Could it be histamine?
Nutritionist Micki Rose looks at the symptoms, possible causes and ways to diagnose and treat histamine 'intolerance'/excess

As a clinician, I suggest two things to people if they are suffering chronic illness.
The first is a biochemical liver and gut MOT with a wheat and dairy free diet. The second is to look for four key types of food sensitivity: gluten, fructose, lactose and histamine.

Obviously, things are a LOT more complex than that, but I always find that makes a good start. Most things I have come across over the years have gut, liver, toxicity and sensitivity at the heart of them somewhere. To heal, therefore, a person needs to remove key sensitive food types (and environmental substances in some cases) to lower inflammation generally, and re-heal a usually very leaky gut and other body barriers.

As I know many of you are acutely aware, looking for food allergens is like looking for a needle in a haystack, but looking for gluten, fructose, lactose and histamine sensitivities – any or all of them – gives you a place to begin. Once you know, you can then get an idea of what diet you need to enable optimal healing.

Testing The Key Four

Diet trial is always the gold standard, but sometimes people (and even more often their partners and families) need to see it on paper. It helps them make the emotional switch from ‘Am I going mad?’ to ‘Ah, I KNEW there was something wrong!’

I could wax lyrical on the confusion surrounding proper gluten testing. Suffice to say: a negative coeliac test or biopsy does not rule out gluten related disorders like non-coeliac gluten sensitivity. It doesn’t even rule out coeliac disease necessarily. I mostly advise diet trial and full DQA and B gene testing nowadays if a coeliac test is negative.

Fructose malabsorption can be tested via a simple breath test.
For lactase deficiency, you can do a genetic cheek swab and/or a breath test.
For dairy allergy, use IgE antibody or via GP, and/or skin prick/RAST test.
For dairy intolerance: diet trial and, if necessary, test for IgG, IgA and/or IgM antibodies.

The one most people don’t tend to think of, though, is histamine. So I shall concentrate on this lesser-known one of the key four..

Histamine Intolerance (or Excess)

This is commonly called histamine ‘intolerance’, but is actually a condition of histamine excess. It is also known as Histaminosis and is shortened to HIT.

There are some estimates that up to 10% of the population suffer from some degree of histamine sensitivity and possibly 2% who have severe histamine excess. Basically, we need histamine. It’s just that some people can have too much in their system and they overload, triggering the classic histamine symptoms that include mood changes, head pain, hives, sensitivity reactions etc.

In essence, there are three main routes to histamine excess that I see in-clinic – there are probably others, but these are the ones I come across.

Poor Methylation

For years, testing histamine levels for me, as a clinician, has meant looking for signs of a methylation problem in cases of depression and OCD (Obsessive Compulsive Disorder).

Methylation is a key body process that happens millions of times a day. It helps repair DNA, regulates homocysteine levels (and therefore your risk of cardiovascular problems), is needed for detoxification of certain molecules (including histamine) and controls inflammation. It is entirely dependent upon having the right level of B vitamins in the right place at the right time.  

According to research by Dr Carl Pfeiffer in the 50s, some people don’t methylate well enough during liver detoxification. This means they over-produce and over-retain histamine, resulting in an excess of histamine in the blood. He called this ‘histadelia’ and describes it as an inherited disorder which usually shows itself in compulsive behaviours, anxiety and depression as well as increased allergic reactions, headaches, itching etc .

Symptoms of histadelia tend to include mood disorders like depression, OCD and SAD (Seasonal Affective Disorder) because methylation is partly needed for the production of serotonin. Sufferers are often quite perfectionist and competitive. They are fast oxidisers, so often need ‘highs’ like alcohol, sugar, carbs etc and they use up nutrients pretty fast so are hungry a lot! They tend to be very low in calcium, magnesium, methionine, and B6 with excessive levels of folic acid. In fact, folate and B12 can make people feel much worse – and I use that as a clue for HIT if someone mentions it.

Methylation testing

People tend to assume poor methylation if blood histamine levels are too high but, as you can see below, there are other causes of high histamine, so that assumption is not really good enough.
I prefer a homocysteine test (if raised, you are more than likely under-methylating) or urine metabolic analysis, which gives a specific methylation rating you can then track.

Enzyme Deficiency

In some people, a histamine excess may result from enzymatic issues in the body.

A person might have a problem producing the DAO (diamine oxidase) enzyme that helps break down histamine in the body so you get a build-up of histamine and the consequent symptoms.
They might not have enough Monoamine oxidase-b (MAO-b) either, another enzyme required to help break down histamine during metabolism.
Or, they might not produce enough Histamine N-methyltransferase (HMNT), which inactivates histamine, so their histamine remains very active.
They could even have too much Histidine decarboxylase, an enzyme that converts histidine into histamine, so they are very efficient at making histamine.

Of course, they might have none, one or all of those going on!

Enzyme testing

You can test DAO in plasma and I advise it combined with a whole blood histamine test so that you can see the balance between the two results. It’s not perfect, by any means, but it can give an easy answer for some people, and, to be honest, it is relatively simple to get a test, unlike the rest of the enzyme problems.

The DAO enzyme level will tell someone if they have enough of it or not at the point of testing and the whole blood gives them the levels of histamine they have in their body. People often do comparative tests - when they can feel their histamine is high and again when they are not feeling so reactive.

If the histamine is high and there is a lack of DAO, then low DAO is likely involved, although you could have normal levels of histamine and low DAO and that’s sometimes enough. It’s the difference between how much histamine there is and the ability to break it down, really. Some experts swear by it; others question it since DAO is thought to fluctuate in the body quite a bit.

I believe testing for MAO-b, methyltransferase and decarboxylase can be done by some specialist labs, but I haven’t got that far yet.

Diet trials

It’s important to note that, if there is a suspicion of histamine intolerance, we do the DAO/whole blood test to see if we can get an easy answer but, even if the results are negative, it’s best to trial a low histamine diet if the clues are there. If the person responds well, you have an answer. As always in ‘intolerance’, the diet is the gold standard test; the body normally tells you what’s what.

Small Intestinal Bacterial Overgrowth (SIBO)

It’s well known that some people have too much bacterial activity and fermentation in the small intestine. What is perhaps less well-known is that some by-products of that bacteria are thought to trigger histamine.

Clues that a person may have SIBO might be fatty stools, diarrhoea, malabsorption especially of carbohydrates, bloating and nutrient deficiency.

It might actually be the same issue lower down in the gut where dysbiosis – an imbalance of bacteria – can lead to a prevalence of bacteria that feed off undigested foods and release histamine in the gut.

Either way, worth looking for and doing something about. You can do a breath test for SIBO and a stool test for colonic bacteria levels. A CDSA can give you indications of both.

What Else Should I Consider?

I suspect much of the problem behind HIT is genetic predisposition, but I am beginning to wonder if it is acquired too in some people.


There is clearly a gut link. DAO is produced by intestinal cells in the gut lining so, yet again, we have gut involvement in chronic disease and we need to think about what is affecting the cells’ productivity levels and, very probably, the gut lining. People with inflammatory bowel disorders are known to have lower DAO and H pylori infection makes things worse.

My specialist area is gluten sensitivity and one thing we do know is that gluten can cause inflammation and auto-immune damage to pretty much anywhere in the body. We know it can affect the parietal cells in the stomach, for example, and people then go on to have problems producing stomach acid and intrinsic factor etc.

Does the gluten – or something else entirely - damage the enzymatic processes in some way or are we just born that way? I suspect there is a genetic predisposition that gets ‘switched on’ by the usual triggers – allergy, stress, drugs, viruses, environmental toxins etc - but that is pure conjecture on my part! Certainly, I am seeing quite a few HIT sufferers go on to test positive for gluten sensitivity and vice versa. Perhaps the gluten attacking the mucosal gut lining – as we know it does – is also affecting the mucosal gut cell production of the DAO. I wouldn’t be surprised.

Obviously, any amount of stress is going to have an effect on health generally and on the gut particularly, as would a poor diet, especially in relation to the gut flora levels.
Poor methylation is often the result of specific nutrient deficiencies, so are we not absorbing as well as we might? We also know that many HIT sufferers are deficient in B6, and that DAO production is very dependent on having enough B6.


Many painkillers can block DAO production or increase the release of histamine from mast cells. So can some sleeping pills, asthma medication, mucolytics, anti-hypertension drugs and antibiotics – remember the link to bacteria levels above; antibiotics are just not going to help.


It is interesting, from what I have read, that many women especially seem to become histamine intolerant in their late 40s. Is there a hormone element or trigger maybe?

Clinically, I do find that gluten sensitivity and leaky gut does seem to ‘suddenly’ show around that age – is it just that it takes that amount of time for the body to show the problem outwardly, or we have lost the ability to keep it under control by that point somehow..?

Allergen intake

The release of histamine in the body is going to be much higher in someone who is constantly taking in an allergen, whether they realise it is an allergen or not. That’s why I advise trying to find allergens if at all possible, to heal the gut to try and stop the allergens getting through, triggering the histamine reaction. If you’re already predisposed to having too much histamine, you really don’t need anything else ratcheting it up!

Treatment for Histamine Excess


In terms of treatment, I usually refer people to sites like FoodsMatter, Low Histamine Chef, Histaminosis and Histamine-Intolerance and to books by Ella Orton and Genny Masterman to learn about histamine foods first of all.

The lists do vary and people need to find their level of tolerance to histamine foods. There is no real one-diet-fits-all I have found. The best approach is to trial off the key high histamine foods and then off other food groups only if symptoms have not abated enough.

A totally histamine-free diet is impossible, I would imagine, so you are aiming at low histamine and particularly those foods that give you personally the most jip. I have come across lots of people who have tried to remove pretty much everything and have ended up with very few foods they can eat. That is not always (I hope ever) necessary but every case is different.

In most cases, histamine excess is cumulative so, if people keep really low much of the time, they can sometimes get away with small and infrequent amounts of histamine foods. Some can, some can’t: I’m making no promises! My advice is usually to bring it down really well first and then see what you can reintroduce before you reach your own individual tolerance level, then drop back a bit, continue your healing protocols and try again in a couple of months.

It’s important when you are on a restricted diet that you try and still eat plenty of nourishing foods from the different food groups like proteins, carbs and fats, and get plenty of colour to maintain antioxidant levels. It’s no good just taking stuff out without replacing it with foods and/or supplements because the whole point is to nourish the body well enough for healing and repair. I advocate at least an anti-inflammatory, mucosal barrier repair diet to calm things down and start gut repair.


In terms of medication, obviously there are anti-histamines for when you really need them. Specialists may prescribe steroids or H2 agonists, which are more commonly used in stomach problems.

There are also DAO enzyme products like DAOSin, which sadly are not grain free, but could be used by most others to increase DAO levels and thereby decrease excess histamine.


Supplement-wise, many people with intolerances are malabsorbers too in my opinion, which makes it all the more important to eat well and maintain nutrient levels – not easy on such a restricted diet.

People with histamine excess have been found to be particularly low in B6, as I noted above, so that might be one to follow up. Could you be low in Nature’s main anti-histamine, Vitamin C, maybe? Quite likely, but get a grain-free source, preferably, most are from corn. Interestingly, flavonoids like quercetin have been found to specifically help down regulate histidine decarboxylase.

I encourage a nourish/calm/repair supplement protocol generally, if people are able.
For the histadelia, there is a specific supplement protocol to follow to correct the poor methylation. Find someone who can help with that specifically if you need to. It centres around methionine which helps to detoxify the histamine in the body and calcium which releases the body stores of it. The Brain Bio Centre in London should be able to help.

In my limited experience, histamine intolerance tends not to occur in isolation. As I said at the start, my advice is to seek other types of intolerance if you are not better after a few months on low histamine.  We will never be able to identify all allergens or processes in multiple sensitives, so the aim should be to find the key ones and do all you can to repair anything found.

Good luck!


  1. For more info, use the sites and books listed. A good technical article worth reading too is: Histamine and Histamine Intolerance in the American Journal of Clinical Nutrition.
  2. Tests can be conducted via several labs such as Biolab, Genova and TDL Pathology. I have linked to some to give you more info and sample reports. You will need to go through your practitioner or via Purehealth.
  3.  DaoSin is recommended at 3 per day and this is equivalent to 15mg of Dirk Budka’s HistRelief which I believe is now out of production. You can get DAOSin at AllergyBestBuys or Sciotec. Here are the ingredients as these are difficult to find until you have bought it!

Ingredients of DAOSiN®
Stabilizer: microcrystalline cellulose; capsule wrapping: gelatin; saccharose; ascorbic acid; stabilizer: rice starch; coating material: shellac; hydroxypropylcellulose; pig kidney protein extract with 7% diamine oxidase (DAO); stabilizer: olyvinylpyrrolidone; separating agent: talc; thickening agent: acetic acid, carboxymethyl cellulose; dye: titanium dioxide; wetting agent: glycerine

If you want to contact Micki you can do so via the Pure Health site.

First published in August 2013

If you found this article interesting you can find a number of other articles on histamine intolerance both by Dr Joneja and others here, reports on histamine research here and a Q & A section on histamine with Dr Joneja here.

For many, many other articles on every type of food allergy and intolerance click here; for coeliac disease and other food related conditions, go here.

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