Cyclo (His-Pro)

Overview

Cyclo (his-pro) is a naturally occurring cyclic dipeptide consisting of histidyl and proline. Concentrations of cyclo (his-pro) have been found in the blood, cerebrospinal fluid (CSF), semen, brain, spinal cord, and gastrointestinal tract of humans. (1) It has been determined that cyclo (his-pro) has several biological activities and stereospecific cyclo (his-pro) receptors have been identified in the liver. (2) Research indicates that cyclo (his-pro) is one of the primary metabolites of thyrotropin-releasing hormone (TRH) and the greatest concentration of this substance has been found to occur in the prostate gland. (3)

Consequently, numerous trials have utilized powdered prostate gland or extracts from the prostate glands of various species of animals to study the effects of cyclo (his-pro). Studies suggest that cyclo (his-pro) is one of numerous compounds in the prostate gland that regulate the intestinal absorption of zinc. (4) Both animals and humans with diabetes have altered zinc metabolism (5) , (6) and zinc is known to play a key role in synthesis, storage, and secretion of insulin. (7) Zinc is also required for proper glucose utilization by muscle and fat cells. (8) Cyclo (his-pro) enhances both zinc absorption and glucose utilization, which results in a significant decline in both blood and urine glucose levels of diabetic patients. (9) It appears that cyclo (his-pro) is an important new agent that can help improve glucose metabolism in patients with type 2 diabetes. Currently the source of cyclo (his-pro) in commercial products is powdered animal prostate, which contains approximately 1% cyclo (his-pro).

Dosage Info

Dosage Range

300 mg, four times a day

Most Common Dosage

One capsule 4 times daily, taken 30 to 45 minutes before meals and bedtime. Each capsule consists of 300 mg of powdered bovine prostate complex, which contains approximately 1% cyclo (his-pro).

Dosage Forms

Capsules

Adult RDI

None established

Adult ODA

None established

Active Forms

Animal prostate powder, which contains approximately 1% cyclo (his-pro).

Absorption

Cyclo (his-pro) is well absorbed when taken orally.

Toxicities & Precautions

General

There are no known toxicity side effects associated with cyclo (his-pro).

Functions in the Body

Intestinal Absorption of Zinc

Cyclo (his-pro) enhances the intestinal absorption of zinc. (10)

Lowers Blood Glucose Levels

Cyclo (his-pro) helps lower blood glucose levels. (11)

Reduces Hemoglobin A1C

Cyclo (his-pro) causes a significant reduction in hemoglobin A1C (HbA1C). (12)

Clinical Applications

Diabetes, Type 2

Results from animal studies and clinical trials in patients with non-insulin dependent diabetes indicate that cyclo (his-pro) helps ameliorate diabetic symptoms. It appears that the mechanism of action is due to cyclo (his-pro)'s ability to stimulate intestinal zinc absorption, which produces a reduction in blood glucose levels. (13) , (14) , (15)

Symptoms and Causes of Deficiency

Studies have not been conducted to determine the symptoms or causes of a deficiency of cyclo (his-pro) in humans.

Dietary Sources

It has been determined that some common foods contain substantial amounts of cyclo (his-pro). Examples include dried shrimp, fish sauce, tuna, ham, potted meat, non-dairy creamer, white bread, and noodles. Research suggests that cyclo (his-pro) may not occur naturally in these foods, but rather is a consequence of the thermal manipulation of hydrolyzed proteins during the manufacturing (food processing) process. (16) Researchers have also discovered that some nutritional supplements that contain proteins that are partly hydrolyzed and thermally treated during manufacturing also contain substantial amounts of cyclo (his-pro). Products in which the protein sources are casein and/or soy include Ensure, Ensure-Plus, and Osmolite. (17)

References

  1. View Abstract: Prasad C. Cyclo(His-Pro): its distribution, origin and function in the human. Neurosci Biobehav Rev. Apr1988;12(1):19-22.
  2. Hilton CW, Prasad C, Svec F, Vo P, Reddy S. Cyclo (His-Pro) in nutritional supplements. Lancet. Dec1990;336(8728):1455.
  3. View Abstract: Pekary AE, Sharp B, Briggs J, et al. High concentrations of p-Glu-His-Pro-NH2 (thyrotropin-releasing hormone) occur in rat prostate. Peptides. Nov1983;4(6):915-9.
  4. Song MK, Rosenthal MJ, Kang KW, et al. Animal prostate extract ameliorates diabetic symptoms by stimulating intestinal zinc absorption in rats. Diabetes Research. 1996;31:157-170.
  5. View Abstract: Johnson WT, Canfield WK. Intestinal absorption and excretion of zinc in streptozotocin-diabetic rats as affected by dietary zinc and protein. J Nutr. Sep1985;115(9):1217-27.
  6. Kinlaw WB, Levine AS, Morley JE, et al. Abnormal zinc metabolism in type II diabetes mellitus. Am J Med. Aug1983;75(2):273-7.
  7. View Abstract: Chausmer AB. Zinc, insulin and diabetes. J Am Coll Nutr. Apr1998;17(2):109-15.
  8. View Abstract: Ezaki O. IIb group metal ions (Zn2+, Cd2+, Hg2+) stimulate glucose transport activity by post-insulin receptor kinase mechanism in rat adipocytes. J Biol Chem. Sep1989;264(27):16118-22.
  9. View Abstract: Song MK, Rosenthal MJ, Naliboff BD, et al. Effects of bovine prostate powder on zinc, glucose, and insulin metabolism in old patients with non-insulin-dependent diabetes mellitus. Metabolism. Jan1998;47(1):39-43.
  10. Song MK, Rosenthal MJ, Kang KW, et al. Animal prostate extract ameliorates diabetic symptoms by stimulating intestinal zinc absorption in rats. Diabetes Research. 1996;31:157-170.
  11. View Abstract: Song MK, Rosenthal MJ, Naliboff BD, et al. Effects of bovine prostate powder on zinc, glucose, and insulin metabolism in old patients with non-insulin-dependent diabetes mellitus. Metabolism. Jan1998;47(1):39-43.
  12. View Abstract: Song MK, Rosenthal MJ, Naliboff BD, et al. Effects of bovine prostate powder on zinc, glucose, and insulin metabolism in old patients with non-insulin-dependent diabetes mellitus. Metabolism. Jan1998;47(1):39-43.
  13. View Abstract: Song MK, Rosenthal MJ, Naliboff BD, et al. Effects of bovine prostate powder on zinc, glucose, and insulin metabolism in old patients with non-insulin-dependent diabetes mellitus. Metabolism. Jan1998;47(1):39-43.
  14. Song MK, Rosenthal MJ, Kang KW, et al. Animal prostate extract ameliorates diabetic symptoms by stimulating intestinal zinc absorption in rats. Diabetes Research. 1996;31:157-170.
  15. View Abstract: Song MK, Rosenthal MJ, Hong S, et al. Synergistic antidiabetic activities of zinc, cyclo (his-pro), and arachidonic acid. Metabolism. Jan2001;50(1):53-9.
  16. View Abstract: Hilton CW, Prasad C, Vo P, Mouton C. Food contains the bioactive peptide, cyclo(His-Pro). J Clin Endocrinol Metab. Aug1992;75(2):375-8.
  17. Hilton CW, Prasad C, Svec F, Vo P, Reddy S. Cyclo (His-Pro) in nutritional supplements. Lancet. Dec1990;336(8728):1455.