undeather

In general mechanical (i.e high blood pressure) and chemical (i.e high blood sugar-> glycation) stressors, As you can imagine, it's an incredibly complex mechanism that over time wears down the structural and functional integrity of your blood vessles. This then leads to up-regulation of adhesion molecules, increased chemokine secretion and leukocyte adherence, increased cell permeability, enhanced low-density lipoprotein oxidation, platelet activation, cytokine elaboration, and vascular smooth muscle cell proliferation and migration. Basically all that shit you dont want It's nature & nurture. Nature being genetics - meaning your individual tissue specific resistance which is mainly defined by your genetics. Then of course nurture - which are all the risk factors that are invoved in atherogenesis. Blood flow in arteries is not laminar, but pulsatory. Your left ventricle pumping creates a "puls wave" and your blood moves accordingly. The strength of that pulse wave (pulse pressure) and the total pressures (general blood pressure) will define the mechanical tear on your artieries. Damage occurs over time of course. Just like your stomach musculature is not perfectly consistent -> which might create hernias ..some parts of your arteries might not be consistently vested with the same amount of protective fibers! This is HUGELY speculative though and only based on some histological studies I read I have no idea how antioxidant status and collagen repair could play a role in that. Particle size comes in later in the process of atherogenesis itself. A huge topic in itself. OH boy, histamine and endothelial permeability is very complex and we need would need whole thread for that topic alone. There seems to be a strong correlation with histamine, endothelial permeability and your general cardiovascular diesase risk. It makes sense mechanistacally ( kind of ) but we need more data to act clincially. I have my own heuristic for that, maybe I can go deeper into that in the future - but it would exhaust my time window for now

I dont think coronary heart diesease starts in one particular area. In fact, one of the most surprising facts about heart catheter or ultrasound examinations is how unintuitively scattered plaque-formations can be in certain patients. You see someone with a completely fucked up left main coronary artery (multiple high grade blockages) but an almost juvenile right coronary artery with zero signs of atherosclerosis. Patients whose aorta looks like a corroded ruber tube, but whose coronary arteries are seemingly untouched. Others who show zero sign of plaque formation in their carotids, but completely end stage atherogenesis in their heart. There are of course clusters, for example in bifurcation types - where you clearly see one kind of plaque formation much more often than others: Also, in general - if you find atherosclerosis in one place, the chance is high that you have it somewhere else as well (its a systemic occurance). That said, there is a big individual component which makes it really difficult to predict where it might cause serious problems down the line. My heuristic is that our individual vascular anatomy is the main predictor where plaques might gain a foothold faster. Differences in flow dynamics which make the endothelium in one specific place more susceptible to dysfunction - where it's almost prone to create an inflammatory response and ApoB emplacement. Besides that, there seem to be "structural" weak spots, which could stem from saltatory downregulations of protective fibers (like elastin) in our arterial tissues. All this and much more will at the end decide where damage occurs fastest. But then again, this is somewhat speculative

Bro, I asked if YOU understand it - not if the video covered it. So again, since you obviously know everything, please explain to me the simple connection between follow up period, age distribution and absolute/relative risk. It can't be that difficult to explain, right? Any medical student who passed his basic statistic course can answer that question. Either you know the answer - then you need to explain to me why you would ignore it in your argument. Or you dont - in which case, let me at least explain it to you. Funnily enough, the tabacco industry used the same AR/RR-game to "prove" that smoking isn't really that bad. But you didn't know that, did you? Statin AR/RR-reduction arguments have been around since the 90's - but of course, you dont know that either. Nor what the most likely explanation for that is. You posted the video - you just posted the bar chart. Now back it up with some knowledge how to interpret the data. Without knowing that, you are just running on a 24/7 confirmation bias. Iam not closed off to most perspectives. In fact, I have been highly critical of our medical system before - publically with my colleagues and also here on the forum. I have had debates about alternative healing paradigms and defended even stuff like homeopathy and energy healing. The big difference is that you need to have those discussions on eye level. You know way less than my the medical students I teach, yet you act like can show some sort of expertise, which is not the case. It's pseudo-knowledge based on youtube videos you just referred to. If you want to criticise statins and the pharma-drug complex in general, I am all on your side. But AT LEAST do the work to know what the fuck you are talking about.

It's really a textbook example of what's wrong with online health culture and how it leads people with superficial knowledge towards certain "truths". When you are not equipped to deal with the complexity of research and basic human pathophysiology, this is exactly where you will end up at. Do you really think a 10 minute video from a fringe online MD (who spouts all kind of nonsense on his channel) will give you an adequate representation of statin evidence we have gathered in the last 50 years? Also, cherry picking - who just picked the one ambivalent meta analysis out of dozens to support his own bias? That's YOU, my friend! Did you even read the analysis and the inclusion citeria/statistical analysis that lead to such outcome? My guess would be that you watched the video and read that blog post. As if this has anything to do with doing the real work. Why not go through all the data ever released on statins? Wouldn't that be the real integral thing to do? But, right - that requires work, knowledge and time - things you are not willing to invest I guess. Ugh, I have seen this JAMA-study being discussed all over the internet when it came out. I am happy to help you through that analysis and why it "did nto change my mind on statins". It's not even that complicated to understand ... Let me first check where we have to start: 1) Do you know the difference between absolute/relative risk and how follow up periods tend to influence both? 2) Do you know how age and health conditions influence effect sizes in statin trials? 3) Have you looked at the studies included/inclusion criteria?

Sure.

It depends on the severity and duration of the underlying condition. We regularly observe low levels of B12 in patients with all kinds of chronic GI-disorders. In fact, I would argue that most patients who visit us come with some form of vitamin/mineral defficiency - it's part of our general screening procedure but we tend to be conservative with long term supplementation since most of it will normalize under a adequate diet when der underlying issue is solved. Late stage manifestations like pernicious anaemia or neurological disorders are very rare. It's especially prevalent in small intestine centered Crohn's or celiac disease. However, outside the edge cases - the most common cause is a fucked up diet or drug induced side effect (metformin for example) Personally? Puhh, difficult to say - I have worked with many patients + study populations over the years. The great thing about deficiencies is that once you give the body what it needs, people tend to get better rapidly. How do I know if they are healthier? Well, patients tell me that they feel better. Their biomarkers improve. They act and move differently. It's in concordance with scientific evidence. I dont know what you want me to say. I guess all of those reasons and more. Yes, doctors are humans too and sometimes they deceive themselves. Yet years of training and experiences treating patients are not worth nothing. It's laughable when people on the internet somehow think they know "more" - when in reality, their whole knowledge is based on fringe online personalities and youtube university.

I did not assume anything. You said "once a week" and I calculated the requirement accordingly. It takes a long time to deplete the B12-reservoir, but intake needs to happen periodically and withthe right circumstances. Part of my job as a gastroentrologist is to treat people with malabsorption issues. B12 is particularly tricky because some GI-patients just lack so called "intrinsic factor", which is produced in your stomach. Intrinsic factor is the key to B12-absorption in the terminal Ileum (small intestines). Besides that, there are functional B12-issues, which can be even more tricky to pin down. I have co-authored papers and give lectures to students about this topic. I am pretty confident I got the basics down.

Please tell me how "eating an egg and drinking milk once a week" is beating out B12 supplementation for example. Even if you use the commonly used RDA of 2,4 micograms B12 a day (which is the low end) - you need to eat at least 25 eggs or drink 3+ litres of cow milk to get to meet your weekly B12-requirement. I am not even accounting for absorption dynamics if you do this in one day, which would make the calculation even more ridicolous. Either supplement B12 as a vegan or include animal prodcuts as a whole food group in your diet. Again, you are giving advice without knowing what you are talking about. Potentially harming people.

You are kidding, right?

Interesting! Have you read Christopher Bache's "LSD and the mind of the universe"? In that book he describes his experiences after 72 well-orchestrated, super high dose LSD-sessions. He talks about this annihilation aspect a lot, which he experienced as well - yet for him, this "death of body and psyche" was the mechanism to gain access to deeper parts of the mind, deeper aspects of the non-dual nature - almost like layers. I love his map because it combines both obvious insides like ego-death and no-self with seemingly true aspects like reincarnation and purpose. If you are interested, I can link you a very good podcast episode: Besides that, are you aware of something called "past life regression therapy"? I am very skeptical about it because the mechanism of action could be manifold and it doesn't prove anything by itself. Also, most people practicing this kind of stuff are spiritual weirdos! But I also know some very sober people with insane stories - so who knows!

Here is the thing... Once you ask such question, people will come up with all sorts of opinions and believes. Which are entirely based on their (spiritual) conditioning. What is true is that there is an overwhelming amount of case reports regarding young children refering to previous lifes. We know that this has been true across cultures and across time (Pythagoras could remember most of his previous lifes). We know that there is the phenomenon of between life memories. We know that this is a reocurring theme in near death experiences. We know that this is a reocurring theme in psychodelic transmissions. The truth is that there many facets of experience that hint at reincarnation. I personally do not think that this is just a "string of memories seemingly attached to different minds and bodies across time.". Such assumption would create more questions than it would solve. If you ask Leo, he would say that all this reincarnation stuff is something YOU (GOD!) is imagining. I know a deeply realized individual who once told me that during "his shift" (enlightenment) he felt this strong energetic intuition that he went through multiple lifes to end up where he is now. I do hold my own believe, which is: Of course reincarnation is real. Which is based on bayesian reasoning and the best evidence we have. But then again, its "just" a believe. I guess we will find out soon enough anyway

Did you critically read through the study itself to control for possible bias and deduction synthesis... or did you read the dailymail version, felt good because it fit your paradigm and decided to post it as "science catching up to the truth"? Come on, let's be honest. Let's not forget that newspaper articles about science findings are in general terrible tools for getting to what's TRUE! Also, lets not forget this gem:

We dont need to ask the question - we have the answer. Thats what randomized, controlled trials are for. You randomize patients in 2 homogenous groups and treat one with statins, the other with placebo. Then you follow them up for some years and ovserve what happens. This has been repeated propably hundreds of times - different groups, pharma-independent and completely in concordance with epidemiological observations (increased life-span in countries with increased healthcare output). See, I dont need a believe system. It's you that creates the believe. I base my decision on the best available data & my expereince as a docotor. I agree with you that culture effects the paradigm doctors view health - but then again, this is exactly the issue I described in my previous post: Dont throw the baby out with the bathwater. True integral medicine INVOLVES studies, data & drugs and does not shunt it on any way or form. If you have a lung infection with a deadly bacteria, do I need to know you intimately to perscribe you an antibiotic? No, of course not. It will just help because we know it helps. It's generally true that our modern medical system lacks in interpersonal relationships between doctors and patients but thats a different issue. Also, this is not always the case. I grew up on the countryside and there was 1 general practitioner responsible for the whole village. He was part of everyone's family basically - and guess what, he was perscribed all the medications as well - because he saw it helped. Again, a complete misconception of actually practicing medicine. I dont just "put them on drugs" - I think about their risk profile and tell them the smartest choiced based on all the evidence and my experience. This ALWAYS involves lifestyle modification as the most important pillar because it's highly effective. But I dont know at this moment in the hopsital how far they are willing to go with that - and frankly, if you had ANY experience at all, you would know that most people just dont give a shit. Also, it's perfectly fine to go off a statin medication once they implemented healthy lifestyle behaviour. Maybe they can reach their lipid goals without them, maybe they wont. Of course we are following up patients - university hopsitals have statistics about all sorts of stuff. Private practice physicians see the same patients all the time and that includes when they report medication side effects. Do you think we are idiots? Yes, there is a shitload of data showing that statins WILL change things. How can you ignore all the studies just like that? But I guess this is all big industiry sponsered right? (Which is not the case if you had any clue at all). What do you mean lived the entire lives without statins? This is about RISK and PREVENTION in the FUTURE. We want to PREVENT that heart attack that's been building up for years in the coronary artery. We want to PREVENT that stroke that would create a big hole in the family. This is insane logic my friend. See, this is a perfect example how you create your believe system. From 1 ancedote. You father and your brother do not have the same genetics - even if they were twins, there are many more components that would make such correlations extremely complicated. I can come up with dozens of counter-examples. It literally doesn't matter. Anecdotes are valuable but you can't just pull up a whole worldview from them. I cant help you if you think this is good sensemaking. Statins have been tested on healthy people. Again, you lack knowledge. No I can not preclude any weird side effects that might occur in some patients - I have to take the (sometimes imperfect) data we have and work with it. And that data clearly shows that statins safe lives.

Yes and no. Again, we laugh about statements like these because it shows the naiveté of a person who does not have any clinical experience. That's just wrong. No doctor in my hospital get's money from perscribing a statin. Nobody ever told me I have to perscribe a certain drug over recommending lifestyle modification. The truth is that statins are a terrible way of making money as a pharmaceutical company - it's an old drug and generic versions are all over the place. The drugs which make you money, like PCSK-9 inhibtors, are highly regulated. Also, iff you would read any current guideline, you will notice that lifestyle is still the basis of any further intervention. Only in high risk indivudals, further drug treatment is necessary. All this is based on actual data and we can talk about this as well if you want. I would immediatly if I had to. I take antihypertensive medicine because I have a rare genetic disroder - and guess what, I feel completely fine. Yes, propably. I have been practicing for years as an internal med. doctor and statins are one of the most perscribed drugs. I perscribe them at least once a day when I am doing rounds. Any older person with a fucked up lipid profile gets a statin for protection. That adds up. Of course they have side effets. Every drug does. No drug is harmless. But thats not the point. The data is showing a benificial effect is just overwhelming. Not implementing a statin would do more harm. Again, if people manage to get to their ApoB goal without statins, than thets even better - cheers to that. But that's just not how it works outreality. People need drugs and it's good that we have them. If you have a good coutnerpoint to that, then please tell me. Whats your experience with side effects? How many people have you treated? Your point of view would change if you are actually involved with patients every day, trust me.

Sure. let's not even look far - let's pick Statins. I agree with you that the "health care industry" is limited by it's own epistemic standard. That's why my private practice generally consists of an integral approach that combines both the allopathic, guideline-oriented practice with an alternative, complex-system informed framework. Ia m not shy disagreeing with mainstream medical advice and I have had multiple debates with colleagues about all sorts of stuff. That said, my problem with most of the "alternative medicien" crowd is that almost without exception dont know shit about about evidence and data. This is a problem because it results in all sorts of crazy theories and nonsense. I mean, just look at the shitshow that's influencer medicine on youtube and twitter. People like "Dr" Eric Berg have millions of subscribers while talking nothing but nonsnse. And I think a statement like yours is a further symptome of this paradigm. Anyway, please put down your argument for why Statins are doing more harm than good. I can shower you with data that says otherwise - I can give you multiple lines of arguments, from biomechanics to epidemilogy to controlled trails. I can give you an argument that involves patient psychology and a spiral dynamics/Wilberian integral perspective on this. Iam listening with interest...

With all due respect, but this is in an insanely short-sighted, reductive and plain out stupid take. I am outright shocked to read such words from a moderator.

https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.114.014310 https://pubmed.ncbi.nlm.nih.gov/34529050/ https://www.atherosclerosis-journal.com/article/S0021-9150(20)30378-6/fulltext https://www.ahajournals.org/doi/epub/10.1161/CIRCULATIONAHA.119.045026 https://jamanetwork.com/journals/jamacardiology/fullarticle/2785586 https://jamanetwork.com/journals/jamacardiology/fullarticle/2795671 Statins are second instance right after lifestyle changes. I am all for avoiding drugs until it's just absolutely necessary - but sometimes that's the way to go. Especially older folks experience difficulty getting into a acceptable ApoB-ranges just with exercise & diet alone. Also, let me tell you this with years of experience practicing internal medicine, most people just don't give a shit and prefer the drug over lifestyle. Contrary to the opinion of youtube & twitter university doctors, Statins are incredible safe. I remember being very uncertain about Statins because of all the online hysteria I came in contact with. But once you start reading into it rationally and actually have your hands on patients (and I have propably perscribed hundreds of not thousands doses of Statins so far), you will realise that most of them tolerate Statins really well and there is nothing to worry about. I think the worst side effect i have ever encountered was a significant rise in liver enzymes, which went away after discontinouing the drug, There will a huge interindividual difference with almost no pre-test predictibility. Welcome to complex systems. But again, most inflammatory markers are not eligible for suchpurpose - a more accurate assessment would be through Ig-specification after eating a consuming a certain meal. If you believe Jordan Peterson's story (which I tend to do), then he propably reduced his inflammatory response by cutting out most food groups. Personally, I feel best on a mixed, whole food diet with a strong emphasis on plants and some high quality pieces of meat & fish. But then, I also like to enjoy life and indulge in some junk food as well

LDL-C and non-HDL-C are (in general) perfectly fine indicators for cardiovascular disease risk, especially in "the average" population. LDL-C can be determined directly using enzymatic methods or calculated from the other parameters using the Friedewald formula: LDL-C = Total-C – HDL-C – (TG/2,2) in mmol/L If you have a very sick patient with a high metabolic burden (high triglycerides, diabetes, obesity..), then the Fridewald formula should not be used to determine LDL-C because the result might be inaccurate. Enzymatic methods are better but also not perfect in that regard. -> Most physicians don't know this! Non-HDL-C is a very good marker which is also used in out best risk stratification tools like SCORE-2. In most patients, Non-HDL-C will present a very accurate picture of individual risk. The reason why ApoB is superior is because at the end of the day, LDL-C & non-HDL-C are surrogate markers. There is also evidence thgat an additional ApoB measurement as an extension of the standard profile can also detect increased particle counts, which often cannot be identified on the basis of LDL-C or even non-HDL-C alone. -> https://pubmed.ncbi.nlm.nih.gov/23068583/ In most patients, this is not an issues - especially if you do a rough lipid screening which usually doesn't end in a different therapeutic decision. However, if you really want to go full health nerd, then ApoB is the way to go! As far as I know, its pretty much set for life. It's important to point out that there is some disconcordance in the data - some individuakls with high Lp(a) dont seem to get the the same level of fucked upness. I have seen people getting stressed out over high Lp(a) values and frame it as the unavoidable death sentence, which it isn't. Nevertheless, high Lp(a) individuals should be treated more agressively - just in case!

What do you mean with pharmacodynamic life? Half life? Pharmakokinetics? Dose-response? We are slowly but surely entering the ApoB-era, leaving the other markers behind. As you know, ApoB particle quality & quantity is the single most important factor in atherogenesis from a lipid-perspective. It comes with all the benefits of a surrogate marker like LDL-C and doesn't have the same downfalls (LDL-C measurement can sometimes be inaccurate in patients with DM or high triglycerides etc.). The reason we still use the "old ones" is because we are simply used to it. Cheap and effective assessments are ubiquitously available. Maybe there is an argument to be made about all our lipid-drug-reserach reserach in the last 50 years using LDL-C as the endpoint, but we do know for a fact that the real culprit is ApoB - so there is that. HDL-C becomes less and less relevant by the minute. Ratios are overrated if you have ApoB. Lp(a) expression is mostly genetic - in fact, its the most prevalent genetic lipid abnormality and also mostly overlooked. Almost 20% run around with high Lp(a) and dont know it. Its super atherogenic and increases CVD risk substentially. If I got a patient with high ApoB & high Lp(a), then I know its time to agressively lower his ApoB burden. Lp(a) lowering is difficult - Statins won't do it - PCSK9-inhibitors will do it by about 25%. New drugs which look promising are in development. Lp(a) doesn't respond to diet, but ApoB does - people with high Lp(a) just need to look at their other risk factors more clearly.

It takes years - sometimes even decades for measureable atherosclerotic plaques to form. Most modalities, especially vascular-ultrasound are very crude measurement techniques with very low specificity. MRI-angiography would be a gold standard but is expensive and sometimes difficult to interpret. Calcium-scores are useful, but it comes with a shitload of limitations: Calcification is a late-stage process of atherogenesis, soft plaques are much more common in young people, there are a shitton of heart attacks in young people with CAC=0. Funfact: Statins tend to increase CAC-Scores but decrease the rate of heart attacks. Funnily enough, more calcified plaques tend to rapture less frequently - which makes sense if you think about it. hs-CRP and other acute phase proteins CAN correlate with atherogenesis but it's a terrible proxy because it's regulated by all sorts of processes. If somebody sneezes in front of you, your CRP will go up - good luck decoupling this from tiny changes in plaque formation.

Good advice. Maybe to mention that PCSK9-inhibitors are super expensive (~6-10k $/ year), while statins are cheap as hell. Also, check your Lipoprotein A (Lp(a)) at least once in your lifetime - even if your ApoB is known.

The imperial college London recently published the most elaborate DMT-study ever conducted. They gave 20mg of intravenous N,N-Dimethyltryptamine (DMT) to 20 healthy adults and measured brain activity through multimodal neuroimaging (EEG-fMRI (electroencephalography-functional MRI)). One of the findings was the following: "The results, published in the journal Proceedings of the National Academy of Sciences, provide the most advanced picture yet of the human brain on psychedelics. The recordings show how the brain’s normal hierarchical organisation breaks down, electrical activity becomes anarchic, and connectivity between regions soars, particularly those handling “higher level” functions such as imagination, which evolved most recently in humans. “The stronger the intensity of the experience, the more hyperconnected were those brain areas,” said Timmermann. This ability to make brain activity more fluid and flexible is thought to underpin not only the profound psychedelic experience but the promising results from early clinical trial patients who were given DMT in combination with psychotherapy to treat depression. “DMT is short-acting, so it’s a very flexible tool compared with psilocybin [the active ingredient in magic mushrooms] and LSD which can last for six to 10 hours,” said Timmermann." I know this following statement might be triggering (esp. for Leo) but is the "I am GOD"-experience nothing more than an illusion caused by overclocked imagination? Let's discuss this. Link to study: https://www.pnas.org/doi/full/10.1073/pnas.2218949120 Link to article which is more accessible for most: https://www.theguardian.com/science/2023/mar/20/psychedelic-brew-ayahuasca-profound-impact-brain-scans-dmt?CMP=share_btn_tw

Working in the medical field will do that to you - inevitably so. It takes an unduly heterodox attitude to embrace both worlds in my experience

I like Peter and after having worked with him in the past, I do also respect him as a sincere colleague. Besides that, please take those numbers with a grain of salt. There is a lot of reverse causation and other dynamics at play. Anything that sounds "too good to be true" usually isn't the whole story. Read his book, take his advice - but let's be smart about it!