Histidine is a semi-essential amino acid which is formed in the breakdown of carnosine. Red meat is a common source of carnosine, and therefore histadine. Other food sources include poultry, fish, nuts, seeds, and grains. Histidine and histamine have a unique relationship. The amino acid histadine becomes histamine via a vitamin B6- dependent enzyme called histidine decarboxylase. With this, decreased amounts of histidine and insufficient vitamin B6 can subsequently lead to a decrease in histamine concentration. This may impair digestion, since histamine binds to H2 receptors located on the surface of parietal cells to stimulate gastric acid secretion, necessary for protein breakdown. Histidine also inhibits the production of proinflammatory cytokines by monocytes and is therefore anti-inflammatory and antioxidant. With these beneficial effects, histidine supplementation has been shown to improve insulin resistance, reduce BMI, suppress inflammation, and lower oxidative stress in obese women with metabolic syndrome. Interestingly, histadine can also be broken down to form urocanic acid in the liver and skin. Urocanic acid absorbs UV light and is thought to act as a natural sunscreen.
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Low levels of essential amino acids may indicate a poor-quality diet, or maldigestion due to deficient digestive peptidase activity or pancreatic dysfunction. Low histadine levels are clinically significant because as outlined above, histadine converts to histamine. Deficient histidine can contribute to gastric hypochlorhydria. This gastrointestinal dysfunction can, in turn, perpetuate histidine deficiency and therefore impair all protein digestion. Low histidine has been reported in rheumatoid arthritis, chronic kidney disease, and cholecystitis.
High levels of histadine are seen in high protein diets. Vitamin B6 is needed to convert histadine to histamine, therefore a functional need for vitamin B6 may elevate levels of histadine. There is also a relationship between histadine and folate metabolism. Histadine metabolizes to glutamic acid with FIGLU as an intermediary and tetrahydrofolate as a cofactor. Therefore, elevated histadine can be seen with vitamin B12 and folate insufficiencies.
Urinary levels have been shown to normalize with folate administration and plasma levels have been altered in supplementation with vitamin B12.
Lastly, there is a rare inborn error of metabolism involving impairment of histidase, which breaks down histamine and causes elevated histadine.
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