What Is GHK-Cu? How It Actually Works

Alright, before you spend any money on GHK-Cu for anti-aging in your skin, you need to know that GHK is already built in your collagen, and damage is what cuts it loose. And if you've seen GHK-Cu inside a blend, it's the piece that's in there for your skin.

GHK-Cu is a small peptide made of three amino acids, glycine, histidine and lysine, attached to a copper atom. That's the Cu in the name.

Your body already makes it, and it was first found in human blood back in 1973, when Loren Pickart and Thaler isolated a tripeptide out of human serum that kept liver cells alive longer in culture.

Copper is where the story starts, because your body needs copper for more than a dozen enzymes, including the ones that build connective tissue, but a free copper ion floating loose in your blood will cycle between two charge states and generate the kind of oxidative damage you do not want anywhere near your skin.

When copper sits inside the GHK molecule, that redox activity goes quiet, so the copper can be carried into the cell and handed off without doing damage on the way in (Pickart, Vasquez-Soltero and Margolina, 2015).

You see, collagen is the protein that holds your skin together, and the GHK piece is built into the main collagen in your skin. Specifically, that three-amino-acid sequence sits inside the alpha 2 chain of type I collagen, which is the dominant structural protein in your dermis.

When that collagen gets damaged, the enzymes that break it down cut GHK loose at the exact spot where the damage is.

So the damage itself releases the signal to rebuild, and it releases it precisely where the rebuilding needs to happen, which is why GHK has been described as a built-in modulator of dermal repair rather than something your body has to go manufacture on demand.

That signal goes to cells called fibroblasts, and fibroblasts are the cells that build the framework of your skin. GHK-Cu tells them to make new collagen, and in human adult dermal fibroblasts that shows up as increased collagen production (Pickart and Margolina, 2018).

Now, here's why this matters for you. When you're in your 20s, your blood carries a lot of GHK-Cu, but by age 60, those levels drop by more than a half. The plasma figures run around 200 nanograms per milliliter at age 20 down to roughly 80 by 60.

That drop tracks with how your skin gets thinner as you age. So GHK-Cu is basically an easy way of giving your body back the resources it had when you were younger.

But building new collagen is only part of the job.

Your skin is always breaking down old collagen and replacing it with new collagen. That process is called remodeling, and if the breakdown runs too far, you actually lose collagen. If the damaged collagen ever gets cleared out, it builds up.

The enzymes doing the tearing down are called matrix metalloproteinases, and your body keeps them in check with blockers called TIMPs, which stand for tissue inhibitors of metalloproteinases.

GHK-Cu actually works on both sides of that. In adult dermal fibroblasts it raised MMP1 and MMP2 expression at the lowest concentration tested while raising TIMP1 at every concentration, which is the signature of a system being tuned rather than pushed in one direction (Pickart and Margolina, 2018).

It helps clear out the damaged collagen and keeps the breakdown in balance so the healthy collagen can stay.

So the bottom line is GHK-Cu can help to keep your skin's remodeling running as you age, but your body still has to build the collagen.

Collagen is made of protein. It's about a third of all the protein in your body.

So before you spend all this money on GHK-Cu, you should probably look at how much protein you're eating every day. If you're not eating enough, your fibroblasts have no raw materials to build with.

Research: Pickart and Thaler 1973; Pickart, Vasquez-Soltero and Margolina 2015; Pickart and Margolina 2018.

References

Pickart L, Thaler MM. Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Nat New Biol. 1973;243(124):85-7. PMID 4349963. [TIER: biochemistry, human serum] CARRIED (his 08-01 block, identical). PubMed carries no abstract; the title confirms the human-serum tripeptide and reference 3 confirms the 1973 isolation from human albumin. Backs "first found in human blood back in 1973". https://pubmed.ncbi.nlm.nih.gov/4349963/ https://pubmed.ncbi.nlm.nih.gov/4349963/

Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Int J Mol Sci. 2018;19(7):1987. PMID 29986520, PMC6073405. [TIER: review, by the discovering lab; cell, animal and human topical data] CARRIED (his 08-01 and 06-20 blocks; the 06-20 block lists Vasquez-Soltero as a co-author, but this 2018 paper is Pickart and Margolina only, caption-side correction). Backs: plasma GHK about 200 ng/mL at 20 declining to 80 ng/mL by 60 (camera says "levels drop by more than half"; production is unmeasured, so never "makes less"); the GHK sequence in the alpha 2(I) chain of type I collagen, released into the injury when damage activates proteolytic enzymes ("an early signal for skin repair"); SPARC release after injury; modulation of metalloproteinases AND anti-proteases, "helping to prevent both buildup of damaged proteins and excessive proteolysis" (in adult dermal fibroblasts: MMP1 and MMP2 gene expression up at the lowest concentration, TIMP1 up at all; captions say "balances", never "MMP-1 down"); increased collagen production in human adult dermal fibroblasts; copper enzymes including connective tissue formation; "tissue remodeling". https://doi.org/10.3390/ijms19071987 https://pubmed.ncbi.nlm.nih.gov/29986520/

Pickart L, Vasquez-Soltero JM, Margolina A. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. PMID 26236730, PMC4508379. [TIER: review] CARRIED (his 08-01 block; his 06-20 block dates it 2016, caption-side correction). Backs: three amino acids, glycyl-histidyl-lysine, with strong copper affinity; plasma level decline coinciding with the decline in regenerative capacity; the GHK triplet in the alpha 2(I) chain of type I collagen "liberated by proteases at the site of a wound"; SPARC breakdown after injury generates GHK-Cu; "a natural built-in modulator of dermal repair"; stimulates both synthesis and breakdown of collagen and modulates metalloproteinases and their inhibitors (TIMP-1, TIMP-2); copper(II) redox activity silenced when bound to GHK, allowing nontoxic copper delivery into the cell; GHK lowers free ionic copper, preventing oxidative damage; copper required for more than a dozen enzymes including those of connective tissue formation; fibroblast collagen stimulation. WARNING: its conclusion prints human dose estimates; no caption ever quotes them. https://doi.org/10.1155/2015/648108 https://pubmed.ncbi.nlm.nih.gov/26236730/