Description
Complete Research Guide to GHK-Cu (Copper) Peptide
GHK-Cu, found naturally in the blood plasma, has many health effects – all of which are known to be positive as per clinical studies – and will be discussed further in this article.
Peptides have proven to exhibit several health benefits to people over the last few years. While various synthetic peptides have been developed via artificial synthesis and advanced science technologies, there is one such naturally occurring peptide that has multiple biological actions in the human body.
What is GHK-Cu Copper?
GHK-Cu is a naturally occurring copper binding peptide composed of 3 amino acids, i.e. glycyl-L-histidyl-L-lysine (1). The Cu in the name refers to the chemical symbol of copper.
GHK-Cu (Copper) is a small, tripeptide found in the human plasma and also released at the time of injury. GHK-Cu is known for having wound healing and regenerative properties and since its discovery, the peptide is found to be extremely beneficial to human health (1).
However, with increasing age, the concentration of GHK-Cu declines in the body, which leads to reduced effects. At 20 years of age, the average concentration of GHK-Cu is around 200 ng/mL which declines to 80 ng/mL by the age of 60 years (1). This is why artificial synthesis of GHK-Cu was begun, to help maintain the optimal levels in the body as needed; and is now largely available in the market and also used in cosmetics.
Peptide History
GHK-Cu was first discovered in 1973 by scientist Loren Pickart (1), (2).
During the study (3) of liver cells of elderly patients aged between 60 and 80 years, it was noticed that they had high levels of fibrinogen. When these liver tissues were isolated and incubated in the blood from younger subjects, it was discovered that these tissues restored their functionality and levels were reduced, almost up to the same extent as in liver tissue of younger people. It was then that it was discovered that this was due to a growth modulating peptide, specifically glycyl-L-histidyl-L-lysine peptide, commonly called the GHK peptide.
Several studies were then carried out to understand the full potency and peptide mechanism, which are discussed further in this article.
How Does Copper Peptide Work?
Studies(4) have shown when the plasma GHK peptide is added to the cell culture in nanomolar amounts, the peptide produces a wide range of responses from growth stimulation to toxic cell differentiation.
During the isolation of the peptide, it was found that it contained chelating properties and would co-isolate with almost the same amount of copper ions and 1/5th amount of iron found in the cells. When the peptide was incubated in the isolated cells as a bound complex with copper and iron molecules, maximal effects were seen. This study demonstrated that GHK peptide had a high affinity towards the copper ions and can hence readily form a complex with copper II ions.
Since 2010, a new mechanism by which the peptide governs has been brought to light.
Studies(5) have shown that the peptide affects the gene expression and has the ability to reset the human genome to a healthy status. By this mechanism, GHK-Cu peptide is able to restore the diseased cells, including carcinogenic cells and COPD cells, to healthy status.
Benefits of Copper Peptide
GHK-Cu peptide has several health benefits as outlined below (1):
- Anti-aging effects: Can tighten and reverse the thinning of the aged, wrinkled skin
- Skin regeneration properties: Can restore the skin protein barrier
- Improve skin structure by reducing fine lines and increasing skin firmness and elasticity
- Smoothes skin texture by decreasing hyperpigmentation and lesions
- Induce wound healing and tissue repair
- Decrease inflammation
- Stimulate hair growth and increased hair thickness, by increasing hair follicle size
- Possess antioxidant properties
- Possess gene restructuring properties: May demonstrate anticancer actions
Research and Clinical Studies
Initial studies to better understand the role of natural GHK peptide
This 1980s study (6) demonstrated the biological role of the naturally occurring peptide in the wound healing process.
When the GHK peptide, found in human plasma, is released in the body, it binds with copper (II) ions due to high copper affinity and thereby stimulates the synthesis of collagen and increases the accumulation of total proteins and DNA at the injury site.
Dermal (or skin) wounded rats were used for this study. At the time of injury, the release of GHK peptide was induced. ‘Emergency response molecules’ were released from the matrix at the site of injury. Once released, GHK would bind with Cu ions found in the human blood and then stimulate the synthesis of decorin protein.
Decorin protein is responsible for the synthesis of collagen and regulation of wound healing and anti-tumor defense mechanism.
Further studies in the 2000s (7), demonstrated that the GHK-Cu peptide not only stimulates the collagen synthesis but also stimulates the production of tissue inhibitors, TIMP-1 and TIMP-2. Hence, this suggests that GHK-Cu regulates both skin cell synthesis as well as their breakdown – and thus should be used with caution.
Studies Demonstrating GHK-Cu Wound Healing Properties
Studies in rabbits – compared to zinc oxide
In this study (8), the main aim was to understand the clinical effects of the GHK-Cu peptide complex when topically applied to the open wounds in comparison to zinc oxide.
18 New Zealand white rabbits were used for this study, who were divided into three groups – one group was treated with GHK-Cu, second group with zinc oxide and third group was treated with placebo. One full wound was created on each rabbit and the rabbits were treated with the respective compounds for 21 consecutive days.
After 21 days, it was noted that the group treated with the GHK-Cu peptide complex demonstrated better healing results compared to the group treated with zinc oxide and placebo.
Studies in rabbits – compared to helium neon laser
In this study (9), the main aim was to understand the clinical effects of the GHK-Cu peptide complex when topically applied to the open wounds in comparison to two different doses of helium neon laser.
The two doses of laser application were 1 J cm2 and 3 J cm2.
24 New Zealand white rabbits were used for this study, who were divided into three groups and treated with respective doses of the GHK-Cu peptide complex and two doses of the helium neon laser application. Experimental wounds were created on all the rabbits and all rabbits were treated for 28 consecutive days with the respective compound doses.
After the study, it was noted that rabbits treated with GHK-Cu peptide and higher dose of the laser application were more receptive toward wound healing than the other group. The rabbits treated with GHK-Cu peptide showed a significant decline in the neutrophil counts and increase in neovascularization process – which are key characteristics of the wound healing process.
Early studies demonstrating anticancer peptide properties
In this 1983 study (1), the effects of the mixture of GHK-Cu complex and ascorbic acid (Vitamin C) on the growth of the sarcoma (tumor) cells was studied. 180 mice suffering from cancer were administered with this mixture for the purpose of this study. This study was successful as the mixture induced a significant decline in the growth of carcinogenic cells in the subject mice.
While this outcome was not publicly published until 2014, but once the results were found on a later date, it supported the later discovery of the tissue remodeling effects of GHK-Cu peptide.
It was later discovered that GHK-Cu peptide complex increased the expression of caspase and the associated genes, and also increased gene expression associated with DNA repair. These were relevant to having anticancer effects, which was supported by the 1983 study.
Clinical trials for ulcer treatment in diabetic patients
This study(10) was carried out in the diabetic patients who were suffering from diabetic neuropathic ulcers. All patients were enrolled in a standard wound care protocol, where only the patients with sharp ulcer wound or debridement were entered into this randomized, placebo controlled clinical trial.
The study was carried out using 2% GHK-Cu peptide complex gel, called Lamin Gel. All patients were divided into different groups, where one group was treated with Lamin Gel, whereas others were given standard care and treatment with placebo application.
After the study, it was noted that the patients treated with Lamin Gel showed an elevated healing of at least 98%. Lamin Gel treatment induced closure of 98.5% of plantar ulcers whereas the standard treatment only induced 60.8% of ulcer healing.
Furthermore, it was noted that when the gel treatment was commenced immediately after the debridement, the efficacy was much higher than usual. Only 7% incidents of ulcer infections were reported in patients treated with the Lamin gel, immediately after the debridement.
Clinical trials on COPD patients
The main aim of this study(11) was to understand the effects of GHK-Cu peptide complex in the patients suffering from Chronic obstructive pulmonary disease (COPD) and potential use of GHK-Cu in COPD treatment.
COPD patients were treated with GHK-Cu as per the trial protocol. After administration, 64 lung tissue samples were collected from 8 patients to quantify the emphysema severity through the means of CT scans.
Upon analysis, it was determined that GHK-Cu treated tissue cells demonstrated the activation of the TGF-beta pathway. In COPD patients, the gene expression would govern the emphysematous destruction by decreasing the gene activation in the TGF-beta pathway. Upon treatment with GHK-Cu, it reversed these gene expressions and restore this pathway.
What’s more, lung fibroblasts, which were impaired in the COPD patients, were now restored and able to restructure those collagen tissue cells. This was possible only after the treatment with the GHK-Cu peptide complex.
This study demonstrated that GHK-Cu has the ability to reverse the gene expression which can potentially reverse the COPD progression in patients.
GHK-Cu Pain Relief, Anti-anxiety and Anti-aggression Properties
Several research studies were carried out which demonstrated that GHK-Cu has other benefits such as pain relief, reduced anxiety and anti-aggression properties.
Anti-pain Effects
In this study(1), GHK-Cu was induced in the mice at a dose of 0.5 milligrams/kg body weight. Mice were placed on a moderately hot plate. Due to heat and the pain, it would usually take longer for mice to lick their paws; however, upon administering the peptide, the time taken to lick their paws reduced. This demonstrated the mice got ‘comfortable’ and their pain was eased faster on GHK-Cu administration.
Anti-anxiety Effects
In this study(12), GHK peptide was administered in male rats via intraperitoneal route of administration at the doses of 0.5, 5 and 50 microg/kg body weight 12 minutes before the start of the experiment. The experiment was to place the male rats in a maze, which would induce anxiety in them and change their posture.
If anxious, rats would be in ‘close arms’, which essentially means they are feeling numb and have their arms tight; whereas ‘open arms’ refers to the rats being more free and hovering around quickly, with less anxiety.
As a part of the study, once the peptide was administered, the time spent by the rats in ‘open arms’ state in the maze was monitored.
After the study, it was noted that the maximum anti-anxiety effect was observed at 0.5 micro/kg dose. The anti-anxiety effects decreased with increase in the peptide dose.
Anti-aggression Effects
In this study (13), two rats were placed in a small cage and were then given minor electric shocks. As a result of these shocks, the subject rat would become agitated and attack the second rat.
Twelve minutes before this experiment, a dose of 0.5 microg/kg body weight of GHK-Cu peptide was administered in both the rats. It was noticed that the number of attacks, after the electric shocks, reduced by 5 times than usual.
There is currently no similar study conducted with human volunteers. So, in order to obtain an estimate of the safe and effective dose in humans, this experimental dose of 0.5 microg/kg body weight was scaled up to human weight. Upon scaling up, the optimal dose that may stimulate similar effects in humans was found to be 35 microg/kg body weight – however, further studies are yet to be conducted to confirm whether this theoretical dose calculation is practically efficacious in humans.
Disadvantages or Side Effects of GHK-Cu
GHK-Cu has been used for decades and no serious adverse events have been reported with the use of this peptide (1).
However, as with all medications, there may be some common side effects, commonly seen in overly sensitive people such as skin irritation and redness at the site of injection administration. No serious side effects have been reported with the use of this peptide.
Recommended route of delivery and available formulations
To increase the drug penetration and absorption in the human body, scientists recommend the use of nano-sized particles of the GHK-Cu peptide (1) in the formulations.
Owing to the promising drug safety profile, various benefits and low cost of the peptide, GHK-Cu can be used in several skin care formulations including sunscreens and anti-wrinkle creams and lotions (1).
As the peptide possesses potent wound healing effects, GHK-Cu can be used after surgeries to heal wounds, including use after plastic surgery, laser treatment and chemical peels (1). Additionally, based on the studies (10), it can be used for wound dressing, especially for diabetic wounds.
Lately, due to the recent discovery of tissue remodeling and gene expression altering capabilities of the GHK-Cu peptide, it can also be used as a dietary supplement to support cellular health and vitality of the human body (1).
Summary
GHK is a naturally occurring tripeptide that has the unique ability to bind with the copper ions (mainly copper (II) ions(1)) in the body and form the GHK-Cu peptide complex. Owing to this unique ability, GHK-Cu complex produces several effects to the human body including tissue repair, wound healing, anti-inflammatory, and antioxidant effects.
Recently, new studies have revealed that GHK-Cu also has tissue remodeling and gene modulating effects. While further studies still need to be conducted to understand the mechanism in a more robust fashion, this discovery and supporting studies indicate the potential use of GHK-Cu in the treatment of cancer and COPD patients.
Currently, GHK-Cu is used by various topical skin care treatments including creams, dermal patches and even administered via microneedles (1). People of varied age have been using GHK-Cu in some form or the other for decades now with no reported adverse effects. Presently, it is not formulated as a dietary supplement, however, with recent advances in GHK-Cu studies, there is a high possibility it can be potentially used as supplements to improve overall cellular health of the human body.
While further studies are yet to be conducted, GHK-Cu continues to demonstrate remarkable benefits to human health, making it a promising candidate to potentially treat disorders such as anxiety, cancer and COPD.
References:
1. Pickart, Loren, and Anna Margolina. “Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data.” International journal of molecular sciences vol. 19,7 1987. 7 Jul. 2018, doi:10.3390/ijms19071987. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073405/
2. Pickart L, Freedman JH, Loker WJ, Peisach J, Perkins CM, Stenkamp RE, Weinstein B. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature. 1980 Dec 25;288(5792):715-7. doi: 10.1038/288715a0. PMID: 7453802. https://pubmed.ncbi.nlm.nih.gov/7453802/
3. L.O. Pilgeram, L.R. Pickart, Control of fibrinogen biosynthesis: The role of free fatty acid, Journal of Atherosclerosis Research, Volume 8, Issue 1, 1968, Pages 155-166, ISSN 0368-1319, https://doi.org/10.1016/S0368-1319(68)80089-4
4. Pickart L, Freedman JH, Loker WJ, Peisach J, Perkins CM, Stenkamp RE, Weinstein B. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature. 1980 Dec 25;288(5792):715-7. doi: 10.1038/288715a0. PMID: 7453802. https://pubmed.ncbi.nlm.nih.gov/7453802/
5. Pickart L, Vasquez-Soltero JM, Margolina A. GHK and DNA: resetting the human genome to health. Biomed Res Int. 2014;2014:151479. doi: 10.1155/2014/151479. Epub 2014 Sep 11. PMID: 25302294; PMCID: PMC4180391. https://pubmed.ncbi.nlm.nih.gov/25302294/
6. Maquart FX, Pickart L, Laurent M, Gillery P, Monboisse JC, Borel JP. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Lett. 1988 Oct 10;238(2):343-6. doi: 10.1016/0014-5793(88)80509-x. PMID: 3169264. https://pubmed.ncbi.nlm.nih.gov/3169264/
7. Siméon A, Emonard H, Hornebeck W, Maquart FX. The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures. Life Sci. 2000 Sep 22;67(18):2257-65. doi: 10.1016/s0024-3205(00)00803-1. PMID: 11045606. https://pubmed.ncbi.nlm.nih.gov/11045606/
8. Cangul IT, Gul NY, Topal A, Yilmaz R. Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits. Vet Dermatol. 2006 Dec;17(6):417-23. doi: 10.1111/j.1365-3164.2006.00551.x. PMID: 17083573. https://pubmed.ncbi.nlm.nih.gov/17083573/
9. Gul NY, Topal A, Cangul IT, Yanik K. The effects of topical tripeptide copper complex and helium-neon laser on wound healing in rabbits. Vet Dermatol. 2008 Feb;19(1):7-14. doi: 10.1111/j.1365-3164.2007.00647.x. PMID: 18177285. https://pubmed.ncbi.nlm.nih.gov/18177285/
10. Mulder GD, Patt LM, Sanders L, Rosenstock J, Altman MI, Hanley ME, Duncan GW. Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Wound Repair Regen. 1994 Oct;2(4):259-69. doi: 10.1046/j.1524-475X.1994.20406.x. PMID: 17147644. https://pubmed.ncbi.nlm.nih.gov/17147644/
11. Campbell JD, McDonough JE, Zeskind JE, Hackett TL, Pechkovsky DV, Brandsma CA, Suzuki M, Gosselink JV, Liu G, Alekseyev YO, Xiao J, Zhang X, Hayashi S, Cooper JD, Timens W, Postma DS, Knight DA, Lenburg ME, Hogg JC, Spira A. A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK. Genome Med. 2012 Aug 31;4(8):67. doi: 10.1186/gm367. PMID: 22937864; PMCID: PMC4064320. https://pubmed.ncbi.nlm.nih.gov/22937864/
12. Bobyntsev II, Chernysheva OI, Dolgintsev ME, Smakhtin MY, Belykh AE. Anxiolytic effects of Gly-His-Lys peptide and its analogs. Bull Exp Biol Med. 2015 Apr;158(6):726-8. doi: 10.1007/s10517-015-2847-3. Epub 2015 Apr 23. PMID: 25900608. https://pubmed.ncbi.nlm.nih.gov/25900608/
13. Sever’yanova LА, Dolgintsev ME. Effects of Tripeptide Gly-His-Lys in Pain-Induced Aggressive-Defensive Behavior in Rats. Bull Exp Biol Med. 2017 Dec;164(2):140-143. doi: 10.1007/s10517-017-3943-3. Epub 2017 Nov 27. PMID: 29181666. https://pubmed.ncbi.nlm.nih.gov/29181666/
Synonyms: GHK Copper peptide, Copper peptide, GHK peptide
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