The interplay between oestrogen, histamine and the liver represents a significant biochemical triad. There are wide-ranging effects on hormonal balance, inflammation and detoxification. Oestrogen is a key sex hormone that influences reproductive health, mood and metabolism. Histamine, commonly known for its role in allergic reactions, functions as a neurotransmitter and modulator of immune responses. The liver acts as the body's primary detoxification organ, metabolising both oestrogen and histamine to maintain homeostasis.
Imbalances in this triad can create a feedback loop, where elevated oestrogen impairs histamine breakdown and excess histamine stimulates oestrogen production. The liver’s capacity to metabolise both compounds is central to regulating this cycle. Therefore, understanding the interplay of this triad is essential for addressing hormonal imbalances, histamine intolerance and liver-related issues in naturopathic practice.
The liver
The liver is the body’s detoxification powerhouse. It is responsible for processing toxic metabolites, hormones and xenobiotics.
Liver detoxification is categorised into two phases. Phase one depends on CYP450 enzymes to convert toxic metabolites into less harmful compounds, through a series of oxidation, reduction and hydrolysis reactions. Phase two concerns conjugation of the metabolites produced in phase one, enhancing their water-solubility in preparation for excretion via the gastrointestinal (GIT) system. 1
Impairment in either phase can result in an accumulation of toxic metabolites and free radicals, which are recirculated throughout the body causing inflammation and symptoms such as PMS, urticaria, acne, GIT upset, headaches and fatigue. 2
The final stage of detoxification occurs through the GIT system. This stage emphasises the importance of healthy bowel patterns, as conjugated metabolites are excreted through stool.
Oestrogen and liver detoxification pathways
Oestrogen plays an essential role in many physiological processes. These include assisting reproductive function, maintaining bone density, supporting cardiovascular health and modulating cognitive function. Therefore, both excess and deficiency of oestrogen can be harmful. The liver is critical for oestrogen metabolism, using phase one oxidative reactions and phase two conjugation for elimination via bile, urine and stool. It is not until the detoxification process is overburdened by gut dysbiosis, poor diet, endocrine disruptors and chronic stress that we begin to observe oestrogen dominance. This is observed through its associated symptoms such as heavy menstrual bleeding, breast tenderness, sleep disturbances, breast lumps, mood instability, headaches, anxiety and fatigue. 3 Oestrogen dominance is implicated in the pathophysiology of conditions such as endometriosis and adenomyosis. 4
Histamine breakdown
Histamine is a signalling molecule in many body systems, including the immune, nervous, integumentary and GIT systems. Histamine is released from mast cells and basophils and is the primary mediator of inflammatory processes. 5,6 It is important for histamine to be metabolised successfully.
There are two enzymatic pathways for histamine metabolism, oxidation and methylation. Oxidation is carried out by diamine oxidase (DAO) and methylation is facilitated by histamine N-methyltransferase (HNMT). Both pathways regulate histamine metabolism, ensuring it does not accumulate to excessive levels. Impaired methylation, genetic mutations, certain medications, high alcohol intake, gut dysbiosis, nutritional deficiencies, insomnia and chronic stress can inhibit the activity of these enzymes. If inhibited, there may be an adverse effect on the body’s capacity for histamine tolerance. Poor clearance through either pathway can result in histamine intolerance. The symptoms of which include urticaria, pruritis, congestion, headaches, fatigue, bloating and changes to bowel patterns. 7,8
The oestrogen-histamine feedback loop
Oestrogen and histamine have an intimate relationship. As oestrogen levels rise, histamine follows suit and encourages the ovaries to release additional oestrogen, marking the beginning of a bothersome feedback loop. Additionally, high levels of oestrogen may suppress the DAO enzyme and prevent it from working effectively. Due to this feedback loop, it is common to observe symptoms of histamine intolerance during the menstrual cycle, perimenopause and in oestrogen-dominant conditions such as endometriosis and adenomyosis. 9,10
Practical detoxification strategies
Supporting the body to detoxify effectively using naturopathic strategies helps manage the liver, oestrogen and histamine triad.
Nutrients for liver detoxification
There is an emphasis on antioxidants in phase one due to the number of free radicals produced. Vitamins A, C and E, selenium and zinc are powerful antioxidants that support phase one by scavenging free radicals. 2 Iron and B vitamins are also critical in phase one, as they function as cofactors for various enzymes required during this phase. 11,12 Glutathione, the body’s dominant endogenous antioxidant, relies on a spectrum of B vitamins for its formation. 11 Consumption of brightly coloured fruits and vegetables for their high bioflavonoid content is recommended during this phase, due to their ability to neutralise free radicals and mitigate oxidative damage. 2
Phase two detoxification requires a range of amino acids and sulphur-containing foods to support its six conjugation pathways. Animal proteins such as beef, chicken, lamb, seafood and shellfish, along with plant-based proteins from legumes, nuts and seeds, provide essential amino acids which are critical for effective phase two detoxification. Cruciferous vegetables like broccoli, kale, cauliflower, Bok choy, and Brussels sprouts are rich in sulforaphane, a key element in supporting enzymatic activity during this phase. Additionally, sulphur is an important precursor to glutathione synthesis, making foods such as eggs, garlic, onions and leeks valuable dietary components during this process. 11
Hydration
Adequate hydration is imperative for successful detoxification processes in the liver and the GIT system. Water regulates liver detoxification by improving blood circulation and increasing clearance of toxic metabolites from the body through urine, sweat and stool.
The final phase of detoxification is elimination, employing the GIT system for its success. The elimination process is reliant on adequate hydration levels to support healthy bowel patterns, as wastes and secondary metabolites are transported out of the body through stool. 13
Herbal detoxifiers
There are numerous herbal allies to support liver detoxification, with a focus on hepatoprotective, antioxidant and anti-inflammatory properties.
- Milk thistle (Silybum marianum) has an affinity for the liver and its associated disorders. Silymarin is a constituent in Milk thistle that induces phase one detoxification and protects hepatocytes from lipid peroxidation. Silymarin has also proved benefit for increasing hepatic glutathione and supporting hepatocyte regeneration. 14
- Globe artichoke (Cynara scolymus) works to protect and restore hepatocytes. It is a popular herb for any complaints related to the liver or inefficient detoxification processes. 15
- Dandelion (Taraxacum officinale) supports the liver and the GIT system to ensure successful detoxification. Recent evidence affirms Dandelion’s protective role against liver damage, due to the modulatory effect its bioactive taraxasterol has on inflammatory and oxidative pathways. 16 Dandelion’s mild laxative action further supports detoxification, if there is concern of ineffective elimination pathways. 17
- Schisandra (Schisandra chinensis) displays a hepatoprotective action by increasing antioxidant activity in the liver and stimulating glutathione regeneration during phase two of detoxification. 17
Nourish the gut microbiome
The gut microbiome is a dynamic ecosystem that plays a crucial role in the development and progression of numerous disorders. While the liver is traditionally recognised as the primary organ for detoxification, the gut microbiome significantly influences this process by modulating inflammatory and immune pathways. One important area where this connection is increasingly evident is in oestrogen metabolism. The gut microbiome, through a subset of genes collectively known as the Estrobolome, helps regulate the balance of circulating oestrogens. These microbial genes influence whether oestrogen is excreted or reabsorbed into the bloodstream after being processed by the liver and excreted into the gut via bile. When gut dysbiosis occurs, this regulatory mechanism can become impaired, allowing excess oestrogen to recirculate in the body and contribute to oestrogen-dominant conditions. Notably, individuals with endometriosis often exhibit altered gut microbiota, including an abundance of pathogenic bacterial species, which may further contribute to hormonal imbalances and disease progression. 18
To support a healthy gut microbiome, it is essential to nourish the gut with a diet rich in prebiotic and probiotic foods, along with adequate dietary fibre. This optimises oestrogen and histamine clearance. Prebiotics found in foods like onions, garlic, leeks, asparagus and bananas fuel beneficial gut bacteria, while probiotic-rich options such as kefir, sauerkraut and yoghurt, help restore microbial balance and strengthen gut integrity. As fibre promotes bowel clearance, it reduces the opportunity for oestrogen reabsorption in the colon, further supporting hormonal balance.
Recent research highlights the gut microbiome’s influence on oestrogen metabolism via the Estrobolome, a group of bacteria that produce β-glucuronidase, an enzyme capable of regulating oestrogen levels when dysbiosis is present.19 Similarly, studies show that reducing histamine-secreting bacteria through dietary manipulation can alleviate symptoms of histamine intolerance and improve gut function. 20 Together, these dietary strategies enhance microbial diversity, regulate hormone and histamine levels and support efficient detoxification.
Histamine balance
As histamine metabolism is predominantly facilitated by the DAO enzyme, practitioners can look to support the activity of this enzyme through targeted herbal supports and supplements.
- Recent research proposed DAO deficiency secondary to gut dysbiosis as an underlying cause of histamine intolerance. 20 Probiotic strain Lactiplantibacillus plantarum has been revealed to markedly increase DAO secretion, offering a therapeutic solution to histamine intolerance driven by inactivity of this enzyme. 21
- Stabilising mast cell activity is another strategy for mitigating histamine excess. Quercetin is a bioflavonoid that exhibits strong inhibitory effects on mast cell degranulation and subsequent histamine release. 22
- Baical skullcap (Scutellaria baicalensis) is a potent anti-allergy herb, that slows histamine release by modulating the inflammatory response. 17
- Nettle leaf (Urtica dioica) displays an inhibitory effect on H1 histamine receptors, working to stabilise mast cell activity, resulting in decreased signalling to inflammatory and allergy receptors. 23
Conclusion
The complex interplay between oestrogen, histamine and the liver forms an important triad that influences hormonal balance, inflammation and detoxification. Oestrogen and histamine are closely linked in a feedback loop that can exacerbate hormonal and immune-related symptoms when dysregulated. The liver plays a central role in metabolising both compounds. Efficient liver detoxification through its two-phase system is vital to prevent the buildup of harmful metabolites. Nutritional and herbal strategies, including antioxidants, amino acids, sulphur-rich foods and liver-supportive herbs, are key to supporting detoxification processes. The gut microbiome further influences this triad, particularly through the Estrobolome, which regulates oestrogen recirculation and impacts histamine levels. Addressing gut health through prebiotics, probiotics and fibre-rich foods can enhance hormonal and histamine clearance.
Together, these integrative strategies help to restore balance within the oestrogen, histamine, liver triad and support overall wellbeing.
References
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