Growth was totally suppressed by L-histidine, and its impact on viability was inversely connected with the expression of FLO11. L-histidine had no effect on the S288c and Δflo11 strains' capacity to survive. Saccharomyces floresii's air-liquid biofilm formation and polysiloxane traces were greatly inhibited by L-histidine, while the altered levels of the FLO11 gene remained unaffected. Moreover, L-histidine can alter the amount of lipid and chitin in the flor yeast cell wall [1].

Brain edema treated with thioacetamide is completely inhibited by L-histidine (100 mg/kg) [2]. 60% of the cerebral edema in the L-histidine diet group was caused by the histamine release in the hypothalamus under strong K+ stimulation. The L-histidine diet, however, has no effect on other monoamines and does not change the substance's concentration. While the L-histidine diet group stopped in the light box during their entire stay in the light/dark box test performance, they stopped in the center zone during the open field test performance. This suggests that the L-histidine diet group may cause anxiety-like behavior [3].

Absorption, Distribution and Excretion
Absorption occurs in the small intestine via active transport mechanisms, a process requiring sodium. Essential amino acids are transferred to the fetus against their concentration gradient; for example, histidine, the natural L-isomer, crosses the blood-brain barrier several times faster than the D-isomer. Metabolism/Metabolites The product of L-histidine oxidative deamination or transamination is β-imidazolium pyruvate; the product of decarboxylation is histamine. Histamine enters other metabolic pathways, producing more metabolites. /Excerpt from a table/

Toxicity Summary
Since the mechanism of action of L-histidine supplementation is not fully understood, any hypothetical mechanisms are purely speculative. However, some known information about L-histidine and some of its metabolites (such as histamine and trans-uric acid) suggests that L-histidine supplementation may one day be shown to have immunomodulatory and/or antioxidant activities. Low levels of free histidine have been found in the serum of some patients with rheumatoid arthritis. The concentrations of other amino acids in the serum of these patients are normal. L-histidine is an excellent chelator for metals such as copper, iron, and zinc. The Fenton reaction involving copper and iron produces potent reactive oxygen species (ROS), which can damage tissues, including joints. L-histidine is an essential precursor to histamine, which is produced through the decarboxylation of amino acids. In experimental animals, tissue histamine levels increase with increasing dietary L-histidine intake. This likely also applies to humans. Histamine is known to have immunomodulatory and antioxidant activities. Suppressive T cells have H2 receptors, which histamine can activate. Promoting the activity of suppressor T cells may be beneficial for rheumatoid arthritis. Furthermore, studies have shown that histamine can downregulate the production of reactive oxygen species (ROS) in phagocytes, such as monocytes, by binding to H2 receptors. This reduction in ROS production by phagocytes may exert antioxidant, anti-inflammatory, and immunomodulatory effects in diseases such as rheumatoid arthritis. Based on this latter mechanism, histamine itself has been used in numerous clinical trials to investigate its efficacy in treating certain types of cancer and viral diseases. In these trials, histamine's downregulation of ROS production appeared to suppress natural killer (NK) cells and cytotoxic T lymphocytes, enabling these cells to more effectively attack cancer cells and virus-infected cells.

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Toxicity Data
Oral LD50 in rats > 15000 mg/kg, Intraperitoneal LD50 in rats > 8000 mg/kg, Oral LD50 in mice > 15000 mg/kg, Intravenous LD50 in mice > 2000 mg/kg

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Interactions
Warfarin alone (5 mg/kg bait) killed 37% of rooftop rats, but the mortality rate was higher when used in combination with L-histidine (40 mg/kg). The mortality rates of rats were 100%, 88%, 75%, and 63% respectively when used with the bait, activated clay, charcoal, and carbon (10 g/kg bait).

[1]. Bou Zeidan M, et al. L-histidine inhibits biofilm formation and FLO11-associated phenotypes in Saccharomyces cerevisiae flor yeasts. PLoS One. 2014 Nov 4;9(11):e112141.
[2]. Rama Rao KV, et al. Brain edema in acute liver failure: inhibition by L-histidine. Am J Pathol. 2010 Mar;176(3):1400-8.
[3]. Yoshikawa T, et al. Insufficient intake of L-histidine reduces brain histamine and causes anxiety-like behaviors in male mice. J Nutr. 2014 Oct;144(10):1637-41

Pharmacodynamics
It is abundant in hemoglobin; it has been used to treat rheumatoid arthritis, allergic diseases, ulcers, and anemia. Deficiency can lead to hearing loss.

C6H9N3O2

155.15

155.069

71-00-1

L-Histidine-15N3;1217456-12-6;L-Histidine-13C6,15N3 hydrochloride;L-Histidine dihydrochloride;6027-02-7

6274

Needles or plates
COLORLESS

1.4±0.1 g/cm3

458.9±35.0 °C at 760 mmHg

282 °C (dec.)(lit.)

231.3±25.9 °C

0.0±1.2 mmHg at 25°C

1.615

-1.26

3

4

3

11

151

1

C1=C(NC=N1)C[C@@H](C(=O)O)N

HNDVDQJCIGZPNO-YFKPBYRVSA-N

InChI=1S/C6H9N3O2/c7-5(6(10)11)1-4-2-8-3-9-4/h2-3,5H,1,7H2,(H,8,9)(H,10,11)/t5-/m0/s1

(2S)-2-amino-3-(1H-imidazol-5-yl)propanoic acid

Histidine NSC137773 NSC 137773 NSC-137773L-Histidine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~20.83 mg/mL (~134.26 mM)
DMSO : ~1 mg/mL (~6.45 mM)

Solubility in Formulation 1: 25 mg/mL (161.13 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)