Mike Lustgarten Posted December 15, 2020 Report Share Posted December 15, 2020 LDL is arguably the most debated biomarker in terms of what's optimal for health. In the video, I present data showing that 100 - 140, not 50 - 70 mg/dL may be optimal in terms of minimizing disease risk and maximizing longevity. Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted December 17, 2020 Report Share Posted December 17, 2020 I also find the evidence somewhat compelling of low LDL being problematic. Which makes me suspect these guidelines are dangerously misguided as they promote pushing LDL below 100 for most everyone and below 70 for many: 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary I find it amusing that since Dave Feldman showed how easy it is to drop LDL https://cholesterolcode.com/extreme-cholesterol-drop-experiment/ a large and rapidly growing number of people are choosing to keep their LDL in the 300 to 800 range and then drop it below 100 just for the day they get it tested when needed for purposes of insurance or employer health programs. Quote Link to comment Share on other sites More sharing options...
Mike Lustgarten Posted December 18, 2020 Author Report Share Posted December 18, 2020 I think the data is clear that if you have CVD, lower LDL is then better, which explains the AHA's position. But for the rest of the population that doesn't have CVD? Low LDL in that case may be problematic, at least based on the evidence in the video. Quote Link to comment Share on other sites More sharing options...
Mike41 Posted December 18, 2020 Report Share Posted December 18, 2020 14 hours ago, Mike Lustgarten said: I think the data is clear that if you have CVD, lower LDL is then better, which explains the AHA's position. But for the rest of the population that doesn't have CVD? Low LDL in that case may be problematic, at least based on the evidence in the video. Totally agree. It’s a risk factor for some and not for others. Some people are virtually immune from developing CAD and would not benefit from extreme lowering, whereas people who already have it clearly do benefit form very low levels Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted December 18, 2020 Report Share Posted December 18, 2020 16 hours ago, Mike Lustgarten said: I think the data is clear that if you have CVD, lower LDL is then better, which explains the AHA's position. No it doesn't explain their position. They endorse the guidelines I posted which push statins for prevention based on estimated risk without any evidence of preexisting or developing CVD. For example: Quote 7. In adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels >=70 mg/dL (>=1.8 mmol/L), at a 10-year ASCVD risk of >=7.5%, start a moderate-intensity statin if a discussion of treatment options favors statin therapy. Risk-enhancing factors favor statin therapy (see No. 8). If risk status is uncertain, consider using coronary artery calcium (CAC) to improve specificity (see No. 9). If statins are indicated, reduce LDL-C levels by >30%, and if 10-year risk is >20%, reduce LDL-C levels by >50%. These criteria merely an LDL of 70 mg/dL and an ASCVD risk of 7.5% and it is time to discuss treatment options and initiate moderate intensity statin therapy to push LDL below 50! Here is the risk calculator: http://tools.acc.org/ascvd-risk-estimator-plus/#!/calculate/estimate/ Age is by far the biggest factor in risk and according to this if you are 63 or older and still have a pulse you should be taking statins. Quote Link to comment Share on other sites More sharing options...
Ron Put Posted December 18, 2020 Report Share Posted December 18, 2020 17 hours ago, Mike Lustgarten said: Low LDL in that case may be problematic, at least based on the evidence in the video. It may be a bit more complex than that. My understanding is that LDL particle size accounts for much of the inconsistencies in LDL studies. It seems to me that lower LDL is beneficial, but that about 30%-40% of the population has small. dense LDL particles, even among those with low LDL-C count. Small, dense LDL particles increase one's likelihood of developing CVD up to three times and it appears to be a better predictor than LDL-C alone.https://pubmed.ncbi.nlm.nih.gov/19657464/ Quote Link to comment Share on other sites More sharing options...
Mike Lustgarten Posted December 21, 2020 Author Report Share Posted December 21, 2020 On 12/18/2020 at 1:16 PM, Todd Allen said: "Age is by far the biggest factor in risk and according to this if you are 63 or older and still have a pulse you should be taking statins." How would you explain the reduced mortality risk in older adults who have higher LDL and total cholesterol, when compared with lower values? Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted December 22, 2020 Report Share Posted December 22, 2020 1 hour ago, Mike Lustgarten said: How would you explain the reduced mortality risk in older adults who have higher LDL and total cholesterol, when compared with lower values? Low density lipoproteins and the cholesterol they traffic have numerous essential functions. I expect their benefits outweigh any contribution to heart disease. I don't believe cholesterol causes heart disease although it might accelerate it under some circumstances. I believe this paper raises many good points: LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature Quote Link to comment Share on other sites More sharing options...
mccoy Posted December 22, 2020 Report Share Posted December 22, 2020 (edited) Todd, I remain skeptical about such a literature, and my main point is not scientific. I have no time to delve into this huge rabbit hole. But those who have time, or more correctly have a team of people who collect all the relevant literature, elaborate executive summaries, and keep up to date with the most recent developments, still believe that LDL is a big risk factor in CVD. So, I'm presently basing my belief system on people like Peter Attia, who was previously a supporter of the low-carb and paleo narrative but now seems to have evolved into more traditional and coherent outlook. He now seems to be one of the most unbiased sources in health risks posed by blood lipids. LDL-C might not be significant, and apparently better parameters are around, like LDL-p and APOB. LDL-c remains a proxy though, although sometimes inaccurate. Edited December 22, 2020 by mccoy Quote Link to comment Share on other sites More sharing options...
drewab Posted December 22, 2020 Report Share Posted December 22, 2020 I'll still take lower LDL as better as is showcased by my most recent lipid panel from about two weeks ago. Simply put, Dr. Esselstyn and Dr. Ornish didn't arrest and reverse heart disease with higher cholesterol levels. The only diet proven to arrest and reverse CVD, most of the modern world's number one killer of women and men should be the default diet until it is proven that other diets can do the same. YMMV. Triglycerides = 74 mg/dl (0.84mmol/L) Total Cholesterol = 114 mg/dl (2.96mmol/L) HDL Cholesterol = 39 mg/dl (1.00mmol/L) LDL Cholesterol = 61 mg/dl (1.58mmol/L) Some other lab values measured include the ones below, some of which are admittedly outside the normal range and have been consistently at that level for years and years for me now. In March I will have been practicing a WFPB mildly CR's diet for a decade. Even though I have low WBC and low platelet counts, I have zero symptoms of either. Quote Link to comment Share on other sites More sharing options...
Sibiriak Posted December 22, 2020 Report Share Posted December 22, 2020 (edited) 14 hours ago, Todd Allen said: Low density lipoproteins and the cholesterol they traffic have numerous essential functions. That's right. Crucially, various lipoproteins have evolved as protective agents against cancer and infectious diseases. Super low values may or may not be optimal for cardiovascular health, but its all-cause-mortality/longevity that counts, not just CVD. Therefore, the following statement is just wrong conceptually: Quote "The only diet proven to arrest and reverse CVD, most of the modern world's number one killer of women and men should be the default diet until it is proven that other diets can do the same. " The only group that definitely may need such a diet are those suffering from serious CVD. Any proposed general "default diet" would have to be judged on the full spectrum of health and longevity effects, not just the effect on a single disease. A diet good a treating CVD patients by no means can simply be assumed to be a good "default diet" for everyone. And, btw, perhaps someone would care to refute Michael Rae's take on Esselstyn's claims: Quote On Esselsyn/Ornish/Pritikin/McDougall: the studies purported to support the ultra-low-fat approach are not worth the paper on which they're written (to the extent that anyone keeps hardcopies any more). Esselsyn's and Ornish's reports are in very small numbers of intensely-managed patients with existing CVD; neither of them have reported any actual improvement in survivorship; and there are major confounders for both. Esselstyn is reporting a case series from his personal practice, and not (as is often claimed) a clinical trial: there was no control group, and moreover ALL of his subjects were on cholesterol-lowering drugs.(3) https://www.crsociety.org/topic/11161-macro-nutrient-ratios/?tab=comments#comment-12429 Edited December 22, 2020 by Sibiriak Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted December 22, 2020 Report Share Posted December 22, 2020 Does anyone else find it comical that there are people who are optimistic that we can slow, stop and even reverse aging when we still can't even reach scientific consensus on the optimal level of LDL cholesterol for health and longevity? This debate has been going on for over 65 years since Ancel Keys proposed diet-lipid-heart disease hypothesis in the mid 1950s. --Dean Quote Link to comment Share on other sites More sharing options...
Mike41 Posted December 22, 2020 Report Share Posted December 22, 2020 (edited) 7 hours ago, Dean Pomerleau said: Does anyone else find it comical that there are people who are optimistic that we can slow, stop and even reverse aging when we still can't even reach scientific consensus on the optimal level of LDL cholesterol for health and longevity? This debate has been going on for over 65 years since Ancel Keys proposed diet-lipid-heart disease hypothesis in the mid 1950s. --Dean We humans are quite arrogant about our science and smartness. But we live in a mysterious universe and we ain’t anywhere near understanding it! Biology is know known to have quantum effects like tunneling which is too damn bizarre and logic defying for any one to understand cause no one understands quantum physics. NO ONE! https://www.nytimes.com/2019/09/07/opinion/sunday/quantum-physics.html?referringSource=articleShare “I think I can safely say that nobody really understands quantum mechanics,” observed the physicist and Nobel laureate Richard Feynman https://youtube.com/watch?v=Bjh9n2Cw0TY&feature=share Edited December 23, 2020 by Mike41 Quote Link to comment Share on other sites More sharing options...
mccoy Posted December 23, 2020 Report Share Posted December 23, 2020 Another aspect to consider is the overall dietary optimization. If I'm not suffering CVD, it would be a significant cost to me to lower my lipids intake. For many reasons: I would surely be compelled to increase carbs, and that may increase glycemia (unless the IML factor governs in my system). My body and neurologic system appear to respond well to fats, especially so those from the vegetable kingdom, the so-called healthy ones: mainly EVOO, nuts and seeds. My neurologic system suggests to me that saturated fats are all right until a certain threshold, after which I feel bloated and nauseated. The only time I'm able to eat lowfat is during the hot season, eating fruit, drinking lots of low-fat yogurt with a high-protein, moderate carbs diet. It's a diet high in animal protein and EAAs, but I usually loose weight on it. The final effect of a lowfat diet to me has always been a significant loss of body weight, which I do not desire. The above is all anecdotal and personal, but that's an example of the complex interaction of the numerous factors involving a personal dietary regime. Quote Link to comment Share on other sites More sharing options...
mccoy Posted December 23, 2020 Report Share Posted December 23, 2020 On 12/22/2020 at 6:17 PM, Dean Pomerleau said: Does anyone else find it comical that there are people who are optimistic that we can slow, stop and even reverse aging when we still can't even reach scientific consensus on the optimal level of LDL cholesterol for health and longevity? I come from a technical, engineering background and my mind often cringes when I see authoritative papers publishing articles with sometimes exactly the opposite conclusions. In science, this almost never happens. In nutrition and biology, this seems to be the rule. Really nonplussing. Quote Link to comment Share on other sites More sharing options...
AlPater Posted December 23, 2020 Report Share Posted December 23, 2020 46 minutes ago, mccoy said: I come from a technical, engineering background and my mind often cringes when I see authoritative papers publishing articles with sometimes exactly the opposite conclusions. In science, this almost never happens. In nutrition and biology, this seems to be the rule. The concrete and steel of engineering is more defined than human nutrition and biology. Human nutrition and biology studies are also science, just studies of a much more complex system. Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted December 23, 2020 Report Share Posted December 23, 2020 22 hours ago, Dean Pomerleau said: Does anyone else find it comical that there are people who are optimistic that we can slow, stop and even reverse aging when we still can't even reach scientific consensus on the optimal level of LDL cholesterol for health and longevity? I'm hopeful of future progress versus aging although I'm not betting my life that it happens in a time frame meaningful to me. Which is why I place more emphasis on short term results for how I look, feel and perform versus speculation of what produces ultimate longevity. I think the lack of consensus for optimal LDL level might be due to it not being the most directly relevant factor. There is some evidence that OxLDL and particle size correlate better to CVD and related chronic diseases of aging. I speculate those are related to LDL turnover such that LDL which stays in circulation longer is prone to depletion and degradation becoming more problematic for disease. Perhaps the benefits when seen of low LDL are due to increased turnover. But it is also possible to have low LDL with slow turnover and high LDL with fast turnover and perhaps this accounts for those with "optimal" LDL levels who die from CVD and some with ridiculously high LDL having no signs of CVD. Here is a case study which is presented to discuss why the traditional interpretation of LDL might be inappropriate for those who see a dramatic increase in LDL level on a ketogenic diet. The pattern identified is common; I share it and find it of interest: A Standard Lipid Panel Is Insufficient for the Care of a Patient on a High-Fat, Low-Carbohyd,rate Ketogenic Diet Quote Next, we can examine LDL cholesterol as a major contributor to the subject's total cholesterol increase. Between baseline and follow-up, the subject's LDL-C increased from 90 to 321 mg/dL, the former measure being marked as “optimal,” and the latter, in alarming red, being twice the threshold of “high-risk” (Figure 1A). However, not all LDL particles are equal. The association between LDL-C and cardiovascular risk is driven by the association between LDL-C and atherogenic small dense and/or oxidized LDL (12, 13). It is primarily the small dense and/or oxidized LDL particles that can penetrate the endothelial wall, be taken up by circulating macrophages, and contribute to foam cell and plaque formation (31, 32). Large LDL particles, by contrast, do not display an association with cardiovascular risk and may, in fact, be cardioprotective (13, 33). A review of the subject's change in LDL-P (from 1,143 to 2,259) and size-based LDL subfractionation reveals that the increase in his LDL is driven exclusively by an increase in large LDL. Both his small and medium LDL even exhibited decreases of 8 and 11%, respectively (Figure 1A). Since the biological function of LDL is, at least in part, to carry triglycerides from the liver to peripheral tissues as a source of fuel, it is not at all surprising that the subject exhibited an increase in large LDL given his high-fat diet. Furthermore, the fact that only his large LDL increased suggests the subject's large LDL particles did not tend to decay over time into medium and small LDL. Stated more directly, the subject's specific increase in large LDL is consistent with an increase in LDL turnover rate and liver uptake. This represents a positive and adaptive response to the subject's switching from carbohydrate-based metabolic fuels to fat-based metabolic fuels. This analysis and discussion of LDL metabolism also explains why the increase in LDL-P and Apo(B), both driven by an increase in large LDL-P, may likewise represent healthy and positive adaptions. Quote Link to comment Share on other sites More sharing options...
mccoy Posted December 25, 2020 Report Share Posted December 25, 2020 (edited) On 12/23/2020 at 7:11 PM, AlPater said: Human nutrition and biology studies are also science, just studies of a much more complex system. I agree in part. There is some consensus on many complex systems, like for example atmospheric weather, circulation patterns, and their uncertainty. Other complex systems like the stress-strain interactions in the earth crust are partly understood but not very usefully (the unpredictability of earthquakes). But, presently, the science of human biology and nutrition has evidently a long, long way to go to achieve some degree of clarity and consensus on optimal health and longevity. Can we call it a failure? Edited December 25, 2020 by mccoy Quote Link to comment Share on other sites More sharing options...
mccoy Posted December 25, 2020 Report Share Posted December 25, 2020 On 12/23/2020 at 8:31 PM, Todd Allen said: Since the biological function of LDL is, at least in part, to carry triglycerides from the liver to peripheral tissues as a source of fuel, it is not at all surprising that the subject exhibited an increase in large LDL given his high-fat diet. Furthermore, the fact that only his large LDL increased suggests the subject's large LDL particles did not tend to decay over time into medium and small LDL. Stated more directly, the subject's specific increase in large LDL is consistent with an increase in LDL turnover rate and liver uptake. This represents a positive and adaptive response to the subject's switching from carbohydrate-based metabolic fuels to fat-based metabolic fuels. This analysis and discussion of LDL metabolism also explains why the increase in LDL-P and Apo(B), both driven by an increase in large LDL-P, may likewise represent healthy and positive adaptions. The above is an interesting interpretation, but it grants further extensive and costly studies to be validated... Quote Link to comment Share on other sites More sharing options...
drewab Posted December 25, 2020 Report Share Posted December 25, 2020 On 12/22/2020 at 8:05 AM, Sibiriak said: The only group that definitely may need such a diet are those suffering from serious CVD. In a way, I fall into this category despite being fairly young. Some of the details of my journey can be found below. Let's just say that after having open heart surgery twice in my twenties, there is absolutely no way that I want even the tiniest morsel of plaque accumulating. Coronary artery disease on top of congenital defects could be a death sentence for me. Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted December 25, 2020 Report Share Posted December 25, 2020 (edited) 11 hours ago, mccoy said: The above is an interesting interpretation, but it grants further extensive and costly studies to be validated... If we discount every paper with the phrase "further studies needed" there wouldn't be much left to consider at least in the nutrition and health fields. Getting to the point where further studies are not needed could make a good plot for a dystopian science fiction story of societies dragged down by hordes of unemployed researchers unqualified to do anything else putting tremendous pressure on social safety nets while a handful such as David Sinclair successfully transition into marketing and sales. Edited December 25, 2020 by Todd Allen Quote Link to comment Share on other sites More sharing options...
mccoy Posted December 25, 2020 Report Share Posted December 25, 2020 Todd, I partly agree, it remains the fact though that low-carb and hi-fat keto are recent dietary regimes which have not been studied as extensively as more common regimes. And again, sorry if I repeat myself, if Peter Attia has a team of five researchers collecting literature on lipids and talked for hours with Tom Daysprings and others on lipid optimization and he's still convinced that LDL and APoB must be usually below a certain moderate threshold, I tend to follow his advise of moderating LDL-ApoB. Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted December 25, 2020 Report Share Posted December 25, 2020 (edited) 2 hours ago, mccoy said: he's still convinced that LDL and APoB must be usually below a certain moderate threshold Dr. Attia has stated quite clearly he believes LDL is not sufficient for atherosclerosis. LDL might be essential for atherosclerosis although it is essential for life and can't be eliminated. Dr. Attia advises keeping LDL low on the basis that the medical system currently isn't very good at evaluating or modulating other essential factors of CVD such as endothelial injury and inflammation. He has also stated he has patients following low carb diets with very high LDL who decline his advice to address it. Edited December 25, 2020 by Todd Allen Quote Link to comment Share on other sites More sharing options...
Alex K Chen Posted December 26, 2020 Report Share Posted December 26, 2020 Alex K. Chen So should I eat more saturated fat if I have low ldl 1 · Reply · 1w Mike Lustgarten Alex K. Chen That's not as easy to answer without more info. Are your arteries free and clear, CAC score = 0? What are the leading causes of death for LDL < 100, and how can you track those diseases to make sure that any change that you make is going in the right direction? Your blood test data is mostly reflective of youth, but there is room for improvement. I'm not sure that sat fat or LDL would be the place to start. 1 · Reply · 1w Olafur Pall Olafsson Alex K. Chen I agree with Mike in that it's hard to say. I do not agree with him on the optimal LDL being that high, I think it's far below 100 mg/dl. However if your level is very low then I think it's more important to watch your HDL level. If your HDL level is also kind of low then maybe a bit of extra saturated fat would be more beneficial than harmful because it would likely elevate your HDL too not just your LDL and that is in many ways more important unless you have high LDL levels. The HDL/LDL ratio is very important because the HDL participates in reverse cholesterol transport and can basically partially reverse calcification of the vascular system if it's high. Also it is important to focus on oxidation and inflammation since it's predominantly oxidized LDL that gets stuck on the insides of the vasculature and inflammation drives that process through increasing foam cell formation. 1 · Reply · 1w Alex K. Chen Yeah, high saturated fat in a low oxidation/ inflammation environment might be ideal ESPECIALLY bc if incorporated into cell membranes it also guards against oxidation 1 · Reply · 1w Alex K. Chen You want your cell membranes to have high saturation 1 · Reply · 1w Mike Lustgarten Olafur Pall Olafsson Ha, I only agree that LDL < 100 is optimal if you have CVD, and then lower LDL is better. There's no data for all-cause mortality risk that shows < 100 for LDL is optimal, at any age group. 1 · Reply · 1w Mike Lustgarten Alex , whatever changes that you make, log them, and see what impacts your biomarkers. You're young and most of your biomarkers reflect that, so it's minor tweaks to get it all perfect and keep it there for decades. Knowing what impacts what in terms of the diet-biomarker link takes a bit of time. 2 · Reply · 1w Olafur Pall Olafsson FYI my LDL level is super low so my HDL/LDL ratio is even slightly higher than 1. I haven't been convinced in trying to raise my LDL level but I would like my HDL a little higher still so I am quite relaxed on intake of saturated fat because it should raise both my HDL and my LDL and with such low levels as mine the resulting higher HDL might be more optimal. 1 · Reply · 1w Mike Lustgarten It's easy for me to have LDL that low, too, and when considering the ACM data, that scares me. I don't want to avoid CVD but then die from cancer or a bad infection, both of which are more likely with LDL < 100, when compared with somewhat higher values. 1 · Reply · 1w Olafur Pall Olafsson Mike Lustgarten Maybe the relationship with cancer and infections is related, since both could be caused by suboptimal immune responses. In any case I'm curious to find out what explains this relationship with low LDL. Hopefully we won't have to wait too long for more answers. 1 · Reply · 1w Alex K. Chen Has Peter attia written about it · Reply · 1w Olafur Pall Olafsson Regarding infections, I just checked my notes and see that there is some evidence of cholesterol possibly playing a protective role against inflammation during infections. Mike Lustgarten you're going to like this. It may help dampen the responses to endotoxins. http://pmid.us/8450032 However HDL cholesterol seems to work for this purpose so it may be better to focus on raising HDL than LDL if the latter is very low. http://pmid.us/1930690 I mean if there is some significant effect of low cholesterol on immunity then it is likely the total cholesterol rather than LDL in particular that is responsible for it. If true then an unusually high HDL might protect against an unusually low LDL in this respect. PUBMED.NCBI.NLM.NIH.GOV Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death - PubMed Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death - PubMed 1 · Reply · 1w Mike Lustgarten Ha, Olafur I wrote about the LDL, HDL and LPS connection in my book, so I'm well aware! My average HDL over the past 5 years is in the mid-40s, and I'm working on getting it into the 50's again for my next blood test next week. 1 · Reply · 1w Alex K. Chen Does blood cholesterol correlate with membrane cholesterol index · Reply · 1w Olafur Pall Olafsson Alex K. Chen "Does blood cholesterol correlate with membrane cholesterol index" I am not sure. Blood cholesterol levels influence the membrane composition of platelets and erythrocytes but those two cell types lack a nucleus so they are not reflective of most other cells in the body. http://pmid.us/8740244 I think the membrane cholesterol is mostly under genetic control in other cells. I don't remember seeing studies on the influence of blood cholesterol on membrane cholesterol index but I can't say I have looked into that in the past specifically. PUBMED.NCBI.NLM.NIH.GOV Influence of cholesterol-lowering on plasma membrane lipids and function - PubMed Influence of cholesterol-lowering on plasma membrane lipids and function - PubMed · Reply · 1w Write a reply… Quote Link to comment Share on other sites More sharing options...
mccoy Posted December 26, 2020 Report Share Posted December 26, 2020 (edited) 14 hours ago, Todd Allen said: He has also stated he has patients following low carb diets with very high LDL who decline his advice to address it. I don't remember everything which has been told in those podcast, although I tend to concentrate on the points I believe are more significant. As an MD, Attia has also legal responsibilities, if some of his patients die with a very high cholesterol, that may spell big trouble for him in a court, unless the DAs consultants follows a keto diet! Edited December 26, 2020 by mccoy Quote Link to comment Share on other sites More sharing options...
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