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Skin & hair · Cream

GHK-Cu Fragment

Gray market

Checked · 21 sources · 12 corrections on this page · No vendors · No affiliates · No one buys a word of it

0 human trials published

Preclinical · skin cells in culture

Gray market · No FDA ruling — not on any list

Sold as a research chemical. Some clinics and pharmacies still supply it; that’s their risk, not a change in the rule.

Bottom line

A cosmetic ingredient and a lab chemical with no human data; whether injected copper-free GHK stays copper-free in the body has not been measured.

Also called
  • Copper-Free GHK
  • GHK Basic
  • Glycyl-L-Histidyl-L-Lysine (Gly-His-Lys)
  • Apo-GHK
  • CAS 49557-75-7
Category
Tripeptide — Copper-Free GHK (Matrikine / Research Peptide)
Sequence
Gly-His-Lys (3 aa)
Molecular Weight
340.38 g/mol (apopeptide) vs 403.93 (GHK-Cu)
Copper Coordination
None (parent carries Cu²⁺)
Half-life
Short — minutes (extrapolated)
Route (studied)
Not stated in its studies
Route (sold)
Topical serums and creams (cosmetic); SubQ vials (research)
FDA Status
Cosmetic topical; research-only parenteral
Human Trials
None for parenteral copper-free form
WADA Status
Not specifically named — prohibited at all times under S0 (no government has approved it for human use)
Cost & Access
Research-only

Also for skin & hair

The other four questions

What does it do? In lab tests without copper, it lowered reactive oxygen species in gut cells and quenched hydroxyl and peroxyl radicals (Sakuma et al., 2018), bound the lipid-peroxidation product 4-HNE (Beretta et al., 2007), and in skin-cell models acted much as GHK-Cu did (Choi et al., 2012).
Who uses it? Skin-care makers, who use GHK with or without copper (Choi et al., 2012), and research-chemical sellers, who sell the powder for lab use.
Does the evidence hold up? Thin: a handful of lab studies (Choi et al., 2012; Sakuma et al., 2018; Beretta et al., 2007), and no human trial of copper-free GHK, published or registered (ClinicalTrials.gov).
Bottom line? A cosmetic ingredient and a lab chemical with no human data; whether injected copper-free GHK stays copper-free in the body has not been measured.

Dosing from the Literature

Published for skin: no human study; the concentrations cosmetics makers reported using in leave-on skin products, 0.00002–0.001% (Johnson et al., 2018); community doses borrowed from GHK-Cu. Not published: any human dose of copper-free GHK.

No human dose-finding study has been performed for copper-free GHK, and no approved dose exists. The first row gives the concentrations cosmetics makers reported for it, as tripeptide-1, its name on ingredient labels; the others give what community use describes, borrowed from GHK-Cu.

RouteDose RangeFrequencyNotes
Topical, in leave-on cosmetic products0.00002–0.001% of the product (0.2–10 ppm)Not given in the surveyConcentrations cosmetics makers reported for leave-on products in the Personal Care Products Council’s 2013–2014 survey (one rinse-off product: 0.00003%); FDA’s voluntary registrations counted 35 leave-on and 1 rinse-off product uses in 2014. Both as the Cosmetic Ingredient Review reported them (Johnson et al., 2018). No study has tested copper-free GHK on human skin.
Subcutaneous (community)1–3 mgOnce dailyWhat community use describes, borrowed from GHK-Cu; some report 200–500 mcg, others 5 mg. Not studied in people.
Oral / sublingual (community)1–3 mgOnce dailyWhat community use describes. Not studied in people.
Dosing Disclaimer

Copper-free GHK has never been dose-tested in people; the community figures are borrowed from GHK-Cu, and whether the two forms differ in dose, half-life or route has not been studied. Consult a licensed healthcare provider.

→ Calculator — vial-to-syringe math

What It Is

"GHK-Cu Fragment" is vendor shorthand for the copper-free form of glycyl-L-histidyl-L-lysine (GHK) — the tripeptide (a chain of 3 amino acids) Gly-His-Lys without its copper(II) ion coordination partner. The "fragment" nomenclature is slightly misleading because the peptide sequence itself is the same three amino acids (Gly-His-Lys) as the parent GHK-Cu. What is actually missing is the copper ion that the parent peptide chelates very tightly: at pH 7.4 its conditional dissociation constant is 7.0 × 10−14 M (Trapaidze et al. 2012, J Biol Inorg Chem). Different vendors variously market the same product as "GHK Basic," "free GHK," "copper-free GHK," or "apo-GHK."

The GHK sequence was originally isolated from human plasma albumin in 1973 by Loren Pickart, then at the University of California, San Francisco, who identified it as a small tripeptide that promoted the growth of cultured hepatoma cells and prolonged the survival of normal hepatocytes (Pickart and Thaler, Nat New Biol 1973;243:85-87). Subsequent work showed that under physiological conditions the tripeptide rapidly binds Cu²⁺ to form the GHK-Cu complex, and the copper-bound form has since dominated research and commercial development. The 1988 Maquart et al. FEBS Letters paper that first demonstrated collagen-stimulating activity in fibroblast (a cell that builds collagen) cultures explicitly used the copper complex, and the bulk of subsequent research has continued to use that form.

The case for studying GHK without copper grew in 2012, when Choi et al. (J Pept Sci 2012) reported in cultured keratinocytes and skin-equivalent models that the copper-free tripeptide raised markers of basal stem cells, with more integrin expressed by the keratinocytes, much as copper-GHK did. A subsequent body of work has shown that GHK alone has radical-scavenger antioxidant activity (Sakuma et al. 2018), sequesters lipid-peroxidation byproducts such as 4-HNE and acrolein through direct histidine-residue chemistry (Beretta et al. 2007, 2008), and modulates a meaningful number of human genes via mechanisms that do not strictly require its bound copper. The implication: GHK and GHK-Cu share overlapping but non-identical biological profiles, and the copper-free form may have application contexts where copper supplementation is unwanted or where the application vehicle makes a non-chelating form preferable.

Research-chemical sellers sell “GHK-Cu Fragment” beside GHK-Cu. The two are not interchangeable: the copper-free form has less published evidence, and how much of an injected dose binds the body’s own copper has not been measured.

Mechanism of Action

Two kinds of finding concern GHK without copper: its chemistry as a copper binder and scavenger, and its effects on skin cells in culture.

  • Copper sequestration vs copper delivery — Pickart’s early work proposed that GHK works by helping cells take up copper (Pickart et al., 1980). Copper-free GHK binds copper(II) very tightly (Trapaidze et al., 2012); what it does to the body’s copper after injection has not been studied.
  • Direct antioxidant / radical-scavenger activity (copper-independent) — Sakuma et al. (2018, PMC6055086) demonstrated that free GHK quenches hydroxyl (·OH) and peroxyl (ROO·) radicals at low micromolar concentrations in living cells. The chemistry does not require bound copper and is sequence-specific to GHK rather than to its copper complex.
  • 4-HNE and acrolein sequestration (copper-independent) — In solution, GHK formed adducts with 4-hydroxy-2-nonenal (4-HNE), a toxic product of lipid peroxidation, though it was a weaker quencher than the dipeptide carnosine (Beretta et al., 2007); a second study reported it binds acrolein (Beretta et al., 2008).
  • Skin stem-cell and basal-cell preservation (Choi 2012) — In cultured human keratinocytes and skin-equivalent models, copper-free GHK raised the number of p63-positive basal cells, raised keratinocyte proliferation and integrin expression along the basement membrane, and worked much as copper-GHK did.
  • Gene-expression modulation (partially shared with GHK-Cu) — Pickart and Margolina (2014, 2015, 2018) report that GHK modulates expression of large gene sets in cultured cells — up to >4,000 genes in Connectivity Map-style analyses — with broad upregulation of DNA-repair, antioxidant, regeneration, and matrix genes. A fraction of these changes are copper-dependent; others are not. Independent replication outside Pickart's group is thin.
  • Anxiolytic / CNS activity in rodents (Bobyntsev group) — A review by GHK’s discoverer lists anti-anxiety, anti-pain and anti-aggression activities among GHK’s reported actions (Pickart et al., 2018); the Russian rodent papers behind them are not in this page’s references.
  • In-vivo copper coordination — GHK binds copper(II) at a conditional dissociation constant of 7.0 × 10−14 M at pH 7.4 (Trapaidze et al., 2012), and when it was first isolated from plasma it came with about an equimolar amount of copper (Pickart et al., 1980); how much of an injected copper-free dose ends up bound has not been measured.

What the Research Shows

Research specific to the copper-free form — as distinct from GHK-Cu — is thinner but not empty. Key findings:

  • Skin stem-cell preservation (Choi 2012) — In cultured normal human keratinocytes and skin-equivalent models, copper-free GHK raised the number of p63-positive basal cells and their integrin expression, and the authors conclude it showed similar effects to copper-GHK. Foundational paper for the "GHK without copper still does meaningful things" hypothesis (J Pept Sci 2012;18(11):685-690).
  • Antioxidant activity in living cells (Sakuma 2018) — Demonstrates copper-independent hydroxyl- and peroxyl-radical quenching by free GHK in living systems. Provides clear mechanistic basis for one therapeutic action that does not depend on copper.
  • 4-HNE / acrolein sequestration (Beretta 2007, 2008) — Direct histidine-residue conjugation with reactive aldehydes, removing toxic lipid-peroxidation byproducts. Copper-independent.
  • Gene-expression modulation (Pickart and Margolina, 2014, 2015, 2018) — Microarray analyses of GHK-treated cells (with and without copper) report modulation of thousands of genes toward a "younger" expression profile. Anti-aging gene signatures include DNA repair, antioxidant, and regeneration pathway upregulation and inflammatory / tumor-promoting pathway downregulation.
  • Anti-cancer gene-expression signal (Pickart 2014, J Anal Oncol) — Reported GHK-induced expression of pro-apoptotic caspase, growth-regulatory, and DNA-repair genes. Whether the copper-free form replicates every gene-level effect of GHK-Cu has not been dissected.
  • Anxiolytic activity in rodents (Bobyntsev group) — Multiple papers from the Bobyntsev group show parenteral free GHK produces anxiolytic activity and influences neurotransmitter systems. Sequence-specific (D-amino-acid substitutions attenuate activity). Western replication is thin; protocols are heterogeneous.
  • Hair-follicle stimulation (mostly GHK-Cu) — Reported in cultured follicle models for both GHK and GHK-Cu. Whether copper-free GHK retains the full hair-growth signal in human use has not been tested in a controlled trial.
  • Cosmetic ingredient evidence (dominated by GHK-Cu) — Placebo-controlled topical cosmetic facial studies (Abdulghani 1998; Leyden 2002) use the copper-bound form. They do not transfer directly to copper-free GHK product claims.
  • What is absent — No published human clinical trial of injected or systemically dosed copper-free GHK. No head-to-head efficacy comparison vs GHK-Cu in matched human applications. No formal human pharmacokinetic data for either form.
Research Limitation — Most Evidence Is on the Copper Form

The vast majority of GHK-family research uses the copper-bound form. Research-channel marketing of "GHK-Cu Fragment" often cites GHK-Cu evidence as if it applied to the copper-free form. It does not, except in the specific cases where a study demonstrated copper-independent activity (Choi 2012, the antioxidant literature, and the aldehyde-sequestration chemistry).

Human Data

There is no published clinical trial of injected or systemically dosed copper-free GHK in humans. The published human evidence base for the GHK family sits on topical GHK-Cu cosmetic studies, none of which directly apply to parenteral copper-free GHK use.

  • Topical GHK-Cu cosmetic studies — Multiple placebo-controlled 12-week facial cosmetic studies have reported anti-aging benefits of topical GHK-Cu cream / serum. All used the copper-bound form.
  • No registered trial of copper-free GHK — A search of ClinicalTrials.gov for "copper-free GHK," "free GHK," or "apo-GHK" returns no registered trials as of April 2026.
  • No published human PK data — Neither GHK nor GHK-Cu has been formally characterized for human pharmacokinetics after parenteral administration in peer-reviewed literature.
  • Anecdotal SubQ and oral community use — Forum and practitioner reports describe SubQ injection of GHK (typically near hairline for hair growth, abdominal SubQ for systemic effect) and occasional oral / sublingual use. These are uncontrolled, selection-biased, and frequently confounded by concurrent skincare or other peptides.
  • Practical implication — Anyone using copper-free GHK by injection or systemic route is operating outside the published human evidence base entirely.

Reconstitution & Storage

Copper-free GHK has no approved label, so no official storage or handling instructions exist. Research-chemical sellers list it as freeze-dried powder in 50 mg or 100 mg vials. The 1 mg and 2 mg columns are arithmetic for the community figures in Dosing.

Vial SizeBAC WaterConcentration1 mg Dose2 mg Dose
50 mg2 mL25 mg/mL4 units (0.04 mL)8 units (0.08 mL)
100 mg2 mL50 mg/mL2 units (0.02 mL)4 units (0.04 mL)

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Side Effects & Risks

Important

Copper-free GHK has no published human safety data for injection. Consult a licensed healthcare provider.

The points below are what is known for GHK and its copper complex, and what has not been studied for the copper-free form.

  • Topical use — Reviews describe GHK and its copper complex as well tolerated on skin (Gruchlik et al., 2012), with a long history of use in wound healing and anti-aging products (Pickart et al., 2012).
  • Copper binding (theoretical) — GHK binds copper very tightly (Trapaidze et al., 2012); whether injected copper-free GHK lowers the body’s available copper has not been studied.
  • Growth signals (theoretical) — GHK is reported to stimulate blood-vessel and nerve outgrowth (Pickart et al., 2018), which raises a theoretical question about existing tumors; the same group reports anti-cancer gene-expression effects (Pickart et al., 2014). Neither has been tested in people.
  • WADA status — Not named on the Prohibited List, but prohibited at all times under S0, non-approved substances, because no government has approved it for human therapeutic use (WADA Prohibited List 2026).
  • Sourcing — Sold as a research chemical for injection, unregulated for quality.
  • Long-term safety unknown — No human safety data have been published for injected GHK in either form.

Bloodwork & Monitoring

No trial, label or guideline sets monitoring for copper-free GHK, and no human study of it has been published.

Commonly Stacked With

GHK-Cu (parent peptide)

The copper-bound parent, with far more published research.

Tested together in people: none published · Read the receipt →

BPC-157

Tested together in people: none published · Read the receipt →

Stacking this? Read the receipt →

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Legal Status

Current Status — April 2026

Copper-free GHK (Gly-His-Lys tripeptide) is not FDA-approved for any therapeutic indication. As a peptide, it is research-only for parenteral or systemic use. Topical GHK-Cu (the copper-bound form; INCI: "Copper tripeptide-1") is widely used as a cosmetic ingredient. Copper-free GHK is also used in cosmetic formulations, listed as "Tripeptide-1" on INCI labels: in 2014 FDA’s voluntary cosmetic registration program held 36 product uses of tripeptide-1 and 18 of copper tripeptide-1 (Johnson et al., 2018).

Parent GHK-Cu has appeared on FDA's compounding bulk-substance evaluation lists, with status that has shifted across category designations over recent years. In late February 2026 the HHS secretary said on a podcast that he expected FDA to change the status of “about 14” peptides within “a couple of weeks” (NPR, March 31, 2026); those were public remarks, reported, not a rule. FDA’s documented step came on April 15, 2026: notice that 12 peptides would leave Category 2 because their nominations had been withdrawn, removed on April 22, which left them in no category rather than Category 1 (FDA 503A categories list, April 22, 2026). Injectable GHK-Cu was among the 12; non-injectable GHK-Cu, taken off Category 1 at the same time, went back on it on May 14, 2026 (FDA 503A categories list, May 14, 2026).

The copper-free GHK form has not been specifically named on FDA’s lists: the April 2026 removal from Category 2 and the May 14, 2026 return to Category 1 both name GHK-Cu, the copper-bound form (FDA 503A categories list, April 22 and May 14, 2026). Practically, copper-free GHK is currently outside both the approved-cosmetic-ingredient pathway (for parenteral use) and the compounding-pharmacy pathway.

WADA: copper-free GHK is not named on the Prohibited List, but it is prohibited at all times under S0, non-approved substances, because no government has approved it for human therapeutic use (WADA Prohibited List 2026).

Cost & Access

Copper-free GHK is not approved for human use as a parenteral peptide therapeutic. It is available through two legitimate channels: (1) as an ingredient in topical cosmetic products sold over the counter; and (2) through research-chemical suppliers for laboratory research purposes only, supplied as lyophilized powder in 50 mg or 100 mg vials.

U.S. compounding pharmacies cannot legally compound copper-free GHK for parenteral use under current FDA bulk-substance rules. The apopeptide has not been specifically named on any compounding-pathway list — regulatory attention has focused on the copper-bound form. Non-injectable GHK-Cu is on FDA's 503A Category 1 list (updated May 14, 2026); copper-free GHK is not on any FDA 503A bulk-substance list.

Topical cosmetic products containing copper-free GHK are widely available in consumer skincare. The research-chemical channel is the standard route for parenteral research use. Kalios does not sell compounds.

Access and regulatory status as of April 2026. Actual availability varies by jurisdiction, channel, and prescription status. Kalios does not sell compounds.

References

  1. 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):85-87. PMID: 4349963. (Original peer-reviewed report — isolation of GHK from human plasma.)
  2. 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;238(2):343-346. PMID: 3169264. (Foundational copper-bound collagen-stimulation paper.)
  3. Choi HR, Kang YA, Ryoo SJ, Shin JW, Na JI, Huh CH, Park KC. Stem cell recovering effect of copper-free GHK in skin. J Pept Sci. 2012;18(11):685-690. doi:10.1002/psc.2455. (Key paper for the copper-free form: stem-cell preservation in human skin-equivalent models without copper coordination.)
  4. Pickart L, Vasquez-Soltero JM, Margolina A. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging. Oxid Med Cell Longev. 2012;2012:324832. PMID: 22666519.
  5. 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.
  6. 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. (Comprehensive review noting copper-free findings.)
  7. Pickart L, Vasquez-Soltero JM, Pickart FD, Majnarich J. GHK, the Human Skin Remodeling Peptide, Induces Anti-Cancer Expression of Numerous Caspase, Growth Regulatory, and DNA Repair Genes. J Anal Oncol. 2014;3(2):79-87.
  8. Beretta G, Aldini G, Facino RM, Russell RM, Krinsky NI, Yeum KJ. Glycyl-histidyl-lysine (GHK) is a quencher of α,β-4-Hydroxy-trans-2-nonenal: a comparison with carnosine. Chem Res Toxicol. 2007;20(9):1309-1314. doi:10.1021/tx700185s. (Copper-independent aldehyde sequestration.)
  9. Beretta G, Arlandini E, Artali R, Anton JM, Maffei Facino R. Acrolein sequestering ability of the endogenous tripeptide glycyl-histidyl-lysine (GHK). J Pharm Biomed Anal. 2008;47(3):596-602.
  10. Trapaidze A, Hureau C, Bal W, Winterhalter M, Faller P. Thermodynamic study of Cu²⁺ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine. J Biol Inorg Chem. 2012;17(1):37-47. PMID: 21898044. (Quantifies very high copper-binding affinity driving in-vivo coordination after administration.)
  11. 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;288(5792):715-717. PMID: 7453802.
  12. Pickart L, Vasquez-Soltero JM, Margolina A. The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline. Brain Sci. 2017;7(2):20. PMID: 28212278.
  13. Pollard JD, Quan S, Kang T, Koch RJ. Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts. Arch Facial Plast Surg. 2005;7(1):27-31. PMID: 15655171.
  14. Kang YA, Choi HR, Na JI, Huh CH, Kim MJ, Youn SW, Kim KH, Park KC. Copper-GHK increases integrin expression and p63 positivity by keratinocytes. Arch Dermatol Res. 2009;301(4):301-306. PMID: 19319546.
  15. Hostynek JJ, Dreher F, Maibach HI. Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Inflamm Res. 2011;60(1):79-86. PMID: 20721598.
  16. Gruchlik A, Jurzak M, Chodurek E, Dzierzewicz Z. Effect of Gly-Gly-His, Gly-His-Lys and their copper complexes on TNF-alpha-dependent IL-6 secretion in normal human dermal fibroblasts. Acta Pol Pharm. 2012;69(6):1303-1306. PMID: 23285694.
  17. FDA. Bulk Drug Substances Nominated for Use in Compounding — 503A and 503B Categories. FDA.gov. Updated 2025-2026.
  18. WADA Prohibited List 2026. World Anti-Doping Agency. wada-ama.org.
  19. Stone W. The wellness world is eager for RFK Jr.’s promised move on peptides. NPR, March 31, 2026. npr.org/2026/03/31/nx-s1-5768206/peptides-rfk-fda-compounding-pharmacies. Read October 3, 2026. (The HHS secretary’s late-February podcast remarks, “about 14” peptides; reported, not a rule.)
  20. Johnson W Jr, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks JG Jr, Shank RC, Slaga TJ, Snyder PW, Gill LJ, Heldreth B. Safety Assessment of Tripeptide-1, Hexapeptide-12, Their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics. International Journal of Toxicology. 2018;37(3 suppl):90S-102S. doi:10.1177/1091581818807863. (Cosmetic Ingredient Review final report, released June 30, 2014: cir-safety.org/sites/default/files/tripep062014final.pdf, read October 12, 2026. Its Table 2: the 2014 voluntary-registration use counts and the 2013–2014 industry survey of use concentrations for tripeptide-1 and copper tripeptide-1.)
  21. Sakuma S, Ishimura M, Yuba Y, Itoh Y, Fujimoto Y. The peptide glycyl-L-histidyl-L-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals. Int J Physiol Pathophysiol Pharmacol. 2018;10(3):132-138. PMID: 30042814.

Also for skin & hair

Tested together in people

None published · Read the receipt →

See every change to this page → · Status now →

Checked 18 Oct 2026