KPV
Also known as: Lysine-Proline-Valine, Alpha-MSH C-terminal Fragment, α-MSH(11-13)
What Is KPV?
KPV is the C-terminal tripeptide of alpha-melanocyte-stimulating hormone (α-MSH), consisting of just three amino acids: Lysine-Proline-Valine. It’s one of the smallest peptides sold in the supplement market, with a molecular weight of only 342.43 Da. The central proline residue creates a conformational constraint that is critical for its biological activity.
KPV has gained significant popularity in the gut health and IBD communities, driven by its potent anti-inflammatory effects in animal models. However, the enthusiasm has far outpaced the evidence: no human being has ever been given KPV in a clinical trial.
How It Works
KPV’s mechanism is genuinely interesting and well-characterized — in laboratory and animal studies. The landmark study by Dalmasso G et al. (Gastroenterology, 2008) made a surprising discovery: KPV’s anti-inflammatory effect is not mediated through melanocortin receptors (the pathway used by full-length α-MSH). Instead, KPV is transported directly into cells via the PepT1 di/tripeptide transporter, where it inhibits IκB-α degradation, blocking NF-κB nuclear translocation — one of the master switches of inflammatory gene expression.
This matters because PepT1 is upregulated in inflamed colonic epithelium in IBD patients, creating a theoretical mechanism by which KPV could selectively target inflamed gut tissue. Getting SJ et al. (J Pharmacol Exp Ther, 2003) independently confirmed that the anti-inflammatory effect persists in mice with nonfunctional MC1-R receptors, validating the non-melanocortin pathway.
Importantly, KPV does not cause skin pigmentation — unlike full-length α-MSH analogues such as melanotan II, which act through melanocortin receptors.
What the Research Shows
Animal Studies: Impressive but Preclinical
Colitis models: Kannengiesser K et al. (Inflamm Bowel Dis, 2008) — KPV rescued 100% of animals from death during DSS-induced colitis in MC1R-deficient mice. This is a striking result in a severe colitis model. Xiao B et al. (Molecular Therapy, 2017) — HA-functionalized KPV nanoparticles were effective at 12,000-fold lower concentration than free KPV, suggesting that targeted delivery could dramatically enhance efficacy.
Corneal healing: Bonfiglio V et al. (Exp Eye Res, 2006) — Topical KPV achieved 100% corneal re-epithelialization (8/8 eyes) vs 0% placebo in rabbit corneal wounds.
Antimicrobial: Cutuli M et al. (J Leukoc Biol, 2000) — KPV inhibited S. aureus growth at physiological (picomolar) concentrations without reducing neutrophil killing capacity — a dual anti-inflammatory/antimicrobial profile.
Human Evidence: Zero
No published human clinical trial of KPV exists. No Phase I, II, or III trials are listed on ClinicalTrials.gov. No formal pharmacokinetic study has been published. No toxicology study in humans has been conducted. The entire evidence base for KPV is preclinical.
PeptideIntel Evidence Assessment: KPV has a well-characterized mechanism and genuinely impressive animal data, particularly for colitis. But the gap between animal colitis models and human IBD treatment is enormous — many compounds that cure colitis in mice have failed spectacularly in human trials. Without any human data, KPV’s therapeutic potential remains entirely theoretical.
Oral Bioavailability: Theoretical Plausibility, No Data
As a tripeptide and PepT1 substrate, KPV’s oral absorption is theoretically possible — PepT1 is expressed on intestinal epithelial cells and actively transports di- and tripeptides. This is a better theoretical argument for oral bioavailability than exists for most peptides. However, no study has measured actual systemic bioavailability after oral administration. It’s plausible that oral KPV acts locally on gut tissue (where PepT1 is expressed) without significant systemic absorption — which would mean it might help gut inflammation but not systemic conditions.
Safety Profile
No formal safety data exists. As a naturally-occurring fragment of a human hormone (α-MSH), there’s a reasonable theoretical safety argument, but theoretical safety and proven safety are different things. The lack of melanocortin receptor activation is encouraging — it suggests KPV won’t cause the pigmentation side effects associated with melanotan compounds. But without any human dosing data, the safety profile is simply unknown.
Legal and Regulatory Status
FDA: Category 2 — prohibited for compounding. Not approved for any indication.
Supplement status: Some vendors sell KPV as a dietary supplement, but like BPC-157, it is a synthetic peptide without New Dietary Ingredient Notification, making this classification legally questionable.
WADA: Not explicitly listed. Potentially falls under S0 (Non-Approved Substances) for competitive athletes.
Common Vendor Claims vs. Reality
| What vendors say | What the evidence shows |
|---|---|
| ”Treats IBD/colitis” | 100% survival in mouse colitis model — zero human trials |
| ”Heals gut lining” | Animal models only; no human endoscopy data |
| ”Anti-inflammatory” | Well-characterized NF-κB inhibition in cells and mice |
| ”Clinically studied” | False — no human clinical trial has ever been conducted |
| ”Safe for daily use” | No human safety data of any kind exists |
| ”Better than mesalamine” | No head-to-head comparison exists, even in animals |
The Bottom Line
KPV is one of the more scientifically interesting peptides on the grey market. The PepT1-mediated mechanism is elegant, the colitis animal data is genuinely impressive, and the absence of melanocortin-mediated side effects is a meaningful advantage over other α-MSH derivatives. But impressive preclinical science is not the same as a proven therapy. If you have IBD, there are FDA-approved medications with decades of human safety and efficacy data. KPV might someday join them — but first, someone needs to actually give it to a human being in a controlled trial and publish the results. That hasn’t happened yet.