New Study Finds DAO Deficiency Accounts for Over 70% Of All Histamine Intolerance

November 21, 2015  |  Histamine Intolerance

A study just published on 16 November 2015 has confirmed that DAO deficiency remains the leading cause of histamine intolerance.

The study was conducted using 14 patients from one Italian hospital clinic. The participants were selected from past patients whom had benefited from a low histamine diet.

Patients had a blood DAO test, and 10 of the 14 study participants, had on average less than one fifth of a healthy person’s DAO.

The study concluded that in patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity, can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.

The study also demonstrates that DAO deficiency is the primary cause of intolerance to histamine-rich foods.


DAO (diamine oxidase) is the main enzyme involved in the break-down of histamine.

It is mostly concentrated in the small intestine where most food is ingested and food derived histamine is degraded.

DAO deficiency occurs where DAO in the small intestine is insufficient to metabolise ingested histamine in the diet. This means that histamine tolerance is lower in these individuals.

How DAO Deficiency Is Acquired

DAO deficiency can also be acquired through:

– Genetic DAO mutation (although the precise enzyme has yet to be identified).

– DAO inhibiting medications.

– Alcohol consumptions (which is a DAO inhibitor).

– A compromised gut lining; including NSAID intolerance, coeliac or gluten intolerance, bowel disease, or leaky gut.

– Vitamin b6, vitamin c, and copper deficiencies.

Other Causes

Other causes of histamine intolerance include other enzyme deficiencies, mast-cell activation, and mastocytosis.

Within my practice, the most common differential diagnosis for histamine intolerance includes SIBO, mineral deficiencies, and adrenal and hormone imbalances.

Additional Reading

Manzotti G, Breda D, Di Gioacchino M, Burastero SE, Serum diamine oxidase activity in patients with histamine intolerance, Int J Immunopathol Pharmacol. 2015 Nov 16. pii: 0394632015617170.

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  • Alicia Palmer

    You are an absolute life saver!!!
    Thank you so much for sharing your knowledge and insight with the rest of the world.
    I have been searching the internet for years about histamine intolerance. I have had so much trouble finding a reliable source for food lists that are based on scientific evidence and not someone’s personal experience. I have downloaded your free histamine intolerance food list, and I am so excited to compare it to all my other lists I have sourced over the years. I’ve only read 2 of your blogs so far, but will be pleased to spend the rest of the day perusing your website. I have never commented on anything on the internet before, but I felt too overwhelmed with joy not to. I too live in Australia, on the Mid North Coast, and it’s so refreshing to read information on this topic from an intelligent Aussie!

    Thank you, thank you, thank you!!!

    • Hi Alicia thanks so much for your kind comments. Welcome.

      • yvonne

        Why don’t you suggest the enzyme use?

        • This blog article is not about a treatment protocol. DAO enzymes can be used if you have DAO deficiency. However, they are expensive, some people do not tolerate them, and they are only a bandaid. I prefer to remove the cause – with most histamine intolerance in my opinion being reversible and only a small portion being genetic.

          • yvonne

            Yes, they are expensive that’s why I asked, I hate to keep throwing money away on supplements. Thanks, your opinion helps!

  • Sara Fiser

    Your blog is amazing! Thank you for sharing all this information! I have had many symptoms of a mast cell disorder most of my life. I only recently began to put the pieces together when my symptoms increased alot during perimenopause. My naturopath clued me into histamine intolerance, which started me researching and recognizing myself in so much of the mast cell disorder info. I couldn’t believe it! Maybe there is a reason for all these oddities! So, my naturopath suggested SIBO as the root of my issues. However, I do not have much in the way of gi issues at all, other than extremely bloated belly many days. No gas, or other bowel issues. I am ‘regular’ daily with no stomach aches. My bloat coincides with my cycle. So, my question is how to best find out if I have a mast cell disorder due to a genetic issue, or if I have SIBO causing all of this. Naturpath suggested hydrogen breath test to dx SIBO. I am reluctant since I don’t have SIBO symptoms. Thank you again for all this great information! I have devoured every post!

    • It is not possible for me to give specific advice on this blog. I believe that histamine intolerance can be greatly improved (if not resolved) through addressing underlying health. Lab testing is required to do this. You are welcome to make an appointment if you need help. Check the diagnosis tab above for how to get diagnosed for MACD.

    • Sara Fiser

      Of course. I will probably print this post and take to my family doctor. Naturopaths are not recognized in Ohio. 🙁 Are you able to help with dx from another continent?
      Thank you!

  • Michelle

    Hi Alison
    Thanks so much for your fantastic blog that I have been following for many months now. Alison why can’t we get DAO enzyme in Australia – I understand it’s not TGA approved is this correct? I see that it’s available from overseas is this the only way to access it in Australia or do some naturopaths/doctors have the capacity to prescribe it?

    Thanks so much for the wonderful information you provide!


    • Hi Michelle nice to hear from you and I am glad what I am providing is helpful (I feel a little guilty I have not had more time lately to write some more posts).

      I am not sure who told you you cannot get the tests in Australia and that they are not TGA approved because yes you can! Here they are;

      DAO ; You can just order it direct and ask for it to go to your doctor/naturopath.

      HNMT (extra-cellular histamine); methyl histamine (urine) from Healthscope.

      I can help with most testing also.

      with thanks

      • Michelle

        Hi Alison

        Thanks I actually mean the DAO enzyme that’s sold overseas. I’ve tried to buy it in Australia but have been told it’s only available by ordering in via post. I find this very difficult to understand when studies like the one in this post demonstrate its efficacy. Seems that it’s taken before meals just as you’d take lactase for lactose intolerance. Have you experienced this issue In buying DAO enzyme Alison?

        Thanks again & really appreciate you taking the time to reply too!


        • Oh sorry I did not understand I rarely suggest/use these enzymes so I am not aware of whether they are sold in Australia or not. When I have suggested them I have just ordered via the web. with thanks Alison

          • Michelle

            Thanks Alison!

    • sleeping_sheople†††

      You can also get dao from green pea sprouts get sprouting jars put half a cup of sprouts in jar soak 12 hours drain and rinse sprouts make sure they fully drain the put in dark cool area no light rinse 3 times a day for 10 days the eat ? cup before meals

  • Michelle

    Hi Again Alison
    I have read in a number of your posts that you work with a doctor – can you help me access a doctor assist with intolerances, I need to start there with some medical issues on board. Looking in Brisbane area Australia if possible but will travel if required Many thanks!

    • Hi Michelle I can run most tests. I do not work with anyone in Brisbane – although you might try the Qld allergy unit doctors in brisbane. They could run allergy tests but not resolve histamine intolerance. I do hope that helps.

  • Rebecca

    Hello Alison,

    Do you / are you able to, provide the tests for women living in the UK?

    What would the total costs/ charges be?

    Many thanks.

    • yes rebecca I work with people all over the world including in the UK. The cost depends on what tests we need to run so you would need to download the patient intake form and return it for me to determine.

  • michellenj

    Hi, Thanks to your site we found DAO and have a big improvement in migraine and other symptoms! The organization in Spain, DAODeficit, they have a partner organization which sells DAO and a few other related items. If you search you will find they have a patent which covers the DAO supplement, but interestingly also a topical cream and an adhesive patch! I don’t see the product on their site, but it is in the patent filed in 2011 or 2012. Do you know of any topical DAO creams??? I have been told that DAO remains in the gut if taken orally and does the job of breaking down L-histidine, but that it does not escape into the blood stream. Might be very helpful if there was a transdermal option to further help break down L-histidine in serum before HDT got a hold of it! I wonder if the molecule is small enough for transdermal delivery, you’d think they would have checked that out before patent.

    • hello michellenj glad that DAO supplementation has helped you. I suspect that they have not commercialised the product het. However you could check with a compounding pharmacy. In terms of histamine outside of the gut it is my understand we are mostly concerned with HNMT.

      • michellenj

        Thank you, yes, we are working on supporting HNMT with supplements. I had just been thinking how super wonderful I felt during pregnancy, due to now I know high DAO. That DAO gets into circulation via the placenta. I was looking at a chart of the levels which increase dramatically in the first trimester and then level off high and then dip again towards the end. I wonder if that is why you get so tired first thrimester and why it goes up gradually. Reminded me of the way you have titer up doses of Amitryptiline slowly (been on that for migraine). You feel very tired each time you incrementally raise until you reach final dose. Then body adjusts. I am in NJ, I am going to fill out your patient intake form. You can do labs remote to US, right? I want stool testing for h.pylori and other gut infections, and urine acid test and tryptase (and whatever you recommend). Suspect mast cell activation

      • michellenj

        Allison, here in the US we had been able to purchase DAO capsules. Supply has completely dried up from all sources. Are there any in Australia or any other international location you are aware of??? Some really desperate people with migraine and cyclic vomiting syndrome seeking it.

        • Oh dear. They are not sold in Australia. I’m not sure of an alternate supply (the one I often recommend is out of stock).