Histidine (His or H)


    • Histidine was first isolated by German physician Albrecht Kossel and Sven Hedin in 1896.
    • Encoded by the codons CAUand CAC, is an α-amino acid that is one of the 20 standard amino acids used in the biosynthesis of proteins. Initially thought essential only for infants, longer-term studies have shown it is essential for adults also.
    • It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the deprotonated –COO− form under biological conditions), and an imidazole side chain (which is partially protonated), classifying it as a positively charged amino acid at physiological pH.
    • It is a precursor to histamine, a vital inflammatory agent in immune responses and carnosine biosynthesis. The acyl radical is histidyl.
    • The imidazole side chain of histidine is a common coordinating ligand in metalloproteins and is a part of catalytic sites in certain enzymes. In catalytic triads, the basic nitrogen of histidine is used to abstract a proton from serine, threonine or cysteine to activate it as a nucleophile.
    • In a histidine proton shuttle, histidine is used to quickly shuttle protons, it can do this by abstracting a proton with its basic nitrogen to make a positively-charged intermediate and then use another molecule, a buffer, to extract the proton from its acidic nitrogen.
    • In carbonic anhydrases, a histidine proton shuttle is utilized to rapidly shuttle protons away from a zinc-bound water molecule to quickly regenerate the active form of the enzyme.
    • α-Methyl amino acids, which inhibit decarboxylase activity, find application as antihypertensive agents. Decarboxylation of histidine to histamine is catalyzed by a broad-specificity aromatic L-amino acid decarboxylase that also catalyzes the decarboxylation of dopa, 5-hydroxytryptophan, phenylalanine, tyrosine, and tryptophan.
    • Histidine compounds present in the human body include ergothioneine, carnosine, and dietary anserine.

L-Histidine SNPs

    • rs2073440 HDC A1932C G
    • rs854158 HDC T10086C G
    • rs16963486 HDC T1657C G

L-Histidine Health Effects:

    • Anti arteriosclerotic
    • Anti nephritic
    • Antioxidant
    • Anti-ulcer
    • Anti uremic
    • Essential
    • Oxidant


  • Is found abundantly in hemoglobin. Inborn errors of histidine metabolism exist and are marked by increased histidine levels in the blood.
  • Elevated blood histidine is accompanied by a wide range of symptoms, from mental and physical retardation to poor intellectual functioning, emotional instability, tremor, ataxia, and psychosis.
  • Low blood histamine with low serum histidine occurs in rheumatoid arthritis patients.
  • Low blood histamine also occurs in some manic, schizophrenic, high copper and hyperactive groups of psychiatric patients, histidine is a useful therapy for all low histamine patients.


    • Flavoring ingredient; dietary supplement, nutrient.
    • Nutritionally, histidine is considered an essential amino acid in human infants. After reaching several years of age, humans begin to synthesize it and it thus becomes a non-essential amino acid.
    • It is not clear how adults make small amounts of histidine, and dietary sources probably account for most of the histidine in the body. Histidine may accomplish this function through a complex interaction with threonine or cysteine and possibly copper. However, copper is usually elevated in rheumatoid arthritis patients and worsens the disease. Other patients besides arthritis patients that have been found to be low in serum histidine are those with chronic renal failure.

Associated Problems:

  • Urinary levels of 3-methylhistidine are unusually low in patients with Wilson’s disease.


  • The actions of supplemental L-histidine are entirely unclear. It may have some immunomodulatory as well as antioxidant activity. Histidine increases histamine in the blood and probably in the brain.
  • Histidine has been claimed to have been useful in hypertension because of its vasodilatory effects.
  • It is not indicated for the treatment of anemia or uremia or for lowering serum cholesterol.
  • Claims of its use to improve libido and counteract allergy are without proof at present.
  • May have many other possible functions because it is the precursor of the ubiquitous neurohormone-neurotransmitter histamine.


    • L-histidine may be indicated for use in some with rheumatoid arthritis. Histidine in medical therapies has its most promising trials in rheumatoid arthritis where up to 4.5 g daily have been used effectively in severely affected patients. Arthritis patients have been found to have low serum histidine levels, apparently because of too-rapid removal of histidine from their blood. Histidine and other imidazole compounds have anti-inflammatory properties. Low free histidine has been found in the serum of some rheumatoid arthritis patients. Serum concentrations of other amino acids have been found to be normal in these patients.
    • Histamine is known to possess immunomodulatory and antioxidant activity. Suppressor T cells have H2 receptors, and histamine activates them. Promotion of suppressor T cell activity could be beneficial in rheumatoid arthritis. Further, histamine has been shown to down-regulate the production of reactive oxygen species in phagocytic cells, such as monocytes, by binding to the H2 receptors on these cells. Decreased reactive oxygen species production by phagocytes could play antioxidant, anti-inflammatory and immunomodulatory roles in such diseases as rheumatoid arthritis.
    • This latter mechanism is the rationale for the use of histamine itself in several clinical trials studying histamine for the treatment of certain types of cancer and viral diseases. In these trials, down-regulation by histamine of reactive oxygen species formation appears to inhibit the suppression of natural killer (NK) cells and cytotoxic T lymphocytes, allowing these cells to be more effective in attacking cancer cells and virally infected cells.

Route of Exposure:

    • Absorbed from the small intestine via an active transport mechanism requiring the presence of sodium.

Supplemental L-histidine:

    • L-histidine is the obligate precursor of histamine, which is produced via the decarboxylation of the amino acid.
    • In experimental animals, tissue histamine levels increase as the amount of dietary L-histidine increases. It is likely that this would be the case in humans as well.
    • Has metabolites, such as histamine and trans-urocanic acid, which suggest that supplemental L-histidine may one day be shown to have immunomodulatory and/or antioxidant activities.
    • L-histidine is an excellent chelating agent for such metals as copper, iron, and zinc. Copper and iron participate in a reaction (Fenton reaction) that generates potent reactive oxygen species that could be destructive to tissues, including joints.
    • Infants four to six months old require 33 mg/kg of histidine.