Cyclic Glycine-Proline
A ring-shaped dipeptide left over from IGF-1 that may tune how much IGF-1 is free to act, measured in people and given only to animals
Cyclic glycine-proline (cGP) is a tiny ring of two amino acids, glycine and proline, that forms from the front end of insulin-like growth factor-1 (IGF-1). It competes with IGF-1 for its main carrier protein in blood, and researchers in New Zealand propose that the ratio of cGP to IGF-1 shows how much IGF-1 is actually available to tissues. That ratio has been measured in stroke, Parkinson disease, obesity and breast milk. Given to rats and mice, cGP lowered blood pressure and improved memory tests. It has never been given to people as a treatment, and it is not a medicine.
No established human dose Details ↓
Recommended Dosing
No established human dose
No study has given cyclic glycine-proline itself to people. The human studies measured the body's own cGP in blood, spinal fluid, brain tissue and breast milk, and the one intervention gave a blackcurrant extract that happens to contain cGP, without stating how much cGP that delivered.
What is it?
IGF-1 is the hormone through which growth hormone does much of its work, and it also supports nerve cells, blood vessels and metabolism. Almost all IGF-1 in blood is bound to carrier proteins, mainly insulin-like growth factor binding protein-3 (IGFBP-3), and only the small unbound share can reach tissues. When the body breaks IGF-1 down, its first three amino acids, glycine-proline-glutamate (glypromate), can be released, and the glycine and proline can close into a ring. That ring is cyclic glycine-proline, also written cGP or cyclo(Gly-Pro).
A research group at the University of Auckland has published on cGP for over a decade. Their central idea, from cell work and mathematical modelling published in 2014, is that cGP still fits the spot on IGFBP-3 where IGF-1 binds, so it competes for the carrier. When IGF-1 activity is too low, cGP frees more of it; when it is too high, the same competition dampens it. On that view, the molar ratio of cGP to IGF-1 in blood tracks the bioavailable IGF-1 better than IGF-1 alone. The idea is plausible and internally consistent, but almost all the evidence for it comes from this one group.
In people, cGP has only been measured. In 34 stroke patients, cGP and the cGP/IGF-1 ratio were lower than in controls soon after the stroke and rose as patients recovered, and a higher ratio at admission went with more improvement by day 90. In Parkinson disease the ratio rose with age in patients with normal thinking and fell with age in those with dementia. In women followed from pregnancy, a higher ratio went with obesity and lower cGP with high blood pressure. Post-mortem brains with Alzheimer disease held more bound cGP and less free IGF-1 than control brains. All of these are small association studies that cannot show cause.
cGP is also a natural part of food. Human breast milk contains it, and in a Finnish cohort of about 500 mothers, higher milk cGP went with lower infant weight over five years but slightly higher BMI at five. Blackcurrant anthocyanin extract contains cGP too; when 11 men with Parkinson disease took the extract for 28 days, cGP rose in their spinal fluid. That study gave a fruit extract, not purified cGP, so it shows uptake into the nervous system, not an effect of cGP on Parkinson disease.
In animals, cGP has been given by mouth or injection. It normalised systolic blood pressure and reduced belly fat in rats made obese on a high-fat diet, restored brain synapse markers in the same model, improved memory and reduced amyloid plaques in a mouse model of Alzheimer disease, and, given to nursing rat mothers, improved their pups' memory into adulthood. Separate groups reported pain relief in mice that naloxone blocked, and a dry mouth as a side effect. A synthetic analogue, NNZ-2591, has gone into children's trials as a different drug. For cGP itself there is no human trial, no approved product and no known safe amount.
Mechanism of Action
cGP is proposed to act as a regulator of IGF-1 rather than as a hormone in its own right: it shares IGF-1's binding site on IGFBP-3 and so changes how much IGF-1 is free.
Competes with IGF-1 for IGFBP-3
By binding the carrier, cGP shifts the balance between bound and free IGF-1, raising activity when IGF-1 is low and damping it when high (PMID 24633053).
Reaches the brain
Taken by mouth it entered rat milk and pups, and in people cGP from blackcurrant extract rose in spinal fluid (PMIDs 27355491, 29865234).
Opioid-linked effects in mice
Pain relief and reduced saliva were reversed by naloxone, suggesting a separate opioid-related action (PMIDs 26277051, 32155179).
Published Research
These are the studies of cyclic glycine-proline read from their PubMed abstracts on October 29, 2026: seven that measured it in people (blood, spinal fluid, brain tissue and breast milk), eight in rats and mice, four in cells or bacteria, and two reviews. No study gave cGP itself to people.
Stroke recovery and the cGP/IGF-1 ratio
In 34 patients sampled within three days of stroke and 50 controls, cGP, IGFBP-3 and the cGP/IGF-1 ratio started lower in patients. cGP and the ratio rose as neurological scores improved, and the ratio at admission correlated with stroke scale scores and their change at day 90.
Parkinson disease and cognition
Among 178 people with Parkinson disease and 23 controls, the cGP/IGF-1 ratio rose with age in patients with normal cognition and fell with age in those with dementia. In healthy controls a higher ratio went with better cognitive scores. Cross-sectional; the authors call for longitudinal confirmation.
Pregnancy, obesity and blood pressure
In women followed from the 15th week of their first pregnancy to six years after birth, obesity went with lower IGF-1 and a higher cGP/IGF-1 ratio, and high blood pressure with lower IGFBP-3 and cGP. Women who lost weight had a rising ratio; those who gained had falling IGFBP-3.
Blackcurrant extract raised spinal fluid cGP
Eleven men with Parkinson disease took blackcurrant anthocyanin extract for 28 days. The extract itself contained cGP, and cGP rose in spinal fluid while IGF-1 and IGFBP-3 did not; spinal fluid and plasma cGP correlated. The extract was given, not purified cGP, and there was no control group.
Alzheimer brains: more bound cGP
In two frontal brain regions from 15 people with Alzheimer disease and 15 controls, free IGF-1 was lower and bound cGP and IGFBP-3 higher in Alzheimer cases. The authors read the extra bound cGP as the brain trying to free more IGF-1.
Breast milk cGP and child growth
In milk from 501 Finnish mothers about 2.6 months after birth, higher cGP was associated with lower child weight across five years but higher BMI at age five, after adjusting for birth weight, breastfeeding and maternal BMI. Higher milk IGF-1 showed a different pattern over time.
What shapes milk cGP
In the same 501 milk samples, maternal factors interacted with the baby's sex: maternal education was linked to the milk IGF-1 to cGP ratio differently for boys and girls. An association study of milk composition.
How cGP regulates IGF-1
Earlier work had shown cGP helped recovery after brain ischaemia in rats and slowed lymphoma growth in mice. In cells it boosted IGF-1 activity when IGF-1 was scarce and blunted it when IGF-1 was in excess, and modelling explained this by competition for IGFBP-3.
Blood pressure in obese rats
Male rats fed a high-fat diet had higher systolic pressure, more fat and more plasma cGP than chow-fed rats. Four weeks of cGP lowered systolic pressure and abdominal fat but did not change total body composition or insulin.
Brain synapse markers in obese rats
In the same model, a high-fat diet lowered IGF-1 and several synaptic markers in the brain. cGP raised brain cGP without changing brain IGF-1 and normalised synaptophysin, GFAP and tyrosine hydroxylase, though not glutamate receptor-1.
Given in infancy, memory in adulthood
Rat pups received cGP through their nursing mothers from day 8 to 22. As adults they navigated a water maze more accurately and had more capillaries, larger astrocytes and more glutamate receptor-1 in the hippocampus; the authors describe the memory gain as moderate.
Taken by mouth, passed through milk
Rat milk naturally contained cGP. When dams were dosed by mouth, cGP reached their milk and their pups, showing oral availability, and the pups recognised new objects better, with no change in movement or anxiety-like behaviour.
Faster breast gland regression after weaning
In rat mothers given cGP by mouth, mammary glands regressed faster after nursing ended through more cell death, and IGF-1 receptor activity fell late in the process. Milk production and composition were unchanged.
Alzheimer model mice
In APP/PS1 mice, which develop amyloid plaques and memory loss, cGP improved spatial memory and reduced amyloid plaque burden.
Pain and inflammation in mice
Injected into the abdomen, cyclo-Gly-Pro reduced pain behaviour in several tests for up to six hours without impairing movement; naloxone blocked the effect in the hot-plate test, pointing to opioid pathways. It also reduced paw swelling and neutrophil activity.
Dry mouth, reversed by naloxone
In mice, cyclo-Gly-Pro, like morphine, reduced saliva flow and its protein content and changed the submandibular gland, and naloxone restored them; docking suggested contact with an opioid receptor.
Human neural stem cells under oxidative stress
In human fetal neural stem cells exposed to hydrogen peroxide, cyclo-glycylproline reduced cell death in a dose-dependent way through Akt signalling and the MDM2-p53 pathway; an MDM2 inhibitor cancelled the protection.
Blocking a gut bacterial enzyme
Cyclo(Gly-Pro) inhibited the bacterial enzyme that turns tryptophan into indole, the precursor of a kidney toxin, with a Ki of 17 µM, and cut indole production in bacterial cultures and human stool samples.
Made by skin bacteria
Streptococcus strains from human skin all produced cyclo(-Gly-Pro), most at 25 °C, and the compound was tested on inflammatory markers in a keratinocyte model of atopic dermatitis; the authors call for animal work.
cGP and IGF-1 in the ageing brain
The Auckland group reviews its model: cGP competes with IGF-1 for IGFBP-3, the cGP/IGF-1 ratio is low in hypertension, stroke and cognitive impairment, and cGP given to animals lowers blood pressure, improves memory and aids stroke recovery.
A marine and endogenous dipeptide
A review of where cGP comes from (marine organisms, the body and synthesis), its activities in cells and animals, and its role in IGF-1 regulation, arguing it deserves more drug-discovery attention.
No Established Human Dose
No study has given cyclic glycine-proline itself to people. The human studies measured the body's own cGP in blood, spinal fluid, brain tissue and breast milk, and the one intervention gave a blackcurrant extract that happens to contain cGP, without stating how much cGP that delivered. The amounts used in rats and mice come from animal experiments and do not translate into a human dose.
What this rests on: PMID 31019991, PMID 32671179, PMID 29865234, PMID 32850934.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, 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 Cyclic Glycine-Proline is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Cyclic Glycine-Proline has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Cyclic Glycine-Proline, 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 Cyclic Glycine-Proline stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Cyclic Glycine-Proline. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long Cyclic Glycine-Proline lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: Reduced saliva flow in mice, reversed by naloxone (PMID 32155179); Faster regression of the breast gland after weaning in rats, with no change in milk production (PMID 28063218); No change in movement or anxiety-like behaviour in rat pups exposed through milk (PMID 27355491). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Cyclic Glycine-Proline. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“No human safety data exist for cGP given as a substance”).
Interactions
Unknown: a PubMed search for human interaction studies of Cyclic Glycine-Proline (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 Cyclic Glycine-Proline 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 Cyclic Glycine-Proline's expected mass, 154.2 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
No human safety data exist for cGP given as a substance. From the animal studies:
Contraindications & Cautions
Not a medicine. These cautions follow from the evidence.
Legal Status
cGP is an endogenous metabolite studied in research, not a drug.
Frequently Asked Questions
?What is cyclic glycine-proline?
A two-amino-acid ring, cyclo(Gly-Pro), thought to form from the first three amino acids of IGF-1. It is also found in breast milk, blackcurrants and many microbes.
?What does it do?
The leading idea is that it competes with IGF-1 for the carrier protein IGFBP-3 and so adjusts how much IGF-1 is free to act. That model comes mostly from one research group and is supported by cell, animal and human measurement studies.
?Has it been tested as a treatment in people?
No. People have only had their own cGP measured. A study in Parkinson disease gave blackcurrant extract, which contains cGP, and found more cGP in spinal fluid; that is not a trial of cGP.
?Is it the same as trofinetide or NNZ-2591?
No. Trofinetide is a modified version of IGF-1's three-amino-acid fragment and is approved for Rett syndrome; NNZ-2591 is a synthetic analogue of cGP in children's trials. Both are different molecules.
References
- [other] PubChem CID 193540, Cyclo(glycylprolyl): formula C7H10N2O2, molecular weight 154.17. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/193540
- [pubmed] Fan D, et al. "Plasma cyclic glycine proline/IGF-1 ratio predicts clinical outcome and recovery in stroke patients." Ann Clin Transl Neurol, 2019;6(4):669-677. PMID: 31019991.
- [pubmed] Fan D, et al. "Changes of plasma cGP/IGF-1 molar ratio with age is associated with cognitive status of Parkinson disease." Alzheimers Dement (Amst), 2020;12(1):e12025. PMID: 32671179.
- [pubmed] Guan J, et al. "The role for cyclic Glycine-Proline, a biological regulator of insulin-like growth factor-1 in pregnancy-related obesity and weight changes." J Biol Regul Homeost Agents, 2018;32(3):465-478. PMID: 29921371.
- [pubmed] Fan D, et al. "Supplementation of Blackcurrant Anthocyanins Increased Cyclic Glycine-Proline in the Cerebrospinal Fluid of Parkinson Patients: Potential Treatment to Improve Insulin-Like Growth Factor-1 Function." Nutrients, 2018;10(6). PMID: 29865234.
- [pubmed] Kang D, et al. "The autocrine regulation of insulin-like growth factor-1 in human brain of Alzheimer's disease." Psychoneuroendocrinology, 2021;127:105191. PMID: 33706042.
- [pubmed] Galante L, et al. "Growth Factor Concentrations in Human Milk Are Associated With Infant Weight and BMI From Birth to 5 Years." Front Nutr, 2020;7:110. PMID: 32850934.
- [pubmed] Galante L, et al. "Sexually Dimorphic Associations between Maternal Factors and Human Milk Hormonal Concentrations." Nutrients, 2020;12(1). PMID: 31935821.
- [pubmed] Guan J, et al. "Cyclic glycine-proline regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1." Sci Rep, 2014;4:4388. PMID: 24633053.
- [pubmed] Li F, et al. "Cyclic glycine-proline normalizes systolic blood pressure in high-fat diet-induced obese male rats." Nutr Metab Cardiovasc Dis, 2020;30(2):339-346. PMID: 31753784.
- [pubmed] Li F, et al. "Cyclic glycine-proline administration normalizes high-fat diet-induced synaptophysin expression in obese rats." Neuropeptides, 2019;76:101935. PMID: 31146894.
- [pubmed] Singh-Mallah G, et al. "Administration of cyclic glycine-proline during infancy improves adult spatial memory, astrocyte plasticity, vascularization and GluR-1 expression in rats." Nutr Neurosci, 2022;25(12):2517-2527. PMID: 34565308.
- [pubmed] Singh-Mallah G, et al. "Maternally Administered Cyclic Glycine-Proline Increases Insulin-Like Growth Factor-1 Bioavailability and Novelty Recognition in Developing Offspring." Endocrinology, 2016;157(8):3130-9. PMID: 27355491.
- [pubmed] Singh-Mallah G, et al. "Cyclic-glycine-proline accelerates mammary involution by promoting apoptosis and inhibiting IGF-1 function." J Cell Physiol, 2017;232(12):3369-3383. PMID: 28063218.
- [pubmed] Arora T, et al. "Cyclic Glycine-Proline Improves Memory and Reduces Amyloid Plaque Load in APP/PS1 Transgenic Mouse Model of Alzheimer's Disease." Int J Alzheimers Dis, 2023;2023:1753791. PMID: 36909366.
- [pubmed] Ferro JN, et al. "Cyclo-Gly-Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice." Clin Exp Pharmacol Physiol, 2015;42(12):1287-95. PMID: 26277051.
- [pubmed] Melo IS, et al. "Restoration of Cyclo-Gly-Pro-induced salivary hyposecretion and submandibular composition by naloxone in mice." PLoS One, 2020;15(3):e0229761. PMID: 32155179.
- [pubmed] Murotomi K, et al. "Cyclo-glycylproline attenuates hydrogen peroxide-induced cellular damage mediated by the MDM2-p53 pathway in human neural stem cells." J Cell Physiol, 2023;238(2):434-446. PMID: 36585955.
- [pubmed] Oikawa D, et al. "Cyclo-glycylproline, a food-derived diketopiperazine, inhibits bacterial indole production: implications for diabetic nephropathy prevention." Biosci Biotechnol Biochem, 2025;90(1):57-65. PMID: 41143739.
- [pubmed] Lee H, et al. "Exploring Cyclo (-Gly-Pro) for inflammation modulation in atopic dermatitis: a study on streptococcal postbiotics." Genes Genomics, 2026;48(6):883-894. PMID: 41872622.
- [review] Guan J, et al. "Cyclic Glycine-Proline (cGP) Normalises Insulin-Like Growth Factor-1 (IGF-1) Function: Clinical Significance in the Ageing Brain and in Age-Related Neurological Conditions." Molecules, 2023;28(3). PMID: 36770687.
- [review] Hu L, et al. "Exploring Sources, Biological Functions, and Potential Applications of the Ubiquitous Marine Cyclic Dipeptide: A Concise Review of Cyclic Glycine-Proline." Mar Drugs, 2024;22(6). PMID: 38921582.
- [pubmed] Neumeyer AM, et al. "NNZ-2591 in Children and Adolescents With Phelan-McDermid Syndrome: Single-Group, Open-Label, Phase 2 Trial Results." Neurol Genet, 2026;12(1):e200338. PMID: 41450730.
Sources & Citations
Studies were read from their PubMed records on October 29, 2026. Formula and weight come from PubChem CID 193540; status from Drugs@FDA, the EMA medicines list and ClinicalTrials.gov, searched October 28-29, 2026. 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.