# Endotoxin (Lipopolysaccharide, LPS)

Category: Metabolism

Also known as: Lipopolysaccharide, lipopolysaccharide, Endotoxin, endotoxin, LPS

Bacteria and plants produce a variety of lipids that serve some purposes analogous to our cholesterol phospholipids. Some of the common intestinal bacteria produce a molecule containing amino sugars and fatty acids (lipopolysaccharide, LPS), that's called endotoxin. The "endo"…

11 passages · 3 authors · 2006–2023 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/endotoxin-lipopolysaccharide-lps

## Synthesis

**Endotoxin**, chemically known as **lipopolysaccharide (LPS)**, is a structural molecule produced by gram-negative intestinal bacteria that Peat identified as a central driver of systemic stress and metabolic dysfunction. [Source 1, 2, 6] It consists of a starch-like polysaccharide chain attached to fatty acids, giving it a *soap-like physical action* that destabilizes cells upon contact. [Source 2, 3, 7] Peat argued that while textbooks historically claimed endotoxin is only released when bacteria are broken apart, it likely leaks continuously during normal bacterial growth and division. [Source 3, 5] This molecule is so ubiquitous that all animals have evolved innate immune systems to recognize its presence, triggering the release of **serotonin**, **histamine**, and **nitric oxide** as primary defense reactions. [Source 2, 4]

Under healthy conditions, the intestinal barrier and liver work in concert to prevent significant amounts of endotoxin from reaching the general circulation. The bile acids, a major end product of cholesterol, act as detergents that keep endotoxin in solution away from the absorptive surfaces of the intestine, while liver enzymes break down any LPS that does enter the portal vein. [Source 1, 6] Peat emphasized that the microscopic integrity of the intestinal cells, protected by a mucus lining, ultimately regulates passage into the blood and lymphatic vessels. [Source 1, 6] However, this barrier is weakened by stress, malnutrition, and reduced circulation, all of which increase intestinal permeability and allow endotoxin to flood the system. [Source 1, 6, 11] Peat specifically noted that **estrogen** can inhibit bile flow and shut off blood supply to the intestine, directly compromising the body's primary defenses against LPS absorption. [Source 1, 6]

Once in the bloodstream, endotoxin becomes a profound metabolic poison that shifts cellular energy production away from efficient oxidative metabolism. Peat explained that LPS and estrogen converge mechanistically by interfering with the metabolic use of oxygen, turning on **glycolysis** and forcing the conversion of sugar into lactic acid rather than carbon dioxide. [Source 8] This creates a state of *reductive stress*, where an excess of electrons and insufficient oxygen drive degenerative processes. [Source 8] The liver is particularly vulnerable; high endotoxin levels slow liver function, impairing its ability to detoxify estrogen and other substances, which creates a vicious cycle of increasing estrogen burden and further metabolic suppression. [Source 7] Dinkov has written that endotoxin's degenerative effects, including fibrosis and cancer, are largely driven by activation of the **TLR4 receptor**, which triggers a downstream cascade of inflammatory mediators. [Source 10] Roddy notes that endotoxin synergizes with and increases the effects of serotonin, histamine, estrogen, and cortisol, while directly decreasing thyroid production and inducing insulin resistance. [Source 11]

The production and absorption of endotoxin are heavily influenced by diet and digestive efficiency. Peat taught that poorly digested foods, particularly undercooked cereals, starchy foods, and poorly cooked vegetable material, pass undigested into the lower intestine where they feed the bacteria that produce LPS. [Source 2, 4] In contrast, quickly digested foods like fruit allow sugars and minerals to be absorbed before reaching the bacterial area of the intestine, reducing the substrate for endotoxin production. [Source 4, 9] Peat recommended raw carrots for their bactericidal effect, which suppresses bacterial growth, while their fiber absorbs and stimulates excretion of endotoxin. [Source 8] He also identified **calcium** as a specific suppressor of the fermentation of fiber and starch, and noted that saturated fats have a germicidal effect that helps keep the intestine relatively sterile. [Source 2] Antibiotics lower endotoxin formation and protect against its induction of serotonin, histamine, estrogen, and cortisol. [Source 1]

The systemic consequences of chronic endotoxin absorption extend far beyond the gut. Peat described how a "leaky intestine" allows toxins to enter the general circulation and travel directly to the brain, heart, and lungs, contributing to conditions including obstructive pulmonary disease, emphysema, reduced heart function, heart failure, insomnia, and sleep apnea. [Source 7] He also observed that reverse peristalsis, driven by local irritation in an over-excited, under-energized state, is extremely common and can move material from the rectum to the mouth overnight. [Source 7] Dinkov has highlighted that serum endotoxin levels directly correlate with the severity of liver disease, including NAFLD, NASH, hepatitis, and cirrhosis, and that vitamin E may be a viable tool for preventing and treating the damage endotoxin causes. [Source 10] Peat maintained that a small amount of endotoxin absorption is normal and acts as a stimulant to the immune system, but when liver function slows, it massively breaches the liver's barriers and begins poisoning the entire organism. [Source 3, 8]

## People also ask

### How does endotoxin interfere with cellular energy production?

Peat argued that endotoxin shifts metabolism away from oxidative phosphorylation by forcing the conversion of sugar into lactic acid rather than carbon dioxide, creating a state of reductive stress that suppresses efficient energy production.

### Why did Peat recommend raw carrots for managing endotoxin?

Peat identified raw carrots as having a bactericidal effect that suppresses bacterial growth, while their fiber absorbs and stimulates the excretion of endotoxin from the intestine.

### What role does estrogen play in worsening endotoxin absorption?

Peat noted that estrogen can inhibit bile flow and shut off blood supply to the intestine, directly compromising the body's primary defenses against lipopolysaccharide absorption.

## Related concepts

- [Free radicals](https://bioenergeticoracle.com/md/concepts/free-radicals/index.md)
- [Saccharide](https://bioenergeticoracle.com/md/concepts/saccharide/index.md)
- [Adrenaline](https://bioenergeticoracle.com/md/concepts/adrenaline/index.md)
- [Albumin](https://bioenergeticoracle.com/md/concepts/albumin/index.md)
- [Aldosterone](https://bioenergeticoracle.com/md/concepts/aldosterone/index.md)
- [Estrogen](https://bioenergeticoracle.com/md/concepts/estrogen/index.md)

## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — Glossary

Ray Peat · Glossary

> Endotoxin (Lipopolysaccharide, LPS)
>
> Bacteria and plants produce a variety of lipids that serve some purposes analogous to our cholesterol phospholipids. Some of the common intestinal bacteria produce a molecule containing amino sugars and fatty acids (lipopolysaccharide, LPS), that's called endotoxin. The "endo" root distinguishes it from the "exotoxins" secreted by some bacteria, because the endotoxin is a structural part of the bacterium, that protects the bacteria against some of the exotoxins produced by other microorganisms. Normally, our intestine and liver destroy most of the LPS endotoxin before it reaches the general circulation. The bile acids, a major end product of cholesterol, have detergent action in the intestine that usually keeps endotoxin in solution, away from the absorptive surfaces of the intestine. If the flow of bile is obstructed, endtoxin is allowed to enter the system. Estrogen can inhibit the flow of bile. A mucus lining is part of the protective barrier, but the microscopic integrity of the intestinal cells themselves finally regulated the passage of materials into the blood and lymphatic vessels.
>
> Stress and shock tend to increase our absorption of bacterial endotoxin from the intestine, and endotoxin causes the release of serotonin from platelets in the blood.
>
> Chronic constipation, and anxiety which decreases blood circulation in the intestine, can increase the liver's exposure to endotoxin.
>
> Antibiotics, for example, lower endotoxin formation in the intestine, protect against the induction by endotoxin of serotonin, histamine, estrogen, and cortisol.

### Source 2 — EastWest Healing Serotonin and Endotoxin

Ray Peat · Interview · Aug 24, 2011 · http://l-i-g-h-t.com/files/east-west-serotonin-and-endotoxin.mp4

> ## Endotoxin
>
> **Josh Rubin:** Let's move on to endotoxin. What is it?
>
> **Ray Peat:** Its technical name is lipopolysaccharide (LPS). It is some fatty acids attached to a short starch-like molecule. It's made by a variety of bacteria, specifically the gram-negative type. Animals have evolved to recognize the presence of lipopolysaccharide as the presence of bacteria. It activates the innate immune system. It seems to have a soaping type of action on cells that destabilizes them. That physical irritation is enough to activate the production of serotonin, release of histamine, and nitric oxide. We normally can destroy all of it that gets into the bloodstream by the time it gets to the liver. But if your liver is overworked or under-energized, the endotoxin gets through into your bloodstream.
>
> **Josh Rubin:** So something as simple as the stress reaction could cause an increased production of endotoxin?
>
> **Ray Peat:** Increased absorption of it, yes. A lot of starchy food, undercooked cereals, and poorly cooked vegetable material will feed the bacteria and increase their production of it.

### Source 3 — Endotoxin, Free Radicals, and Inflammation — KMUD July 2009

Ray Peat · Interview · 2009 · http://www.l-i-g-h-t.com/files/herb-doctors-bowel-endotoxinnew.mp4

> **Ray Peat:** Uhm, I'm not sure that people really know what it's doing in the bacterium but it's been known since 1892, it was called endotoxin to distinguish it from the older known bacterial toxins that the bacteria secrete to poison something on their environment, and, supposedly, the endotoxin it only comes out when the bacterium is broken apart but I think that it actually leaks a little bit all the time. So, I wouldn't that strictly like textbooks used to say, that it's somewhat of a structural protein but it's a medium to smallish molecule that can leak out in the process of growth, and cell division, and so on. It's other name is lipopolysaccharide, because its structure is a chain of sugar molecules with fatty acids attached, that gives it a soap-like behaviour that is part of why it's toxic so generally. They are so common in their environment that organisms have their basic defenses against them, one of our basic defenses is the high-density lipoprotein; they talk about it in terms of carrying cholesterol but I think its really historical main function is that it's our first defense against endotoxin once the endotoxin gets into the bloodstream. Normally the intestine is a good barrier against absorbing the endotoxins, and if some of it leaks through the walls of the intestines into the blood vessels and gets fwafbawf to the liver, the liver enzymes break it down, so it shouldn't normally reach the bloodstream in significant amounts; but it's a matter of 10's of mg that can circulate in the blood stream every day.

### Source 4 — Endotoxin

Ray Peat · Interview · Nov 19, 2010

> **Herb Doctor:** Would you just describe endotoxin?
>
> **Ray Peat:** Its chemical name is lipopolysaccharide. There are several kinds of bacteria that make similar things. But this combination of a starch-like molecule with some fatty acids attached to it and it's so widely distributed that all animals have a system for reacting to it and defending themselves against it. And it seems to be partly a bacterial defence against the bacteria's environment. So there's an evolved back and forth relationship between the animals and the bacteria. And it's a matter of things getting out of balance that causes the endotoxin to be a problem.
>
> **Herb Doctor:** Okay, so I hear of many foods that promote this production. Would you be able to list some specific foods that people should think about before they consume them, given that we are going to open up the negative effects of endotoxin.

### Source 5 — Endotoxin, Free Radicals, and Inflammation — KMUD July 2009

Ray Peat · Interview · 2009 · http://www.l-i-g-h-t.com/files/herb-doctors-bowel-endotoxinnew.mp4

> **Andrew Murray:** So this month, again, we're very pleased and fortunate to welcome Dr. Ray Peat back to the show, and we'll be exploring the emerging revelation concerning endotoxemia - and how unsaturated fats further burden our bodies in ways that we couldn't ever imagine. So, welcome to tonight's show Dr. Peat.
>
> **Ray Peat:** Thanks!
>
> **Andrew Murray:** Ok, perhaps, for those people that are tuning in this evening, if you could outline what is endotoxin, how is it formed, and how is it harmful to our health.

### Source 6 — Inflammation, endotoxin, estrogen, and other problems

Ray Peat · Article · 2006

> Carbon dioxide and the major steroids stabilize cells against excessive stimulation, and protect the cell structure.
>
> Bacteria and plants produce a variety of lipids that serve some purposes analogous to our cholesterol and phospholipids. Some of the common intestinal bacteria produce a molecule containing amino sugars and fatty acids (lipopolysaccharide, LPS), that's called endotoxin. The "endo" root distinguishes it from the "exotoxins" secreted by some bacteria, because the endotoxin is a structural part of the bacterium, that protects the bacterium against some of the exotoxins produced by other microorganisms. Normally, our intestine and liver destroy most of the LPS endotoxin before it reaches the general circulation. The bile acids, a major end product of cholesterol, have a detergent action in the intestine that usually keeps endotoxin in solution, away from the absorptive surfaces of the intestine. If the flow of bile is obstructed, endotoxin is allowed to enter the system (Bertok, 2004). Estrogen can inhibit the flow of bile (Stieger, et al., 2000).
>
> A mucus lining is part of the protective barrier, but the microscopic integrity of the intestinal cells themselves finally regulates the passage of materials into the blood and lymphatic vessels. The barrier function of the intestine is weakened by poisons, malnutrition, and the reduced circulation that can result from stress. Estrogens, such as oral contraceptives or Premarin, can cause colitis by shutting off the blood supply (Gurbuz, et al., 1994; Deana and Dean, 1995).
>
> When our cells are exposed to LPS, they produce many of the same reactions that they would produce in response to our endogenous phospholipids. The major proteins that interact with cholesterol contain lipophilic regions called beta sheets, in which a relatively flat surface is formed by parallel strands of the protein. LPS contains a group of fatty acids bound together by the polysaccharide, that strongly binds to these proteins. The alarm reaction produced either by damage of some of our own tissue or by the entrance of LPS into the circulation can, under ideal circumstances, lead to a series of protective and defensive reactions, that resolve the problem.

### Source 7 — Jodellefit: How to Fix Your Digestion & Poop

Ray Peat · Interview · Sep 10, 2019

> ## Liver Function, Gallbladder, and Endotoxins
>
> **Ray Peat:** Its chemical name is lipopolysaccharide (LPS). It is a group of fatty acids attached to a carbohydrate that has a physical "soaping" action. The fat is absorbed in the cells and drags in this carbohydrate that acts as an irritant. Every tissue is damaged by endotoxin. In the gallbladder, receiving chemicals like estrogen and endotoxin causes inflammation. If estrogen is high—such as in pregnancy—cholesterol tends to accumulate, forming sludge or stones. Thyroid deficiency is extremely closely associated with gallbladder problems because of the lowered detoxifying function of the liver. Estrogen can also cause spasms in the smooth muscles, starting with the gallbladder duct or the small intestine. When you get into that over-excited, under-energized state, local irritation can send out waves of contraction that go backwards. This is reverse peristalsis. Embryologists experimented on medical students by putting microscopic particles—club moss spores—into their rectums in the afternoon. In the morning, they took swabs from their mouths. Those who regularly had morning breath found the spores in their saliva, showing it is extremely common to have reverse peristalsis all the way from the rectum to the mouth during the night.

### Source 8 — Ask the Herb Doctor: Rheumatoid Arthritis

Ray Peat · Interview · Oct 21, 2016

> ## Endotoxin and Metabolic Stress
>
> **Sarah Murray:** Dr. Peat, can you recap where endotoxin mostly comes from?
>
> **Ray Peat:** It is produced by bacteria. It is a combination of fatty acids and carbohydrate called lipopolysaccharide (LPS).
>
> **Sarah Murray:** And the main source is from the intestinal tract?
>
> **Ray Peat:** Yes, the intestinal bacteria are always producing it. We absorb a little bit all the time, and it acts as a stimulant to the immune system. In everyday life, a small amount doesn't have a harmful effect.
>
> **Sarah Murray:** This is why you're a proponent of raw carrots, because they help to protect against some of that absorption of endotoxin.
>
> **Ray Peat:** The bactericidal effect of the carrot suppresses the growth of the bacteria, and the fiber absorbs and stimulates excretion.
>
> **Andrew Murray:** So even in a healthy person, this lipopolysaccharide is still going to be produced?
>
> **Ray Peat:** Yes, there is always a little getting into the liver and seeping into the general bloodstream. But when liver function slows down, it massively gets past the liver barriers and starts poisoning your systems, increasing nitric oxide and drastically lowering oxygen metabolism. This is where endotoxin and estrogen come together. They both interfere with the metabolic use of oxygen and turn on glycolysis—turning sugar into lactic acid. The more irritated a tissue is, the more reduced it is, meaning it has an electron excess. This shifts everything through that tissue and eventually the whole organism.

### Source 9 — Herb Doctors: Endotoxins

Ray Peat · Interview · Nov 19, 2010

> **Andrew Murray:** Hi. Thank you so much for joining. As always, new people can be listening who perhaps have never heard you before. So would you please just give an outline of your expertise.
>
> **Ray Peat:** I'm studying hormones and nutrition mostly. I count my PhD in physiology with a biochemical orientation, concentrating on reproductive aging. And that was when I got interested in the interactions of estrogen, oxygen, unsaturated fatty acids, and the toxic interactions of some of our natural materials with environmental materials and processes.
>
> **Andrew Murray:** Okay. So talk about this month, the role of endotoxin. Would you just describe endotoxin?
>
> **Ray Peat:** Chemical name is lipopolysaccharide. There are several kinds of bacteria that make similar things. But this combination of a starch-like molecule with some fatty acids attached to it and it's so widely distributed that all animals have a system for reacting to it and defending themselves against it. And it seems to be partly a bacterial defence against the bacteria's environment. So there's an evolved back and forth relationship between the animals and the bacteria. And it's a matter of things getting out of balance that causes the endotoxin to be a problem.

### Source 10 — Serum endotoxin level is a reliable biomarker of liver disease

Georgi Dinkov · Article · Feb 28, 2023 · https://haidut.me/?p=2162

> It looks like the interest in gut-derived pathogenic substances is steadily increasing in the medical field. After claiming for decades (and still doing so) that liver disease is either genetic in origin or driven mostly by sugar (especially fructose) consumption, now studies like the one below are wisening up to the real culprit – endotoxin (LPS), generated by our own microbiome. This endotoxin, produced every time undigested food reaches the colon, causes a chronic low-grade inflammatory reaction in the intestinal wall, which over time compromises the so-called “gut barrier” and causes a condition known as “leaky gut”. Once leaky gut is established, a lot of the endotoxin released (potentially after every meal) gets into the portal vein, which drains into the liver. Endotoxin itself is a highly inflammatory molecule and is known to cause tissue degeneration, including fibrosis and even cancer. Most of these effects of endotoxin are driven by activation of the TLR4 receptor, which triggers a downstream cascade of nitric oxide (NO, serotonin, histamine, IL-1/6, NF-kB, etc. However, up until recently, mainstream medicine claimed that little to no endotoxin gets into the blood stream, and as such is not a factor in chronic diseases, including liver disease. The study below found the exact opposite – i.e. not only is endotoxin a likely cause of all forms of liver disease (e.g. NAFLD, NASH, hepatitis, fibrosis/cirrhosis, etc), but its levels in the blood directly correlate with the severity/stage of liver disease. The solution to all this? It looks like humble vitamin E (first study below) may be a viable tool for both prevention and treatment of the damage that endotoxin causes.
>
> [references]

### Source 11 — The Peat Whisperer

Danny Roddy · Book · 2012

> ## Pro-Thyroid Blueprint Suggestion #5 Reduce Bacterial Endotoxin
>
> **Danny Roddy:** Endotoxin (sometimes also called lipopolysacharide or LPS) is an internally created toxin that resides in the lower intestine. In a stressed state, circulation is reduced increasing the permeability of the intestine. This can increase the absorption of endotoxin in the blood, which acts as a metabolic burden to the liver, which produces 2/3 of the active thyroid hormone in the body.1 An increase in endotoxin can synergize with and increase the effects of serotonin, histamine, estrogen, and cortisol.2 Endotoxin’s suppression of the metabolic rate is multifaceted. It has been found to decrease thyroid production,3 increase iron oxidation,4 decrease progesterone, increase estrogen,5 burden the liver,6,7 suppress the immune system,8 and induce insulin resistance.9,10 Ridding the body of endotoxin is neither possible nor the goal, but simply suppressing its production by bacteria in the gut, inhibiting its absorption into the blood, and assuring its residency in the large intestine, will decrease its destructive effects.

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