Journal of Drug Metabolism & Toxicology
Open Access

Abstract

Metabolism and Toxicity of High Doses of Cyclo (his-pro) Plus Zinc in Healthy Human Subjects

Koichi Uyemura, Shawkat Dhanani, Dean T Yamaguchi and Moon K Song

In our previous studies, Cyclo-Z (Cyclo [His-Pro], [CHP] plus zinc) treatment in animals improved insulin sensitivity. However, the adverse effects of these ingredients in humans have not yet been established. His study was to evaluate the pharmacokinetics and possible toxicity of CHP and zinc in healthy human subjects. Forty-nine healthy subjects were randomly divided into 4 groups of 11-15 subjects. ll the subjects consumed 8 study capsules and then submit to a battery of blood draws. Group 1 consisted of subjects who received 8 placebo control capsules. Individuals in Group 2 received 2 capsules of Cyclo-Z containing 3 mg CHP plus 20 mg zinc, in addition to 6 capsules of placebo. Group 3 subjects received 4 capsules of Cyclo-Z and 4 capsules of placebo. Finally, Group 4 individuals received 8 capsules of Cyclo-Z. Blood samples were collected at 0, 2, 4, 8, and 24 hours for the analysis of liver, kidney and lipid panels. Biochemical analyses were also conducted to measure CHP, zinc, and cooper levels for pharmacokinetic analyses. No side effects were experienced in any of the subjects based on physical and blood chemistry examinations. Plasma CHP levels increased at 4 hours in each subject treated with CHP. However, all plasma CHP levels returned to normal levels by 24 hours. Plasma zinc levels were stable and did not increase beyond normal levels. However, a slight increase of plasma zinc at 4 hours was found for Group 4 who received160 mg zinc. There was no copper deficiency found in any of the test subjects. This clinical study demonstrated that acute intake of 24 mg CHP plus 160 mg zinc did not show any clinical side effects or copper deficiency in healthy subjects.