---
title: "Histamine Intolerance and Inflammatory Bowel Disease: Any Connection?"
description: Reduced DAO enzyme activity behind histamine intolerance may worsen gut barrier function, and studies link low DAO levels to inflammatory bowel disease.
image: https://www.casi.org/hubfs/casi/featured/10-5-histamine-ibd.jpeg
---

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# Histamine Intolerance and Inflammatory Bowel Disease: Any Connection?

DM Danielle C. Male, MS, CNS, LDN Oct 05, 2023

![Histamine Intolerance and Inflammatory Bowel Disease: Any Connection?](https://www.casi.org/hs-fs/hubfs/casi/featured/10-5-histamine-ibd.jpeg?width=960)

[Inflammatory bowel disease](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297875/) (IBD) is a term for two chronic, autoimmune diseases in the gastrointestinal (GI) tract: [Crohn’s disease](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297875/) and [ulcerative colitis](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297875/). Research is investigating the potential connection between IBD and histamine intolerance, which affects approximately [1% of the total population](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806734/), of which [80% are middle-aged](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806734/). 

## What is histamine intolerance?

[Histamine intolerance](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069563/) (HIT) is similar to lactose intolerance and is characterized by a deficiency of [diamine oxidase (DAO) enzymes](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069563/). In the GI tract, DAO is the primary enzyme that metabolizes and degrades histamine. DAO is located at the [apical end of mature villous cells](https://academic.oup.com/ibdjournal/article/17/2/E23/4636187?login=false) in the GI tract. It is proposed that DAO activity can reflect the [small intestinal mucosa's integrity and maturity](https://academic.oup.com/ibdjournal/article/17/2/E23/4636187?login=false). 

HIT can result in [insufficient histamine degradation](https://pubmed.ncbi.nlm.nih.gov/30552302/) and [elevated plasma histamine concentrations](https://pubmed.ncbi.nlm.nih.gov/30552302/). Consumption of histamine-containing foods in individuals with HIT may result in [nonspecific, undesirable symptoms](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069563/), such as [GI complaints](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102523/) (i.e., bloating, postprandial fullness, abdominal pain) or [headaches](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102523/). HIT may result from [genetic polymorphisms, certain medications, or inflammatory or GI disorders](https://pubmed.ncbi.nlm.nih.gov/29475774/). Human clinical studies by [Schnedl et al.](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859183/), [Izquierdo-Casas et al.](https://pubmed.ncbi.nlm.nih.gov/29475774/), and [Manzotti et al.](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806734/) demonstrate that patients with HIT who were administered DAO supplements exhibited significantly improved HIT-related complaints. 

## What foods contain histamine?

Histamine is a [biogenic amine](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463562/) that can be synthesized endogenously or obtained exogenously and has [various roles in the body](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463562/). Many foods contain [moderate-to-high histamine levels](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463562/), such as alcohol, fish, meat, fermented foods, cheese, and certain fruits and vegetables. Histamine concentrations of a food product can vary based on [manufacturing processes, hygiene of raw materials, microbial composition, and fermentation duration](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069563/). Due to the vast and variable distribution of histamine-rich foods, adhering to a histamine-free diet may be challenging and increase the risk of [nutrient deficiencies](https://pubmed.ncbi.nlm.nih.gov/29475774/). 

## What is the connection between histamine intolerance and IBD?

The exact [mechanism](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297875/) underlying the connection between histamine, histamine-associated signaling pathways, and inflammatory responses in patients with IBD [remains unclear](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297875/). However, research suggests that [dysregulated histamine homeostasis](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297875/) may be associated with [IBD etiology and pathogenesis](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297875/). 

Human and animal studies suggest that a DAO deficiency may correlate negatively with [intestinal barrier dysfunction](https://pubmed.ncbi.nlm.nih.gov/30552302/) and [colonic inflammatory responses](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069563/). Some studies propose that DAO activity could potentially be considered a [marker of intestinal mucosa integrity](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069563/) of the small intestine, though more research is needed. 

In [patients diagnosed with IBD](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069563/), it was observed that the [histamine content and secretion of affected mucosa](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069563/) were significantly increased, which could potentially be associated with a DAO deficiency. Among [115 patients](https://academic.oup.com/ibdjournal/article/17/2/E23/4636187?login=false), those with IBD had significantly lower serum DAO activity than controls, [regardless of disease activity level](https://academic.oup.com/ibdjournal/article/17/2/E23/4636187?login=false). Notably, serum DAO activity was [significantly lower](https://academic.oup.com/ibdjournal/article/17/2/E23/4636187?login=false) in patients with ulcerative colitis in whom small intestinal inflammation was [not involved](https://academic.oup.com/ibdjournal/article/17/2/E23/4636187?login=false) compared to healthy controls. 

## Conclusion

Although more research is needed on the exact mechanism, evidence suggests a connection between HIT and IBD. Since [HIT is known to originate in the gut](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463562/), promoting normal histamine homeostasis may benefit overall GI health and function and vice versa.  

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### Danielle C. Male, MS, CNS, LDN

Clinical Application

## Clinical Considerations in Practice

 In clinical practice, practitioners considering the topics discussed above may also weigh nutrient form, delivery and formulation, alongside individual patient variability.

### Practitioner Formulation Example

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HistaGest-DAO™

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