The six / KPV
KPV
Also: Lys-Pro-Val, alpha-MSH(11-13)
Three amino acids from the tail of a natural anti-inflammatory hormone, with good mouse data and no human trial.
Class
Tripeptide, 3 amino acids
Sequence
Lys-Pro-Val, the C-terminal 11-13 fragment of alpha-MSH
Origin
Identified around 1990 as the minimal anti-inflammatory fragment of alpha-melanocyte-stimulating hormone
Policy form
KPV acetate
Permitted routes
Topical and oral only
Human evidence
Low: no controlled human trial
What people ask for it for
Gut inflammation, skin inflammation and wound care. It is the peptide people with skin or digestive complaints ask about, and the only one of the six with a topical route.
What the policy allows
KPV acetate. Topical and oral only. Injectable KPV, offered by some grey-market sellers, is outside the policy.
Strength of the evidence
LowA clean mechanism and consistent mouse colitis data from more than one laboratory, which is more independent replication than most of the six have. Nothing in people.
Where it comes from
Alpha-melanocyte-stimulating hormone (alpha-MSH) is a natural 13-amino-acid hormone best known for controlling pigmentation, and also a potent anti-inflammatory signal. Around 1990 researchers found that its last three amino acids, Lys-Pro-Val, carried most of the anti-inflammatory activity without the pigmentation effect.
KPV is that fragment, made synthetically. Because it is so small and stable it can be given by mouth and applied to skin, which sets it apart from the injectable peptides in this group and is why the policy permits those two routes.
Most of the research has been in gut inflammation, driven by a 2008 Gastroenterology paper from Emory University showing that KPV enters intestinal cells through the PepT1 transporter and calms inflammation from the inside.
How it is thought to work
From cell and animal models unless stated
KPV reduces activation of NF-kB, the master switch for inflammatory gene expression, and lowers downstream messengers such as TNF-alpha and IL-6 in cell and animal models.
In the gut it is taken up by PepT1, a transporter on intestinal cells that is more active in inflamed tissue, so the peptide concentrates where the inflammation is.
Part of its activity is independent of the melanocortin receptor MC1R, which is why it does not darken skin the way the parent hormone can.
What the research shows
Study by study, labelled by what it was. The third column is the citation; the full references are at the foot of the page.
In cells and animals
Mouse colitis, KPV by mouth or in drinking water
Reduced inflammation, weight loss and histological damage; the effect depended on PepT1 and was absent in PepT1-knockout mice.
Dalmasso et al., Gastroenterology 2008; PubMed 18061177
Mouse models of inflammatory bowel disease
Anti-inflammatory effect confirmed by a separate group, partly independent of MC1R.
Kannengiesser et al., Inflamm Bowel Dis 2008
Nanoparticle-delivered oral KPV in colitis
Mucosal healing and reduced TNF-alpha at a fraction of the free-peptide dose.
Xiao et al., Mol Ther 2017
Human bronchial epithelial cells
Inhibited inflammatory signalling; mechanism of KPV action characterised.
PMC3403564
In people
Controlled human trial, any indication
None published.
Superpower guide, 2026; FDA briefing
Human safety or pharmacokinetic study
None published.
FDA briefing, 2026
Safety, and what is not known
- There are no human safety data. The policy's Appendix B says plainly that its safety conclusion reflects missing information rather than any observed signal.
- The parent hormone is a natural human molecule and the fragment is tiny, which makes serious toxicity less likely in principle; principle is not data.
- Topical and oral routes carry less risk of the sterility and endotoxin problems that come with injectables, which is one reason the committee was comfortable with those routes and not injection.
- An oral product is covered only with documentation that the specific formulation is absorbed in humans. For KPV, which is transported by PepT1, that documentation is plausible to produce, but it must exist.
What the HHS policy says about KPV
KPV acetate
Topical and oral only. Injectable KPV, offered by some grey-market sellers, is outside the policy.
- Appendix B records that use is documented and that acetate lots confirm identity and report endotoxin and microbial results.
- Oral forms need documented human bioavailability for the specific formulation.
All ten conditions of the policy →
Sport
Not named individually. WADA's S0 category covers any substance not approved for human therapeutic use, so a tested athlete should treat it as prohibited.
Regulatory status
-
Never
FDA approval. No application for approval of this substance has been filed in the US, and no trial exists that could support one.
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September 2023
Placed in Category 2 of FDA's interim 503A bulk substances list, the category for substances where FDA identified significant safety risks. Reputable pharmacies stopped compounding it.
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April 2026
Removed from the active Category 2 table after the Federal Register notice announcing advisory committee review.
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July 2026
Pharmacy Compounding Advisory Committee recommended it for the 503A bulks list on July 23, by 8 votes to 6 with one abstention.
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October 28, 2026
Covered by the HHS enforcement discretion policy. Compoundable by state-licensed pharmacies and physicians that meet all ten of the policy's conditions, for an individual patient on a valid prescription. Still not on the 503A bulks list and still not approved.
Getting KPV through Healthy Peptides
You complete a health intake. An independent clinician at Beluga Health reviews it and decides whether KPV is appropriate for you, and by which permitted route. If prescribed, a state-licensed pharmacy that meets every condition of the HHS policy compounds the single-ingredient product and ships it to you. Healthy Peptides sells you the program; Local Healthcare bills you as its agent.
What we will and will not tell you
- WillWhat the research on KPV actually shows, graded honestly, and the routes a pharmacy may prepare.
- WillWho made it, who prescribed it, who billed you, and how to report a problem.
- Will notCall KPV approved, proven, safe or natural, or promise a result.
- Will notPublish a dose or protocol. That is between you, the clinician and the pharmacy label.
Questions about KPV
What is KPV?
The last three amino acids of alpha-MSH, a natural hormone with anti-inflammatory activity. The fragment keeps the anti-inflammatory effect and drops the pigmentation effect. It is small enough to be taken by mouth or applied to skin.
What does the research show?
In mice with colitis, oral KPV reduced inflammation and tissue damage, in work from at least two independent laboratories. In human cells it dampens inflammatory signalling. There is no human trial of any kind.
Why topical and oral, not injection?
Those are the routes the policy names in Appendix B, matching the documented use. KPV's size and its uptake by the gut transporter PepT1 are what make the oral route credible. Injectable KPV is outside the policy.
Is it safe?
Nobody has studied it in people. The policy itself says the safety conclusion reflects missing information rather than an observed problem. Topical and oral routes avoid the sterility risks of injection, which is some comfort and not a safety profile.
Can a salon offer it?
A salon can offer a program on which an independent clinician may prescribe topical KPV where appropriate. The salon does not stock it, apply it or recommend it. That line is what keeps a salon on the right side of the policy and of state law.
KPV is not FDA-approved and no clinical trial has established that it is safe or effective for any use. The research described on this page is reported as what it is, cell, animal or small human studies, and is not a benefit you should expect. Programs are provided only where an independent, licensed clinician determines they are clinically appropriate after reviewing your health history, and not everyone qualifies. Compounded KPV is prepared by a state-licensed pharmacy under a patient-specific prescription and the conditions of the HHS enforcement discretion policy of October 28, 2026, which is not an approval and may be withdrawn. Availability varies by state. This page is general information, not medical advice. Last reviewed October 29, 2026.
Sources
- Dalmasso G et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology 2008
- Kannengiesser K et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis 2008
- Xiao B et al. Nanoparticle-mediated oral delivery of KPV in colitis. Mol Ther 2017
- Inhibition of inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action
- Superpower peptide guide: KPV
- HHS: Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances, with Appendices A and B (October 28, 2026)
- AJMC: FDA panel backs 6 peptides for compounding (July 2026)
- FDA: Bulk drug substances used in compounding under section 503A
- WADA: 2026 Prohibited List