Testing histamine levels and evaluating potential histamine intolerance or disorders related to histamine like Mast Cell Activation Syndrome (MCAS) can involve several different testing methods, though it’s important to note that these tests can sometimes have limitations and sometimes provide misinformation.

Histamine intolerance occurs when the body is unable to properly break down histamine, a compound involved in immune responses, regulation of physiological functions, and acting as a neurotransmitter. So, I recently got an email asking about the reliability of testing for histamine. I thought this was a really good question because when we have a problem in the body, we usually can go to a doctor and we can get tested. And that testing can tell us within a certain degree of reliability, yes I have that problem or not I don’t have that problem.

So you would think that testing for histamine intolerance is like testing your blood sugar or cholesterol or checking your Thyroid. But that’s not the case when it comes to testing the levels of histamine. So in today’s article, I want to talk about Testing for Histamine intolerance in the blood and some of the problems and limitations to testing histamine levels as well as How Functional Medicine approaches high histamine levels.

Testing the Levels of Histamine

So here’s the thing…..While testing histamine levels in the blood can provide some useful information, the problem when it comes to testing histamine levels is that it’s not always the most accurate method for diagnosing histamine intolerance and histamine-related issues, and this comes down to several factors: lets take a look at three problems that related to the testing accuracy of histamine in blood.

Is Testing Histamine Levels Accurate

1. Histamine Fluctuations:

Histamine levels can fluctuate widely during the day and can be influenced by many external factors like the food you eat, your stress and cortisol levels, your physical activity, estrogen, low progesterone, DHEA and testosterone levels, gut microbiome, and allergies. This can make it difficult to obtain a single blood test result that adequately represents an individual’s typical histamine levels.

Read: Stress, Cortisol and Histamine Intolerance

2. Half-life.

Histamine has a very short half-life in the blood, meaning it is quickly broken down and cleared from the system. Histamine is normally cleared from the circulation within minutes. This rapid turnover, as you can imagine, makes it challenging to capture accurate levels with a blood draw. Due to the short half-life, histamine in the blood doesn’t often reflect or correlate with a person’s histamine levels.

The clearance of histamine from the body can vary depending on several factors, including individual enzymatic activity, particularly of diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT), both of which are crucial for histamine metabolism.

 Key Factors Influencing Histamine Levels and Clearance:

1. Enzyme Activity: Diamine Oxidase (DAO) breaks down and clears extracellular histamine in the gut or histamine produced by gut bacteria. Variability in DAO activity significantly influences how quickly histamine is broken down after consuming foods.
2. Genetic Variability: We have genes that break down histamine. Problems in these genes, called SNPs, pronounced as SNIPS, can affect how well we clear histamine. If testing for these genetic SNPs, we are looking at DAO and HNMT variants.
3. Health Conditions:  Conditions such as gastrointestinal disorders, allergies, Parasites, Intestinal dysbiois, and mast cell disorders can impact histamine levels and their clearance rate.
4. Lifestyle Factors: Diet, alcohol consumption, certain medications, antidepressants, and stress can affect histamine metabolism by either blocking DAO or increasing histamine release.

Read: Histamine Intolerance Gut Health and SIBO-Another Piece of the Puzzle

3. Accuracy of Histamine Levels Within The Tissue

When it comes to testing and treating patients, doctors have to be able to rely on testing accuracy. Otherwise, that test is just a waste of money and time. Different laboratories may use different techniques as well as different reference ranges to measure histamine levels in the blood. So this can create a problem. Another potential problem when it comes to testing histamine in blood is knowing if those histamine levels are a reflection of what’s in the tissue vs what’s just high in blood.

Let’s talk about histamine in the Brain for a moment.

Over the last few months, I have done several videos on histamine and brain fog, histamine and anxiety, and histamine and depression. If you were to get a histamine blood test and your histamine levels were normal. Still, you suffer from depression, brain fog, and anxiety, could we rule out that your normal blood histamine levels reflect the levels of histamine in your brain? And the answer to that is NO.

Histamine levels in the blood do not reflect histamine levels in other tissues, organs, or the brain. So, if testing is not accurate for all the reasons I mentioned, how do you know if you have histamine intolerance? While blood testing is not 100% accurate as far as correlating the symptoms you have to the levels in your blood, Blood tests and urine tests can be used as a broader diagnostic approach.

DNA Testing for Histamine Intolerance

In Clinical practice, it is generally more useful to consider a range of tests and assessments, including symptom questionnaires.

Functional Medicine and Histamine Intolerance

When we talk about the cause of histamine intolerance and MCAS, keep in mind that there is no one singular cause or reason. There are many things that activate Mast Cells and cause them to release histamine and other inflammatory chemicals.

You will often see these referred to as histamine triggers. These Triggers fill up your histamine/MCAS bucket, and when the bucket is filled to the brim, it starts to overflow. These Histamine/MCAS Triggers may include.

1. Genetic SNP in the DAO or HNMT enzyme– this is where the enzyme doesn’t work the way it should- you have a mutation in the gene
2. Gluten intolerance or Celiac Disease- due to the damage it causes to the intestinal mucosa.
3. Mold biotoxins
4. Gut Dysbiosis, Small Intestinal Bacterial Overgrowth or SIBO- Here are some of the Best Ways To Address Histamine Intolerance/MCAS when you have SIBO
5. Gut bacterial infection such as H. pylori,
6. DAO-blocking foods
7. Reheating foods increases the amount of Histamine, better known as histamine liberators.
8. Foods that are High in Histamine
9. Inflammation in the GI tract- Maybe you have Crohn’s, Ulcerative colitis, Celiac and Inflammatory Bowel Disease.
10. LPS bacteria- These are bacteria that elicit a very powerful inflammatory response from the immune system. LPS bacteria also cause a Leaky gut.  Here’s a video on my YouTube Channel
11. Medications: These may be from medications like
    1. Anti-inflammatories such as (ibuprofen, aspirin),
    2. Anti-depressants (Cymbalta, Effexor, Prozac, Zoloft)
    3. Anti-histamines (Allegra, Zyrtec, Benadryl) H1 blockers
    4. Immune suppressants such as (Humira, Enbrel, Plaquenil)- these are medications for people who have Rheumatoid arthritis or inflammatory bowel disease
    5. Histamine (H2) blockers (Tagamet, Pepcid, Zantac)- Many of these medications will either release excess histamine or will block the enzyme that breaks down histamine. Either way, you end up with excess histamine.
12. Food Additives that contain High Levels of Histamine
13. Nutritional status- Several vitamins and minerals serve as enzymatic cofactors. These vitamins activate the DAO and HNMT enzymes. If the enzyme fails to be activated, we can’t break down histamine, and it accumulates. Learn more about Natural Ways to Increase DAO enzyme Activity here
14. Hormones- The complexity of histamine intolerance extends to the interaction between histamine receptors and hormones like estrogen,  progesterone, testosterone, and DHEA. Estrogen can also influence endogenous histamine levels by downregulating DAO activity. This ultimately leads to high histamine levels in the body. Learn more about the connection between histamine and hormones here.

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