Histidine

Optimal Result: 6.4 - 11.7 qmol/dL.

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.

References:

- Cuparencu C, Pratico G, Hemeryck LY, et al. Biomarkers of meat and seafood intake: an extensive literature review. Genes Nutr. 2019;14:35.

- Wu F, Yu J, Gehring H. Inhibitory and structural studies of novel coenzyme-substrate analogs of human histidine decarboxylase. FASEB J. 2008;22(3):890-897.

- Adrych K, Smoczynski M, Stojek M, et al. Decreased serum essential and aromatic amino acids in patients with chronic pancreatitis. World J Gastroenterol. 2010;16(35):4422-4427.

- Sasaki C, Hiraishi T, Oku T, et al. Metabolomic approach to the exploration of biomarkers associated with disease activity in rheumatoid arthritis. PloS one. 2019;14(7):e0219400.

- Wade AM, Tucker HN. Antioxidant characteristics of L-histidine. J Nutr Biochem. 1998;9(6):308-315.

- Feng RN, Niu YC, Sun XW, et al. Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial. Diabetologia. 2013;56(5):985-994.

- Scott IR. Factors controlling the expressed activity of histidine ammonia-lyase in the epidermis and the resulting accumulation of urocanic acid. Biochem J. 1981;194(3):829- 838.

- Cooperman JM, Lopez R. The role of histidine in the anemia of folate deficiency. Exp Biol Medicine. 2002;227(11):998- 1000.

- Bhat DS, Gruca LL, Bennett CD, et al. Evaluation of tracer labelled methionine load test in vitamin B-12 deficient adolescent women. PloS one. 2018;13(5):e0196970.

- Kanarek N, Keys HR, Cantor JR, et al. Histidine catabolism is a major determinant of methotrexate sensitivity. Nature. 2018;559(7715):632-636.

- Medicine NUSNLo. FTCD gene. Genetics Home Reference 2020.

- Kawaguchi Y, Ogawa M, Ito H, Mine T. Alterations in plasma amino acid levels in alcoholic chronic pancreatitis in Japanese. Digestion. 2012;86(2):155-160.

What does it mean if your Histidine result is too low?

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.

What does it mean if your Histidine result is too high?

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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