Antioxidant characteristics of L-histidine

Proprietary formulations of the amino acid L-histidine are under development as pharmaceutical agents because of the molecule's antioxidant and anti-inflammatory properties. L-histidine has been well characterized in terms of probable dietary requirements, plasma and tissue concentrations, pharmacokinetics, metabolism and excretion, and medical conditions related to physiologic handling. Previous experience with histidine dosing in the literature is extensive, and both clinical and preclinical data suggest that histidine administration is very safe. L-histidine has been shown to scavenge bath the hydroxyl radical and singlet oxygen (O-1(2)) in many studies. These interactions may involve free histidine, small histidine-containing peptides such as carnosine, and histidine residues in proteins. Histidine appears to interfere with redox reactions involving iron and perhaps other metal ions and to interact directly with O-t(2) the ability of histidine to scavenge O-1(2), a toxic oxygen species of increasing concern, has been well established in the laboratory. Many recent studies have demonstrated the therapeutic efficacy of "pharmacologic" doses of L-histidine in animal models of inflammatory conditions, particularly gastrointestinal conditions and cardiac ischemia-reperfusion injury, and have specifically linked the anti-inflammatory capabilities of histidine to its ability to scavenge toxic oxygen species. The maintenance of histidine pools, therefore, may contribute to the body's physiologic antioxidant capacity. Taken together, the data suggest that histidine supplementation could provide a safe, efficacious method to increase antioxidant protection. (J. Nutr. Biochem. 9:308-315, 1998) (C) Elsevier Science Inc.1998.