Headaches, anxiety, insomnia, brain fog, hives, and nasal congestion. These are just a few of the symptoms of mast cell activation or high histamine.
Histamine symptoms are more common in women and often track with the menstrual cycle, occurring when estrogen is high at ovulation and about a week before the period.
The connection between mast cells, histamine, and hormones is that:
- Estrogen stimulates mast cells to release histamine and downregulates the DAO enzyme that clears histamine. At the same time, histamine stimulates the ovaries to make more estrogen. The net result can be a vicious cycle of estrogen → histamine → estrogen → histamine.
- Progesterone stabilizes mast cells, upregulates DAO, and can therefore reduce histamine.
Many of the symptoms attributed to so-called “estrogen dominance” (a term I do not use) are actually symptoms of histamine or mast cell activation. For example, mast cells and histamine play a role in endometriosis, premenstrual dysphoric disorder (PMDD), and heavy menstrual bleeding.
What is histamine?
Histamine is an immune or inflammatory mediator that causes allergies, swelling, and many other effects, such as stimulating stomach acid and helping to regulate ovulation and female reproduction. Histamine is also a stimulating neurotransmitter, so can cause anxiety and agitation.
Did you know? Histamine boosts libido, which is why estrogen increases libido and antihistamines decrease it.
The normal regulation of histamine is by making it with mast cells and then clearing it with the enzymes histamine N-methyltransferase (HNMT) and diamine oxidase (DAO). It’s a fine balance between “histamine in” and “histamine out.”
Did you know? The placenta makes a huge amount of DAO, which is why mast cell activation and histamine intolerance can improve with pregnancy.
Causes of too much “histamine in”
- Mast cell activation as a result of chronic inflammation, alcohol, and food sensitivities, especially cow’s dairy.
- Histamine-containing foods, including wine, sauerkraut, and smoked meat.
- Intestinal dysbiosis because some species of gut bacteria manufacture histamine.
- Estrogen excess because estrogen stimulates mast cells.
Causes of too little “histamine out”
- A genetic variant of the histamine-clearing enzymes HNMT and DAO.
- SIBO (small intestinal bacterial overgrowth) because it impairs DAO activity.
- Vitamin B6 deficiency because vitamin B6 is an essential cofactor of DAO.
- Estrogen excess because it downregulates DAO.
- Progesterone deficiency because progesterone stabilises mast cells and upregulates DAO. That’s why you probably feel better early in the luteal phase when progesterone is high.
- Hormonal birth control because it causes estrogen excess and progesterone deficiency.
Treating high histamine
Start with a few months on an antihistamine medication. Read The role of histamine and mast cells in PMS and PMDD.
Avoid histamine-stimulating foods such as alcohol and cow’s dairy. Read, listen, or watch What’s the story with dairy and periods.
Improve gut health. This usually means identifying and correcting dysbiosis and small intestinal bacterial overgrowth (SIBO). I provide an in-depth discussion of SIBO in my metabolism book.
You could also try reducing histamine-containing foods, but only in the short term. Long-term restriction is usually not necessary once you address underlying gut issues.
Histamine-containing foods:
- red wine and champagne
- hard cheese
- avocado
- smoked or canned fish
- shellfish
- soy sauce
- deli meats
- yeast
- dried fruit
- dried nuts
- bone broth and fish stock
- vinegar and fermented foods like sauerkraut
- chocolate
Supplement vitamin B6 because it upregulates DAO. This is one reason vitamin B6 is so incredibly helpful for PMS. B6 also boosts the calming neurotransmitter GABA. Food sources of vitamin B6 include meat, chicken, and sunflower seeds. For B6 safety considerations, see my B6 article.
Try increasing bitter foods like coffee and cruciferous veggies, because bitter constituents can stabilise mast cells by activating the bitter receptors (TAS2Rs) found almost everywhere in the body, including on immune cells. Other natural bitters include dandelion root, milk thistle, berberine, perilla seed, and reishi mushroom.
Promote the healthy clearance of estrogen. Read How to lower estrogen.
Consider taking natural progesterone because it upregulates the DAO enzyme.
👉 Tip: Histamine reduction is a big part of why a dairy-free diet, vitamin B6, and natural progesterone work so well for women’s health.
For more, read The role of histamine and mast cells in PMS and PMDD.
