Episode 53: Reviewing Dayspring and Attia
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- Опубліковано 26 лип 2024
- “Fuzzy science” abounds in the world, and even luminaries fall into its trap sometimes. This review clarifies the mis-explanations of important concepts in lipid science that were discussed in Peter Attia’s podcast. The interview with Dr. Thomas Dayspring resulted in a 7 hour series that promised a deep dive into cholesterol and lipoproteins. Lipid science is a complex and ever-evolving field. Understanding some of the basic tenets of the field helps us traverse more complicated topics. The intention of this review is to help clarify the important points Dr. Dayspring made and to open up the scope of the discussion by examining less considered aspects of cholesterol, lipoproteins and their functions. The deep dive into the topic by Drs. Attia and Dayspring was indeed much needed and appreciated and this review acts merely as supplementary commentary or footnotes to the discussion. Since Attia and Dayspring devoted an impressive 7 hours to their discussion, the 2 hour length in this episode respects the time and effort that went into their series by attending to their points in detail.
Let me know your thoughts in the comments. What questions do you have from Dr. Dayspring’s interview?
Links:
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mTOR, Episode 21: • Caveats on mTOR! | Epi...
HDL, Episode 33: • Unlocking the Mysterio...
Oxysterols, Episode 36: • Cholesterol, Oxidized ...
Cholesterol, Episode 46: • Cholesterol's Secret R...
TB & Atherosclerosis, Episode 52: • Why Tuberculosis & Ath...
Time stamps:
00:00 Intro
05:11 Criteria for review
06:53 Aligning with their intention
09:29 Feynman's scientific principles
11:28 Phospholipids
18:46 Lipid Rafts
30:54 TD: "All cells make cholesterol."
45:28 The Rare Exceptions
50:45 Lipoproteins & cholesterol in artery walls
1:05:59 Pools of Cholesterol
1:09:50 Lipoprotein density
1:12:23 How apoproteins are bound
1:15:04 Statins & liver selectivity
1:21:05 Cholesterol functions & metabolism
1:31:02 HDL
1:34:11 RBC membrane cholesterol
1:36:59 Lipoprotein lineages
1:40:48 ApoE
1:50:40 Cholesterol's function in lipoproteins
1:59:55 Unregulated apoB
2:02:23 Conclusion
My practice: vyvyanelohmd.com/work-with-me/ - Наука та технологія
Very, very insightful ..., at the same time kind & respectful to other medical colleagues.
Thank you. Hope it was helpful.
Fantastic episode! Thank you for your insight and thank you for the enormous effort required to prepare this presentation. I know the others here share my appreciation for your investment of time to produce these episodes and your selection of topics.
@Straycurrent Thank you! It's heartwarming to see so many people who really care about science. Gives me hope!
This was brilliant! Thank you. Fantastic parting message too.
Thank you, my pleasure. What was your favorite part? My personal favorite was the one about cholesterol's function...
Hmm, maybe the discussion of gtpase prenalylation and insulin as a potential contribution to T2DM when using statins, along with their effect of RBC and iron levels. I mean, I've mentioned two things there when there are so many. I will listen again but with a pen and paper. There are many basic things I didn't know like cell production of cholesterol. I presumed it was mainly delivered via apoelipoproteins.
@@conradnorton6799 Yes, the prenylation is so important, and yet we never hear cardiologists or even lipidologists talk about it. And with the rbcs and iron--ooo, maybe I will do an episode...tempting. My dear macrophages will take center stage!
That sounds great. It'd be great to hear you talk about it in more detail.
@@conradnorton6799 You got it! I'm never one to turn down a macrophage discussion!
Thank you for this video. I have a huge amount of respect for the effort you put into this, even though as a layperson, much of the science is above my understanding. I was actively seeking out critical reviews, as the skeptic in me wants to find balance on bold panacea statements. I will say that Tom Dayspring has had a massive impact on my own layperson understanding of the mechanisms of lipids and atherosclerosis, to the point that I did my own Boston Heart Cholesterol Balance test and found high levels of cholesterol absorption markers (camposterol and beta-sitosterol) and low levels of production markers (lathosterol and desmosterol), which led me to question whether ezetimibe monotherapy might be a more appropriate first line drug than a statin which targets synthesis. I now feel cognitively suspended between trusting current guidelines (statin first) vs what seems to be a different emerging view toward individualising the therapy (ezetimibe first).
I’d be very interested in hearing your thoughts about tailoring treatments for hyper-absorbers vs. hyper-producers, as Tom Dayspring spent quite a lot of time differentiating between. Is this based on fuzzy science and thus the guidelines haven’t validated this, or is this a valid approach that just has not yet been adopted due to the slow pace of change.
Sorry if my terminology is off - I’m just a patient interested in learning more to advocate for my own primary prevention in a family with lots of cardiovascular issues. (I am also aware of the Dunning-Kruger effect of the danger of knowing a little bit and making large sweeping assumptions, as a layperson)
Thank you for watching/listening. Cholesterol metabolism is exquisitely regulated. When absorption is high, synthesis goes down and vice versa. That is a very, very simplistic view--the accessible pool of cholesterol is impacted by immune signaling, rbcs, hepcidin levels (see spisode 54) and different tissues may have different responses. Attention is shifting now to the immune aspects of atherosclerosis and factors impacting apoB levels. This is part of what I emphasize to physicians in my training program on metabolic health.
I agree that it is frustrating that current medical practice is so far behind the latest science. As an MD I have to careful not to give medical advice to non-patients and I have to restrict myself to medical education on social media. My hope is that more awareness of how current medical paradigms leave much to be desired in terms of getting patients healthy. We need a better curriculum! 🙏
@@vlmdroundswhat would you recommend to a *hypothetical* patient who has high absorption but low production and overall high ApoB? Assuming they exhausted lifestyle interventions, would you recommend that hypothetical person starts with a statin or with Ezetimibe?
Nice..would like to hear more from you
Thank you! Working on the next episode--wish I had more time! Thanks for listening.
Your approach is admirable and tough to follow as well. I have learned so much in the last year about cardiovascular disease in particular and health in general. I think you should continue with this format and let the viewer let you know how to improve the delivery of the information. I will check out your other videos. Formats like this force us to increase the depth of our understanding and improve our ability to concentrate, be patient and hone our ability to digest complex subjects. Thank you!
I am working on a different channel for just what you suggested. I will do all the technical stuff on this podcast for reference and have a more compressed and succinct format that summarizes the main points. So thanks for the suggestion. I was torn about making this less complex but I felt that I wanted to lay out the scope of the field. I'm afraid we oversimplify things so much that we get off-course and off-science. Thank you for your patience and like I said, I'll work on a more compressed format.
I agree that in depth explanations to assure a better understanding is necessary.@@vlmdrounds
Thank you for the presentation. I’m very impressed. Can you do future episodes on 1) LMHR; 2) Lp(a) and oxidized phospholipids?
@justsaying7065 Thank you! I will put them on the ever-growing request list (!!) but it will take quite a while since I do all of this alone. I'll keep plodding!
@@vlmdrounds Thank you for responding to me! No worries; take your time. I know it takes a lot of research/work to put together the episodes. Appreciate everything you do!
Thank you for your efforts to convey highly complex subject matter to the non-medical community. Drs. Attia and Dayspring are part of a group of doctors and researchers that believe that ASCVD is a function of lifetime exposure to ApoB - and to avoid ASCVD individuals should take more aggressive steps to lower ApoB than is currently recommended by the American Heart Association (which is to treat high LDL cholesterol with lifestyle and meds (statins as first line, ezetimibe and PSCK-9 inhibitors as second line). Dr. Attia has said - you should "slam your ApoB" and by this he means get it to a level of 30 mg/dl, and do so with statins, ezetimibe and/or psck-9 inhibitors. Of course, there are side effects and risks (like increasing insulin resistance, etc.), but the subtext is that these risks are most certainly worth taking to avoid the plaque buildup in arteries. Your discussion seems to indicate the artery wall has issues that lead to susceptibility to ApoB particles causing further damage, but without that arterial wall damage, the ApoB would not have such an effect. This is not equivalent to the "limit ApoB lifetime exposure" model which seems to indicate there is just some probability of ApoB causing damage so the more of it the higher the probability and eventually you have full blown ASCVD. Can you speak to this, and would you agree that limiting ApoB is indicated based on what is known presently? Thanks,
While modified apoB has greatly increased risk of ending up in the vessel wall, simply having a lot of apoB alone does increase risk since we cannot ignore probability. However, I believe the increased risk with apoB count is not linear. Personally I do not subscribe to the annihilation game with apoB. We always talk about homeostasis being an important regulator of health and the extreme goal of apoB extinction appears directly contradictory to homeostatic regulation. 😁
@@vlmdroundsproponents of apob “extinction” would argue that 30mg/dl is far from extinct and is actually a physiologic level in many healthy people who happen to he blessed with good genetics, and they would argue no adverse effects are seen in this population.
Thank you very much for the information. 3 things that i hope gets addressed and which I am curious about:
1. What roles does exclusive zone (4th phase of water) in the serum, if any, play in the allowing molecules to pass through arterial walls?
2. When cells take in lipoproteins, they incorporate the phospolipids into the cell membrane (whether they shrink in size from chylomicrons/vldl or totally incorporated for ldl). Its either that or they are scavenged by HDL, would that be correct?
3. The last point that apolipoproteins don't deliver cholesterol seems contradict the first part that you mentioned where a cell do express Ldl receptors when they need cholesterol, right?
@thekword22 Good questions. As far as I know, the exclusion zone you mention is likely due to the Glycocalyx which is not easily visualized (generally visualized via electron microscope). This layer over lying the endothelial cells prevents RBCs and other substances from having direct contact with the endothelial cells.
The remodeling of lipoproteins happens whenever they transfer apoproteins and contents. Loss or gain of these elements will mean the lipoprotein has to change its structure to accommodate those changes.
Yes, cells express many receptors for lipoproteins to help bring them in. The difference is that the scavenger receptors are not under homeostatic control and are not under negative feedback like the LDL receptor. But you are correct, cholesterol is very important to cells for many reasons and it makes energetic sense to take in cholesterol when needed. They will also synthesize cholesterol but the synthesis does not exclude intake of cholesterol.
Hope that helps!
Thank you. An aside related to RBCs - the Levine Phenoage algorithm gives most weight to red blood cell distribution width (RDW as show on CBC panel) with lower values being favorable (lower phenotypic age). Seems there might be a correlation between LDL-C and HDL-C with RDW. I'll have to see if that holds with my blood work over time.
You're welcome!
Yes, I did find this (not specific to LDL-C and HDL-C): www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.107.727545
For HDL-C: www.ncbi.nlm.nih.gov/pmc/articles/PMC5857101/
Statins and RDW: cms.ijcva.org/Uploads/Article_57354/ijca-8-110-En.pdf
Blood lipids and RDW: journals.viamedica.pl/kardiologia_polska/article/viewFile/77562/56796
yikes.
thank you for investing time in this.
You're welcome. There were so many inaccuracies that I felt compelled to do this episode.