GHK-cu – Deep Dive

A comprehensive look at GHK-cu,

everything you need to know about what the studies actually say.

 

Today I wanted to bestow upon you all the truth about the trendy copper peptide. What does the research actually say, do we know correct dosing, is it safe, and is it even worth using?

 

GHK is a tripeptide and its effects exist both in copper-bound and unbound forms. The endogenous system relies on GHK binding copper released from albumin during tissue damage. The copper complex is a critical component here, as, from what I can gather it is donated copper to copper dependent enzymes like lysyl oxidase (collagen cross linking) as well as SOD1 (decreases oxidative stress). GHK is found highest in the brain and second to kidneys when administered to mice. 

 

 GHK-cu in the peptide you might buy is bound to copper 1:1, but chemistry wise it can bind another copper atom— which perhaps could help with copper buffering in copper excessive states! Free copper is an oxidative stress, meaning GHK-cu has the potential to decrease it– and studies have mentioned GHK as having advantages over synthetic copper chelators which have toxicity issues. (Pugliese) 

 GHK has been shown to prevent copper and zinc induced protein aggregation and central nervous system death in vitro (Min). If you know anything about alzheimers, these findings are very fascinating! I will not sperg about this here but certainly it is worthwhile to check out that study. 

 

Anyhow, we must build our understanding up from the evidence– so follow me and we will unearth great knowledge. Or try to. 

 

Let’s start with topical. 

 

In vitro studies show there might be skin penetration (Mazurowska). But GHK is hydrophilic and the corneum is lipophilic, so I was skeptical of this– but bind it to copper and the charges change, making it less polar but still hydrophilic. This 2025 review basically concludes we can’t measure it well enough to even conclude (Ogórek). Despite this, clues do emerge as this study shows microneedling improves absorption by around 10,000% (ex vivo) from baseline (if I did the math right)– and crosses all the way down into the dermis (Li). But, this study showed no deep absorption without microneedling! This, of course does not mean that topical copper peptide doesn’t have an effect– but it certainly means that microneedling could be an important adjunct.

 Despite this, topical use has had a handful of positive clinical trials– examples being eye cream and face cream studies finding improvements in wrinkles (Pickart). Another small trial found a 70% increase in collagen production compared to vitamin C using skin biopsies (Schagen). Similarly, we have a tiny RCT showing potentially increased hair density, although this is our only hint on its hair effects. 

These are all small trials and no definites can be garnered. Personally, I have firsthand seen topical GKHcu to have the most pull out of anything I have ever used for acne. I theorize that it could help with acne via local suppression of inflammation and improvement of ECM repair– as GHK-cu has been shown to suppress il-6, tnf-a, and nf-kb locally. My acne was mostly due to skin barrier damage and inflammation, not hormones. CHK-cu possibly also affects keratinocyte proliferation and migration yielding faster wound healing, which might have been why I saw such fast acne clearance. But damn, this unfortunately is the extent of the evidence we have regarding topical use. 

 

Okay so what are the proposed benefits of its injection?

Copper pep is a very safe peptide, which is one of the reasons I like it. It is, after all, an endogenous molecule, and one that is persistently shown to decrease with age.  At age 20, levels sit around ~200 ng/mL. By about 60, they drop to ~80 ng/mL (roughly a 60% decline), and they likely continue trending downward with advancing age. Recall the cu & zn buffering study I mentioned at the beginning– the authors actually attributed some amount of age-related neurodegeneration to this decrease in GHK. GHK comes from a bigger plasma protein called A2M, which under chronic inflammation (bad sleep, allergies, constant stress, overtraining), gets used up. A2M also decreases with poor liver functioning or inadequate nutrition. This potentially could reduce GHK levels in young folks– so it is important to be aware of. 

 

Research based benefits 

 

GHK/GHK-Cu is fundamentally repair-signaling… NOT growth signalling. 

 

It is normally released from plasma proteins at sites of injury, where it binds copper and orchestrates the following which I have compiled and summarized from studies. Since these are all animals studies I figured a quick summary is preferable to me trying to extrapolate what this all means from low quality animal studies. 

• • Suppression of inflammatory cytokines (IL-6, TNF-α, IL-1β, NF-κB) (Animal models) (Park)
  • Reduction in fibrotic signaling (TGF-β1/Smad) (In vitro & in vivo models) (Ma)
  • Antioxidant activation (Nrf2/HO-1, SOD1) (cell + animal data) (Pickart)
  • Normalization of MMP-9/TIMP-1 ratio (ECM protection / anti-degradation) (preclinical models) (Ma, Badenhorst)
  • Improved collagen and ECM remodeling (animal models + small human skin trials) (Pickart)
  • Accelerated wound healing in skin, cornea, lung, stomach, and intestine (preclinical models) (Pickart)
  • Reduced fibrinogen gene expression (30-60%) (Fibrinogen is the most powerful risk factor for CVD or death, more predictive than cholesterol) (Gene transcription) (Lee, pickart)

• Increased angiogenesis in damage tissue (Animal models) 

• Antiapoptotic effects in damaged tissues (animal lung models, potentially anticancer)

• Decreasing oxidation of LDL (50-70%) (in vitro)
• Binding of excess copper and zinc (In vitro) (Min)
  
  

I must emphasize again that this is all what I consider to be low quality data! It is only a mere clue!

 

 To illustrate the potentially therapeutic use case of GHK-cu, it has been identified as a potential treatment for emphysema, a progressive disease that destroys lung tissue– having a background in this I would say although its MOA seems plausible it’s just unfortunate that there’s no money in a tripeptide as it is hard to patent. 

Okay so this is cool and all, but if you are young, is there any additional benefit from a super physiological amount of GHK-cu? Recall in the endogenous system it responds to damage– if there is no damage beyond baseline, there is nothing for supraphysiological levels to repair. But, if you are an athlete, or even have general damage like sunburns, that is indeed a repair process a super physiological amount could yield additional benefits. 

 

Even for bodybuilding I would state that supraphysiological GHK-cu could be relevant as a recovery and tissue quality tool in the stack. Its antifibrotic effects via downregulation of tgf-b1 and improvement in collagen architecture in the long run could aid in recovery from pesky injuries. In animal models, it seemed to increase angiogenesis (Pickart). Critically, this angiogenesis is context dependent and only seems to happen when there is a trigger, like decreased oxygen tension. Under these circumstances, GHK-cu seems to increase it above baseline. These effects are probably more noticeable when you have a physiological sub-optimal level, aka if you’re past your 20s. 

 

Dosage?

 

With no PK studies, we can’t give a dose recommendation. I swear most influencer claims or whatever are so off and literally have no basis, but luckily for y’all I loveeee looking at patents, as they can elucidate the actual deliverability and constraints at the compound at hand! The only place I could find any pharmacokinetics was a patent for a transdermal delivery system to maintain steady state, targeted plasma levels.

And after reading through this 40 page patent I was delighted to find a human GHK-cu elimination table! I did the math and extrapolated this to injection in an effort to actually be able to give hypothetical research purposes only dosing guidance!

 

C₀(subQ) ≈ (Dose × 1000 / 2.75 L) × 0.8 

 

SUBQ DOSE OF GHK-cu	Cmax
.5 mg	~145–160 µg/L
1mg	~290–320 µg/L
2mg	~580–640 µg/L
5mg	~1450–1600 µg/L

 

.5mg puts you in the physiological replacement zone– but of course, the half life entails that it would need to be injected multiple times a day. 

This is the best I got folks. I just always like to get to the bottom of things so we can have a legitimately scientific routine. If you want me to drop a patch for copper pep lmk! But other than that perhaps on your research models inject .5 mg 3x a day. :p I model this without knowing if copper peptide follows a biphasic curve, but assume diminishing returns over a certain dose. GHK-cu’s gene activation seems to follow a saturation curve in vivo. Of course, your exact curve may vary as it is likely dependent on the amount of toll your body is in– an athlete might be able to push far more and get positive responses.

 

A quick note on nerve regrow potential

 

Despite that data being inconclusive, it does seem like GHK-cu has some capacity or mechanistically aids in nerve outgrowth / regeneration. This is in conjunction with both in vitro mechanistic data and transcriptomic data showing an upregulation in NGF synthesis gene clusters, synaptic scaffolding proteins, and neurite outgrowth factors. There is a study that seems to show accelerated healing of injured nerves and spinal tissue in rodents but unfortunately it was not open access so I was unable to read it. Blahhhh make science freeee– but I will say it’s reasonable to suggest this could be a part of an MMA fighter post fight head trauma recovery stack in conjunction with propranolol, cerebrolysin, creatine, and ketone bodies. But I will write about that another time ;).

 

This, conclusively, was my read of all of the available evidence regarding GHK-cu. I say this with a sad tinge in my heart as I tried to present the scant understanding we have– but I hope my research has aided on your understanding in some capacity. Most people making content about it lack a comprehensive understanding and seem to be misguided, so I publish this to hopefully elucidate things. 

My TLDR:

 

–I would say that microneedling at least .25 using a derma stamp could give you more bank for your buck for topical use. I overall am a large fan of topical GHK-cu as I think it could have wonderful effects for its rather low price point! I think it is up there with tretinoin in regards to anti skin aging treatments. 

– you must inject multiple times a day at your ideal targeted serum level. It is still a bit of a shot in the dark regardless but luckily is effective even as smaller doses (just must be doses consistently). 

– Even if you are younger, personally I would put it in any sort of recovery routine. If you are an athlete, especially regular and persistent dosing could give you an edge in being able to keep up with the demands.
– GHK-cu is very safe, which is why I feel comfortable using it with this amount of information. The benefits are that we have a general mechanistic understanding of it since it is endogenous. We do not have the cancer fears as with BPC-157, and although they do not do precisely the same thing, they both will certainly help with injury recovery hypothetically. Additionally, ghk-cu has been shown to be apoptotic! 

– Longevity wise, I truly do think copper pep is worthwhile as we experience a sharp decrease with. Whether or not that is causal to certain age-related declines we cannot know for certain yet, but when looking at all of the available evidence with an open mind I have come to the conclusion that it is certainly worth it. 

 

SOURCES

 

Pugliese   M., Biondi   V., Gugliandolo   E., Licata   P., Peritore   A. F., Crupi   R., Passantino   A., D-Penicillamine: the state of the art in humans and in dogs from a pharmacological and regulatory perspective, Antibiotics, 2021, 10(6), 648. https://doi.org/10.3390/antibiotics10060648

Google Scholar

CrossrefPubMed

WorldCat

 

Jin-Hong Min, Heela Sarlus, Robert A Harris, Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro, Metallomics, Volume 16, Issue 5, May 2024, mfae019, https://doi.org/10.1093/mtomcs/mfae019

 

 Mazurowska L., Mojski M. Biological activities of selected peptides: skin penetration ability of copper complexes with peptides. Journal of Cosmetic Science. 2008;59(1):59–69. [PubMed] [Google Scholar][Ref list]

 

Li, H., Low, Y. S. J., Chong, H. P., Zin, M. T., Lee, C.-Y., Li, B., Leolukman, M., & Kang, L. (2015). Microneedle-mediated delivery of copper peptide through skin. Pharmaceutical Research, 32, 2678–2689. https://doi.org/10.1007/s11095-015-1652-z

 

 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 Jul 7;19(7):1987. doi: 10.3390/ijms19071987. PMID: 29986520; PMCID: PMC6073405.

 

 Park JR, Lee H, Kim SI, Yang SR. The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget. 2016 Sep 6;7(36):58405-58417. doi: 10.18632/oncotarget.11168. PMID: 27517151; PMCID: PMC5295439.

 

Ma W et al., “Protective effects of GHK-Cu in bleomycin-induced pulmonary fibrosis via …” (2020) – suppressed TGFβ1/Smad2/3 in mice. 

 

Badenhorst T et al., “Effects of GHK-Cu on MMP and TIMP Expression…” (2016) – in fibroblasts, increased TIMP1 expression