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.

Scientific Evidence

Tradition/Theory

The below uses are based on tradition or scientific theories. 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 health care professional.

• Alcohol abuse, antioxidant, diabetes, drug withdrawal, hyperglycemia (high blood sugar), immune function, neuroprotective (protects the nervous system), obesity, wound healing.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

• Supplementation with 300 milligrams of cyclo(His-Pro) by mouth has been used four times daily.

Children (under 18 years old)

• There is no proven safe or effective dose for cyclo(His-Pro) in children.

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.

Allergies

• Avoid in people with a known allergy or sensitivity to cyclo(His-Pro) or other ingredients in the supplement cyclo(His-Pro).

Side Effects and Warnings

• Cyclo(His-Pro) may be safe when used to lower blood sugar for up to two years, according to the manufacturer's claims. However, data on the safety or effectiveness of cyclo(His-Pro) plus zinc are lacking.

• Cyclo(His-Pro) may lower blood sugar levels. Caution is advised in people with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

• Avoid in people with a known allergy or sensitivity to cyclo(His-Pro) or other ingredients in the supplement cyclo(His-Pro).

Pregnancy and Breastfeeding

• There is currently a lack of scientific evidence on the use of cyclo(His-Pro) during pregnancy or breastfeeding.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. 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.

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.

Interactions with Herbs and Dietary Supplements

• Cyclo(His-Pro) may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

• Cyclo(His-Pro) may also interact with anticancer herbs and supplements, antioxidants, and zinc.

Author Information

• 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).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. Bhargava, H. N. Antagonism of ketamine-induced anesthesia and hypothermia by thyrotropin releasing hormone and cyclo(His-Pro). Neuropharmacology 1981;20(7):699-702. View Abstract

2. Bhargava, H. N. Inhibition of abstinence syndrome in opiate dependent mice by cyclo (His-Pro). Life Sci 3-16-1981;28(11):1261-1267. View Abstract

3. 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. View Abstract

4. Imamura, M. and Prasad, C. Cyclo (His-Pro) potentiates GABA/ethanol-mediated chloride uptake by neurosynaptosomes. Peptides 2003;24(3):445-448. View Abstract

5. 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. View Abstract

6. 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. View Abstract

7. 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. View Abstract

8. 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. View Abstract

9. 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. View Abstract

10. Prasad, C. Role of endogenous cyclo(His-Pro) in voluntary alcohol consumption by alcohol-preferring C57BL mice. Peptides 2001;22(12):2113-2117. View Abstract

11. 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. View Abstract

12. 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. View Abstract

13. 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. View Abstract

14. 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. View Abstract

15. 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. View Abstract