The Dangers of Metabolic Endotoxemia - Part 1

Written by Anil Bajnath, MD
Posted October 19, 2021

Dear Longevity Insider,

Metabolic endotoxemia is the presence of too much lipopolysaccharides (LPS) in the blood. LPS are toxins that reside on the outer membrane of bacteria that would otherwise not be allowed into our bloodstream. The American Diabetes Association identified bacterial lipopolysaccharide (LPS) as the inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes.

LPS triggers a cascade of immune responses. For example, after binding to its receptor TLR4 (TLR4 is a receptor found on the surface of cells that can detect LPS) or CD 14, there is an elevated level of tumor necrosis factor alpha (TNFα). TNFα is protein signaling molecule that is an inflammatory mediator that triggers the innate immune response. The innate immune system, as its name implies, is a primitive type of immunity that all living organisms have. In contrast to the adaptive immune system (which is found in humans and other higher-order species), there are no actual distinguishing features between cells belonging to the innate system or adaptive immune system – they simply look different. TNFα activates more TLR4 which results in more TNFα. As you can see, it becomes a vicious cycle leading to chronic inflammation.

LPS also induces cytokine production by activating inflammatory transcription factors known as nuclear factor kappa B (NF-κB). NF-κB is a protein complex that controls the expression of genes involved in immunity and inflammation, inducing cytokine production helps our bodies fight off infections. However, it also activates the immune response to clear away cells that are injured or damaged by short-term inflammation. If this clearing of dead cells occurs chronically, it can lead to tissue damage and autoimmune diseases where the body starts attacking its own healthy tissues.


Paracelsus, a renaissance physician said: "All things are poison; everything is poisonous; there is nothing without poisonous qualities. Only the dose permits something not to be poisonous." 

The severity of this disorder depends on how much LPS enters circulation and how sensitive an individual's body is to these inflammatory agents. As expected, diet, and lifestyle are critical when it comes to metabolic endotoxemia and other diseases. 

Inflammatory transcription factors are also activated in response to a high-fat, diet-rich in saturated fats and low in fruits and vegetables. Inflammatory transcription factors are transcription factors that contribute to the initiation, regulation, and mediation of inflammation.

Saturated fatty acids trigger macrophages to create a cascade of inflammatory signals. Saturated fats refer to a type of dietary fat with no double bonds between the carbon atoms. They are typically solid at room temperature and found in foods such as beef, pork, poultry, butterfat (in dairy products), palm kernel oil, lard (in meat products), and cocoa butter. Inflammatory foods have been linked to cause an inflammatory immune response that results in endotoxemia, which is the presence of bacterial endotoxin (LPS) in the blood stream.


The relationship between metabolic endotoxemia and the onset of diabetes, obesity, and heart disease is well established. Metabolic endotoxemia causes the body to have increased cortisol levels. This causes increased insulin resistance, which can contribute to type 2 diabetes. In a healthy body, insulin resistance may be caused by high cortisol levels in response to stress. This insulin resistance is typically temporary as a protective mechanism for the body, but in most people who are insulin resistant, a high carbohydrate diet makes them even more insulin resistant. So, these individuals will typically crave carbohydrates when their blood sugar is low from the stress cortisol is causing on their bodies with elevated insulin resistance...

Before we dive into more on Thursday, here's some of my most-prized research on early aging, disease, and your cellular health.

To your longevity,

Anil Bajnath MD
CEO/Founder, Institute for Human Optimization
Chief Medical Officer, Longevity Insider HQ

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