Endotoxin And Fat Consumption

[Kartoffel]

Thanks. As I suspected, there is no true high SFA diet in this study. The ratio of SFA/(MUFA+PUFA) even in the SFA diet is <1. A true SFA diet not only has a ratio of >1 but in animal research it is usually defined as a at least 75% of the fat being SFA. For that reason, some studies won't even consider palm oil suitable as SFA diet, and the truly well-done SFA diet studies use mostly coconut oil or fully hydrogenated peanut/soy oils.
It is hard to explain this in any other way than deliberate manipulation. The lack of a high-PUFA diet is especially telling since the high PUFA diet would mirror much more closely the dietary patterns of most Westerners.

I would say that it might be unfair to call this deliberate manipulation in this context, because we are talking about a long-term intervention with humans. I guess you can't feed people a true SFA diet for 12 weeks, and expect them to stick to it. As they say: "The composition of the meals was as follows: HSFA meal (21% MUFA, 38% SFA, 6%PUFA), based on butter, whole milk, white bread, and egg". I think this is the maximum you can expect to normal people to eat for a high-saturated fat diet.
What you can call deliberate manipulation or dishonesty is when they state:

"Interestingly, fasting plamsa LPS and LBP levels were not significantly altered by feeding either high-fat diets (HSFA, HMUFA) or both diets low-fat, high-complex carbohydrate (LFHCC, LFHCC n-3) with differing fatt y acid composition for 12 weeks in subjects[...]"
​

I think fasting levels that are almost twice as high in the other groups compared to the SFA qualify as a significant difference. It would be cool, if they had an AUC for 24h LPS.

 

[haidut]

I would say that it might be unfair to call this deliberate manipulation in this context, because we are talking about a long-term intervention with humans. I guess you can't feed people a true SFA diet for 12 weeks, and expect them to stick to it. As they say: "The composition of the meals was as follows: HSFA meal (21% MUFA, 38% SFA, 6%PUFA), based on butter, whole milk, white bread, and egg". I think this is the maximum you can expect to normal people to eat for a high-saturated fat diet.
What you can call deliberate manipulation or dishonesty is when they state:

"Interestingly, fasting plamsa LPS and LBP levels were not significantly altered by feeding either high-fat diets (HSFA, HMUFA) or both diets low-fat, high-complex carbohydrate (LFHCC, LFHCC n-3) with differing fatt y acid composition for 12 weeks in subjects[...]"
​

I think fasting levels that are almost twice as high in the other groups compared to the SFA qualify as a significant difference. It would be cool, if they had an AUC for 24h LPS.

Well, couple of things.
First, that quote you found makes my opinion this being deliberate even stronger.
Second, the 38% SFA number is just the postprandial study that lasted 4 hours. The diet fed for 12 weeks had 16% SFA, which is nothing and cannot by any measure be called high SFA diet.
Third, the argument that humans would not stick to something for 12 weeks cannot be used. Actually, in this case they did not even feed 38% SFA for 12 weeks, they fed 16%. But even if a true SFA diet (75%+ from SFA) had to be fed for 12 weeks then a good scientist can find a way. If animal trials can feed diets where all fat came from coconut oil then why can't this one as well? There are odor-free coconut oil varieties that can be used to cook all of the food for these people. I doubt they will note the difference and you can add some butter to make it more palatable and taste like a homemade meal. That is the purpose of a controlled trial - you control variables you want to test for. Otherwise there is no point in doing it. It's like saying "people won't take pure antibiotic for 12 weeks because it tastes foul. So, we will add tons of pure glucose to it and then we will title the study 'Antibioitc X raises insulin in humans'". Do you see my point? Either it has to be a properly designed study or the title and conclusions have to change.
So, back to my first comment - either deliberate manipulation or stupidity. And nobody is that stupid.

 

[Kartoffel]

Well, couple of things.
First, that quote you found makes my opinion this being deliberate even stronger.
Second, the 38% SFA number is just the postprandial study that lasted 4 hours. The diet fed for 12 weeks had 16% SFA, which is nothing and cannot by any measure be called high SFA diet.
Third, the argument that humans would not stick to something for 12 weeks cannot be used. Actually, in this case they did not even feed 38% SFA for 12 weeks, they fed 16%. But even if a true SFA diet (75%+ from SFA) had to be fed for 12 weeks then a good scientist can find a way. If animal trials can feed diets where all fat came from coconut oil then why can't this one as well? There are odor-free coconut oil varieties that can be used to cook all of the food for these people. I doubt they will note the difference and you can add some butter to make it more palatable and taste like a homemade meal. That is the purpose of a controlled trial - you control variables you want to test for. Otherwise there is no point in doing it. It's like saying "people won't take pure antibiotic for 12 weeks because it tastes foul. So, we will add tons of pure glucose to it and then we will title the study 'Antibioitc X raises insulin in humans'". Do you see my point? Either it has to be a properly designed study or the title and conclusions have to change.
So, back to my first comment - either deliberate manipulation or stupidity. And nobody is that stupid.

Sometimes, I am not sure. When I ask Peat about specific studies he frequently metnions that some researchers might actually be genuinly dumb instead of corrupt. I also guess researchers are always (especially when they are still young and building their careers) under pressure to conform to mainstream opinion. That's why they refuse to point out very significant and meaningful differences like here. I don't want to excuse their behavior, just saying. I still think their results are useful, because even when they didn't use a true high-SFA diet, they still show that more saturated fat is better than less when it comes to fasting LPS levels.

 

[haidut]

Sometimes, I am not sure. When I ask Peat about specific studies he frequently metnions that some researchers might actually be genuinly dumb instead of corrupt. I also guess researchers are always (especially when they are still young and building their careers) under pressure to conform to mainstream opinion. That's why they refuse to point out very significant and meaningful differences like here. I don't want to excuse their behavior, just saying. I still think their results are useful, because even when they didn't use a true high-SFA diet, they still show that more saturated fat is better than less when it comes to fasting LPS levels.

By all means, I like the study. It just irritates me that a study that could have been a blockbuster and sticky on the forum was (possibly) deliberately handicapped to conform to long-held beliefs.

 

[lvysaur]

Thanks. I was always a bit puzzled by the studies seemingly implicating that SFA does the exact opposite of what it does in rat studies.

It perfectly reflects my experience with regard to facial hair thickening, which happens right after an SFA meal but is generally soft in the long run. And the fact that it was formerly very coarse on a PUFA diet.

 

[Kartoffel]

I found another interesting study that pretty much confirms the idea that saturated fats result in increased postprandial endotoxin levels (which is not the same as endotoxemia) because they destroy gram-negative bacteria and lower endotoxin in the gut. It also puts the absurd theory about PUFA not increasing endotoxin to rest (actually there are many studies that do that). Zhong et al. used corn oil, cocoa fat, and mct oil to see how these modulate endotoxemia and liver damage in combination with ethanol. The ethanol is of course an irritating variable, but I don't think it changes the picture.

Besides measuring serum LPS, they also measured the concentration in the colon. Cocoa butter and MCT reduced the amount of LPS by more than half. It's also interesting that a standard chow diet plus corn oil seems to be worsen than ethanol and saturated fats in many respects. As far as the liver is concerned, cocoa butter and MCT were of course highly protective while corn oil proved to be universally toxic, yet again.
While cocoa butter wasn't able to prevent tight junction "leakage"of LPS into the blood, it completely prevented hepatic endotoxin accumulation. Since serum endotoxin levels increased significantly in both the corn and cocoa group, it's very likely that endotoxin translocation requires long-chain fatty acids, while the shorter MCTs seem to "seal" the intestinal barrier. The reason that one time experiments usually see no increase after PUFA administration (the original Mani study in this thread, for example) then should be that they don't have any immediate anti-bacterial properties as opposed to saturated fats. However, in the long-term they will produce much more severe endotoxemia due to their inflammatory nature.

"The protectiveeffects of dietary saturated fats in preventing alcohol-induced cytokine production and inflammation in the liver occur via different mechanisms at the gut-liver axis. In contrast to MCT,which abrogates the inflammatory response at the intestine level, the protective actions of dietary CB against endotoxin signaling mainly occurred in the liver, at least partially through activating ASS1."​

Source: Wei Zhong, Qiong Li, Guoxiang Xie, Xiuhua Sun, Xiaobing Tan, Xinguo Sun, Wei Jia, and Zhanxiang Zhou. Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats. Am J Physiol Gastrointest Liver Physiol 305: G919–G932, 2013.

@haidut @Amazoniac @tyw @tankasnowgod

 

[haidut]

It's also interesting that a standard chow diet plus corn oil seems to be worsen than ethanol and saturated fats in many respects. As far as the liver is concerned, cocoa butter and MCT were of course highly protective while corn oil proved to be universally toxic, yet again.

Excellent study! Thanks so much for sharing!
As far as the corn oil - here is something I posted about it years ago.
PUFA Are Carcinogenic, Dietary Glycine Blocks Their Effect

Isn't it amazing how the authors of that study kept openly calling corn oil "tumor pormoter" (as if it is a widely known fact) yet most doctors will literally order you to replace your butter "addiction" with Mazola Oil??
I think the MCT in coconut oil have the strongest antibacterial effect and as such are probably the most hepatoprotective. The studies on reversing cirrhosis with butter and MCT showed the MCT to be more effective. In fact, the MCT oil not only reversed the cirrhosis but prevents any future development despite the rats being raging alcoholics and continuing to drink alcohol in amounts similar to their normal daily water intake. I think we have a thread on that topic somewhere on the forum but I can't find it using my phone right now.

 

[michael94]

Guess thats why people with access to very little options eat dirt/clay often,

 

[Hgreen56]

after reading this 14 page topic i am confused now.
Study a tells that a diet with high saturated fat intake endotoxin into the bloodstream.

(2) The more double bonds in a fat, the LESS endotoxin gets into the serum. A PUFA like DHA will cause less endotoxin to be transferred into the bloodstream, as compared to a Saturated Fat like Coconut Oil. [paper (a)]

but other posts in this topic tell how anti bacterial and into inflammatory coconut oil is.

so is coconut oil good or bad for fighting endotoxin?
or is a low fat diet the best approach?
which has also been mentioned here a few times

 

[Jessie]

after reading this 14 page topic i am confused now.
Study a tells that a diet with high saturated fat intake endotoxin into the bloodstream.


but other posts in this topic tell how anti bacterial and into inflammatory coconut oil is.

so is coconut oil good or bad for fighting endotoxin?
or is a low fat diet the best approach?
which has also been mentioned here a few times

Yeah, I'm not sure why people try to make a very uncontroversial topic so controversial, but I think it's scientifically obvious that saturated fats should never come at the expense of carbohydrate if you're trying to improve glucose metabolism, which is the basis of Peat's entire work. Small amounts of MCTs with your meals may result in less endotoxin by antagonizing the TLR4 receptors. However that is not an endorsement of high fat diets. Literally a teaspoon of MCT/coconut oils with meals is enough, that's like 5 grams of fat, lol.

 

[Maljam]

after reading this 14 page topic i am confused now.
Study a tells that a diet with high saturated fat intake endotoxin into the bloodstream.


but other posts in this topic tell how anti bacterial and into inflammatory coconut oil is.

so is coconut oil good or bad for fighting endotoxin?
or is a low fat diet the best approach?
which has also been mentioned here a few times

Just keep reading the first post of tyw's until it clicks, it is a bit confusing at first. I'll highlight the most important parts to help below. Also, beware of low fat fear mongerers that talk about endotoxin being in the blood (sounds super scary, right?) without fully understanding the mechanisms of what's going on, and what the purpose of fat induced chlyomicrons are. Endotoxin "in the blood" bound by chylomicrons IS A GOOD THING! If it means anything to you, Ray Peat also agrees that chylomicrons bind to endotoxin and neutralise them, just like tyw explains in the first post, so this is nothing too woo-woo.

Tldr saturated fat helps your body deal with endotoxin as long as your immune system isn't already highly damaged.

Note: this doesnt mean a free pass to eat saturated fat by the boat load, but simply moderate levels of saturated fat lead to endotoxin clean up and proper immune response.

"This transport of endotoxin by Chylomicrons is a normal immune response. Chylomicrons "neutralise" endotoxin during transport (endotoxin is not free to disperse like in a case of sepsis), while simultaneously stimulating the inflammatory cascade required for healthy immune response.

It is important to remember that you must have acute inflammation in order for proper immune responses to be established."

"All that eating fat does, is to provide the mechanical pathway for a "as safe as possible" endotoxin-mediated immune response to whatever endotoxin is already present in the gut. ie: Bundling up endotoxin into chylomicrons, is like a "quarantine function", whereby the invaders are then delivered to immune cells to be dealt with."

"Paper (a) will elaborate on why PUFAs do not cause as big of a response -- they suppress the initial inflammatory cascade within intestinal cells. The pro-PUFA observer sees this as a "good thing", because "less inflammation bro".

This is faulty logic -- the pro-PUFA stance claims that suppressing the alarm bells (stuff like NF-kB and TNF-alpha) is equivalent to decreasing the harm caused by the objects that are raising the alarm in the first place. I will elaborate more in the "Personal interpretations" section below."

 

[Maljam]

Yeah, I'm not sure why people try to make a very uncontroversial topic so controversial, but I think it's scientifically obvious that saturated fats should never come at the expense of carbohydrate if you're trying to improve glucose metabolism, which is the basis of Peat's entire work. Small amounts of MCTs with your meals may result in less endotoxin by antagonizing the TLR4 receptors. However that is not an endorsement of high fat diets. Literally a teaspoon of MCT/coconut oils with meals is enough, that's like 5 grams of fat, lol.

The topic that the previous gentleman was asking about is related to saturated fats protective effect against endotoxin, nothing to do with glucose metabolism. Unless you are talking about endotoxins damaging effects on the metabolism, then, as tyw's original post explains, the eating of saturated fat in the diet will allow the body to clear endotoxin and allow it to function better as the immune system deals with it.

Have another read through tyw's fantastic first post, it is dense at first but it will click eventually.

Re: MCT's from tyw first post, trying to get only MCT's doesnt seem like a wise move. Less chylomicrons doesn't = less endotoxin, the endotoxin is still there. It just means less (neutralised) endotoxin in the blood, which as we learn from tyw's first post is a way which the immune system can deal with endotoxin and isn't

"Medium Chain Triglycerides (MCTs) do not stimulate chylomicron production, and thus do not provide this immune regulated endotoxin transport. They can be incorporated into chylomicrons, but do not actually stimulate the formation of chylomicrons."

 

[Bogdar]

OKOK, highly interesting thread.

After reading through all this thread, I have some questions:

-If PUFAs cause less endotoxemia, why in the study posted by kartoffel above does the CORN OIL cause the most endotoxemia rush ? Or maybe when I understood "pufa cause less endotoxemia" I should have understood "they cause SAME endotoxemia but LESS inflammatory response to it " ? However the author told that the most double bonds in a fat (i.e the most unsaturated) the less it carries LPS with it ?

-If chylomicron-bounding-LPS property is normal and a process to detox LPS in the gut, this LPS in the gut is bad, right ?
However why not just letting it sit in the gut, get excreted in faeces,
AS in low fat diet when we feel less endotoxine-symptoms, we actually JUST prevent them from going gut into the bloodstream. So they actually accumulate,
and if the body created that process to detox them with chylomicrons as mediators, it means it should be bad to accumulate, so they (very low fat dieters) should feel bad symptoms or even endotoxemia symptoms if suddenly they reached the bloodstream ?

-also there's a difference between free-flowing LPS in bloodstream and bound-to-protein-LPS, the latter can cause endotoxemia symptoms as the author said if we don't have proper materials to neutralize it whatever that means, but what are the symptoms of free flowing lps compared to that ?

-Also hehe the final point, how can we minimize LPS-causing-symptoms, it means maybe total LPS quantity and capacity to handle them without these bad symptoms ? Author told that FODMAP, fermentiscible food if I understand correctly, produce LPS. Is it the only things that produce LPS ?

I feel like I understood lots of things with this thread but still some missing parts

 

[Maljam]

OKOK, highly interesting thread.

After reading through all this thread, I have some questions:

-If PUFAs cause less endotoxemia, why in the study posted by kartoffel above does the CORN OIL cause the most endotoxemia rush ? Or maybe when I understood "pufa cause less endotoxemia" I should have understood "they cause SAME endotoxemia but LESS inflammatory response to it " ? However the author told that the most double bonds in a fat (i.e the most unsaturated) the less it carries LPS with it ?

-If chylomicron-bounding-LPS property is normal and a process to detox LPS in the gut, this LPS in the gut is bad, right ?
However why not just letting it sit in the gut, get excreted in faeces,
AS in low fat diet when we feel less endotoxine-symptoms, we actually JUST prevent them from going gut into the bloodstream. So they actually accumulate,
and if the body created that process to detox them with chylomicrons as mediators, it means it should be bad to accumulate, so they (very low fat dieters) should feel bad symptoms or even endotoxemia symptoms if suddenly they reached the bloodstream ?

-also there's a difference between free-flowing LPS in bloodstream and bound-to-protein-LPS, the latter can cause endotoxemia symptoms as the author said if we don't have proper materials to neutralize it whatever that means, but what are the symptoms of free flowing lps compared to that ?

-Also hehe the final point, how can we minimize LPS-causing-symptoms, it means maybe total LPS quantity and capacity to handle them without these bad symptoms ? Author told that FODMAP, fermentiscible food if I understand correctly, produce LPS. Is it the only things that produce LPS ?

I feel like I understood lots of things with this thread but still some missing parts

1. As far as I understand it, PUFA makes less endotoxin transfer into the blood stream and also retards the immune systems response so it, so I guess in studies they can make this look like a good thing, ignoring that a robust immune response is a good thing. (Peat has said before about drugs that activate the immune system being used against cancer.)

2. That seems to be my understanding too. You want endotoxin in the gut you dont want it flowing freely around the body unattached to chylomicrons. Low fat would keep it all in the gut, but this is simply a band aid, because the endotoxin would accumulate to an extent and when the gut does become damaged (aging, eating wheat) the endotoxin will cause issues. I also believe saturated fat contributes to gut health and keeps the junctions tight and prevents permability, so in the long term, low fat would also contribute to the damage to the gut that would allow the endotoxin to spill out.

3. Endotoxin are created by foods not properly digested, produced by bacteria that consume a food and then produce the endotoxin. There was also a post by haidut about emulsifiers in food having a similar action as endotoxin.

The liver also processes endotoxin, low choline diets are a known contributor to NAFLD, so the avoidance of egg yolks in someone going for a very low fat diet could theoretically compound the issues with endotoxin. Also the damage to the liver from PUFA would be another way to show it shouldn't be included in the diet for someone concerned about endotoxin.

 

[Bogdar]

1. As far as I understand it, PUFA makes less endotoxin transfer into the blood stream and also retards the immune systems response so it, so I guess in studies they can make this look like a good thing, ignoring that a robust immune response is a good thing. (Peat has said before about drugs that activate the immune system being used against cancer.)

2. That seems to be my understanding too. You want endotoxin in the gut you dont want it flowing freely around the body unattached to chylomicrons. Low fat would keep it all in the gut, but this is simply a band aid, because the endotoxin would accumulate to an extent and when the gut does become damaged (aging, eating wheat) the endotoxin will cause issues. I also believe saturated fat contributes to gut health and keeps the junctions tight and prevents permability, so in the long term, low fat would also contribute to the damage to the gut that would allow the endotoxin to spill out.

3. Endotoxin are created by foods not properly digested, produced by bacteria that consume a food and then produce the endotoxin. There was also a post by haidut about emulsifiers in food having a similar action as endotoxin.

The liver also processes endotoxin, low choline diets are a known contributor to NAFLD, so the avoidance of egg yolks in someone going for a very low fat diet could theoretically compound the issues with endotoxin. Also the damage to the liver from PUFA would be another way to show it shouldn't be included in the diet for someone concerned about endotoxin.

1. Yes precisely, however in the above study, corn oil compared to cocoa butter caused more endotoxemia, despite being highly more insaturated
https://raypeatforum.com/community/attachments/upload_2019-2-17_23-11-17-png.12263/

2. Okok I see. One point still questions me tho. Some people feel high LPS symptoms after eatong sat fats, the author explains this with something like "chylomicrons transport LPS into the system as they normally do, BUT the immune system doesn't work properly so there's not the natural good response". It's in his "personnal interpretations" part tho, we don't have proof of it, nor of it (lps symptoms) being caused by another mecanism

3. Yes I read it, carregenanes (or smth) and other emulsifiers doing same brain damages than endotoxins, leading to hemmoragic brain damages

anyway as you're saying LPS-detoxification (wether the term is correct or not) puts its burden on the liver, so I guess good liver function => less LPS damages and vice versa

 

[Sapien]

potatoes have higher iron

Potato’s are super high in copper :)

 

[peter88]

Thant's interesting, thanks for sharing this. Some people say that it is a reservoir for "good bacterias" in case you have a dysbiosis, what do you think about it? I think that the people I know having difficulties with starch are the ones that don't have an appendix anymore (like me).

Do you still have issues with starch? I had my appendix removed years ago and lost my tolerance to lots of foods.