Dr Joneja's Guides to Histamine Intolerance

Dr Janice Joneja, a world expert on histamine intolerance, has published two books on histamine intolerance:

A Beginner's Guide to Histamine Intolerance – read more about it here.

Buy the paperback from Amazon here; buy the e-book from Amazon here.

Histamine Intolerance: The Comprehensive Guide for Healthcare Professionals – read more about it here.

Buy the ebook from Amazon here.

You can buy all of Dr Joneja's books here in the UK or here in the US.

Histamine release mechanisms
Dr Joneja takes the opportunity to explain some of the scientific processes involved in histamine intolerance and mast cell activation disorders that so many people find somewhat confusing.


I suffer from histamine intolerance and quite severely at that. I suspect I may also suffer from a degree of mast cell disorder. I follow a very strict diet, although I have yet to find the strength to give up chocolate. I very much want to widen the range of foods I eat but can't seem to get to a point of tolerance to do that.

I have recently been prescribed Nalcrom by a specialist doctor to see if it helps. Nalcrom acts only within the GI tract to inhibit antigen-stimulated release of histamine by the intestines.

I have always for years assumed that histamine-releasing foods could stimulate histamine release at sites throughout the whole body via antigen exposure within the blood. However it has started to ocur to me that histamine-releasing foods may simply act in the GI tract alone and that it is the lack of endogenous DAO within the GI tract allowing for absorption of the excess histamine from the GI tract into the systemic circulation that results in histaminosis. Which of these two mechanisms is believed to be the actual mechanism at play in histamine intolerance?

I am hoping it is the latter. If so then in theory Nalcrom should enable me to eat any histamine-releasing foods which would be incredible. I am thinking that the fact that DAOSin and Histame are marketed as having the capacity to deal with both histamine-containing and histamine-releasing foods in the GI tract and since the enzyme cannot be absorbed and can only mediate its action in the GI tract that this infers the latter of my two queried scenarios is the correct one. I just can't seem to find any obvious literature stating the actual bodily site of histamine-release triggered by histamine-releasing foods.
I would greatly appreciate any insights you might have?

Dr Joneja says:

Thank you for your question, which gives me a nice opportunity to explain some of the scientific processes involved in histamine intolerance and mast cell activation disorders that are becoming rather confusing to people in general.

First of all, Nalcrom, or sodium cromoglycate, is a mast cell stabilizer.  Like other mast cell stabilizers such as ketotifen, it acts by making the mast cells less able to release the granules within the cell that contain inflammatory mediators, one of which is histamine.  It is commonly used in cases of gastrointestinal allergy where allergens (usually in food) couple with IgE antibodies on the cell surface, leading to degranulation and mediator release into the surrounding tissues.  Nalcrom therefore will only control histamine release in the gastrointestinal tract when the source of the histamine is the primed mast cell.  I am assuming that your doctor prescribed the Nalcrom for you on the assumption that you might have a mast cell activation disorder which could result in excess mast cells in the digestive tract.  The Nalcrom would help to reduce the release of mediators from these mast cells and thus help to decrease the amount of histamine released in the area. 

You are correct in stating that diamine oxidase (DAO) acts within the digestive tract to break down excess histamine.  In fact it is thought, based on scientific evidence, that only 1% of histamine in the digestive tract is absorbed into the body when normal levels of DAO are present in the jejunum and ileum.  The histamine is usually contained in food and beverages with a high histamine content, but DAO would obviously break down histamine from any source within the gut.  However, there are other sources of DAO, namely the kidneys and thymus, which would indicate that excess histamine is also controlled at sites distant from the GI tract.  In addition, histamine N-methyl transferase (HNMT) has the capacity, albeit rather limited in comparison to DAO, to break down histamine and is found in various sites within the body, including the stomach, lungs, thymus, kidneys and brain.

DAO supplements such as DAOSin and Histame deliver DAO to the GI tract, thereby supplementing a person’s own level of DAO in the area.  Many people find this extra source of DAO quite effective in controlling symptoms of histamine sensitivity, or intolerance, while following a histamine-restricted diet.  However, it is rare that the supplement alone will allow a person with a DAO deficiency to consume a “normal” diet - typically one with several sources of histamine.  DAO supplements work most effectively in conjunction with a histamine-restricted diet  - see this article.

The definition of “histamine-releasing foods” is rather confusing because many of the mechanisms associated with histamine release when allergy and other histamine sources are ruled out are still somewhat obscure. There is evidence that histamine from foods such as strawberries and other berries is a result of the presence of benzoates that in some people results in histamine release. Other benzoate-containing foods such as tea have a similar effect.  Tartrazine, and other azo dyes have also proven to result in a rise in histamine, so these should be avoided on a histamine-restricted diet.  People sensitive to sulphites tend to experience a rise in histamine levels after consuming foods containing this additive, so a successful histamine-restricted diet will exclude benzoates, tartrazine and sulphites in addition to histamine-rich foods and beverages.  There is no evidence at present that would suggest that any of these sources of histamine would be controlled by stabilizing mast cells with Nalcrom.  Unfortunately, there is no scientific evidence that would help us to determine the site of the release of histamine in these processes at the present time.  Because research indicates that histamine levels rise in plasma when benzoates, tartrazine and sulphites triggers the response, it would be logical to assume that histamine release is within the body rather in the digestive tract, so your hope that Nalcrom might allow you to consume histamine-releasing foods is unfortunately without foundation as far as we know at present.

The histamine-restricted diet that I have developed as a result of careful research eliminates all the known sources of histamine-containing and histamine-releasing foods, additives and beverages, so you should be able to remain symptom-free as long as your reactions are due to histamine excess alone.  If any of your symptoms are a result of reacting to inflammatory mediators other than histamine, for example prostaglandins, leukotrienes, several specific enzymes and other reactive compounds released from mast cells, you will still experience adverse effects on a histamine-restricted diet.  However, these should be reduced by taking Nalcrom to limit their release.

April 2016

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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Dr Janice Joneja, Ph.D., RDDr. Janice Joneja is a researcher, educator, author, and clinical counsellor with over thirty years of experience in the area of biochemical and immunological reactions involved in food allergy and intolerances. Dr. Joneja holds a Ph.D. in medical microbiology and immunology and was a registered dietitian (RD) – now retired. 

She has been a member of the faculty at several Canadian universities, starting her career as an Assistant Professor in the Department of Microbiology, Faculty of Science, and in the Faculty of Dentistry, at the University of British Columbia, Vancouver. Since 2001 Dr. Joneja has been a faculty member in the School of Biomedical and Molecular Sciences, at the University of Surrey, in England, teaching in the M.Sc. course in Nutritional Medicine.  For 12 years she was head of the Allergy Nutrition Program at the Vancouver Hospital and Health Sciences Centre.

Dr. Joneja is the author of six books and a dietetic practice manual on food allergy, a textbook on Irritable Bowel Syndrome, and several distance education courses. Her most recent books include “The Health Professional’s Guide to Food Allergies and Intolerances”, “Dealing with Food Allergies”, and “Dealing with Food Allergies in Babies and Children”.  Dr. Joneja’s work has been published in peer-reviewed scientific and medical journals, as well as in popular magazines.  She is a respected lecturer at universities, colleges and hospitals internationally, and regularly appears on television and radio call-in shows as an expert in her field.

Dr. Joneja is President of Vickerstaff Health Services, Inc., a practice that provides counselling for people suffering from all aspects of adverse reactions to food, and resources for the professionals and care-givers who support them.

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