Supporting Healthy Intestinal Permeability with the Use of Collagen

What is Intestinal Permeability?

Intestinal permeability is the scientific term for the ability of the gut to absorb from the intestinal tract into the blood stream.  This is essential for the absorption of vital nutrients.  In some instances, the gut can become overly permeable, a condition known as intestinal hyperpermeability, often referred to as “leaky gut.” The intestine is supposed to be a barrier with tight junctions between epithelial cells that prevent larger food allergens, microbes, and their toxins from entering the circulation, while allowing smaller digested nutrients in.  In the case of hyper permeability, larger particles that would normally be kept out are able to go through the gut lining.  This condition has been shown to be present in Inflammatory Bowel Disease and Celiac Disease where inflammation is a primary driver of the disease.1 Leaky gut has also been associated with other digestive disorders such as Irritable Bowel Syndrome.2 Medical conditions such as autoimmune disease, mood disorders, food allergies, neurodegenerative conditions, and liver disease have been associated with leaky gut.2,3 

Why is it important to maintain healthy intestinal permeability?

Intestinal hyperpermeability or leaky gut has been found in many chronic diseases.1 Research has shown that many inflammatory diseases begin in the gut with the hyperpermeability and imbalanced microbiome.1 The question then becomes why do people develop leaky gut?  The initial microbiome of an infant that influences their long term microbiome is gained from their mother at delivery.4 From there, the microbiome can be influenced by medicines such as antibiotics and NSAID’s such as ibuprofen.5,6 The classic western high sugar and high fat processed food diet also contributes to an unhealthy microbiome and increased intestinal hyperpermeability.7  Stress, a common factor in everyday life, when chronic leads to a leaky gut and this includes stress from extreme exercise.8 

How does collagen help support healthy intestinal permeability?

Collagen is the largest protein in the body and is broken down into 5 types. Type 1 is 90% of the collagen in the body.  Collagen is essential for the structure and strength of connective tissue including the bones, cartilage, skin, and blood vessels.  It also plays a role in the formation of the epithelial lining of the intestines, blood vessels, and other organs.  Epithelial cells are in contact with connective tissue that secretes collagen to form the structure of the epithelial lining.  Three amino acids make up the majority of collagen and include glycine, proline, and hydroxyproline. The other amino acids include glutamine often used alone for gut health. Since collagen is made up of amino acids, it breaks down into those amino acids when taken orally. For better oral absorption of collagen, it is hydrolyzed to peptides.

Research has shown that collagen is an important component to help repair and heal the intestinal lining.9  Low collagen levels have been associated with digestive issues including an association with Inflammatory Bowel Disease.10   Therefore collagen peptides appear to both help prevent and heal intestinal inflammation leading to damage in the digestive lining seen in leaky gut.11  An inhibition of NFKB and a decrease in inflammatory promoting TNF alpha may be part of the mechanism of prevention and repair.12

What are the concerns with using high doses of glutamine?

A widespread practice is the use of high doses of glutamine to repair the intestinal lining. Several concerns have been raised concerning the use of one amino acid in high doses.  Elevated levels of glutamine can lead to an imbalance of amino acids which can cause elevation for some amino acids and a decrease in others.13   It may also impact the distribution and uptake of amino acids including alteration in ammonia transport and glutamine metabolism.13 One area of particular concern is the role of glutamine in cancer.  Both regular cells and cancer cells use glutamine as an energy source.  Higher doses of glutamine may feed cancer cells increasing their growth.14   Because of this, glutamine blockers are being investigated for use in cancer.14

Do I need to worry about increase histamine levels with collagen?

Elevated histamine can cause problems with increased allergy and mast cell activation symptoms.  Because of this, people will try to decrease the amount of histamine in their diet and supplements.    Collagen is made primarily of glycine, proline, and hydroxyproline but also includes small amounts of many other amino acids including histidine, which is the precursor of histamine. Despite this, it is important to recognize that many common foods in the diet contain histidine including meat, poultry, fish, dairy, and some grain products and vegetables.  The body requires histidine as an amino acid so foods with histidine should not be avoided.

What else helps to support healthy intestinal permeability?

In addition to collagen, several other nutrients contribute to supporting a healthy gut lining.  Part of the mechanism of collagen is to support the gut lining by promoting tight junctions.  Zinc Carnosine, deglycrrhized licorice (DGL) and N-acetylglucosamine are helpful additions to collagen for this purpose. 15-19 Improving the mucin layer on top of the endothelium lined intestinal lining can be improved with DGL and n-acetylglucosamine.15-22   Excess histamine can cause damage to the digestive tract so natural antihistamines such as luteolin and black cumin are an important part of gut health.22-24 Improving the microbiome with beneficial probiotic bacteria and prebiotics is also crucial.


Leaky gut is a common component of many chronic diseases in addition to digestive illnesses. Understanding the mechanisms involved in the development of leaky gut helps determine the best way to support healthy permeability.  Collagen is a source of amino acids that helps safely support healthy intestinal permeability, and is anti-inflammatory, making it a good addition for overall digestive health.9,12 


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