The Root Causes of Histamine Intolerance: Gut Health, DAO Deficiency & More

Runny nose, itching and watery eyes, skin hives… It sounds like allergies, right? 

But when bloating, gas and cramping, menstrual irregularities, brain fog, depression, anxiety, and insomnia are part of the picture, it becomes clear something more must be going on!

That’s histamine intolerance for you. 

While it looks like an allergy at first, histamine intolerance is so much more. Histamine affects every system in your body, leaving you with numerous, difficult to control symptoms. It can seriously affect your quality of life, which is why it’s important to determine what has caused your histamine intolerance so you can address it and heal your body. It’s the only way to live a life full of vitality  and free from histamine-induced symptoms. 

Ok, so where do you begin? 

Today, I’ll break down the most common root causes of histamine intolerance backed by research, clinical experience and the understanding of histamine’s role in your immune, digestive, neurological and hormonal systems. With an understanding of what may be going on in your body, you’ll be armed with a starting point for overcoming the condition and moving towards true healing. 

And because it’s always the most important, I’m going to start with how your gut may be influencing your histamine load. 

 

Get the free diet guide!

 

Gut Health and Its Role in Histamine Intolerance

When you’re looking into the root cause of histamine intolerance, it’s important to look at the influence your gut has on your condition. Nearly everyone with histamine intolerance will have some degree of gut involvement (1). Changes in the environment of your digestive tract may cause more histamine to be produced, worsen the levels of inflammation in your gut and even impair the breakdown of histamine. 

A healthy gut has a diverse community of different bacteria, each contributing to a well functioning system. But, multiple courses of antibiotics, infections, chronic stress and poor diet can cause a shift in how these little critters in your gut function. When the bugs fall out of balance, histamine can quickly become a serious problem. Histamine-producing species may take the opportunity to flourish, leaving you with a higher histamine load and the inability to keep it under control. Common culprits include morganella morganii, proteus mirabilis, klebsiella pneumoniae, enterobacter cloacae and lactobacillus reuteri species. 

Gut bacteria can also contribute to histamine intolerance when they begin to grow and flourish in the wrong place. What does this mean? Well, most of your bacteria should be in your colon, or large intestine where fermentation takes place and your stool begins to form. Your small intestine should only house a few bacterial populations. If there are too many, it can cause excessive fermentation of food, interfere with nutrient absorption, slow down the passage of food in your gut, cause gas and bloating, and of course, more histamine release. There’s also a well-documented link between small intestinal bacterial overgrowth (SIBO) and histamine intolerance. And another direct connections between SIBO and low DAO activity. 

Chronic gut inflammation can weaken the digestive lining causing increased permeability, commonly referred to as leaky gut. A leaky gut wall not only allows more compounds like histamine to pass through into your bloodstream, it also increases inflammation in the gut, leading to a vicious cycle. Leaky gut often manifests in headaches, anxiety, brain fog, changes in your hormone levels, skin rashes and fatigue. 

Changes in the diversity of your gut microbiome can increase inflammation, but so can chronic stress, infections, alcohol use, poor diet, food sensitivities and certain medications. As more histamine enters your system, more histamine-related symptoms can be felt, triggering reactions in every organ system such as your brain, skin, and joints, and those affecting your hormones and sleep. 

Your gut is also a major producer of the histamine-degrading enzyme diamine oxidase (DAO) (2). If your gut lining is damaged, less DAO is able to be made. And if you have too many histamine-producing critters in your gut, there won’t be enough DAO to go around. In this case, even though you may be making the ‘right’ amount of DAO, it simply cannot keep up with the increase in its demand. So you can see how the gut environment can have a significant two-fold effect on histamine control!

There are other reasons DAO may not be able to keep up with an increase in demand.

 

Get the free diet guide!

 

DAO Deficiency: Histamine Intolerance Cause

There are several reasons you may not produce enough DAO to keep your histamine levels in check, namely:

• Your genes: some people may have genetic variants that are not able to make the right levels of DAO. Polymorphisms in the AOC1 gene (3) have been shown to inhibit DAO production by a staggering 50-90% in some cases. When histamine intolerance has a genetic involvement, symptoms usually start earlier in life. 
  
  
• Nutrient inadequacies: for DAO to be made in the right amounts, your body needs the appropriate DAO building blocks. When there are inadequate levels of copper, vitamin C, vitamin B6, zinc or magnesium, DAO levels may decline. Eating a variety of fresh foods is key to maintaining adequate nutrient intake. Understandably, when your diet is limited but to histamine intolerance, it can feel difficult to maintain a diverse diet. Use my comprehensive low histamine food list to ensure you’re eating as much of a variety of foods as possible to keep providing your body with the nutritional components you need to make enough DAO. Gut inflammation can also compromise the breakdown and absorption of nutrients, which again refers to the importance of addressing gut imbalances when taking a holistic approach to healing from histamine intolerance. 
  
  
• Medications blocking DAO: if you’re on antidepressants, taking chronic antihistamines, have been using anti-inflammatories for a long time, using acid suppressing medications like PPIs or H2-blockers, have had multiple rounds of antibiotics or need to take immune suppressants, they could be affecting your ability to make DAO. It is, of course, essential to speak to your healthcare provider about these medications before stopping them, but it’s likely there are more appropriate alternatives you can use if you do feel they are affecting your ability to make DOA or are contributing to your symptoms of histamine intolerance.

While direct changes affecting your gut are the main culprits causing histamine intolerance, another key aspect of healing is to look at another complex system in the body and how it may contribute to your symptoms: your endocrine system.

Hormones As A Root Cause of Histamine Intolerance 

 

Estrogen and cortisol are two important hormones to consider when you’re dealing with histamine intolerance. 

Estrogen dominance is closely linked to histamine intolerance due to the effect higher levels have on your mast cells. Mast cells have estrogen receptors, and when there’s more estrogen flowing around your body, the more it triggers mast cells to release their contents, which includes histamine and many inflammatory compounds. In turn, your ovaries have histamine receptors on them because histamine is involved in critical processes involved in normal ovarian function. But high histamine will trigger more estrogen than needed to be released, causing a cyclical release of the two compounds involved in more bothersome symptoms (4). 

You don’t need an estrogen test to determine whether your estrogen levels are high. Simply take a closer look at your symptoms. If you’ve experienced heavy menstrual bleeding, have been diagnosed with fibroids, experience severe pain at the start of your period or around ovulation, deal with chronic PMS, or experience migraine around ovulation, it may be caused by estrogen dominance (which could also be caused by low progesterone, but may have the same outcome) (5). Helping your body to detoxify estrogen may have a significant impact on your symptoms of histamine intolerance. 

The stress hormone cortisol can also activate the release of histamine by mast cells. It has also been shown to impair DAO production, further worsening the symptoms of histamine intolerance. 

Your Complete Checklist: Understanding the Root Cause of Histamine Intolerance To Start Your Healing Journey 

Here’s a quick checklist you can use to determine and address the root causes of your histamine intolerance. You can refer back to this list at any time during your healing from histamine journey to ensure you’ve addressed everything you need to for complete recovery. 

• CHECK whether it is a true allergy or histamine intolerance. If you’ve been dealing with allergies but have not been able to get a positive allergy test (6) and you have co-existing symptoms affecting your gut, mood, hormones and sleep, it’s likely a histamine issue.
  
  Sometimes, when you have histamine intolerance, there may be other food intolerances you’ll have to address, but start with managing your histamine levels to determine the effects it has on your symptoms.
  
  Once your histamine burden is reduced, you’ll quickly be able to tell if you need to address a different form of food sensitivity, or whether you’ll have to look for another cause of your symptoms outside of histamine intolerance and food sensitivities.
  
  
• CHECK your gut, it can give you some helpful clues. If you’ve had numerous prior gut infections, have been on multiple courses of antibiotics or have dealt with chronic and significant gut symptoms such as bloating, intolerances, and stool irregularities, your gut barrier may be compromised. If your gut barrier is not functioning optimally, more histamine will be able to flow into your blood stream and trigger symptoms.
  
  Other dysfunctional factors affecting your gut environment may also be at play. You may also be dealing with the opportunistic growth of histamine-producing bacteria and/or dysbiosis with a poor capacity for healthy bacteria to flourish and keep your gut in good working order.
  
  Even when you lower your histamine levels through your diet, for example, your gut will tell you if it needs some extra TLC, which is usually the case when you have histamine intolerance.  
  
  
• CHECK your diet and lifestyle factors that could be loading your body with histamine. From eating aged or fermented foods to consuming even small amounts of alcohol, you could be inadvertently increasing your overall histamine burden and not even know it. Yes, fermented foods are often great for gut health, but in histamine intolerance they should be avoided. Even leftovers, some medications, chronic stress and lack of sleep may cause your histamine levels to increase above your body’s threshold, leading to severe unmanageable symptoms.
  
  There’s also merit in determining whether you’ve been exposed to mold (7) or chemicals that may have triggered your histamine intolerance.
  
  To be on the safe side, every aspect of your diet and lifestyle should be assessed and imbalances addressed to help you to achieve overall symptom control and begin healing. 
  
  
• CHECK you have enough DAO to go around. Whether your body is not making enough DAO or an aspect of your diet or lifestyle is causing DAO to work ineffectively, taking action to support histamine breakdown by DAO is a key step in the healing journey.
  
  You may find your symptoms dramatically decrease when you start to take a DAO supplement. If this is the case, the supplement can be continued long term should you feel you need it.
  
  It’s a safe and effective way to decrease symptoms while you work on other root causes of your histamine intolerance.  
  
  
• CHECK your hormones. From cortisol to estrogen, it’s essential to determine the state of your hormones if you want true relief from histamine intolerance. Because there’s a deep connection between estrogen and histamine, assessing your estrogen levels may be a key step in managing your condition.
  
  You see, higher estrogen levels can stimulate mast cells to release histamine, and higher histamine levels then subsequently stimulate more estrogen to be released from your ovaries. So, if you’ve experienced hormonal issues such as PMS, heavy bleeding while on your period, or chronic period pain, it might be time to address your hormones to help balance your histamine.
  
  Cortisol is another important hormone when it comes to histamine intolerance as it also has a significant effect on mast cells. Chronic stress can sensitize your mast cells, causing them to rupture and release histamine even when no threat is present.
  
  Stress can also lower DAO production, increase inflammation, cause nutrient deficiencies, disrupt other hormones such as estrogen, and cause an overall rise in histamine production.
  
  Addressing high estrogen (or low progesterone), and managing stress is a critical step in healing every aspect of your body, not only for beating symptoms of histamine intolerance. 

 

Get the free diet guide!

 

The Power of Healing Is in Discovery of the Root Cause of Histamine Intolerance

Figuring out how to heal from histamine intolerance may seem like a daunting task. But, once you know why you have the condition in the first place, you’ll have key information to help you along your way. 

Addressing the root cause and restoring balance across all systems of your body will help you to build resilience and it can leave you with the very real possibility of feeling vibrant and symptom-free once again.

References

1. Schnedl WJ, Enko D. Histamine Intolerance Originates in the Gut. Nutrients. 2021 Apr 12;13(4):1262. doi: 10.3390/nu13041262.
2. Neree, A.T., Soret, R., Marcocci, L. et al. Vegetal diamine oxidase alleviates histamine-induced contraction of colonic muscles. Sci Rep 10, 21563 (2020).
3. He, D., et al. Diamine oxidase acts as a novel risk factor in abnormal inflammation via mediating “cytosolic ROS-autophagy-IFN-γ” axis in NK cells. Life Sciences. 2025. 377:123775.
4. Zierau O, Zenclussen AC, Jensen F. Role of female sex hormones, estradiol and progesterone, in mast cell behavior. Front Immunol. 2012 Jun 19;3:169. 
5. Kalogeromitros D, et al. Influence of the menstrual cycle on skin-prick test reactions to histamine, morphine and allergen. Clin Exp Allergy, 25 (1995), pp. 461-466
6. Zhao Y, Zhang X, Jin H, Chen L, Ji J, Zhang Z. Histamine Intolerance-A Kind of Pseudoallergic Reaction. Biomolecules. 2022 Mar 15;12(3):454.
7. Kritas SK, Gallenga CE, D Ovidio C, Ronconi G, Caraffa Al, Toniato E, Lauritano D, Conti P. Impact of mold on mast cell-cytokine immune response. J Biol Regul Homeost Agents. 2018 Jul-Aug;32(4):763-768.