L-histidine is a protein amino acid that is found in the proteins of all life forms. Although most L-histidine is found in proteins, a small amount of free L-histidine does exist in plants and fermented foods. The naturally occurring dipeptides found in muscle, carnosine and anserine are both comprised of L-histidine and beta-alanine.
L-histidine is one of the 10 essential amino acids for infants. It has never been clear if L-histidine is an essential amino acid for adults. At the very least, it is a conditional essential amino acid for adults. That is, even though L-histidine is synthesized in adult human tissues, sufficient quantities may not be made to meet the physiological requirements imposed by certain stress or disease situations.
L-histidine is a solid water-soluble substance. Chemically, it is called (S)-alpha-amino-1H-imidazole-4-propanoic acid; alpha-amino-4 (or 5)-imidazolepropionic acid; L-2-amino-3- (1H-imidazol-4yl) propionic acid, and glyoxaline-5-alanine. Its IUPAC abbreviation is His, and its one-letter abbreviation is H. L-histidine is classified as a basic amino acid. L-histidine has the following structural formula:
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 H 2 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 H 2 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.
L-histidine is absorbed from the small intestine via an active transport mechanism requiring the presence of sodium. From the small intestine, L-histidine is transported to the liver by means of the portal circulation, where some is metabolized and from whence some enters the systemic circulation to be distributed to various tissues in the body.
L-histidine is metabolized in several different ways. It is a substrate for protein synthesis; decarboxylation produces histamine; it is converted to trans-urocanate in the skin; it forms the dipeptides carnosine and anserine in muscle; it is a precursor of the thiol antioxidant, L-ergothioneine; and it forms alpha-ketoglutarate.
INDICATIONS AND USAGE
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.
It has been reported that rheumatoid arthritis (RA) sufferers have abnormally low blood levels of this amino acid. In a pilot study, RA patients received up to 6 grams of supplemental histidine daily and were said to benefit with as little as 1 gram daily. A subsequent study with 4.5 grams daily in some with more active and prolonged disease found much less benefití¬but still enough to warrant further research.
FOOD SOURCES OF HISTIDINE:
Dairy, meat, poultry and fish are good sources of histidine as well as rice, wheat and rye.
BEST USED WITH:
Best taken with vitamin B3 ( niacin ) and B6 ( pyridoxine ).
WHEN MORE MANY BE REQUIRED:
Although not conclusively proven ?it is thought that histidine may be beneficial to people suffering from arthritis and nerve deafness.
OTHER INTERESTING POINTS:
Histidine is also used for sexual arousal, functioning and enjoyment
Histidinemia is an inborn error of the metabolism of histidine due to a deficiency of the enzyme histidase, where high levels of histidine are found in the blood and urine, and may manifest in speech disorders and mental retardation.
1. Effect of L-histidine in vivo on human platelet function and arachidonic acid metabolism.
The effect of the amino acid l-histidine on human platelet function and arachidonic acid metabolism was studied in 18 healthy subjects with increased spontaneous platelet aggregation. The participants received placebo or l-histidine 3g/day for 7 days. The intake of l-histidine reduced the degree of spontaneous platelet aggregation (p less than 0.05) and inhibited the generation of platelet TXB2 by 47% (p less than 0.001) whereas platelet PGE2 synthesis was not affected. The mean l-histidine plasma concentration increased from 83.1 +/- 2.4 to 108 +/- 8.1 mumol/l (p less than 0.01) during the study. L-histidine was found to be an effective inhibitor of spontaneous platelet aggregation and platelet TXB2 generation. The present data verify interactions of histidine with human platelet function, probably mediated by arachidonic acid metabolites.