The LDL Myth: Report Shows Weak Link to Heart Outcomes (NEW)

And we are almost there. We are back. Okay. In today's show, we're going to talk more about LDL cholesterol. Now, I've said it many times. I didn't think we'd have to go into LDL again, but I was looking at Nick Norwood's Instagram page over the weekend, and I came across this paper that I had printed out right here titled trial level surrogacy of non highdensity and lowdensity lipoprotein cholesterol reduction on the clinical efficacy of statins. Now this was a really interesting metaanalysis looking at 20 different studies looking at uh involving 184,000 individuals and wanted to see what surrogate effect LDL cholesterol reduction had on heart outcome like myocardial inffection and death from heart disease. And so we're going to talk a little bit more about this, review Nick's uh excellent Twitter thread on this subject, and address your questions on cholesterol because, as many of you know, I've been coaching individuals and clients for now 19 years. And one of the biggest concerns that clients have when it comes to their health is my LDL cholesterol is high and my doctor is concerned about it, right? But many people have low triglycerides, low body fat percentage, low blood pressure, waist hip ratios, and all of the things. So, should we really be monomomanically focused on LDL cholesterol reduction considering all of the not so equivocal research that has been emerging in recent years? And so, that's what I want to share with you. We got a few folks here with us now. Thank you all for being here. We got uh Tom from Heert, Arizona. My business partner actually has a cabin up in Heert. I've yet to uh visit, but I would like to. So, um, again, really grateful that you're all here with us. If you're enjoying the content, hit that like button. Any questions are fair game. Uh, there's a lot of scientific jargon that we're going to go through tonight, but I don't want to lose you in the weeds of complexity, uh, with this and just give you the highle overview of what this study actually found. So, uh, let's do that right now. So, we're going to clear this layer here. Uh, clear that, get that out of the way. We're going to get me into the smaller screen and here we go. Okay, so this is a study here trial level surrogacy of non- highdensity and LDL lowdensity lipoprotein cholesterol production on the clinical efficacy of statins. Okay. Uh and as you can read for yourself uh I think this is very interesting. Uh the investigators say research studies published between the years 1987 and August of 2023 from Puned Cochran Library and MBASE baseline lipid levels absolute risk differences and hazard ratios for major carvascular events and all caused carvascular mortality were analyzed. What they found out of 20 randomized control trials involving 194,686 participants were included with a median follow-up of 4. 85 years. the uh sort of limiting factors here is the follow-up period was relatively short. what they essentially found here although uh you know the they're referring to LDL and HL here they say although they LDL and HLL are relevant biomarkers for the follow-up of patients treated with statins their reduction does not reliably predict a similar reduction in cardiovascular ris risk as such they should not be used as pivotal evidence in drug trials now this is right from the horse's mouth this was published in the European heart journal cardiovascular phicotherapy uh late November 2025. Now, that's not to say that if you're on a statin, you just get off the statin right away. That's not to say that all drugs are terrible. This is just to say that this is more likely a much more nuanced conversation when it comes to the subspecies and the other metabolic health parameters in millu that is going on and LDL reduction is not equivocally linked with favorable outcomes in primary prevention of major adverse cardiovascular events and cardiovascular disease specifically and we know this to be true in the context of type 2 diabetes. So, this is where I'm going to uh offer uh some perspective because I have a huge interest in metabolic health. As many of you know, as individuals become more insulin resistant and type 2 diabetic, guess what happens to their LDL cholesterol levels? It actually goes down. Okay? Now, this is sort of paradoxical because we know that insulin resistance, pre-diabetes and type 2 diabetes is unequivocally linked with worse cardiovascular outcomes. So this is sort of where we need to have a better understanding of the physiology and we hear a lot of people like to basing and pure and I love most of their work but they do sort of have an antiquated perception in my opinion and based upon what the research is actually showing and by the way my opinion it's not just opinion I've been selling advanced lipoprotein particle testing I started doing that in 2007 for four years in the state of Colorado worked with a lot of cardiologists and primary health professionals uh internal medicine doctors physicians assistants and nurse practitioners and beyond. And when you look at, you know, the lipid species at a more granular level, total particle count, the remnant lipoproteins and VLDL uh and so forth, you see a much better picture than just looking at LDL cholesterol. And so this is, you know, going back to the thesis uh and the impetus for making this video is many doctors are monomomaniacally focused on just LDL reduction without looking at other pieces of the puzzle. And so that's what sort of my perspective on this and again you know doing this work for the past 19 years working with you know many uh doctors and primary health professionals uh all throughout the world um you know we see uh interesting things. So, uh, what I want to do is continue on. And if you're, again, if you're enjoying the content, hit that like button, uh, would love to know where you're watching, uh, this from. Okay. Uh, the investigators. And now, here's some of these, uh, different the inclusion criteria for these 20 randomized control trials involving 894,000 people. um you know and uh you know some of the associations um with regards to LDL cholesterol levels and risk reduction for major adverse cardiovascular events. Uh you can see uh these uh different regression analysis and so forth. Um but what I want to do is just get to uh get to that as well as look at our pal over here Nick Norwitz. as many of you know uh he's an amazing individual has a uh his medical degree from Harvard University he also has a PhD as well so he's one of the rare MD PhDs uh in our space and he has some interesting uh insights here so um [snorts] Nick thank you for your work and uh gosh my mouse is giving me trouble okay so he says when the cholesterol levels drop misses the mark we have seven tweets that we're going to review and then we're also going to talk back look back at the study. We can assume that how much LDL drops tells us how much cardiovascular risk is reduced. Can we assume that? Well, a new meta analysis in the European Heart Journal says no. In fact, it suggests the link between LDL cholesterol reduction and actual cardiovascular risk is incredibly weak. And that is exactly what this paper found. Okay. He says, let's unpack that. So, let's look at uh tweet two of seven. This was an umbrella review of metaanalysis of randomized control trials. In total, the review included 20 randomized control trials comprising 194,686 participants with a median follow period as I mentioned of 4. 85 years. So what did they find? Okay. Um they looked at uh did a lot of complex statistical analysis that uh many of you and including myself do not quite understand. Uh but what they find is that you know an R squar of one means perfectly predictable right so if there was a 1:1 ratio of you know for every you know 1 milligram per deciliter decrease in carvascular or LDL cholesterol there would be an incremental and proportional um you know reduction in cardiovascular disease risk and or death from heart disease but that's not what the data shows uh in fact as the authors themselves concluded these associations were too weak to ful fulfill the conditions required for a surrogate marker like LDL cholesterol to be considered as a valid endpoint when it comes to looking at major adverse cardiovascular events and death from cardiovascular disease. Okay, simply put, this calls into serious question whether LVL can be used as a surrogate for clinical outcomes in cardiovascular in statin trials. Okay, they go on to say these data aren't an outlier. These data are not an outlier. So I'm having to read this below. Um there was another study that corroborated this. This was published in the Journal of the American Medical Association internal medicine uh reviewing 21 randomized control trials uh finding a similar lack of uh you know strong correlation here. Now Nick says but I'm not done. Understanding evidence advances when we resolve apparent contradictions. So let's talk about what else do the stats do in the body. Okay, so this he goes on to talk about um potentially how you know statins adverse normal biologic functions and we know this to be true. We've known for a long time that statins suppress the body's ability to make a wonderfully and critically important nutrient for the mitochondria known as co-enzyme Q10. Right? This is part of the isoprenoid pathway, the jarnol jarol just below the HMG COA reductase enzyme by which statin inhibits. And it turns out that statins really uh do a great job of lowering co-enzyme Q10 which is vitally important for synthesis of energy in the mitochondria. The ATP that we hear so much about in the mitochondria. Uh it turns out that statins lower that. Statins also have unintended harms uh such as many of you know uh increasing risk for blood sugar issues but they also have some potential benefits. As many of you might know statins have pleotropic anti-inflammatory effects and this might be why you do see uh some uh improvement in outcomes in certain studies with regards to statins. But new data also shows that statins lower this critically important gastrointestinal peptide that has become popularized in recent years known as GLP-1, glucagon-like peptide 1. There's GLP2 as well. There's GIP. There's 26 different increin hormones. GLP-1 is just one of many of them. Uh we hear a lot about the pharmacologic uh semiglutide and ompc and the sort because they are uh GOP1 agonist and or the uh whole hormone. Uh and so he goes on and talks a little bit more uh about that. Uh going on down there's a lot of comments on uh this tweet. Okay. Uh let's see. Gosh. Uh a lot of people are talking about this paper which is really uh interesting stuff. Where is the rest of the tweet here directly? Hold on. Let me see here. We can go back to the actual study. Just give me one second. All right. We're back. I get excited about this. Sorry that I'm speaking so quickly uh for you all, but I do want to pop into the comment section. Uh as always, if you're enjoying the content, hit that like button. I would love to know where you're from and if this content is helpful. I know it's a little bit of a rapid fire. Uh but essentially what this research shows, again, involving an analysis of 20 randomized control trials involving, as I've already mentioned, 194,000 participants with a median follow-up period of close to 5 years. you know there's not a strong connection linear connection uh with the conccommittent LDL reduction and a uh respective reduction in mortality from heart disease. So you know should we be looking at more expanded biomarkers? Should we open up our lens a little bit when it comes to the clinical management and prevention of cardiovascular disease? Of course yes. looking at metabolic health, physical fitness, coronary artery, calcium scanning, waist circumference. All of these things are really important. Uh I do want to acknowledge a few of our live listeners here. Um we have folks from Virginia in the house. We have uh ketones and glucose 4978 from Mission Viejo. I think that's Orange County, California. Um we have folks from Texas on the line. Uh and I just have a little anecdotal story from uh someone in my life who's uh only 33 years young and it turns out her LDL cholesterol is 130 milligrams per deciliter. And guess what? Her primary health professional although she did have uh you know immune system antibodies suggesting some preclinical autoimmunity developing. She wrote those off entirely and said well you know your LDL is high so we might want to consider reducing your cardiovascular risk by putting you on a lipid lowering medication. And uh that just totally baffled me because her anti-uclear antibbody and other markers of uh lupus and autoimmunity was high but that was completely disregarded. Uh and there was this monommonia uh you know just this focus on lowering um her LDL. Okay. We have folks from Indianapolis. We have folks from South Africa but currently living in Thailand. Wow. Amazing. I like that. Uh polish Mike says LDL has weaker cardiovascular link with patients with high insulin sensitivity. Yes. Uh yeah we know that to be true. As individuals get more insulin resistant the link between LDL cholesterol and adverse cardiovascular outcomes becomes weaker and weaker. Okay. And we also know that this is from the Amoris lipoprotein cohort study out of Sweden that individuals with higher LDL cholesterol over the age of 65 are much more likely to become a centinarian that is achieving 100 years of age compared to their age match counterparts that have lower LDL cholesterol. Isn't that interesting? Okay. Um so what do we make of the study? again uh you know we're talking about this study that is generating a lot of airtime over on Twitter and on the interwebs. So when we look at the uh surrogacy of LDL uh and its surrogate relationship to adverse carvascular events uh sensitivity analysis suggests that expression you know expressing treatment effect on clinical outcomes on lipid levels uh you know does not change uh as much meaning that there isn't a strong connection between the degree of LDL cholesterol reduction and the benefits from cardiovascular mortality. at least in based upon the data that we have the follow-up period being a median of 4. 85 years. Okay. Um let's see let's go on down the list. Okay. So the present work shows that trial level surrogacy is not met. Meaning we can't definitively use LDL cholesterol as a surrogate biioarker for increased cardiovascular risk and likelihood of major adverse carvascular events. They say although previous studies have shown a significant association between the reduction of LDL cholesterol and/or nonHDL cholesterol with statins and their clinical benefit, the association is too weak for the mean reduction of in lipid levels to reliably predict a similar reduction in cardiovascular events and all cause mortality. Let me just read that one again. And for those of you that are listening on your cell phone, you may want to just hit that record button because this is right from the horse's mouth. Uh I think this is uh really interesting stuff. Again, published in the European Heart Journal. I'm going to speak very slowly and deliberately so that we can conceptualize this a little bit better and help decrease the fear-mongering around LDL cholesterol. Okay. The investigators say although previous studies have shown a significant association between the reduction of LDL and nonHDL cholesterol with statins and their clinical benefit. This association is too weak for the mean reduction in lipo lipid levels to reliably predict a similar reduction in cardiovascular events and all cause mortality. So again, the purpose, the impetus of the study of looking at the 20 randomized control trials involving 194,000 subjects over the course of 5 years was to see what conccommittant decreased risk there was with a step-wise decrease in LDL cholesterol. And they didn't find a strong connection. Okay. So what does that mean? That doesn't mean that statins don't do don't offer any benefit whatsoever. That's not what this is saying. This is saying that we probably can't rely solely on LDL cholesterol reduction and have that be a surrogant biomarker for a reduction in major adverse carvascular events. That's what the research is saying here. And so what else should we be looking at? Well, we've talked about this a lot. What about fitness? Researchers have actually found that being physically unfit, and I've shared with you, there's someone here from Indiana, so you should know about this study in Indiana firefighters that were tracked for 11 years. The subjects were just instructed to do as many push-ups as they could in under a minute. And they were followed for over 11 years. At the end of the 11-year study, the researchers put the number of push-ups between 1 and 10 push-ups in a minute, between 11 and 20, 20 and 30, and 40 and 50 uh push-ups and put uh the study subjects in different quartortiles. And what they found was that comparing the lowest quartile to the highest quartile of push-ups, there was a 4. 65 65 increased risk of allc cause mortality and carvescular death over the course of 11 years in people who could do more push-ups more than 40 push-ups compared to those who could do less than 10. So this if you're going to just look at a surrogate marker of mortality from heart disease was you know more strongly associated than LDL cholesterol. In fact there were no between group differences in LDL cholesterol in this study. Now this was not uh a randomized control trial. This is epidemological. This is a sort of a retrospective uh analysis to look at associations. It doesn't sus out the direction of causality. So we know that to be true. Um but we also know something else to be true and that is that when individuals go to the hospital and their lipid levels are tested, uh more than 50% of those individuals have lower LDL cholesterol that is recommended compared to the guidelines. meaning their cholesterol levels are healthy uh in terms of you know the standard of care. Now some people will say well they're already sick by the time they go to the hospital and that's why their LDL cholesterol uh levels are uh reduced and so forth. We also saw lower LDL cholesterol levels linked with adverse outcomes from uh CO 19 infections. And we now have data uh finding that higher LDL cholesterol levels over the age of 65 is linked with uh better mortality and greater likelihood of achieving uh 100 uh years of age. So, you know, the data is all over the place. And so, I just I say this not to say don't listen to your doctor. That's not what I'm saying. But to encourage more nuanced conversations about reducing cardiovascular risk, improving fitness, reducing body fat percentage, reducing blood pressure. I mean, these are all things uh that we should be looking at. Uh you know, increasing step counts throughout the day. We know that people that that walk more than 12,000 steps per day have a lower risk of all cause mortality, including carvascular specific mortality. So, there's a lot of things that we uh could and should be focusing on, but for some reason, we don't. So friends, uh if you're here right now, hit that like button. That just lets me know that we should uh keep doing uh these videos. We have quite a few uh comments here that I do want to address. Uh we have uh Polish Mike from Illinois. We have Rose says, "My LDL was high. However, my HDL was 120 milligrams per deciliter. " Okay. Uh so amazing. Okay. Stephanie Sen is worth talking with. Yes, I've already interviewed her back in 2017. She's great. Um, my LDL level is 272 and the doctors want to put me on medications. I'm 60 years and healthy uh and within my uh maintenance weight. Okay. Um, well, again, as the study found, you know, we can't make sweeping inferences uh on your LDL and risk of future heart disease, but I would encourage you to look at your remnant lipoproteins, your VLDL, your fasting and non-fasting triglycerides, as well as insulin, fibbrinogen, uh, feritin. These are all things that we should look at. Okay. Nick said that high LDL is present in fat adapted lean mass hyperresponders because it's acting as a transport system to carry fat for fuel. Yes, we know that to be true. Uh, did this study include men and women or both? Yes, this was a mixed gender study. Okay. My LDL is 294, but my triglycerides are 50 and HDL is 117. Yes. Uh, you definitely fit the lean mass hyperresponder phenotype. Okay. Uh, my LDL was 108 and my total is 209. Mitroglycerides are chef's kiss. Okay, so um any questions? Oh, we got folks from Flagstaff, Arizona. We have uh several people here from Arizona. Uh just so you know, our business has moved to Chandler, Arizona. So if you're in the area, be sure to stop by. Um we have Kundale says, "I walk about four miles a day, which is awesome. " Uh I thought 167 was high. Um, but some of you guys are in the stratosphere. Yeah. I mean, here's the thing about uh LDL, just this is super anecdotal. Um, but someone near and dear to me, uh, who's very metabolically healthy, very low blood pressure, very physically fit, uh, looks excellent for her age, normally has a, you know, fasting LDL of around 130 milligs per deciliter. She went and did a hit workout and then we ran some labs and her LDL jumped to over 430 milligrams per deciliter. So high that lab core flagged the report and called us to say hey what is going on and and so thinking we know that exercise especially highintensity interval training is healthpromoting. So again you know just raises more questions than answered. If exercise raises LDL then how is that really a bad thing right? This person uh at the time was doing a one meal a day low carb approach and just as someone had mentioned here about uh how Nick Norwit says that in lean mass hyperresponders LDL is a sort of shuttling system for fat uh you know based energy throughout the body. That was exactly the case which uh was super interesting. So yeah that's what I have here. Any questions, y'all? Um, yeah. So, um, not a lot of questions, it seems. Just a lot of comments. So, yeah, I just wanted to share this paper with you. I think it's interesting. We're going to talk a little bit more about this. I'm sure Nick will be sharing more about this paper uh over time. uh this paper was just published in uh European heart finding uh lack of a strong statistical association with LDL reduction and it's conc committant decrease in cardiovascular disease risk and event risk and all cause mortality. So uh interesting stuff my friends. What do y'all think? Again if you're here right now hit that like button. It's always great uh to see your likes. Um, another comment says LDL is fine to be high so long as particle type A. Yeah, I think you know again I think if someone is not eating a lot of uh industrialized seed oils uh and has low blood pressure, low waist up ratio and so forth, I think that's um probably okay if you have a high LDL. Uh I do worry about high LDL in people that are eating packaged processed foods because of the uh linoleic acid oxidation potentially and things of the sort. So that's uh interesting stuff. Okay. Rose Fischer says, "Interesting. I run 8 miles a day with some sprinting. Maybe that's why my LDL is a little higher. " Yeah, I that could be especially if you're a low carb individuals a low carb individual. Cholesterol numbers are easy to change, but particle size not that easy at a fixed diet. Yes, I agree with that. Okay. Uh folks, really appreciate you coming on and uh being here live. Interesting to note that we probably can't reliably use LDL cholesterol as a surrogate marker for uh improvement in cardascer risk. So again, I think we have more questions than answers about LDL. I think we've really oversimplified the pathophysiology and there's a lot more nuance that needs to be had. So that was the impetus for making uh this video. Uh Kerandale says, "Stop listening to the negative news because it can increase your blood pressure. " Yes, I would agree with that 100%. Uh folks, really appreciate you all being here. Thanks for watching the replay. Thanks for your comments, your likes, your shares. We will catch you on a future video down the road. Take care. Bye.