Clinical2019
Higher plasma cGP/IGF-1 ratio at admission predicted better clinical outcome and recovery in stroke patients.
Neuroprotection
clinical
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Cyclic Glycine-Proline
Cyclic glycine-proline (cGP) is a naturally occurring small cyclic dipeptide belonging to the 2,5-diketopiperazine family.
Overview
Cyclic glycine-proline (cGP) is a naturally occurring small cyclic dipeptide belonging to the 2,5-diketopiperazine family. It is endogenous to the human body, found in plasma, breast milk, and cerebrospinal fluid. cGP is a metabolite of insulin-like growth factor-1 (IGF-1) and plays a key role in regulating IGF-1 bioavailability by competing with IGF-1 for binding to IGFBP-3. Research suggests cGP has neuroprotective, nootropic, and cardioprotective properties, with clinical trials showing benefits for cognitive function, stroke recovery, and metabolic health.
Last reviewed: 2026-08-18
Identity & Aliases
Also known as
cGPcyclo(Gly-Pro)cyclic glycyl-prolineGly-Pro diketopiperazine2,5-diketopiperazine of Gly-Pro
Status: Research compound - endogenous peptide with clinical studies; not FDA approved
Full composition (formula, molecular weight, sequence) in Quick Facts →
Research Areas
IGF-1 signaling regulationStroke recovery biomarkerAge-related cognitive declineNeuroprotection
Available Evidence
Human
An observational clinical study (Ann Clin Transl Neurol, 2019) found the plasma cyclic glycine-proline/IGF-1 ratio predicts clinical outcome and recovery in stroke patients. A clinical pharmacology review describes cGP as normalising IGF-1 function with potential clinical significance in the ageing brain, though no interventional trials of cGP supplementation were found.
Animal
Preclinical studies, largely from one research group, report that cGP restores IGF-1 bioavailability and improves outcomes in rodent models of ischemic brain injury and aging-related cognitive decline.
In Vitro
Cell and binding assays show cGP binds insulin-like growth factor-binding protein 3 (IGFBP-3), displacing IGF-1 and restoring IGF-1 bioavailability - the mechanism proposed for its effects.
Uncertain
Claims that cGP supplementation slows aging or enhances cognition in humans remain unproven; no human efficacy trials exist.
Key Studies & Findings
Clinical2023
Review of clinical pharmacology and preclinical data concludes cGP normalises IGF-1 function with clinical significance in the ageing brain and age-related neurological conditions.
Benefits & Effects
cognitive enhancement
clinical
IGF-1 optimization
clinical
cardiovascular support
clinical
metabolic health
clinical
convenient oral administration
clinical
crosses blood-brain barrier
clinical
No side effects data available yet.
This peptide may have limited safety data.
Limitations & Open Questions
The evidence base is small: a limited number of observational human studies and mostly single-group preclinical work, much of it from one research group. No large randomized clinical trials of cGP exist, and commercial cGP supplements are not regulated as medicines.
Pharmacology
An endogenous cyclic dipeptide formed from IGF-1 metabolism. Studied via oral and parenteral administration in preclinical models; human pharmacokinetics of exogenous cGP are not well characterized.
Reported Research Dosing
Reported values from research literature and community protocols. Educational reference only — not a dosing recommendation or medical advice.
20-40 μg
Route: Oral
Half-life: ~15-30 minutes systemic
Research Protocols
General cognitive support
- Dose
- 20-40 μg
- Frequency
- 1x daily
- Route
- Oral (capsule)
Neuroprotection/anti-aging
- Dose
- 40-50 μg
- Frequency
- 1x daily
- Route
- Oral (capsule)
Metabolic/cardiovascular support
- Dose
- 40-100 μg
- Frequency
- 1x daily
- Route
- Oral (capsule)
Via blackcurrant extract
- Dose
- 300 mg BCA
- Frequency
- 2x daily
- Route
- Oral (capsule)
Research protocols are for educational purposes only. Always consult qualified medical professionals.
Frequently Asked Questions
Is cGP a synthetic peptide?
It is an endogenous cyclic dipeptide (glycine-proline diketopiperazine) generated during IGF-1 breakdown, and it is also produced synthetically for research and supplements.
What does cGP do?
It binds to IGFBP-3 and displaces IGF-1, restoring IGF-1 bioavailability. Proposed downstream effects are neuroprotective, with observational data linking cGP/IGF-1 ratios to stroke recovery.
Does cGP have proven benefits in humans?
No. Current human data are observational (e.g., stroke recovery prediction) plus a clinical pharmacology review; interventional evidence of benefit is lacking.
Research Citations
1
Alzheimer's Mouse Model Study (2023)
(2023)
2
Stroke Recovery & Cognitive Function Review (2023)
(2023)
3
Parkinson's Disease Clinical Study (2018)
(2018)
Related Resources
Quick Facts
Molecular Weight
154.17
Mechanism
cGP competes with IGF-1 for binding to IGFBP-3, thereby regulating the amount of bioavailable IGF-1 in circulation. It normalizes IGF-1 function - promoting activity when insufficient and inhibiting when excessive. Also acts as positive allosteric modulator of AMPA and GABA-A receptors and increases BDNF levels.
Safety Information
cGP is endogenous to the human body - naturally found in plasma, breast milk, and CSF. Generally well-tolerated with excellent safety profile in clinical studies. No significant adverse events reported in available research. Start with lower dose to assess individual response. Consult healthcare provider if taking medications affecting IGF-1 or growth hormone. Limited long-term human data - most studies are short to medium term.
Citations
31.Alzheimer's Mouse Model Study (2023)
(2023)
2.Stroke Recovery & Cognitive Function Review (2023)
(2023)
3.Parkinson's Disease Clinical Study (2018)
(2018)