Loren Pickart and the question why old blood does not regenerate — the discovery of GHK-Cu
In 1973, a postdoctoral fellow in San Francisco asked whether there is a small substance in the blood serum of younger people that prompts older hepatocytes to regenerate. He found a tripeptide with copper affinity — Gly-His-Lys — that has accompanied wound-healing and cosmetic research for the next 50 years.
The original question
Loren Pickart did his doctorate in biochemistry at the University of California, San Francisco in the early 1970s. His experimental question came from early regeneration biology: hepatocytes — the central cells of the liver — lose their ability to regenerate after injury with age. But when older liver cells are cultured with serum from younger donors, they take up more youthful behaviour again. What in the young serum does that?
Pickart isolated from human albumin a low-molecular fraction that carried this rejuvenating effect in the cell-culture model. In 1973 he published the identification of the active component: a tripeptide with the sequence glycyl-L-histidyl-L-lysine (GHK). Later work showed that GHK at physiological concentrations forms a stable complex with divalent copper ions (Cu²⁺) — GHK-Cu — and that this copper complex is the actually biologically active form.
A substance that declines — and does a lot biologically
One of the early observations was that GHK concentration in plasma declines with age — from about 200 ng/mL around age 20 to about 80 ng/mL at age 60 (per Pickart data). This correlation has fed the hypothesis for decades that substitution could have an 'anti-aging' effect. Methodologically, however, this conclusion is not compelling: an age-associated decline in concentration alone does not establish a causal contribution to aging, and no controlled human study has tested GHK substitution against clinical endpoints in humans.
The biological effects of GHK-Cu are well documented in preclinical studies: stimulation of collagen and glycosaminoglycan synthesis in fibroblasts, acceleration of wound healing in animal models, antioxidative action via modulation of superoxide dismutase. Pickart and co-authors have over decades described gene-regulatory effects — at the RNA-profile level GHK-Cu modulates numerous genes in vitro, which 2010s publications refined with RNA-Seq methods.
The path into cosmetics
A pharmaceutical program in the 1990s (ProCyte Corporation, founded by Pickart) developed GHK-Cu-containing wound-healing preparations. Iamin Gel received approval in the US as a skin wound-healing product; the substance also found use in some veterinary applications. The broader clinical breakthrough did not materialise.
Instead, GHK-Cu became a central component of the cosmetic peptide industry from the late 1990s. Creams and serums with low GHK-Cu concentrations (typically 0.1–1%) are marketed for anti-aging, wound-healing and anti-inflammatory indications. Effect sizes in use studies are small to moderate, often formulation-dependent, and comparability with high-quality moisturisers is not systematically documented.
The black-market wave
In parallel with the cosmetic application, injectable GHK-Cu spread from the 2010s in bio-hacking and sports communities. Reported uses range from wound healing to hair growth to skin rejuvenation. The human data base on systemic application is extremely thin: no published placebo-controlled RCT with clinical endpoints, no established dosing standards, no systematic safety data.
„GHK-Cu is an impressively potent substance in the test tube and the Petri dish. What it does in the living human under realistic conditions is a different question — and that question has never been cleanly answered."
What the story methodologically shows
GHK-Cu is a teaching case for a phenomenon that occurs more often in the peptide world: a biologically genuinely active substance with well-documented cellular effects never reaches an ICH-GCP-compliant clinical evidence base. The reason rarely lies in the substance itself, but in incentive structures: a tripeptide with a long patent history is not an attractive investment object for a modern pharmaceutical approval program. At the same time it is cosmetically lucrative enough to build an industry around itself.
For assessment of the substance this means: cellular pharmacology is well documented, cosmetic effect is small and formulation-dependent, systemic application in humans is not sufficiently studied. That is a differentiated assessment, not a simple verdict.
Open questions
- How large is the clinical effect of topical GHK-Cu compared with modern moisturisers and retinoid therapies?
- Would a modern ICH-GCP-compliant study of systemic GHK-Cu for wound healing or hair growth be feasible — and who would fund it?
- How reproducible are the gene-regulatory effects from the 2010s Pickart studies in independent laboratories?
- How should the cosmetic industry deal with the spectrum from 'pure marketing' to 'biologically documented' in peptide advertising?