In this episode, we discuss: -The lipidology of apoB and apoA [4:00]; -A primer on the high-density lipoprotein (HDL): genesis, structure, and more [9:30]; -How the lipoprotein system differs in humans compared to other mammals [20:00]; -Clarifying the terminology around HDL and apoA [25:30]; HDL metabolism [31:45]; -CETP inhibitors for raising HDL-C: does it reduce CVD risk? [34:45]; -Why it’s so important to have hard outcome trials in the field of cardiovascular medicine [42:30]; -SR-B1: an HDL receptor important for cholesterol efflux [48:00]; -The association between HDL levels and atherosclerosis: are they causally linked? [53:15]; -How insulin resistance is impacting HDL, and how HDL-C provides insights into triglyceride metabolism [58:00]; -Disappointing results from the studies of niacin-a drug that raises HDL-C and lowers apoB [1:08:15]; -HDL lipidation, dilapidation, and reverse cholesterol transport [1:12:00]; -Measuring the cholesterol efflux capacity of HDL: a better predictor of ASCVD risk than HDL-C? [1:22:00]; -A promising new intervention that may promote cholesterol efflux and reverse cholesterol transport [1:32:45]; -The association between HDL cholesterol and neurodegenerative diseases [1:34:00]; -Challenges ahead, a promising outlook, and the next frontier in lipidology [1:44:45];
Hi Dr Attia, I can't listen to your podcasts (the Drive) on Google smart speakers anymore. I just get silence. I just started listening and it worked 2 weeks ago, but nothing now. Any suggestions on how I could get it back? Or what might be the problem? Thanks
Peter, do you know that SR-BI has pro-atherogenic effect in endothelial cells? Look this up: "Estrogen Inhibits LDL (Low-Density Lipoprotein) Transcytosis by Human Coronary Artery Endothelial Cells via GPER (G-Protein-Coupled Estrogen Receptor) and SR-BI (Scavenger Receptor Class B Type 1)"
Very interesting but what do I do? I’m a little old (87) lady with very high 118 HDL. I am very active, dance, gym, tennis yoga something every day. My natural inclination is to do nothing which has served me well thus far.
I’m sorry I’m a pathologist and I’ve never seen a single human Being who died after midlife not to have sone degree of sortie atherosclerosis. I don’t think there’s si ha thing as not getting atherosclerosis. The clue is not to get the level of atherosclerosis that blocks your carotids coronaries etc
I am French and I love your podcast. You and and those of dr huberman. Unfortunately, there are not many videos of this quality in French. I discovered your youtube channel because I am a biologist and passionate about strenght training. You deal with both subjects. Thank you for all the hard work and I wish you all the best with your work
You say that we need to get the APOB count down to 20 ml to prevent artery disease. Therefore we need to clear cholesterol at a faster rate from the blood. So we need to eat zero fat. Then we say that the liver and cells produce yheir own cholesterol because the body use cholesterol to repair itself. So why is there so much manufactured cholesterol still hanging put in the blood. Is it needed in large amounts to repair the damage to the ARTERIES that are caused by the high glucose circulating in the blood , lifestyle way of eating , and the damage to the arteries also caused by the high amount of insulin needed to remove the glucose from the blood. That the cholesterol deposited in the arteries to repair them appear to clog the repaired arteries ?
The test involving the high fat shake and a subsequent measurement of both transient HDL and triglycerides is incredibly interesting. It makes me wonder about the relationship between HDL and triglyceride transport generally. Unfortunately, they did not discuss triglyceride transport due to exercise (E.g. as in Zone 2 training). Might it be possible to affect *HDL functionality* via prompting its action through demanding beta oxidation of fatty acids? Might it matter if the triglycerides are coming from adipose tissue (as might be released from hormone sensitive lipase and carried via albumin) vs. from the diet through the action of chylomicrons? For example, if the HDL more intimately interacts with chylomicrons rather than albumin, might it be possible that having something like MCT oil before a zone 2 could affect HDL *function*?
Can you build out on your comment here? I am a novice on this type of stuff--I started listening to Attia through interest in athletic performance goals meshing with long term health goals, so many of these discussions i listen to a couple times to fully digest the jargon and the “direction” and implication of the discussion. Specific to your comment, are you asking the question about MCT oil and Z2 training for the purposes of some type of performance enhancer or as a way to move HDL levels in a generally favorable direction as we understand it now? Or, is your question leading to another reason or desired outcome? Thanks.
@@quengmingmeow hell yeah man! I love that motivation you had for embarking on this journey and I'd say we are all novices in some sense since there's so much that the entire field doesn't know. My question was geared towards health rather than performance, but it could definitely have ramifications for both I think. In this video, Attia and his guest here discuss that the absolute amount of HDL cholesterol (i.e. ApoA containing particles) doesn't seem to correlate with cardiovascular health in the same way that just knowing ApoB does. So there's something beyond simply the *amount* of ApoA, and perhaps there is something about the structure/functionality of the lipoproteins themselves that affect how they do their job(s). My question is also somewhat geared towards actionable information - can we take an action to improve the way HDL particles do their jobs? If those jobs are related to both the rate transport of fatty acids to muscle tissue as well as reverse cholesterol transport (I.e. From artery wall foam cells back to the liver), then that actually might be a benefit to both performance and health. There probably is no way to answer this without additional experiments and would require some ability to quantify how well HDL is working and I don't know if those experimental techniques exist yet.
@@JohnSlack89 thanks for your quick reply. Your summary is a good one; I’m mostly getting about 80% of what Attia and guests are spitting, but without a medical background, many times it’s as if I walked into the advanced class without getting the prerequisites out of the way. Attia has at times referred to the “levers” we can push to affect health outcomes. I’m totally on board with his nutrition and exercise levers…..and his constant testing of himself has given me valuable info even if it’s just N=1. I’m a non-drug taker, so I’m not on board with his pharmacological solutions to problems that can be solved in other ways even if those ways are difficult to execute and even identify. However, I have learned a ton from his explanations of what is happening inside the body as a result of pharmacological solutions--and that’s been extremely valuable.
@@quengmingmeow totally hear you. It's a lot to take in. Good luck with the journey! I personally do agree with Attia that pharmaceuticals have their place - sometimes even being very strict with diet and exercise, health can still be improved with them.
Thank you so much Peter for shedding light on one of the most important and not much understood subject matters of lipidology. This was a huge episode! All your podcasts are indispensable both for a general public and MDs. Great Job!
WHY do researchers think mere chemical manipulation is an answer to what they (already) assume is an imbalance, without any examination of diet as a causation? Not examining that makes ‘treatment’ a Bandaid. Insulin resistance is mentioned, but no questioning why that condition exists.
You don't know Peter Attia. If you want to hear about IR, he has explored that seriously. Also fructose/glucose etc. Very interesting. Maybe not as simple as we like. He's done real diet research scientifically and serious N=1 all along. Google NuSI if you want to see where that started. Attia has constantly adjusted his view and what he does himself as more came forward. Just because he is sorting out lipidology here doesn't mean he's ignoring the other stuff. But no he's not gonna be a "we have the simple answer and it's one thing" guru that spouts low carb as the cure-all. You'll have to look elsewhere for simplistic approaches. But recently, like many sources I trust (R Patrick, A Huberman) he's all about exercise and sleep, diet and CGM learning. But he's the only one really sorting out lipids in a full clear way.
I was looking forward to clarifying my understanding about HDL when I started watching this video. There are some golden nuggets but then we tend to jump all over the place with no reference screens or in-between-summarization which gets to be a bit too much ... I am giving up watching the video after 30 minutes - two hours of this is too long for me ... I will check out some text at my own pace.
Superb talk. I appreciate the depth and detail, even when I should do some homework afterwards in the fundamentals. Makes me vant to grab a lipid physiology textbook to my bedside. And I am only an engineer.
Jeepers. Here I was feeling good about my HDL being over 100 with triglycerides in the 50’s. Now I’m not so sure. This all seems like a balancing act on a high wire with no net. Does a zero CAC score help? I want a doughnut all of a sudden…
zero CAC doesn't mean much if you're 40 or 50, even beyond that it doesn't mean a lot, kinda like saying the x ray shows I don't have lung cancer so I might as well keep smoking, a CT angiogram is a lot more useful in that sense.
Your LpL activity is probably exceptional and you’re losing surface components of your VLDL-p to HDL-p, including cholesterol - this is unlikely pathological but get some imaging to hedge your bet. Peter and Dan are both still trying to find the key under the light when they should be looking elsewhere - trying to jam jigsaw pieces into a puzzle which simply don’t fit.
@@abrahamkarr12 I have borderline high LDL to go with normal Triglyceride (70). I recently read some articles that says fish oil supplement and diet (lots of healthy fats) may increase both HDL and LDL. So, to increase HDL safely without negative impact of LDL, all I could think of for now is exercise. Even if exercise does not move your HDL meaningfully, it can always improve your metabolic health and cardiovascular disease risk. Good luck.
This is the sad reality of these podcasts, Libby Collins could probably lower her ApoB by eating donuts in this context (I could almost guarantee it) but it is completely idiotic to think eating donuts is lowering the risk of ASCVD but based on current lipid hypothesis, this is the case. There is clearly something glaringly wrong here; I can’t understand how Peter doesn’t see this. Bizarre to me. Idk maybe I’m wrong.
RanRader's knowledge in this area seems very important. The cholesterol theoretical frameworks for LDL and HDL are awful and have engendered considerable rock throwing. The existing drugs proposed for use are highly speculative and one could argue that blood removing leeches are just as effective. I am holding out hope for a sister-device to the CGM which would be a Continuous Ketone Monitor that would give us insight into the lipid flux.
The field's preoccupation with the lipoprotein system tends to come at the cost of attention to the elephant in the room - spontaneous glycation damage from elevated blood glucose to most structures ... that aside though, have you come across Stephen Cunnane's work on ketones?
When you spoke about the fatty milkshake experiment, was it one with sugar added? Could excess sugar/glucose be a confounder when you’re speaking in the context of triglycerides increasing?
I tried to look it up, I think those is the study. They don't say the specifics ingredients, but they say with either strawberry or chocolate syrup. Since the study started in 2005, it's probably safe to say it had a fair amount of sugar, unless they were using an artificial sweetener, also not good for you though. I would be interested in hearing them discuss that.
Interesting that Peter thinks about mechanisms in the human body and their evolution based on the negative impact they may have in the past couple of centuries or even the past few millennia when those time scales are ENTIRELY irrelevant to our bodies naturally function
Wow, very informative Podcast although I am getting more educated in the Nutritonal science of my Coaching career. I went to the Dr. He's trying to steer me to Statins (LDL-124 HDL 68 Triglycerides 38) I am 90% plant based (sardines 2x per week) Run. cycle and strength train about 8 to 10 hours per week. I told him I'm not keen about Statins. BTW, I'm 60 years old. Anyone have a similar experience or some input? Thanks!
Once again, interesting content, but really Peter you are one lousy interviewer. This is especially true when you feel you know something about the topic and it becomes a competition. It is also incredibly disorganized. We aren't told the function of HDL until you reveal HDL's role in cholesterol efflux until literally half way through. Before then we are regaled with Peter's fluency in an ocean of acronyms. This as though we are listening to two subjects talking in code about "going somewhere." Then the mystery destination is finally revealed. Perhaps you should be renamed Dr. Peter Acronym? You should take some hints from your buddy Andrew Huberman on how to conduct a coherent interview.
I have always had genetically high hdl (136) and moderately high ldl (130) …..possibly genetic again…. and normal triglycerides (90). Testing ApoB Friday. No doctor has been concerned but I find the numbers strange. I’ve been decently healthy American diet. Recently switched to clean keto. Hdl went down to 110 and triglycerides went to 140. LDL is the same.
My HDL was in high 40s… I started doing intermittent fasting and exercising. Now my HDL last I checked was 112....and my total cholesterol is 176… should I worry about this high HDL level?
Wow my hdl-cholesterol has been historically high(140) but the only treatment I've ever gotten for it or been offered is being razzed. My last doctor told me I could become an HDL doner, ha ha.. Not helpful. Documented light ascvd score at 3.6%. Later I was given a heart x-ray with contrast but nobody really bothered to translate it for me. And since learning it's not necessarily protective --my total cholesterol was 297 at the last test, and knowing that my parents and their parents had heart disease and died from either heart attacks or neurodegenerative diseases like Alzheimer's, Parkinson's, ALS, and three of us suffer from peripheral neuropathy, I'm very interested in knowing how I should move forward at 66 years old, female and worried about all implications associated with everything that correlates, good or bad with high HDL. I eat a pretty good diet but I'm sure there's room for improvement but that's all I can think of doing at this point. The last time I asked my primary care physician a medical question she said if I wanted to know the answer to go to medical school so that's kind of how the medical community where I am treats patients, especially women from my experience.
Make sure you reduce inflammation in your body. I assume your diet is free of any seed oil and low in carbs? Make sure you insulin levels are not chronically elevated.
Hello Peter, excelent content. Please talk about fatty liver, insuline resistance, and how it is related to insomnia, and what to do about for a nonalcoholic but overweight person. Thank you.
Check out Ben Bickman's vids on insulin. insulin resistance is the cause of many major diseases. I reversed my insulin resistance, hence pre-diabeties, CKD, NAFLD, high BP, increased testosterone thru keto/carnivore lifestyle. See Dr Ken Berry's vids on Proper Human Diet.
My HDL is high and my LDL is low, making my total cholesterol normal. I'm in my early thirties. My doctor has no idea if or how to treat it. Any suggestions?
@wocket42 Recent research suggests that very high HDL can be harmful. People with very high HDL are at increased risk of heart attack or dying from heart disease.
Dear Peter Attia and Dan Rader: I am a 73YO female with HDL of 125 mg/dl. Also high LP(a) 40 mg/dl. All other data and lifestyle, everything, points to my having low SRB1. I have family history and Promethease shows many gene polymorphisms to coronary artery disease. Please, please point me to what I can do. I recently started rosuvastatin and Repatha but I know that these won't lower HDL.
A brilliant conversation by two wonderful people that started off in the weeds and ended up in the forest. I did enjoy the two or three big pieces I could understand.
A trial by Merck....manufacturer of the statin Zocor to check the efficacy of over the counter niacin supplementation (which has been shown to improve lipid profiles) found them not effective? Hahahaha.....perfect example of follow the money. You think Merck wants to give up the money they make on Zocor? Really disappointed in Peter for not calling this BS out.
@@BestLifeMD no… they were discussing the good doctor explaining how he used to prescribe niacin supplementation… which does work.. to a drug manufactured by Merck to discredit the use of niacin, convincing patients to quit using niacin and instead use some new med manufactured by Merck. The guy is in Mercks pocket.
@@timothy5988 no, you need to listen again. Niacin used to be thought to be more effective than it is. It may raise HDL but clinically does not improve any outcomes. Mercks own studies on a drug similar also showed no effect. He used to prescribe Niacin, but now does not.
A third of keto dieters get the elevated ldl cholesterol , which ordinary Docs think needs a statin . Docs don't seem to understand the differance between elevated ldl for non keto people and elevated ldl for long term keto dieters .
Do you prescribe statins if Coronary Artery Calcium score is high? I am 65, 35 lbs overweight with high cholesterol for years, CAC of 567. Lost 20 lbs lately but 35 more to go. Exercise regularly 5-7 days per week includes weights, HIIT, basketball, biking. Mostly Keto diet for last 6 months. My Dr prescribed statin but I’m not taking.
I would try low dose in your case. Research the types they are not all the same. I was totally against the whole idea but now convinced it's a fairly safe intervention. Even safer stuff in the pipeline too.
These discussions are a lot like particle physics. There are many associations and correlations with disease. The underlying solution hasn’t been determined. Science is incomplete and many past assumptions are wrong.
Talking for almost 2 hours without saying any numbers that we can refer to. Disappointing podcast with this guest. Treating as more advanced listeners as idiots
The calorie in/calorie out assertion continues to trip me up in trying to understand weight fluctuation. Does the data actually prove that if I eat 2000 calories of Twix bars for 30 days, my weight will be the same as eating 2000 calories of broccoli and fish? Every time I hear the CI/CO theory, I cringe as I know the body processes sugar, fat, protein differently. Please help me out.
It's a mass equation, not calories which is a unit of heat and has no mass. Read this article to understand what really happens. Ref: Where fat goes when you lose weight CNN Health
I have heart disease, >60% blockage in my LAD, and naturally high cholesterol. I take statins, bit the only thing that has gotten my LDL under 70 is a vegan diet. That with exercise, strength and cardio, work for me.
Not surprising not vegan diet produced lower LDL-c, not sure this is translating to reduced ASCVD risk - but hopefully you’re eating a whole food minimally processed vegan diet and not a bunch of Oreos and Coca Cola lol😅
@@AZ89231 whole food as much as I can. Very high maintenance, but worth it because of all the crap in processed foods. Very disturbing what they put in that and call it food
Bodybuilders have chronically ultra low HDL due to steroid use. Most coaches believe it is not a problem as long as LDL is kept low. Wonder how true that is.
Peter your war against “good cholesterol” is so pedantic. cholesterol contained within HDL is good relatively. That makes good cholesterol an absolutely appropriate short hand for people. Otherwise I love your show
