Headaches. Anxiety. Insomnia. Brain fog. Hives. 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 then again just before the period.
The connection between mast cells, histamine, and hormones is that:
- Estrogen stimulates mast cells to release histamine and down-regulates 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 stabilises mast cells, up-regulates 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 both endometriosis and premenstrual dysphoric disorder (PMDD).
What is histamine?
Histamine is the immune signalling protein that causes allergies and swelling. But it has lots of other jobs. Histamine also regulates stomach acid, stimulates the brain, and plays a key role in ovulation and female reproduction.
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.
Reasons for too much “histamine in”
- Mast cell activation due to 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.
Reasons for not enough “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 down-regulates DAO.
- Progesterone deficiency because progesterone stabilises mast cells and up-regulates 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.
What’s the solution?
Reduce histamine-containing foods. This is the fastest and simplest way to feel better, but it can become restrictive and difficult in the long-term. If you address underlying gut issues, you should find that you improve your tolerance of histamine foods.
- red wine and champagne
- hard cheese
- smoked or canned fish
- soy sauce
- deli meats
- dried fruit
- dried nuts
- bone broth and fish stock
- vinegar and fermented foods such as sauerkraut
Improve gut health. This usually means identifying and correcting dysbiosis and small intestinal bacterial overgrowth (SIBO). I discuss SIBO in Chapter 11 of Period Repair Manual.
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.
Promote the healthy clearance of estrogen. Read How to lower estrogen.
Consider taking natural progesterone because it up-regulates the DAO enzyme.
👉 Tip: Histamine reduction is a big part of why dairy-free diet, vitamin B6, and natural progesterone work so well for women’s health.
For more information, read The role of histamine and mast cells in PMS and PMDD.
ps. I’ve had a few comments thinking this article means that estrogen is bad. As I discuss in both my books, estrogen is a wonderful hormone and estrogen therapy can be helpful in some situations.