Mast cell activation syndrome treatment: What’s the best diet?

Mast cell activation syndrome treatment currently centers around the use of anti-histamines and mast cell stabilizers. Mast cells are immune cells found in connective tissues in your body. Organs and tissues exposed to the external environment such as the gut have the highest density of mast cells.

Activation of mast cells causes the release of histamine and other inflammatory molecules. As a result, people who suffer from mast cell activation syndrome regularly suffer from symptoms of allergy. This includes sneezing, coughing, headache, dry and irritated eyes, and fatigue.

But what does this do in the gut? Mast cell activation induces profound changes in the gut, causing:

  • Pain through visceral hypersensitivity
  • Impaired motility
  • Increased intestinal permeability

Not surprisingly, people with functional gastrointestinal disorders, especially IBS, have higher mast cell density in their gut. Subsequently, intestinal juice from those with IBS activates mast cells more effectively than that from healthy controls.

Mast cells, digestive health, and beyond

What’s with the relationship between mast cells and digestive issues? Interestingly, in the gut where mast cells are highly prevalent, they are located next to sensory neurons. When mast cells activate, they release histamine and other mediators which increase the sensitivity in these neurons.

This can lead to the classic symptoms of IBS of visceral hypersensitivity, bloating, impaired motility, and diarrhea. It also may be why stress is such an important trigger in IBS.

Furthermore, chronic activation of mast cells in the gut may cause allergy-type symptoms elsewhere by increasing serum histamine and other inflammatory mediators. If the primary cause in this situation stems from the gut, you would assume that treating the gut would improve symptoms elsewhere.

A recent paper found relationships between GI symptoms and symptoms such as dizziness, headache, and fatigue. They also found that treating the GI symptoms improved dizziness, headache, and fatigue within a month.

Importantly, they only treated patients for their GI symptoms, so improvements were due specifically to addressing the gut. This shows that the gut can be the source of the problem, and correcting the issue in the gut improves symptoms elsewhere.

Now all we need to find is a mechanism through which mast cells are activated inappropriately in the gut.

A low FODMAP diet for mast cell activation syndrome treatment?

A low FODMAP diet is effective for addressing gastrointestinal symptoms in people with IBS. A majority of IBS patients that undergo treatment with a low FODMAP diet see significant improvements in their symptoms.

Are the improvements in IBS symptoms with a low FODMAP diet from changes in mast cells? Several lines of evidence point in that direction. First, one study showed that a low FODMAP diet decreased histamine by eight-fold.

Secondly, a mechanistic study in mice found that a high FODMAP diet causes “leaky gut” by inducing dysbiosis, increasing LPS in the gut. Dysbiosis caused transcellular leak of LPS, which caused activation of mast cells.

Mast cell activation syndrome treatment: Addressing leaky gut

This “leak” of LPS is important because it won’t activate mast cells if LPS remains in the gut. Mast cells are on the other side of the intestinal barrier, so this movement of LPS between cells when levels are high triggers a series of events that increases permeability more.

Further, this study went on to show that human subjects with IBS-D experienced a decrease in “leaky gut” and measures of mast cell activation on a low FODMAP diet. Finally, intestinal juice from patients before and after a low FODMAP diet showed a similar trend when mice were exposed to it.

In other words, intestinal juice from IBS-D patients on a normal diet triggered increased permeability and mast cell activation in mice. Conversely, when exposed to intestinal juice from patients on the low FODMAP diet, results were similar between IBS-D patients and healthy controls.

Given that improvements in IBS-D appear to occur through changes in mast cell activation and sensitivity, a low FODMAP dietary approach may be worthwhile as a mast cell activation syndrome treatment.


Typically, mast cell activation syndrome treatment doesn’t take diet into account. And even when it does, it normally looks at decreasing histamine in the diet or increasing the intake of mast cell stabilizers.

Several lines of evidence point to a low FODMAP diet as a potential strategy to address mast cell activation syndrome. It’s clear that diet-induced dysbiosis can lead to activation of mast cells in the gut. This appears to be due to increased LPS “leaking” across the barrier and activating mast cells.

As a result, this increases permeability which also increases mast cell activation. In people with IBS, a low FODMAP diet improves barrier integrity and decreases markers of mast cell activation.

Therefore, a low FODMAP diet may be a suitable approach for treating those with mast cell activation syndrome. This approach should include both an elimination period followed by reintroduction to find your specific dietary triggers.

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