Diamine Oxidase & Histamine: How to Increase DAO Enzymes Naturally

If you always seem to struggle with itchy eyes, a runny nose, hives, headaches, period cramps and chronic fatigue, you may be living with histamine intolerance. 

You may know this already, but do you know what's causing it? 

If you've tried everything to reduce your intake of histamine-rich foods but still suffer from recurring symptoms, the root cause of your histamine intolerance might just be because something is lacking in your body. 

That's right! A simple, yet fixable, deficiency, might be your problem. 

Now, before we get into how to tackle it, let’s take a look at what histamine intolerance is and what role this deficiency plays in the control - or lack thereof - of your histamine levels.

DAO Deficiency and Its Role in Histamine Intolerance

Histamine is a chemical biogenic amine produced by the body in response to a compound entering the body the immune system deems as a threat. Histamine supports the role of the immune system, where it helps to bring more blood flow to the area, facilitating the movement of immune cells to manage that said threat. When the threat is neutralized, the body produces two enzymes, known as the diamine oxidase (DAO) enzyme and histamine N-methyltransferase (HNMT) to break histamine down.

If these enzymes aren’t available or, if your body cannot produce enough of them for the amount of histamine that was produced, it can cause a histamine build-up. This increase in circulating histamine can then cause symptoms of histamine intolerance. 

Studies show almost 1% of the world's population is histamine intolerant (1). And almost 80% of those affected are women (2). While there is still a debate about why this is the case, it has been suggested that a woman's hormonal composition might be the cause. It might also be because of a deficiency in one of these enzymes needed to break histamine down. 

Of the two enzymes, a diamine oxidase (DAO) deficiency is one of the most common causes of histamine intolerance (3). In fact, studies show that DAO deficiency accounts for over 70% of all causes of histamine intolerance.

When it comes to women, this might also be part of the histamine intolerance picture. 

You see, we have evidence to believe the cyclical changes in hormones may have a great influence on the DAO enzyme, where there is typically a spike in the symptoms of histamine intolerance during the premenstrual or luteal phase of the cycle (4). Interestingly, DAO should also increase significantly at this time, which means, if your body actually needs more DAO in the second half of your cycle but you don't have enough of a supply due to a deficiency, not only are you likely to experience more histamine intolerance symptoms, but your period may be more painful, too (5). 

So, you can see there's a possibility of having a DAO deficiency in both those with a uterus and testes being the root cause of histamine intolerance... let's look into what the causes could be. 

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Diamine Oxidase Deficiency: Common Causes Relating to Histamine Intolerance 

Several factors influence the body's ability to produce DAO. If these factors come into play, a DAO deficiency may occur. These factors include:

• Genetic inheritance - Individuals may have a genetic mutation that results in a diamine oxidase enzyme deficiency. One of the more common genes studied is called the  Amine Oxidase Copper Containing 1 (AOC1) gene. When this gene code has a typo, it may not be able to tell the body how to make DAO correctly (6). 
  
  
• Medications – Both prescription and over-the-counter medications may contribute to reduced diamine oxidase enzyme levels. Those medications include proton pump inhibitors (7) used for reflux and even NSAIDs (8) used for pain. Before stopping any of your medication, it’s important to talk to your doctor whether an alternative would suit you better. 
  
  
• Hormonal imbalances - I mentioned the fact that women are more at risk of histamine imbalances due to hormonal changes. But changes in oestrogen and progesterone levels overall can impact many of your body’s normal functions, including how the DAO enzyme works (9). 
  
  
• Gastrointestinal disorders - Disorders such as irritable bowel syndrome (IBS), Crohn’s disease, ulcerative colitis, Celiac disease and small intestinal bacterial overgrowth (SIBO) may all contribute to inflammation in your body causing similar symptoms as a histamine intolerance and even impacting your body’s ability to produce proper amounts of the DAO enzyme. Estrogen particularly, has been shown to slow down the output of DAO. 
  
  
• Nutrient deficiencies - Low levels of B vitamins, vitamin C (10), zinc or copper may put you at risk or contribute to a DAO deficiency. These nutrients are important cofactors in the production of DAO and without them, the availability of the enzyme may be compromised (11,12). 
  
  
• Consuming histamine-rich food - Some foods may inhibit the functioning of the DAO enzyme, or contribute to symptoms by overloading the body with more histamine than your enzymes can break down. Foods well know to do this include alcohol, black tea, energy drinks and fermented foods like sauerkraut and kimchi. 
  
  
• Alcohol - Alcohol is a very potent inhibitor of the DAO enzyme, thus contributing to increased histamine symptoms. Additionally, because alcohol has gone through a process of fermentation, it will contribute to higher histamine levels in the body leaving you with a double punch causing histamine intolerance symptoms. 

Some or all of these factors may be in effect in your body, leading to recurring symptoms of histamine intolerance. So, what do you do about it? 

8 Ways to Increase DAO Enzymes Naturally To Beat Histamine Intolerance 

To date, there have been many studies looking into the ways you can prevent DAO deficiency in the body. Fortunately, researchers have even identified options to potentially prevent and even reverse histamine intolerance through optimization of the DAO enzyme. Here they are: 

1. Adopt a low histamine diet

One study found that dietary modification is the first step for reducing symptoms associated with histamine intolerance (13). By eliminating high histamine foods from your diet, you are allowing your body to catch up to and process the amount that is already present. The study also discovered that these dietary modifications positively impacted how DAO enzymes move throughout your body.

If you aren’t sure how the right diet can reduce your histamine levels and support healthy DAO production, click the button below to download my free eBook. It is a master list of 102 high histamine foods to avoid, along with step-by-step guide for reducing your symptoms and discovering the root cause of your intolerance.

Get the free low histamine guide!

2. Balance your fat intake

When it comes to updating your diet, some of the most interesting and relevant results for increasing DAO enzymes have been in relation to fat consumption.

Studies have shown favourable results when patients increased their intake of the Omega-9 fatty acid - monounsaturated fats, a primary source of oleic acid. Olive oil in particular was shown to increase the the release of the DAO enzyme into the bloodstream by up to 500%!

Oleic acid has been shown to have other health benefits, too, such as reduced blood pressure, especially when consumed as part of a Mediterranean-style diet (14). You can cook with olive oil or include nuts like macadamias (also high in oleic acid) in your meal plan to help prevent a DAO deficiency.

Meanwhile, the inflammatory Arachidonic Acid (15), a polyunsaturated omega-6 fatty acid, found in offal, fatty red meat and dairy (especially hard cheeses, butter and eggs) was found to cause the highest increase in histamine, when compared to other foods.

Reducing the amount of Omega-6 in your diet - the kind found in processed foods and vegetable oils - while increasing the amount of Omega-3 fatty acids you eat has been shown to moderate inflammation and reduce symptoms of histamine intolerance.

Important factors in balancing fats include using heat stable oils, including ghee and pressed coconut oil for baking and cooking at high temperatures. You can regularly use olive oil and macadamia oil for light, low heat cooking.

3. Eat the right proteins

When you eat protein, certain digestive processes are set in motion to promote digestion of the said protein. These digestive processes also include promoting the release of the DAO enzyme in the gut (13). When DAO is released, it helps your body deal with ingested amines such as histamine. As long as DAO is released in the right quantities, it may help to prevent a build-up of histamine levels in the body.

What I recommend to ensure you're always getting your DAO hit as a result of eating protein, is to always add a clean, healthy protein source to all of your meals from breakfast to lunch and dinner, and everything in between. Look for grass-fed, organic protein and fresh seafood sources of protein, or use a low-histamine protein powder like pumpkin seed protein to increase DAO activity.

4. Minimize harmful ingredients

A common theme in this list of ways to increase and optimize DAO in the body is to include healthy, whole low-histamine foods in your diet.

That’s not an accident! It’s important to understand avoiding artificial ingredients, herbicides, pesticides and other toxins can make a huge impact on your digestion, DAO production and even your risk of developing food allergies overall. 

Because they have a significant impact on your gut health, leaving at risk of developing leaky gut, you're also at risk of developing general digestive inflammation, which can increase the release of histamine from mast cells in the gut and increase the demand on your DAO production. 

Eating as naturally and as toxin-free as possible is going to indirectly decrease the demand on your DAO by reducing the histamine in your gut, and is always going to be a positive for your health overall! 

So avoid heavily processed and packaged foods and, if you can't buy organically grown produce for any reason, be sure to take the time to wash them well before packing them away. 

5. Supporting gut health

As mentioned, the majority of DAO histamine is produced in the gut. And similarly to the above point about toxins, when there is increased permeability in the digestive tract, DAO can quickly leak out into the blood and so less is available in the gut to manage the histamine levels in that location. 

Leaky gut can also be brought on by changes in the composition of your gut bacteria, so promoting your gut health and supporting your gut microbiome through the use of low histamine probiotics provides an important foundation for reducing histamine symptoms.

6. Take vitamin supplements

Deficiencies of zinc, copper, vitamin B6 and vitamin C, have also been associated with inflammation, elevated histamine concentrations and reduced DAO activities. Regular supplementation of these nutrients can increase DAO enzymes and may offer further relief from the symptoms of histamine intolerance.

Of course, we'd prefer you to get them from your diet due to the array of vitamins and minerals food can provide, however, not only do some people have limited access to these types of foods but following a low-histamine diet can be quite restrictive. A helpful way to ensure you're meeting your nutrient needs is to take a low histamine multivitamin with minerals, which can prevent or improve existing nutrient deficiencies.

7. Find a DAO supplement

Another simple way to increase your DAO enzyme levels are with a natural DAO supplement. These can be taken as a capsule and may offer an easy way to help reduce symptoms of histamine intolerance.

Supplementing with DAO enzymes directly is one of the fastest and most powerful ways to increase DAO levels. They go right into the digestive system and are usually fast-acting to help break down incoming histamine and reduce symptoms. They can be conveniently taken with each meal and snack. 

8. Reduce histamine release with natural antihistamines 

One of the most common ways I help my clients with histamine intolerance is by adding a specific natural antihistamine supplement to their routine, especially if they have evidence of widespread inflammation, which is very typical in histamine intolerance.

This natural antihistamine supplement contains natural plant extracts proven to have antihistamine effects, which help to stabilize your mast cells and reduce their release of inflammation (16). Although reducing histamine release doesn't directly increase the DAO enzyme, it does give your body a break from the symptoms a histamine overload can cause, and may allow your DAO enzyme to catch up and calm your symptoms.

Additionally, by controlling the body's natural histamine release, my clients typically find they can tolerate much higher levels of dietary histamine before their body becomes overloaded and shows symptoms.

This means less dietary restrictions and fewer symptoms. And yes, it means you can likely eat a wider variety of foods and live a normal daily life with histamine intolerance! In fact, some of my clients have called Anti-Hist their "miracle in a bottle" or their "wonder-drug."

Implementing Changes to Improve Histamine Symptoms

Now that you have 8 ways to naturally prevent support your body's DAO levels, it's time to get started.

The steps above are all simple and can be done in your own home so, I encourage you to begin implementing them right away. Why wait?

And, if you haven't already read the low histamine diet eBook I've created, click on the button below. It is the most comprehensive high histamine foods list available online, with additional step-by-step instructions on what you can do for symptom relief as well as more information about how to discover the root cause of your histamine intolerance.

Get the free histamine eBook!

 
While that's all the information you need to get started with supporting your body's DAO levels, I often get questions regarding DAO supplements. For this reason, I have included a Q&A about them below...

FAQ: DAO Enzyme Supplements

Does everyone with histamine intolerance need to supplement DAO enzymes?

No. There is no hard and fast rule that will apply to everyone who has histamine intolerance, and therapies should be individually tailored. As research shows 70% of histamine intolerance stems from some level of a DAO deficiency, these individuals in particular may benefit from supplementing DAO enzymes.

Additionally, those who do not have a DAO enzyme deficiency but are still histamine intolerant may for other reasons choose to supplement with DAO and still experience benefits. In other words, DAO is helpful for most histamine intolerant individuals, but not necessarily all. My advice is to give it a try to see if it benefits you. If it does, then continue to use it. If it doesn't seem to help, you may need to do some more digging about your individual root cause. 

Can diet increase DAO enzyme levels as much as DAO supplements?

Although diet can increase levels of DAO enzymes, it will of course not be as potent as supplementing enzymes. However, not all individuals need such a strong dose of DAO as is obtained through supplementation.

If you have very mild histamine symptoms, for example, then using dietary methods of increasing DAO can be sufficient to improve these. If you struggle with more symptoms that are not controlled through a strict low-histamine diet, for example, you may need a supplement, and at a higher dose. 

Are DAO enzyme supplements suitable for vegans and vegetarians?

Unfortunately not. DAO enzyme supplements are a porcine kidney extract, meaning they are extracted directly from an animal. For this reason, these supplements are not compatible with vegan and vegetarian diets.

Do diamine oxidase enzyme supplements have to be taken forever?

This comes down to your root cause. For example, if you currently have a nutrient deficiency preventing you from producing enough diamine oxidase enzymes naturally, then you can attend to the nutrient deficiency and fix it at the root, which will most likely result in an ability to produce DAO normally.

In this case, DAO supplementation would no longer be necessary and individuals could wean off.

If, however, you have a genetic inability to produce sufficient DAO, this may be unalterable. It would depend on the severity of the issue and if it could be managed using another route such as limiting your histamine intake. In my experience, however, cases like these, where genetics are a factors, suggest people are likely to need to continue relying on diamine oxidase supplements in the long run if they want to include a variety of foods in their diet and not have to continue strict restrictions.

Can DAO supplements help with other disorders?

There are major crossovers between histamine intolerance and a variety of other disorders such as IBS, SIBO, chronic migraines, mood disorders and even fibromyalgia.

For this reason, DAO enzyme supplements can often improve overlapping symptoms. One study, for example, showed that supplementing with DAO enzymes for 8 weeks improved symptoms of fibromyalgia (17).

References

1. Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MDC. Histamine Intolerance: The Current State of the Art. Biomolecules. 2020;10(8):1181. Published 2020 Aug 14. doi:10.3390/biom10081181
2. Jarisch, R. (2015). Histamine Intolerance in Women. In: Jarisch, R. (eds) Histamine Intolerance. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55447-6_6
3. Van Odijk J, Weisheit A, Arvidsson M, Miron N, Nwaru B, Ekerljung L. The Use of DAO as a Marker for Histamine Intolerance: Measurements and Determinants in a Large Random Population-Based Survey. Nutrients. 2023;15(13):2887. Published 2023 Jun 26. doi:10.3390/nu15132887
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6. Maintz L., Yu C.-F., Rodríguez E., Baurecht H., Bieber T., Illig T., Weidinger S., Novak N. Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities. Allergy. 2011;66:893–902. doi: 10.1111/j.1398-9995.2011.02548.x.
7. Siletsky S.A. Proton Pumps: Molecular Mechanisms, Inhibitors and Activators of Proton Pumping. Int. J. Mol. Sci. 2023;24:9070. doi: 10.3390/ijms24109070.
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10. Jarisch, R., Weyer, D., Ehlert, E., Koch, C., Pinkowski, E., Jung, P., … Koch, A. (2011). Influence of Orally Taken Vitamin C on Histamine Levels and Motion Sickness. Journal of Allergy and Clinical Immunology, 127(2), AB261–AB261. doi:10.1016/j.jaci.2010.12.1
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12. Ruscin JM, Page RL 2nd, Valuck RJ. Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother. 2002;36(5):812-816. doi:10.1345/aph.10325
13. Wollin, A., Wang, X., & Tso, P. (1998). Nutrients regulate diamine oxidase release from intestinal mucosa. American journal of physiology. Regulatory, integrative and comparative physiology, 275 4, R969-R975.
14. Terés, G. Barceló-Coblijn, M. Benet, R. Álvarez, R. Bressani, J.E. Halver, P.V. Escribá, Oleic acid content is responsible for the reduction in blood pressure induced by olive oil, Proc. Natl. Acad. Sci. U.S.A. 105 (37) 13811-13816. https://doi.org/10.1073/pnas.0807500105 (2008).
15. Peter Jandus. Arachidonic acid metabolism and its use in the diagnosis of mastocytosis[J]. AIMS Allergy and Immunology, 2023, 7(1): 82-91. doi: 10.3934/Allergy.2023006
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17. Okutan G, Sánchez Niño GM, Terrén Lora A, López Oliva S, San Mauro Martín I. Exogenous Supplementation with DAO Enzyme in Women with Fibromyalgia: A Double-Blind Placebo-Controlled Clinical Trial. J Clin Med. 2023;12(20):6449. Published 2023 Oct 10. doi:10.3390/jcm12206449