Blood Lipids and Cardiovascular Risk: Everything You Need to Know

[@stevelanghorn1407]

Thankyou for this excellent video and the effort you’ve clearly made to clarify this (apparently never-ending) “hot” & divisive topic…which so often attracts downright eccentric & biased opinion…from both sides of the lipids / statins debate. It’s actually a relief to hear calm, rational, well-researched…& balanced…”sanity” communicated this well. Fantastic job!

[@nourishedbyscience]

Thank you for your kind feedback. Cheers Mario

[@robbyvillabona]

By far the clearest explanation of the subject in the six months I have been looking through KZbin videos. Thank you for this video.

[@azgirl5265]

Mario, this video is one of the best I’ve seen on most things lipid. Thank you for including feedback on some of the current opinions regarding lipid size & type, particle numbers and also ketogenic diets. I am not a med prof nor have a science background. Your explanation and use of charts is most helpful in understanding a complex subject. I have saved this one and will watch again. Btw, I don’t think it was too long, at all. Just right, imo. Some presenters have 3 hr vids and those are hard to get thru. Thank you so much for clearing up some questions and confusion I have been struggling with. Keep up the great work! You are very much appreciated!!

[@nourishedbyscience]

Thanks for the kind feedback, AZgirl!

[@jbzoom]

Excellent video. I am a 71 year old cardiac patient. A year ago, I required a lateral heart artery stent. Your video clarified much of what my cardiologist had told me and has given me the incentive to take my LDL level more seriously. Thank you.

[@dalialovesdoggies4361]

how did you end up lowering your ldl please?

[@jbzoom]

@@dalialovesdoggies4361 - diet (less carbs and red meat) and swimming 3km (2 miles) a week. I progressively increased my swimming and the ldl gradually fell. Less vigorous exercise doesn't work (for me, anyway).

[@AchilleRemi]

@@jbzoom you lowered your LDL by eating less carbs and less red meat? What did you usually eat?

[@jbzoom]

@@AchilleRemi I used to eat more junk food, more carbs and more red meat. Now I eat red meat maximum twice in a week, moderate carbs in two meals a day. I eat at least five a day of fruit and vegetables. Lunch is vegetarian at least four days a week. Evening meal is typically an apple, a banana or both.

[@AchilleRemi]

@@jbzoom Thanks much for your reply. I understand. And what about your HDL? Did it go up, down?

[@realDaveFeldman]

Thank you for this comprehensive video and your coverage of our work with LMHRs and the Lipid Energy Model. In fact, your assessment of the match analysis is arguably the best I've seen to date from someone outside our group, particularly in your calling attention to residual risk expectation for the age of our compared cohorts. Very good, video, Mario. 👏

[@nourishedbyscience]

Thanks, Dave. The more I think about LMHRs, the more I am intrigued by your hypothesis. I also do think that there clearly was a chance that a difference in total plaque volume could be seen at this baseline comparison. At the same time, the importance of the cumulative exposure does make it increasingly likely that differences between groups will emerge (by the way, are you going to follow the Miami Heart participants as well, to have a 'control'?). Considering the data on cumulative exposure, the risk of a clinical ASCVD event should now double every 5 years in LMHRs, and maybe every 12 years in the Miami Heart controls. That's considerable, but it also shows that your effort would almost certainly benefit from greater sample sizes. As intrigued as I am, I wanted to make sure to emphasize that the baseline data do not conclusively prove (as some people put it) that elevated LDL-chol can safely be ignored on keto, or even that these data show that the Lipid-Heart hypothesis is wrong. I loved that you and Nick emphasized that as well in the interview with Ken Barry. It would be so understandable for you guys to get carried away in your justified excitement of the study and these first data, and maintaining an appropriate mindset is not easy in a situation like that. Cheers Mario

[@andreac5152]

Dear Mario, I think that if they really wanted to match the control group they could've included people with the same triglycerides, HDL and BMI as well but not on keto, hence with normal LDL. I don't see a point in comparing two groups that are different in such a relevant way, the effect of LDL cholesterol can't be isolated. Moreover given that 30% of people in the control are on statins I'm not so sure that the lifetime cholesterol burden is higher in the lmhr group.

[@nourishedbyscience]

I actually like their study design. The goal was to assess the implications of the LMHR phenotype on ASCVD. And the LMHR phenotype is characterized by low BMI, high LDL-chol, high HDL-chol, and low TG. So as long as we consider that in the interpretation of the results, I do think this is fine. Also, practically, it would have been next to impossible to find normal people, particularly men, who have such high HDL-chol but who are not on keto. The point you make about statin use in controls, however, is an important one, I agree. If some of these controls have the current LDL-chol only on statins, then their lifetime LDL-chol exposure would include a time off statins, and that could raise their exposure substantially, which could dilute the effect of LMHR-driven hypercholesterolemia. Good observation! Do you have thoughts, or even data, on this, Dave? Cheers Mario

[@andreac5152]

@@nourishedbyscience thanks Mario, I mostly agree with you. Nonetheless, along with cholesterol before statins, it would be interesting to know Triglycerides before keto, as they add up to the non-HDL burden.

[@themekfrommars]

Dear Dave, Are you also capturing the "advanced lipoproteins" this video references within your LMHR study cohort? Also, did these lipoproteins come into consideration when determining the LMHR phenotype, or else study member suitability, e.g. exclusion of high lp(a) individuals? Thanks

[@jackonsville]

Thank you for this video. I have watched many hours of videos on this general topic and have been left confused but for the first time I feel I have a basic understanding of the different types of lipoproteins and the role they play in contributing to heart disease. You seem to have the ability to present information in a clear, not overly complicated manner.

[@nourishedbyscience]

Thank you for the kind feedback. That is exactly why I felt it needed to be pretty detailed and thorough. Cheers Mario

[@bonnieo8]

I was also a bit confused about how both”sides” might be right until I listened to David Diamond. He brought it all together for me. You might try listening to his presentation at Low Carb Denver 2023.

[@frank2096]

Thank you, Dr. Kratz. Your approach to a variety of health/nutritional topics and responses to trendy, single focus health topics is reassuring. Honestly, it is a miracle that I am still alive and here's why: Diagnosis of Hashimoto's in my late 30's in an effort to address 300+ Cholesterol lab results; began treatment combining thyroid replacement and high doses of statins; "Widow Maker" heart attack at 43. Afterward, I continued to drink alcohol and work in a very high stress job and eventually became morbidly obese. Later, the possibility that I suffer from familial hyper cholesterolemia was brought to my attention and I was placed on a pks9 inhibitor with considerable improvement in my lipid panel. Viewing your videos has led me to the reasonable conclusion that I have metobolic syndrome. I started OMAD 6 months ago and my dietary restrictions include; no fructose/refined sugar. Otherwise, I avoid high quantity carbohydrate consumption from bread, pasta, noodles, rice and potatoes. I do eat vegetable based proteins (excluding soy) and lean meats. I have lost nearly 30 lbs and I am feeling much better. My goal is to lose an additional 30 or 40 pounds over the next 6 months. Other KZbin resources would have me believe that stuffing my face with organic bison meat after a V02 max session is the key to longevity. I doubt it. In fact, my heart attack occurred in the early morning hours after a high intensity training session the previous evening. Some of the advice I have seen and heard on KZbin could be really dangerous for some people.

[@gordonmcculloch8763]

Excellent. Balanced and sufficiently detailed to allow someone, more than superficially interested, to understand the issues and the presenters assessments.

[@tadeupinheiro5250]

This is the best KZbin I have watched about the topic. It is unusual, because here we have 100% knowledge associated with 0% bias. Thanks Mario.

[@nourishedbyscience]

Thank you. I wish I could offer 0% bias; we all have our biases, but I try to stay clear of diet tribalism and stick to what the data are telling us.

[@markotrieste]

I'm not on a keto diet. I drastically improved my IR markers with intermittent and prolonged fasting. I do however feel that eating low carb in the feeding window makes it much easier to fast later on. Also, with carbs it's much easier to overeat. Lost a good amount of weight, improved VO2 max, drastically lowered triglycerides but APOB still above 100...

[@myoung48281]

That is by far the most complete and understandable explanation on this subject. I've bookmarked the video and subscribed.

[@skiing101]

Excellent, as all your videos. Would you be willing to go over ways to lower risk factors for atherosclerosis or, even better, dicrease the plaque itself? Particularly, evidence quality for non-medicated ones, e g. plant-based diet, HIIT, berberine, etc?

[@jrkob1156]

Mario, thank you for the video, it is an absolute masterpiece. I see that you have stayed clear of commenting on the potential and often claimed benefits of elevated HDL on CVD risk. A lot of people who have genetic hyperlipidemia (such as myself) have both elevated LDL and elevated HDL, but because they have elevated HDL, they will downplay the relevance of their elevated LDL. The 2019 ESC (European Society of Cardiology) Guidelines say, let me quote section 5.3.3. in its entirety: "5.3.3 High-density lipoprotein cholesterol and risk of atherosclerosis The inverse association between plasma HDL-C and the risk of ASCVD is among the most consistent and reproducible associa tions in observational epidemiology. In contrast, Mendelian randomization studies do not provide compelling evidence that HDL-C is causally associated with the risk of ASCVD. However, this evidence must be interpreted with caution because most genetic variants associated with HDL-C are also associated with directionally opposite changes in TGs, LDL-C, or both, thus making estimates of the effect of HDL-C on the risk of ASCVD very difficult using the Mendelian randomization study design. Furthermore, there is no evidence from randomized trials that therapeutically increasing plasma HDL-C reduces the risk of CV events. In the Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome (dal-OUTCOMES) trial, treatment with the cholesteryl ester transfer protein (CETP) inhibitor dalce trapib increased HDL-C without any effect on LDL-C or ApoB, but did not reduce the risk of major CV events. Similarly, in the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High-Risk for Vascular Outcomes (ACCELERATE) and Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification (REVEAL) trials, treatment with CETP inhibitors more than doubled HDL-C levels, but did not appear to reduce the risk of ASCVD events beyond that expected from the modest reductions in ApoB levels. Furthermore, several randomized trials have shown that directly infused HDL mimetics increase plasma HDL C concentrations, but do not reduce the progression of atherosclerosis as measured by intravascular ultrasound. Therefore, there is currently no randomized trial or genetic evidence to suggest that raising plasma HDL-C is likely to reduce the risk of ASCVD events. Whether therapies that alter the function of HDL particles will reduce the risk of ASCVD is unknown". Also, I note that the 2019 ESC Guidelines (along with the previous ones) advertise targets, dependings on the level of CVD risk of individuals, that are in terms of LDL exclusively, and are NOT dependent on any level of HDL. In other words, HDL isn't part of the equation when deciding on LDL-control treatments. I would like to know if, in your research, you have found compelling evidence that elevated HDL was a definitive, contributing factor to CVD risk reduction ? And by this I don't mean a mere "correlation" between higher HDL levels and lower CVD risk (I believe such correlation exists), I mean a direct "causality". Or... is this just... a myth. (as a side note, you are showing an incredible amount of restrain when responding to some of the silly, tiktok-level-of-science comments from some of the people who comment on this video, kudos for that !) - Jean, from Hong-Kong

[@nourishedbyscience]

Hi Jean, What a great question. HDL is one aspect that we now see quite differently than we did when I wrote my dissertation on the topic, more than 20 years ago. The main changes have been (summarized briefly): - We no longer consider HDL when assessing whether elevated LDL-chol/apo B+ particles should be treated. In other words, people with genetically elevated apo B should not refuse treatment with the justification that their HDL-chol is high, or that their ratios (apo B/apo A1, for example) are not so bad. By the way, HDL-chol is still used in overall risk prediction models, to assess the overall risk and the need for risk factor control. These are slightly different issues. - HDL particles are still thought to be a major player in ASCVD. However, we now understand much better that functional capacities of HDL particles are what matters, associated with more than 50 different proteins that are carried around the body on HDL particles. And it does seem that changes in the composition and activity of these enzymes plays a critical role, more so than the amount of cholesterol the particles carry. Overall, much is still not fully understood about the role of HDL particles, but you are correct to not ignore high apo B/LDL-chol with the justification that HDL-chol is also high. Best, Mario

[@jrkob1156]

@@nourishedbyscience Thanks for the response Mario, very clear, I appreciate it - Jean.

[@saapproved]

Fair and very helpful doctor. Thank you for your work. I will do everything I can without the medicine first, and see how that goes.

[@JasonPhillip303]

wow you are natural teacher am so amazed at the way you bring across these topics please continue

[@corinayuen2487]

Your video is fantastic! I always get so confused by the Lp(a), Apo(B), etc. Your charts made everything so clear. I now have a basic understanding of where to put each particle. Thank you!

[@KoiRun50]

I downloaded this video and really enjoyed listening to it on my bike home from work. I will watch it will tomorrow as I know your illustrations are awesome. So far you have added much needed clarity on this issue. Thank you for your hard work.

[@barz3rk808]

I find your videos the most helpful to understand the theory behind these controversial and very important topics that others just gloss over. You really provide the most comprehensive information in an easy to follow manner, honestly. Could I make a request for a video discussing the best approaches to lower LDL cholesterol that's definitely backed up by science and the literature, and not just speculation from nutritionist content creators? Thank you.

[@vith83]

I've watch a TON of health and blood lipids vdos on KZbin, and this vdo is one of the best, if not the best explanation on blood lipids I've found so far. Thank you for the explanation.

[@themekfrommars]

I requested an advanced lipid test earlier this year. LP(a) was measured at 180mg/dl. My family doctor just waved me away. This is the best video I have seen on this topic by far, and I've watched them all, and I wasn't clear on the relationship between lp(a) and Apo B previously. My Apo B is actually top end of the "normal" range, and My Apo A1 is high. I'll add lipids to the list of topics my family doctor is clueless about! Looks like I need to find a cardiologist.

[@nourishedbyscience]

Thank you for the kind feedback. One thing that you may want to understand fully, given your lab results: if your apo B is at the top of the normal range, it probably is around 100-120 mg/dL. That may confuse you given that your Lp(a) is 180 mg/dL, and I said in the video that Lp(a) is included in the apo B measurement. How can this be true? Well, here is the thing: apo B measures just the apo B protein itself, which is a portion of the apo B-carrying lipoproteins. The test for Lp(a) measures the entire particle, i.e., both proteins (apo B and apo(a)) and all of the lipids (cholesterol, triglycerides, phospholipids). Therefore, my guess is that your Lp(a) particles contribute 20-30 mg/dL to your total blood apo B concentration. Or phrased another way: about 20-30% of your atherogenic lipoproteins are Lp(a) particles. The rest of your apo B sits on VLDL, IDL, and LDL particles. Makes sense? Overall, it's reassuring that your apo B is still in the normal range even though your Lp(a) is quite high. However, the high Lp(a) itself poses a risk, which may still be very low overall, depending on what your other risk factors look like. However, I do think it's a good idea to discuss this with a good preventive cardiologist and make a plan on how to rigorously control all of those risk factors that you can control. Unfortunately, we currently have no treatment to selectively lower Lp(a), although several medications are in end-stage clinical testing. Best, Mario

[@JMK-vo8pv]

Unfortunately, I think you will find that MOST cardiologists are clueles when it comes to the nuances of lipoproteins.🔬

[@IoannisPanagiotopoulos]

​@@nourishedbyscience thanks for the fantastic explanation again Mario! An additional question, assuming that LDL measurement includes the whole particle, is it safe to assume that in a given test, Lpa is lower than LDL? And if not, would you question the quality of the lab?

[@nourishedbyscience]

No, again: Lp(a) measures the entire Lp(a) particle, including all of the cholesterol, triglycerides, phospholipids, and protein carried on Lp(a) particles. When we measure LDL-cholesterol, we only measure the cholesterol portion of all LDL and Lp(a) particles. In other words, Lp(a) in mg/dL will sometimes be higher than LDL-cholesterol in mg/dL.

[@IoannisPanagiotopoulos]

@@nourishedbyscience thanks so much for clearing it out! Grateful to all your awesome content and help!

[@deborahlee3621]

Thanks Mario. You just helped me recommit to an attack on all fronts of my metabolic syndrome. Can't just focus on one component as primary.

[@BillyBoy66]

Saw your comment here and wanted to ask how the "attack on all fronts" of your metabolic syndrome is going. Hope its going well.

[@MichaelTexas70]

This guy needs to be the US Surgeon General.... immediately

[@bikeman9899]

I had to listen to this a few times to digest the material. It's objective and fact based. Excellent. Well done Marco.

[@andrewgreenfield9000]

Thank you for this excellent video. Can you explain why lifestyle advice to lower cholesterol includes reducing saturated fat but not unsaturated fat? Also, does most of the standard healthy eating advice for lowering cholesterol affect the lipid profile indirectly by helping with weight and insulin resistance, rather than directly? Many thanks

[@dr.samierasadoonalhassani2669]

Saturated fats affect the microbiome, causes inflammation, constrict blood vessels after eating such fat especially from animals products, weight is the result of good metabolic health leads to ideal body weight. Even polyunsaturated fats go to sources like olives, nuts ,seeds,flaxseeds,I did experiment on myself stopped all animals products and all fats. , I always practiced healthy life style, no salt, walking, sleep.In two weeks reduced my total cholesterol from 7.4 to 4.8 milimole/ litres. But checked my liver enzymes started to be raised a little in just these 2 weeks.why I answered you not Mario? It is because I am a medical doctor interested in health and thought to spread health is good.Thanks.

[@kennethyuman1940]

Excellent video. I highly appreciate the balanced view. I wish you could address another claim: Long living people, especially those healthy at age 80 or above, usually have high LDL-c readings. Not as outsiders like some smokers live long, but as a pattern.

[@miguelmiranda9122]

Wow! Very well explained video. Thank you very much for sharing this information. The manner in which you deliver the information is superb. Very understandable and concise. The slides are wonderful and very well organized. Once again thank you.

[@grahamlucas6033]

Thanks so much for this video Mario, i have been researching this topic for years and although found out lots of good reliable info and facts I have yet to find a presentation compiled in this way. I have Familial Hypercholesterolemia and a CA score of 540 mainly in the left descending artery. and I had to explain to my doctor what LPa was and it took persistence to convince him to send me for a CA Scan. Most grateful for your videos.

[@susibul5320]

Outstanding talk, thank you. I am LMHR with pre-diabetes and some liver fat, low carb diet, normal range cholesterol for nhs.

[@lizzerlou2042]

Thank you so very much! This is just the overall information I needed to make a good decision about my health going forward. This content will most likely save some lives. There is so much flaky info out there. I can't thank you enough for post this. 🙂

[@mariomenezes1153]

This was a truly brilliant video. The first I have seen that takes an impartial view of both sides of the argument. And it includes reference and a critical look at Dave Feldman's and Nick Norwitz's ongoing study on LMHRs. Have seen, and not appreciated, the knee jerk reaction of too many lipid "specialists" that the study is incorrect. It is almost as if they know the cause of heart disease and are still not seeing that all current theories are based on correlation without understanding causation. This should alway leaves room for doubt. This brought up a good point where you talked about LDL and glucose/insulin as both being produced by the body and damaging when out of range. I do not agree with this completely. The underlying mechanism of why high or low glucose and/or insulin do damage in the body is pretty well understood (we do have more to learn but we know enough already). The underlying mechanism of why LDL is dangerous has never been understood. Is LDL by itself dangerous and plaque forming? Is cholesterol a repair mechanism and the plaque formation a response to arterial damage caused by other factors, what causes plaque (like using a tub of tar to patch up holes in a driveway leaves a patch). This may be similar to blood clotting in cuts. Will reducing LDL in the presence of arterial damaging factors help, even though plaque buildup is prevented (like preventing you from access to tubs of tar but the holes in the driveway remain)? And as you pointed out, there is most likely a confluence of the risk factors. LMHRs lead a lifestyle that most likely means the other risk factors are not present. However, understanding their results will lead to a better understanding and growth in medical knowledge. Lots of questions to be answered still. In any case, I really appreciate the unbiased and nuanced view you have taken towards the topic. This is what moves science and learning forward, and not knee jerk reactions when reputational knowledge is challenged. This should not be like the Catholic church's reaction when Galileo proposed that the earth was not the center of the universe but should be like when Einstein proposed his theory that proved that physics, as known till then, behaved differently as we approach the speed of light.

[@jackgoldman1]

What to do? My retired MD stated "Exercise, lose weight, eat whole food, not ultra processed food." At least that is something I can do. Thanks Mario. You are helping extend people's quality and quantity of life. Thanks for your good deeds.

[@bonnieo8]

I’m already doing all that too, but only recently. I’m 74, started out slim, adding about a pound a year until after menopause where my weight dramatically went up. Even though I had a stroke this year after losing 40 lbs (now 80 post stroke), I assuming it was the high sugar and junk food diet that caused my atherosclerosis on top of maybe having FH, and not the recent change to low carb that ultimately caused my stroke. I could be in that subset of people with FH who also have clotting factors that lead to my stroke. I’m hoping my no sugar, no grains, no seed oils will make a difference. I’m much more afraid of the impact of sugar on my endothelium than I am of eating fat even if it does raise my LDL. Anthropologically, this kind of diet makes more sense than one high in carbs, even healthy ones. But will switch if I continue to get more inflammation and atherosclerosis.

[@nourishedbyscience]

As I explain in the video, I do share your assumption that insulin resistance and it's sequelae as well as high blood sugar are major contributors to ASCVD, but I would not gamble and ignore high LDL-cholesterol, particularly not if I had had a stroke. Just my 2 cents, and not medical or nutrition advice. Best, Mario

[@catherinewilson1079]

Thank you for this video and the notification I received of it’s creation. I have chosen at age 70 to reduce my susceptibility to type 2 diabetes by changing to a vegan diet. The two people I know who follow these type of diets have very low LDL cholesterol. I also think that excess quantities of meat in the diet can have other bad side effects than simply high cholesterol. So far, following a low-fat vegan diet is working very well in reducing my BMI. I will find out in February if it has also helped my other numbers.

[@bonnieo8]

So far, I’ve been going in the other direction (low carb) so am very interested in your results. Still reading and learning. Best of luck!

[@trend0000]

Excellent video and finally cholesterol issue was dissected thorougly for better understanding! Thank you very much! It’s really great chanel you have!

[@johannnagl5637]

Hallo Mario, wie immer ein ausgezeichneter Vortrag zu einem überaus wichtigem Thema. Ich glaube, dass alle Abonnenten und Zuseher gespannt auf jeden neuen Vortrag von Dir warten. Besten Dank und weiterhin viel Erfolg !

[@jobl5505]

Excellent video, riveting, doesn’t get much better. Brings it all together and up to date. I am what was classed as LMHR, had been LCHF for about 4y, but after finding I had some stenosis I decided not to take the risk. Reduced my non hdl to about 110 using diet, I will look at my lp(a) now.

[@nourishedbyscience]

Thank you for the feedback, and thank you for sharing. I have heard from so many that they do best on keto, for other medical reasons, and the massively elevated LDL-chol are a real issue in these cases. For others, if strict keto is not medically required, then re-introducing some carbs can make a huge difference to apo B/non-HDL-chol/LDL-chol, and at this point, until we have better long-term data, I do think this is the prudent thing to do. Bst wishes, Mario

[@jobl5505]

@@nourishedbyscience thanks Mario, you have articulated the evidence perfectly and of course I agree. I will get an lp(a) test when I’m feeling brave :) and this will inform my next step.

[@ebluz]

Another excellent presentation. I love the detail you go into, and your diagrams help greatly to visualize the material. It is rare I will even start viewing a video I know is an hour long, but I am sure to watch yours. Generally, the focus of cardiovascular disease seems to be its impact on the heart, but it can also affect the brain (and other parts of the body). I'm a 70 year old white male whose LDL-C has ranged from 136 to 185 over the past 20 years. As for other risk factors, I have never smoked, but my BMI had gradually increased from 24 to 28, and I gradually transitioned into pre-diabetes over those same 20 years. My blood pressure has been traditionally elevated (130s/80s - doctors never pushed taking meds until this year). Seems I was a poster-child for pre-diabetes and CVD. Blood pressure and weight would probably have been worse if I had not been running 3-5 hours a week for a majority of that time. I now have my BP under control with meds, my BMI back down to 24 (mostly by cutting out junk food), and according to my most recent blood test am no longer pre-diabetic (A1C of 5.5). During an ER visit this past June due to a sudden blood pressure spike (185/110), they took an MRI of my brain, and made an incidental finding of "Mild Ischemic Changes", or Cranial Small Vessel Disease. It's my understanding this is fairly common with people my age, but not commonly tested for. The most likely culprit for this disease is Arteriosclerosis. That finding led to Cardio Calcium Score, Echo Cardiogram and Stress tests to verify my heart can safely withstand strenuous exercise. I passed all those tests with flying colors, including a calcium score of zero, despite my chronically elevated LDL-C (guess I'm genetically lucky). I have read there are other conditions that can lead to CSVD, but my doctor is convinced Arteriosclerosis is the cause despite the Calcium Score of zero, and strongly advises I continue taking a statin to lower my LDL. Intuitively, my thinking is if you have CVD, it would tend to build up everywhere. Perhaps you could touch on the probability that even with a Cardio Calcium score of zero CVD could still affect other parts of the body, and how that comes about.

[@nourishedbyscience]

Sorry the video is so long ...! There is just so much to talk about, and so much misinformation, I felt that a short video just describing the common risk factors would be useless for most people. Regarding your question: the most common test to measure the coronary artery calcium (or CAC) score is only able to measure plaque at an advanced stage that has been calcified. It is still possible to have so-called soft plaque that doesn't show yet in the CAC assessment. You would need to have a more involved test done to assess soft plaque called coronary CT angiography. Also, most people have generalized atherosclerosis to some degree, but it is not uncommon that one part of the body, or even one artery, could be affected more than others, Sometimes that can be because of greater blood flow shear forces as a certain spot, just because of little anatomical quirks in how the blood vessel is built. Hope this helps!? Best wishes, Mario

[@ebluz]

@@nourishedbyscience Yes, thanks. Much appreciated!

[@azgirl5265]

It’s really not too long. For some, it may be bc of the technical aspect, but you need to give it the time to get a ‘whole picture’ understanding. Really appreciate your balanced & informed approach to conflicting opinions.A+++

[@2009raindrop]

I am so glad I stumbled upon your channel while trying to understand better how to use my new OTC CGM. You are an *amazing* communicator! I will probably have to watch this one a couple more times because there is so much great information. But it is an important topic to me because of my concern about taking statins. Thank you very much!!

[@plantreport4690]

Thank you for the explanation! Your content is fantastic!

[@danguee1]

This is such an excellent video. Please don't apologise for 'going technical' - it *_is_* a technical subject.... Simplistification would have been a mistake. I note from the comments that even people confessing not to be technical or good with numbers actually appreciated you doing a (relatively) deep dive on this

[@quaternion-pi]

superb, balanced , thoughtful analysis of available literature on this important topic. Thanks.

[@yassennikolov3519]

By far the most detailed, concise and accessible information on the topic I've seen!

[@davidbarnes774]

This is the best presentation that I have seen on the subject. Well balanced presentation of the research that can be understood by all.

[@LifeofBrianP]

Great vid Mario. I was an ultradist runner 30 yrs ago. I had a chol panel w 3x tot/LDL chol and it caused quite a stir. I know some in the study, I beleive most are on keto/low carb diets as is me today. Basically, if their bodies are preferring fat burning they will be LMHR. When I ate/lived like everyone else I had a normal panel.

[@ralphbuschmann740]

I really would Like to hear your opinion on the optimal Distribution of the macro nutrients. I am more confused than ever on this „simple“ topic as there are so many different recommendations. Apart from that the „optimal“ uptake of macro nutrients is certainly the first step to Health.

[@mattzilla331]

Look up dr esselstyn. He got the best heart disease reversal results. Look up his "make yourself heart attack proof" lecture.

[@jillbetts1241]

Such an excellent, comprehensive and informative video that cleared up much of my confusion. Thank you

[@tames307]

A very informative and detailed explanation. One thing I wish to know more about is related to the role of artery health in ACVD risk. The role that LDL plays appears to be well documented, but it seems there are two participants in this problem: the LDL particles and the artery walls they get embedded into. I don't know if you've address this before, but I've heard about a negative effect of elevated insulin levels in the blood that can damage/irritate artery walls over time, causing them to be more vulnerable to particles getting embedded. It would seem, then, that maintaining normal glucose levels and avoiding foods that elevate blood insulin levels (or mitigating the effect by choosing optimal times to eat those foods) also has a key role to play in preventing ACVD.

[@GigaFan1989]

A truly exceptional video !!! Thanks a lot for your extreme clarity !!! Mario, thanks to you I finally understand Lipids !!!

[@azdhan]

Excellent video! This is by far the best explanation I have come across on the topic. I agree with much of you say as it is consistent with the totality of evidence, hierarchy of evidence, and converging lines of evidence. Having said that here are my thoughts on this, so please feel free to correct me Mario (1) The LMHR theory is intersting. But when the LMHR participnts were vetted was an assessment done as to what dietary fats they were mostly consuming. Keto can be done two ways: one is getting all your fats from saturated fats from lots of butter, bacon, keto desserts, red meat, other meats. The other is to get most of these fats from polyunsaturated or monosaturated fats from salmon, avocados, nuts and seeds. (2) If an LMHR phenotype exists, I don’t believe it is a total vindication of keto diets high in saturated fats or an outright carnivore diet. We are talking about a relatively small percentage of a relative participant siize. And in absolute terms, the majority of people doing keto may not fit the LMHR phenotype if it exists and any protection that would be afforded to them from running their LDL numbers through the roof. Most people on keto may not have such long term protections, especially if consuming a high saturated fat keto diet Finally just for the record, I am not against any diet that gets people to totally stop consuming aSAD diet of highly processed pallitable foods, and that they can best sustain long term. Healthwise, it will give them more benefit than a consistent junk food diet. I personally experimented with “text book keto” where I used My Fitness Pal to track all my foods and ensure I was hitting the prescribed keto macros of fat, protein, and carbs. I lost a lot of body fat but also ended up shedding a lot of hard earned lean muscle mass together with the bf as measured before and after via DEXXA Scan. My metabolic and blood markers were not significantly better or worse vs my peior mediterranean diet. As someone trying to preserve as much muscle mass as possible, I opted to not continue with keto as I didn’t want to be one of those who ended up fast tracking my way to sarcopenia as an elderly person.

[@nourishedbyscience]

Good comment. I haven't seen any dietary data on this cohort. There are a lot of details of the study design that were, understandably, not shared in the oral presentation, so I'll be looking to the paper once it's published to get a better sense of these. Cheers Mario

[@azdhan]

@@nourishedbyscience Thanks Mario. I always look forward to your videos and content. Keep up the great work! Thanks again for sharing. Best regards from Winnipeg Canada.

[@glendahopp]

Excellent video that pulls together everything I've been learning in an easily understandable package. The graphics were very helpful. I'm sharing this with family members.

[@deborahbrown4775]

Excellent tutorial!

[@SomeRandomOldGuy]

Thank you. This was very helpful. I appreciate all the research and synthesis that you put into your videos.

[@jawadnimri9989]

What a piece of work, much appreciated.

[@Worldly40]

Very educational. Thank you!

[@waldguy]

Your explanation was well balanced. Thank you. One other thing noted on other channels claims the oldest of people consistently have higher LDL than those who do not survive. The lipid profile may well provide a heightened degree of immune response (eg. to cancer). Although these folks may be a heightened risk of heart attack, all cause mortality is often lower. Some studies seem to support this.

[@nourishedbyscience]

Yes, this is an observation I am curious about. High apo B-carrying lipoprotein concentrations are almost certainly not just 'bad'. For example, any lipid-lowering (not just statins) also seems to increase insulin resistance and raise the risk of type 2 diabetes. To me, it's about acknowledging the data and making a well-informed decision about how to minimize the overall risk of disease. One issue is that the potentially protective effects of apo B-carrying lipoproteins are a lot less conclusive (i.e., there is more uncertainty), and that makes it difficult to weigh the benefits vs. risks of elevated vs. low apo B. I may make a separate video about this at some point. Thanks for commenting. Cheers Mario

[@waldguy]

@@nourishedbyscience Mario, your openness to ideas of all types and your active curiosity makes your presentations top-tier, practical, and refreshing. I would be very interested in the video, should you have time to research and produce it. Best to you.

[@sam2wmc]

Mario - This is an incredibly detailed and comprehenisive video. Your logic is always well though through, and it is always based on facts and years of experience. I (unfortunately) now think that I know more about this topic that my primary care provider. It is unfortunate that, in the US, long term progression of illness is not a focus, and little or no education is provided to patients. In the past, it was possible to get some limited help, such as having visits to a dieticiian paid for by insurance. WIth my current insuance (Medicare) I can not get any nutritional counseling paid for unless I have full diabetes, although I know I am at high risk. It is unfortunate that the heathcare system is only focused on clinical "cliffs", where one day you are fine, and the next day, the doctor tell you that you have a problem. Nutritional education should start in elementary school and be reinforced through the primary care system, rather than just waiting for the invevitable problems that come from eating an improper diet. - Meant to post this comment with my "Thank You" contribution.

[@nourishedbyscience]

Thanks, Sam! Good to 'see' you here ...;-) Yes, I so agree. We need a total re-do of the health care system in most countries. Thanks for your (additional) support! Cheers Mario

[@Cindy-ee5ou]

Thank you for your series- I am a junky of sort for health related videos. And yours are my fav - some I like to hear some I don’t but need to hear.

[@cassieoz1702]

What other (non LDL) metabolic factors may be affecting outcome in FHL? People with FHL who survive to about 40yrs, seem to live as long or longer than everyone else. Recent preliminary data on 'lean mass hyper-responders' needs follow up but shakes the serum LDL being 'causally' relationship. Waiting to see where this goes.

[@nourishedbyscience]

I think it's important to be clear that there are people with FH who do not have overly premature ASCVD. But they usually have LDL-chols up to 200 mg/dL, not much higher. Those with homozygous FH, with LDL-cholesterol levels similar to the LMHRs (250 mg/dL +) do almost always have major athersclerotic plaque and usually clinical ASCVD in their 30s and 40s. As you, I am very interested in the longitudinal follow-up, and think there are some reasonable hypotheses that could explain why the atherogenic potential of the LDL particles may be lower in LMHRs, but I also think it's much too early to be certain. Cheers Mario

[@silkenissen7409]

This video is an absolute masterpiece! Thank you so much 😊

[@briankellner970]

Thanks for another excellent video. I had the experience you mentioned with losing a lot of weight on a keto diet and then seeing a strong increase in LDL-C / ApoB (peak measured LDL-C was 194). By just changing my diet, I dropped my ApoB from 109 to 54 in six months. (LDL-C went from 156 to 64 in the same timeframe.)

[@nourishedbyscience]

Thanks, Brian. Happy New Year! Cheers Mario

[@fenz4rt]

How did you adjust your diet from keto?

[@leandrobecker123]

Excelent class! An outstanding issue! As atherosclerosis comes from many possible individual caracteristics (randing from genetics to ambient) I like dr. David spence way of thinking. I treat arteries instead ofcrusk factors!

[@rykiejansevanrensburg3843]

Thank you, thank you Mario! I was one of those people who asked for this video 😂. This is such an informative video!

[@nourishedbyscience]

Glad it's helpful. For you as someone who is interested in this topic, is this too long or too detailed? I continue to struggle finding the right balance between providing the information in a way that is most helpful, while also making it 'watchable'. Cheers Mario

[@testuser3167]

@@nourishedbyscience I'm going to go out on a limb, and suggest that the majority of viewers will agree with my position on this, but as long as you have high quality content to share, we're not watching the clock! A person with nothing useful to say, can make a 3-minute video that is TOO long, but a person with both useful & riveting content can make a 2-hour video that was TOO short... Thanks for clarity, as I made changes to move into the LMHR category, and my LDL shot up.

[@nourishedbyscience]

Thank you for the feedback. All the best, Mario

[@SanchirDashnyam-s2n]

Great video! In your future videos can you please add your thoughts on concrete steps on how to lower LDL, Apob, etc…..that would be great! Thanks again!

[@MyPDDaily]

Long, but well organized! Thanks for the chapters and great information!

[@yu-tingkuo6547]

Thank you so much. Very informative and constructive, and based on good scientific evidence.

[@pradipray1251]

I have to listen to him at least 10 times.

[@sharkair2839]

i am at a loss for words. what a brilliant podcast.

[@nourishedbyscience]

Thank you.

[@stephaniesmith1095]

Does LDL cholesterol play a roll in the inflammatory response in the endothelial wall. Your thoughts on that?

[@nourishedbyscience]

That's a great question. I don't think we know for sure. We do know for sure that the different stages of atherosclerosis have an important immunological and inflammatory component, so inflammation plays a role in the process. I actually worked for several years in a lab that studied the role of macrophages (white blood cells) in the early and late stages of the atherosclerotic process, and there is no doubt that processed we could call 'inflammation' (defined as an activation of immune cells) are critical in atherogenesis. It is also clear that people who suffer from a chronic inflammatory condition, be it low-grade inflammation due to obesity or diabetes, or fulminant inflammation as in RA or Lupus, have substantially increased progression of atherosclerosis. So it does seem very likely that having systemic inflammation can accelerate atherosclerotic plaque formation. Now, to your question, which we have less clear evidence on: does LDL-cholesterol itself trigger the inflammatory process? My best guess would be yes. According to the current model, apo B-containing lipoproteins become trapped in the subendothelial space, and that will be more likely to happen whenever apo B/LDL-chol concentrations are elevated, but also when blood pressure is higher or in smokers, for example. Macrophages would then be called in to remove these particles, which could lead to foam cell formation, the earliest stage of atherosclerotic plaque formation. And within that process, monocyte-derived macrophages are activated/changed to become lipid-handling cells, and that process could probably be called 'inflammation'. Consistent with that idea is that if LDL-chol is high enough, as in homozygous familial hypercholesterolemia, massive atherosclerotic plaque can form very rapidly without any evidence of systemic inflammation, hypertension, smoking, diabetes, etc. So I think the case could be made that either LDL-chol, if high enough, is sufficient for the initiation and progression of atherosclerosis, or that other factors (such as increased shear forces in the bloodstream, endothelial dysfunction, or inflammation) need to be present, but that these can be caused by other circumstances that we all experience from time to time, such as an acute illness, a temporary rise in blood pressure during stress. Cheers Mario

[@MissMoonshineDance]

what a gift, this Mario

[@MarinaVeder]

Thank you very much. It's very detailed information to think about

[@rajeshtanwar2445]

Thank you so much for sharing this insightful and valuable analysis covering various aspects of Lipid profile vis a vis the heart ailments..❤🎉❤🎉

[@steveroedde1]

Mario. This, like your previous video’s is superb. I have shared this one widely as I did with the others. I have several comments about style, and impact. You are clearly curious, open, and not dogmatic. This retired MD, is curious, but so far, not immune from cognitive biases that have impacted personal preventive interventions. I taught EBM for much of my career, and at one time knew this material pretty well. I am now behind the times. I will have to see if there is data comparing therapy duration and ARR to see if this supports the belief/assertion that lifetime area under the LDL curve holds true, and ongoing separation of events in treatment vs controls occurs as study duration increases, but it seems plausible. My case is not “typical”, but not a huge outlier. I’m 70, 12% fat by DEXA, BP 90/60 (life-long), life-long aerobic exercise of 8-15 h per week. However, I have always had high LDL (~5 mmol/L and (recently) Apo B of 1.4g/DL. HDL is OK. I also have Myasthenia gravis which necessitates moderate daily prednisone doses. Unfortunately, i seem to have developed a bit of insulin resistance as a result. CRP is < 0.3, so systemic inflammation currently low. I have started a low carb diet to address the sugars and will reassess shortly, but fasting and PC sugars are now all very good. So, I am doing all I can from a lifestyle point of view. What you have done, because of both clear presentation of both evidence and logic, coupled with openness and non-dogmatic thinking, is cause me to pause, think, and assess whether I am “resisting” therapy for the one remaining modifiable risk factor. I don’t know what I will decide, but the decision will be based more on logic, evidence and reason, than if you had not put this video out. Physicians could learn a lot from you. Not do this or that, but present the evidence, and allow patients to choose. It is our life, and we run all of the risks… and benefits of our choices. I hope you know both how incredibly good you are as a communicator, and what a massive impact you will have. I really, really like what you do! Keep up this critically important work. Steve Roedde MD CCFP (EM)

[@nourishedbyscience]

Hi Steve, Thank you for your incredibly encouraging feedback. After a 25+ year career as an academic researcher, I do consider myself an apprentice in the art of communicating science to a more general audience. Hearing that these videos are already being appreciated is very valuable, and feedback like yours gives me a lot of motivation to continue and try to get better (shorter, more concise would, for example, be a good start ...;-). Your case is unusual, and I can appreciate that it may be difficult to make a decision on whether to start lipid-lowering therapy. Not only do you not have other ASCVD risk factors, but the data you shared suggest that many risk factors have been ideal for a long time, such as your exercise habits and blood pressure. And as much as I feel that the data linking LDL-cholesterol and apo B to ASCVD are convincing, I do wonder whether the relationship could be modified by optimal blood pressure and metabolic health (which may also explain a less atherogenic potential of elevated LDL-cholesterol in LMHRs on keto, who have a similar phenotype to you). At the same time, if you've had a lifelong LDL-chol around 5 mmol/L (190 mg/dL), that does suggest a genetic component. We would estimate your lifetime cumulative LDL-cholesterol exposure at >~11,000 to 12,000 mg/dL years. Based on population-based estimates (see link to paper below), this would lead to a lifetime risk of a ASCVD event of ~32%, and roughly doubling every six years. However, that's at the population level, and not considering other ASCVD risk factors, which IMO leads to an overestimation of the LDL-cholesterol-related ASCVD risk. I think it is well possible that the relationship between the cumulative LDL-cholesterol exposure and clinical ASCVD is quite different in metabolically healthy people with very low blood pressure. We know for sure that directionally this is the case, but we don't have good data to quantify that effect. Either way, I understand that you may worry that having an autoimmune disease and insulin resistance may have changed the overall risk. Have you considered getting a coronary angiogram? Also, do you have a family history of ASCVD events? That could give you an idea of how atherogenic the genetic dyslipidemia in your family is. And both the results from a CT angiogram and the family history may make the decision of whether to start lipid-lowering therapy easier!? Overall, the data do suggest that lipid-lowering therapy does lower the risk of an ASCVD event independent of age. At the same time, the effect size of the association between LDL-cholesterol and ASCVD event risk decreases with age, which is consistent with the cumulative exposure hypothesis: the absolute risk of an event is is certainly higher in older people, partly because they tend to have a greater lifetime cumulative exposure. However, a 1 mmol/L higher LDL-cholesterol level in, say, 70 year olds raises the relative ASCVD event risk only half as much as in a 50-year old (Fig 2 in the NEJM paper below shows this for non-HDL-cholesterol). I have added links to papers discussing these issues below, and hope they are helpful. pubmed.ncbi.nlm.nih.gov/30165986/ pubmed.ncbi.nlm.nih.gov/30712900/ www.nejm.org/doi/full/10.1056/NEJMoa2206916 Best wishes, Mario

[@RXP91]

What a fantastic video. FANTASTIC. LMHR is so interesting. I wonder if energy is constantly used at a high rate that atherogenic lipoproteins simply have less mechanically force to "stick" to the endothelium. The heart is causing laminar flow of the blood to increase, it's a system under higher pressure. I know pumping blood causes white cells to dislodge from the endothelium which increases immunity, simply by those same mechanical forces. If there's less white cells in that lining, less inflammation, less plaque etc.

[@Nicole-in1od]

I would love to see an episode (or blog post) about relative energy deficiency. My recent blood work showed high LDL but HDL cholesterol and triglycerides were totally fine/normal. My endocrinologist said it's not "real high cholesterol", it's actually an indication of relative energy deficiency . This explanation fits given my other lab values and current diet. So I was curious about what the literature says about RED-S and cholesterol and/or the effect of relative energy deficiency on various markers of health. Thanks so much for your work!

[@HannahWeisheit]

Thank you for this detailed and highly informative video. Really helpful!!

[@nourishedbyscience]

Vielen Dank, Hannah (oder Wiebke?)! Sehr nett von Euch... LG Mario

[@TheBuddhasSon]

Hello Mario, thanks for the indepth exposition! Perhaps we need to differentiate between acute and chronic measures, considering the mechanism of action of LDL being one causal risk factor for ASVD. Since macrophages at the sites of clogging are involved involved, we can safely conclude that the primary cause for clogging at the sites is inflammation. Then we can conclude that LDL is a helpful solution in the short term (acute phase), but chronically will lead to ASVD, thereby making LDL only a cause in this case. The many uses and benefits of LDL are otherwise lost, if we try to use measures appropriate in the acute phase for a chronic situation. Please correct me if you disagree! Again thanks

[@nourishedbyscience]

The current model suggests that apo B-carrying particles getting trapped in the subendothelial space is a triggering event, and that macropahges move into the tissue to deal with the accumulation of these atherogenic particles. I am not aware of any evidence that the activation of immune cells occurs first and independent of apo B-positive particles. Cheers Mario

[@bonnieo8]

But why are they getting trapped? It seems like given the impact of insulin resistance on cvd that something (inflammation?) would be drawing in the LDL particles.

[@kkmong]

How come the smaller HDL particles dont pass thru the endothelium first?@@nourishedbyscience

[@aussiesam01]

An excellent talk n this crucial subject. One thing I would like to have seen/heard is your thoughts on glycated or oxidized small LDL particles. Thank you.

[@wellnesssecrets2014]

Appreciate detailed explanation on lipids.

[@alexm7310]

Thank you Mario. Excellent as usual

[@worldnomad2301]

The critique I’ve heard is the imaging they used in the LMHR study cannot pick up plaque in the walls of the artery, only in the lumen, which occurs only in late stages of atherosclerosis.

[@nourishedbyscience]

That critique was not justified. The technique used can quantify all kinds of plaque, and constitutes the gold standard assessment. Cheers Mario

[@larissasouto2537]

Excellent video!! Thank you!

[@anahitawilson9682]

This was very interesting. I am still conflicted about the origin of cholesterol within the atherosclerotic plaques. It would be good to have a good exploration of the mechanisms leading to the formation of plaques. Malcolm Kendrick a GP writes in “The Clot Thickens” that cholesterol is more likely to originate from the cholesterol present in red blood cells (not LDL) and has proposed the thromobogenesis theory (originated by Pfizer), damage to the glycocalyx (from AGEs, smoking, hypertension, IR) that exposes the endothelium, poor progenitor cell replacement of endothelium, leading to localised clot formation and plaques. I would be interested in your view on the mechanism of plaque formation and the relative contribution (and probability) of cholesterol in plaques resulting from red blood cells versus that of LDL. For example have appreciable levels of apoe B protein been found within the plaques?

[@davidbarnes774]

The terms "insulin resistance", "metabolic syndrome", "Pre- diabetes"and "type 2 diabetes" are all terms that appear in YT videos and appear to be used almost inter-changeably. I think I know the difference but it would be great if you can explain these using your excellent communication skills. I know this may seem like a dumb question but a clarification from you would be great. (I personally don't like the term metabolic syndrome as it seems pretty abstract and could mean almost anything to do with metabolic issues).

[@nourishedbyscience]

If I may suggest, these two videos here should answer all of your questions: kzbin.info/www/bejne/j5iccoZoqMuMb7ssi=BbAYl1bO5NFjLdlo kzbin.info/www/bejne/fJiWn2Csnpenabssi=GTnFV-90fX9WC08M These are dense videos, and these issues are complex, so please ask if anything remains unclear after watching these. I do think it's worth the effort for people to really understand these issues. Best wishes, Mario

[@deborahstensvaag2033]

Best video ever on this topic!!!

[@johnny7808]

just want to point out that according to lmhr theory and community experience, the slide at minute 44 showing when joe drops his bmi from 24 to 22 which causes his hdl to increase to to 90 and trigs to drop to 50, ldl should not remain unchanged as shown in the slide but should rather increase substantially. This means his 10 year risk calculation would likely increase, not decrease.

[@nourishedbyscience]

It is possible. I will be honest, I haven't seen enough individual data from LMHRs to be able to know what the most typical phenotype looks like. From the cumulative data I have seen, there does seem to be wide variability, and the main case I wanted to make is that yes, all other things being equal, the higher HDL-chol and lower TG in LMHRs would reduce risk further. However, the higher LDL-chol should still be taken seriously, until we have convincing longer-term data. And you are certainly correct that if the LDL-chol was even higher than in the example, then that would be even more the case. Thanks for the comment. Cheers Mario

[@8_bit_Geek]

No and there are risk models based on. High trigs to hdl. Triglycerides in blood are really bad

[@neatengineering]

Why relative risk is problematic. If the control suffers 2 in 10, and the intervention 1 in 10 the relative risk is halved, but the absolute risk is reduced 10%. For 2 in 100 vs 1 in 100 the relative risk is the same, but the absolute risk is ten times lower. For 1 in 10,000 vs 2 in 10,000 the relative is still halved, but people have stopped caring. Drug companies use relative risk for benefits and absolute risk for side effects. Also, statistics apply to populations, not individuals, so if you're an obese hypertensive diabetic person your absolute risk is going to be way higher than a slim metabolically healthy person with the same LDL.

[@nourishedbyscience]

Yes, agree with everything you say. At the same time, as outlined in the video, I still think it's a mistake to use the relative vs. absolute risk reduction issue as a justification to discount LDL-chol, apo B, or lipid-lowering therapy. Best, Mario

[@neatengineering]

@@nourishedbyscience I agree that people overplay it both ways. People with atherosclerosis and other risk factors should absolutely be concerned about their LDL levels.

[@renus6015]

Great video! My small dense ldl is 49mg/dl(cut off is 21mg/dl) Trig - 41mg/dl Hdl- 69mg/dl Ldl-96mg/dl Hba1c 5.4% I do low carb and eat nuts....no meat/dairy... Why is small dense ldl high? I have family history of premature CAD

[@nourishedbyscience]

You are an untypical individual with a large percentage of small, dense LDL. There are genetic factors that can lead to a shift towards small, dense LDL. I also wonder whether some tests for small, dense LDL actually also measure Lp(a). Have you had your Lp(a) measured? Best, Mario

[@SuzanneHutton-it1pi]

Very interesting and certainly makes sense of conflicting ideas that are everywhere. I have a question- is very high HDL a risk factor for coronary heart disease? Thank you

[@nourishedbyscience]

Yes, there are some data to suggest that very ASCVD and mortality risks increase (modestly) at very high HDL-cholesterol concentrations (>80/90 mg/dL). I don't think it's clear why that is, and the magnitude of that association is much smaller than that for very low HDL-cholesterol, but it's there in several studies. Best, Mario

[@ignacioa1638]

Statins increase risk of type II diabetes, along with other serious side effects, such as cognitive function, muscle pain, etc.

[@nourishedbyscience]

Yes, and hopefully every doctor discusses these potential side effects with a patient before prescribing them. Cheers Mario

[@khariat00]

Excellent and excellent presentation. Everything you say makes sense. It is good scientific work, as far as I understand. Still the relative/absolute difference and why we should be more interested in relative reductions is not clear for me. I think there is some weight in this claim that 1% is almost nothing against 25%.

[@bennyg199]

Great lesson!!! Great teacher!

[@nourishedbyscience]

Thank you for the kind words, and the support. Much are appreciated. Best, Mario

[@daniel9907]

U can you explain that very very high triglycerides I triglycerides I'd like to know the proper human diet. I'm slowly getting weaker from stress of my love life..not being able to work much do to cramping and gout.ive always been athletic but pain slows me down.i had hi triglycerides since I was 12 years old. I'm getting sugar spikes and need some advice Dr ur voice is very impressive ❤❤

[@johnny7808]

Regarding potentially protective lmhr mechanisms, lp-ir stands out. It was the most significant cvd predictor in Dugani et al 2021 and its six components (vldl size, large vldl-p, ldl size, small ldl-p, hdl size, large hdl-p) are each directly impacted favorably by the proposed lmhr mechanisms within the lipid energy model. Anecdotal reports from lmhr individuals indicate super low lp-ir may be common to this phenotype and if so, could quite favorably impact cvd risk according to the Dugani study. If the progression data happens to show good news for the lmhr group my money is on lp-ir as the key reason, we will have to wait and see

[@nourishedbyscience]

Yes, you are correct. The entire lipoprotein phenotype in LMHRs does look favorable (except for the high apo B/LDL-chol), and does provide some hope. I am also eager to hear about the follow-up data in the LMHR study. Cheers Mario

[@8_bit_Geek]

If you watch feldman’s videos then you can see why high VLDL levels are bad

[@UnCoolDad]

So what does the science say is the ideal diet for someone who has both T2D and is on a low-carb diet to help control it, and also has high LDL/Triglycerides? Something you will discuss in a future video?

[@BensTradingServices]

On Keto my LDL goes to around 200 and my HDL to around 60 with triglycerides in the 60’s. I was on a statin for 13 years and stopped it a year ago. The issue I have when on the statin is that it takes my HDL way down to below 30. Based on what you discussed in the video, I assume you would agree it’s better to have an LDL of 70-80 on a statin and an HDL of 28-30 than to have an LDL of 200 and and HDL of 60. Is that correct? Also, just for reference, at 39 years old after being on a statin since age 26 I already a calcium score on CAC and some light plaque on the CT angiogram. My cholesterol on the statin for those 13 years was very low (as described above), yet I still had plaguing and calcification in my 30’s. I don’t have hypertension, BMI in the high 20’s, A1C is 5.2, fasting insulin 5, never smoked or drank alcohol… diet was pretty poor for a long time… exercise daily, and still have plaguing all while having a very low LDL cholesterol for many years. I’m on a keto diet now, so my question is, minus taking the statin again, what else can I do to lower my risk since I already have signs of atherosclerotic heart disease in my 30s?

[@nourishedbyscience]

Hi Ben, From what you have shared, it's unclear to me why you have coronary plaque and calcium. If I were you, I would have a detailed discussion with my doctor about what may be causing this. For example, could you have a hidden autoimmune or chronic inflammatory condition, or chronic kidney disease, that could have contributed to this? Or iron storage disease, i.e., hemochromatosis? There are a number of rare genetic conditions that predispose for early ASCVD, and I would want to be certain to exclude all of them. Because of these are the cause then that's what you need to address, in addition to controlling your traditional ASCVD risk factors. To answer your question, yes, I would interpret the literature such that lowering LDL-chol from 200 to 70 mg/dL is beneficial even if HDL-chol drops as well. Best wishes, Mario

[@llicit1833]

Particularly clear video thanks 🥇 Wrt the LHMR study, an argument has been made that CCTA was not suitable as it images plaque in the lumen, but not in the arterial where it starts & it takes a long time to migrate to the lumen. CAC also not suitable as a late stage test. Any thoughts on those points? I guess, as you pointed out, that the participants already had 50 years of exposure so it perhaps comes down to whether you would normally see plaque in the lumen by then or not. This comment was made by cardiologist Dr Alo in his podcast on the study, so presumably he thinks not. In any case preliminary data as you say and it will be interesting to see results after a longer time frame.

[@nourishedbyscience]

I was astonished by that comment, to be honest. It is my understanding that the method used can quantify any plaque. However, even if Dr. Aloo was correct, I don't think this matters here. Whatever percentage of plaque can be detected would be the same between these two groups, right? So the fact that no difference was seen is still informative, even if some percentage of early-stage plaque were to remain undetected by this method. I am much more concerned by the duration of exposure, and feel that the most informative data will be available in another 5 years, simply because the LDL-chol concentration over time is such a major factor. If the results are still negative after about 10 years on keto, I will start to feel a sense of optimism that maybe something special is going on here. Anything sooner than that could very easily be a false negative, considering the short duration of exposure and small sample size. Best, Mario

[@llicit1833]

Thanks Mario. If Dr Alo is correct, then I think it's possible to see a scenario where plaque is actually progressing significantly more in the LMHR group, compared to control but progression appears equal. His assertion is that both tests are essentially blind to this earlier stage plaque, so one group could have quite a bit, the other a little, but there is no discrimination between the two due to this lack of resolution as it were. Or possibly I'm just getting befuddled. All preliminary (but interesting), so will just have to wait and see how it plays out as you say. Btw with Claim 1 (heart attacks with normal LDL-C), another factor could be that having a heart attack itself causes quite a major LDL-C drop apparently (again Dr Alo is the source 🙂)

[@alansnyder8448]

@Nourished by Science. This is a great channel. You give information that I can trust and don't give us great insight into what the current start of diet research is. I hope you can at some point talk about diet for blood pressure control. I've had high blood pressure and now do things like add beet juice to my water bottle (30% beet juice and 70% water) when I go exercise. I do a strict "test" set of a 100-yard IM all out at the end of each workout and do (anecdotally) notice a 1 or 2-second improvement on weeks I had beet juice vs weeks I didn't. I've noticed that I'm also able to keep a specific interval better with beet juice. So, that is a long way of asking if you could do something on beet juice and blood pressure or performance of aerobic exercise for athletes. :)

[@nourishedbyscience]

I will talk about blood pressure and how to keep it low at some point. For now, please note that a common factor in hypertension is often insulin resistance. I talk about this here: kzbin.info/www/bejne/fJiWn2Csnpenabssi=vaOj_3B5Ztfq79YK Regarding beet juice, I am totally in favor of eating beets occasionally, but if you drink large amounts of beet juice regularly (daily?), please be aware that beets and beet juice are rich sources of oxalic acid. I'll make a separate video about oxalic acid in the near future, but I do believe that chronic excessive consumption of foods that are extremely rich in oxalic acid MAY be harmful for some people (and not just because of an increased risk of kidney stones). There is just a handful of foods that are so rich in oxalic acid that this could be a concern: spinach, chard, beets and beet greens, chocolate, and certain nuts such as peanuts, almonds, and cashews. The gist is that excessive consumption of any of these foods COULD, IMO, be problematic over the long term, because oxalic acid accumulates in the body. I personally would not regularly consume large quantities of beet juice (or spinach smoothies, or such), and my recommendation is to consume these foods that are extremely rich in oxalic acid only occasionally and in small quantities. More to come on these topics later. Best, Mario

[@alansnyder8448]

@@nourishedbyscience This is great information. RE: My beet juice consumption. It is only on days that I swim, which is 3 to 5 days per week, and my protocol "i.e. for habit stacking" is to do 30% beet juice and 70% water in the water bottle I take to the pool with me. I also put a 1/2 scoop of whey protein, a tablespoon of collagen powder, and a tablespoon of creatine. I only do those on days I exercise, so my consumption goes up and down with days that I exercise. I'm 56. My resting heart rate is in the low 40s. (45-41 bpm) and my blood pressure is elevated. 130-77 "athletes heart". I also have a DNA mutation that increases the iron in my blood, so have more viscous blood than the typical person. I've been a runner all my life. cross-country high school and college. Soccer late 20s to late 40s, and now swims due to bad knees. Too much info, I'm sure. Cheers. great channel.

[@alansnyder8448]

More info for context. I get about a one-quart bottle of beet juice per week, so that is my total consumption. I don't do spinach smoothies currently, but to prefer spinach salads. For nuts, I eat a lot of pistachios, walnuts, and almonds. But not so much for any of the other foods you listed as being high in oxalic acid. I'll learn more about oxalic acid to see if I'm overdoing it, and look forward to that video.

[@Optimizemore]

Could you do a video going through Levels rational and sources for for their glucos level (and max increase) recommendations? Search levels and: What should your glucose levels be? What is blood sugar spike and why does it matter?

[@nourishedbyscience]

I found this page here: www.levelshealth.com/blog/what-should-my-glucose-levels-be-ultimate-guide Interestingly, they are looking at largely the same literature as I did in the article/video linked below, but in addition to defining 'normal' blood glucose levels, they also define 'optimal' blood glucose levels, which are a lot more strict. Personally, I don't see good evidence for these stricter definitions of optimal blood glucose levels. For example, under 'optimal', they state that an increase in blood sugar after a meal should not exceed 30 mg/dL. They base this on the observation that healthy people who eat a balanced/healthy meal do not experience blood glucose increases exceeding 30 mg/dL from baseline. That's not an unreasonable interpretation, but to me, it would be a lot more convincing if we had any data to suggest that a 30 mg/dL increase in blood sugar is associated with better health outcomes or lower chronic disease risk than, say, an increase by 50 mg/dL. To my knowledge, we do not have any such evidence, and I would not want to restrict people's dietary choices so substantially based on a single study that didn't even include any health outcomes. Personally, I do believe it is preferable to have options, and I think we should have good, evidence-based reasons to make dietary recommendations that lead to dramatic restrictions in food choices. In this case, the presented evidence does not nearly reach the threshold of evidence that I would require to tell people to limit their postprandial blood glucose rises to

[@Optimizemore]

Wow. Impressive response and well worded reasoning. I really hope you get the views you deserve. As someone with a applied science communication master (with focus on nutrition and sustainability) I appreciate your balance between empowering base knowledge and practical resources and recommendations (with the written blog post and references as iceing on the cake).

[@strengthbeauty8033]

Could you please do a video on how vegetarians & vegans can reverse insulin resistance on a purely plant based diet. Many thanks!

[@yangtse55]

My own anecdotal experience . I don't count calories, Once eliminating the low-hanging fruit, I rely on calorie density. I replaced grain in my meals with more beans. Though not protein-obsessed, I set a "quality threshold" to 4.25g of protein per 100 kcals to supply 1g of protein per healthy kg at 2000 kcals. This helps spot other things to reduce Scary to have learned that 1 extra BMI point = an extra 50 kcals per day.

[@DavidFeig]

I lost about 100 lbs on a keto diet. But my last set of blood work was not so good with my cholesterol, so I switch backed to lower fat diet with balance between protein and carbs--so far weight is stable and monitoring blood sugars--added back oatmeal, apples/pears, beans to diet--so far my blood sugar doesn't love a lot of sweet potatoes but trying boiled/microwaved or small portions! Tracking calories using cronometer and weight is stable so far....seems to be easier to sleep back on carbs! oh, added back eating salmon fish to my diet twice a week. I'm debating statin anyway to see if it would reduce alzheimers risk..really welcome your analysis and some tips on this channel (especially retrograding carbs!)

[@StephenDuncan]

Higher LDL would be expected with keto, but lower triglycerides, higher HDL should also be a consideration in evaluating a "healthy" LDL level. Would like to hear Mario's input. Especially if higher glucose, like your sweet potatoes, could induces oxidative stress. With keto, transporting more LDL, for energy, not storage is expected, therefore higher LDL, but no reason for it to form plaques or get stored as excess fat.

[@dianadeejarvis7074]

Statins are one of those drugs that hurt more people than they help. They do NOT live up to their advertising.

[@scottevans1244]

Best diet for me is the Pesco-Mediterranean diet. In fact, studies are showing it’s even better than the Mediterranean diet which has won best cardiovascular diet for 7 years in a row. I personally do lower carb Pesco-Mediterranean and my lipids are better than ever.

[@nourishedbyscience]

@StephenDuncan, I talk about the specific lipoprotein profile on keto, LMHR, and would suggest you check out my coverage of claims #4 and 5 in the video: kzbin.info/www/bejne/rpuzdXRmeMifa5Isi=tdKWkVyiYHy8nYLe&t=2164 Cheers Mario

[@nourishedbyscience]

@DavidFeig, have you tried staying on low-carb, but just not keto, by re-introducing just a little bit of carbs with each meal (important to do a little bit each meal, because if some meals are zero carbs, then your first-phase insulin response is reduced and any carbs you DO eat at a later meal lead to a blood sugar spike). Then also focus heavily, as much as you can, on fiber, and fats rich in unsaturated fatty acids (avocado, olives, and their oils; nuts; seeds). That could quite plausibly provide a good overall balanced approach to help with the weight, blood sugar, and blood lipid issues. It's a bit different for everyone, but may be worth a try. I am mentioning this here not as individual advice to you, but as a general science backed-strategy for someone in a case like yours, which I think is common these days. I obviously recommend that anyone who is curious about this strategy discusses it with their doctor or nutritionist personally, so that their individual medical and health history can be considered in making tailored suggestions. Best, Mario

[@jovanajovanovic9]

Hello dr Mario, thank you vey much for sharing your knowledge… 🙏🏼one question: Are you familiar with increasing triaglycerides or cholesterol (on lab tested) during active fat loss? Does it can be because of mobilization of fatty acids? Should not they be burned for energy if kcal deficit? Thank you in advance 🤝

[@hannesforster1845]

Sehr informatives Video! Vielen Dank! Grüße aus Österreich!