Confused by a negative histamine test result?


A negative histamine result doesn’t rule out mast cell disorder or some kind of chronic inflammatory condition. 

When I arrived to meet with my new doctor at the Virgen del Valle hospital in Toledo, Spain, I was a little surprised by the tests they ordered to diagnose me with mast cell activation.

While very thorough in testing that would exclude other diagnoses, I was unhappy to see that n-methylhistamine, prostaglandin d2 and interleukins were not on the list. Having seen the list of tests recommended by doctors in the US (Dr. Theoharides at Tufts for example), I didn’t see how we could paint an accurate picture of what was going on with me, but by that point, I was there and ready to get on with it no matter what. After a five and a half hour consultation during which I presented my medical history, previous tests, photographic evidence and went over the new diagnoses we had excluded, I was diagnosed with MCAS (mast cell activation syndrome). Though my symptoms were so much better by that point, really so much better, there was a feeling that it might be a temporary remission due to the extreme diet I was on. I was prescribed a mast cell stabiliser called sodium cromolyn [1], which I was told would help me eat a “normal” diet.

Rather than take it, I chose to try a natural mast cell stabiliser made from a bioflavonoid called quercetin, which is found in many plant foods. First the Twinlab quercetin and vitamin c and then Neuroprotek, created by mast cell researcher Dr. Theoharides. Both relieved my symptoms immeasurably, the latter far more than the former. I was later told by mast cell specialist and dermatologist Dr. Grattan in London that the definitive diagnosis of mast cell activation comes after a resolution of symptoms thanks to sodium cromolyn. He had no opinion on quercetin as a treatment, despite it being shown to be more effective than sodium cromolyn at preventing mast cell degranulation in medical studies [2].  I think this was more of an issue of my seeing him as an NHS patient (i.e. for free) and it not being an approved treatment.

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

Take the hassle out of meal planning and healing histamine with this four week meal planner and stress relieving program. 

Given that every test I have ever taken in my life has come back negative, I really wouldn’t have been surprised to see mast cell ones come back that way too. And that’s what happens to a lot of people. Now, it may be that histamine/mast cells aren’t their issue, or just that their doctors don’t know enough about them to diagnose it, or that the tests were done when they were not reactive (tryptase for example often comes back negative unless “caught” during a mast cell/allergy crisis). Some in the states will diagnose on just symptoms and remission of symptoms once taking sodium cromolyn, but unless they’re mast cell specialists, they may be doing their patients a disservice. That’s because histamine excess/mast cell activation can be secondary to a primary infection or health dysfunction, so doctors need to be sure they’re not missing something.

The team that saw me in Spain had at the time treated more mastocytosis patients than anyone in the world. 

I keep asking my readers to keep in mind that even if we’re dealing with histamine intolerance, which is characterised by high plasma histamine and low histamine degrading enzyme (diamine oxidase), ignoring other sources of inflammation is a mistake.

Histamine is just one of many inflammatory mediators released or synthesised when mast cells break open in a process called degranulation. This happens when healing needs to take place and for many other reasons. So a bunch of other inflammation causing molecules are dumped into the blood stream along with the histamine.

As outlined in my post on diagnosis, immunologists, allergists or dermatologists with experience in mast cell diagnosis will often recommend a number of tests to paint a full picture.

Please, also remember, test results may come back negative if you are not reactive when getting tested!

A few I’ll highlight for the purposes of this post:

N-methylhistamine: a 24 hour urine collection test. Plasma histamine is rarely a good indicator because histamine fluctuates throughout the day. Hence the 24 hour collection being used by specialists.

Prostaglandins: they can fight or encourage inflammation. PGD2 is synthesised when mast cells degranulate and has been linked to hair loss [2].

Interleukins: like prostaglandins, these signalling molecules can fight or enhance inflammation. They have been linked to an increased risk of cancer [3]

Dr. Theoharides specifically recommends testing IL-6 and TNF.

Here’s the thing. You can have a normal histamine level, but high prostaglandins or interleukins. That might indicate that you have some kind of mast cell degranulation going on.

But also, and here’s what blew my mind when I first read it years ago, is that prostaglandin D2 (PGD2) has been shown in studies to enhance the release of histamine from human mast cells [4] and in one particular animal study to increase by 1000 times the effect nasal histamine in rats [5].

So whatever is going on with you histamine-wise, if your prostaglandin is off, the histamine you have or are exposed to, is going to be much more potent in its effects on the body. Foods that fight prostaglandin induced inflammation are in all of my meals! 

Interleukins and histamine also have a complicated relationship that I would love a doctor to explain to me it its entirety [5]. I’m hoping to develop a relationship with a mast cell doctor whereby I can go talk to them once a month to get their feedback and explanation of the intricacies of the research I’m reading when I move to the states in February (visa gods willing!)

I also recommend reading my post on COX induced inflammation and how I fight it with foods. 

This is one of the reasons I started thinking of my recovery in terms of the inflammation rather than histamine bucket. In this model, rather than it just being histamine or histamine releasing triggers and foods going into the bucket that eventually spills over, it’s a bucket where everything that causes inflammation generally causes us to spill over. Which is why eliminating histamine, at the expense of superior nutrition, or just rather than going on a anti-inflammatory diet alone, is not the best approach in my opinion. You’ll find more in my post here where I explain how following this approach is helping me heal. 

By all means, trigger avoidance is a great idea, especially when starting out. But continued avoidance of triggers at the expense of weakening our body’s nutritional defences, an approach I followed to my detriment for the first few years, is not.


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

Take the hassle out of meal planning and healing histamine with this four week meal planner and stress relieving program. 

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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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