Histidine

What is 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.

Histidine is a proteinogenic and an aromatic amino acid with an imidazole functional group. There are a total of 23 proteinogenic amino acids.

Histidine plays a role in many of the body’s functions which includes forming proteins, tissue repair, build haemoglobin, utilize minerals, strengthen immune system and plays a role in various metabolic reactions in the body.

Health Benefits of Histidine

Strengthens immune system

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.

Reduce allergies and inflammation

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

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.

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.

In the brain histamine functions as a neurotransmitter but is also a hormone. 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.

The body needs histidine to make enough histamine which can reduce sensitivity to allergens. 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 protective barrier during infections.

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

Needed for healthy digestion

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, glutamin 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.

Helps build haemoglobin

Histidine involved in several metabolic reactions within the body and has a part in helping supplying oxygen throughout the body.

Histidine plays an important role in the production of red blood cells and may be helpful for anaemia. Haemoglobin is essential to carry oxygen in the blood within the body to all the organs and tissues. The body can convert histidine to haemoglobin. Histidine is also needed to regulate the pH value of blood and maintain sufficient haemoglobin levels within the body.

Histidine is an essential component for many iron containing molecules needed for various functions by the body which includes ferritin. [R]

The enzyme cysteine dioxygenase (CDO) is a non heme iron enzyme that requires histidine.

Histamine production requires vitamin B12 and folic acid (B9).

Involved in tissue repair and myelin sheath

Histidine is needed to regulate growth and tissue repair and involved in wound healing. Histidine may be useful to help speed up the healing process following an injury. It is needed by the body to form the myelin sheath which protects nerve cells. The myelin sheath is implicated in many degenerative health conditions which includes Alzheimer’s disease and Parkinson’s disease. Multiple Sclerosis (MS) is also another health condition where problems with myelin sheath has been linked.

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

This amino acid is especially important for children for growth and development. Deficiency of this amino acid can lead to growth and development problems in children.

Protects from radiation

Histidine also helps protect the skin from UVA damage which causes oxidative stress and symptoms to manifest on the skin as ‘age spots’ or ‘liver spots’. Being an aromatic amino acid histidine can absorb UV rays and protect the skin from radiation damage. Much of this protection comes from the production of the chemical urocanic acid which helps absorb UV rays.

Studies have shown that histidine preparations in medical treatment has many benefits especially where ionising radiation is used and can protect the body from harmful effects of radiation. [R] [R].

Blood Pressure

Histidine has been used to treat high blood pressure. It helps to relax blood vessels and helps formation of haemoglobin. Research has shown that histidine can significantly reduce the risk of cardiovascular disease and arteriosclerosis and prevent heart attacks.

Kidney disease

Histidine has been used in the treatment of chronic kidney failure. Kidney problems and kidney failure is common in older people and especially elderly people. The research on histidine on kidney failure has been well documented to show positive results. [R]

Histidine supplementation has been linked to reduced mortality rate.

Heavy metal detoxification

Histidine has an interesting effect of chelating nickel and may be useful in heavy metal detoxification. When in excess nickel can accumulate in the prostrates and toxic levels linked with many health conditions. L-Carnosine (beta-alanyl-L-histidine) removes nickel [R].

Nickel can also excrete through sweating. An excess of nickel can lead to low levels of histidine.

Histidine can also chelate mercury.

Histidine helps transport zinc. An impaired zinc transportation can potentially cause an excessive amount of zinc to build up in the body. Zinc is required for prostaglandin E1 (PGE1) production, however too much zinc can cause excess PGE1 production leading to various health problems such as gastrointestinal problems which includes diarrhea. This is due to high levels of prostaglandins that cause the smooth muscles in the intestines to excessively contract and produce excess cytokines.

The amino acid histidine can help with the excess production of prostaglandin levels through its ability to transport zinc. The use of histidine can reduce zinc levels and may benefit if zinc is in excess and potentially reduce symptoms associated with excess PGE1 production from excess zinc levels.

Histidine is an important building block for ferritin which is converted into ferrous iron, a more bioavailable form of iron the body can utilize. Ferritin is also involved in heavy metal detoxification due to its heavy metal binding activity. [R]

Helps utilize trace minerals

Histidine supports the body to regulate and utilize essential trace minerals which includes copper, zinc, iron, manganese and molybdenum. Histidine is needed for the transportation of zinc and is also able which can also act as a chelator if zinc levels at a high level.

May help skin health

People have used histidine to treat eczema, a patch of dry and itchy skin that may form around different body parts such as arms, legs, hands, neck, legs and chest area. Use of histidine for eczema type conditions may have less adverse reactions than long term use of steroids. Medical study has shown that L-histidine helps to rebuild skin barrier. Some people with the condition have taken up to 3g per day for several weeks and up to 2 months successfully eliminating eczema symptoms. Histidine may help eczema as this seems to be linked to nickel which can cause skin reactions in those who have accumulated too much nickel. [R]

The amino acids histidine and glycine seem to be mostly involved with eczema and deficiency may lead to a worsening of symptoms.

Histidine is needed for Histamine

Histidine is needed to synthesise histamine. Histamine is an important neurotransmitter that is needed for the immune system and involved in the inflammatory response. A deficiency of histidine can lead to insufficient production of histamine.

Studies have also shown that Histidine intake can improve cognitive function which is likely due to its role in histamine synthesis.

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

[R]

Histidine and IBS

Histidine may potentially help IBS symptoms which involves diarrhea and if the issue is related to excess zinc which when present in high levels can cause diarrhea.

Abnormally high levels of prostaglandin E1 (PGE1) may be linked to excess zinc levels which is a cofactor needed for PGE1 production. If zinc levels are high and causing excess PGE1 prostaglandin production which can cause an over contraction of the smooth muscle and excess cytokine production in the intestines leading to diarrhea then it may be helpful to lower zinc levels. Histidine effectively both utilizes and chelates zinc. However histidine supplementation may require zinc supplementation to avoid a deficiency in zinc. 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].

The dosage in the case of IBS may be different for each individual requirement. However beginning with a 250mg dose may be the best starting point to see if it moderates the symptom of diarrhea in IBS sufferers. It is also advisable to keep track of zinc levels and supplementation may be necessary when taking histidine supplements for a prolonged period.

Avoiding vitamin B6 in some cases may be necessary as this vitamin influences effects of histidine in the body and its effect on zinc.

May help women climax

Histimines play a vital and often overlooked role in regulating ejaculations and orgasms.

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]

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 either through supplementation or obtained from the diet.

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.

On the other spectrum women who orgasm easily may have excess histamine, and are known as histadelics. Histadelics have excess histidine and therefore an excess production of histamine. 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 lower dose.

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 and prior to menstruation when estrogen is at its highest levels and higher than progesterone as estrogen increases histamine. 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 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.

Histidine also helps transport zinc, and 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.

Agonist / Synergist

Vitamins B6

Minerals Cu, Zn, Fe, Mn, Mo, I

L-histidine is a precursor of histamine, the body uses histidine to help synthesise histamine

Histidine helps metabolize and utilize many of the trace elements which includes copper, zinc, iron, manganese and molybdenum

It acts as a regulator of minerals which are essential to the body an example of this regulatory process can be seen in the minerals zinc and copper which are two essential minerals that can inhibit each other. Histidine can enhance uptake of zinc whilst inhibit copper absorption.

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

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

DAO 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.

DAO needs cofactors copper and pyrroloquinoline quinone (PQQ)

Iodine inhibits conversion of histidine to histamine

Histidine can convert to glutamate

Histidine to histamine conversion requires B6

Histidine helps with iron uptake

Histidine may increase serum levels of zinc and reduce copper levels possibly through utilisation

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

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

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

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

High doses of vitamin b12 increases histamine levels

Methionine helps with histamine breakdown (methylates and deactivates histamine) (histamine is involved in allergies and asthma)

Histidine transports zinc but this may increase zinc requirements if zinc is low*

*Zinc is a cofactor in the production of PGE1

The enzyme histidine decarboxylase needs amino acid histidine to synthesise histamine

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

Monoamine Oxidase (MAO) which helps break down catecholamine neurotransmitters as well as serotonin contains histidine

Antagonists

Minerals Cu, Zn

Metals Nickel, Mercury

Excess nickel (commonly acquired through stainless steel pots and pans, jewellery and other exposure) can deplete histidine increasing histidine requirements. An excess of nickel also linked to lithium deficiency which can stop functions of the spleen

Histidine can cause deficiency of copper as it chelates copper and can possibly help with copper utilisation. This may require an increased need for copper either through diet or supplementation

Histidine can cause zinc levels to decrease as it is involved in the transportation of this trace element. If zinc is low supplementation or including foods rich in zinc may be required

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 MAO which can lead to excess build-up of histamine – this can be a problem if too much histidine is converted to histamine

Food Sources of Histidine

All amino acids are found mostly in protein rich foods and animal based proteins are a good source of amino acids.

Foods that contain histidine include, chicken, beef, salmon, soy beans and wheat germ.

Although plant based foods may contain some amino acids these are usually not enough to meet daily requirements. Histidine can also be found in Maca along with the amino acid arginine.

The way food is prepared and stored can significantly affect amino acid levels. It is important to store foods away from directly sunlight and sealed properly to avoid uv radiation and oxygen from destroying the protein. Extreme frying and excess heat may also denature proteins.

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 helps with copper storage and transportation from the liver into the bloodstream carrying it to parts of the body where it is needed.

Ceruloplasmin regulates copper and is also involved in homeostasis of both iron and copper.

Recommended Daily Allowance

Recommended daily histidine intake is between 8 and 12 mg per kg body weight with main recommended daily intake of histidine at 10mg per kg body weight.

There is insufficient data on the maximum dose that can be taken safely in all age groups. A tolerable upper level has not been established of histidine intake at doses between 4.5 and 24 g per day due to insufficient studies.

However doses of up to 4.5g of histidine for 30 days have shown to be safe

Histidine Supplementation

Most histidine supplements are suitable for vegans or vegetarians and are indicated on supplement packaging. Histidine is available as a single amino acid or in combination amino acid supplements. It can also be found in some multivitamin supplements and food supplements. Histidine can be found in tablet, capsule, powder and liquid form.

Histidine can also be found in protein bars which have added amino acids.

Amino acids cannot be absorbed through the skin.

Vitamin B6 influences the effects of zinc in the body and it may be ideal to try histidine without vitamin B6 in some cases.

Taking single amino acid supplements are not always recommended and may be harmful for those with damaged liver or kidneys.

Deficiency Symptoms of Histidine

Histidine is an essential amino acid and cannot be synthesised by the body and needs to be obtained from the diet.

Most people with a healthy balanced diet can meet the requirements of histidine, however deficiencies may occur due to certain factors which may increase the daily requirement for this amino acid.

Deficiency signs and symptoms of histidine include:

Increased inflammatory activity
Inflammatory conditions of the skin (eczema) and mucus membranes
Susceptibility to infections
Increased oxidative stress
Increased allergic reactions and allergy symptoms
Slower recovery from operations or surgical procedures
Development and growth problems in children and young people
Fibromyalgia (painful or inflamed muscles)
Anxiety

Causes of histidine deficiency include:

Stress
Chronic health conditions
Injuries
Operations or surgical procedures
Anaemia
Lack of dietary histidine

If the causes above are consistent then the body’s requirement for histidine can greatly increase and supplementation may be needed to return to normal levels.

Low blood plasma levels of histidine increases inflammatory activity

Histidine supplementation is linked to a reduced mortality rate

Low levels of histidine is linked to all-cause mortality [R]

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

Toxicity Symptoms of Histidine

Too much histidine in the body is known as histidinemia. Histidine is considered to be some of the more toxic amino acids for humans and animals. The other most toxic amino acids for both animals and humans include methionine and cysteine.

High histidine intake through diet or supplementation has been shown to cause toxic effects.

Signs and symptoms of high histidine include:

Increased histidine in blood and urine (histidinemia)
Urocante (Urocanic acidueria) excretion
Excretion of figlu (Folic acid deficiency)
Retarded growth [R]
Enlarged liver
High cholesterol levels
Increased ammonia
Increased glutamine
Decreased BCAAs (branched-chain amino acids (valine, leucine, and isoleucine))

Supplementation may not be appropriate for people with liver disease [R]

Histidine should not be used if a folic acid deficiency is present as it can cause a chemical called formiminoglutamic acid (FIGLU) to build up in the body.

In some studies up to 4.5g per day for 30 days did not lead to adverse effects.

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

Excess amino acids are excreted by the liver through liver cells releasing urea and water which are transported to the kidneys to filter the blood and then excreting urea through urine.

If histidine helps to relieve the diarrhoea symptoms of IBS, extra histidine may potentionally cause constipation.