh. Over many, many years and studies, particle counts, rather than mass concentrations, have proved to have little predictive power. Numerous studies have assessed particle counts for at least the last 20 years or so, since the advent of NMR based testing by LipoSciences (now LabCorp), (and further by Quest (Cleveland heart Lab), ARUP, and Mayo Clinic. The lack of evidence is so bad that these tests are no longer covered by insurance due to lack of clinical utility. (And all the listed labs would love to get coverage back, but alas, clinical utility is yet to be proved). Move on to Lp(a). And I forgot to mention James Otvos (LipoSciences / LabCorp), who has been the person working so very hard to prove this case over decades. Ironic that a recent study of his is mentioned, added to the mountain of net equivocal results over the years.
I love the nuance and think it's good for the nerds to discuss and go back and fourth. The mainstream needs to do the high level changes. Everyone here already know. Love you dave. You were part of my journey to consider the information and then do you own research.
If I understand you correctly, it's the remnants that add the predictive power to ApoB. Which would mean that: Remnants > ApoB > LDL-C So why is everyone still going on about ApoB? I guess it would challenge the lipid hypothesis.
I’m so confused on all this. I just got my blood work and my APOB is 212 and apolipoprotein B is 250. My LDL is 307. Trigs 125 and HDL 66. I don’t know what this APOA 1 is but says it’s 174. A1C went down from 5.8 to 5.6 and I’ve been a dirty carnivore for 6 months now. CAC was a 7 and I’m almost 57 and was a light smoker.
@@laurengianna9944 Hi, I am confused too, but I think your APOB and apolipoprotein B should be the same number , not different numbers. APOA 1 sounds like apolipoproteinA, but I would ask about that. Your APOB and LDL-C seem very high to me, though I am not a physician. If it were me, I would seek a knowledgeable cardiologist or lipidologist. Best of luck.
Hi Dave. Very interesting. Totally agree re lack of confidence in statistical adjustments. May I please ask, how does this new metric perform against fasting TG:HDL ratio as a predictor of CV risk? Isn't that already known to be a strong predictor from Dr David Diamond's work so wouldn't it be interesting to see how they compare?
Outside of biological indications, you & Nick are modeling how to have a discussion, differing beliefs (nuanced or not), ect. without "gunning" for each other
Dave thanks for this - I was previously struggling to understand your concern on statistical treatments in the Simon Hill's podcast but you struck a chord with me as I too am very suspicious of statistical removal of effects. I (sorry to say) have been very skeptical of the general quality of statistics applied in the biomedical field other than the amazing work of Emeritus Professor Frank E Harrell. There can be any multitude of hidden explanations that one is only subtracting "on average" and giving the appearance of causality. My personal criteria for causality is a much higher one (1) an proposed physical/biochemical mechanism (2) separate measurement of the components of the mechanism (3) isolation of the effect. It seems like that next project for your LMHR cohort is taking shape!
Nice - I love Nick's video's, and I love both of your hedges and nuances. I'm still surprised when you guys differ on anything. In this case, I'm much more with you. Keep up the good work - stay skeptical! BTW, my.. layman's nuance.. informs me that LDL cholesterol is necessary for human metabolism. There must be some other underlying thing that might make it harmful, or an indicator for something harmful. So the Jshaped curve for ApoB makes sense. But I've also kept in mind the remnants, and was pleasantly surprised when you brought it up again. I'd like to see the all-cause (ahem - metabolically caused) deaths vs ApoB remnants. If we can establish that this is actual thing we are looking for, then we can focus on its causes and interventions related to those.
I will attempt to mechanistically explain how someone becomes metabolically unhealthy, and how you can potentially reverse this phenomenon; and how the abnormal markers fit into this model....... As a response to each meal, the body produces insulin. Insulin's main job is to store. Glucose, the breakdown products of carbohydrates, enter predominantly liver, where under the influence of enzymes that are activated by insulin, most of it eventually gets converted into triglycerides (the fat storage form related to energy). The liver packages some of these triglycerides in ApoB particles, which take it to peripheral adipose tissue mediated by the surface enzyme lipoprotein lipase. These ApoB - VLDL has a lot of triglycerides and some cholesterol (fats with other functions - like for repair, enzymes function, structure of cell membranes etc). Over time, fat accumulates in your liver and your peripheral adipose tissue, and the body produces more and more insulin to push in the same amount of glucose into liver cells. This is a crude definition for insulin resistance. The fat accumulation in the adipose tissue makes it much less receptive to the triglycerides being delivered by the ApoB particles as well. This will lead to accumulation of triglycerides and lipoprotein particles in the blood stream as well. This also triggers another protein (CETP) which alters the content of your lipoproteins (exchanges the triglyceride in the ApoB particles for cholesterol from other ApoB or HDL particles) Certain genetic and lifestyle factors and significantly increase the rate at which this happens. High fructose, processed food can cause mitochondrial and behavioral changes which can increase the rate at which this develops. A higher carbohydrate diet, increased frequency of meals and a short fasting period can all keep the insulin switch turned on (the metabolic enzymes in your body either work to store, or in reverse to use what you have stored.....it takes about 12-16 hrs without an insulin spike for you to start utilizing the energy that you store in your fat cells). A sedentary lifestyle reduces the amount of energy you use. A higher calorie intake in the presence of insulin may worsen the accumulation. And seed oils may reduce the amount of absorption of dietary cholesterol and induce inflammation. Accumulation of fat in your liver -> fatty liver Persistence of lipoproteins and inefficient delivery of triglycerides -> Dyslipidemia When hyperinsulinemia cannot deal with glucose load -> diabetes Hyperinsulinemia also has other effects, like holding on to water and salt in the kidneys, cause endothelial dysfunction etc which can lead to hypertension Hyperinsulinemia is also associated with an inflammatory environment which can induce vessel damage, atherosclerosis etc. To put in the biomarkers, you will see an increase in triglycerides and a decrease in HDL-c (cholesterol concentration in HDL particles). There may or maynot be an increase in LDL-c (cholesterol concentration), but there is an increase in LDL-p (LDL particle number). ApoB includes VLDL,IDL and LDL particles (mostly LDL; the rest are together categorized as remnants - they are triglyceride rich). A high ApoB remnant is a good indicator of a lot of undelivered triglycerides and thus a good indicator of this underlying metabolic state
Now, when you through lifestyle measures reverse this process (exercise, fasting, low carbohydrate intake), you notice that as your weight reduces (body fat maybe a better factor to corelate with than just BMI @Dave Feldman ) you notice a reduction in triglycerides, an increase in HDL and an increase in LDL-c and an increase in LDL-p (ApoB particles as well), but a reduction in remnants.
Hope it makes some sense, and has given some perspective for further reading. This is a combination of the lipid energy model and the carbohydrate insulin model. Maybe you can do your own research into these.
Hey Elias I just want to thank you from the bottom of my heart. You did amazing summary and help me understand much better metabolism function. Appreciate your effort and time. 🙏
Key insights 🧠 Appo B is a marker of LDL particle number, which is better than LDL cholesterol for cardiovascular risk assessment. 📊 Metabolic vulnerability, including malnutrition and inflammation, is the primary predictor of all cause mortality, overshadowing factors like cholesterol and age. 📊 The association between ApoB and all-cause mortality shows a j-shaped curve, indicating that very low levels of ApoB may lead to higher mortality. 📊 Lower ApoB continues to associate with lower all cause mortality, highlighting the importance of metabolic vulnerability in individual therapy. 📊 Metabolic poor health tends to increase remnants, leading to a much greater association with cardiovascular disease mortality. 🧬 The physiological patterns and signatures inform us about metabolism and are important to overall health.
Thanks for the continued updates on LMHR research. Is there a marker for remnants? Or a simple way to determine remnants from apob and ldl...to calculate the Delta?
It still doesn't mean that Apo b is the reason for the increased mortality. Correlation versus causation. Markers are NOT causes! It also matters in which population the markers were determined. Who was included and how many people were included in the determination of this vulnerability index and who was included?
Nick's standard of proof is a reasonable preponderance of the evidence, which he states up front may be provocative. Nothing wrong with that. Then Dave criticizes what Nick says as not being a causative inference, although it may be (by luck), so he's not disagreeing with it (i.e. sayin' the opposite). Thus Dave makes a strawman error compounded by a non-sequitur fallacy (the Remnant example). Podcasting of all sorts is freewheeling entertainment, not calculating from formulas or structuring a study. A podcast criticizing another podcast is like shooting ducks in a barrel, as is commenting on a podcast. The simplest takeaway is that small HDL (SHDL-P) may be more important than realized - but more study is needed because it's more complex than just that. While waiting for causation, eat meat, butter, and eggs, and nothing else.
What is missing is the lipid fraction score of individual partical numbers, sizes and the apoB particle number in light of fasted versus nonfasted lipid profile to look at the reverse cholesterol synthesis that should be very apparent in a good metabolic system that shows a decrease in TG and increase in HdL in the fasted state. One more interesting observation: high cholesterol falsely raises A1C. With high cholesterol the A1C will be much higher than the actual A1c. I found this to be true as I looked at my continual glucose monitor 3 month average that was significantly lower than the calculated average glucose from the reported A1c.
I believe the LMHR is irrelevant in this discussion since at no point is any measure used for MVX or whatever that fictional measure is called or used in the cohort studies (poor quality) that Nick referred to originally that would be utility to LMHR. LMHR were not identified in these studies, now perhaps if you received the data you could hypothesise certain people with the triad but does LMHR numbers appear without being low carb? if so this would be a largely pointless attempt. As a minor counter the study posted by Dr Tro on X about a month back demonstrating similar studies to what Nick referenced that indicated LDL status (low) had as much impact as VLDL status.(high).
After listening and watching hundreds of hours of videos and reading some of the studies and theories on CVD. I am convinced that atherosclerosis is the body trying to repair itself from arterial injury. There are tons of risk factors however it seems around 80%:are related to metabolic disorder. Discounting things like heavy metal poisoning, mold toxicity, nicotine, sickle cell anemia, etc. the majority risk factors are metabolic. There are also genetic risk factors the most troubling one that is used to support the lipid hypothesis is the type of hyper familial Dis lipidemia that is associated with very early CVD and death at a young age.. The main question that should be asked about that are how are the arteries being damaged ? The lipid theory is saying by ABO B. I don’t know much k about it but have heard that diabetes isn’t involved. If so how was that determined? Did they not have high blood glucose and high insulin levels? along with insulin resistance? Because those things are clearly implicated in CVD for metabolic disfunction along with the issuing inflammation,. Dr. Ford Brewer along with others are saying inflammation is damaging the artery walls due to extremely high insulin levels and glucose levels. Is the high insulin and glucose levels damaging the glycocalix? A messes up glucokalix can increase blood pressure. Another risk factor. Which in turn is causing inflammation of the endothelium? Is this mechanism causing the prtoglycans to proliferate which is causing the LDL to infiltrate the endothelium? I believe so and of course the ABOB molecule is involved as part of the repair mechanism. Clearly smooth muscle cells start to cover the inflamed area and build up of LDL. Maybe the remnant particles of LDL are what is left over from the LDL dropping off the cholesterol for the repair, Also you see fibrogen activated to help cover the damaged area. Lots of questions remain. Why is the damage in certain areas? It seems turbulent areas near artery junctions. Why are statins helpful if high LDL isn’t the cause?> 1. Statins are pleotropic they are an anti inflammatory and fibrogenic and help reduce the inflammation which may help more than the lowering of LDL which increases to help fix the artery damage.. Dave please look at Dr Roy Taylor’s research on diabetes. He has a fat tolerance model for diabetes. He wondered why thin people are getting type 2 diabetes. He concluded that they have visceral fat causing insulin resistance. He called these thinner people with fatty livers and pancreas TOFI. Thin outside fat inside. He suggests that people have different fat tolerance levels some can have more adipose fat and no visceral fat and some can have more visceral fat and less adipose fat. He put the TOFI subjects on a vigors diet when they loss their visceral fat their insulin resistance was reversed along with their type 2 diabetes. I think I am. TOFI and not a lean mass hyper responder, However when I went on a low carb diet my LDL shot up quite a bit much to my doctors dismay. However after a short time and losing some visceral fat all of my of methabolic markers improved. One exception was my HA1c which went up slightly. I am taking stains and niacin both can raise blood glucose and cause diabetes. . I am working on getting that below 5.6. With diet and exercise, I am trying to put on muscle mass which I lost for a period of time by being on a high dose of Lipitor. I since switched to a low dose Crestor which has better anti inflammatory properties. All of you please keep up the interchange of ideas and keep this dialog moving along and forward. As someone with skin in the game I really appreciate,all of the research and discussion happening lately. Thank you .
I’m so confused Dave 😢. CAC a 7 CIMT showed no blockage. Trigs went from 116-125 HDL 66, then did NMR and apoB is 212 and the apolipoprotein B is 250. Lipoprotein a is 12. I don’t know the difference between the two B ones 🤷🏼♀️.
This is my hypothesis. The LDL particle becomes modified/atherogenic when it stays in circulation for a longer period than it is supposed to. In Familial hypercholesterolemia, there is a defective LDL receptor. So the increased LDL level is due to the individual LDL particle persisting inside the circulation for a longer time. In the case of a lean mass hyper responder, there is increased production of LDL, leading to increased LDL levels in blood. But this LDL particle is cleared off within the same time as that of a normal person. In other words, the time for which an individual LDL particle stays in circulation is the same as that of a normal person. The longer the individual LDL particle stays in circulation it is more and more subjected to the forces of entropy, and structural modifications can happen to the particle which makes it atherogenic or inflammatory. Leading to plaque formation.
LPa is missing from this discussion . As a subset of LDL contributing 30% of the host level to LDL it needs to be considered separately. Treatment with stains typically raise levels by an average of 11% and can be as high as 50% Therefore it is a separate
I have high ldl-c and have been reading a lot of medical papers etc, and studies have shown apo(a) in plaque at levels that show it's at least the 30% you say. And LP(a) at least has a mechanism to be there that makes biological, logical, and scientific sense, supported by medical studies.
Nick, I am a physics guy. I am a LMHR. Nick I am hearing only chemistry here. Have you knowledge of magnetism, Body DC electrics, BioQuantum phenomena driving the protein opening folding and electron hydrogen ion tunneling? Have you looked into it? I have. As a researcher of semiconductors I am fascinated how nature has all these figured out billoins of years ago on planet earth under our sun. But the bulk of us are more like spaced out in our hubris. Water and solar radiation is not what you might expect. So the entire biology falls apart until you build it back from scratch. Hmm. Maby in twenty years more will follow. I trust the sub atomic since all the biology and chemstry they let you learn is subordinat to it. We the mitochodriacs or biohackers or what ever one might want to call us can not be concidered as the populus. Statistics aside. After all we are the LMHRs. The healthiest bunch of them all???? time will tell.
Dave thank you for all of your work. We have one important question. With the evidence of your studies and trials, is their any information at all of any reduced atherosclerosis or plaque for those LMHR with higher LDL, HDL and lower TG while on a low carbohydrate diet? In other words I know y’all have looked at this just as the low fat diets have these study outcomes. If you can not tell us now then please just say you can not say now.
I think the assumption that lowering ApoB will hold metabolic vulnerability constant is a big assumption. Statins do all sorts of things to metabolism, not all of them good. Maybe PCSK9 inhibitors are more benign, but they're new and expensive enough that we don't have excellent data on long-term effects. If you can snap your fingers and do magic, why not directly magic up a 300 year healthspan? Other than magic, if you remove ApoB from somebody's blood, you have to deal with the causal impacts of the way you did it, and they'll probably affect metabolism.
The body is an amazing organ and is constantly trying to regain homeostasis. Change one thing, whether by diet or drug, causes a domino effect of changes in the body to get back to the norm. Just my personal opinion.
9:31 "If you subtract LDL from ApoB and look just at remnants. That has a much stronger Association by far... towards both All Cause Mortality [ACM] and cardiovascular disease [CVD] mortality."
And there in lies how we got here to begin with. Trust of others to figure it out for us resulted in the big farma medical machine we have today. I do understand that it is tough to follow all of it but we have to because in the end we have to make our own decisions. In a nut shell. Here is what I thought I heard in laymen’s terms. We have proven the “LDL is evil model” and statins are the answer is a fallacy. So we are investigating the unknowns. key pieces are starting to emerge. 1) Metabolic health trumps all in terms of impact. By a 3x more important than age and a margin of something like 30x more important than any cholesterol or POB marker. 2) That said APOB is a better indicator than LDL cholesterol as a predictor of all cause mortality. (APOB is a protein found on the low density lipoproteins including LDL, triglycerides and remnants.) 3) Remnants are oxidized LDL that is like trash that floats through your system. Sugar in your blood glycates the lipoprotein and causes it to stop interacting with the body as it is supposed too. so it can’t be removed and floats around like trash piling up and causing issues in the body.
Been low carb/keto/carnivore for last 3 months. I lost 23 lbs in 3 months but now I have 314 total cholesterol 87 triglycerides. I’m not below 70 triglycerides so not sure if I could be close to LMHR or what? I feel great, no more soreness/inflammation, no longer tired and I think much clearer. So wish I knew how to find out if I’m in danger of Atherosclerosis?
I’m so confused 🫤 last Sep. my ApoB was 198 and my remnant cholesterol was 1. Last month my ApoB down to 168, but remnant cholesterol go up to 16. Which one is better🧐I assume l am LMHR. BMI 19, hdl 105, triglycerides 49, HS CRP
What are your thoughts re Dr Thomas Dayspring’s fascinating ApoB / Cholesterol “tutorial” on Simon’s channel last week? He seems a highly experienced, knowledgeable & esteemed Lipidologist. But has he got particular biases / agenda?
We need more engineers like Dave studying physiology. The human body is a system. We will never get at the root of health by looking at biomarkers.
Yeah, the biggest issue I have with the entire medical field (coming from the perspective of a software engineer who's worked on large scale systems) is their propensity to try and derive mechanism from statistical analysis. Any of us engineers who've worked on large scale systems use statistical analysis to derive hypothesis for potential mechanisms, but we *never* view data teased out statistically as deterministic of mechanism.
The medical field assigns causality to a single measurement in ways that are unquestionably unscientific and without sound basis. Make no mistake, if you assign causality to an element you are making a statement about the mechanics of the system.
Deriving mechanism from statistical analysis is to put it frankly, asinine.
Totally agree. Statistics is just statistics. It may show correlation, and that in itself may be of some use (e.g. for public policies, trends etc.), but it is far from showing causation. For that you also need a mechnism that explains HOW a certain feature DRIVES a certain outcome.
@@NimrodGilAd to be fair, Nick seems to mostly agree with this, and I personally *want* to have low apob, because it does have a correlation, but if I don't have a low apob, I have seen zero evidence that the apob measurement by itself means that I have a problem. If all my other labs are absolutely perfect, I have zero reason to believe that the apob teat is correlating with disease in my case (clearly it does correlate with disease in many cases).
@@homomorphic I share your frustration - regarding the lack of refined data in these studies mentioned (most of them conclude "further research is needed"). But, the type of broad statistical study quoted is not what was used in determining the mechanistic drivers & processes of ASCVD. There's over 100 years of research. It's the totality of animal studies, metabolic ward studies, genetics, lab tracer studies, pharmacological studies, nutritional research & so on with the epidemiological studies that lead to the consensus that a high concentration of LDL particles (ApoB) over years of exposure is causal, necessary & sufficient in the development of ASCVD. And the totality of these studies DO find on average that the lowering of ApoB / LDL particles significantly reduces the risk of ASCVD deaths AND all cause mortality.
@@kazoz3520 while pointing to one factor as causal is a statement *about* mechanism. It isn't a mechanism. What is the exact mechanism of action? Surely after 100 years of statistical analysis this would be known (if statistical analysis could lead to understanding of mechanism which it can't, which is why you can't explain the precise mechanism).
We have insights that apob is involved in the mechanism, but stating that it is *solely* causal in arterial disease, is to make an absolutely fraudulent statement that can not be backed by any evidence at all.
To reiterate how science works, it goes like this:
1. Ask a question (thats done: "what causes arterial disease")
2. Do background research to provide the necessary material to develop a hypothesis about mechanism (this is where we've been for the last 80 years)
3. Construct a hypothesis of mechanism (many of these exist)
4. Test the hypothesis with tests deaigned to establish the hypothetical mechanism is viable (which means that not a single test can show the hypothetical mechanism is not a viable mechanism) - note here that in a complex system there can be multiple mechanisms of action.
5. Test the test to ensure that the test itself isn't flawed and producing bad data (this is where medical research falls down badly with far too high a frequency)
6. Once the test has been established as producing good data, then analyze that data and rule in or out the hypothetical mechanism (this is where the medical field is widely engaged in fraud, because step 5 was not properly done so the data being analyzed is just meaningless statistical data because either the hypothesis has been ruled out in which case the process is *over* for the current hypothesis, or the test Itself is demonstrably invalid)
Very well put. Causality implies the mechanism and the role something plays, and one only might need to add a primary driver to finish the topic. Keeping in mind of course the many things that might also cause the issue at hand.
I acutally love that you are differing slightly in your opinions. That makes the research-context more healthy :-D .
With regard to the statistical adjustments used, I think many people (I don't think Nick and William are included here) do not realise, what assumptions go into them and that it less a question of if they are violated but more so how bad the effects of a violation are.
I appreciate Mr. Feldman’s carefully-reasoned approach.
I might be wrong here, but I think that 99% of all statistics on LDL, ApoB and whatever, is done on populations where refined carbs are as natural as breathing. Once your HBA1c starts creeping up then, I believe, should you worry about lipoprotein and cholesterol. Or you could just work on lowering HBA1c?
This is what I hope (and think) the LMHR study will end up showing.
And seed oils.
"is done on populations where refined carbs are as natural as breathing." That is something that Dr Ken Berry points out about blood test ranges and also blood pressure numbers. I went to see a GP who has an interest in low carb and he ordered a fasting insulin test; no other doctor had requested this. I had been low carb for about 14 months at the time. The test says that it should be under 10. Mine was 7. He said he likes it to be between 2 and 5. My next test was 5; I was over the moon! I also agree with @stevemc2626 who mentioned seed oils.
@@stevemc2626 key point. carbs are not evil
There's something no one talks about. You sort of stumbled on it. When blood sugars creep up on a1c, it does affect lipids...this is called the synergistic effect. It's like adding ammonia and bleech together....by themselves they are stable. The synergistic effect of different foods can lead to mitochondrial dysfunction. The foods I'm referring to are carbs and simple sugar combined synergistically with different foods creates a BOMB....metabolic syndrome.
I love love that you and Nick are really shedding new light on Cholesterol and lipoproteins. Dave, you are correct to pause and reflect on statistical methods used to model something.. this can be so problematic across so many areas of science. Keep pausing and reflecting. An observation I would like to make is that using isolated particles or molecules as measures/biomarkers/causes of mortality all cause or heart disease is super problematic in the absence of systemic view of the roles these particles play. C27H46O is a molecule of mammalian life that has so so so many roles in our bodies that it is extremely difficult to tease things apart. You know all these roles very well, I'm sure as they stretch from repair, to building blocks for cell membranes, to precursors for much of our hormones, to the essential building block of Vit D. If we then look at Lipoproteins it is even more amazing since they themselves have complex functions with in our bodies as carriers essential to enabling everything. ApoB is a marker on the lipoprotein that allows it to be recognized by cells in the body that want something from the lipoprotein carrier. What is missing in this type of analysis is an appreciation of how lipoproteins rise and fall for so many reasons it is hard to even keep track of them. This is like trying to hit a moving target in a system so complex that it rivals our own galaxy. I wish you guys would take a step back and follow the path of Dr. Nadir Ali (Cardiologist) who spends so much time teasing out the actual functions and behavior of these essential molecules of life, rather than constant analysis of associative or correlative relationships with Disease X. Take a step back look at the bigger picture and that will provide the important answers we are all seeking. THe body makes all these molecules for a reason. There is no way that they are causal. Insulin does damage to the human body when in excess, but ultimately it is not causal. The root cause is something else. Nick takes about ApoB in a causal chain.. and already I know that he has lost sight of human evolution and is now following the path of allopathic medicine which cannot ever see the big picture.
Points we can agree on being the use of LDLc & APOB as bio makers of metabolic dis-regulation. However the more I look at it, the more LDLc and APOB look like markers not drivers. Very low LDL,and it seems APOB, associates with higher ACM until other cofounders are accounted for. In an earlier study low serum albumin (marking clinical malnutrition) needed to be factored to quench the rapidly increase in mortality as LDL was lowered. Consist with your lipid energy model, interrupting LDL metabolism will result in increased ACM through clinical malnutrition unless energy transport can be supported by other pathways!
Concise and Very well put
"Points we can agree on being the use of LDLc & APOB as bio makers of metabolic dis-regulation."
High LDL-C/ApoB can have various causes. The most important one in the general population is mitochondrial dysfunction. If mitochondria is unable to burn all the substrate for energy it will convert AcetylCoa into the citrate and push it out into the cytosol (via the citrate shuttle).
In order to get rid of this AcetylCoa the cell will convert it either into fatty acids / triglycerides or it will convert AcetylCoa into HMGCoa and down all the way to cholesterol.
If this happens in the liver, both TG and cholesterol will get released into the blood stream (to prevent accumulation and damage to the hepatocytes) in a (V)LDL particle.
This is exactly what happens in the so called "atherogenic dyslipidaemia".
But it is just a consequence of dysfunctional mitochondria and that is caused by chronically elevated insulin.
AND chronically elevated insulin is the primary cause of atherosclerosis, not cholesterol/LDL/ApoB !!!
I listened very carefully and although he talked about MVX score as a measure of the overall risk, they did not use that to adjust the apob graph, they used undefined "nutritional factors" so the graph is next to USELESS, without these nutritional factors being explained, which he completed failed to do so. At the least the apob graph was based on real data and not some "mythical" nutritional model. By describing apob as a "peddle" he is causes me to dismiss it as a major risk factor, even if it is accepted as such. As Dave mentioned it goes back to the terminology I know about of pattern A and pattern B LDL . Too much pattern B, remnants, is the bad sign., mainly pattern A and hence high HDL and low triglycerides is good . I will stick with this.
Dave thank you for speaking at a moderate pace - I’m no expert so it takes a moment or two to follow some of Nick’ s points but then I find I’ve been run over by the next flood of expert knowledge
@vickilahtinen7254 When I listen to Nick's videos, I usually slow the playback speed so I can understand him. Even then I must regularly pause. Nick talks so fast that when playback is slowed, he just slurs his words and sounds drunk - haha!
Meh. Over many, many years and studies, particle counts, rather than mass concentrations, have proved to have little predictive power. Numerous studies have assessed particle counts for at least the last 20 years or so, since the advent of NMR based testing by LipoSciences (now LabCorp), (and further by Quest (Cleveland heart Lab), ARUP, and Mayo Clinic. The lack of evidence is so bad that these tests are no longer covered by insurance due to lack of clinical utility. (And all the listed labs would love to get coverage back, but alas, clinical utility is yet to be proved). Move on to Lp(a). And I forgot to mention James Otvos (LipoSciences / LabCorp), who has been the person working so very hard to prove this case over decades. Ironic that a recent study of his is mentioned, added to the mountain of net equivocal results over the years.
Not true - Labcorp and Quest cover NMR
@@catherineoneill1322 “Cover NMR” What does this mean?
I love the nuance and think it's good for the nerds to discuss and go back and fourth. The mainstream needs to do the high level changes. Everyone here already know. Love you dave. You were part of my journey to consider the information and then do you own research.
If I understand you correctly, it's the remnants that add the predictive power to ApoB. Which would mean that:
Remnants > ApoB > LDL-C
So why is everyone still going on about ApoB?
I guess it would challenge the lipid hypothesis.
Nonsense. Lipids nor lipoproteins are not the primary cause of atherosclerosis.
Chronic hyperinsulinaemia and mitochondrial dysfunction are!
I’m so confused on all this.
I just got my blood work and my APOB is 212 and apolipoprotein B is 250. My LDL is 307. Trigs 125 and HDL 66. I don’t know what this APOA 1 is but says it’s 174. A1C went down from 5.8 to 5.6 and I’ve been a dirty carnivore for 6 months now. CAC was a 7 and I’m almost 57 and was a light smoker.
@@laurengianna9944 Hi, I am confused too, but I think your APOB and apolipoprotein B should be the same number , not different numbers. APOA 1 sounds like apolipoproteinA, but I would ask about that. Your APOB and LDL-C seem very high to me, though I am not a physician. If it were me, I would seek a knowledgeable cardiologist or lipidologist. Best of luck.
Thank you for the extreme nuance you bring to this debate.
Hi Dave. Very interesting. Totally agree re lack of confidence in statistical adjustments. May I please ask, how does this new metric perform against fasting TG:HDL ratio as a predictor of CV risk? Isn't that already known to be a strong predictor from Dr David Diamond's work so wouldn't it be interesting to see how they compare?
Outside of biological indications, you & Nick are modeling how to have a discussion, differing beliefs (nuanced or not), ect. without "gunning" for each other
Modeling? Sheesh.
@@edithrowland These mealy-mouth wimps, so afraid of making a pearl-clutching subscriber "uncomfortable," (OMG!) are making me uncomfortable.
Dave thanks for this - I was previously struggling to understand your concern on statistical treatments in the Simon Hill's podcast but you struck a chord with me as I too am very suspicious of statistical removal of effects.
I (sorry to say) have been very skeptical of the general quality of statistics applied in the biomedical field other than the amazing work of Emeritus Professor Frank E Harrell.
There can be any multitude of hidden explanations that one is only subtracting "on average" and giving the appearance of causality. My personal criteria for causality is a much higher one (1) an proposed physical/biochemical mechanism (2) separate measurement of the components of the mechanism (3) isolation of the effect.
It seems like that next project for your LMHR cohort is taking shape!
Nice - I love Nick's video's, and I love both of your hedges and nuances. I'm still surprised when you guys differ on anything. In this case, I'm much more with you. Keep up the good work - stay skeptical!
BTW, my.. layman's nuance.. informs me that LDL cholesterol is necessary for human metabolism. There must be some other underlying thing that might make it harmful, or an indicator for something harmful. So the Jshaped curve for ApoB makes sense. But I've also kept in mind the remnants, and was pleasantly surprised when you brought it up again. I'd like to see the all-cause (ahem - metabolically caused) deaths vs ApoB remnants. If we can establish that this is actual thing we are looking for, then we can focus on its causes and interventions related to those.
I would like someone to explain mechanistically what it actually means to be in good or poor metabolic health.
I will attempt to mechanistically explain how someone becomes metabolically unhealthy, and how you can potentially reverse this phenomenon; and how the abnormal markers fit into this model.......
As a response to each meal, the body produces insulin. Insulin's main job is to store. Glucose, the breakdown products of carbohydrates, enter predominantly liver, where under the influence of enzymes that are activated by insulin, most of it eventually gets converted into triglycerides (the fat storage form related to energy).
The liver packages some of these triglycerides in ApoB particles, which take it to peripheral adipose tissue mediated by the surface enzyme lipoprotein lipase. These ApoB - VLDL has a lot of triglycerides and some cholesterol (fats with other functions - like for repair, enzymes function, structure of cell membranes etc).
Over time, fat accumulates in your liver and your peripheral adipose tissue, and the body produces more and more insulin to push in the same amount of glucose into liver cells. This is a crude definition for insulin resistance. The fat accumulation in the adipose tissue makes it much less receptive to the triglycerides being delivered by the ApoB particles as well. This will lead to accumulation of triglycerides and lipoprotein particles in the blood stream as well. This also triggers another protein (CETP) which alters the content of your lipoproteins (exchanges the triglyceride in the ApoB particles for cholesterol from other ApoB or HDL particles)
Certain genetic and lifestyle factors and significantly increase the rate at which this happens. High fructose, processed food can cause mitochondrial and behavioral changes which can increase the rate at which this develops. A higher carbohydrate diet, increased frequency of meals and a short fasting period can all keep the insulin switch turned on (the metabolic enzymes in your body either work to store, or in reverse to use what you have stored.....it takes about 12-16 hrs without an insulin spike for you to start utilizing the energy that you store in your fat cells). A sedentary lifestyle reduces the amount of energy you use. A higher calorie intake in the presence of insulin may worsen the accumulation. And seed oils may reduce the amount of absorption of dietary cholesterol and induce inflammation.
Accumulation of fat in your liver -> fatty liver
Persistence of lipoproteins and inefficient delivery of triglycerides -> Dyslipidemia
When hyperinsulinemia cannot deal with glucose load -> diabetes
Hyperinsulinemia also has other effects, like holding on to water and salt in the kidneys, cause endothelial dysfunction etc which can lead to hypertension
Hyperinsulinemia is also associated with an inflammatory environment which can induce vessel damage, atherosclerosis etc.
To put in the biomarkers, you will see an increase in triglycerides and a decrease in HDL-c (cholesterol concentration in HDL particles). There may or maynot be an increase in LDL-c (cholesterol concentration), but there is an increase in LDL-p (LDL particle number).
ApoB includes VLDL,IDL and LDL particles (mostly LDL; the rest are together categorized as remnants - they are triglyceride rich).
A high ApoB remnant is a good indicator of a lot of undelivered triglycerides and thus a good indicator of this underlying metabolic state
Now, when you through lifestyle measures reverse this process (exercise, fasting, low carbohydrate intake), you notice that as your weight reduces (body fat maybe a better factor to corelate with than just BMI @Dave Feldman ) you notice a reduction in triglycerides, an increase in HDL and an increase in LDL-c and an increase in LDL-p (ApoB particles as well), but a reduction in remnants.
Hope it makes some sense, and has given some perspective for further reading.
This is a combination of the lipid energy model and the carbohydrate insulin model. Maybe you can do your own research into these.
@@Elias00713Brilliant summary. Thanks. 👍
Hey Elias I just want to thank you from the bottom of my heart. You did amazing summary and help me understand much better metabolism function. Appreciate your effort and time. 🙏
so how do we summarize it in a simple way that people like me can understand it ?
Good question!
VLDL is a better predictor for all-cause mortality than ApoB.
Apo-B still doesn’t cause heart disease. That’s my summary.
Key insights
🧠
Appo B is a marker of LDL particle number, which is better than LDL cholesterol for cardiovascular risk assessment.
📊
Metabolic vulnerability, including malnutrition and inflammation, is the primary predictor of all cause mortality, overshadowing factors like cholesterol and age.
📊
The association between ApoB and all-cause mortality shows a j-shaped curve, indicating that very low levels of ApoB may lead to higher mortality.
📊
Lower ApoB continues to associate with lower all cause mortality, highlighting the importance of metabolic vulnerability in individual therapy.
📊
Metabolic poor health tends to increase remnants, leading to a much greater association with cardiovascular disease mortality.
🧬
The physiological patterns and signatures inform us about metabolism and are important to overall health.
You make so much more sense than Nick. Thanks also for speaking slower so one can understand the words individually as well.. lol..
Metabolic health, the final frontier!
Thanks again
Bob the welder
Thanks for the continued updates on LMHR research. Is there a marker for remnants? Or a simple way to determine remnants from apob and ldl...to calculate the Delta?
I’m thinking particle size will be the answer you’re looking for.
I'm with you guys but gotta say *"I give"!*
Dave you’re the man get rid of nick and especially Cromwell before you get all messed up with these guys. Great work again Dave your stand on top
What was the average ApoB in the LMHR study? Or where can I find it?
It still doesn't mean that Apo b is the reason for the increased mortality.
Correlation versus causation.
Markers are NOT causes!
It also matters in which population the markers were determined. Who was included and how many people were included in the determination of this vulnerability index and who was included?
Nick's standard of proof is a reasonable preponderance of the evidence, which he states up front may be provocative. Nothing wrong with that.
Then Dave criticizes what Nick says as not being a causative inference, although it may be (by luck), so he's not disagreeing with it (i.e. sayin' the opposite).
Thus Dave makes a strawman error compounded by a non-sequitur fallacy (the Remnant example).
Podcasting of all sorts is freewheeling entertainment, not calculating from formulas or structuring a study. A podcast criticizing another podcast is like shooting ducks in a barrel, as is commenting on a podcast. The simplest takeaway is that small HDL (SHDL-P) may be more important than realized - but more study is needed because it's more complex than just that. While waiting for causation, eat meat, butter, and eggs, and nothing else.
I agree with " eat meat".
I’m trying to understand both of their points of view but I really don’t get it. 😂 I agree with your last comment.
What is missing is the lipid fraction score of individual partical numbers, sizes and the apoB particle number in light of fasted versus nonfasted lipid profile to look at the reverse cholesterol synthesis that should be very apparent in a good metabolic system that shows a decrease in TG and increase in HdL in the fasted state.
One more interesting observation: high cholesterol falsely raises A1C. With high cholesterol the A1C will be much higher than the actual A1c. I found this to be true as I looked at my continual glucose monitor 3 month average that was significantly lower than the calculated average glucose from the reported A1c.
This is an interesting observation.m. As my A1c has gone up slightly as my other lipid profile improved.
I believe the LMHR is irrelevant in this discussion since at no point is any measure used for MVX or whatever that fictional measure is called or used in the cohort studies (poor quality) that Nick referred to originally that would be utility to LMHR. LMHR were not identified in these studies, now perhaps if you received the data you could hypothesise certain people with the triad but does LMHR numbers appear without being low carb? if so this would be a largely pointless attempt.
As a minor counter the study posted by Dr Tro on X about a month back demonstrating similar studies to what Nick referenced that indicated LDL status (low) had as much impact as VLDL status.(high).
Please include LDL Fractionation test in LMHR trial. Pattern A or Pattern B
Thank you for another excellent video.
After listening and watching hundreds of hours of videos and reading some of the studies and theories on CVD. I am convinced that atherosclerosis is the body trying to repair itself from arterial injury. There are tons of risk factors however it seems around 80%:are related to metabolic disorder. Discounting things like heavy metal poisoning, mold toxicity, nicotine, sickle cell anemia, etc. the majority risk factors are metabolic. There are also genetic risk factors the most troubling one that is used to support the lipid hypothesis is the type of hyper familial Dis lipidemia that is associated with very early CVD and death at a young age.. The main question that should be asked about that are how are the arteries being damaged ? The lipid theory is saying by ABO B. I don’t know much k about it but have heard that diabetes isn’t involved. If so how was that determined? Did they not have high blood glucose and high insulin levels? along with insulin resistance? Because those things are clearly implicated in CVD for metabolic disfunction along with the issuing inflammation,. Dr. Ford Brewer along with others are saying inflammation is damaging the artery walls due to extremely high insulin levels and glucose levels. Is the high insulin and glucose levels damaging the glycocalix? A messes up glucokalix can increase blood pressure. Another risk factor. Which in turn is causing inflammation of the endothelium? Is this mechanism causing the prtoglycans to proliferate which is causing the LDL to infiltrate the endothelium? I believe so and of course the ABOB molecule is involved as part of the repair mechanism. Clearly smooth muscle cells start to cover the inflamed area and build up of LDL. Maybe the remnant particles of LDL are what is left over from the LDL dropping off the cholesterol for the repair, Also you see fibrogen activated to help cover the damaged area. Lots of questions remain. Why is the damage in certain areas? It seems turbulent areas near artery junctions. Why are statins helpful if high LDL isn’t the cause?> 1. Statins are pleotropic they are an anti inflammatory and fibrogenic and help reduce the inflammation which may help more than the lowering of LDL which increases to help fix the artery damage.. Dave please look at Dr Roy Taylor’s research on diabetes. He has a fat tolerance model for diabetes. He wondered why thin people are getting type 2 diabetes. He concluded that they have visceral fat causing insulin resistance. He called these thinner people with fatty livers and pancreas TOFI. Thin outside fat inside. He suggests that people have different fat tolerance levels some can have more adipose fat and no visceral fat and some can have more visceral fat and less adipose fat. He put the TOFI subjects on a vigors diet when they loss their visceral fat their insulin resistance was reversed along with their type 2 diabetes. I think I am. TOFI and not a lean mass hyper responder, However when I went on a low carb diet my LDL shot up quite a bit much to my doctors dismay. However after a short time and losing some visceral fat all of my of methabolic markers improved. One exception was my HA1c which went up slightly. I am taking stains and niacin both can raise blood glucose and cause diabetes. . I am working on getting that below 5.6. With diet and exercise, I am trying to put on muscle mass which I lost for a period of time by being on a high dose of Lipitor. I since switched to a low dose Crestor which has better anti inflammatory properties. All of you please keep up the interchange of ideas and keep this dialog moving along and forward. As someone with skin in the game I really appreciate,all of the research and discussion happening lately. Thank you .
I’m so confused Dave 😢. CAC a 7 CIMT showed no blockage. Trigs went from 116-125 HDL 66, then did NMR and apoB is 212 and the apolipoprotein B is 250. Lipoprotein a is 12. I don’t know the difference between the two B ones 🤷🏼♀️.
This is my hypothesis.
The LDL particle becomes modified/atherogenic when it stays in circulation for a longer period than it is supposed to.
In Familial hypercholesterolemia, there is a defective LDL receptor. So the increased LDL level is due to the individual LDL particle persisting inside the circulation for a longer time.
In the case of a lean mass hyper responder, there is increased production of LDL, leading to increased LDL levels in blood. But this LDL particle is cleared off within the same time as that of a normal person. In other words, the time for which an individual LDL particle stays in circulation is the same as that of a normal person.
The longer the individual LDL particle stays in circulation it is more and more subjected to the forces of entropy, and structural modifications can happen to the particle which makes it atherogenic or inflammatory. Leading to plaque formation.
LPa is missing from this discussion . As a subset of LDL contributing 30% of the host level to LDL it needs to be considered separately.
Treatment with stains typically raise levels by an average of 11% and can be as high as 50% Therefore it is a separate
I have high ldl-c and have been reading a lot of medical papers etc, and studies have shown apo(a) in plaque at levels that show it's at least the 30% you say.
And LP(a) at least has a mechanism to be there that makes biological, logical, and scientific sense, supported by medical studies.
@@Klunge ... and is lowered by saturated fat
Is the MVX over-fitting of data, or does changing one's MVX predictably modify their risk?
Nick, I am a physics guy. I am a LMHR. Nick I am hearing only chemistry here. Have you knowledge of magnetism, Body DC electrics, BioQuantum phenomena driving the protein opening folding and electron hydrogen ion tunneling? Have you looked into it? I have. As a researcher of semiconductors I am fascinated how nature has all these figured out billoins of years ago on planet earth under our sun. But the bulk of us are more like spaced out in our hubris. Water and solar radiation is not what you might expect. So the entire biology falls apart until you build it back from scratch. Hmm. Maby in twenty years more will follow. I trust the sub atomic since all the biology and chemstry they let you learn is subordinat to it. We the mitochodriacs or biohackers or what ever one might want to call us can not be concidered as the populus. Statistics aside. After all we are the LMHRs. The healthiest bunch of them all???? time will tell.
Dave thank you for all of your work. We have one important question. With the evidence of your studies and trials, is their any information at all of any reduced atherosclerosis or plaque for those LMHR with higher LDL, HDL and lower TG while on a low carbohydrate diet? In other words I know y’all have looked at this just as the low fat diets have these study outcomes. If you can not tell us now then please just say you can not say now.
I think the assumption that lowering ApoB will hold metabolic vulnerability constant is a big assumption. Statins do all sorts of things to metabolism, not all of them good. Maybe PCSK9 inhibitors are more benign, but they're new and expensive enough that we don't have excellent data on long-term effects.
If you can snap your fingers and do magic, why not directly magic up a 300 year healthspan? Other than magic, if you remove ApoB from somebody's blood, you have to deal with the causal impacts of the way you did it, and they'll probably affect metabolism.
The body is an amazing organ and is constantly trying to regain homeostasis. Change one thing, whether by diet or drug, causes a domino effect of changes in the body to get back to the norm. Just my personal opinion.
Dude's beard and jaw reflect radar in opposite directions.
Arent these all just associations ? Isnt the overall difference quite weak ? 1.5 ?
9:31 "If you subtract LDL from ApoB and look just at remnants. That has a much stronger Association by far... towards both All Cause Mortality [ACM] and cardiovascular disease [CVD] mortality."
What is the layman’s bottomline ?
Exactly, who the hell has the time or even wants to listen to a 5 HOUR discussion.
We're all Fu**ed !
And there in lies how we got here to begin with. Trust of others to figure it out for us resulted in the big farma medical machine we have today.
I do understand that it is tough to follow all of it but we have to because in the end we have to make our own decisions.
In a nut shell. Here is what I thought I heard in laymen’s terms. We have proven the “LDL is evil model” and statins are the answer is a fallacy. So we are investigating the unknowns. key pieces are starting to emerge.
1) Metabolic health trumps all in terms of impact. By a 3x more important than age and a margin of something like 30x more important than any cholesterol or POB marker.
2) That said APOB is a better indicator than LDL cholesterol as a predictor of all cause mortality. (APOB is a protein found on the low density lipoproteins including LDL, triglycerides and remnants.)
3) Remnants are oxidized LDL that is like trash that floats through your system. Sugar in your blood glycates the lipoprotein and causes it to stop interacting with the body as it is supposed too. so it can’t be removed and floats around like trash piling up and causing issues in the body.
He’s FOS
Don't have metabolic syndrome.
Is it easy to measure the number of Apob remnant particles with a blood test?
You need to have a discussion with Thomas Dayspring. Let me know if you me to set it up.
I probably missed it…I still don’t understand is high ApoB “bad” or it’s not really a factor in people who are very metabolically heading?!? 🤷🏼
Been low carb/keto/carnivore for last 3 months. I lost 23 lbs in 3 months but now I have 314 total cholesterol 87 triglycerides. I’m not below 70 triglycerides so not sure if I could be close to LMHR or what? I feel great, no more soreness/inflammation, no longer tired and I think much clearer. So wish I knew how to find out if I’m in danger of Atherosclerosis?
Include MVX in LMHR trial compare results with the triad, High LDL, Low Tri and high HDL
He really loves the term steel man
I’m so confused 🫤 last Sep. my ApoB was 198 and my remnant cholesterol was 1. Last month my ApoB down to 168, but remnant cholesterol go up to 16. Which one is better🧐I assume l am LMHR. BMI 19, hdl 105, triglycerides 49, HS CRP
Does Lp(a) fit into remnants?
Abo b always normal. Have heart disease. Always had very low ldl cholesterol. Heart disease is caused by hyperlipidemia. I've been living in for years
Slow down..your only confusing me more..
Don’t worry. He’s so full of shit, and what he’s rabbiting on about has no clinical significance whatsoever.
Nick's metaphors only serve to weaken his argument.
Nuance is being used way too forgivingly here.
What are your thoughts re Dr Thomas Dayspring’s fascinating ApoB / Cholesterol “tutorial” on Simon’s channel last week? He seems a highly experienced, knowledgeable & esteemed Lipidologist. But has he got particular biases / agenda?
Pleeeaase slow down “!
Just set "Playback speed" to "0.75x".
This is no way to do a reaction video - you need to throw in some profanity... maybe cast some aspersions about Nick's ancestry and so on :)
If Dave and Nick were politicians, we’d have world peace ❤
People like you ?
Blah, blah, blah