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

[undeather]

Hey, 
I wanted to share a super interesting study which just got published today in JAMA. They took 22 healthy, adult twin-pairs (share the exact same genes) and randomized them into following one of two diets: One twin would go on a healthy vegan and the other on a healthy omnivorous diet - both emphasized minimally processed foods, vegetables, fruits, meats (omnivorous diets) and whole grains while limiting added sugars and refined grains.  Participants were told to eat until they were satiated throughout the study.

Here is what blood-markers & weight looked like after 8 weeks of following the diet:

 

LDL-C = LDL-Cholesterol: Lower is better (statistically significant)
HDL-C = HDL- Cholesterol: Higher is better 
Tryclycerides: Lower is better
Glucose: Lower is better 
Fasting Insulin: Lower is better (statistically significant)
Vitamin B12: Higher is better -> Would become statistically significant in longer follow-up period!
Weight: (statistically significant) -> Depends if lost mass is fat or lean muscle!
TMAO: Is associated with cardiovascular disease - so lower is better! (based on weak evidence!) Precursors of TMAO are found in meat products - however, the difference came out as not significant and only showed up as that after controlling for outliers! 

Dietary satisfaction: Vegan diet had a significantly lower dietary satisfaction!

Edited November 30, 2023 by undeather

[Schizophonia]

28 minutes ago, undeather said:

Hey, 
I wanted to share a super interesting study which just got published today in JAMA. They took 22 healthy, adult twin-pairs (share the exact same genes) and randomized them into following one of two diets: One twin would go on a healthy vegan and the other on a healthy omnivorous diet - both emphasized minimally processed foods, vegetables, fruits, meats (omnivorous diets) and whole grains while limiting added sugars and refined grains.  Participants were told to eat until they were satiated throughout the study.

Here is what blood-markers & weight looked like after 8 weeks of following the diet:

 

LDL-C = LDL-Cholesterol: Lower is better (statistically significant)
HDL-C = HDL- Cholesterol: Higher is better 
Tryclycerides: Lower is better
Glucose: Lower is better 
Fasting Insulin: Lower is better (statistically significant)
Vitamin B12: Higher is better -> Would become statistically significant in longer follow-up period!
Weight: (statistically significant) -> Depends if lost mass is fat or lean muscle!
TMAO: Is associated with cardiovascular disease - so lower is better! (based on weak evidence!) Precursors of TMAO are found in meat products - however, the difference came out as not significant and only showed up as that after controlling for outliers! 

Dietary satisfaction: Vegan diet had a significantly lower dietary satisfaction!

I expected that the group with the highest glucose would also have the highest insulin.
Usually one goes with the other, but maybe I'm wrong.

For the TMAO, I haven't looked and so I don't know what it's worth but it seems to me that Bart Kay made a video "to debunker" that 

[undeather]

Quote

I expected that the group with the highest glucose would also have the highest insulin.

Might be the higher fiber content, but it's an intersting finding!
 

Quote

For the TMAO, I haven't looked and so I don't know what it's worth but it seems to me that Bart Kay made a video "to debunker" that 

I don't buy the TMAO - heart disease connection either! 
But Bart Kay, really?  

Edited November 30, 2023 by undeather

[Schizophonia]

7 minutes ago, undeather said:

Might be the higher fiber content, but it's an intersting finding!
 

You're probably right 🤔

7 minutes ago, undeather said:

I don't buy the TMAO - heart disease connection either! 
But Bart Kay, really?  

I like Bart

At first I seriously doubted seeing his strange and aggressive behavior, but in fact it turns out that he suffers from autism. He actually did an interview about it. 

[Leo Gura]

So basically no meaningful difference.

8 weeks is not a lot of time. 8 years might show something interesting.

Edited November 30, 2023 by Leo Gura

[undeather]

1 hour ago, Leo Gura said:

So basically no meaningful difference.

8 weeks is not a lot of time. 8 years might show something interesting.

LDL-C down by 10%+ is an incredibly meaningfuly difference, especially if you take into account that the average LDL-C in the inverntion group was 114mg/dl. There is an about  20% reduction of cardiovascular disease risk per mmol/L(=38mg/dL) LDL-C lowering. Now, notice that the difference we observer is between two healthy diets - imagine the difference between the standard american diet and veganism.

As I alerady mentioned multiple times, I don't care about the ethical reasons of a vegan diet - I personally love meat and cheese, but this is just a result we can't/shouold not ignore. When it comes to CVD-risk, the more plants - the better! If you would run that trial for 8+ years, you would propably see shocking differnces. 

Edited November 30, 2023 by undeather

[Leo Gura]

58 minutes ago, undeather said:

LDL-C down by 10%+

Meh

[ZenAlex]

Vegan 8 years. My bloodwork is fantastic, doctor said so themselves numerous times. 

[undeather]

1 hour ago, nuwu said:

Please do not gaslight empathy.

 ?

[Carl-Richard]

Cool. Now replicate it  

Is there anything to note from the variance between subjects? This idea that what is a healthy diet (or healthy behavior in general) might be an individual thing keeps entering my mind (thank you, Bryan Johnson). It's obvious, but even if the results (which is based on data from multiple individuals) skew clearly in one direction, that doesn't mean that you as a single individual couldn't deviate from that data. It would be interesting to have some clear quantitative studies on that too ("how much do people differ?", "which types of people respond better to which interventions?", etc.). Quantitative science is so focused on presenting general results that it might forget that people are indeed different.

Edited December 4, 2023 by Carl-Richard

[Carl-Richard]

On 30.11.2023 at 11:12 PM, undeather said:

LDL-C down by 10%+ is an incredibly meaningfuly difference, especially if you take into account that the average LDL-C in the inverntion group was 114mg/dl. There is an about  20% reduction of cardiovascular disease risk per mmol/L(=38mg/dL) LDL-C lowering.

So the (healthy) vegans had about a 6% reduction of cardiovascular disease risk compared to the healthy omnivores (in that time frame). Hmm... I guess it's not nothing (?)

 

On 30.11.2023 at 11:12 PM, undeather said:

Now, notice that the difference we observer is between two healthy diets - imagine the difference between the standard american diet and veganism.

Now, imagine the difference between the standard american diet and the healthy omnivore diet 

 

On 30.11.2023 at 11:12 PM, undeather said:

If you would run that trial for 8+ years, you would propably see shocking differnces. 

Dew it! If you had to guess, how large do you think the differences would be?

[undeather]

9 hours ago, Carl-Richard said:

Cool. Now replicate it  

Is there anything to note from the variance between subjects? This idea that what is a healthy diet (or healthy behavior in general) might be an individual thing keeps entering my mind (thank you, Bryan Johnson). It's obvious, but even if the results (which is based on data from multiple individuals) skew clearly in one direction, that doesn't mean that you as a single individual couldn't deviate from that data. It would be interesting to have some clear quantitative studies on that too ("how much do people differ?", "which types of people respond better to which interventions?", etc.). Quantitative science is so focused on presenting general results that it might forget that people are indeed different.

Health is more than LDL-C and even though it's proapbly the most important risk factor when it comes to cardiovascular disease progression, there is a lot to say about individual approaches and bio-phentypical proclivities. That said, it's pretty much a undeniable fact that a reduction in saturated fat and dietary cholesterol goes hand in hand with benificial effects on blood lipids and insulin-sensitivity - in MOST individuals. Since >90% of those ingredients are found in animal products, the results of the study make a lot of sense. 

I am not advocating for a vegan diet because of many reasons. There are downsides, especially if you don't know what you are doing - and since most people fall into that category, a healthy omivorous diet is the way to go. However, if you want to max out on potential longevity, then one should consider giving it a try and compare health parameters before/after.

 

Quote

So the (healthy) vegans had about a 6% reduction of cardiovascular disease risk compared to the healthy omnivores (in that time frame). Hmm... I guess it's not nothing (?)

Quote

Dew it! If you had to guess, how large do you think the differences would be?

Since cardiovascular risk factors are cumulative, the potentially benificial effect will increase over time. There is some evidence looking at lifetime vegans vs meat eaters but those studies are usually heavily biased & confounded. If you would ask me personally, I would argue that it will propably give you 2-4 years of additional lifetime if you start early. 

[sholomar]

Somewhere between the extremes of eating all carnivore and no meat at all there's a happy medium that I prefer to follow. Eliminating all baked or deep fried anything would be the single best thing a person could do to improve their diet.  Deep fried and baked items compose probably 95% of the dietary problem areas in people's diets, encompassing all the "junk carbs" like potato chips that are carbs and fat mixed that are addictive and promote weight gain and the development of metabolic syndrome.

A ribeye steak or a fresh salmon isn't the problem area of one's diet. Eggs are a good source of choline which is an important methyl donor and for liver health. I get the "certified humane" only personally, to keep to my compassionate side.

What I'm going to make after I finish editing this post:  Egg salad with 3 hard boiled eggs, one can of salt free peas, TBSP of italian seasoning, large spoon of cream of mushroom soup, medium spoon of light mayonaisse, squart of yellow mustard, large spoonful of pickle relish, potassium salt, and some liquid sucralose. Throw in my 10 grams of daily glycine into this salad also. Mix well.

Edited December 5, 2023 by sholomar

[Schizophonia]

2 hours ago, sholomar said:

Somewhere between the extremes of eating all carnivore and no meat at all there's a happy medium that I prefer to follow. Eliminating all baked or deep fried anything would be the single best thing a person could do to improve their diet.  Deep fried and baked items compose probably 95% of the dietary problem areas in people's diets, encompassing all the "junk carbs" like potato chips that are carbs and fat mixed that are addictive and promote weight gain and the development of metabolic syndrome.

A ribeye steak or a fresh salmon isn't the problem area of one's diet. Eggs are a good source of choline which is an important methyl donor and for liver health. I get the "certified humane" only personally, to keep to my compassionate side.

What I'm going to make after I finish editing this post:  Egg salad with 3 hard boiled eggs, one can of salt free peas, TBSP of italian seasoning, large spoon of cream of mushroom soup, medium spoon of light mayonaisse, squart of yellow mustard, large spoonful of pickle relish, potassium salt, and some liquid sucralose. Throw in my 10 grams of daily glycine into this salad also. Mix well.

nutrition is WAY overrated

[undeather]

1 hour ago, Schizophonia said:

nutrition is WAY overrated

Nutrition is way overrated in individuals who already have a decent diet & general healthy lifestyle.
Nutrition is way underrated in everyone else. 

[Jason Actualization]

On 11/30/2023 at 6:10 PM, Leo Gura said:

Meh

Exactly. Even if it were 50%, the issue is that LDL in and of itself is not actually atherogenic until it becomes oxidized, and measuring circulating LDL cholesterol sheds zero light on this matter.

The single greatest cognitive error of the 21st century is the lipid heart hypothesis and the "health advice" that such gave rise to, rendering erroneous assertions with dire consequences that could only be measured on a Richter scale. I would liken this misunderstanding to that of the time period in which cigarette smoking was not only condoned, but shamelessly celebrated in office by doctors themselves.  

In short, the lipid heart hypothesis gave rise for the optimization of the wrong metric, namely the mitigation of LDL cholesterol, when, in fact, what we need to optimize for is rendering said cholesterol impervious to oxidation. As it turns out, this is actually accomplished by a hybrid of ideologies that are effectively at odds with one another, i.e., the so-called "vegans" and "carnivores." Ultimately, omnivore eating is optimal, and conferring your cholesterol with protection from oxidation is accomplished via embracing the predominant fatty acid profile of the carnivores, i.e., saturated and monounsaturated, with minimal PUFA, while concurrently consuming the antioxidant rich foods found in a vegan diet. Refraining from the consumption of industrial oils and the cigarette smoking, as well as avoiding exposure to toxic exhaust fumes, are a few of the major action steps that will also prevent your cholesterol from becoming oxidized, and, by extension, atherogenic.

For folks curious, this is why the so-called "lean mass hyper responders" with sky high LDL cholesterols (far north of 200, 300, even as high as 500) are showing, via CT angiogram, no statistically significant increase in plaque formation with respect to matched controls with "normal" LDL cholesterol. This is not to say that higher LDL cholesterol is better, and in fact, all else equal, it is surely not, because with more cholesterol in circulation there are more opportunities for oxidation. What it does mean, however, is that in the absence of oxidation, native LDL is entirely benign, and what we need to optimize for is a reduction in Ox-LDL (the best metric currently available, although still imperfect as a surrogate marker) a more expensive test that virtually nobody has done.

[Jason Actualization]

On 12/5/2023 at 2:22 PM, undeather said:

Nutrition is way overrated in individuals who already have a decent diet & general healthy lifestyle.
Nutrition is way underrated in everyone else. 

Yes, nutrition is extremely underrated, especially regarding its' utility in reversing and preventing chronic disease. It is, bar none, the strongest lever in affecting the quality of one's human experience. Everything else pales in comparison with the exception of deep, restorative sleep, which proper nutrition effectively enhances.

[undeather]

10 hours ago, Jason Actualization said:

Exactly. Even if it were 50%, the issue is that LDL in and of itself is not actually atherogenic until it becomes oxidized, and measuring circulating LDL cholesterol sheds zero light on this matter.

The single greatest cognitive error of the 21st century is the lipid heart hypothesis and the "health advice" that such gave rise to, rendering erroneous assertions with dire consequences that could only be measured on a Richter scale. I would liken this misunderstanding to that of the time period in which cigarette smoking was not only condoned, but shamelessly celebrated in office by doctors themselves.  

In short, the lipid heart hypothesis gave rise for the optimization of the wrong metric, namely the mitigation of LDL cholesterol, when, in fact, what we need to optimize for is rendering said cholesterol impervious to oxidation. As it turns out, this is actually accomplished by a hybrid of ideologies that are effectively at odds with one another, i.e., the so-called "vegans" and "carnivores." Ultimately, omnivore eating is optimal, and conferring your cholesterol with protection from oxidation is accomplished via embracing the predominant fatty acid profile of the carnivores, i.e., saturated and monounsaturated, with minimal PUFA, while concurrently consuming the antioxidant rich foods found in a vegan diet. Refraining from the consumption of industrial oils and the cigarette smoking, as well as avoiding exposure to toxic exhaust fumes, are a few of the major action steps that will also prevent your cholesterol from becoming oxidized, and, by extension, atherogenic.

For folks curious, this is why the so-called "lean mass hyper responders" with sky high LDL cholesterols (far north of 200, 300, even as high as 500) are showing, via CT angiogram, no statistically significant increase in plaque formation with respect to matched controls with "normal" LDL cholesterol. This is not to say that higher LDL cholesterol is better, and in fact, all else equal, it is surely not, because with more cholesterol in circulation there are more opportunities for oxidation. What it does mean, however, is that in the absence of oxidation, native LDL is entirely benign, and what we need to optimize for is a reduction in Ox-LDL (the best metric currently available, although still imperfect as a surrogate marker) a more expensive test that virtually nobody has done.

The lipid hypothesis of atherosclerosis is one of the most coherent and consistent theories in all medical science. Denying the causal role of apolipoproteins in plaque formation is a bit like denying germ theory or the globe earth. There is over 100 years of bullet proof research behind it. Will there be adaptions of this theory in the future? Sure! Just like Einstein adapted newtonian gravity, the same thing could happen to lipids. However, analogous to this physics example, the core axiom of lipoproteins & atherogenesis will remain true nontheless.

The problem with Ox-LDL as a marker for cardiovascular disease (CVD), and we have talked about this Jason, is that it foods on a limited understanding of the atherogenic mechanism. When you measure your Ox-LDL in a lab, you ONLY get a picture of the minimally oxidized version that was in your bloodstream when the blood was drawn. However, we have known for at least 30-40 years now, that lipoprotein-oxidation happens for the most part IN the sub-endothelium (IN the walls of the artery), right after the lipoprotein entered the wall and reacted with the proteoglycan/lipoxygenase. You can NOT measure the ox-LDL in your endothelium. In fact, the assays used in most laboratories can only measure minimally oxidized LDL. You also can not infer that lower ox-LDL in blood equlas lower oxidation-rates in the sub-endothelium.  And guess what, we do not have a single good study that shows substantially higher CVD-risk with ox-LDL WHILE sufficiently controlling for ApoB (+ good primaryendpoints). There is no reason to believe this would be true. 

 

Lean mass hyper responders (LMHR) are a poorly studied subject-group. Saying that those individuals don't develop early-life heart disease is problematic for many reasons. It takes years for atherogeneic plaques to show up on screening tools like CTA's. There are NO long term studies (I am aware of) that compare LMHR's with "normal LDL". There are case reports, subgroup analyses and one study including a web survey (lol) for data collection - which is horribly confounded & low quality in general of course. 

Look, I am open that we might learn something new about LMHR-phenotypes in the future - but you just can't make that point at the moment. Maybe the higher HDL often seen in those individuals actually protects some of them from ASCVD - who knows! But at the moment, there really is no good reason to believe that. 

Edited December 11, 2023 by undeather

[Jason Actualization]

14 hours ago, undeather said:

Denying the causal role of apolipoproteins in plaque formation is a bit like denying germ theory or the globe earth.

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

14 hours ago, undeather said:

You can NOT measure the ox-LDL in your endothelium. 

Yes, which is unfortunate because it is precisely oxidized lipoproteins (not merely LDL) in the endothelium that induce atherosclerosis, which is effectively the body's immune system chronically self attacking. That being said, what ox-LDL (measured in the blood) does shed light on is the susceptibility of one's lipoproteins to oxidation.

15 hours ago, undeather said:

And guess what, we do not have a single good study that shows substantially higher CVD-risk with ox-LDL WHILE sufficiently controlling for ApoB (+ good primaryendpoints). There is no reason to believe this would be true. 

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).

15 hours ago, undeather said:

There are NO long term studies (I am aware of) that compare LMHR's with "normal LDL".

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.

15 hours ago, undeather said:

Look, I am open that we might learn something new about LMHR-phenotypes in the future - but you just can't make that point at the moment. Maybe the higher HDL often seen in those individuals actually protects some of them from ASCVD - who knows!

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.

[undeather]

Quote

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!
 

Quote

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

Quote

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! 

 

Quote

 

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.

Quote

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