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Endotoxin (LPS) as a cause of liver disease, obesity and diabetes

haidut

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The first article below is actually about praising fermented foods, which I don't really agree with. So, I am posting it mostly because of the quote on endotoxin/LPS, which is a very rare finding in published medical literature since medicine does not recognize chronic, low-grade endotoxemia as a cause of any disease and claims the "liver will quickly take care of it (endotoxin)". Well, apparently the liver itself is a victim of endotoxin, as the second study below shows, and even a minor drop in HDL ("good" cholesterol) production quickly leads to liver inflammation (and ultimately fibrosis/cirrhosis). So, endotoxin is a systemic burden even in ostensibly healthy people and measures should be taken to keep its production and systemic absorption down to a minimum.

Redirecting

"...“Gut inflammation and decreased gut microbial diversity are linked to stress, alcohol, and high-sugar diet among other causes. Low microbial diversity leads to an increase in gut permeability (aka leaky gut), which increases influx of lipopolysaccharide (aka endotoxin) from the gut. Studies have shown that a rise in circulating endotoxin levels precedes metabolic syndrome, weight gain, eventually leading to an elevated BMI with obesity, and diabetes,” said Vincent M. Pedre, MD, medical director of Pedre Integrative Health and author of the book Happy Gut."

Enterically derived high-density lipoprotein restrains liver injury through the portal vein | Science
Good cholesterol may prevent liver inflammation

"...To understand why this happens, scientists studied the problem in a mouse model with the same condition. They remove a portion of the small intestine in mice and study the liver fibrosis that results. There were hints in the literature that HDL cholesterol might interfere with lipopolysaccharide detection by immune cells. The receptor for lipopolysaccharide might be linked to liver disease following bowel surgery."

"...Randolph said, “The surgery seems to cause two problems. A shorter intestine means making less HDL3, and the surgery itself leads to an injurious state in the gut, allowing more lipopolysaccharide to spill over into the portal blood. When you remove the part of the intestine that makes the most HDL3, you get the worst liver outcome. When you have a mouse that cannot genetically make HDL3, liver inflammation is also worse. We also wanted to see if this dynamic was present in other forms of intestinal injury, so we looked at mouse models of a high-fat diet and alcoholic liver disease.” “In all of these models of intestinal injury, HDL3 was protective, binding to the additional lipopolysaccharide released from the injured intestine and blocking its downstream inflammatory effects in the liver.”
 

scoobydoo

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I’m confused I thought that higher HDL was a sign of higher endotoxin load? Is it there to help mitigate the damage it does?
 

Dr. B

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what can we use to detox endotoxin besides hormones? i have heard saturated fat helps yet also heard saturated fat only helps kill bacteria, it doesnt help remove the actual endotoxin from the body. ive heard charcoal can help
 

jomamma007

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It is (and other toxins). Similar to how a high white blood cell count is a sign of infection.

Yep.
Haidut says that a drop in HDL is a sign of liver inflammation, but also high HDL is a sign of high endotoxin which causes liver issues as well. So to me, it is a bit confusing. I suppose a drop in production of HDL would cause the inflammation, while high HDL is a definite sign of endotoxin burden?
 

Ben.

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what can we use to detox endotoxin besides hormones? i have heard saturated fat helps yet also heard saturated fat only helps kill bacteria, it doesnt help remove the actual endotoxin from the body. ive heard charcoal can help

Your organs take care of the endotoxins that got into the bloodstream eventually unless they are not overburdend so the idea/goal is to not have/create as much endotoxins in the future so you do not end up with to much endotoxins to begin with. Peaty measures to reduce the amount of endotoxins by taking care of the gut is trough the classic carrot salad, white button mushrooms or bambo shoots. Everything basicly that helps with digestion and the proper intestinal permeability such as bone broth (gelatince/glycine) for example.

Charcoal and other binding agents might help/work too but stuff like charcoal binds also to anything good aswell so its contraindicated with medications/supplements.

But haidut said it at the end of the first paragraph already :

measures should be taken to keep its production and systemic absorption down to a minimum.
 

tankasnowgod

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Haidut says that a drop in HDL is a sign of liver inflammation, but also high HDL is a sign of high endotoxin which causes liver issues as well. So to me, it is a bit confusing. I suppose a drop in production of HDL would cause the inflammation, while high HDL is a definite sign of endotoxin burden?

A natural drop in HDL due to a lower toxin load would be a good thing, just like a drop in white blood cells after an infection is cured.

Artificially stopping production of either without addressing underlying issues would certainly result in worse health outcomes.
 

Dr. B

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Your organs take care of the endotoxins that got into the bloodstream eventually unless they are not overburdend so the idea/goal is to not have/create as much endotoxins in the future so you do not end up with to much endotoxins to begin with. Peaty measures to reduce the amount of endotoxins by taking care of the gut is trough the classic carrot salad, white button mushrooms or bambo shoots. Everything basicly that helps with digestion and the proper intestinal permeability such as bone broth (gelatince/glycine) for example.

Charcoal and other binding agents might help/work too but stuff like charcoal binds also to anything good aswell so its contraindicated with medications/supplements.

But haidut said it at the end of the first paragraph already :
how do you reduce creation of endotoxin?
not eating starches mostly? or avoiding pufa?
didnt someone post something about fish oil having better effect on endotoxin than saturated fat or something like that
i heard starches can cause them, and anything difficult to digest. so probably too many fibers, too many raw veggies etc..?
 

khan

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how do you reduce creation of endotoxin?
not eating starches mostly? or avoiding pufa?
didnt someone post something about fish oil having better effect on endotoxin than saturated fat or something like that
i heard starches can cause them, and anything difficult to digest. so probably too many fibers, too many raw veggies etc..?
Please search the forum. These questions has been discussed many times.
 

haidut

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Haidut says that a drop in HDL is a sign of liver inflammation, but also high HDL is a sign of high endotoxin which causes liver issues as well. So to me, it is a bit confusing. I suppose a drop in production of HDL would cause the inflammation, while high HDL is a definite sign of endotoxin burden?

Failure to produce HDL (which is mostly done by the liver, but also in the intestine, as the study says) when needed (i.e. elevated endotoxin in the blood) is a bad sign as not only does the endotoxin have more ability to harm liver (and other organs - i.e. common occurrence in severe COVID-19) but also it means there may be already present liver/intestinal dysfunction. On the other hand, elevated HDL levels are a good sign in regards to the response the body is able to mount when faced with (endo)toxins but is a bad sign in terms of being a biomarker of elevated (endo)toxin load. So, it is hard to say which situation a person has just by testing HDL in the blood once a year as doctors usually do. If HDL is consistently low it is probably not a good sign as it may signal liver/intestine dysfunction (happens often in people with IBD), while repeated tests showing elevated HDL are also not a good sign as it means the person is exposed to a high amount of (endo)toxin. I guess the second case is a "lesser evil" as at least the body demonstrates ability to mount a response, but I would investigate it further if it happens on repeated blood tests.
 

aliml

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Replenishing HDL with synthetic HDL has multiple protective effects against sepsis in mice

Sepsis is a major health issue with mortality exceeding 30% and few treatment options. We found that high-density lipoprotein cholesterol (HDL-C) abundance was reduced by 45% in septic patients compared to that in nonseptic patients. Furthermore, HDL-C abundance in nonsurviving septic patients was substantially lower than in those patients who survived. We therefore hypothesized that replenishing HDL might be a therapeutic approach for treating sepsis and found that supplementing HDL with synthetic HDL (sHDL) provided protection against sepsis in mice. In mice subjected to cecal ligation and puncture (CLP), infusing the sHDL ETC-642 increased plasma HDL-C amounts and improved the 7-day survival rate. Septic mice treated with sHDL showed improved kidney function and reduced inflammation, as indicated by marked decreases in the plasma concentrations of blood urea nitrogen (BUN) and the cytokines interleukin-6 (IL-6) and IL-10, respectively. We found that sHDL inhibited the ability of the endotoxins LPS and LPA to activate inflammatory pathways in RAW264.7 cells and HEK-Blue cells expressing the receptors TLR4 or TLR2 and NF-κB reporters. In addition, sHDL inhibited the activation of HUVECs by LPS, LTA, and TNF-α. Together, these data indicate that sHDL treatment protects mice from sepsis in multiple ways and that it might be an effective therapy for patients with sepsis.
 

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