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Overview
What is Cyclic Glycine-Proline?
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.
Key Benefits
Neuroprotection, cognitive enhancement, IGF-1 optimization, cardiovascular support, metabolic health, convenient oral administration, crosses blood-brain barrier
Mechanism of Action
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.
Molecular Information
Weight
154.17 Da
Length
2 amino acids (cyclic)
Type
Cyclic dipeptide (2,5-diketopiperazine)
Amino Acid Sequence:
cyclo(Gly-Pro)
* Cyclic structure formed by peptide bond between glycine and proline termini
Research Indications
Cognitive Enhancement
Research shows higher cGP levels correlate with better memory retention in elderly. cGP increases BDNF and acts on AMPA receptors for pro-cognitive effects.
Neuroprotection
Protects neural stem cells from oxidative stress via Akt/MDM2-p53 pathway. Demonstrated efficacy in stroke and hypoxic-ischemic brain injury models.
Alzheimer's Disease
Mouse studies show significant reduction in amyloid plaque load and improved spatial memory. Clinical trials of cGP analogs ongoing for neurodegenerative conditions.
Parkinson's Disease
Clinical study showed increased CSF cGP levels and reduced anxiety/depression scores in PD patients following supplementation.
Research Protocols
Disclaimer
These are commonly discussed research protocols and not medical advice. Consult a healthcare provider before use.
Timing
cGP is orally bioavailable with effective brain uptake. Take consistently at the same time daily. Can be used long-term as it is an endogenous compound naturally found in the body.
Peptide Interactions
How to Reconstitute
Important
Always use bacteriostatic water (BAC). Sterile technique is essential.
cGP is typically available as pre-made capsules or in blackcurrant-derived supplements
Take capsule with water, preferably with food for optimal absorption
If using raw powder, measure precise dose with accurate milligram scale
Maintain consistent daily timing for best results
Store in cool, dry place away from direct sunlight
No refrigeration typically required for oral formulations
Quality Indicators
Third-party tested
Quality cGP supplements should have independent purity and potency testing from reputable labs
Clear concentration labeling
Product should clearly state cGP content per serving (typically in micrograms)
Natural source (blackcurrant-derived)
New Zealand blackcurrant extracts are a well-researched natural source of cGP
Proper packaging
Sealed containers protected from moisture and light to maintain stability
No concentration specified
Avoid products that don't clearly state cGP content or use only vague descriptions
Excessive claims
Be wary of products making extreme therapeutic claims not supported by research
What to Expect
- Week 1-2: Possible subtle improvements in mental clarity
- Week 2-4: Enhanced cognitive function and focus may become noticeable
- Week 4-8: Neuroprotective and metabolic benefits accumulating
- Week 8-12: Optimal IGF-1 regulation and sustained cognitive support
- Individual responses vary based on baseline cGP/IGF-1 ratio
- Most effective for: Cognitive decline prevention, healthy aging, metabolic support
Side Effects & Safety
- 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
References
Alzheimer's Mouse Model Study (2023)
cGP treatment significantly improved spatial memory and reduced amyloid plaque density in hippocampus (42.3 to 14.5 plaques/mm²) and cortex (42.7 to 15.4 plaques/mm²) in Alzheimer's disease mouse model.
View Study (opens in new tab) →Stroke Recovery & Cognitive Function Review (2023)
Comprehensive review showing stroke patients with higher cGP/IGF-1 ratios have more favorable outcomes. Elderly with higher cGP levels show better memory retention. Decrease in cGP/IGF-1 ratio with age associated with dementia.
View Study (opens in new tab) →Parkinson's Disease Clinical Study (2018)
Blackcurrant anthocyanin supplementation (containing cGP) increased cerebrospinal fluid cGP by 74% and reduced anxiety/depression scores in Parkinson's patients. Demonstrated oral bioavailability and brain penetration.
View Study (opens in new tab) →Quick Start Guide
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Community Insights
Self-reported by PepPedia users. Not clinical evidence. Health changes reflect all users, including those taking multiple compounds.
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