Encyclopedia entry

The Pickart hypothesis

In 1973, biochemist Loren Pickart published the isolation of a small tripeptide, glycyl-histidyl-lysine (GHK), from human plasma. Pickart\'s subsequent work, particularly the characterisation of the GHK-copper complex (GHK-Cu), established the hypothesis that this peptide acts as a signal for tissue repair. Five decades of follow-on research have made GHK-Cu the most-studied cosmetic peptide.

The original observation

Pickart noticed that GHK levels in human plasma decline with age (from approximately 200 ng/ml at age 20 to under 80 ng/ml after age 60). He hypothesised that this decline was linked to the reduced tissue-repair capacity of older skin and wounds. Subsequent in-vitro work supported a signal-peptide role: GHK-Cu appears to upregulate collagen synthesis, glycosaminoglycan synthesis, and angiogenesis in cultured skin cells.

Why copper

Free GHK chelates copper from the body with very high affinity, forming the GHK-Cu complex. The copper bound to the peptide appears to be essential for the observed signalling effects. Topical GHK without copper, or copper without GHK, do not replicate the GHK-Cu effects in published studies.

Where the evidence is strongest and weakest

Strongest evidence: in-vitro skin cell studies, animal wound-healing models, and a body of small human trials on skin firmness and barrier repair (mostly industry-funded). Weakest evidence: large independent RCTs on skin appearance outcomes are limited. Most large-scale data is on the wound-healing applications, less on the cosmetic-only use case.

Related: copper peptide hub · best UK GHK-Cu serums.