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The Peptide Effect
preclinicalAnti-Aging & Skin

GHK

Also known as: Glycyl-L-Histidyl-L-Lysine, GHK tripeptide, Liver Cell Growth Factor, GHK peptide

GHK is a naturally occurring tripeptide (Gly-His-Lys) found in human plasma, saliva, and urine that declines significantly with age. It is the base form of the well-known GHK-Cu (copper peptide) and can bind copper ions in vivo. Groundbreaking genomic studies have revealed that GHK modulates the expression of over 4,000 human genes, generally resetting gene activity patterns toward a healthier, more youthful state.

Key Facts

Mechanism
GHK is a tripeptide composed of glycine, histidine, and lysine. It naturally binds copper(II) ions with high affinity to form the GHK-Cu complex, but the peptide backbone itself also possesses independent biological activity. GHK modulates gene expression through mechanisms that are not yet fully elucidated, but Broad Institute Connectivity Map studies show it affects 4,000+ genes — upregulating genes involved in tissue repair, antioxidant defense, and stem cell maintenance while downregulating genes associated with inflammation, fibrosis, and tissue destruction. It stimulates collagen synthesis, glycosaminoglycan production, and decorin expression. GHK also promotes angiogenesis, nerve outgrowth, and activates wound repair processes. Plasma levels of GHK drop from approximately 200 ng/mL at age 20 to 80 ng/mL by age 60, correlating with the decline in regenerative capacity associated with aging.
Research Status
preclinical
Half-Life
Estimated at minutes to hours (similar to GHK-Cu); rapidly binds copper in plasma
Molecular Formula
C₁₄H₂₂N₆O₄
Primary Use
Anti-Aging & Skin

Benefits

  • Broad gene expression modulation — resets expression of 4,000+ genes toward healthier patterns, as demonstrated in Connectivity Map studiespreliminary
  • Promotes wound healing — stimulates collagen synthesis, angiogenesis, and dermal remodelingmoderate
  • Anti-inflammatory activity — suppresses pro-inflammatory cytokines including TGF-beta, TNF-alpha, and IL-6 expressionmoderate
  • Potential cancer gene suppression — genomic analysis shows GHK upregulates 47 cancer-suppressor genes while downregulating 7 cancer-promoting genespreliminary
  • May improve lung and organ function — gene expression analysis suggests GHK could restore healthy gene patterns in damaged organs, including COPD-affected lungspreliminary
  • Antioxidant properties — reduces oxidative damage markers and upregulates antioxidant defense gene networksmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Topical (serum or cream)0.5–2% concentration1–2× dailyMost common form for skin rejuvenation. Applied to clean skin before moisturizer. Can be used indefinitely. Often found in combination with other peptides like Matrixyl or hyaluronic acid.
Subcutaneous injection (as GHK-Cu complex)1–2 mgOnce dailyWhen injected, GHK rapidly binds available copper in plasma to form GHK-Cu. Injected form is used for systemic anti-aging and tissue repair effects beyond what topical application can achieve. Typical cycles run 2–4 weeks.
Topical (targeted application)1–2% in carrier serum2× daily to specific areasApplied to areas of concern — wound sites, aging skin, or hair loss areas. Use morning and evening. Allow 5 minutes to absorb before applying other products.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Skin irritation in sensitive individuals when applied topicallyrare
  • Mild redness or warmth at the application site with topical usecommon
  • Very limited injectable safety data — long-term effects of exogenous GHK supplementation are not well studiedserious
  • Potential copper imbalance — excessive GHK could theoretically alter copper metabolism, though this has not been documented at typical dosesrare

Frequently Asked Questions

What is the difference between GHK and GHK-Cu?
GHK is the base tripeptide (glycine-histidine-lysine) without any metal ion attached. GHK-Cu is the same tripeptide bound to a copper(II) ion. In the body, free GHK naturally binds to available copper to form GHK-Cu, so the distinction is partly academic — exogenous GHK will complex with copper in your plasma. However, GHK-Cu products provide the copper directly, ensuring the active complex is formed immediately. For topical use, GHK-Cu is generally preferred because the copper ion is integral to many of its skin repair and collagen-stimulating functions.
How was the 4,000-gene study conducted?
The groundbreaking gene expression work was performed using the Broad Institute Connectivity Map (CMap), a database that catalogs how different compounds affect gene expression in human cell lines. Researchers found that GHK could modulate the expression of 4,000+ genes, and that the pattern of changes consistently trended toward a younger, healthier gene expression profile. This included upregulation of DNA repair genes, antioxidant enzymes, and collagen production, alongside downregulation of inflammatory and tissue-destruction pathways. This was an in vitro computational study, and in vivo validation is still ongoing.
Why do GHK levels decline with age?
GHK levels in human plasma decline from approximately 200 ng/mL at age 20 to about 80 ng/mL by age 60 — a 60% reduction. The exact reason for this decline is not fully understood, but it likely relates to decreased production by tissues as part of the broader decline in regenerative signaling with aging. This natural decline correlates with reduced wound healing capacity, thinner skin, and diminished tissue repair that characterize aging, which has led researchers to hypothesize that GHK supplementation could partially restore youthful regenerative capacity.
How well does GHK absorb through the skin topically?
GHK is a small tripeptide (molecular weight ~340 Da), which is below the general 500 Da cutoff for skin penetration. It can penetrate the epidermis, though absorption is enhanced by proper formulation — liposomal delivery systems, penetration enhancers, and serum bases improve bioavailability compared to simple creams. Iontophoresis and microneedling have also been used to enhance delivery. For systemic effects beyond the skin, injectable administration is preferred.
Can GHK bind copper that is already in my body?
Yes. GHK has a strong affinity for copper(II) ions and will readily bind available copper in plasma and extracellular fluid to form the GHK-Cu complex. This means that taking GHK (without copper) can still produce GHK-Cu-mediated effects in vivo, assuming normal copper levels. However, individuals with copper deficiency may not form adequate GHK-Cu complexes, and those with copper excess conditions (like Wilson disease) should avoid GHK supplementation.

References

  1. 1
    GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration(2010)PubMed ↗
  2. 2
    GHK and DNA: resetting the human genome to health(2014)PubMed ↗
  3. 3
    Tripeptide GHK induces programmed cell death in SH-SY5Y neuroblastoma cells(2012)PubMed ↗
  4. 4
    The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging(2012)PubMed ↗

Last updated: 2026-02-14