Ciclo(His-Pro)

Related Terms

C(HP), C.HP, cHP, CHP, cyclo (His-Pro), Cyclo (his-pro), Cyclo [His-Pro], cyclo His-Pro, cyclo-(His-Pro), cyclo-[His-Pro], cyclo-his-pro, cyclo-His-Pro, cyclo(his-pro), cyclo(His-Pro), cyclo(HIS-PRO), cyclo[His-Pro], (cyclo)-His-Pro, cyclo(histidyl-proline), cyclo(Histidyl-Proline), His-Pro diketopiperazine, histidine-proline diketopiperazine, histidyl proline diketopiperazine, histidyl-proline, histidyl-proline diketopiperazine, Histidyl-proline diketopiperazine, Histidyl-Proline diketopiperazine, Histidyl-Proline Diketopiperazine, histidyl-proline-diketopiperazine, histidylproline diketopiperazine.
Combination product examples: Midecose? (cyclo(His-Pro), amino acid chelated zinc, amino acid chelated chromium, inositol).

Background

Cyclo(His-Pro) is a naturally occurring molecule found in the brain, spinal fluid, and blood. It was first discovered in 1976 in the hamster hypothalamus, the region of the brain that regulates hunger, thirst, and body temperature.
Cyclo(His-Pro) has been used as a dietary supplement. Limited research suggests that consuming cyclo(His-Pro) and zinc may help reduce blood sugar levels. However, more evidence is needed before conclusions can be made on the use of this supplement in improving blood sugar control.
Preliminary evidence has found that cyclo(His-Pro) may improve zinc absorption and aid in wound healing and immune function, particularly in diabetic patients. Although confirmation is needed, supplementation with cyclo(His-Pro) plus zinc is a promising treatment for high blood sugar.

Evidence Table

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)

Tradition / Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

Dosing

Adults (18 years and older)
Supplementation with 300 milligrams of cyclo(His-Pro) by mouth has been used four times daily.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Interactions

Interactions with Drugs
Cyclo(His-Pro) may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. People taking insulin or drugs for diabetes by mouth should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
Cyclo(His-Pro) may also interact with alcohol, anesthesia, anticancer agents, depressants, and stimulants.

Attribution

This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Bhargava, H. N. Antagonism of ketamine-induced anesthesia and hypothermia by thyrotropin releasing hormone and cyclo(His-Pro). Neuropharmacology 1981;20(7):699-702.
Bhargava, H. N. Inhibition of abstinence syndrome in opiate dependent mice by cyclo (His-Pro). Life Sci 3-16-1981;28(11):1261-1267.
Hwang, I. K., Go, V. L., Harris, D. M., Yip, I., Kang, K. W., and Song, M. K. Effects of cyclo (his-pro) plus zinc on glucose metabolism in genetically diabetic obese mice. Diabetes Obes.Metab 2003;5(5):317-324.
Imamura, M. and Prasad, C. Cyclo (His-Pro) potentiates GABA/ethanol-mediated chloride uptake by neurosynaptosomes. Peptides 2003;24(3):445-448.
Minelli, A., Bellezza, I., Grottelli, S., and Galli, F. Focus on cyclo(His-Pro): history and perspectives as antioxidant peptide. Amino.Acids 2008;35(2):283-289.
Minelli, A., Bellezza, I., Grottelli, S., Pinnen, F., Brunetti, L., and Vacca, M. Phosphoproteomic analysis of the effect of cyclo-[His-Pro] dipeptide on PC12 cells. Peptides 2006;27(1):105-113.
Minelli, A., Conte, C., Grottelli, S., Bellezza, I., Emiliani, C., and Bolanos, J. P. Cyclo(His-Pro) up-regulates heme oxygenase 1 via activation of Nrf2-ARE signalling. J Neurochem. 2009;111(4):956-966.
Mizumo, H., Svec, F., Prasad, C., and Hilton, C. Cyclo(His-Pro) augments the insulin response to oral glucose in rats. Life Sci 1997;60(6):369-374.
Prasad, C. Neuropeptide-dopamine interactions. II. Cyclo (His-Pro) augmentation of amphetamine- but not apomorphine-induced stereotypic behavior. Behav Brain Res 1988;27(3):241-245.
Prasad, C. Role of endogenous cyclo(His-Pro) in voluntary alcohol consumption by alcohol-preferring C57BL mice. Peptides 2001;22(12):2113-2117.
Rosenthal, M. J., Hwang, I. K., and Song, M. K. Effects of arachidonic acid and cyclo (his-pro) on zinc transport across small intestine and muscle tissues. Life Sci 12-7-2001;70(3):337-348.
Song, M. K., Hwang, I. K., Rosenthal, M. J., Harris, D. M., Yamaguchi, D. T., Yip, I., and Go, V. L. Anti-hyperglycemic activity of zinc plus cyclo (his-pro) in genetically diabetic Goto-Kakizaki and aged rats. Exp.Biol Med (Maywood.) 2003;228(11):1338-1345.
Song, M. K., Rosenthal, M. J., Hong, S., Harris, D. M., Hwang, I., Yip, I., Golub, M. S., Ament, M. E., and Go, V. L. Synergistic antidiabetic activities of zinc, cyclo (his-pro), and arachidonic acid. Metabolism 2001;50(1):53-59.
Song, M. K., Rosenthal, M. J., Song, A. M., Uyemura, K., Yang, H., Ament, M. E., Yamaguchi, D. T., and Cornford, E. M. Body weight reduction in rats by oral treatment with zinc plus cyclo-(His-Pro). Br.J Pharmacol 2009;158(2):442-450.
Suzuki, T., Sakurada, T., Tadano, T., Kisara, K., Sasaki, Y., and Suzuki, K. Effect of cyclic dipeptides containing histidine on pentobarbital narcosis. J Pharmacobiodyn. 1981;4(5):377-379.