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Description: An essential amino acid that is required for the production of histamine. [PubChem]
Drug Type: Small Molecule; Nutraceutical; Approved
Pharmacology: Is found abundantly in hemoglobin; has been used in the treatment of rheumatoid arthritis, allergic diseases, ulcers and anemia. A deficiency can cause poor hearing.
Mechanism of Action: Since the actions of supplemental L-histidine are unclear, any postulated mechanism is entirely speculative. However, some facts are known about L-histidine and some of its 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. 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. 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.
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. 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.
Indication: The actions of supplemental L-histidine are entirely unclear. It may have some immunomodulatory as well as antioxidant activity. L-histidine may be indicated for use in some with rheumatoid arthritis. It is not indicated for treatment of anemia or uremia or for lowering serum cholesterol.
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Thought leaders and organizations working on research involving histidine.

  • Steen Brøndsted Nielsen
  • Preben Hvelplund
  • Subhasis Panja
  • Frantisek Turecek
  • John D Helmann
  • Genentech
  • Eunice Kennedy Shriver National Institute of Child Health and Human De…
  • China Medical University Hospital
  • Assistance Publique - Hôpitaux de Paris
  • MedImmune LLC
  • University of Pennsylvania
  • University of Washington
  • University of Copenhagen
  • University of Basel
  • University of Michigan Medical School

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