Subject: GHK-Cu: What Happens at the Cellular Level When a Protocol Ends?
From: Derek from Research Radar <[email-masked]>
To: [email-masked]
Date: Fri, 10 Apr 2026 18:26:57 +0000
List-Id: <derekpruski.substack.com>

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What is GHK-Cu?
GHK-Cu (glycyl-L-histidyl-L-lysine-copper) is a naturally occurring copper peptide first isolated from plasma in 1973. It is found naturally in the body and has been studied extensively in research settings.
Rather than acting as a filler or surface compound, GHK-Cu functions as a biological signaling molecule. Research has documented it activating the cellular machinery responsible for building and remodeling connective tissue, including stimulating collagen and elastin synthesis, reducing inflammation markers, and influencing gene expression across thousands of pathways associated with tissue aging.
Topical vs Sub-Q: Why administration format matters
Topical application delivers GHK-Cu to the upper dermal layers with localized fibroblast activation and collagen upregulation in the application area. Penetration is naturally limited by the skin barrier.
Sub-Q administration bypasses the skin barrier entirely, entering systemic circulation more readily. Research documents faster onset of measurable biological activity and broader distribution of effect with sub-Q models, consistent with higher bioavailability through this route.
Simply put: sub-Q reaches more tissue, faster, and builds a larger foundation of structural remodeling going into the post-protocol window.
Observed onset timelines during active research protocols
Topical models:
Weeks 2 to 4: Measurable increases in fibroblast activity and early collagen synthesis markers
Weeks 4 to 8: Documented upregulation of collagen I and III gene expression, elastin synthesis begins
Months 3 to 6: Cumulative collagen deposition and structural remodeling most apparent in tissue analysis
Sub-Q models:
Weeks 1 to 2: Earlier measurable increases in collagen synthesis markers due to higher bioavailability
Weeks 3 to 6: More pronounced fibroblast activation and extracellular matrix remodeling compared to topical
Months 2 to 4: Deeper structural remodeling documented at the tissue level
What happens week by week after discontinuation?
This is the part most researchers want to understand clearly.
The important foundation to know first: collagen, once synthesized, has a biological half-life measured in months to years. Type I collagen specifically has a documented half-life of over a year under stable tissue conditions. So the collagen produced during an active protocol does not rapidly break down the moment administration stops.
What does change immediately is the upstream signaling. Without continued GHK-Cu, the gene expression activity driving collagen synthesis begins returning toward baseline. Here is how that plays out week by week:
Weeks 1 to 2 post-discontinuation The cellular signaling driven by GHK-Cu begins declining, but collagen and structural proteins already deposited remain largely intact. Research markers for active synthesis start pulling back but have not yet shown meaningful regression. This window looks very similar to the tail end of an active protocol.
Weeks 2 to 4 post-discontinuation Fibroblast activation begins normalizing toward baseline. Active collagen synthesis rates measurably decline during this window. However, the structural proteins already built continue to exist given their biological half-life. The gap between peak synthesis activity and current activity widens, but deposited collagen is not yet meaningfully degrading.
Weeks 4 to 8 post-discontinuation This is the window where research documents the most meaningful regression in active remodeling markers. The upstream signaling has largely normalized toward pre-protocol baseline by this point. Existing collagen continues its natural biological turnover, but the replacement rate has dropped significantly without the GHK-Cu stimulus driving synthesis. This is when the difference between peak protocol activity and post-discontinuation state becomes most measurable.
Beyond 8 weeks post-discontinuation Without reintroduction of the signaling stimulus, collagen synthesis rates settle at age-appropriate baseline levels. Previously deposited collagen continues normal biological turnover without being replaced at the elevated rate seen during the active protocol. Over months to a year or more, the cumulative structural remodeling achieved during the protocol gradually diminishes as natural degradation outpaces baseline synthesis.
Sub-Q protocols show a similar post-discontinuation pattern, though the larger baseline of structural remodeling achieved during the active phase means the absolute level of collagen present remains higher for longer compared to topical models.
Does everything return to pre-protocol baseline?
Not immediately, and research suggests not fully in the short term. GHK-Cu’s influence on gene expression includes epigenetic markers that may persist beyond active administration. Whether these changes are durable long term remains an active area of research interest.
What the literature consistently supports is that maintenance dosing sustains elevated collagen synthesis activity more effectively than repeated cold-start protocols, given the cumulative nature of structural remodeling.
Bottom line
GHK-Cu drives collagen synthesis through well-documented signaling mechanisms. The structural proteins built during a protocol have biological staying power well beyond discontinuation due to collagen’s natural half-life. However, the cellular signal driving continued production begins fading within the first few weeks of stopping, with the most meaningful regression in active synthesis markers occurring in the 4 to 8 week post-discontinuation window. Peak activity will not be maintained without continued administration, and maintenance dosing is better supported in the literature than cycling repeatedly from baseline.

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