Imagine if symptoms like allergies, headaches, or anxiety could be traced to a single molecule: histamine. This powerful chemical influences much more than seasonal sniffles. It influences immune responses, impacts gut health, and affects brain chemistry. To understand how your body reacts to stress, food, and the environment, you must first unlock the secrets of histamine. Its balance is crucial for your health.
Histamine levels fluctuate throughout the day as they protect you. Levels change in response to stress or the presence of pathogens. The most reliable way to measure histamine is by collecting all urine over a 24-hour period and testing for methylhistamine, a stable byproduct. Although found in blood, urine, and the gut, histamine itself is generally unstable and hard to measure directly.
More useful tests for assessing histamine activity include the eosinophil count, which measures the number of eosinophil cells. These white blood cells increase when mast cells, key immune cells involved in allergic reactions, are active. Another useful test is IgE antibody levels. IgE antibodies are immune proteins that bind to mast cells, triggering the release of histamine, the molecule responsible for many allergy symptoms.
It is essential to note that one may exhibit all the symptoms, yet no markers may be detectable on a blood test, while the histamine count remains elevated (measurable only by a specialised laboratory test for methylated histamine, a modified form used to assess levels).
The cells that release histamine do so to defend against foreign invaders, such as bacteria, viruses, or allergens. This is an important point. These cells contain histamine and help defend us from invaders. Histamine also has other actions. It contracts smooth muscles in organs like the intestines and blood vessels. It dilates small blood vessels and increases their leakiness, allowing white blood cells to neutralise pathogens. Histamine can also trigger tissue swelling. This leads to effects like welts or dermatographia, where slight scratching causes raised red lines. If you have an allergy, tissues swell up—this is what histamine does.
Mast cells are immune cells in connective tissue that respond to triggers such as allergens or injuries, releasing histamine to mobilise the immune system.
Basophil cells, another type of white blood cell, are mainly responsible for the prolonged onset (delayed appearance) of allergic dermatitis (inflammation of the skin due to allergy).
An elevated level of histamine is needed for many body processes and is considered to have an important physiological role (meaning it is necessary for normal body function).
Elevated histamine can cause symptoms in both the body and nervous system, particularly if it isn’t removed quickly. Histamine intolerance is associated with a reduced ability to metabolise histamine, often triggered by certain foods. Symptoms arise only when histamine production or exposure exceeds the body’s ability to metabolise it.
In effect, the release of histamine by the M Cells is more important than the absorbed histamine in the food itself or from the gut.
Alcohol, spices, or other foods can interact with mast cells, triggering the release of histamine.
Total histamine from both internal and external sources causes symptoms when it exceeds the body’s ability to eliminate it efficiently.
Heavy metals, mould, high oestrogen, genetic SNPs (mutations), unfriendly bacteria, histamine foods, a
A drop in DAO (diamine oxidase, the main enzyme that breaks down histamine in the gut), cross-reactive pollen allergies, and IgE allergies (IgE: a class of antibodies involved in allergic responses) can all contribute to a build-up of histamine. These factors are not listed in any particular order.
This differs from sensitivity to food histamines, where the issue is excessive histamine production and slow elimination.
Being sensitive to food histamine can trigger anaphylactic shock, posing risks such as suffocation and death.
For instance, if you get injured, histamine will be released to allow the immune system to respond. This occurs due to vasodilation, which is the widening of blood vessels, often triggered by increased levels of nitric oxide—a molecule that helps relax the vessel walls. Histamine also stimulates gastric secretion and contracts smooth muscles, such as those in the bronchi of the lungs or causes uterine contractions during menstruation. It also stimulates nerves.
Excess oxidative stress occurs when there is an imbalance between harmful free radicals and the body’s ability to neutralise them. This stress will increase both histamine and nitric oxide, a molecule involved in widening blood vessels.
Histamine is stored in the brain and is an endogenous neurotransmitter (produced within the body and acting as a chemical messenger that helps nerve cells communicate). It acts as a messenger between nerve cells in the nervous system, promoting wakefulness.
Histamine receptors (molecules on cell surfaces that respond to histamine) are mainly found in peripheral tissues (areas of the body outside the brain and spinal cord), such as the bone marrow and white blood cells. Smaller amounts are present in the colon, liver, lung, small intestine, spleen, testes, thymus, tonsils, and trachea.
What symptoms are caused by Elevated Histamine:
Anxiety, Depression ,Motion Sickness, Insomnia, Adrenal fatigue ,Thyroid issues.
Abdominal cramps and diarrhoea.
affects the regulation of the bone marrow and triggers the release of MAST CELLS.
Osteopenia and osteoporosis (MCAS)
Diarrhoea, bloating, and abdominal pain.
Heat flushes.
Migraines.
Asthma.
Painful, heavy periods and water retention (period shedding releases histamine).
Vertigo.
Palpitations and Cardiac arrhythmia.
Low blood pressure.
Urticaria, rashes, sinusitis, hay fever, chronic hives, dermatographia, and some eczema (not all itching is histamine-related).
Rosacea.
Heartburns and abdominal pains.
Taking antibiotics for prolonged periods is associated with SIBO (Small Intestinal Bacterial Overgrowth), a condition characterised by an abnormal increase in bacteria in the small intestine.
Travelled to underdeveloped countries (Parasites).
Taking antihistamines and experiencing relief may indicate a role for histamine.
Let’s now explore the link between histamine and gut health, as this connection helps explain the relationship between allergies and the microbiome.
Histamine plays roles beyond allergies and allergic reactions. Many people may not be aware that histamine also serves as a neurotransmitter and plays a role in regulating gastrointestinal processes.
A connection exists between histamine and the gastrointestinal tract. I will explore the most frequently observed connections between elevated histamine levels and acute or chronic gastrointestinal symptoms.
1. Histamine and your diet
Histamine is a naturally occurring compound found in the highest concentrations in the skin, mouth, sinuses, lungs, and digestive tract. It can also come from outside sources, mostly in food such as:
- Fermented foods – sauerkraut, natto , miso, soy sauce, pickles, and other relishes
- Cured meats – pepperoni, salami, chorizo
- Cultured dairy products – cheese (esp. cheddar, gouda, parmesan, Swiss), yoghurt, sour cream, kefir, buttermilk
- Smoked foods
- Beverages – coffee, beer, red wine, white wine, and champagne
- Plant foods – eggplant, spinach, tomatoes and tomato-based products, legumes (peanuts, chickpeas), wheat.
- The metabolites (breakdown products) of alcohol compete with histamine for the enzyme aldehyde dehydrogenase, which is involved in both histamine and alcohol metabolism. (Metabolism refers to the body’s process of breaking down substances for energy or removal.)
An increased presence of histamine may lead to the development of histamine intolerance.
Plasma histamine concentrations of 0.3-1.0 ng/ml are considered normal (however, from a functional medicine range, we are looking more at .3-.6 ng/ml being the norm), and anything higher gives rise to histamine-mediated symptoms. Even healthy individuals with no gastrointestinal problems can develop symptoms (i.e. severe headaches, allergy-like symptoms, hives, rashes, redness, sneezing) due to ingestion of excessive amounts of histamine.
Some foods are not high in histamine but may also trigger symptoms by causing histamine levels to rise. These foods are known as “histamine liberators”, and they include food substances such as additives, crustaceans, citrus fruits, and egg whites.
Unlike food allergies or sensitivities, symptoms of histamine intolerance do not appear immediately. They develop when a concentration threshold is reached, making histamine intolerance harder to recognise.
It can also be challenging to identify which specific food triggers the symptoms, especially since the amount of histamine in food varies and is dependent on the food’s ripeness, processing, and storage duration.
Going on a low-histamine diet is the most logical solution to reduce histamine levels in our gut. Adhering to a low-histamine diet for an extended period (or indefinitely if necessary) has been shown to alleviate symptoms in most cases. Identifying specific trigger foods by starting an accurate food diary, rather than indefinitely following a strict low-histamine diet, is also an option.
Next, beyond diet, gut bacteria, fungi, and parasites also influence histamine levels.
The histamine content of foods increases over time because of microbial fermentation (the breakdown of substances by bacteria, yeasts, or other microorganisms). This process is facilitated by some species of bacteria found in the gut (also known as histamine-producing bacteria).
- Lactobacillus species: Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus delbrueckii, Lactobacillus lactis, and Lactobacillus reuteri.
- Enterococcus species: Enterococcus faecalis, and some types of E. coli.
- Klebsiella
- Enterobacter and Citrobacter
- Helicobacteria.
- Blastocystis Hominis( Parasite).
- Candida Albicans.
- Mold release Mycotoxins.
- Parasites ( Elevated Eosinophils , Elevated IGE)
To maintain balance, there are also certain types of bacteria that degrade histamine. These histamine-degrading bacteria are:
- Bifidobacteria species: particularly Bifidobacterium infantis.
- Lactobacillus species: Lactobacillus gasseri, Lactobacillus Plantarum, Lactobacillus rhamnosusGG (25Billion daily) , and Lactobacillus salivarius( excess acidification of the gut)
- Saccharomyces Boulardi ( Competes with Candida Albicans)
If the histamine-producing bacteria proliferate and outnumber the histamine-degrading bacteria, histamine build-up occurs. This overwhelms the ability of the histamine-degrading bacteria to break down the excess histamine, which causes the symptoms of histamine intolerance to appear.
This gut flora imbalance is otherwise known as gut dysbiosis or SIBO, which stands for Small Intestine Bacterial Overgrowth. SIBO is one of the main reasons why histamine intolerance has become prevalent over the past 20 years.
And SIFO : Small intestine fungal overgrowth.
The most common symptom of SIBO is bloating after consuming any food or drink, as it triggers fermentation in the small intestine.
Fermentation should and can only take place in the large intestine, as there are few bacteria in the small intestine, which is the site of absorption.
The reason for this is that you do not want normal bacterial flora competing with you, instead of allowing the nutrients to be absorbed for your own metabolism.
3. Histamine and DAO
Two mechanisms have been proposed as the cause of histamine intolerance.
First is due to the increased availability of histamine, while the other is brought about by impaired histamine degradation. Impaired histamine degradation is caused by the overgrowth of histamine-producing bacteria that occurs when there is inflammation of the gut, which impairs the enzymatic function of DAO or even damages the gut lining.
DAO, which stands for diamine oxidase, is the main enzyme that breaks down histamine in the digestive tract and helps maintain histamine balance in the body. In healthy individuals, histamine from diet can be rapidly detoxified by the DAO enzyme( requires copper)
The impairment of DAO is linked to histamine intolerance. This impairment may be genetic or acquired due to gut inflammation or a deficiency in copper.
There is mostly an enzyme called histamine N-methyltransferase or HNMT. Additionally, this is a system-wide process, as it’s located in many different tissues and is responsible for breaking down histamine. And , this particular enzyme requires SAME (a cofactor).
This HNMT enzyme, present in the liver, can also be impaired by taking a variety of medications and block the function of breaking down Histamine, causing it to accumulate and resulting in a variety of symptoms.
There is the Gut-Skin axis: Whatever happens on the skin is due to gut dysbiosis.
There is this interesting interaction between Oestrogen and Histamine.
They increase the effect of each other.
When histamine rises, it increases the effect of oestrogen and vice versa.
During a woman’s menstrual cycle, oestrogen peaks before menstruation. This can cause a decrease in the amount of DAO produced, leading to eczema, rashes, and even a head cold that occurs just before the onset of the period; all these symptoms are due to a decrease in histamine clearance.
Interestingly, during a pregnancy, the amount of DAO rises to prevent an abortion, probably due to the rise of progesterone by forty times, pushing up the amount of DAO available.
During menopause, allergies tend to decline as both oestrogen and histamine levels decrease.
Unless there is severe SIBO present during this time of one’s life.
Genetic DAO impairment results from mutations in the gene that encodes the DAO enzyme. Individuals with a DAO gene mutation may present with high levels of histamine because the defect results in inadequate DAO production. This mutation is common among people of Asian descent.
Acquired DAO impairment, on the other hand, is brought about by gastrointestinal diseases like Crohn’s, colitis, inflammatory bowel disease (IBS), leaky gut, and SIBO. It can also be due to alcohol or medications.
Medications that can affect DAO function are antihistamines and histamine blockers, antibiotics, antidepressants, some diuretics, immunosuppressants, and NSAIDs –mostly aspirin and ibuprofen. Antihistamines and histamine blockers, specifically, although they help with histamine intolerance, can actually deplete DAO levels.
Acquired DAO impairment is often transient and reversible after eliminating the cause (i.e. treatment of the GI disease, quitting alcohol, discontinuing the medication, or food allergens).
4. Histamine and gastric secretion
Histamine is found in large amounts in the stomach lining, where it also plays a role in gastric acid secretion.
Gastric acid facilitates the digestion of proteins and the absorption of vitamins and minerals. They also inhibit bacterial growth, which helps prevent enteric infections and SIBO. A peptide hormone called gastrin elicits the release of histamine, which stimulates the cells to secrete gastric acids. This is the basis of using histamine blockers in the management of gastrointestinal ulcers, gastrinoma, and gastritis.
5. Histamine and GI problems
The presence of gastric problems is one of the primary factors contributing to the accumulation of histamine. The Majority of patients with histamine intolerance actually have gut problems due to the lack of hydrochloric acid production by the stomach.
This will cause :
1. The inability to produce the enzyme (DAO) that breaks down histamine.
2. The overgrowth of bacteria that produce histamine by fermenting the eaten foods.
3. The direct increase in the production of histamine released by food triggers.
Certain gastrointestinal diseases, such as gastrinoma and gastritis, result in increased levels of histamine due to elevated levels of gastrin.
Gastrinoma is a non-cancerous tumour that causes excess gastrin production. It often grows in the duodenum of the small intestine or in the pancreas.
Gastritis, or inflammation of the stomach lining, leads to a decrease in the production of stomach acid. To compensate for the low acidity, the body increases its production of gastrin.
Treating these GI problems and maintaining gut health are therefore the top priorities for reducing histamine intolerance.
Side note: In Sea Sickness, the levels of histamine are high.
The drugs for vertigo and sea sickness are histamine-based!
Pigs have very high levels of DAO, which is extracted from the pig and used as an adjuvant to neutralise Histamine in the diet.
It must be noted that at all times, there is one thousand times more histamine present and produced by the mast cells, even after eating histamine-rich foods.
This can explain why, occasionally, the patient does not improve solely on an elimination diet, and in such cases, the treatment will require a regimen that removes histamine and corrects the dysbiosis as well.
Anti-histamines do not remove histamine; they only block the receptors, and histamine remains in circulation until broken down by specific enzymes mediated by the following genes: MAOB, DAO, SHMT, and SUOX.
What are the effects of Histamine in the central nervous system?
According to the location of its receptors in the central nervous system, histamine can trigger different responses in the human body, for example:
Alertness.
Anxiety.
Arousal
wakefulness
sedation….
· Sleep disorders
· Eating disorders and metabolic syndrome
· Neuro-inflammation
· Migraine
· Dementia, Epilepsy and Vestibular disorders.
How Histamine Imbalance Could be Ruining Your Mood
One of the many functions of histamine in the body is to act as a neurotransmitter, where it helps regulate important brain functions such as alertness, attention, learning, memory, stress response, sleep-wake cycles, and sexual function. When the body’s histamine levels go out of control, many behavioural and psychological symptoms manifest.
While there is no solid evidence to prove the connection between histamine and mental disorders, symptoms like hyperactivity, obsessive-compulsive behaviour, panic, anxiety, and depression are often observed among those who suffer from histamine imbalance.
This is intriguing since histamine does not cross the blood-brain barrier – meaning, no matter how much histamine is in your blood, none of the excess should enter your brain.
The question remains: What causes these behavioural and psychological symptoms?
Histamine in the Brain
If histamine does not cross the blood-brain barrier, then the explanation as to how it causes behavioural and psychological symptoms is pretty simple: the brain produces its own histamine in the hypothalamus.
The brain has receptors for histamine, and mental disorders result when there is an abnormality of any of these receptors.
- H1R excites the neurons in the brain and is responsible for the sleep-wake cycle. The activation of these receptors by histamine explains why insomnia is one of the most common symptoms of histamine intolerance and how antihistamines that act on them produce a sedative effect. These receptors are also known to trigger the body’s danger response, resulting in the release of the chemical norepinephrine. Norepinephrine plays a role in anxiety and depression.
- H2R, like H1R, is also excitatory; however, its primary role is in perception, memory, learning, reward, pleasure, and pain. This explains why antihistamines that act on H2 receptors affect our perception of pain. Addiction and compulsive disorders also have something to do with these receptors, as addictive substances like alcohol and illicit drugs have been found to interfere with histamine activity in H2R. Meanwhile, compulsive behaviours such as anorexia and bulimia are related to the histamine’s effect on the reward systems of the brain.
- H3R, on the other hand, inhibits neurons from releasing histamine. These receptors are also responsible for regulating the release of other neurotransmitters from the central nervous system. Experts see drugs that target H3 receptors as a promising solution to address the effects of histamine in the brain.
Histamine and Epinephrine
An alternative explanation for the majority of behavioural and psychological symptoms of histamine intolerance, especially anxiety, is that they are generated in the body and not in the brain. This is through the ability of histamine to trigger the release of epinephrine, the major player in the body’s fight-or-flight response.
Epinephrine, like histamine, cannot cross the blood-brain barrier, but it can trigger a wide array of panic symptoms like fast heartbeat, sweating, shaking, shortness of breath, nausea, and anxiety.
Histamine and Oestrogen.
Another interesting explanation is that histamine causes oestrogen levels to rise, and this hormone can actually cross the blood-brain barrier.
As you can see in women, oestrogen has powerful effects on mood, both positive and negative. Histamine and oestrogen are synergistic, meaning they create a vicious cycle wherein one induces the release of the other and vice versa. In this case, once oestrogen crosses the blood-brain barrier and reaches the brain, it stimulates the production of histamine. Histamine in the brain, in turn, acts on its receptors to produce the behavioural and psychological symptoms seen in the imbalance.
A rare condition is progesterone hypersensitivity. This is actually an IgE reaction to your body’s progesterone.
It has been noted that with progesterone hypersensitivity, there is the inability to become pregnant and to have recurrent miscarriages.
The effect of Histamine on the bone Marrow will cause the release of MAST CELLS, which will aggravate the so-called Histamine Syndrome by 10-fold.
A particular Symptom present in MCAS is “Coat Hanger Syndrome,” characterised by severe tension in the neck and trapezius muscles.
MOUTH MICROBIOME
It is essential to address periodontal disease and to try to seal the gums back tightly, as leaky gums can occur just as leaky gut can, and this can certainly contribute to various issues. Additionally, you may also develop infections in the mouth, which is another factor to consider if you have periodontal disease.
MAST CELL ACTIVATION SYNDROME:
A more severe form of a heightened histamine imbalance is MCAS, characterised by a mutation of the receptors on the surface of mast cells.
They now become hyperactive, reactive and release histamine at a constant rate and ongoing without a trigger.
A preliminary sign of this condition is the development of acute anaphylactic shock in response to a food (such as shellfish or seeds), bees, or iodine.
All the symptoms listed above stay constant and are exacerbated in MCAS.
If one suspects that we are dealing with MCAS, an accurate test is to measure Trypsin in a non-reactive state and then during an attack. If the level increases by more than 20%, the diagnosis is made.
Treatment:
Obviously, to go on to a low-histamine diet for at least three weeks and then bring in modest amounts of histamine-containing foods.
There can be an overlap with Foods containing Sulphur and causing symptoms.
Reduce Oestrogen dominance: Dim, Sulfurofane , Calcium D-Glucarate.
It is essential to address periodontal disease and have the gums sealed to prevent leaky gums, just as we can have a leaky gut. Be sure to avoid infections in the mouth, particularly in cases of periodontal disease.
Low Histamine diet, and if no intolerance to sulphur foods, to increase them so as to produce enough Glutathione to remove Histamine via the transsulfuration pathway.
A Midsummer Night’s Dream by William Shakespeare is playfully written about the exploration of love, marriage, and the unrealistic expectations that can inexorably come along with them. This essay will examine how marriage is often portrayed as limiting and challenging, yet ultimately considered worthwhile.
Commensurate with its origins in a court marriage, this drama speaks throughout for a sophisticated Renaissance philosophy of love in both its rational and irrational forms. This is illustrated by the fact that a significant disparity existed in the expectations placed on men and women. Hermia embodies this struggle as she defies her father Egeus’s wishes to marry Demetrius, showcasing her desire for autonomy and true love rather than just fulfilling her duty to her society.
Conversely, men are generally afforded a broader range of achievements and aspirations. They are encouraged to pursue careers, adventures, and personal accomplishments that can lead to social recognition and fulfilment. Demetrius, for instance, initially pursues Hermia out of a sense of entitlement, thinking he can claim her because that is what society expects of her.
Another example is the marriage of Theseus and Hippolyta. Their relationship is rooted in conquest and power dynamics, which reflect the expectations of a hierarchical society. Theseus, as the Duke of Athens, represents a figure that signifies his authority, and his marriage to the conquered queen Hippolyta suggests that marriage can also be about control and possession rather than something more pure.
If you would like help with your condition and symptoms, contact Dr Alain Sanua for an appointment.