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Heart Health: Leaky Gut, Histamine, & Mast Cells



In today's blog, we take you on a meandering walk to help explore just what is the connection between your heart and your gut, and how the latter has the potential of seriously impacting the former. Especially when it comes to histamine!



Your gut has incredible dual, yet opposing functions. On the one hand, it acts as an absorptive surface allowing you to absorb nutrients from the food you eat. On the other hand, it is meant to be a protective barrier to prevent pathogenic microbes, and toxins from being absorbed into your body.


Mast cells are found in abundance in barrier tissue, with your gut being one of those barriers. They have a role in supporting digestion, but more importantly they are involved in the protective action of the gut as a barrier.


Mast cells release chemical mediators that are involved in functions such as stimulating the production of stomach acid, maintaining the integrity of gut barrier function, and stimulating peristalsis (motility to push contents through the GI tract).




Leaky Gut


When the gut barrier becomes compromised there is a loss of that barrier function. This loss is known as intestinal permeability or leaky gut.


Leaky gut, as the name suggests, means that substances that should normally get pooped out are able to leak from your gut and get into your blood stream. These substances are supposed to get pooped out for good reason—they can trigger an immune response when they leak in to your system.


Your digestive tract is designed to absorb nutrients. When leaky gut is present, larger undigested food particles, toxins, and microbial metabolites are some of the things that can move across the barrier. These larger molecules are not absorbed by cells as with normal absorption, but rather leak through openings between the intestinal cells. These gaps between cells, as shown in the image above, should not be present in healthy intestinal tissue.


Leaky Gut & Mast Cells


When things get through the gut lining, your immune system responds. This is a normal, healthy response meant to protect you from things like food poisoning or a GI infection.



Imagine a sentinel of soldiers lined up on the inside of a castle wall. It’s the same with your gut.



If things leak through the gut, then it’s like the castle wall has been breached, but instead of soldiers waiting to defend the wall, you have mast cells (and other immune cells too) that are waiting and ready to defend your intestinal barrier. When the mast cells respond, they release inflammatory chemicals including histamine.


If you have food poisoning or a GI infection, these inflammatory chemicals signal other immune cells to carry out the task of eliminating the infection.


But what happens when the things that are leaking through are normally occurring compounds?


What’s Leaking?


To understand some of the things that can leak through the gut, we have to understand a bit about the gut microbiome. (Need a good primer? Check out this video here by the good folks at NPR.)


Microbes living in your gut produce all kinds of wonderful things that we need like short chain fatty acids, B vitamins and vitamin K. Depending on what species are part of your unique microbial community, they can also make things like lipopolysaccharides (LPS), trimethylamine (TMA), or histamine.


Each of these three compounds are made in the gut by your microbiome, leak in to your system when there is leaky gut, and have been researched in relation to heart health.



Mast Cell Response


Mast cells have a wide variety of receptors on their surface. It turns out that much of what leaks through the gut can bind to these receptors. That is the case with LPS and histamine.


Sometimes the compound undergoes a conversion before binding. That’s what happens with TMA. TMA (trimethylamine) gets metabolized in the liver to become Trimethylamine N-Oxide (TMAO) which can now bind to mast cell receptors.


There are two different receptors that are impacted by these compounds.

  1. Mast cells have toll-like receptors (1) that LPS (2) and TMAO (3) can bind to. Once bound to, these receptors signal the release of inflammatory chemical mediators from the mast cells (4) . In plain words, this means LPS and TMAO (produced by your gut microbiome) can land on the outside of a mast cell and trigger it to release compounds that drive inflammation.

  2. Histamine binds to different receptors on mast cells called (not surprisingly) histamine receptors, also triggering the release of a variety of chemical mediators, or more compounds that further drive inflammation in the gut, exacerbating that leaky gut.



How does this binding of LPS, TMAO and histamine to mast cells create heart problems?


Histamine, LPS, TMAO & The Heart


Once histamine, LPS, and TMAO are in the bloodstream -- having successfully gone through the leaky gut -- they can bind to mast cells in the arteries and in the heart, contributing to atherosclerosis and cardiac disease (5).


Mast cells in the heart have been shown to release a variety of chemical mediators resulting in scarring of the heart (myocardial remodeling) (6). Scarring changes how the heart functions and leads to chronic hypertension, congenital heart disease and heart failure (7). This is serious stuff!


Histamine has long been known to lead to heart arrhythmias (8), and histamine blocking drugs have not only be shown to reduce arrhythmias, but also to reduce heart rate, blood pressure and to reduce congestive heart failure (9).




LPS and TMAO have been widely studied to show they activate inflammation in blood vessels, but there are no effective drugs to target these. We propose here that they can be regulated by focusing on gut health, the microbiome especially, while also working at mending that leaky gut.


Restore Gut Health


If having a leaky gut means that histamine, LPS and TMA get into the bloodstream where they can then travel to the heart, doesn’t it make sense that gut health should be considered?



Research supports this idea for LPS (10).


So YES! But also NO.



Wait. What?.... Read on.


If histamine, LPS, and TMAO have contributed to mast cell activation in your heart, then the mast cells in your gut will likely also be activated. Mast cell activation in the gut will perpetuate inflammation in the gut and contribute to leaky gut.





And further to that, consumption of fermented foods and bone broth, which are touted as gut healthy and gut mending foods, are high in histamine, and can further drive mast cells to contribute to leaky gut. These foods are beneficial to many people, but not when histamine is contributing to your mast cell response, which is driving this inflammation.


We’ve Got You Covered!

Here at Histamine Haven we have built gut health into our low histamine, mast cell stabilizing approach. We offer low histamine alternatives to bone broth and fermented foods.



We also work in some of those foods that can do double duty and enhance a balanced microbiome, as well as providing your body with those nutrients that help stabilize mast cells. When you do this work, now you really get at the root of what is driving your mast cells to release histamine, along with those other compounds LPS and TMO, and how they all play a role in impacting your heart health.



We have done all the work for you, so you don’t have to figure it all out on your own.


This is how you start getting at the root of what is driving your symptoms and health concerns. If you haven’t started our protocol yet, get started with First Steps.




And be sure to grab a copy of our book! Purchase directly from us here on the site, or at your favourite book retailer.





PS: This is not intended to replace any medical advice. We always advise that you check in with your primary healthcare team and Doctor to get heart issues checked out.

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