Diagnosing histamine intolerance & mast cell activation

diagnosing histamine intolerance

I’ve been told, by a number of doctors, that it takes, on average, a decade to diagnose someone with a mast cell disorder. I personally consider histamine intolerance to be a mast cell disorder. It took me almost 30 years and 68 doctors to get to histamine intolerance, and then another three years and two doctors to get to mast cell activation disorder. To complicate matters, many are diagnosed with a mast cell disorder, despite suspected mastocytosis, only because they have not had a bone marrow biopsy or comprehensive testing within an hour of having a serious episode (ie anaphylaxis).

No matter the diagnosis, I believe, and have seen, that histamine/mast cell disorders, are totally manageable through dietary changes, a healthy but low impact exercise regime, regular meditation and stress management, and a whole heap of positivity – with or without meds. I don’t take meds.

Don’t just take my word for it, check out my testimonials page and my interview with leading mast cell expert Dr Castells (on the role of diet and exercise in mast cell disorders).

diagnosing histamine intolerance


Diagnosed by: nutritionists, GPs/primary care physicians, functional/integrative medicine doctors.

You’ll have a tough time convincing: allergists and immunologists that it exists.

Best countries for diagnosis: Germany, Austria, UK.

Histamine Plasma

What it is: the level of histamine currently found in your blood.

Why measure it: histamine intolerance is thought to be too much histamine in the body.

Reliability: given that histamine is found in the body as well as food, and is released by mast cells (white blood cells) as needed to wake us up, control appetite and metabolism, as neurotransmitter, and much more, any doctor worth their salt will tell you that histamine fluctuates wildly in your body, and as such this is not a reliable test of your average histamine level.

DAO (diamine oxidase)

What it is: DAO is an enzyme found in the gut. It’s responsible for degrading histamine there.

Why measure it: the theory is that low DAO makes it hard/impossible to clear histamine from the body, leading to histamine intolerance/symptoms of high histamine.

Reliability: DAO is one of two histamine-degrading enzymes we know of (HNMT being the other), therefore just relying on DAO as a measure isn’t likely to give us the full picture. Throw in the fact that DAO also fluctuates wildly, and that we don’t know where else, other than the gut, DAO might live, and whether we’re even measuring it in the right spot! I also always point out to people – if you’re not eating high histamine foods anymore, why is there still so much left (supposedly) for DAO to eliminate? Read on for the answer.

Elimination diet

What it is: a four-week elimination of all foods on the high histamine lists.

Why try it: the theory is that no matter the test results, if eliminating these foods makes you feel better, you have your answer.

Reliability: let’s start with the fact that all high histamine food lists contradict each other, that many high histamine foods are also junk/bad for you generally, so cutting them out would make most people feel better anyways, and that restricting foods is rarely healthy. Add in that most people, sadly, are told that they must continue restricting these foods, thereby starving themselves of nutrition, thereby further weakening their body and ensuring they will continue to react.

You’ll find recipes full of foods with antihistamine and anti-inflammatory properties my books Anti-Recipes and The Anti-Cookbook


Histamine prick test

A study on the prick test method to print for your doctor.

What it is: Austrian docs figured out that injecting patients with histamine causes a significant reaction (when compared to controls) and as such is a reliable way to diagnose patients with histamine intolerance.

Why try it: my allergy scratch tests came back negative for years, but docs always commented on my unusually severe response to the control (pure histamine!). I would be very careful if you have ever had major reactions and good luck convincing a doc to do it for you!

Reliability: I can’t really speak to this one as I don’t have enough information on it yet.

Ok, a final word on why all these tests must be taken with a pinch of salt: histamine, an inflammatory agent in the body, is contained within mast cells. Mast cells, white blood cells that are an integral part of our immune system, also contain dozens of other inflammatory elements, that are not addressed in the tests above. I continue to say, that focusing on just histamine as a method of diagnosis, treatment, or diet, is the BIGGEST mistake anyone can make. I made it myself, for many years, and continued to get sicker.

Once I researched why mast cells release too much histamine in the first place, I understood I needed to widen my scope to inflammation in general, rather than just histamine. I talk about this in depth in the Anti-Cookbook.


Diagnosed by: functional/integrative medicine doctors, immunologists, haematologists, some allergists (rare though), some GPs (also very rare).

You’ll have a tough time convincing: European doctors who deal in mastocytosis, nutritionists (may fob you off with an inaccurate diagnosis based on symptoms).

Best countries for diagnosis: United States, Spain (Virgen del Valle Hospital in Toledo).

Mast cell activation syndrome is usually diagnosed (mainly) on the basis of symptoms and exclusion of all other possible diagnoses. Mast cell activation disorder usually requires a number of positive tests (see below).

Diagnosing mast cell activation syndrome

“Diagnosis of MCAS is often difficult for many reasons, principally the cognitive challenge it poses to the diagnostician. The average physician is capable of considering only a handful of clinical elements at a time when attempting to recognize diagnostic patterns of presentation (e.g., fever, night sweats, and hemoptysis suggest a possibility of tuberculosis).

Temporal factors are important to human cognition, too. The human mind is increasingly challenged at recognizing patterns when events occur with less temporal regularity and less temporal proximity to one another. Furthermore, repetition of presentation is key for diagnostic efficiency. The physician who repeatedly sees the same set of elements present in the same temporal pattern will be able to recognize the same pattern more efficiently in the future.

MCAS, though, seems almost artificially engineered to confound diagnosticians. Its great menagerie of underlying activating mutations, combined with the mast cell’s normal function of producing and releasing a cornucopia of highly potent mediators (each with multiple direct and indirect, local and remote effects), ensures a tremendous range of clinical presentations. Once a full history is obtained, it is evident that the average MCAS patient presents with a large number of symptoms and findings, and many of these presenting elements wax and wane over time periods ranging from minutes to years, often with no clear temporal relationship to one another.” – Dr Afrin.

Criteria for diagnosing mast cell activation

(You could just print this document off and take it to your doctor)

Mast cell activation syndrome is mainly diagnosed on the basis of symptoms:

As per Dr Afrin:

(1)…the general presenting motif of MCAS is chronic multisystem polymorbidity, generally of an inflammatory theme and with assorted elements waxing and waning over time, sometimes in synchronization with one another but more often cycling with different periods and amplitudes.

(2) When there are symptoms and findings not classically expected with, or not easy to attribute to, the patient’s established diagnoses, alternative diagnoses must be entertained to account for these “leftover” elements, and given the universal truth of Occam’s Razor, it becomes more likely that the same diagnosis that accounts for the leftover elements also accounts for the established diagnoses.

(3) The range of mast cell mediators and their effects is so great that “unusual” presentations actually become de rigeur. That is to say, although any given unusual presentation remains unusual, the full set of unusual presentations constitutes a large fraction of the total set of presentations. Thus, when the clinician recognizes an “unusual,” “odd”, “weird”, “bizarre,” or “strange” element in the patient’s presentation–e.g., “allergies” to typically innocuous medications, migratory rather than dependent edema, severe and highly variable hyperferritinemia not attributable to the patient’s transfusion and chelation history, etc. – his “MCAS radar” should go on alert. The presence of an unusual element in the presentation by no means establishes a diagnosis of MCAS, but it sometimes can be the first spark toward lighting a fire of recognition.

Thus, the largest impediment to diagnosing MCAS may simply be suspecting it.

As per Dr Theoharides

(From a recent presentation)

(1) Dermatologic: flushing, pruritus, urticaria pigmentosa, angioedema, dermatographism (sometimes)

(2) Respiratory: wheezing, sore throat

(3) Cardiovascular: chest pain, hypotension, tachycardia

(4) Gastrointestinal: abdominal pain, nausea, vomiting, diarrhea, bloating, malabsorption, esophagitis

(5) Naso-ocular: nasal stuffiness, pruritus

(6) Neurologic: headache, memory and concentration difficulties/brain fog, paresthesia, peripheral neuropathy

(7) Muscoskeletal: bone/muscle pain, degenerative disc disease, osteoporosis/osteopenia

(8) Systemic: anaphylaxis, fatigue

Diagnosing mast cell activation disorder

All the symptoms and indications above, plus positive:

N-methylhistamine 24 hour urine test

Prostaglandin D2


Tryptase (this doesn’t have to come back out of range, it’s usually done to rule out mastocytosis)


Diagnosed by: functional/integrative medicine doctors, immunologists, haematologists, some allergists (rare though), some GPs (also very rare), dermatologists (mostly in the case of cutaneous mastocytosis or urticaria pigmentosa).

You’ll have a tough time convincing: nutritionists (may fob you off with an inaccurate diagnosis based on symptoms), almost any other kind of doctor.

Best countries for diagnosis: United States, Spain (Virgen del Valle Hospital in Toledo), United Kingdom.

Diagnosing mastocytosis

As per Dr Afrin

(1) Multifocal or disseminated dense infiltrates of mast cells in bone marrow biopsies and/or in sections of other extracutaneous organ(s) (CD117-, tryptase-, and CD25-stained)

(2) Unique constellation of clinical symptoms secondary to a pathological increase in mast cell activity (mast cell mediator release syndrome)

 Minor criteria:

(1) Mast cells in bone marrow or other extracutaneous organ(s) show abnormal morphology (>25%) in bone marrow smears or on histological examination

(2) Mast cells in bone marrow express CD2 and/or CD25

(3) Detection of genetic alterations in mast cells from blood, bone marrow, or extracutaneous organs, which have been confirmed to result in an increase in the activity of affected mast cells.

(4) Evidence of a pathological increase in mast cell activity through detection of an elevated level of at least one sensitive mast cell-derived mediator, i.e., tryptase, heparin, histamine, PGD2, chromogranin A, leukotrienes (and their assorted metabolites) in blood and/or urine

You’ll find recipes full of foods with antihistamine and anti-inflammatory properties my books Anti-Recipes and The Anti-Cookbook


Please don’t forget antihistamine, pain killing foods can still hurt us, so please always check with your doctor before adding new foods to your diet. 


Check out these other Healing Histamine blog posts


Yasmina was an award-winning broadcast journalist with a decade of experience covering war zones for CNN and the BBC. She devoted her journalism skills to researching and writing about histamine. Click here to learn about her. Each post is carefully and fully referenced with the latest scientific research. Not sure where to start? Here’s a four week meal plan and overall Histamine Reset.

4 Week Histamine Reset

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