histamine

What is Histamine?

Histamine is a neurotransmitter which is synthesised from the amino acid histidine.

Histidine is an essential (aromatic, glucogenic) amino acid as the body cannot synthesise it and needs to be obtained from the diet. It is a precursor for the amine histamine which is produced in the body and is necessary for inflammation.

Histamine does not cross the blood-brain barrier and histamine synthesis occurs in the brain in the hypothalamus stored in histaminergic neurons. When these neurons are stimulated it releases histamine. [R]

There are four different receptors for histamine referred to as H1R, H2R, H3R and H4R. The first three are found in the brain.

These receptors have different functions and reactions when activated.

H1 is involved in the sleep-wake cycle, allergy, inflammatory response and works with the immune system. H1R which has excitatory functions when activated is involved in keeping the brain awake. Insomnia is one of the symptoms of histamine intolerance or high levels of histamine.

Antihistamines that inhibit the action of H1 receptors have shown to have sedative effect and can cause drowsiness. [https://pubmed.ncbi.nlm.nih.gov/23229983/] [https://pubmed.ncbi.nlm.nih.gov/20851648/]

The H1 receptors can trigger the body’s response to danger which stimulates the release of norepinephrine, a neurotransmitter involved in the body’s fight or flight function.

Studies are showing that GABA acts against histamine by counteracting the wakefulness caused by histamine as GABA is inhibitory with calming and relaxing effects.

H2 is a brain receptor and acts as a neurotransmitter and is one of the major neurotransmitter in the hypothalamus. The H2 receptors are also excitatory and involved in perception, memory, learning, reward, pleasure, and pain. Antihistamines that act on H2 receptors affect our perception of pain.

The H2 receptors play a role in addiction and compulsive disorders. Addictive substances such as alcohol and illicit drugs can interfere with histamine activity in these receptors.

Anorexia, bulimia and other compulsive behaviors are linked to H2 receptors and the reward systems of the brain.

H2 is involved in sending messages between nerves and sufficient levels are needed to relay these messages repeatedly, with speed and ease through the activation of the Na+ - K+ pump (sodium-potassium pump).

H3 receptor is involved in mucus production in the stomach and intestines. Unlike the first two receptors H3 receptors are inhibitory which prevent neurons from releasing histamine. These receptors regulate other neurotransmitters from the brain.

Some research is showing certain drugs that target H3 receptors may have therapeutic value for certain diseases related to histamine in the brain [R]

H4 receptors are involved in allergy and inflammation. [R]

Health Benefits of Histamine

Strengthens immune system

Histamine is involved in local immune responses and plays a significant role in immune function.

Histidine helps support the immune system through its role in the production of red and white blood cells. This can help fight infections where pathogens or inflammation is involved. It has also been used for arthritis and relieving allergy symptoms. Histamine which is synthesised from histidine plays an important role in the immune responses. Histidine is needed to help synthesize the antioxidant Superoxide Dismutase (SOD).

Studies have shown that taking histidine with zinc can fight the common cold and shorten the time it takes for recovering from a cold. This combination for colds works well because histidine helps with zinc absorption and has potential to help recovery from bacterial and viral infections.

The H1 receptor when activated by an agonist can relay messages to the immune system to find foreign invaders and start the process of eliminating it. Immune cells such as macrophages or phagocytes are the primary cells to receive the signal to destroy and eliminate the debris from damaged cells. If more foreign invaders are present these cells communicate to the immune system which continues to create natural killer T-cells to clean up the remainder damaged cells. The process continues with an imprint made of the foreign substance which is sent to the B-cells to create antibodies. An antibody is a defence system which can recognize the same foreign invader at a future time and take the necessary action.

The H2 receptor also regulates the immune system, which increases cyclic AMP to increase the production of the T-cells and B-cells.

Plays a role in allergies and inflammation

In the brain histamine functions as a neurotransmitter but can act as a hormone in other parts of the body. Histamine is a well known precursor for allergy type symptoms and having excess histamine often means sufferers need antihistamines to reduce allergies. Vitamin C acts as a natural antihistamine as well as many other key nutrients. Histamine is essential for the inflammatory response.

The body needs histidine to make enough histamine which can reduce sensitivity to allergens. Histamine is produced from histidine by the enzyme decarboxylase. Histamine is commonly known for release of mast cells in response to allergic reactions or tissue damage.

Deficiency of histidine means the body cannot make sufficient amounts of histamine.

Histamine plays an essential role in the inflammatory response of skin and mucous membranes(nose, mouth etc). This inflammatory response provides protection and acts as a barrier during an infection. Histamine is also involved in itching, a symptom often associated with the allergy response.

Histamine also regulates stomach acid production and in allergic reactions mediates immediate hypersensitivity reactions.

High or excess histamine creates allergic reactions and even implicated in inflammatory conditions. However this could be a sign of insufficient enzymes to help break down histamine which can lead to excess levels of this chemical posing many health problems.

The H1 receptor is mostly involved in the histamine allergic reactions and inflammatory responses. It works with the immune system.

Histidine can act as a natural antihistamine as it has shown to reduce histamine levels in the blood. This may be useful in cases where allergy or excess histamine production is present. Histidine also has anti-inflammatory effects and may help reduce inflammation.

This amino acid is recommended for sufferers of chronic allergy and allergic disorders. Histidine reduces allergy related symptoms by lowering or breaking down histamine. Although histidine is a natural anti-histamine, adequate levels of iodine is needed as it is a co-factor and helps utilise histidine thereby facilitating anti-histamine effects. Iodine helps utilise histidine by preventing the conversion of this amino acid into histamine.

Methionine is another amino acid that may reduce symptoms of allergies and allergy related conditions such as asthma by helping to break down and eliminate high histamine.

A mast cell response in the form of allergy symptoms can be a sign of the presence of an allergen and in many cases it is a good indicator that an allergen needs to be removed. Many toxins are exposed in the environment and can easily create a trigger response. Mold, bacterial overgrowth in the gastrointestinal tract and viral infections are also other conditions that can trigger an excessive mast cell response and release histamine.

Needed for healthy digestion

Histamine plays an important role in regulating functions of the gut.

Histidine is needed to help increase stomach acid which aids in healthy digestion. Other nutrients needed for regulating stomach acid production and digestive health includes niacin, glutamine and chlorine (chlorine in the chloride form which is found in sodium chloride or potassium chloride). Histamine, which needs histidine supports release of the digestive enzyme gastrin. Decreased histamine production can impair healthy digestion.

H3 receptor increases the mucous production in the stomach and intestines whilst the H2 receptor increases the production of gastric acid and digestive enzymes.

Histamine plays a role in cognitive function

Histidine is needed to synthesise histamine. Histamine is an important neurotransmitter that is needed for cognitive function, the immune system as well as the inflammatory response.

Studies have also shown that Histidine intake can improve cognitive function which is likely due to its role in histamine synthesis. A deficiency of histidine can lead to insufficient production of histamine.

Helps produce Melatonin

H2 production is involved in the production of melatonin. When H2 increases it stimulates the pineal gland to make melatonin.

H2 agonists activate the pineal gland which stimulates production of melatonin.

Insomnia due to disruptions to the circadian rhythm can be helped by melatonin, an essential hormone that helps regulate sleep. Although supplements can be taken it is better to allow the body to produce this naturally as not much is known in terms of health risks associated with supplemental intake of melatonin.

Melatonin is a natural hormone that regulates sleep.

Melatonin is important for Rapid Eye Movement (REM) sleep which is an important stage of sleep.

Melatonin also helps to lower mast cell activation in the histamine response which suggests that melatonin also regulates histamine functions.

A deficiency of H2 agonists or histamine will reduce melatonin levels that can impact sleep.

Melatonin is also needed for the metabolism of fats such as saturated and unsaturated fats. Melatonin has antioxidant properties preventing damage to cells from toxins and lipid peroxidation. [R] [R]

This makes the H2 receptor and its agonists even more important for the interaction and stimulation of melatonin.

Low levels of melatonin can also reduce or impair absorption of zinc which as a result can reduce immune function and increase risks of infections.

Although melatonin can also be made through the conversion of serotonin to melatonin which needs sunlight (ultraviolet rays) or vitamin D3 and other cofactors, histamine and melatonin are directly linked and have some regulatory functions on each other.

Helps with mood and satisfaction

H2 receptor acts mostly as a neurotransmitter found in the hypothalamus. Low levels of histamine can make people feel low and uninterested. Very little satisfaction is derived from enjoyable activities such as food and sex. Low histamine levels are linked to a low sex drive.

Histamine may reduce stress and anxiety as well as helping with sleep which is needed for overall health and well-being.

May help women climax

Histamine is involved in regulating ejaculations, orgasms and plays a role in sexual libido.

Histidine is needed for normal sexual function. Research has shown that increased levels of histidine can help women to climax. This is due to histamine release causing sensations of warmth as it is released. Histamine acts as a vasodilator as it increases blood flow when released which causes blood vessels and capillaries to dilate. The increased blood flow to the genital area can increase the chances of an orgasm or enhance the sexual experience. Histamine needs histidine for its production. Women with low amino acid histidine and therefore low histamine, may find it difficult to climax. [R]

In addition to the warmth sensation during sexual arousal, histidine may also help with vaginal lubrication. It is also involved in secretion of tears from the eyes and is needed for antimicrobial proteins Histatins.

Histidine also helps transport zinc, an essential trace mineral needed for the sexual response. A lack of histidine may prevent the zinc to be effectively utilized and instead get stored in the body causing excess or toxicity symptoms related to zinc.

Involved in women’s health and fertility

Histamine is produced and stored in mast cells which also contain estrogen and progesterone receptors. These hormones interact with histamine throughout a woman’s monthly menstrual cycle. When estrogen binds to its receptors it stimulates the production and release of histamine.

Histamine is more available in the presence of estrogen which peaks in the follicular phase.

Progesterone helps to balance out estrogen levels and peaks in the luteal phase. During this progesterone dominant phase DAO enzyme which helps break down histamine is higher therefore histamine levels will be lower.

Histamine plays an important role in women’s health as it helps with contractions of smooth muscle cells which are needed during menstruation for the shedding of uterus lining and also during childbirth.

Regulates other neurotransmitters

Histamine is involved in the release of other neurotransmitters. Histamine controls the release of acetylcholine, norepinephrine and serotonin. Histamine injected into the hypothalamus has shown to increase metabolism of norepinephrine and serotonin. Histamine has also shown to increase dopamine metabolism but only in some parts of the brain.

Histamine acts as a neurotransmitter with its functions taking place in the brain, spinal cord, and uterus.

Stimulates thyroid glands

The thyroid glands are essential to the entire functioning of the body. The H2 receptor are involved in stimulating thyroid glands which can stimulate sweating.

Low histamine issue can affect gland output.

Having insufficient thyroid gland can affect overall health and a disturbance can cause low body temperature.

H2 histamine can cause vasodilation of the arteries. [R]

Increase of H2 receptor agonists increase water content in the brain. This increase helps cool the brain and prevent dehydration. If dehydration is not prevented this could potentially cause a swelling in the brain which might be a cause for headaches commonly experienced by women during menstruation or the ovulatory phase when histamine levels are likely to be high.

People with MS who have low histamine or H2 tend to have low thyroid function and hormones which affects various bodily processes such as regulating temperature. People with MS tend to have lower body temperature.

Reduced H2 causes vasoconstriction (narrowing) of arteries which can lead to symptoms of dry skin, skin surface feels cold (cold feet and hands), pale or white colour skin and optic neuritis. The narrowing of the arteries can restrict blood flow to the optic nerve which can cause swelling in the area affected. This swelling may explain the headache or sinus like headaches some people experience which also is a symptom of vasoconstriction. H2 blockers can cause headaches which is one of the side effects.

Protects the blood brain barrier of damage from toxins

Histamine has a role in protecting the blood brain barrier (BBB) from damage. Blood-brain barrier is a membrane which is found surrounding the brain and spinal cord. H2 deficiency can reduce the protection of this membrane which can become permeable to harmful substances such as toxins and also organisms.

Agonists or cofactors that support H2 production also activate the pineal gland which in turn produces melatonin and cyclic AMP (cAMP) which support and maintain the BBB.

cAMP is needed to maintain the myelin sheath which insulates and protects nerves found in the brain and spinal cord. Studies have shown the absence of cAMP damages cells that produce myelin in the brain and spinal cord but may not damage the same nerves found in the peripheral nervous system such as in the arms and legs.

People suffering from multiple sclerosis (MS) have a damaged BBB with pineal gland atrophy and low levels of histamine of H2 type. MS studies have shown damaged myelin sheath particularly of the brain and spinal cord.

Sufficient H2 is needed to send messages between the nerves and a deficiency can impair this vital function.

Having a healthy functioning cyclic AMP (cAMP) is necessary for the functions of the body and deficiency has been associated in many health disorders [R] Low levels of H2 or severely deficient levels can cause the body to use up its energy molecule in order to make the cAMP.

Agonist / Synergist

Minerals Zinc, Copper, Calcium

Vitamins B3, B6, B9, B12

Amino Acids Histidine

Probiotics Lactobacillus bulgaricus (Lactobacillus delbrueckii subsp. bulgaricus or Lactobacillus delbrueckii), Lactobacillus casei, Lactobacillus helveticus, S. thermophilus, B Lichenformis, Lactobacillus reuteri

Hormones Estrogen, cortisol

Other heat (hot bath or other heat exposure), rutin

L-histidine is a precursor of histamine, the body uses histidine to help synthesise histamine and needs the enzyme l-histidine decarboxylase (HDC)

Histamine production requires vitamin B12 and B9 (folate or folic acid)

Vitamin B9 (Folic acid or active form folate) is needed when supplementing histidine as a deficiency in this vitamin has been linked to a condition called formiminoglutamic acid (FIGLU) and in excess this can cause health problems

Histidine can also be converted into histamine and glutamate. Low glutamate levels have been linked to Alzheimer’s. [R]

Deficiency of zinc affects histamine release which will diminish sexual response (impotence). Chelating too much zinc may cause nasal congestion or a runny nose. [R].

Copper is needed by the enzyme histaminase which helps to breakdown histamine – a byproduct of histidine

Histidine to histamine conversion requires B6

A healthy digestive system is needed as enzymes are dependent on a balanced system where histidine can be effectively converted to histamine

Niacin (the flush type and not non-flushing niacinamide) converts histidine to histamine

High doses of vitamin B12 increases histamine levels

Although B12 is a water soluble vitamin which means the body can remove excess, too much B12 may affect the methylation cycle or histamine levels

The enzyme histidine decarboxylase (HDC) needs amino acid histidine to synthesise histamine

Histamine is synthesized by decarboxylation of histidine by histidine decarboxylase, and needs cofactor pyridoxal-5′-phosphate which is the active form of vitamin B6

Metallothionein (MT) is an antioxidant that helps regulate copper which is needed for DAO enzymes and can prevent excess copper from building up. Zinc increases levels of metallothionein

Ceruloplasmin is an important copper binding protein, also known as a multicopper ferroxidase, it is made in the liver and helps histamine breakdown with the help of the copper containing enzyme histaminase. Ceruloplasmin regulates copper and helps with copper storage and transportation from the liver into the bloodstream carrying it to parts of the body where it is needed. Ceruloplasmin is also involved in iron homeostasis.

Rutin (high amounts found in buckwheat) prevents the breakdown of hisitidine

Histamine can stimulate the release of dopamine, norepinephrine and serotonin [R]

Histamine can also trigger release of epinephrine but this is more likely to be through its ability to release norepinephrine which can convert to epinephrine

Histaminase or DAO is the copper containing enzyme needed for histidine metabolism

Calcium regulates histamine release and helps release the body store of histamine [R]

Different methods of cooking have different effect on histamine levels. Frying or grilling food has shown to increase histamine whereas boiling certain food has shown to not increase histamine levels [R]

DAO needs cofactors copper and pyrroloquinoline quinone (PQQ)

Estrogen stimulates the production and release of histamine

Histamine stimulates release of glutamate [R]

Histamine influences body temperature.

Heat from exercise, sun, hot room or bathing in hot water increases histamine production (mostly H2) [R]

Histamine modulates sweating [R]

Increase of H2 stimulates the pineal gland synthesis of melatonin

Cortisol (cortisone) which is a hormone released during stress is involved in H2 production in a dose dependent manner. The higher the cortisol the higher the histamine production

Various probiotic strains can help increase histamine levels although very limited studies exist.

L. casei may also produce tyramine.

Lactobacillus acidophilus, Lactobacillus Lactis, Lactococcus Lactis have no effect or neutral effect on histamine levels

Some strains from the Lactobacillus reuteri species increase histamine but the type that has the beneficial effect of increasing cAMP which reduces the inflammatory response. This type of probiotics may not negatively impact people with histamine intolerance whereas the other probiotics which help increase histamine may cause excess symptoms of histamine in the inflammatory response

L. reuteri ATCC PTA 6475 is the strain which can convert the amino acid L-histidine into histamine which can increase histamine levels

DAO and HNMT are enzymes that help break down histamine and both require the cofactors magnesium, copper and B6

Benzodiazepines have shown to increase histamine [R]

Studies have shown that music therapy can affect histamine, the immune system and affect biomarkers of stress such as salivary cortisol levels. Music may be a healthier option in reducing excess histamine and lower biomarkers of stress.

Studies on Receptive Music Therapy found that “feel good music” can reduce and block histamine secretion by the salivary glands in two groups of allergic and non-allergic volunteers. However blood histamine levels remained unchanged. [R] [R]

One study has revealed that music in “major” mode can be more effective at reducing stress conditions (mental fatigue) than “minor” mode music with the ability to reduce cortisol levels and increase a sense of happiness. [R]

Classical music by Mozart or Beethoven in C major may be helpful as well as Jazz music which include major notes. Examples of major mode music in classical symphonies include Mozart (C major), The Blue Danube Waltz by Johann Strauss II, Waltz from Swan Lake by Tchaikovsky.

Major notes can be found in many Jazz music which includes Ain't Misbehavin by Fats Waller, Stormy Weather (1943), and a selection of Glenn Miller big band tunes. Other popular songs in Major mode include Dreams by Fleetwood Mac (C Major), Sway – Dean Martin (C Major), Life by Des’ree, 'Walking On Sunshine' by Katrina And The Waves.

Major mode music tends to be more upbeat and depending on lyrics may even increase dopamine levels however songs will need to be the pleasurable type rather than songs about breakups or mishaps.

In general listening to songs with upbeat or positive lyrics may be better than listening to songs with negative connotations. Songs from the 80s and prior to the 80s are more upbeat than latest and current generation of songs.

Listening to frequencies that create binaural beats in major mode may potentially be helpful in relaxation and reducing stress levels however more studies are needed.

Antagonists

Iodine inhibits conversion of histidine to histamine

SSRI drugs may interfere with the conversion of histidine into histamine and may have an increased need for histidine and its cofactors if deficient

Digestive problems can interfere with absorption of histidine which can subsequently reduce or inhibit production of histamine

Licorice can deplete or inhibit monoamine oxidase (MAO). MAO which can lead to excess build-up of histamine – this can be a problem if too much histidine is converted to histamine

Methionine methylates histamine and deactivates it. Methionine helps with histamine breakdown (histamine is involved in allergies and asthma) Methionine methylates and deactivates histamine through its role in the methylation cycle and synthesis of active nutrient SAM-e

Vitamin B15 (Pangamic acid or calcium pangamate) reduces histamine levels

A diet high in cabbages (Chinese red variety) has shown to lower histamine

Different methods of cooking has different effect on histamine levels. Frying or grilling certain food can increase histamine content of food [R]

Vitamin C acts as a natural antihistamine as well as many other key nutrients

H1 receptor activation may interfere with dopamine release. Some medications that block the H1 receptor have shown to increase dopamine release.

Histamine increases prolactin release through the H2 receptor which subsequently inhibits dopamine production.

High DAO and HNMT will deplete histamine levels

High MAO may also reduce histamine levels

Histamine and GABA govern wakefulness [R]

GABA counteracts effects of histamine – prevents wakefulness which is appropriate for relaxation or sleep

Dairy can cause a mast cell or histamine response

Bifidobacterium infantis, Lactobacillus gasseri, Lactobacillus rhamnosus, Bifidobacterium longum, Lactobacillus plantarum, Bifidobacterium breve, Lactobacillus salivarius, Bifidobacterium lactis, Bifidobacterium Bifidum

The strain is the specific type belonging to a probiotic species. For example Lactobacillus plantarum K-1 is a strain of the Lactobacillus plantarum species.

Several different strains of Lactobacillus plantarum have shown to reduce histamines and other biogenic amines found in wine

Lactobacillus plantarum – strains from this species that help lower histamine includes Lactobacillus plantarum K-1 and L. plantarum LP299v.

Lactobacillus plantarum also reduce or inhibit tyramine and putrescine.

Strains from Lactobacillus rhamnosus species that help lower histamine includes Lactobacillus rhamnosus GG (LGG®) and L. rhamnosus Lc705. Lactobacillus rhamnosus can also downregulate genes linked to mast cell activity. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042653/]

Lactobacillus gasseri SBT2055 strain from the Lactobacillus gasseri species helped supress inflammation

Lactobacillus salivarius shown to help mast cells by balancing Th1/Th2 [R]

Bifidobacterium bifidum BGN4 probiotic strain from the Bifidobacterium bifidum species has shown to suppress allergic symptoms and inflammation

Bifidobacterium breve BR03 probiotic strain from the Bifidobacterium breve species was shown to suppress histamine.

Strains of some probiotic species may help some people with Mast Cell Activation Syndrome (MCAS) or Histamine Intolerance

Stress can block production of H2 receptor. This is a normal response and function which is temporary

Food Sources of Histamine

Histamine can be obtained from food directly but is also synthesised in the body through cofactor nutrients that help the brain and body to produce histamine.

It is important to eat foods rich in the amino acid histidine and other cofactor nutrients.

Histamine content in food increases during fermentation so the longer the food is stored the more histamine will be present. Aged and fermented food are high in histamine and these include pickled foods such as gherkins, kombucha, sauerkraut, pickled chutney (mangos, carrots etc) and kimchi.

Most dairy food contains high histamine as most go through the aging process and these contain cheese, yogurt as well as processed cheese.

Canned foods are a source of histamine. Canned foods have very long shelf life and the increased length of time increases amount of histamine.

Dried meats or fish also contain histamine levels which includes beef jerky, salted dried fish (Pollock). Sausages, lunchmeat and liver also contain histamine.

Alcoholic beverages that go through fermentation process such as wine and beer also contain histamine

Plant based food sources of histamine include various fruits and vegetables such as citrus fruits, strawberries, bananas, pears, pineapple, avocado, tomatoes, eggplant, olives and beans.

Condiments are high in histamine as they are stored for long period of times. Some condiments are also fermented such as vinegar, soy sauce, worcester sauce and hot spices. Many condiments also included these fermented ingredients such as vinegar in mayonnaise.

Bleached wheat flour is a source of histamine. On a low histamine diet it may be better to go for unbleached flour varieties. Some organic flours such as rye flour which is available as a white flour is unbleached and has an off white color as opposed to bright white in plain wheat flour.

Beverages with histamine content include coffee, alcohol (beer, wine etc), black tea, orange juice and lemon water.

Different methods of cooking change the histamine levels in foods. Frying and grilling of meats or vegetables increases histamine whereas boiling does not cause an increase. Leaving food out for longer increases histamine content of food even if refrigerated and is best if frozen to prevent histamine from increasing. [R]

Some food products may also contain high histamine food.

Food additives, food additives and preservatives such as benzoates and sulfites can release histamine.

Spoiled fish such as tuna, mackerel, anchovies, skipjack and shellfish contain high amounts of histamine which causes Scombrotoxic fish poisoning (SFP) or histamine fish poisoning and should be avoided due to their toxic effects.

[R]

Dried fish contains high amounts of histamine [R]

Recommended daily allowance

There are no set amounts of recommended neurotransmitters. Neurotransmitter synthesis depend on the nutrients obtained from the diet or supplementation. Brainwave frequencies and other practices such as meditation can also effect levels of neurotransmitters.

Neurotransmitters are made from protein and amino acids. They also need other cofactors such as vitamins and minerals for synthesis.

Dietary protein is therefore essential and getting adequate, sufficient supply of all nutrients in the correct balance is essential.

A healthy adult needs between 40 and 70 grams of daily protein intake. This can go up to as much as 90 grams for active and athletic people.

Diet and nutritional supplementation can be tweaked to meet the requirement of necessary nutrients and ensuring adequate levels of neurotransmitters.

Neurotransmitters operate at different times of the day and are largely dictated by light exposure. Serotonin and dopamine are produced mostly during daylight hours. During dark hours the serotonin converts to melatonin and more GABA is present.

Brainwaves also correspond with the different neurotransmitters. In the morning the brain has alpha waves which increase to beta waves throughout the day. Gamma waves may also facilitate the daylight hours and ideal for higher learning. The alpha and beta waves facilitate acetylcholine and dopamine.

Other factors such as the seasons and a woman’s monthly menstrual cycle can also determine the amount of specific neurotransmitters needed and at which point of the cycle. For example in the luteal phase GABA is the primary inhibitory neurotransmitter as this part of the phase we see a spike in the hormone progesterone which works synergistically with this calming neurotransmitter. Serotonin will also be present at this time as well as more conversion into melatonin to facilitate sleep.

Dopamine will be more available during the follicular phase which seems to increase with the rise of the female reproductive hormone estrogen.

In northern climates during winter with the lack of sunlight there is likely to be a lower production of serotonin or higher amounts of this may convert to melatonin possibly through daylight hours shortening. This may pick up slightly as spring emerges. Many people also find that spring makes them feel motivated.

Everyone is unique and a person’s life experience may dictate more of what neurotransmitter may be required on any given day. An example is a highly stressed person is very likely to be needing more serotonin and dopamine and possibly other neurotransmitters as the chronic stress quickly depletes all neurotransmitters and can lead to a state of depression.

Checking deficiency levels of neurotransmitters can help determine what may be needed along with using brainwave measuring device which uses electroencephalography (EEG) may help identify the neurotransmitters needed and balancing levels.

The difference in amounts of brain neurotransmitters found in men and women indicate that men need more dopamine than women and women need more serotonin than men.

Dopamine rises during the day and is low during the evening and in sleep. In women dopamine rises along with estradiol (estrogen) which rises in the follicular phase and peaks around ovulation.

Norepinephrine is an excitatory neurotransmitter and levels are found to be lowest during sleep but rise during during wakefulness. Under situations of stress or danger there is a higher level of norepinephrine.

When there is no stress or very little stress norepinephrine and epinephrine levels remain low. Towards mid-morning levels begin to rise and peak in the afternoon. Levels are low closer to bedtime in the evening.

High levels of norepinephrine occur during ovulation and early luteal phase which is also the point where dopamine and estrogen levels peak. There is also a relationship of norepinephrine and melatonin. Melatonin is higher during luteal phase. [R]

In women histamine is highest around ovulation and is aligned with the peak of estrogen which is highest during follicular phase.

Histamine Supplementation

When supplementing with probiotics it is ideal to use formulas in delayed release capsules to reach the intestines without being dissolved in stomach acid. Probiotics need to reach the intestines to carry out their functions. Probiotic supplements will usually display whether the probiotic is delayed release or may be labelled as hydroxypropyl methylcellulose or hypromellose as capsule shell.

Avoid fillers and additives which can trigger allergic reactions and be especially problematic for people with excess histamine production or allergies. The allergens to avoid include maltodextrin, lactose, soy, wheat starch, titanium dioxide, colors and others that can increase histamine or cause an allergic reaction.

High intakes of histidine of more than 24g per day has shown to impair cognitive function and deplete zinc levels.

Deficiency Symptoms of Histamine

Histamine is an important neurotransmitter involved in many functions and reactions within the body and brain.

Histamine deficiency may be linked to deficiency of histidine or the inability to convert histidine to histamine.

Histapenia is a condition where histamine levels in the brain are too low. Low levels of histamine can affect mood and behaviour. Low levels of histidine or impaired conversion from histidine to histamine can cause health problems.

Low intake of histidine has shown to reduce brain content of histamine which has caused anxiety like behaviour in animal studies. [R]

Histamine deficiency signs and symptoms include:

Neurotransmitter imbalance
Rapid mood swings (Mood changes usually on the down side)
Easily frustrated
Irritable (especially under stress)
Daydreaming
Low productivity
Tired (physical fatigue)
Slow metabolism
Sleep disorder (Needing a lot of sleep)
Depression
Low libido (sex drive)
Low tolerance to alcohol (drunk on very small amounts of alcohol)
Low tolerance to most drugs (easily affected by drugs)
High tolerance for pain or high pain threshold (tolerate pain quite easily)
Paranoia
Low estrogen
Racing thoughts (occasional or frequent)
High mean corpuscular volume (MCV)
Anxiety or panic
Poor achiever
Poor motivation
Artistic or musical ability
Overweight
Self harm / mutilation
Self isolation
Nervousness
Tinnitus
Food sensitivities
Chemical sensitivities
ADHD
Schizophrenic symptoms (includes paranoia, grandiosity, hallucinations, religiosity)
Hyperactive psychosis
No family history of histadelia
Hirsutism (excess bodily hair)
Dental Cavities
Normal toes (unlike in histadelia)
Pear shaped body
Eczema/dry skin
Overmethylation

Paranoia such as thinking the world is against them and hallucinations are likely to be present in younger people with low histamine. Depression is more likely in older people with low histamine.

Histamine imbalance may interfere with other neurotransmitters.

People with histamine deficiency are referred to as histapenics. The condition is characterized by some qualities and personality traits as well as physical manifestations. Histapenics may be considered to be thought of as daydreamers appearing to be out of touch with reality and show low productivity in work or career and considered to be low achievers.

Histamine deficiency reduces melatonin production which can decrease fat metabolism of the brain and body and add extra stress on the body.

Histapenics are prone to rapid mood swings which are typically on the down side.

Blood test may show a low basophil count [R]

Mast cells and basophils are a source of histamine [R]

Causes of deficiency:

Low histidine
Vitamin B12 deficiency
Vitamin B9 (folic acid/ folate) deficiency
Vitamin B6 deficiency
Excess Histaminase or DAO
High copper levels (especially inorganic type)
Low copper levels

L-histidine is a precursor of histamine, the body uses histidine to help synthesise histamine and needs the enzyme l-histidine decarboxylase (HDC) for the synthesis of histamine by decarboxylation of histidine. HDC needs the cofactor pyridoxal-5′-phosphate (P5P, active form of vitamin B6).

Histaminase or DAO is the copper containing enzyme involved in various metabolic pathways and is needed for histidine metabolism.

Serum copper levels in histapenics are found to be high and may cause elevated levels of enzymes such as the DAO which break down histamine causing a deficiency. Some studies have shown high blood levels of copper and low levels of zinc. Low urinary copper can also be a sign of copper retention. Inorganic copper is even more problematic as the body is not able to utilize it making bioavailable organic copper essential.

If histamine is low and likely caused by excess copper, then cofactor nutrients which help lower copper levels may support production such as zinc, manganese, vitamin C, vitamin B3 (niacin), vitamin B12, and vitamin B9 (folate / folic acid).

Copper deficiency can also impair the production of H2. The chemical needed to produce H2 is a copper containing chemical and if copper becomes deficient this can impair histamine production. It is possible that in this case the low copper may simply be the inability for utilization of inorganic copper.

Conditions related to histamine deficiency include:

Multiple Sclerosis [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334194/]

SSRI drugs can make it difficult for some people to orgasm easily as the drug can inhibit conversion of histidine into histamine, increasing the need for histidine and or nutrients that are histamine cofactors either through supplementation or obtained from the diet.

Antihistamines has shown to decrease libido possibly through its action on reducing histamine levels. Low histamine is linked to a decrease in libido and high histamine levels is linked to increased libido.

On the other spectrum women who orgasm easily may have excess histamine, and are known as histadelics.

Overmethylation is also linked to histapenia.

Symptoms of overmethylation include:

Low histamine
High levels of serotonin and dopamine
Low zinc
Low basophil count
Copper overload
Low libido
Adverse reaction to SSRI’s and SAMe
Improvement with benzodiazepines (increases histamine)
Dry eyes and mouth
Tendency to be overweight
Restless legs
Sleep disorder
Tinnitus
Hirsutism
Food or chemical sensitivities
Estrogen intolerance
Antihistamine intolerance
Absence of seasonal allergies

Some psychological / mental symptoms and traits of overmethylation include:

High anxiety/panic
Hyperactivity
Rapid speech
Religiosity
Pacing
Low motivation during school years
Depression
Self-mutilation
Artistic or musical ability

Toxicity Symptoms of Histamine

If there is too much histidine this can also lead to excess production of histamine and can cause symptoms of histamine toxicity.

A deficiency of the enzyme histidase (related to a rare metabolic disorder known as histidinemia can impair histidine metabolism causing excess histidine to increase in the blood.

Histadelia is a condition where histamine levels in the brain are too high which can affect mood and behaviour. Histadelia also accompanies elevated blood levels of histamine which will be characterized by adverse symptoms mostly involving the allergic and inflammatory response.

Signs and symptoms of high histamine include:

Histamine intolerance
High tolerance for alcohol
High tolerance for drugs
Stress (lower tolerance for stress)
Pain intolerance / Low pain threshold (Sensitive or intolerant to physical pain, easily burned etc)
High libido (sex drive)
Easily orgasms
Depression
Suicidal tendencies
Less sleep needed than most people
Hyperactivity
Bad stomach (Abdominal cramps)
Stomach ulcers / Peptic ulcers
Low blood-sugar levels (hypoglycaemia)
Adrenal fatigue or exhaustion (hypoadrenocorticism)
Rapid or Fast metabolism
Lean build
Allergies or intolerances
Seasonal allergies (sneezing etc)
Excess mucus production (in nose, throat and other parts)
Excess sweating
Nasal congestion
Frequent colds
Headaches or migraines
Excess salivation
Good oral health and strong teeth
Tissue swelling
High or low blood pressure
Rapid heart rate
Abnormal fears or compulsions
Obsessive-compulsive (OCD) behaviour or tendencies (manifests as ritualistic behaviours, obsessions and compulsions) [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488951/]
Perfectionist
Ritualistic behaviour
Needing routine, order or control over things
Anxiety / Internal anxiety
Inner tensions (displaying calm exterior)
Brain fog (Spacing out or blank mind) [R]
Phobias
Abnormal menstrual cycle
Difficulty falling asleep
Difficulty regulating body temperature
Fatigue
Flushing
Hives
Wheezing (difficulty breathing)
Nausea
Vomiting
Vertigo or dizziness
Undermethylation
Poor short-term memory
Poor dream recall (due to low vitamin B6 and other neurotransmitters)
High achiever (High academic achiever / accomplished)
Highly motivated (Self-motivated)
Highly competitive nature (Competitive, especially in sports and games)
Strong will
Shy (Considered a loner)
Antisocial personality
Adrenal exhaustion or fatigue
Infrequent and terse speech
Intrusive/excessive thoughts
Oversensitive
Cries easily
Poor concentration
Dissatisfied with body (Issues with body image)
Waking up at night (easily woken)
Unwillingness/noncompliance for treatment or therapies (do it yourself)
Denial of illness (hiding problems)
Lack of empathy (psychopathic tendencies in severe cases)
No display of emotions
Catatonic
Episodes of blank mind
Oppositional or defiant as child / youth
Rumination about past events
Delusions
Dietary inflexibility
Lack of interest in music
Low serotonin, dopamine and norepinephrine
High body temperature
Profuse perspiration
Heavy salivary flow/tears etc
Prominent incisors
Veins often prominent
Sunburns form more quickly (from having more capillaries, sunburn rate will be dependent on skin complexion
Frostbites form more quickly (same reasons as for sunburns)
Sparse facial/body hair (beard/chest/arm/leg)
Weaker hair growth (seen in men)
Acne
Early aging (wrinkles, gray hair etc.)
White spots on fingernails (from low Zinc or SAM-e)
May have larger ears (growing due to excessive heat)
Long fingers and toes (depending on other genetics also)
Seasonal allergies
Tends to sneeze in sunlight
Hives
Glue ear (glue-like fluid fills up the empty middle part of the ear canal instead of air)
Headaches
Backaches
Muscle cramps (from low magnesium)

Lean build will often be a consequence of fast metabolism where the person may have a big appetite yet not appear to put on much weight although other factors can play a role such as other illnesses.

Undermethylated mothers are more likely to give birth to autistic children.

If the mother has given birth to mostly male children this is likely to make the child have high histamine with undermethylation issues. Women give birth to male babies due to thin copious vaginal secretion.

A person whose father had mostly brothers or their mothers father mostly had brothers is likely to have the genetic defect which contributes to high histamine and undermethylation.

Blood histamine levels are correlated with histamine levels. The methylation process is affected by histamine levels, when histamine increases methylation decreases and when histamine decreases methylation increases. Low blood histamine may indicate the person is overmethylated and high histamine levels may mean the person is undermethylated. In each case the methylation process may need to be corrected with supplementation. The supplements that support methylation or help lower methylation will also impact the histamine levels accordingly. There is no evidence that genetic methylation defects can be reversed and supplementation may be required to normalize overmethylation or undermethylation conditions.

Some symptoms of undermethylation are the same as high histamine levels (histadelia) which include being a high achiever (before illness), self-motivated through school, having a strong will and high motivation. An inner tension is present though appearing with a calm demeanour and will have ruminations about past. Undermethylators also exhibit sparse hair growth, have high libido, energy, low tolerance for pain and heat as well as addictive behaviour. They tend to be delusional and have various phobias and may be diagnosed with OCD or ODD. Socially they are isolated. They tend to have frequent headaches, seasonal allergies and be in denial of any present illness.

Undermethylators or histadelics are often non-compliant and have difficult transitions. Undermethylation present in those with catatonic psychosis. [R].

Undermethylators tend to have low vitamin B6, magnesium, calcium and methionine with high levels of folate. There is also some family history of undermethylation.

Some physical characteristics of Histadelics are long fingers and toes.

Histadelics are often highly creative and have a tendency to work compulsively. Their fast metabolism can result in hyperactivity. They also carry a great deal of inner anxiety which contributes to inner tensions however may appear to be calm.

Histadalia may be more common in males than having low histamine levels. Histadalia is also quite common in most women who seem to develop histamine intolerance with tell-tale signs in their monthly cycle associated with menstruation and ovulation.

Histapenia which is having too little histamine may be less common in men.

Histamine mostly lowers blood pressure but can cause the release of other hormones or neurotransmitters that raise blood pressure such as adrenaline.

Blood test may show a high basophil count [R]

Blood tests can be used to check histamine levels through a differential white cell count which will indicate a basophil count. The normal range for basophils is between 10 and 140. Amount higher than 140 indicates high histamine levels.

The mean corpuscular volume (MCV) and the mean corpuscular haemoglobin content (MCHC) tests can also give an indication of histamine levels. The MCV test measures the size of red blood cells (large or small). MCHC tests measure the amount of haemoglobin contained in the red blood cells. Low MCV with a high MCHC may be a sign of high histamine levels.

Histamine is synthesised in the brain and does not cross the blood brain barrier which means that much of the behavioural and psychological aspects of histamine will be dependent on brain production of histamine where it acts as a neurotransmitter. The physical symptoms of histamine are more likely to arise from high intake of histamine foods which can cause various allergies especially in those who are histamine intolerant.

People with high histamine levels are referred to as histadelics. The condition is characterized by some personality traits. Histadelics tend to be high achievers often successful in their vocation. They tend to have good teeth from the extra salivation. They tend to also have a bad stomach and which can form into stomach ulcers from being too tense.

When histamine levels are in balance a person can be highly intelligent, very productive, and successful in their career or work and in other aspects of their lives.

However when levels are out of balance and histamine becomes too high this can lead to various health problems.

During stress the body releases histamine and other chemicals and hormones such as cortisol.

A state of high stress can make allergic reactions worse by increasing the release of histamine. High performers and achievers are usually under significant stress which can cause strain and increase histamine levels worsening symptoms of high histamine.

Histadelics can experience bouts of depression, and although this is not frequent and does not last for long periods of time they may entertain suicidal thoughts when the symptoms of depression occurs.

Most symptoms may not be consistent and vary throughout certain periods of time.

Some studies are showing that histamine metabolism may be impaired in people with MS. Histamine levels in the cerebral spinal fluid of MS patients has been found to be 60% higher than that of controls, with lower activity of histamine N-methyltransferase (HNMT, HMT) than that of controls. [R]

Methionine can act as a natural antihistamine as it has shown to reduce histamine levels in the blood. It reduces histamine by helping to break it down. Methionine methylates histamine and deactivates it. This may be useful in cases where allergy or excess histamine production is present.

Histadelics have excess histidine and therefore an excess production of histamine which can make some women orgasm easily. These people are often extremely emotional and cry at the drop of a hat. In these cases extra supplementation may make a person cry emotionally. If emotionality symptoms (weeping or crying at the drop of a hat) increase and orgasm is achieved too quickly and easily it may help to reduce histidine and histamine or lower dose of supplements if they cause these issues.

The emotionality and secretion of tears may also be induced by reduced estrogens in the body as is experienced in menopausal women.

Women are more prone to histamine intolerance than men and are affected at various points of the monthly cycle with the condition being worse during ovulation when estrogen is at its highest levels and higher than progesterone as estrogen increases histamine. Histamine also may be higher prior to menstruation if it has not broken down properly or continues to increase causing some PMS symptoms. Tears contain histamine and the excess unusual weeping by high histamine types may be a biological mechanism to reduce histamine levels via tears as well as other secretions such as excess saliva production. Interestingly high histamine types also have good teeth which is likely due to extra saliva being produced. There may be a link with emotional allergy and high histamine.

If in doubt when supplementing with histidine, if starting with a dose of 500mg causes these symptoms it is better to lower dose to 250mg and reducing until the symptoms wear off. Some people may be unable to take histidine until other cofactors are replenished.

Histamine intolerance, (also known as enteral histaminosis or sensitivity to dietary histamine) is the inability to break down and utilize ingested histamine. The symptoms in these cases may be related to allergy and inflammatory responses of the body. [R]

High or excess histamine creates allergic reactions and even implicated in inflammatory conditions.

Methionine is another amino acid that may reduce symptoms of allergies and allergy related conditions such as asthma by helping to break down and eliminate high histamine.

Although allergy symptoms can persist throughout the day they can get worse during the night when histamine levels are high. As a neurotransmitter histamine is excitatory and most excitatory neurotransmitters are active throughout the day until night time. [R]

Causes of histamine toxicity or intolerance:

DAO deficiency
HNMT deficiency
Allergen triggers
Excess estrogen (estrogen dominance)
High dietary intake from histamine containing food
High supplementation of histamine cofactors.
Stress .
High cortisol.
High histamine is more common in women and correlates with the menstrual cycle and can be worse at ovulation and before menstruation. .
Scombroid poisoning (from spoiled fish) .
DAO helps break down histamine. .
Impaired methylation (usually due to low cofactors) .
Mast Cell Activation Syndrome (MCAS) .
Stress increases H2 production and activity.

Mast cells, basophils, and eosinophils are white blood cells that are involved in allergies and inflammatory reactions.

Immunoglobulin E (IgE, antibodies produced by the immune system) molecules and allergies play a role in triggering mast cell histamine release

IgE bind to mast cells, eosinophils and basophils depending on allergen and cause the white blood cells to release histamine. Although these white blood cells cause the inflammatory response they are essential for immune function.

Health problems start when mast cells proliferate leading to mastocytosis and release high histamine levels. In Mast Cell Activation Syndrome (MCAS) there is a higher number of mast cells which are triggered without being exposed to an allergen where the immune system in effect is attacking the body.

In many cases of allergic reactions antihistamines or other medications with anti-inflammatory properties may be recommended by physicians or general practitioner. These medications act by reducing histamine levels. In MCAS it may be more difficult to reduce symptoms through antihistamines alone.

Neuroinflammation (inflammation of brain or spinal cord) is more likely from excess activation of microglial cells (cells found in the brain). In severe cases it is important to lower IgE levels, identify and eliminate allergy triggers.

High histamine levels are linked to the following health conditions:

PMS and menstrual problems

Parkinson’s disease

Schizophrenia

Autoimmune diseases or disorders

Anorexia and bulimia

Cancer

Respiratory allergies/asthma

Rhinitis

Osteoporosis

Arthritis

Cataracts

Lupus

Menstruating women with DAO deficiency may have higher histamine levels during luteal phase and during the monthly period along with various symptoms which includes:

PMS
Period pain
Painful bloating
Motion sickness
Sweating
Headaches
Anxiety
Acne
Insomnia
Hives
Brain fog
Skin rashes
Prickly heat
Low libido
A red flush with alcohol consumption
Nasal congestion
Itchy throat

DAO can be significantly low if other cofactors are low and people with a deficiency of this enzyme are likely to have high histamine.

If estrogens are high (estrogen dominance) this may increase histamine levels leading to symptoms of histamine intolerance and potentially disturb the balance or increase the requirement of DAO enzyme. Women who are histamine intolerant may notice the symptoms are worse during follicular phase during menstrual bleed and before or around ovulation when estrogen levels peak.

The methylation cycle plays an important role in breaking down histamine as well as other monoamine neurotransmitters. The methylation cycle is also important for inactivating estrogen and eliminating it from the body. An impaired methylation cycle will reduce this important function causing excess circulating estrogen which can stimulate histamine production.

Histamine n-methyltransferase (HMNT) enzyme regulates histamine in the body by converting histamine into N-methylhistamine and then eliminated from the body. This process is dependent on the methylation cycle.

Histamine is involved in the release of norepinephrine and epinephrine which stimulates the fight or flight response. High histamine can potentially raise norepinephrine and epinephrine levels causing symptoms such as anxiety, rapid heartbeat, shaking, sweating, nausea and other symptoms that are related to the release of norepinephrine and epinephrine.

Histamine is released by mast cells as part of the immune response.

Histamine is also released from the cells found in the ovaries and uterus.

Certain conditions related to estrogen dominance such as endometriosis, PCOS, fibroids, cysts, or PMDD can be accompanied with a worsening of symptoms when histidine is high. This can result in increased contractions, painful cramps and heavier bleeding when menstruating.

Similarly histamine also increases estrogen production so having an estrogen dominant condition will simply be made worse if histamine becomes too high.

Estrogen also reduces DAO activity needed for histamine metabolism and therefore increases histamine levels.

An estrogen dominant condition is also a sign of low progesterone which is needed to keep estrogen levels balanced. Progesterone prevents histamine release when binded to its receptors on mast cells.

DAO enzyme levels are increased when progesterone levels peak around luteal phase.

Pregnancy increases DAO by up to 500 times the normal levels and produced by the placenta which protects the developing fetus from histamine toxicity as well as early contractions. This higher level of DAO can alleviate symptoms associated with histamine intolerance during pregnancy.

[R] [R]

Women who are histamine intolerant are likely to experience headaches around ovulation or before menstruation when estrogen levels are highest. Histamine related headaches prior to menstruation may be a sign of a hormonal imbalance that affects histamine levels as seen in estrogen dominance which accounts for the menstrual cramps and contractions in the uterus caused by the histamine.

In a woman’s monthly cycle during the early luteal phase after ovulation there is less histamine present with progesterone peaking. This is the phase where DAO enzymes are higher so that more histamine is broken down. Low progesterone levels with high estrogen can create an imbalance and a higher level of circulating histamine causing various symptoms.

With high histamine or histamine intolerance it is best to avoid foods high in histamine. Eating fresh food is ideal to avoid histamine as much as possible. Some food products may also contain histamine and it is a good idea to always read labels for food additives, food colorings, soy sauce or other histamine based ingredient.

Freezing food is a better method of storing food to avoid histamine production. Slow cooking food also increases histamine and should be avoided. Pasteurized dairy and cheese made from pasteurized milk contains less histamine than raw milk. [R]

Supplements and medications may also be a source of histamine and should be checked on label for list of ingredients.

Boiling food in water rather than frying or grilling will contain less histamine. It may be ideal for women of childbearing age to limit histamine producing food during luteal phase especially if histamine intolerance is worse during menstruation.

Scombroid poisoning can cause histamine toxicity. It is a food poisoning caused by spoiled fish. Certain fish contain high levels of the amino acid histidine which can be rapidly converted to histamine in the presence of bacteria.

This kind of poisoning can cause mast cells to release histamine and trigger an allergic reaction.

Scombroid poisoning is likely to occur from spoiled fish which includes tuna, mackerel, mahi mahi, anchovy, herring, bluefish, amberjack, skipjack, bonito and marlin. Scombroid poisoning is usually found in the dark meat of fish. If fish is not refrigerated properly it causes bacterial overgrowth which converts histidine to high levels of histamine.

Fish will quickly spoil in temperatures above 4 degrees Celsius causing a growth of bacteria that cause histidine to convert to histamine. [R]

Scombroid poisoning can occur within 5 to 30 minutes of eating spoiled fish with high histamine content though it can take longer to experience symptoms of poisoning. The following are symptoms of scombroid poisoning:

Flushing (face and body)
Nausea
Burning mouth
Headache
Faintness (may be accompanied with blurring vision)
Abdominal cramps
Diarrhea
Breathing problems (eg. wheezing)
Swelling (face and tongue)

Scombroid poisoning symptoms can last from a few hours or a day. It can persist for several days however this is rare.

Scombroid poisoning may be detected if it occurs in several people who have eaten the same contaminated food or if it has affected an individual then the poisoning may be traced back to the meal eaten.

Scombroid poisoning may require immediate emergency medical attention depending on the severity of reaction.

Niacin helps convert histidine to histamine, excess niacin and excess histidine may cause higher levels of histamine.

The enzyme Diamine oxidase (DAO) which is also known as "amine oxidase, copper-containing, 1" (AOC1), and previously called histaminase (EC 1.4. 3.22) helps with the metabolism, oxidation, and inactivation of histamine and used in treating allergies. It is also involved in other polyamines such as putrescine or spermidine in animals.

The histaminase enzyme is found in the digestive system and needs cofactors copper and pyrroloquinoline quinone (PQQ).

The systematic name of this enzyme class is amine:oxygen oxidoreductase (deaminating) and is a copper-containing enzyme.

The diamine oxidase (DAO) enzyme is also known by other names which include diamino oxhydrase, histaminase, amine oxidase, monoamine oxidase, amine oxidase (pyridoxal containing), benzylamine oxidase, histamine deaminase, histamine oxidase, Cu-amine oxidase, amine oxygen oxidoreductase, diamine:O2 oxidoreductase (deaminating), semicarbazide-sensitive amine oxidase, and SSAO.

DAO or histaminase enzyme participates in various metabolic pathways which includes urea cycle and metabolism of amino groups, glycine, serine and threonine metabolism, histidine metabolism, tyrosine metabolism, phenylalanine metabolism, tryptophan metabolism, beta-alanine metabolism, and alkaloid biosynthesis ii.

Studies are showing people with hyperthyroidism were found to have low levels of MAO and DAO (histaminase) both of which are copper containing enzymes. This may be an indicator of low copper [R]

Psoriasis patients were found to be high in histamine and low in monoamine oxidase (type B) and diamine oxidase.

Diamine oxidase is a copper-containing enzyme which breaks down histamine.

Histamine can trigger asthma with antihistamines recommended for fast acting relief. [R]

Licorice depletes monoamine oxidase.

Licorice inhibits MAO enzyme activity which can prevent the breakdown of histamine and cause increased levels of histamine

Diamine oxidase (DAO) and monoamine oxidase (MAO) are histamine metabolizing enzymes needed to break down histamine.

Monoamine oxidase may have some connection to thyroid health where some conditions such as hyperthyroidism may get worse when consuming excess licorice as it acts as a monoamine oxidase inhibitor (MAOI). Its effect is mostly unknown and not thoroughly studied in thyroid health but may possibly benefit hypothyroidism.

[R]

Monoamine and diamine oxidase activity may be used to determine diagnosis of carcinoid tumors [R]

Patients with medullary carcinoma of the thyroid have excessive serotonin (5-HT) production from the mast cell tumor and have shown to have high plasma histaminase [R]

Histamine and the methylation cycle are interconnected with high histamine connected to undermethylation and low histamine connected to overmethylation.

Tetrahydrofolate (THF) deficiency can elevate histidine levels. High histidine can convert to high levels of histamine. High histidine with high histamine may be a sign THF is needed.

Some tests such as a Metabolic Analysis Profile Test (MAP test) can reveal FIGLU levels.

Insufficient THF can raise FIGLU if taking high dose histidine.

High FIGLU may be an indication of excess histidine and low THF. High levels of histidine may lower levels or inhibit utilization of other amino acids.

High histidine is also linked to high cholesterol and blood test can help to check cholesterol levels.

Sufficient THF is needed to help process histamine.

The methylation cycle is involved in processing and breaking down histamine and other monoamine neurotransmitters.

Elevated FIGLU levels will cause higher levels of histidine to build up which can then convert to high levels of histamine.

Methyl groups are needed to process histamine. Supporting the methylation cycle, such as the production of SAM-e will help breakdown and lower histamine levels. Methionine is needed for the methylation cycle and also helps with the synthesis of SAM-e.

The enzymes responsible for breaking down histamine include diamine oxidase (DAO) and histamine N-methyltransferase (HNMT).

The HNMT enzyme requires methylation cycle to break down histamine.

The DAO enzyme requires copper to carry out its function on breaking down histamine.

High levels of copper can interfere with the production of serotonin and dopamine as this mineral supports enzymes such as DAO and MAO which is involved in the breakdown of these neurotransmitters. Zinc and copper are two trace minerals needed to remain in balance with each other. Zinc needs to remain higher than copper levels and if copper ends up becoming higher relative to zinc this can create an imbalance and also interfere with other minerals that support overall healthy functions within the body.

Active forms of B vitamins in B complex formulas may be better utilized by the body as it can bypass the conversion into usable forms as most people may have reduced function to convert some non-active forms of B vitamins into active forms.

Higher doses of B6 (pyridoxal 5 phosphate, P5P) may produce increased levels of histamine. Low B6 can help reduce or prevent excess histamine production especially if histamine is already high.

Quercetin inhibits production of histamine. Montmorency cherries contain quercetin often used for inflammation, gout and arthritis which may reduce histamine and protect against oxidative DNA damage. Montmorency cherry are also a natural source of melatonin [R] [R]

Quercetin can inhibit catechol-O-methyltransferase (COMT) not suitable for those who have a COMT mutation. [R]

Butterbur may prevent seasonal allergies as it blocks the action of histamine [R] [R]

Reduce inflammation and causes of inflammatory processes such as impaired organ function especially the liver which is needed for detoxification. Avoid and prevent exposure to common allergens often found in higher amounts in the environment and especially household cleaning products. An overall healthy lifestyle and diet will help balance health and wellbeing.

Impaired gut health (leaky gut, parasites such as H.pylori etc) and insufficient bowel support can increase immune response which can potentially raise histamine levels.

Nitric oxide has also shown to regulate mast cell function. [R] [R]

Tetrahydrobiopterin (BH4) is also used by enzymes nitric oxide synthases (NOS) that help to form nitric oxide (NO). It is also an essential cofactor for aromatic amino acid hydroxylases.

Folate deficiency can decrease BH4 levels [R]

Nutrients that support BH4 levels include folate or supplement Methylfolate (MTHF), Curcumin and vitamin C.

Methyl folate prevents oxidation of BH4 into BH2. Ensuring adequate supply of NOS enzymes will also help prevent breakdown of BH4.

If natural remedying of histamine production does not help to reduce histamine levels medical intervention may be needed. It is important to resolve the underlying cause of MCAS which can be done by identifying, eliminating and preventing allergy triggers. High histamine foods need to be avoided as well as common allergy triggers. Failing this in a situation where MCAS is severe treatments such as antibiotics may be needed.

Physical traits or characteristics of histadelia include little or no hair, good teeth, second toe longer, thin lean body.

Undermethylation is also linked to histadelia. In women methylation balance may correlate with the female monthly cycle where more methylation is needed in one phase and less in another.

Correcting methylation balance can help with histamine balance in the body.

Undermethylation can occur at the same time as pyroluria. Mental health condition is linked to pyroluria which can be caused by stress. Vitamin B6, magnesium, and zinc are likely to be low in undermethylators which can further reduce in the presence of stress.

The following are nutritional signs and symptoms of undermethylation:

High histamine
Low levels of serotonin and dopamine
Low zinc
Low copper
High basophil count
Low homocysteine
High heavy metals on hair analysis

The following are physiologically manifested symptoms linked to undermethylation:

Dry or pale skin
Stretch marks
Acne
Acetonic breath/body odor
Delayed growth puberty
Skin is unable to tan (lack of melanin due to low copper)
Sunburns quickly or easily
White spots on fingernails
Early gray hair
Frequent infections
Morning nausea
Hypersensitive to light and noise
Poor sense of smell/taste
Enjoys and eats a lot of spicy food
Gluten/casein sensitivity
Oxidative stress
Side stitches when running
Extreme mood swings
Poor stress control
Overwhelmed of criticism
Adverse to disruptions or changes in routine
Histrionic behaviour (can be ‘dramatic or theatrical’ in order to get attention)
Impulsive
Fatigue
Less dream recall
Problem with sugar metabolism
Intolerance/sensitivity to some proteins/alcohol and others
High libido
Sparse body hair
Frequent headaches
Slender or lean body
Seasonal allergies
Reacts adversely to benzodiazepines (increases histamine)
Folic acid (increases histamine)
Improvement or good response to SSRI’s
Improvement or good response to anti-histamines

Some psychological / mental symptoms and traits of undermethylation that can manifest in an individual include:

Chronic depression
Perfectionism
Oppositional or defiant as child / youth
Suicidal tendencies
Addictiveness
Phobias (unusual fears)
Denial of illness (hiding problems)
Obsessive compulsive tendencies
Ritualistic
Strong willed
Self-motivated (during school years)
History of competitiveness (especially in sports)
High inner tension but displays calm demeanor
Family history of high accomplishment
Dietary inflexibility (will only eat certain foods and avoid others)
Terse speech