Cyclic Glycine-Proline
IGF-1 Bioavailability Regulator & Neuroprotective Peptide
Endogenous cyclic dipeptide found in plasma, breast milk, and cerebrospinal fluid. Functions as metabolite of IGF-1, regulating its bioavailability through competitive binding to IGFBP-3. Demonstrates neuroprotective, cognitive-enhancing, and cardioprotective properties supported by clinical trials.
Overview
Endogenous cyclic dipeptide found in plasma, breast milk, and cerebrospinal fluid. Functions as metabolite of IGF-1, regulating its bioavailability through competitive binding to IGFBP-3. Demonstrates neuroprotective, cognitive-enhancing, and cardioprotective properties supported by clinical trials.
Competes with IGF-1 for IGFBP-3 binding, normalizing bioavailable IGF-1 levels. Acts as positive allosteric modulator of AMPA and GABA-A receptors. Increases BDNF levels via Akt/MDM2-p53 pathway activation.
Research indications
What the compound has been studied for, grouped by body system. Effect size is the reported magnitude where it was measured — not a recommendation.
Higher cGP levels correlate with improved memory retention in elderly populations
Protects neural stem cells from oxidative stress; efficacy demonstrated in stroke models
Mouse studies show reduced amyloid plaque load and improved spatial memory
Clinical study showed increased CSF cGP and reduced anxiety/depression scores
Clinical trial improved vascular complications and normalized HbA1c%
Demonstrated systolic blood pressure reduction in clinical observations
Higher cGP/IGF-1 ratios associated with favorable clinical outcomes
Maintained ratios correlate with preserved cognitive function with age
A large effect in a weak study and a small effect in a strong one are different things. Effect size is never evidence of use in people.
- Class
- Cyclic dipeptide (2,5-diketopiperazine)
- Chain length
- 2 residues
- Molecular weight
- 154.17 Da
- Typical dose
- 20-100 μg daily (or 300mg blackcurrant extract 2x daily)
- Frequency
- Once daily, preferably in the morning
- Cycle length
- 4-12 weeks
- Storage
- Room temperature in sealed container, protected from moisture and light
Molecular data
- Type
- Cyclic dipeptide (2,5-diketopiperazine)
- Molecular weight
- 154.17 Da
- Chain length
- 2 residues
Dosing reference
Doses reported in the literature and by suppliers. These are a record of what has been used in research — reference, never instruction.
| Context | Route | Amount | Frequency |
|---|---|---|---|
| General cognitive support | Oral capsule | 20-40 μg | 1x daily |
| Neuroprotection/anti-aging | Oral capsule | 40-50 μg | 1x daily |
| Metabolic/cardiovascular support | Oral capsule | 40-100 μg | 1x daily |
| Via blackcurrant extract | Oral capsule | 300 mg BCA | 2x daily |
Interactions
cGP is metabolite of IGF-1; regulates bioavailability through competitive IGFBP-3 binding
Different pathways; BPC-157 promotes tissue repair, cGP modulates IGF-1
Both offer neuroprotection and nootropic effects through distinct pathways
Complementary cognitive effects; Selank addresses anxiety, cGP optimizes IGF-1
Both affect growth hormone/IGF-1 axis; monitor combined effects on levels
Quality checklist
- ✓Third-party tested for purity and potency
- ✓Clear cGP content labeling (typically in micrograms per serving)
- ✓Natural blackcurrant-derived sources from New Zealand
- ✓Sealed containers protected from moisture and light
- !Products lacking clear cGP content specification
- ×Extreme therapeutic claims unsupported by research
- ×Vague concentration descriptions
What to expect
Safety
- Allergic reactions (rash, difficulty breathing, swelling)
- Unexpected blood glucose changes
- Unusual fatigue or weakness
- Consult healthcare provider if taking IGF-1 or growth hormone medications
- Limited long-term human data available
- Not studied in pregnancy
FAQ
Can cyclic glycine-proline improve cognitive function in healthy people, not just disease states?
Yes, research shows higher cGP levels correlate with improved memory retention in healthy elderly populations. Clinical trials demonstrated enhanced cognitive function in normal aging, suggesting benefits for preserving mental sharpness beyond treating disease—relevant for anti-aging protocols.
What's the advantage of blackcurrant extract over pure cGP supplements?
Blackcurrant extract provides cGP at approximately 300mg per serving in a natural, whole-food matrix that may improve bioavailability and provide additional antioxidants. Pure cGP comes in microgram quantities (20-100mcg), so extract forms offer higher doses though containing other compounds alongside cGP.
Does cGP actually help with Parkinson's disease or just animal models?
One human clinical study showed blackcurrant supplementation (which raises CSF cGP by 74%) reduced anxiety and depression scores in Parkinson's patients. While animal models show more dramatic neuroprotection, the human evidence supports cognitive and mood benefits, though larger trials are needed.
Can cyclic glycine-proline be used long-term without breaks?
Most protocols recommend 4-12 week cycles, though human safety data for long-term continuous use is limited. As cGP is an endogenous metabolite naturally found in cerebrospinal fluid and breast milk, extended use appears relatively safe, but cycling allows assessment of individual response and prevents potential tolerance.
References
- 1IGF-1 Homeostasis Regulation StudyScientific Reports · 2014
cGP regulates IGF-1 bioavailability through IGFBP-3 competitive binding
reviewSource ↗ - 2Parkinson's Disease Clinical StudyPMC · 2018
Blackcurrant supplementation increased CSF cGP 74%; reduced anxiety/depression
reviewSource ↗ - 3Alzheimer's Mouse Model StudyPMC · 2023
Significantly improved spatial memory; reduced hippocampal plaques 42.3→14.5 per mm²
animalSource ↗ - 4Stroke Recovery & Cognitive Function ReviewPMC · 2023
Higher cGP/IGF-1 ratios associated with favorable stroke outcomes
reviewSource ↗