Comparison
GHK-Cu vs Spermidine
Side-by-side of GHK-Cu and Spermidine. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
GHK-Cu
GHK-Cu peptide (glycyl-L-histidyl-L-lysine copper) is a topical copper peptide. Trials show fine-line and wound-healing gains; injectable longevity claims rem.
Spermidine
Spermidine supplement benefits cover autophagy induction, longevity signals, and cognition. Wheat germ extract data, doses, and human trials reviewed.
Effects at a glance
GHK-Cu
- •Endogenous tripeptide that binds copper(II); plasma levels decline ~60% from age 20 to 60
- •Topical RCTs show improvement in skin firmness, fine lines, and barrier function over 12 weeks
- •Wound-healing models report accelerated re-epithelialization in diabetic and aged skin
- •Pickart gene-expression analyses show reset of >4000 genes toward a younger expression profile in cell culture
- •Anecdotal subcutaneous longevity protocols use 1 to 3 mg daily; no human longevity RCTs exist
- •Hair-growth claims rest on small open-label trials and topical scalp formulations
Spermidine
- •Endogenous polyamine that induces autophagy via EP300 acetyltransferase inhibition and TFEB activation
- •Concentrated in wheat germ, soybeans, aged cheese, and mushrooms; ~10 to 15 mg/day in Mediterranean diets
- •Eisenberg 2016 reported dietary spermidine extended mouse lifespan and improved cardiac function
- •Wirth 2018 pilot (n=28) reported cognitive signal at 0.9 mg/day in older adults at risk for dementia
- •Larger Wirth 2019 follow-up (n=85) did not replicate the memory benefit at 12 months
- •Generally regarded as safe at supplemental doses; food-source position is reassuring
Side-by-side
| Attribute | GHK-Cu | Spermidine |
|---|---|---|
| Category | peptide | supplement |
| Also known as | Copper Peptide, Glycyl-L-histidyl-L-lysine copper, GHK | spermidine trihydrochloride, wheat-germ-extract spermidine |
| Half-life (hr) ↗ | 0.5 | 6 |
| Typical dose (mg) ↗ | 2 | 1.2 |
| Dosing frequency | daily | daily, typically morning with food |
| Routes | topical, subcutaneous | oral |
| Onset (hr) | 24 | 2 |
| Peak (hr) | 168 | 4 |
| Molecular weight | 340.85 | 145.25 |
| Molecular formula | C14H24N6O4 (GHK alone); C14H22CuN6O4 with Cu(II) | C7H19N3 |
| Mechanism | Tripeptide that chelates Cu(II) and delivers it to copper-dependent enzymes (lysyl oxidase, superoxide dismutase). Modulates expression of >4000 genes toward a younger profile in fibroblast culture, including upregulation of decorin and downregulation of pro-inflammatory cytokines. | Induces macroautophagy via inhibition of EP300 histone acetyltransferase and activation of TFEB-mediated lysosomal biogenesis. Substrate for hypusination of eIF5A, required for translation of mitochondrial respiration proteins. |
| Legal status | Topical cosmetics legal in most jurisdictions; injectable form not FDA approved for any indication; research-use-only grey market | OTC dietary supplement (wheat-germ extract has GRAS status in US) |
| WADA status | allowed | allowed |
| DEA / Rx | Topical OTC (cosmetic); injectable not FDA approved; research-chemical status | OTC supplement (not scheduled) |
| Pregnancy | Insufficient data; topical use likely low-risk; injectable not recommended | Insufficient data; not routinely recommended at supplemental doses |
| CAS | 49557-75-7 | 124-20-9 |
| PubChem CID | 73587 | 1102 |
| Wikidata | Q3104638 | Q411089 |
Safety profile
GHK-Cu
Common side effects
- mild erythema at topical site
- transient itch
- blue-green discoloration of injection site (copper)
- rare contact dermatitis
Contraindications
- copper allergy
- Wilson disease
- open wound near injection site (caution)
- pregnancy (no data)
Interactions
- topical retinoids: additive irritation; alternate days or apply at different times(minor)
- topical vitamin C (ascorbic acid): ascorbate reduces Cu(II) to Cu(I), which can destabilize the GHK-Cu complex; separate by 30 minutes(minor)
Spermidine
Common side effects
- mild GI upset (rare)
- headache (rare)
Contraindications
- wheat-germ allergy or celiac disease (for wheat-germ-extract products)
- active cancer (theoretical)
- pregnancy and lactation (insufficient data)
Interactions
- DFMO (difluoromethylornithine): competing polyamine metabolism; do not combine without oncology guidance(moderate)
Which Should You Take?
Spermidine comes out ahead for most readers on the criteria we weight: 2 catalogued goals, OTC dietary supplement, oral dosing, with a Tier-A outcome catalogued. GHK-Cu is the right call when one of the conditionals below applies.
- → If your priority is skin health, pick GHK-Cu.
- → If your priority is wound healing, pick GHK-Cu.
- → If your priority is focus or working memory, pick Spermidine.
Edge case: If you want to avoid research-only / gray-market sourcing, Spermidine is the more accessible choice.
Default choice: Spermidine. Lower friction to source, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for GHK-Cu only if your priority sits squarely in the goals it owns above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between GHK-Cu and Spermidine?
GHK-Cu and Spermidine differ in category (peptide vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, GHK-Cu or Spermidine?
GHK-Cu half-life is 0.5 hours; Spermidine half-life is 6 hours.
Can you stack GHK-Cu with Spermidine?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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