Liver-estrogens-histamine relationship: Do you feel its effects?

Anna Nadal

Physiotherapist and Postgraduate in PNIE

The Liver Detoxifies and Also Helps with Histamine and Estrogens

One of the liver’s functions is to eliminate internal toxins, whether they are substances produced by bacteria and fungi in the intestine or external toxins (alcohol, tobacco, pesticides, environmental pollution, additives, dyes, and other compounds present in highly processed products).

The liver detoxifies:

  • Internal toxins (substances produced by fungi or bacteria)
  • External toxins (alcohol, tobacco, pesticides, environmental pollution, additives, or toxic food products).
  • And in all cases, lifestyle can favor good liver detoxification function (phase 1 and phase 2), which we discuss in this article.

But in the liver, we also have a series of enzymes responsible for eliminating histamine and estrogens.

Therefore, it’s very important to know that if you have an excess of estrogens and histamine, you need your liver to function properly. Otherwise, it won’t be able to do so if it’s not in good condition.

Excess histamine could lead to an accumulation of estrogens, and vice versa.

Symptoms of Excess Estrogens

  • Premenstrual syndrome (breast tenderness, pain in the ovaries and uterus area, lower back and leg pain, fatigue, irritability or depression, water retention, headaches or migraines, sweet cravings…)
  • Anxiety, irritability, depression
  • Fibroids, fibrous breasts, endometriosis
  • Loss of libido
  • Shallow sleep
  • Muscle contractions
  • Excess vaginal discharge
  • Water retention
  • Hypothyroidism or difficulty losing weight.

Balancing Estrogens and Histamine: Liver Detoxification

In the liver, we have a series of enzymes responsible for eliminating or balancing estrogens. The detoxification process occurs in 2 phases.


In the first phase, the liver begins to eliminate estrogens. The liver works to convert toxins and estrogens into soluble substances for easier elimination.

To facilitate their elimination, a group of liver enzymes adds a hydroxyl group (OH) to estrogens to make them more soluble. This process is known as hydroxylation and produces three types of estrogen metabolites:

  • 2-hydroxyestrone (2-OH).
  • 4-hydroxyestrone (4-OH).
  • 16-alpha-hydroxyestrone (16alpha-OH).

2-hydroxy-estrone has an antiestrogenic effect and is considered beneficial. Whereas 4-hydroxyestrone and 16-alpha-hydroxyestrone have estrogenic effects and are considered less beneficial.

You can assess your balance by conducting a urine test to measure estrogen metabolites over 24 hours.

However, it’s recommended to focus on your diet and lifestyle, following some tips that can help enhance or decrease the positive and less beneficial effects of hydroxylation and its resulting metabolites.

Which Foods Reduce 4-OH and Its Less Positive Effects?

  • Polyphenols: grape seeds and skin, currants, blueberries, raspberries.
  • Resveratrol: grape seeds and skin, currants, blueberries, raspberries, or as a supplement. Resveratrol reduces NF-kappa beta, decreases 4-OH, and protects DNA.
  • Cruciferous Vegetables: INDOL-3-CARBINOL (I3C) and DI-INDOL-METHANE (DIM) and SULFORAPHANE. Foods rich in sulforaphane include broccoli, broccoli sprouts, cauliflower, Brussels sprouts, red cabbage, arugula, watercress, radish, turnip, wasabi, mustard, capers. Sulforaphane enhances the body’s antioxidant capacity by activating the Nrf2 gene.
  • Licorice Root: it also has antibiotic, antiviral, and anti-inflammatory properties.

Take Note of These Extra Tips!

Did you know…

Boiling cruciferous vegetables for 2 or 3 minutes and then stopping the cooking with cold water to keep myrosinase, the enzyme that provides the active principles of cruciferous vegetables, active.

Another way to activate myrosinase is to chew cruciferous vegetables well or consume them in cold-pressed green juice.

Which Foods Improve the Good Metabolite 2-OH?

  • Cruciferous Vegetables: broccoli, collards, sauerkraut at least twice a week.
  • Omega 3: fish, seaweed, nuts, sesame, chia, hemp, or supplementation prescribed by a professional (more EPA than DHA).
  • Lignans: ground flaxseed, flaxseed oil, sesame, nettles, kale, quinoa, rye. Consume a minimum of 10g/day of raw flaxseed oil (not for cooking) and store it in the refrigerator.
  • Resveratrol: grapes (with seeds and skin).
  • Cocoa
  • Caffeine: accelerates CYP1A2 and increases estrogen 2-OH. Coffee, red tea, black tea, green tea, mate, guarana. Keep in mind that they should be consumed in small quantities and in the morning, as they can affect sleep.


In this phase, estrogens are eliminated thanks to the action of different methylation and sulfation enzymes.

What’s the Relationship Between These Enzymes and Histamine?

The relationship is that if some of these enzymes don’t work well, estrogens and histamine will accumulate, leading to the aforementioned symptoms.

We could imagine it as a funnel.

Estrogens cause a greater release of histamine in our body, and in this scenario, the amount of inflammatory substances and mast cells (cells that contain histamine) increases.

During the fertile stage and during the first phase of the menstrual cycle, known as the follicular phase, estrogens are higher. It’s important for the liver phases to function correctly for proper elimination to occur.

However, if it doesn’t happen, in the last days of the follicular phase, which can vary in each woman but usually falls between days 10 and 14 of the menstrual cycle, these days are when higher levels of histamine are present. Many women experience migraines, muscle contractions, or headaches during these days, and one reason could be that the liver’s detoxification pathways that eliminate, among other compounds, estrogens and histamine, are not functioning properly.

Therefore, for women experiencing symptoms of excess estrogens or histaminosis, it’s important to review and adjust their diet, improve the functionality of the digestive system and diversity of intestinal microbiota, and ensure that the liver performs detoxification functions correctly.

Thus, the supplementation of NATURDAO is useful and effective for people with histamine intolerance while taking care of their diet for a better quality of life.

Histamine in Women: Why Does It Affect Them More?

The functionality of the immune system is sexually dimorphic, with women being more prone to the development of autoimmune diseases than men due to the action of estrogens on immune cells. Chakraborty, B. et al. (2022)

In women, histamine is mainly produced by mast cells, endothelial cells, and epithelial cells of the uterus and ovaries. Therefore, the hormonal context will vary in each woman and could lead to variable symptoms related to excess estrogens.

A woman with excess estrogens and/or poor elimination through the liver’s detoxification phases may experience symptoms of excess histamine.

Although low levels of estrogens would not be an optimal situation either. The lack or excess of estrogens is not an ideal context for women. These imbalances have an impact on the functionality of enzymes that degrade histamine.

Therefore, it’s important to understand that women, due to our hormonal condition, are more vulnerable to problems related to histamine.

It’s like a dance of hormones during the fertile stage, and it can condition symptoms related to excess histamine precisely because one of the pathways for the degradation and metabolism of histamine, the liver, is also responsible for balancing estrogens. The interconnection between the liver, estrogens, and histamine can lead to symptoms of excess histamine.

Symptoms of Excess Histamine or Histaminosis

  • Premenstrual syndrome
  • Anxiety, fears
  • Migraines and/or headaches
  • Instability, dizziness and/or vertigo
  • Lack of energy
  • Muscle contractions
  • Joint pain
  • Burning and stomach spasms
  • Gas
  • Constipation and/or pasty stools
  • Irritable bowel syndrome
  • Rhinitis, sneezing, bronchospasms, stuffy nose
  • Dry skin, peeling, eczema
  • Low or high blood pressure, palpitations, arrhythmias
  • Shallow sleep
  • Strong redness of the skin in case of mosquito, bee, or jellyfish stings.

In Conclusion:

Considering that a small part is influenced by genetics and a large part by lifestyle, it’s advisable to analyze and personalize how each woman can improve to achieve a good hormonal balance and health.

Bibliographic References:

Cóppola, F., J. Nader., R. Aguirre. Metabolism of endogenous estrogens and breast cancer. (2005)

Sepkovic, D. W.; H.L. Bradlow. Estrogen hydroxylation, the good and the bad. (2009)

Zhu, B. T; a.H. Conney. Functional role of estrogen metabolism in target cells: review and perspectives. (1998)

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