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

Abstract

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. .

Prevention and Treatment of Obesity and Diabetes and their Related Complications

“…The double-blinded study showed no adverse clinical side effects and no changes in blood chemistry data of subjects administered a onetime oral dose of 0, 2, 4, or 8 capsules of Cyclo-Z in chemistry data and blood cell counts. Although subjects (n = 12) who took 8 capsules of Cyclo-Z before breakfast showed significantly reduced blood glucose levels at 8 hours, their plasma glucose levels were within normal range [89]. Blood glucose levels at twenty-four hours had returned to baseline levels prior to Cyclo-Z intake.…”

Drug Resistance and the Prevention Strategies in Food Borne Bacteria: An Update Review

“…Studies showed that antioxidant peptides have some functional roles and suggested a novel microbial diketopiperazine from the cyclo (His-Leu) which produced by Bacillus subtilis. 120,121 Researchers reported that cyclo (His-Pro) plus high doses of zinc have anti-hyperglycemic effect and stimulating consumption of muscle glucose 122 and reduce obese diabetic (ob/ob) which can have significant positive effect on human health. 123 Furthermore, Cyclo (Phe-Phe) can inhibit the development of dementia and Alzheimer’s disease by preventing acetylcholinesterase and serotonin transporter.…”

Cyclic Peptides in Neurological Disorders: The Case of Cyclo(His-Pro)

“…CDPs released by the coldwater marine sponge Geodia barretti synergistically exert chemical defense (Sj€ ogren et al, 2011). Moreover, CHP, a catabolic product of TRH (thyrotropin releasing hormone), can control blood glucose levels Jung et al, 2011Jung et al, , 2016Koo et al, 2011;Lee et al, , 2013Park et al, 2012) and, associated to zinc, has already been patented in the United States as an antidiabetic drug with no side effects in humans (Uyemura et al, 2010).…”