What Is Histidine?

For the Treatment of Rheumatoid Arthritis and More

Histidine is an amino acid; amino acids are used to make proteins and enzymes in the body. It is sometimes referred to as a “semiessential amino acid” because it is nonessential in adults, but essential in the diet of infants and those with a kidney disorder called uremia. Histidine is also called L-histidine and a-amino-b-[4-imidazole]-propionic acid.

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Essential and Nonessential Amino Acids

Amino acids are compounds which are classified into two groups, essential and non-essential. Essential amino acids are those that the body cannot make. As a result, they must be obtained in the diet. Nonessential amino acids are those that humans can make from other chemicals in the body; thus, they do not necessarily have to be present in the diet. 

Function of Histidine

Histidine is used by the body to make specific hormones and metabolites that impact kidney function, transmission of nerves, stomach secretions, and the immune system. Histidine also has an impact on the repair and growth of tissue, making blood cells and helping to protect nerve cells. It is also used to make histamine in the body.

A primary function of histidine in the body is to regulate and help metabolize (break down and use for energy) trace elements. These trace elements include:

  • Copper
  • Iron
  • Zinc
  • Manganese
  • Molybdenum
  • More 

Histidine also helps to form many different enzymes and compounds in the body. In addition, histidine works to formulate a compound called metallothionein inside of the cells of the brain, liver, and kidneys; metallothionein protects the brain cells and requires histidine to be formed. If a person’s body is toxic with heavy metals (such as mercury and lead), it may result in a depletion of adequate stores of histidine.

Allergies and Histidine

The body uses histidine to make histamine (a common cause of swelling and itching that occurs as a result of an allergic reaction) as a response to allergic reactions or tissue damage.

Histamine—found in elevated levels during an allergic reaction—is a byproduct of histidine. Histamine causes the immune system to launch an inflammatory response (including itching and swelling) as a reaction to allergens.

Histidine contributes to an emergency (and potentially fatal) medical condition called anaphylaxis that can result from an allergic reaction. It is treated with an injection of epinephrine.

What Is Histidine Used For?

Low Histidine Levels

Many health conditions may involve low histidine levels, including:

  • Chronic kidney failure
  • Pneumonia (in pediatric patients)
  • Specific psychiatric disorders (such as mania and schizophrenia)

According to PubChem, “Histidine is a useful therapy in all patients with low histamine levels.”

Health Conditions

Histidine is thought to be beneficial in treating many different conditions, but there is not enough medical research data to back up many of these claims, including:

  • Rheumatoid arthritis
  • Allergies
  • Ulcers
  • Anemia (caused by kidney failure)

According to PubChem, administration of histidine—in high enough quantities—offers the potential for health benefits, including:

  • Inhibiting cytokines and growth factors, found to increase the risk of several common cancers, including those of the breast, prostate, lung, and other cancers
  • Treating arthritis, in doses of up to 4.5 grams per day
  • Treating eczema, a skin condition that results in patches that become inflamed, itchy, red, cracked, and rough, and blisters may occur; histidine supplements may help treat this condition



According to PubChem, “Histidine in medical therapies has its most promising trials [studies] in rheumatoid arthritis.”

Much of the clinical research studies on arthritis and histidine are older studies. One such medical research trial discovered that study subjects with arthritis had low histidine levels.

A randomized, double-blind placebo study (the gold standard of medical research studies) of L-histidine in the treatment of rheumatoid arthritis discovered a beneficial effect of histidine in study subjects with “more active and prolonged disease,” wrote the study authors. A dose of 4.5 grams of histidine was given daily (or a placebo) for 30 days. Although histidine is not considered a mainstream treatment for arthritis, this very old study from 1975 showed a small amount of promise in certain groups of those with rheumatoid arthritis. However, the study authors stated that they did not advocate using histidine as a treatment for rheumatoid arthritis. In the decades since, it has not become a standard medical treatment for this condition.


In a 2013 study, histidine supplements were shown to result in several benefits for obese women with metabolic syndrome, including:

  • Lowering insulin resistance
  • Lowering fat mass
  • Suppressing inflammation and oxidative stress

Brain Health

Histidine increases histamine levels in the blood; it is thought that it may increase histamine in the brain. Because histidine is considered a precursor of histamine, it may offer brain health benefits. Histamine has many functions, including serving as a neurotransmitter in the brain and central nervous system. Low histamine levels are associated with convulsions and seizures.

Possible Side Effects


In a medical situation, a contraindication is when specific drugs (including herbs and supplements), treatments, or procedures should not be administered together, because the combination may cause harm. Often, a specific drug or supplement should not be given when a person has a particular medical condition, because it could worsen it.

Histidine is considered safe for most people, but there may be contraindications for some people, including:

  • Women who are pregnant (there is not enough clinical research available to prove the safety or efficacy of histidine for pregnant women).
  • Breastfeeding mothers (there is not enough clinical research evidence available to prove the safety or efficacy of histamine for infants who are nursing).
  • Those with folic acid deficiency (histidine supplements can cause a chemical called formiminoglutamic acid, or FIGLU, to build up in the body in those with folic acid deficiency). FIGLU is a condition in which the body cannot properly break down and process certain amino acids.

Maximum safe doses of histidine have not been established for small children or for those with severe kidney or liver disease.

Side Effects/Toxicity

Although many medical sources report that histidine is considered safe, the University of Rochester Medical Center also notes: “Using a single amino acid supplement may lead to negative nitrogen balance. This can lessen how well your metabolism works. It can make your kidneys work harder. In children, single amino acid supplements may cause growth problems.”

For those who have an adequate protein intake, single amino acid supplements are not recommended. Taking histidine for long periods of time (particularly in high doses) may result in health complications. These may include psychological issues or mood disorders.

Dosage and Preparation


Amino acid supplements are available as single amino acids or combination amino acids. They also come as an ingredient in protein and food supplements as well as in some multivitamin supplements. 

Histidine can be purchased in several forms, including:

  • Tablets
  • Liquid form
  • Powder form


The average dose of histidine is 4 to 5 grams per day. Doses of up to 4.5 grams each day for 30 days have been found safe—without any noticeable side effects—in clinical research trials such as the obesity trial.

However, high doses have shown toxic effects in animal studies (including retarded growth, enlarged liver, and high cholesterol levels), so taking more than this amount should be avoided.

What to Look For

Natural supplements, including histidine, are not regulated by governmental entities such as the Food and Drug Administration (FDA), which does oversee the safety and purity of prescription medications. What this means is that the burden of finding a safe and pure product is on the consumer.

Look for products that are organic and are certified by third-party agencies, such as the U.S. Pharmacopeia, NSF International, or ConsumerLab.com. These organizations specialize in evaluating and reporting on the purity and safety of natural herbs and supplements.

According to Winchester Hospital, “As with other supplements taken in large doses, it is important to purchase a quality product, as contaminants present even in very small percentages could conceivably add up and become toxic.”

Other Questions

Can a person have a histidine deficiency?

Although histidine can be manufactured by the body, deficiencies of this amino acid can occur (particularly during long periods of very fast growth).

What are common food sources of histidine? 

Common food sources high in histidine include:

  • Meat
  • Poultry
  • Fish
  • Dairy products
  • Other protein-rich foods

Can a person become histidine deficient?

According to the University of Rochester Medical Center: “By eating enough protein in your diet, you get all of the amino acids you need. There are no conditions that increase how much histidine you need.”

A Word from Verywell

While histidine supplementation is thought to have a high potential to provide benefits for those with various maladies (such as rheumatoid arthritis), there has not been sufficient medical research data to support many of these claims. Because the use of histidine—particularly long-term use or taking high doses—could be detrimental to your health, it’s important to consult with a professional healthcare provider before using histidine (or any other nutritional supplement).

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10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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