Cyclo(His-Pro)
A small ring-shaped dipeptide the body makes from TRH and also takes in from food, measured in people since the 1980s and given to them only twice
Cyclo(His-Pro) is two amino acids, histidine and proline, joined head to tail into a ring. The body makes it when thyrotropin-releasing hormone (TRH) loses its first residue, and it is also present in many foods. Researchers have measured it in blood, cerebrospinal fluid, urine, brain and gut, and its level moves with glucose intake, body weight and several illnesses. Studies in rodents report effects on alcohol sedation, insulin, inflammation, muscle and liver, but in people it has been given only in two small studies, and a single intravenous injection changed nothing it was tested for.
Used in human trials: 400 micrograms, Once, Intravenous (Study: healthy volunteers, hypothyroidism and microprolactinoma (ho...) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Cyclo(His-Pro), often shortened to CHP, is a cyclic dipeptide: histidine and proline linked twice so they form a closed ring called a diketopiperazine. It forms when an enzyme clips the pyroglutamic acid off the hypothalamic hormone TRH, and the leftover His-Pro end folds shut. A 1988 review noted that only part of the body's supply can be traced to TRH; in the fetal pancreas it sits in the glucagon-making cells while TRH is in the insulin-making cells, which points to a second source. Food is a third: common foods contain far more of it than human blood does.
Because a ring has no free ends, the molecule resists the enzymes that break down ordinary peptides. In mice, labelled cyclo(His-Pro) stayed in the blood a long time, crossed into the brain slowly, and reached blood and organs when swallowed, with a quarter to a third still intact half an hour after feeding. In eight volunteers who drank a nutritional supplement containing it, blood levels rose modestly within two hours, which suggests some is absorbed in people too.
Most of the human literature is measurement. Laboratories in the United States built radioimmunoassays in the 1980s and found the dipeptide in serum, cerebrospinal fluid, urine, semen, brain, spinal cord, the gut, amniotic fluid and ovarian follicles. Levels in blood rose briefly after a glucose drink, pulsed through a long fast, ran higher in obese women and were raised in diabetic ketoacidosis, lupus, kidney failure and advancing HIV disease. Spinal fluid levels were higher in untreated schizophrenia. None of these studies shows that the dipeptide causes anything; they show where it is and when it moves.
Animal and cell work fills the rest. Early papers reported that it countered alcohol sedation and reduced appetite in rodents and lowered prolactin in monkeys, though a careful 1988 re-test found no effect on food intake in rats. More recent studies, several funded by a company developing it, report anti-inflammatory signalling in cells and protection of muscle, liver and joints in mice and rats. A combination of zinc with cyclo(His-Pro) has reached phase 2 diabetes trials, but that is a different product from the dipeptide alone.
Given to people on its own, cyclo(His-Pro) has a thin record: one 1985 study injected it once into a vein and found no effect on thyroid-stimulating hormone or prolactin, and the 1996 supplement study measured absorption rather than any benefit. It is not an approved medicine anywhere we checked, and there is no tested dose for any use.
Mechanism of Action
Cyclo(His-Pro) is the ring left behind when TRH loses its first residue; it does not act on the TRH receptor in the way TRH does, and its own target in people is unknown.
Made from TRH, and from food
Pyroglutamate aminopeptidase trims TRH and the His-Pro end closes into a ring. Part of the body's supply has another origin, and many foods contain it.
Stable and able to reach the brain
The ring resists enzymes. In mice it stays long in the blood, crosses the blood-brain barrier slowly and is partly absorbed intact by mouth.
Inflammation in cells
In cell studies it switches on Nrf2 and heme oxygenase-1 and damps NF-kB and the inflammasome; whether that happens at the levels found in people is untested.
Insulin handling
In rats it raised insulin after oral glucose without raising C-peptide, pointing to slower insulin clearance by the liver; in obese women higher levels went with a similar pattern.
Published Research
These are studies of cyclo(His-Pro) read from their PubMed abstracts. Twenty are in people, almost all measuring the dipeptide in body fluids or tissue; only two gave it to anyone. Eight are in animals, two in cells, one analyses food and two are reviews. Most human work comes from a small number of US laboratories in the 1980s and 1990s, and most animal work since 2016 from two groups, one of them funded by a company developing the compound.
Where it is found in people
A short review listed blood, spinal fluid, semen, brain, spinal cord and the digestive tract as places the dipeptide occurs in humans. Part of it comes from TRH being trimmed by pyroglutamate aminopeptidase, but where the rest comes from was unknown, and its levels in blood and spinal fluid shift with health and disease.
A review of its role in nerve-cell damage
The authors summarised it as present throughout the central nervous system, carried by organic cation transporters and able to pass the blood-brain barrier. In their reading it alters stress and inflammatory responses in glial cells through the Nrf2 and NF-kB signalling axis, which is why they propose it for diseases driven by brain inflammation, such as ALS.
Serum levels and kidney failure
Using a specific antibody, researchers found the dipeptide in human serum both free and attached to a large protein fraction. Free levels in healthy people ran 11 to 33 pmol/mL and were normal in thyroid disease and alcoholic cirrhosis, but about three times higher in kidney failure. Samples taken every three hours hinted at a daily rhythm.
How the blood sample is handled matters
A direct assay sensitive to 40 pg found a mean of 829 pg/mL in plasma from 14 volunteers frozen straight away. Plasma left at room temperature for 90 minutes read significantly higher, and a sample kept at 4 degrees rose about 50% over 24 hours, so samples must be frozen at the draw to avoid falsely high values.
Present across the adult brain
In brain tissue taken at autopsy, the dipeptide was found in every region examined. The highest concentration was in the pituitary stalk and median eminence (2.2 ng/mg protein), about 20 times that of the whole hypothalamus, with lower and similar amounts in the cerebellum, olfactory bulbs, hippocampus and occipital cortex.
Present along the gut
Measured in autopsy samples and fresh colon biopsies, it occurred in every part of the human digestive tract, from 127 pg/mg protein in the oesophagus to 599 in the stomach. Colon biopsy values matched post-mortem ones, and the authors suggested it may act locally on gut function.
In the glucagon cells of the fetal pancreas
In pancreases from fetuses of 12 to 19 weeks, staining placed the dipeptide in the same cells as glucagon, inside their secretory granules, whereas TRH is found in the insulin-making cells. The authors took this as a sign that the two peptides arise independently.
Spinal fluid in health and neurological illness
In spinal fluid from more than 100 healthy adults and infants, over 70% had levels below 500 pg/mL. Levels were significantly raised in most adults admitted with neurological or psychiatric disorders and tracked TRH, which the authors linked to the nonspecific stress of illness and the spinal-tap procedure.
ALS spinal cord
In spinal cords from seven people who died with ALS and four controls, the dipeptide was significantly higher per unit of protein in ALS, while TRH was not lower relative to protein. Spinal fluid levels of both did not differ.
Higher in untreated schizophrenia
Spinal fluid levels were 53% higher in people with schizophrenia who had never taken medication than in controls, and 25% higher in those on treatment. Because animal work links the dipeptide to dopamine signalling, the authors speculated it could contribute to symptoms; the study shows an association only.
A single IV injection did nothing to TSH or prolactin
Healthy men and women, people with underactive thyroids and people with small prolactin-secreting pituitary tumours each received 400 micrograms intravenously. Basal TSH and prolactin did not change in any group, and the injection did not alter the response to a TRH test in healthy men. The authors concluded it was unlikely to help raised prolactin.
Released in pulses during a fast
Blood was drawn every 10 to 15 minutes from four people, two obese and two lean, over the last 24 hours of a 36-hour fast. Levels rose and fell in pulses in everyone, but a day-night pattern appeared only in the two obese subjects.
A brief rise after a glucose drink
After 75 g of oral glucose, plasma levels in 12 of 14 volunteers rose within 15 minutes, from a fasting mean of 614 to a peak mean of 1,035 pg/mL, then fell below baseline in 11 of 14. The change was quick and reversible.
Some may be absorbed from a supplement
Eight fasting volunteers drank about 250 mL of a nutritional supplement containing the dipeptide on one day and an equal-calorie supplement without it on the next. Two hours after the first, blood levels had risen from 7.69 to 9.18 pmol/mL; the second produced no rise. Glucose, insulin and C-peptide did not differ between the days.
Higher in obese women
In 26 fasting women without diabetes, levels were more than twice as high in the obese (2,075 against 905 pg/mL) and rose with weight and BMI. In the 17 with insulin and C-peptide measured, higher levels went with a lower C-peptide to insulin ratio, a rough sign that the liver was clearing less insulin.
Raised in diabetic ketoacidosis
In nine patients admitted with diabetic ketoacidosis, levels before treatment averaged 15.6 pmol/mL against 8.0 in seven controls. Over 24 hours of treatment they fell to 8.1, moving in step with glucagon. The authors described it as the first report of a changed level in a disease state.
Raised in lupus
Serum levels were significantly higher in 21 people with systemic lupus erythematosus than in 11 controls. The dipeptide inhibits prolactin release in laboratory studies, yet in these patients its level showed no relationship with prolactin.
Tracks nutrition and stage in HIV
Among 100 HIV-positive patients ranging from symptom-free to AIDS with weight loss, serum levels related to albumin and haemoglobin, markers of long-term nutrition, but not to cortisol. Levels also rose with clinical stage, so the authors proposed it as a marker of disease progression.
Through pregnancy
In 81 amniotic fluid and 36 maternal serum samples from 10 to 42 weeks, amniotic levels climbed to about 15,550 pg/mL at term, some thirteen times maternal serum. Fetal urine held similar amounts, suggesting that is where the amniotic supply comes from. Amniotic levels fell as amniotic prolactin rose, but adding the dipeptide to cultured decidua did not suppress prolactin.
Moves with weight in eating disorders
Serum levels were measured in 50 adolescents with anorexia nervosa or bulimia. In restricting anorexia, levels fell as weight rose; in anorexia with bingeing and purging they rose with weight; in a depressed comparison group there was no link. In six patients followed over time, weight changes of about 2 kg came with average shifts in level of 42%.
Concentrated in ovarian follicles
Fluid from 137 follicles collected during fertility treatment held a mean of 13.1 nmol/L, more than the 9.4 nmol/L in matching serum. Follicles of 20 mm or more held the most, and levels rose with the fluid's progesterone and prolactin.
Excreted in urine
The material in urine behaved like the synthetic dipeptide in antibody, drug-effect and chemical tests. Twenty-four-hour urine held about 1,134 nmol/L (range 606 to 1,865), so roughly 1.8 micromoles leave the body each day.
Found in ordinary foods
Every common food tested contained material identical to the dipeptide by antibody and chromatography, at 5 to 1,500 times the levels seen in human plasma. The authors expected some of it to be absorbed, which the 1996 supplement study went on to test.
Lowered prolactin in rhesus monkeys
In awake male rhesus monkeys, an injection of 400 micrograms cut serum prolactin by 27%; under ketamine anaesthesia the fall was dose-dependent at 150 and 400 micrograms, and the higher amount blunted the prolactin rise to TRH. TSH did not change. The 1985 human study with the same amount found no such effect.
A re-test found no effect on appetite in rats
Injected into the brain's ventricles at 14 to 1,000 nmol, or into the abdomen, the dipeptide did not reduce food intake in fed or food-deprived rats over 12 to 24 hours, while TRH and bombesin did. The authors concluded it has no appetite-suppressing activity in the rat, against earlier reports.
Crosses the blood-brain barrier slowly
Radio-labelled dipeptide entered the mouse brain from blood, and left it, without a saturable carrier. Entry was slow for so small a molecule, but a long stay in the blood and strong resistance to enzymes let it build up, enough for an intravenous dose to reverse alcohol-induced sedation. Ageing, diabetes and aluminium did not change its entry.
Absorbed when swallowed by mice
After feeding, radioactivity reached the blood quickly at a quarter to a half of the levels seen after intravenous injection, and 25 to 32% of what was in the blood at 30 minutes was intact peptide. Kidney and liver held the most; brain held some. Oral dosing reversed alcohol sedation.
Raised insulin after oral glucose in rats
Rats given an oral glucose load with the dipeptide had higher insulin peaks and a larger area under the insulin curve than rats given saline, with no change in C-peptide or glucose. The pattern suggests the liver cleared less insulin rather than the pancreas releasing more.
Fatty liver and fibrosis in mice
In mice fed a western diet at thermoneutral temperature and in mice given carbon tetrachloride, treatment reduced fat build-up, inflammation and scarring in the liver and prevented high blood sugar, whether started before or after injury. The ERK pathway was identified as an early responder. The work was partly funded by a company developing the compound.
Muscle in muscular dystrophy and ageing mice
In mdx mice, a model of Duchenne muscular dystrophy, treatment restored muscle contraction and force and reduced muscle fibrosis and inflammation; it also prevented heart muscle disease and diaphragm scarring. In an age-related muscle-loss model it reduced wasting. The same company part-funded the study.
Injected into arthritic rat knees
In rats with chemically induced osteoarthritis, injections into the joint reduced swelling and pain behaviour, preserved the bone under the cartilage, lowered a blood marker of cartilage breakdown and suppressed inflammatory and cartilage-degrading genes. The authors are employees or a board member of the developing company.
Damps inflammatory signalling in cells
In rat PC12 cells and mouse microglia, the dipeptide blocked activation of the inflammatory switch NF-kB by working through Nrf2 and the enzyme heme oxygenase-1; knocking down Nrf2 or blocking the enzyme removed the effect. It also reduced chemically induced ear swelling in mice.
ALS-model microglia
In microglial cells carrying the human SOD1 G93A mutation linked to ALS, it curbed activation of the inflammasome, a protein complex that sets off inflammation, by lowering nitric oxide and reactive oxygen species. It raised the chaperones Hsp70 and Hsp27, which increased soluble SOD1 activity, an effect independent of Nrf2 in this model.
Dosing Data
Cyclo(His-Pro) is not approved anywhere we checked. The only amount stated in a human study is a single intravenous injection given to test hormone responses; the 1996 supplement study did not state how much of the dipeptide the drink held.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Cyclo(His-Pro) is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: intravenous). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Cyclo(His-Pro), before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Cyclo(His-Pro) stays intact once mixed.
How it is taken
As it was given in human studies: Intravenous (Once; Study: healthy volunteers, hypothyroidism and microprolactinoma (hormone-response test)).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: healthy volunteers, hypothyroidism and microprolactinoma (hormone-response test): Single injection.
When effects appear: unknown; no source on this page gives a time to effect for Cyclo(His-Pro). Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: No adverse effects are described in the abstract of the 1985 intravenous study (PMID 3935346); Glucose, insulin and C-peptide did not change after the supplement containing it (PMID 8778149); Animal and cell studies report no toxicity in their abstracts, but none was a formal safety study. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Cyclo(His-Pro). Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“The two human studies that gave the dipeptide reported little about safety”).
Interactions
Unknown: a PubMed search for human interaction studies of Cyclo(His-Pro) (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Cyclo(His-Pro) products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Cyclo(His-Pro)'s expected mass, 234.2 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine: an endogenous metabolite studied in research). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
The two human studies that gave the dipeptide reported little about safety.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Cyclo(His-Pro) is a natural metabolite studied in research; it is not an approved medicine.
Frequently Asked Questions
?What is cyclo(His-Pro)?
A cyclic dipeptide, histidine and proline closed into a ring, formed when TRH loses its first residue. It is also called histidyl-proline diketopiperazine or CHP and occurs in blood, spinal fluid, urine, brain, gut and many foods.
?Has it been tested in people?
Mostly by measuring it. Only two studies gave it to people: a single 400-microgram intravenous injection in 1985, which did not change TSH or prolactin, and a 1996 study in which a supplement containing it raised blood levels slightly. No trial has tested it as a treatment.
?Is it absorbed when swallowed?
Partly. In mice a quarter to a third of the peptide in the blood was intact half an hour after feeding, and in eight volunteers a supplement containing it raised blood levels modestly within two hours.
?Does it reduce appetite?
Early rat studies said so, but a 1988 re-test found no effect on food intake in rats. In people, levels track body weight and eating disorders, which shows an association, not an effect.
?What do the newer animal studies show?
Mouse and rat studies since 2023 report less fatty liver and scarring, better muscle function in muscular dystrophy and ageing models, and protection in arthritic knees. The developing company funded or co-authored all three.
?Is it the same as zinc-plus-cyclo(His-Pro) products?
No. Those combine zinc with the dipeptide, and results with the combination cannot be credited to cyclo(His-Pro) alone. The registered phase 2 diabetes trials used the combination.
References
- [other] PubChem CID 449094, Cyclo(his-pro): formula C11H14N4O2, molecular weight 234.25. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/449094
- [pubmed] Takahara Y, et al. "Detection in human serum by radioimmunoassay of histidyl-proline diketopiperazine, a metabolite of thyrotropin-releasing hormone." J Clin Endocrinol Metab, 1983;56(2):312-9. PMID: 6401750.
- [pubmed] Hilton CW, et al. "Radioimmunoassay of cyclo(His-Pro) in unextracted human plasma: report of a normal range and definition of factors critical for successful assay." Neuropeptides, 1989;13(1):65-70. PMID: 2922107.
- [pubmed] Parker CR Jr, et al. "Evidence for the presence of immunoreactive histidyl-proline diketopiperazine [cyclo (His-Pro)] in the adult human brain." Peptides, 1983;4(6):879-81. PMID: 6672793.
- [pubmed] Diamanti Kandarakis E, et al. "Distribution and characterization of cyclo (His-Pro)-like immunoreactivity in the human gastrointestinal tract." Neuropeptides, 1985;6(1):21-5. PMID: 3990923.
- [pubmed] Leduque P, et al. "Histidyl-proline diketopiperazine (His-Pro DKP) immunoreactivity is present in the glucagon-containing cells of the human fetal pancreas." J Clin Invest, 1987;79(3):875-80. PMID: 3102558.
- [pubmed] Iriuchijima T, et al. "Thyrotropin-releasing hormone and cyclo (His-Pro)-like immunoreactivities in the cerebrospinal fluids of 'normal' infants and adults, and patients with various neuropsychiatric and neurologic disorders." Life Sci, 1987;41(22):2419-28. PMID: 2891013.
- [pubmed] Jackson IM, et al. "Amyotrophic lateral sclerosis: thyrotropin-releasing hormone and histidyl proline diketopiperazine in the spinal cord and cerebrospinal fluid." Neurology, 1986;36(9):1218-23. PMID: 3092130.
- [pubmed] Prasad C, et al. "Increased cerebrospinal fluid cyclo(His-Pro) content in schizophrenia." Neuropeptides, 1991;20(3):187-90. PMID: 1762668.
- [clinical-trial] Peters J, et al. "Lack of effect of the TRH related dipeptide histidyl-proline diketopiperazine on TSH and PRL secretion in normal subjects, in patients with microprolactinomas and in primary hypothyroidism." Clin Endocrinol (Oxf), 1985;23(3):289-93. PMID: 3935346.
- [pubmed] Herminghuysen D, et al. "The gut-brain peptide cyclo(His-Pro) is secreted in a pulsatile fashion in fasting humans." Neuropeptides, 1994;26(4):273-80. PMID: 8028717.
- [pubmed] Hilton CW, et al. "Acute alterations of cyclo(His-Pro) levels after oral ingestion of glucose." Neuropeptides, 1990;15(1):55-9. PMID: 2183084.
- [pubmed] Mizuma H, et al. "The bioactive peptide cyclo(His-Pro) may be absorbed following ingestion of nutritional supplements that contain it." J Am Coll Nutr, 1996;15(2):175-9. PMID: 8778149.
- [pubmed] Hilton CW, et al. "Food contains the bioactive peptide, cyclo(His-Pro)." J Clin Endocrinol Metab, 1992;75(2):375-8. PMID: 1639938.
- [pubmed] Hilton CW, et al. "Relationship between plasma cyclo (His-Pro), a neuropeptide common to processed protein-rich food, and C-peptide/insulin molar ratio in obese women." Nutr Neurosci, 2001;4(6):469-74. PMID: 11843266.
- [pubmed] Deblieux P, et al. "The Neuropeptide Cyclo(His-Pro) Levels are Increased in Diabetic Ketoacidosis and Fall with Treatment in Parallel with Levels of Glucagon." Nutr Neurosci, 1998;1(2):161-4. PMID: 27406021.
- [pubmed] Jara LJ, et al. "Elevated serum levels of cyclo (His-Pro), an endogenous inhibitor of pituitary prolactin secretion, in systemic lupus erythematosus patients." Lupus, 1997;6(3):258-60. PMID: 9104733.
- [pubmed] Wisniewski TL, et al. "Relationship between serum cyclo(His-Pro) concentrations and the nutritional status of HIV-infected patients." South Med J, 1994;87(3):348-51. PMID: 8134857.
- [pubmed] Wolf GC, et al. "The neuropeptide histidyl proline diketopiperazine throughout human pregnancy: an inverse correlation with amniotic fluid prolactin." Am J Obstet Gynecol, 1990;162(3):740-5. PMID: 2316580.
- [pubmed] Steiner H, et al. "Histidyl proline diketopiperazine (Cyclo [His-Pro]) in eating disorders." Neuropeptides, 1989;14(3):185-9. PMID: 2615922.
- [pubmed] Wolf GC, et al. "Identification of cyclo(His-Pro)-like immunoreactivity in human follicular fluid: correlation with steroid and peptide hormones." J Soc Gynecol Investig, 1994;1(3):220-4. PMID: 9419775.
- [pubmed] Prasad C, et al. "Isolation of cyclo(His-Pro)-like immunoreactivity from human urine and demonstration of its immunologic, pharmacologic, and physico-chemical identity with the synthetic peptide." Biochem Int, 1990;21(3):425-34. PMID: 2222490.
- [pubmed] Taubert D, et al. "Identification of the endogenous key substrates of the human organic cation transporter OCT2 and their implication in function of dopaminergic neurons." PLoS One, 2007;2(4):e385. PMID: 17460754.
- [pubmed] Brabant G, et al. "The TRH-metabolic histidyl-proline-diketopiperazine (DKP) inhibits prolactin secretion in male rhesus monkeys." Acta Endocrinol (Copenh), 1981;98(2):189-94. PMID: 6794283.
- [pubmed] Bowden CR, et al. "Re-evaluation of histidyl-proline diketopiperazine [cyclo(His-Pro)] effects on food intake in the rat." Pharmacol Biochem Behav, 1988;29(2):357-63. PMID: 3129742.
- [pubmed] Banks WA, et al. "Radioactively iodinated cyclo(His-Pro) crosses the blood-brain barrier and reverses ethanol-induced narcosis." Am J Physiol, 1993;264(5 Pt 1):E723-9. PMID: 8498494.
- [pubmed] Banks WA, et al. "Orally administered cyclo(His-Pro) reduces ethanol-induced narcosis in mice." Pharmacol Biochem Behav, 1992;43(3):939-41. PMID: 1448489.
- [pubmed] Mizumo H, et al. "Cyclo(His-Pro) augments the insulin response to oral glucose in rats." Life Sci, 1997;60(6):369-74. PMID: 9031682.
- [pubmed] De Masi A, et al. "Cyclo His-Pro Attenuates Muscle Degeneration in Murine Myopathy Models." Adv Sci (Weinh), 2024;11(28):e2305927. PMID: 38728626.
- [pubmed] De Masi A, et al. "Cyclo(His-Pro): A further step in the management of steatohepatitis." JHEP Rep, 2023;5(9):100815. PMID: 37600955.
- [pubmed] Huh G, et al. "Intra-Articular Cyclo(His-Pro) Attenuates Monosodium Iodoacetate-Induced Osteoarthritis by Suppressing COX-2/PGE(2) Signaling and Cartilage Catabolism in Rats." Int J Mol Sci, 2026;27(11). PMID: 42278272.
- [pubmed] Minelli A, et al. "Cyclo(His-Pro) exerts anti-inflammatory effects by modulating NF-κB and Nrf2 signalling." Int J Biochem Cell Biol, 2012;44(3):525-35. PMID: 22185821.
- [pubmed] Grottelli S, et al. "Cyclo(His-Pro) inhibits NLRP3 inflammasome cascade in ALS microglial cells." Mol Cell Neurosci, 2019;94:23-31. PMID: 30439413.
- [review] Grottelli S, et al. "The Role of Cyclo(His-Pro) in Neurodegeneration." Int J Mol Sci, 2016;17(8). PMID: 27529240.
- [review] Prasad C. "Cyclo(His-Pro): its distribution, origin and function in the human." Neurosci Biobehav Rev, 1988;12(1):19-22. PMID: 3287238.
- [pubmed] Mori M, et al. "Histidyl-proline diketopiperazine cyclo (His-Pro): measurement by radioimmunoassay in human blood in normal subjects and in patients with hyper- and hypothyroidism." Biochem Biophys Res Commun, 1982;109(2):541-7. PMID: 6129851.
- [review] Prasad C. "Neurobiology of cyclo(His-Pro)." Ann N Y Acad Sci, 1989;553:232-51. PMID: 2541650.
- [pubmed] Choi BY, et al. "Zinc plus cyclo-(His-Pro) promotes hippocampal neurogenesis in rats." Neuroscience, 2016;339:634-643. PMID: 27773743.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026; most of the human studies are from the 1980s and 1990s. Status comes from Drugs@FDA (openFDA) and the EMA medicines list, searched October 28, 2026, and ClinicalTrials.gov, read October 29, 2026. Searches: PubMed for the dipeptide's names in titles and abstracts (236 records) and with human terms (67), ClinicalTrials.gov for the dipeptide (two zinc-combination trials). Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.