Omnivore vs. Vegan - Randomized Controlled Trial in Twins! (new study)

[undeather]

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Apolipoproteins do cause plaque formation, I agree: but only if 1. they are oxidized and 2. they reside in the endothelium.

Yes -  They need to get trapped in the subendothelium AND go through oxidation processes. That's true.
The vast majority of lipoprotein oxidation happens IN the wall though!
 

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That being said, what ox-LDL (measured in the blood) does shed light on is the susceptibility of one's lipoproteins to oxidation.

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ApoB is a marker for how many lipoproteins you have in general, and LDL is just one of many others (i.e., VLDL, IDL, etc.) and the reason this tracks well with heart disease, is that the more lipoproteins you have, the more oxidized lipoproteins that can appear in artery walls since any one of them can oxidize and become atherogenic. All else being equal, having lower ApoB is of course better because there are less opportunities for oxidation, but in its' native state, none of our lipoproteins are atherogenic, irrespective of how much is in circulation. Ultimately, having higher levels of circulating lipoproteins does not cause heart disease, but does track with it for the aforementioned reasons. All that being said, the solution is not to optimize for the mitigation of circulating lipoproteins, but rather, for rendering them impervious to oxidation, which is why fruit and vegetable intake tracks favorably with heart disease outcomes (i.e., these augment ones' antioxidant status).

There is no credible evidence that ox-LDL is a strong predictor for CVD after controlling for total Apo-B. I know of one study who did that, and it was a highly flawed paper to begin with. If you have evidence for that claim (human data), please provide it! 

Having higher levels of circulating lipoproteins absolutely does cause heart disease. I would again, advice you to take the mendelian randomization papers into account. We find a dose-dependent relationship between ApoB and CHD across approximately two dozen genetic variants across many independent pathways (Graph below!). The study design of mendelian randomization does take oxidation status into account and we see the effect nontheless. 

Also, what you are describing here is the so called oxidative hypothesis of atherosclerosis. There is clear and convincing evidence that oxidation is involved in the pathogenesis of atherosclerosis and this alone provides a compelling argument that antioxidants should decrease the risk of atherothrombotic cardiovascular diseases. Yet, after 20+ years of clinical trials that studied the effect of supplemental antioxidants on incident cardiovascular disease, there is no overarching data to indicate that this intervention works. This is old science my friend! Increasing antioxidants and therefore lowering oxidation in your plasma does not protect you from heart disease. It's much, much, much mor ecomplex than that. Oxidation has it's part in the equation, but all the evidence suggests that there are more important targets than that.

The reason why fruit and vegetables intake tracks favorably with heart disease outcomes is not (only) due to their antioxidative effect. There are many potential health effects due to secondary plant compounds, vitamins, minerals etc. - people who consume a lot of plants also tend to decrease total calorie consumption. But the #1 compound which is consistently associated with incredible health outcomes ...is: FIBER! Yes, and how do we know that? We see that effect REGARDLESS of fiber source and there are a variety of mechanisms that explain this change - foremost a change in total lipoprotein load! 

 

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Matthew Budoff and his research team have an interesting paper in the pipeline comparing LMHRs to a cohort of "normal LDL" individuals. This is a 1 year-long study that used CT angiography which could detect plaque formation with extremely high resolution and precision, detecting as little as 1mm growth in 15 different locations. But yes, I agree, much longer term studies are needed.

 

 

 

 

Ok the Budoff study - which has exactly the problem I mentioned in my previous post. You won't see many changes in someone's CTA after 1-2 years of high LDL, especially in young adults. The sensitivity of CTA-procedure is just not high enough to give you that data. If he shows me the same result after 10 years, I would be impressed.

However, we do have longer term data from the Framingham trial, showing phenotypes involving high LDL, low TG, and high HDL are associated with poorer CHD outcomes compared to low LDL, low TG, and high HDL.

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Yes, LMHRs have higher levels of HDL which escort oxidized lipoproteins out of the endothelium and thus are cardioprotective. But also, folks with this phenotype tend to be very health conscious (i.e., much of the keto community) and do not engage in activities that increase susceptibility of their lipoproteins to oxidation, such as cigarette smoking and seed oil consumption.

The healthy user bias has been systematically ruled out by mendelian randomization studies. 
You can be very health concious ("living a low oxidation lifestyle") while still getting your arteries cloged up by genetrically high ApoB. 
The only thing that consistently stops atheroma-progression is lowering total lipoprotein load. And this has been shown again and again and again....

 

The pro-atherogenic effect of  cigarette smoking is complex, not yet well understood and does not boil down to simply increased oxidative stress. 

Seed oils, which are chemically more prone to oxidation than saturated fat sources, consistently show a LOWER risk of cardiovascular disease - especially if you switch to them from saturated fat sources. We have had that discussion before Jason, and I have linked you at least 10 different studies (Epidemiology, RCT's & mechanisms, mendelian...) which consistently show this effect across all-age groups. We have decades of human data showing this effect - but all I hear from the other side are some rough mechanistical arguments, correlations where no causality can be inferred (seed oil consumption in the US vs. heart disease) and of course, anecdotes. 

Edited December 12, 2023 by undeather

[Jason Actualization]

4 hours ago, undeather said:

Ok the Budoff study - which has exactly the problem I mentioned in my previous post. You won't see many changes in someone's CTA after 1-2 years of high LDL, especially in young adults. The sensitivity of CTA-procedure is just not high enough to give you that data. If he shows me the same result after 10 years, I would be impressed.

I have just marked my Google calendar to revisit this conversation in 10 years, with the hope that such data will have surfaced prior to that point in time.

I truly appreciate your intellect and the depth and breadth that you've brought to this discussion. It would seem, after observing and appreciating the same puzzle pieces as yourself, I have arranged them such that I see a different picture than you do, albeit, one that is extremely self-consistent, at least to me.

I appreciate the difference in conclusions that have been arrived at here, and I hope that the divided opinions on this ordeal will, over time, merge into one unifying understanding that we can all hang our hats on.

If, at any point in time, during the remainder of my human life here, I am overwhelmed with evidence to the contrary of the aforementioned, utter convictions, I will revisit this post and personally apologize for my ignorance.

[undeather]

1 hour ago, Jason Actualization said:

I have just marked my Google calendar to revisit this conversation in 10 years, with the hope that such data will have surfaced prior to that point in time.

I truly appreciate your intellect and the depth and breadth that you've brought to this discussion. It would seem, after observing and appreciating the same puzzle pieces as yourself, I have arranged them such that I see a different picture than you do, albeit, one that is extremely self-consistent, at least to me.

I appreciate the difference in conclusions that have been arrived at here, and I hope that the divided opinions on this ordeal will, over time, merge into one unifying understanding that we can all hang our hats on.

If, at any point in time, during the remainder of my human life here, I am overwhelmed with evidence to the contrary of the aforementioned, utter convictions, I will revisit this post and personally apologize for my ignorance.

Those are very kind words! Thank you! 
I apprechiate your honesty and good faith nature - I also kind of get why you think what you think! Going through a personal health crisis and seeing how the current medical paradigm fails to adress the underlying cause while healing oneself  through alternative approaches ignored by the orthodoxy, changes the way one thinks about this whole situation.

And boy... am I jealous of that hairline! 
Cheers mate!

[Charlotte]

Interesting as I was just looking at this exact study yesterday as it was posted on the UK NHS health app 

[Leo Gura]

Breaking new study:

Eating human flesh lowers LDL by 10%.

[Yimpa]

[Schizophonia]

54 minutes ago, Leo Gura said:

Breaking new study:

Eating human flesh lowers LDL by 10%.

I knew I wasn't crazy, thanks Leo 

[undeather]

7 hours ago, Leo Gura said:

Breaking new study:

Eating human flesh lowers LDL by 10%.

This study was sponsered by the Jeffrey Dahmer foundation.

[Leo Gura]

The other white meat.

[Davino]

I'm a noob in nutrition compared with you all. I always ate a very healthy organic omnivore diet. However, a year and a half ago I switched to a vegetarian diet and just can talk wonders about it. I struggled in the beggining but after going to a nutrionist I was able to feel better than ever!

 

[Charlotte]

4 hours ago, undeather said:

This study was sponsered by the Jeffrey Dahmer foundation.

😅