yetineti

Plant based?

60 posts in this topic

1 minute ago, Unlimited said:

You can get the pdf files for free.

Just reading a wikipedia article is not enough.
This really shows how ignorant you are.

It is your decision tho and I respect that.

You have an aggressive vibe. Beware of orthorexia.


The devil is in the details.

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How you relate to food says a lot about you.


I tried to catch some fog earlier. I mist.

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17 minutes ago, Yimpa said:

How you relate to food says a lot about you.

What do you like eat ?


The devil is in the details.

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45 minutes ago, Unlimited said:

You can get the pdf files for free.

Just reading a wikipedia article is not enough.
This really shows how ignorant you are.

Exactly it shows the degree of my ignorance which is necessary to have. Of course I could be wrong but that's true about everything. If I wanted to be sure about everything it would take me hundreds of years to research everything. But I only have a limited time so you got to be wise how you spent your time and cut through the rest of the bullshit. 

 

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3 minutes ago, Schizophonia said:

What do you like eat ?

I eat pescatarian, but will “cheat” once in a blue moon. 

Staplez include:

  • Oatmeal
  • Blueberries
  • Tofu
  • Tuna (occasionally due to mercury)
  • Beans

I tried to catch some fog earlier. I mist.

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23 minutes ago, Yimpa said:

How you relate to food says a lot about you.

Every piece of the universe is interconnected with the rest of the universe. 

Or as Alan Watts puts it: Every piece of the universe implies the rest of the universe. 

 

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On 6.3.2024 at 9:17 PM, Schizophonia said:

Don't you fear tolerance? :ph34r:
There will be one, sooner or later.

I cycle everything for 5 days on and 2 days off, but you're right, I do notice that tolerance builds up over time with certain substances regardless.

One solution to this would be to cycle through distinct nootropic stacks every few months, so you never become too attached to anything in particular.

The accelerationist solution would be to perpetually keep optimizing and adding new compounds, habits, and technologies.

I'm currently more oriented towards the latter.


“We are most nearly ourselves when we achieve the seriousness of the child at play.” - Heraclitus

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On 3/3/2024 at 10:43 AM, aurum said:

Do you have a source? I’m not seen any human studies claiming that oxysterols are directly atherogenic, only correlated. 

 

On 3/3/2024 at 5:54 PM, Nilsi said:

I consume it in moderation, and feel good doing so. Never heard about that, and some quick research doesn’t confirm this either.

 

On 3/6/2024 at 1:53 AM, MarkKol said:

Saturated fat found in meat will raise ApoB in most/many individuals. Higher ApoB = higher risk of heart disease.

Alright my friends, I am going to be addressing the issue of whether or not ghee, due to its oxysterol content, is directly atherogenic, and this will necessarily morph into a discussion of the actual underpinnings of cardiovascular disease (CVD).

I want to preface the delineation of these ideas by saying that I don't expect anyone to believe me, but that I have confidence in the fact that, as Leo followers, you will honestly entertain this information by at the least ascertaining whether or not it agrees with your own logic. I have zero need or desire to convince anyone of these ideas, I’m simply sharing a perspective that if right, would radically recontextualize a disease that every 33 seconds in America alone, someone drops dead of. This is a perspective that resonates with my own reasoning, but again, if it doesn’t agree with your own logic and intuition, then I completely understand.

I'm about to present an epiphany that one of my close friends and mentor had over 20 years ago after the tragic, sudden cardiac death of his maternal grandmother, which plummeted him into the depths of a rabbit hole, the likes of which necessitated a frankly autistic effort to come out the other side of. This friend Luke had a deep need to know why such a thing could ever happen, and the answer he arrived at, I personally find exceedingly compelling, and one that connects seemingly disparate dots in a self-consistent fashion.

I am going to incorporate a handful of studies since they were requested, but I also want to be very clear that this perspective cannot be found in any one study because it is a synthesis of several thousands of studies and observations germane to the subject matter.

This study here just illustrates the appreciable oxysterol content of ghee, and negligible amount found in butter, and explores the possibility of the sky high ghee intake being implicated in the otherwise unexplained high risk of atherosclerosis in Indian immigrant populations (the full text from The Lancet unfortunately requires institutional access): https://pubmed.ncbi.nlm.nih.gov/2887943/).

This is a great review from 2017 published in "Lipids in Health and Disease" exploring the pro-atherosclerotic properties of oxysterols: https://lipidworld.biomedcentral.com/articles/10.1186/s12944-017-0579-2

This study here demonstrated plaque reversal after supplementing with one of the most potent sources of antioxidants on the planet, pomegranate juice. After one year, the patients who supplemented had a 30% reduction, as opposed to 9% increase (seen in the control group) in their common carotid intima-media thickness. They also showed that these patients who began reversing their cardiovascular disease had serum LDL with reduced basal oxidative state and susceptibility to copper ion-induced oxidation (by 90% and 59%, respectively). https://www.clinicalnutritionjournal.com/article/S0261-5614(03)00213-9/abstract

The bottom line my friends, is that I believe we have misidentified the pathophysiology of cardiovascular disease, and the necessary consequence of that is we have been optimizing for the wrong metric, namely the assault at all cost to bottom out LDL cholesterol. The most profitable drug of all time, Lipitor, having amassed some 131 billion in sales during its protection period, something I have dispensed thousands of tablets of to my everlasting shame, is actually predicated on a lie, or at best, cognitive error.

Having been a pharmacy student during the time my friend Luke communicated this to me some 8 years ago, I'd like to just share with you the reasons why, after being catapulted through much cognitive dissonance, I have come into alignment with Luke's thinking and why I deem it so compelling.

If native LDL were in fact atherogenic, then it's quite odd that the serum concentration we target via statin therapy is akin to a goalpost that is being continually shifted downward. It’s furthermore odd and ostensibly unexplainable within the conventional paradigm how both people with sky high, and bottomed out LDL can both succumb to CVD.

It's also quite odd that smoking is such a strong risk factor for cardiovascular disease despite cigarette smoke not being known to elevate one's circulating lipoproteins (the chemicals in it however do increase LDL, among other lipoproteins, susceptibility to oxidation).

The fact that fruits and vegetables, potent antioxidant sources, correlate favorably with cardiovascular outcomes is then not surprising when viewed through this lens.

The fact that CVD was undetectable and unheard of in the Tokelauan people, who consumed diets wherein north of 60% of their energy intake came from coconuts which are north of 90% saturated fat (which decreases LDL susceptibility to oxidation).

The fact that any condition that increases oxidation, diabetes mellitus among them, increases CVD risk, also aligns favorably with this hypothesis, as do conditions such as familial hypercholesterolemia which increase the number of opportunities for oxidation. I must however underscore that I would submit the best strategy to counteract such conditions, be not to optimize for bottoming our total lipoproteins in circulation, but rather, mitigating the total oxidized species by opting for actions that decrease LDL, for example, susceptibility to oxidation (eating fruits/vegetables, pomegranate juice and wild blueberries most notably, avoiding cigarette smoke and toxic exhaust fumes, keeping ferritin in range, emphasizing saturated and monounsaturated fat relative to PUFA, not overcooking meat which forms oxysterols, not consuming ghee and minimizing phytosterol intake).

The fact that, all else equal, having a higher ApoB (which is a proxy for the number of circulating lipids that could conceivably oxidize) puts one at more risk, is unsurprising given that there then would be more opportunities for oxidation. That said, the notion that ApoB is causal is absurd, and optimizing specifically for its mitigation is not well-founded.

Viewing CVD through the lens of oxidation (any circulating lipoprotein, not merely LDL, but also even the cellular membranes of red blood cells) also explains why these so-called "lean mass hyper-responders" and keto/carnivore proponents at large, are not being shown to have potentiated plaque formation (their diets are extremely low in linoleic acid which will making circulating LDL, for example, less prone to oxidation). That said, folks who adopt this diet are missing out on the strongest lever in the equation which is an augmented antioxidant status (derived from fruits and vegetables).

The increase consumption of linoleic acid over the past century, not least evidenced by adipose tissue biopsies, moreover corroborates with the view that oxysterols are atherogenic because of the increased susceptibility to oxidation that this facilitates.

There are many more lines of logic/reasoning supporting viewing CVD through the lens of oxidation, and there is a 2018 publication from the BMJ titled “Omega-6 vegetable oils as a driver of coronary heart disease: the oxidized linoleic acid hypothesis” which excellently expounds upon such in box 1 with 29 supported rationales: https://openheart.bmj.com/content/5/2/e000898.long

Consuming oxidized cholesterol has been shown to directly increase fatty streak lesions in rabbits (https://www.ahajournals.org/doi/full/10.1161/01.ATV.18.6.977#:~:text=Thus%2C%20very%20small%20quantities%20of,present%20in%20the%20oxidized%20form.) and this has never been replicated in humans for reasons of ethics.

When something is studied, the hope is that the intervention confers an actual benefit. A study feeding humans oxidized cholesterol would never get approved because it’s neutral at best, and fatal at worst, i.e., there is no benefit to be garnered when the hypothesis is that oxysterols are atherosclerotic.

At the end of the day, you have to opt for the nutrition and lifestyle that agrees with your own intuition, because you are the only arbiter of what is and is not worth putting into your body. I just wanted to share this perspective because I find it incredibly compelling, and I’m genuinely happy to have had the opportunity to share this with you guys.

Be well my friends.

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@Jason Actualization Appreciate the thorough response on this. It's certainly got me thinking about my diet, especially since I do consume ghee.

I think you are mostly correct, but I'm going to push back on you on a couple of points:

1) The 2017 Lipids study you provided does not draw a causative link from oxysterols to atherosclerosis, only a correlation. You acknowledge this when it comes for LDL and ApoB, but not oxysterols

2) If you are that concerned about oxysterols, what about meat? I'm assuming you are not eating raw. Therefore you must accept that some level of oxysterols are non-problematic, or that they are simply a worthwhile tradeoff due to the other benefits of meat.

Looking forward to your response if you have one you'd like to share.

 


 

 

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9 hours ago, Schizophonia said:

You have an aggressive vibe.

Didn't want to give that impression.

9 hours ago, Schizophonia said:

You have an aggressive vibe. Beware of orthorexia.

Thank you, I will.

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8 hours ago, Jannes said:

Exactly it shows the degree of my ignorance which is necessary to have. Of course I could be wrong but that's true about everything. If I wanted to be sure about everything it would take me hundreds of years to research everything. But I only have a limited time so you got to be wise how you spent your time and cut through the rest of the bullshit. 

 

I understand, hope you find the right thing for yourself.

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30 minutes ago, aurum said:

@Jason ActualizationLooking forward to your response if you have one you'd like to share.

Sure thing, great questions by the way, I'll do my best here.

1. Yes, I want to be very clear here. There is no shortage of things that correlate with CVD, i.e., LDL, ApoB, diabetes, smoking, OxLDL, hypertension, seed oil consumption, etc.

You are 100% correct in that I acknowledge all of these correlations, even with oxysterols by the way. If something is causative, it is also correlative, but not vice versa. 

So the question we must ask, is if CVD is the smoke, which of the myriad things that correlate is the true gun (surely at least one must be)?

I'm submitting that oxidized cholesterol (oxysterols) is the unifying factor and that in fact, it's our own immune system responding to this oxidation that renders the chronic inflammation that lays down plaque in the end.

LDL and ApoB correlate, but if one mistakes them for the cause, they will employ the wrong strategy to reverse or prevent CVD (lowering LDL via statins will decrease the opportunities for oxidation but if you understand the actual causal pathway of CVD, this strategy seems beyond silly and imposes more issues than it resolves, not least the precipitation of cerebrovascular disease, i.e., Alzheimer's, due to the deprivation of cholesterol in the brain).

To be absolutely crystal clear, cholesterol, irrespective of serum concentration, is not atherogenic in its native state, but all else equal, someone with more circulating lipoproteins will, on average, have more absolute oxidized lipoproteins (the answer still is not to bottom out said lipoproteins).

2. You've hit the nail on the head, that's right, we must accept some degree of oxysterols, both those ingested exogenously and rendered endogenously (both to a certain degree are inevitable). Oxidation of lipoproteins is unavoidable, but it is the unfavorable imbalance (i.e., excess) of oxidation relative to ones antioxidant status that results in net plaque formation. The single best way to protect yourself is with a strong antioxidant (I highly recommend 250 mL of 100% pomegranate juice per day which I consume without fail and is reflected in my bloodwork, including low OxLDL).

I advise against consuming raw food, and rather, I advise folks pressure cook at the lowest heat and pressure possible for the least amount of time. I use an Instant Pot on the low pressure setting for 6 minutes to prepare my beef, eggs and basmati rice.

Overcooking meat, and worse yet, reheating/recooking (people who meal prep) will greatly potentiate oxysterol formation which is bad news, yes.

Meat has myriad benefits, just be sure to not overcook it and to monitor your iron levels (the storage form specifically, ferritin, which is pro oxidative). I know folks aren't going to like this, but yes, the saturated fat in meat, but also coconuts, dairy, etc, is in fact protective, but perhaps that's a story for another time (it entails epistemology and the erroneous pedestalization of human outcome data, which in principle, I agree with, but there are deep issues in this arena that I believe are not being understood).

The study linking ghee to increased heart disease risk should ring the alarm bell for everyone given that it has much, much higher oxysterol levels than that found in cooked meats. I cannot stress enough the importance of this: I would consume industrial seed oils before I would ever touch ghee, and that's because my antioxidant status is amazing, so I'm less worried about oxysterol formation endogenously, which I am protected from, as opposed to oxysterol consumption exogenously which I cannot fight off.

You will not find non-mechanistic studies showing a causative link between oxysterols and heart disease because these studies would never pass ethics. Why haven't we replicated the rabbit study with humans? It would be very simple to do, feed one group of humans oxidized cholesterol and feed another group unoxidized cholesterol and observe the differences. It will never be done because it will never pass ethics.

One last thing I should mention about industrial seed oils that I've never seen pointed it, is their phytosterol content. Just like cholesterol, phytosterols can become oxidized, and they are even more susceptible to it. These industrial oils not only contain ancestrally inconsistent amounts of linoleic acid which increase LDL (and other lipoproteins) susceptibility to oxidation, but considerable amounts of phytosterols which can be independently problematic.

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45 minutes ago, Jason Actualization said:

So the question we must ask, is if CVD is the smoke, which of the myriad things that correlate is the true gun (surely at least one must be)?

I'm submitting that oxidized cholesterol (oxysterols) is the unifying factor and that in fact, it's our own immune system responding to this oxidation that renders the chronic inflammation that lays down plaque in the end.

Interesting. 

I think a potential hole in your theory is that you are suggesting a physiological unifying factor, when in fact there may not be one. Especially when it comes to something complex and holistic like chronic inflammation. But nonetheless I am intrigued and will do some more digging on this.

45 minutes ago, Jason Actualization said:

I cannot stress enough the importance of this: I would consume industrial seed oils before I would ever touch ghee, and that's because my antioxidant status is amazing, so I'm less worried about oxysterol formation endogenously, which I am protected from, as opposed to oxysterol consumption exogenously which I cannot fight off.

Also very interesting.

People in the biohacking / carnivore / keto / animal-based community talk about their issues with seed oils / linoleic acid  all the time, but almost all those same people are proponents of ghee. I think you've convinced me to at least test switching out ghee for some grass-fed butter and to see what happens with my labs. It's a pretty simple swap to make.


 

 

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1 hour ago, aurum said:

Interesting. 

I think a potential hole in your theory is that you are suggesting a physiological unifying factor, when in fact there may not be one. Especially when it comes to something complex and holistic like chronic inflammation. But nonetheless I am intrigued and will do some more digging on this.

Indeed, there may not be, you're correct.

This is simply the best explanation I have encountered that, in my mind, ties up the loose threads that other explanations do not (i.e., viewing CVD through the lens of oxidation).

1 hour ago, aurum said:

People in the biohacking / carnivore / keto / animal-based community talk about their issues with seed oils / linoleic acid  all the time, but almost all those same people are proponents of ghee. I think you've convinced me to at least test switching out ghee for some grass-fed butter and to see what happens with my labs. It's a pretty simple swap to make.

Bingo, they substitute one problem for another, and now that I'm living in Australia I'm trying to get into contact with Paul Mason to explain this to him. In short, he is the closest to arriving at this understanding that I've seen in the influencer sphere, but his clotting theory is still slightly off base.

Grass-fed butter is the way to go, that is a solid substitution you've made.

Carnivore proponents get two things primarily wrong: 1. they demonize all carbohydrates (when it's merely excess fructose that is problematic in metabolically healthy individuals) and 2. they demonize all plant foods which are actually the most potent way to counteract oxidative stress. At the end of the day, being omnivore is optimal, and I would apply that assertion unanimously to mankind (people with severe autoimmune issues may benefit from carnivore as a door to walkthrough, but it's not a room to reside in indefinitely).

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16 hours ago, Yimpa said:

I eat pescatarian, but will “cheat” once in a blue moon. 

Staplez include:

  • Oatmeal
  • Blueberries
  • Tofu
  • Tuna (occasionally due to mercury)
  • Beans

What a horrible Diet :P:/


The devil is in the details.

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Posted (edited)

14 hours ago, Jason Actualization said:

I'm submitting that oxidized cholesterol (oxysterols) is the unifying factor and that in fact, it's our own immune system responding to this oxidation that renders the chronic inflammation that lays down plaque in the end.

I want to explore this theory a bit because to me this is where the rubber meets the road. I like your reasoning and I think we can take the nerdy theory one step further :D

What you are describing is indeed pathophysiology of atherosclerosis which I am no expert in but from literature on CVD I have read, this is roughly how it works. 

Given that, here is the next question: 

The penetration of ApoB containing particles (namely - LDL, VDLD , LP(a))  through tunica intima is, to my understanding, partially unavoidable as it is one of the imperfections of the human body.It is not the penetration itself that is the problem (they can escape back in the flow and this happens all the time same way electrolyte particles penetrate between extra and intracellular space inside the axon of the nerve cells) but it is their irreversible binding to the proreglycan structures, (these proteins hanging around between tunica intima & tunica media) that cause those particles to stay there. Once they are locked, they are fucked. 

So then

  • Is it that ApoB particles (LDL, VLDL, Lp(a) ) get oxidised before they enter the subendothelial space?
  • Or is it that they get oxidised after they get in there through their immobility? - I dont' understan the mechanism tho
  • Is there something that makes oxidative particle more prone to entering the subentothelial space? 

This is what I am not clear about, maybe you have some insights to share.

Are we 100% sure that oxidation does not happen inside subentothelial space rather than inside the circulation?

Purely because those particles, after attaching to proteoglycans trigger immune response - macrophages enter the subendothelial space, trigger chemotaxic response, more immune cells are called on for, and all of that and they trigger inflammation. Inflammation is prooxidative - oxidation creates fallout and increases the odds of ApoB particle oxidation (those that are locked to proteoglycans because they can't escape).

Macrophages gobble up the dead oxLDLs, they grow, turn in foam cells, get too "fat" and get stuck in the subendothelial space, they die & accumulate like a puss but in this case the puss can't get out - plaque starts building up - typical atherosclerosis right? Its kinda like a cyst but it builds in a space where it obstructs blood flow and can kill a person. 

Maybe this is the greatest imperfection of the human body and the reason most of us die as  a result of heart disease? Because it is not 100% avoidable? 

So what if, the oxidative ApoB particles are actually the ones that are already locked in to proteoglycan structures?

  • Are we really looking at the right space when we are testing patients for oxidated LDL through standard blood test
  • Shouldn't we instead be looking at oxLDL content inside the subendothelial space? -  where you would be more likely to see oxidated particles? (for obvious reasons that would be extremely hard to test without arterial biopsy which would be difficult, dangerous, unethical and expensive as heck). But isn't that what we see from tissues of post-mortem studies? Docked in oxidised ApoB particles inside subendotheliual space? @undeather might know more about this form his clinical practice & research
  • Given that maybe the total LDL count that common tests are looking at is indeed the correct way to study this? Plus you want to know how many VLDLs and LP(a) you have so testing for ApoB and for LP(a) is a good idea for those who want to go deeper

Interestingly this connects us to Pomegranate juice. To my knowledge, there are not very successful medication that can dislocate ApoB particles from proteoglycans but I think Punicalagins in PJ actually can. I have been toying around with idea of starting that consumption as well so I absolutely agree with you that there is somethign going on there which helps offset this damage. Maybe PJ is part of the answer. I don't think it can reverse plaque but maybe there is a timespan, say 72 hours (made that up) before those locked particles can still be dislocated before they trigger an army of macrophages? 

But what if that's not the right perspective to look at it? What if looking at it through the lenses of oxidative theory is again looking at consequence and not the cause? 

Maybe we need to be looking at , what increases the risk of ApoB particles (LDL, APoB, Lp(a) penetration into subendothelial space in the first place? Since it is not 100% avoidable, how can we minimise it? 

I would say, it starts with reducing the volume of ApoB particles in blood. There are 3 of them: LDL, VLDL & LP(a). 

  • Lp(a) is mainly driven by genetics to my knowledge so that one is hard to control without medication & strict lifestyle management (weight control etc.) I am not sure to what degree LP(a) is derived form diet. Maybe you know? 
  • LDL & VLDL are more likely to be impacted by diet and genetics for peope with familila hypercholesterolaemia.

So then the ways to control isn't just to focus on antioxidant status but to focus on the penetration factor (as quirky as that sounds

  • Blood pressure is an obvious one - control for blood pressure and you reduce the force driving the APoB particles through the arterial walls into subendothelium. Exercise, stay lean, don't smoke. Helps protect the arterial walls from stiffening, that's good and that's important. 
  • Reduce the total ApoB in diet mainly by reducing highest sources of APoB containing lipoproteins - animal foods with highest saturated fat content. (might be more complicated) 
  • control for total bodyweight, waist circumference and common antropomethric factors associated with hypertension 
  • take medication if diagnosed with FH 

I appreciate that this theory has holes but it makes sense to me that this is they key trigger and this is where it starts. Oxidation should be minimised through diet and I think we should actively be researching substances that help dislocate APoB particles from proteoglycans (such as pomegranate juice), I think PCSK-9 Inhibitors can do that too (and frankly I think this is where the future of cardiovascular medicine lies). 

Statins are helpful fro people who are unable to take control or who have genetic disorder - they prolong life but they do cause other issues, I'm with you on that and don't love them. 

I don't yet know where seed oils come into the mix. I also agree with you that human outcome data based mainly on prospective observation isn't perect but I'd say given the complexity, is the best we have. Maybe seed oils cna be treated as doubkle edged sword? They are more likely to oxidise but because they displace saturated fats (people more likely to eat more PUFA will usually eat less SFA) they decrease the probability of excessive LDL migration into subendothelium? Just a speculation. Honest answer here is I don't know and I haven't yet come to final consensus on seed oils. 

I'm interested to keep this debate going, this is a topic close to my heart as I, same as you, have seen people close to me, succumb to it. I think you make a lot of good and interesting points. Agree with some, disagree with some but overall I love this discussion. 

Edited by Michael569

“If you find yourself acting to impress others, or avoiding action out of fear of what they might think, you have left the path.” ― Epictetus

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Posted (edited)

Binding of proteoglycans induces structural changes in LDL impacting both the configuration of apoB100 and the lipid composition. Hence, the binding of LDL to proteoglycans makes the LDL more susceptible to oxidation and aggregation, which promotes foam cell formation and a proinflammatory response, and the process is self-perpetuating. Oxidized LDL can induce further production of proteoglycans by vascular smooth muscle cells, retaining more LDL in the arterial wall.The causal relationship between ApoB and cardiovascular disease progression is one of the most consistent in all of modern medicine.

What you measure in your serum as "oxLDL" is NOT the same as the particle that goes through the oxidation process in the subendothelial space. A fully oxidized lipoprotein particle, which then  becomes a ligand for the scavenger receptor of the macrophage, shows a high modifcation-state in their phospholipids and the apoB-component. This process doesn't occur directly in your bloodstream, primarily because of the abundance of antioxidants present there. However, minimally oxidized LDL particles in your serum do show a higher propensity to enter the arterial wall and appear to further promote atherosclerotic activities, such as reduced capability for reverse transport and increased production of reactive oxygen species (ROS). Yet, it's important to note that most studies to date haven't definitively pinpointed the direct cause. Ultimately, the crucial factor is total ApoB, and in my view, mendelian randomization studies illustrate this most effectively.

Even with no oxidized LDL (oxLDL) in your serum, having a high ApoB count can still lead to heart disease. Numerous studies indicate that having a higher antioxidative capacity does not guard against atherosclerosis. Intriguingly, exceeding a certain threshold of antioxidative potential might even exacerbate the condition. While I support efforts to reduce serum oxLDL, given the strong mechanistic rationale behind it, it's crucial we don't selectively interpret data. Instead, we should consider the broad spectrum of research findings to guide our understanding and actions. What we definitely can be sure of is that reducing ApoB burden, through lifestyle interventions and sometomes drugs, directly reduces our cardiovascular disease risk. 

Edited by undeather

MD. Internal medicine/gastroenterology - Evidence based integral health approaches

"Perhaps all the dragons in our lives are princesses who are only waiting to see us act, just once, with beauty and courage. Perhaps everything that frightens us is, in its deepest essence, something helpless that wants our love."
- Rainer Maria Rilke

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On 3/10/2024 at 3:38 AM, Michael569 said:

The penetration of ApoB containing particles (namely - LDL, VDLD , LP(a))  through tunica intima is, to my understanding, partially unavoidable

Unavoidable, yes.

On 3/10/2024 at 3:38 AM, Michael569 said:

It is not the penetration itself that is the problem (they can escape back in the flow and this happens all the time same way electrolyte particles penetrate between extra and intracellular space inside the axon of the nerve cells) but it is their irreversible binding to the proreglycan structures, (these proteins hanging around between tunica intima & tunica media) that cause those particles to stay there. Once they are locked, they are fucked. 

 

The immune system will not inherently identify them as foreign and mount an attack unless/until they become oxidized, so their presence alone is necessary but insufficient.

On 3/10/2024 at 3:38 AM, Michael569 said:

Is it that ApoB particles (LDL, VLDL, Lp(a) ) get oxidised before they enter the subendothelial space?

The oxidation can occur both prior and subsequent to entry into the subendothelial space. To be crystal clear here, the fact that these lipoproteins contain ApoB has absolutely nothing to do with the pathophysiology. The only reason ApoB correlates so favorably with CVD is because it is contained within the lipoproteins that are the most prone to oxidation.

Oxidized lipoproteins (or other oxidized things) do not need to enter the subendothelial space to initiate plaque formation, they can simply adhere to the endothelium and initiate it. Oxidized lipoproteins and, for example, red blood cells, etc., are seen as foreign objects and are attacked by the immune system, and that response is responsible for the inflammation and plaque development.

On 3/10/2024 at 3:38 AM, Michael569 said:

Is there something that makes oxidative particle more prone to entering the subentothelial space? 

I believe we should set our sights on ascertaining what makes the particle more prone to oxidation, not to entering the subendothelial space.

On 3/10/2024 at 3:38 AM, Michael569 said:

Are we 100% sure that oxidation does not happen inside subentothelial space rather than inside the circulation?

It happens in both locations: the initiation of atherosclerosis requires oxidation to occur inside the subendothelial space, and the progression will occur within the circulation (once plaque forms, these particles are no longer traversing said plaque to enter the subendothelial space).

On 3/10/2024 at 3:38 AM, Michael569 said:

Purely because those particles, after attaching to proteoglycans trigger immune response - macrophages enter the subendothelial space, trigger chemotaxic response, more immune cells are called on for, and all of that and they trigger inflammation. Inflammation is prooxidative - oxidation creates fallout and increases the odds of ApoB particle oxidation (those that are locked to proteoglycans because they can't escape).

Right, so technically CVD is actually caused by our immune system defending itself in response to the oxidative stress. Again, ApoB has nothing to do with this process, it’s actually an innocent bystander, but I see what you’re saying and believe that’s correct, yes.

On 3/10/2024 at 3:38 AM, Michael569 said:

Macrophages gobble up the dead oxLDLs, they grow, turn in foam cells, get too "fat" and get stuck in the subendothelial space, they die & accumulate like a puss but in this case the puss can't get out - plaque starts building up - typical atherosclerosis right? Its kinda like a cyst but it builds in a space where it obstructs blood flow and can kill a person. 

Yes, I find it obnoxious that every 33 seconds in America alone, someone drops dead of this disease.

On 3/10/2024 at 3:38 AM, Michael569 said:

Maybe this is the greatest imperfection of the human body and the reason most of us die as  a result of heart disease? Because it is not 100% avoidable? 

I will preface what I’m about to suggest by acknowledging its seemingly radical nature, and too I will start by agreeing that it’s not 100% avoidable (without the right information). That said, I honestly believe that this is the easiest disease to prevent and reverse with the right understanding of it.

On 3/10/2024 at 3:38 AM, Michael569 said:

So what if, the oxidative ApoB particles are actually the ones that are already locked in to proteoglycan structures?

They don’t have to be in order to be atherogenic.

On 3/10/2024 at 3:38 AM, Michael569 said:

Are we really looking at the right space when we are testing patients for oxidated LDL through standard blood test

Great point, I see OxLDL in the serum as simply a surrogate for the overall oxidative stress in ones body, which is more insightful than any other cholesterol test currently available, in my estimation.

On 3/10/2024 at 3:38 AM, Michael569 said:

Shouldn't we instead be looking at oxLDL content inside the subendothelial space? -  where you would be more likely to see oxidated particles? (for obvious reasons that would be extremely hard to test without arterial biopsy which would be difficult, dangerous, unethical and expensive as heck). But isn't that what we see from tissues of post-mortem studies? Docked in oxidised ApoB particles inside subendotheliual space?

Whether they enter the subendothelial space or just adhere to the endothelium makes zero difference. After the initial plaque formation, newly oxidized lipoproteins no longer even come in contact with the endothelium, they merely bind to the plaque already there and cause it to thicken.

On 3/10/2024 at 3:38 AM, Michael569 said:

Given that maybe the total LDL count that common tests are looking at is indeed the correct way to study this? Plus you want to know how many VLDLs and LP(a) you have so testing for ApoB and for LP(a) is a good idea for those who want to go deeper

ApoB is a red herring and LP(a), while useful, is simply another lipoprotein that is more susceptible to oxidizing. The strategy still is to lead lives that render more oxidation-resistant lipoproteins.

On 3/10/2024 at 3:38 AM, Michael569 said:

Interestingly this connects us to Pomegranate juice. To my knowledge, there are not very successful medication that can dislocate ApoB particles from proteoglycans but I think Punicalagins in PJ actually can. I have been toying around with idea of starting that consumption as well

Highly recommended man, this is the top health tip I give to everyone.

On 3/10/2024 at 3:38 AM, Michael569 said:

Maybe PJ is part of the answer. I don't think it can reverse plaque but maybe there is a timespan, say 72 hours (made that up) before those locked particles can still be dislocated before they trigger an army of macrophages? 

It can reverse plaque, yes. In the 2004 study cited before, the control group had their carotid intima-media thickness (IMT) increase by 9% after 1 year, whereas the intervention arm entailing PJ consumption, resulted in a significant IMT reduction, by up to 30%, after 1 year.

On 3/10/2024 at 3:38 AM, Michael569 said:

But what if that's not the right perspective to look at it? What if looking at it through the lenses of oxidative theory is again looking at consequence and not the cause? 

What do you hypothesize the cause to be in this case? I should be clear too and say that the cause of heart disease is the defense mechanism employed by our own immune system (chronic inflammation) but what elicits the mounting of that response is the imbalance of oxidative stress relative to antioxidant activity.

On 3/10/2024 at 3:38 AM, Michael569 said:

Lp(a) is mainly driven by genetics to my knowledge so that one is hard to control without medication & strict lifestyle management (weight control etc.) I am not sure to what degree LP(a) is derived form diet. Maybe you know? 

I'm not sure about this one.

On 3/10/2024 at 3:38 AM, Michael569 said:

Statins are helpful fro people who are unable to take control or who have genetic disorder - they prolong life but they do cause other issues, I'm with you on that and don't love them. 

Yes, artificially lowering cholesterol is not without consequence, and my greatest concern are the cerebrovascular conditions that can arise in time.

On 3/10/2024 at 3:38 AM, Michael569 said:

I don't yet know where seed oils come into the mix.

They are rich sources of easily oxidizable phytosterols and they also contain ancestrally inconsistent amounts of linoleic acid which increase LDL susceptibility to oxidation.

On 3/10/2024 at 3:38 AM, Michael569 said:

I also agree with you that human outcome data based mainly on prospective observation isn't perect but I'd say given the complexity, is the best we have.

And this is where we face the fork in the road and may have differing epistemic assumptions.

This may very well be the most important point I’ve ever made on this forum because it cuts to the core of our base assumptions.

There is a lot of talk about valuing the human outcome studies and disregarding, or at best, putting on the backburner, mechanistic data.

Here is the problem: if human outcomes are the truthful territory we wish to explore, the human outcome data is a misleading map that is at best, incomplete, and at worst, entirely erroneous.

So, while I agree wholeheartedly that actual human outcomes are what we actually care about and are the ultimate arbiter dictating what constitutes a healthy lifestyle, the problem is that the data pertaining to such has led us astray.

When we see whether or not linoleic acid increases LDL susceptibility to oxidation, it not only does so, but it happens every single time. It’s very black and white.

If mechanistic studies are black and white portraits, human outcome studies are nebulous water paintings that elicit different moods and feelings for different folks depending on how they happen to view and interpret such.

Mechanistic studies corroborate with one another, but human outcome studies do not. The problem is that the direction that human outcome studies point to is something people cannot unsee.

They aren’t able to scratch the entirety of that data set and construct an entirely new understanding from ground zero, this time, being sure to lay down merely solid bricks, but never broken ones.

On 3/10/2024 at 3:38 AM, Michael569 said:

Maybe seed oils cna be treated as doubkle edged sword? They are more likely to oxidise but because they displace saturated fats (people more likely to eat more PUFA will usually eat less SFA) they decrease the probability of excessive LDL migration into subendothelium? Just a speculation. Honest answer here is I don't know and I haven't yet come to final consensus on seed oils.

I am personally convinced that these oils are in fact the primary driver of heart disease. Unfortunately, you would be hard-pressed to find a person, let alone a cohort of folks with an adipose linoleic acid (LA) level below 10%. These people are becoming increasingly rare due to the landscape of the modern food supply chain. I wish we had data comparing people who have single digit LA levels in their adipose to people with 20%+. This, in my estimation, is absolutely vital to getting human health back on track (i.e., subtracting the seed oil).

On 3/10/2024 at 3:38 AM, Michael569 said:

I'm interested to keep this debate going, this is a topic close to my heart as I, same as you, have seen people close to me, succumb to it. I think you make a lot of good and interesting points. Agree with some, disagree with some but overall I love this discussion. 

Definitely my friend. At the end of the day, the only aspect, as far I know, regarding your practical takeaways, that I disagree with, is the caution you exert pertaining to saturated fat intake. But honestly, even though I prefer a higher saturated fat intake, so long as people are not consuming excess PUFA, I am perfectly fine with that (i.e., we agree that monounsaturated fats are innocuous).

On 3/10/2024 at 5:07 AM, undeather said:

The causal relationship between ApoB and cardiovascular disease progression is one of the most consistent in all of modern medicine.

Could you explain how ApoB exactly it causes CVD progression?

On 3/10/2024 at 5:07 AM, undeather said:

Even with no oxidized LDL (oxLDL) in your serum, having a high ApoB count can still lead to heart disease.

Absolutely not, oxidation is necessary for atherogenic activity, ApoB is a transport protein that is not implicated in the causal pathway. That said, the ApoB number indicates the total number of potentially atherogenic particles, the higher the number the higher the risk, all else equal. But the optimal strategy then is not to bottom this out at all cost, in my strong opinion.

On 3/10/2024 at 5:07 AM, undeather said:

Numerous studies indicate that having a higher antioxidative capacity does not guard against atherosclerosis. Intriguingly, exceeding a certain threshold of antioxidative potential might even exacerbate the condition.

I'd like to read this research if you don't mind taking the time to cite them for me.

On 3/10/2024 at 5:07 AM, undeather said:

we should consider the broad spectrum of research findings to guide our understanding and actions

I would prefer to be selective with the research findings I integrate into my understanding, emphasizing and opting for the quality and replicability of a sniper rifle, as opposed to the magnitude and chaos of Oppenheimer’s atom bomb.

The fastest way to end this debate would be to conduct a RCT wherein one arm of the trial is fed fresh cholesterol, and the other is fed oxidized cholesterol. The confusion would clear very quickly.

That said, I'm confident enough in this causal pathway that I don't need to see this (admittedly) highly unethical study transpire in order to satisfy my curiosity, but nevertheless I do recognize how impactful it would be in advancing our understanding of CVDD.

That said, I recognize not everyone will find my train of thought equally compelling/convincing, and so I must rest my case.

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Posted (edited)

I eat plant based with exception of eggs. 
 

I eat plant based, I am working on making sure I eat a very healthy diet. I eat a lot of beans, brown rice, vegetables like broccoli, carrot, cauliflower, and tofu. I eat fruits, nuts, etc. I also make sure I consume mushrooms like Reishi, Lions Mane, and I take vitamin d and omega 3 oils. The oat mills I drink are fortified with B12 (which comes from bacteria). I want to make sure I am getting all the proper vitamins and minerals, healthy amounts of proteins etc… and I am also concerned with balancing yin and Yang, acid/ Alkaline, eating for the right season, etc
 

Brian Johnson who spends 2million dollars a year on his private team of health scientists also eats plant based. I’ll likely be implementing more from his meal plans, while also considering Taoist and Aruryvedic approaches which are plant based basically.
 

So, people who say plant based isn’t healthy are simply wrong. 
 

I am very healthy. I walk, bike, run, do Qigong daily. Plant based works for me. 
 

I am not against eating meat. I occasionally do under rare circumstances but I overall like to avoid meat. I do feel better when I avoid it. 
 

Plant based is very healthy when done properly. Though, all bodies are different and so nutrition may vary from person to person.

Also, don’t discount the importance of herbs and spices in the maintenance of good health. This is rarely understood.

Edited by Thought Art

 "Unburdened and Becoming" - Bon Iver

                            ◭"89"

                  

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 "Unburdened and Becoming" - Bon Iver

                            ◭"89"

                  

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