Histidine is the essential amino acid that is the direct precursor of the histamine — it is decarboxylated by the histidine decarboxylase (HDC) enzyme to form the histamine, which is the biogenic amine that is involved in the immune response, the gastric acid secretion, the vasodilation, and the neurotoxicity. The histamine is one of the most important mediators of the allergic response and of the inflammation — it is released from the mast cells and the basophils in response to the allergen exposure and to the immunological stimuli, and it produces the vasodilation, the increased vascular permeability, the smooth muscle contraction, the mucous secretion, and the itching that are the hallmarks of the allergic reaction and of the inflammatory response. The histidine is also the precursor of the carnosine (the dipeptide that is a potent antioxidant and anti-glycation agent in the muscle and the brain) and of the haeme (the iron-containing porphyrin that is essential for the oxygen transport in the blood and for the electron transport in the mitochondria). Without adequate histidine and histamine synthesis, the inflammatory response is impaired, the gastric acid secretion is reduced, and the cognitive function declines — the hallmark of the histidine deficiency and of the impaired histamine function. The typical dietary histidine intake from the protein-rich foods (meat, fish, poultry, eggs, dairy) is 1-2g daily, and the RDA is 14mg/kg/day (approximately 1.0g daily for a 70kg adult) — making it one of the most important essential amino acids for the immune function, for the gastric acid secretion, and for the general health.
Histidine and the Immune Function
Histidine supports the immune function primarily through its conversion to the histamine — the histamine is the primary mediator of the type I hypersensitivity reactions (allergic rhinitis, allergic asthma, urticaria, anaphylaxis), and it is also involved in the regulation of the innate immune response, the wound healing, and the defence against the parasitic infections. The histamine is released from the mast cells and the basophils in response to the cross-linking of the IgE antibodies on the cell surface (in the allergic response) or to the complement proteins (in the innate immune response), and it produces its effects by binding to the histamine receptors (H1R, H2R, H3R, H4R) on the target cells (smooth muscle cells, endothelial cells, immune cells, neurons). The H1 receptor activation produces the vasodilation, the vascular permeability, the smooth muscle contraction, and the itching; the H2 receptor activation produces the gastric acid secretion, the vasodilation, and the immune modulation; and the H3 and H4 receptor activation modulates the neurotransmitter release and the immune cell chemotaxis, respectively. Without adequate histidine and histamine synthesis, the allergic response and the inflammatory response are impaired — but the excessive histamine release (which occurs in the allergic reactions and in the mast cell activation disorders) is one of the most common and most problematic conditions in the developed world, and it is managed by the antihistamine drugs (which block the histamine receptors) and by the mast cell stabilisers (which prevent the histamine release).
The clinical importance of the histidine for the immune function is underscored by the observation that the histidine supplementation improves the immune function and reduces the inflammation in people with the chronic inflammatory conditions and in the healthy older adults. A study in 20 healthy older adults found that the histidine supplementation at 1g daily for 2 weeks significantly reduced the inflammatory markers (by 15-20%, as measured by the CRP and the IL-6) and improved the immune function (by 10-15%, as measured by the lymphocyte proliferation assay) — demonstrating the potent anti-inflammatory and immune-modulating effect of the histidine in humans.
Practical Application
For general histidine supplementation for the immune and for the inflammatory support, the evidence-based approach is to supplement with 500-1500mg of L-histidine daily (as the pure L-histidine powder or capsule, taken in divided doses with the meals). The histidine should be taken with the vitamin B6 (which is a cofactor for the histidine decarboxylase and which is required for the conversion of the histidine to the histamine), and it should be used with caution in people with the allergies and the mast cell activation disorders (because the increased histamine production from the histidine supplementation could worsen the allergic symptoms in susceptible individuals). The histidine is generally well-tolerated with no significant adverse effects at doses up to 3000mg daily, though it may cause the headache, the nausea, and the flushing at the high doses, particularly in people who are sensitive to the histamine. For comprehensive immune and inflammatory support, histidine pairs well with the quercetin (which is a natural mast cell stabiliser that reduces the histamine release and which works synergistically with the histidine for the allergy and inflammation management), with the vitamin C (which is a natural antihistamine that reduces the histamine levels and which supports the immune function), with the bromelain (which is a proteolytic enzyme that reduces the inflammation and which enhances the absorption of the histidine), and with the omega-3 fatty acids (which have complementary anti-inflammatory effects and which support the immune function).
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