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The Histamine-Estrogen Connection

Last week I hosted a 5-day Hyperthyroid Healing Diet challenge, and during the challenge I had a bonus presentation on histamine intolerance. A few years ago I also wrote an article entitled “Histamine and Thyroid Health [1]” that you might want to check out, but in this blog post I’m going to discuss the relationship between histamine and estrogen.

Although I’ve written an article on histamine, I’d like to briefly summarize what this is, its function, and some of the common symptoms associated with a histamine intolerance.  Histamine is a chemical messenger which plays a role in several cellular responses. It plays a role in the inflammatory process and allergic reactions, and it also is involved in the control of stomach acid secretion.  Histamine receptors are found in just about all of the tissues.

Histamine is synthesized from the amino acid histidine.  Histamine intolerance is due to an imbalance between levels of released histamine and the ability of the body to metabolize it.  Diamine Oxidase (DAO) is an enzyme that is mainly responsible for the metabolism of ingested histamine, while another enzyme called histamine N-methyl transferase (HNMT) breaks down histamine at the receptor.

Here are some of the common symptoms people with a histamine intolerance may experience:

For those with hyperthyroidism/Graves’ disease, you’ll notice that there is some overlap between symptoms of histamine intolerance and hyperthyroidism. In fact, recently I have been working with a patient who was diagnosed with Graves’ disease, and even though her most recent thyroid hormone levels look excellent she still experiences tachycardia and heart palpitations.  While there can be numerous causes of these two symptoms, I’m pretty sure that this person has a histamine intolerance due to some of her other signs and symptoms.

What Are Mast Cells?

Mast cells are the major producers of histamine, although other cells can also produce histamine, including basophils.  Mast cells play a big role in allergies, and they also are involved in wound healing, defense against pathogens, and immune tolerance (1) [2].  Some reading this might have heard of mast cell activation syndrome (MCAS), and this is a complex condition where the mast cells become overactive and release large amounts of histamine.  Because mast cells are located in most tissues of the body, MCAS can cause many different symptoms, including fatigue, body aches and pains, multiple chemical sensitivities, breathing problems, rashes, digestive issues, brain fog, etc.

The Relationship Between Histamine and Estrogen

As for how estrogen affects histamine, estrogen sensitizes mast cells, and this in turn causes more histamine to be released (2) [3] (3) [4].  Estrogen also downregulates the activity of the DAO enzyme (4) [5], which leads to an increase in estrogen. This would explain why some menstruating women experience histamine-related symptoms at certain points of their cycle.

For example, high histamine causes headaches in some people.  And since estrogen can cause histamine to be released, it makes sense that cycling women who experience headaches due to histamine intolerance are more likely to experience them at certain points of their menstrual cycle (i.e. at the beginning).

Although having healthy estrogen levels is important, due to this relationship you would want to do what is necessary to avoid a state of estrogen dominance.  Oral contraceptives and xenoestrogens are two common causes of estrogen dominance.  Sometimes the problem isn’t overexposure to estrogen, but instead problems with estrogen metabolism. You can improve estrogen metabolism by eating certain foods, such as broccoli sprouts, or by supplementation with diindolylmethane (DIM).  Having healthy phase two detoxification is also important…especially methylation, glucuronidation, and glutathione production.  For more information on supporting estrogen metabolism you might want to read an article I wrote entitled “7 Ways To Positively Influence Estrogen Metabolism [6]”.

It’s also important to mention that histamine can induce estrogen synthesis (5) [7] (6) [8]. So this potentially can lead to a vicious cycle, as estrogen can lead to high histamine, and histamine in turn can cause more estrogen to be produced.

The Relationship Between Histamine and Progesterone

So what’s the connection between histamine and progesterone? Well, progesterone has a direct inhibitory effect on histamine secretion (7) [9]. In addition, progesterone may also upregulate the DAO enzyme.  As a result, if progesterone is low then you might not have enough DAO to break down histamine, which in turn can exacerbate some of the symptoms mentioned earlier.

Progesterone also helps to balance estrogen, and so you want to do what’s necessary in order to have healthy progesterone levels.  The main cause of low progesterone is weak adrenals.  And so you want to do as much as you can through diet and lifestyle to support the adrenals, although supplementation can also be beneficial at times. I’m a big advocate of doing adrenal testing, as I recommend either doing adrenal saliva testing [10] or dried urine testing.

I should also mention that the herb chaste tree, also known as vitex, can help to increase progesterone levels. And of course some people can benefit from taking bioidentical progesterone. But while these can help, you always want to try to address the cause of the progesterone deficiency, which usually is stress resulting in compromised adrenals.

What Is The “Histamine Bucket”?

Before wrapping up this blog post I wanted to mention the “histamine bucket” theory.  This theory explains why some people can experience symptoms during their menstrual cycle and/or when eating high-histamine foods at times, but other times will have no symptoms.  According to this theory, if you were to envision histamine filling up a bucket, as long as the bucket isn’t completely filled the symptoms will be minimal, but once the bucket overflows is when someone is more likely to experience histamine-related symptoms…especially when exposed to high histamine foods and/or at certain times during their menstrual cycle.

This theory doesn’t apply to everyone with a histamine intolerance, as there are people who have issues with histamine even when reducing their “histamine load”.  On the other hand, there are people with a histamine intolerance who do okay eating small amounts of high-histamine foods on an occasional basis.

Getting To the Root Cause of a Histamine Intolerance

If you refer back to my original article “Histamine and Thyroid Health” I discuss some of the potential causes of a histamine intolerance.  Perhaps the most common cause is gut dysbiosis, including small intestinal bacterial overgrowth [11] (SIBO).  In the past article I mentioned how problems with methylation [12]can also be a factor, as histamine N-methyl transferase (HNMT) uses S-adenosyl-L-methionine (SAMe) as the methyl donor and transfers this methyl group to the histamine molecule.  One more potential cause is being deficient in one or more of the nutritional cofactors of DAO, including vitamin C, vitamin B6, and copper.

While the goal is to address the underlying cause of the histamine intolerance, in the meantime it’s a good idea for the person to minimize their consumption of high histamine foods and histamine-liberating foods (i.e. citrus fruits, nuts, alcohol, green tea).  Certain supplements can also be beneficial to take, including quercetin, rutin, stinging nettles, and sometimes a DAO supplement.  You might also want to consider supplement with a probiotic that has histamine-degrading bacteria, such as Lactobacillus plantarum (8) [13].

What’s Your Experience With Histamine?

If you have problems with histamine I’d love to hear from you! Please feel free to post a comment below, especially if you suspect that hormones play a role in your histamine issues and/or you agree (or disagree) with the histamine bucket theory.  Thank you for sharing your experience with others!