Peptide Evidence Index
LL-37
Quick answers
- What is it?
- LL-37 is the active fragment of cathelicidin, an antimicrobial peptide the human body already produces in white blood cells and skin as part of innate immune defense. It has never been approved as a medicine.
- Why are people interested in it?
- It's marketed broadly for skin and antimicrobial use, but people want to know whether the genuine, published human trials support that, or just a narrower use.
- What has actually been studied?
- Two small randomized, placebo-controlled trials tested topical LL-37 on chronic wounds — 34 people with venous leg ulcers and 40 people with diabetic foot ulcers — plus a small dose-finding trial injecting it into melanoma tumors.
- How strong is the evidence?
- Early human data: genuine small randomized trials exist for chronic wound healing, with real positive results at some concentrations, but the total evidence base is thin and narrow.
- What don't we know yet?
- Why the highest concentration tested for leg ulcers performed no better than placebo while lower concentrations did, whether either wound finding would replicate in a larger trial, and whether LL-37 does anything for the general antimicrobial and skincare uses it's marketed for.
- Where can I read the original research?
- Sources at the bottom of this page: Grönberg et al., Wound Repair and Regeneration 2014; Miranda et al., Archives of Dermatological Research 2023.
Plain-English overview
LL-37 is not a synthetic invention but a copy of something the human body already makes: the active fragment of cathelicidin, an antimicrobial protein produced by white blood cells and skin as part of innate immune defense. It has never been approved as a medicine, and its human research comes from small, investigator-initiated academic trials rather than a pharmaceutical company's approval-track development program. Unusually for a compound in this space, genuine small randomized, placebo-controlled human trials exist — but only for a narrow use: topical treatment of chronic skin wounds. A first-in-man trial in 34 people with venous leg ulcers found two lower concentrations of topical LL-37 healed wounds faster than placebo, while the highest concentration tested performed no better than placebo. A second, separate trial in 40 people with diabetic foot ulcers found one topical concentration improved a wound-granulation measure compared with placebo, though it did not reduce inflammatory markers or bacterial colonization. Its broader marketing for general skin and antimicrobial use goes well beyond what any of this research has tested.
What researchers are studying it for
- venous leg ulcers
- diabetic foot ulcers
- melanoma (intratumoral, oncology dose-finding)
- general wound healing and antimicrobial use (marketed, largely untested in trials)
Current evidence level
Regulatory status: Not an approved medicine. Evidence strength and approval are scored separately; approval is a regulatory decision about a specific use, not a measure of how much research exists.
Human research
LL-37 has a small but genuine record of randomized, placebo-controlled human trials, all for topical treatment of chronic wounds. The first, a first-in-man trial in 34 people with hard-to-heal venous leg ulcers, tested three topical concentrations (0.5, 1.6, and 3.2 mg/mL) against placebo; healing rate was roughly six times faster than placebo at the lowest concentration and about three times faster at the middle concentration, but the highest concentration performed no better than placebo, an unexplained non-linear dose-response (Grönberg et al., Wound Repair and Regeneration, 2014). A second randomized, double-blind trial in 40 people with diabetic foot ulcers tested a single concentration (0.5 mg/mL) against placebo cream, applied twice weekly for four weeks alongside standard wound care; the LL-37 group showed consistently greater improvement in a wound-granulation measure at every timepoint checked, but no significant difference from placebo in two inflammatory markers or bacterial colonization (Miranda et al., Archives of Dermatological Research, 2023; this trial is also registered as ClinicalTrials.gov NCT04098562). Separately, a small Phase 1/2 trial at MD Anderson Cancer Center (NCT02225366) tested LL-37 injected directly into melanoma tumors to find a tolerable dose and look for an antitumor immune response; the trial was designed for up to 36 participants but only 4 were ultimately treated before it closed in 2020, and no published results describing what was found have been located. Beyond these interventional studies, a large separate body of research measures LL-37 as a biomarker in saliva, gum fluid, or skin in conditions like periodontitis, rosacea, and vitamin D status, without administering LL-37 as a treatment — these say something about the body's own LL-37 production, not about giving it as a drug.
Animal and preclinical research
Not covered in the published research we reviewed for this page — the source material for LL-37 describes only human interventional and observational studies, with no animal or preclinical data included.
Major findings
- In a first-in-man trial of 34 people with venous leg ulcers, topical LL-37 at 0.5 and 1.6 mg/mL healed wounds roughly six and three times faster than placebo, respectively, but 3.2 mg/mL performed no better than placebo (Grönberg et al., 2014).
- In 40 people with diabetic foot ulcers, topical LL-37 (0.5 mg/mL) improved a wound-granulation measure at every timepoint checked compared with placebo, but did not significantly change inflammatory markers or bacterial colonization (Miranda et al., 2023).
- A Phase 1/2 melanoma trial injecting LL-37 directly into tumors closed in 2020 after treating only 4 of a planned 36 participants, and no results have been published.
- A large separate body of observational research measures the body's own naturally occurring LL-37 levels in conditions like periodontitis, rosacea, and PCOS, without ever administering LL-37 as a treatment.
- The dose-response relationship in the leg-ulcer trial was non-linear — a lower concentration outperformed a higher one — a pattern the study authors did not fully explain.
What has not been established
- Why the highest concentration tested for venous leg ulcers performed no better than placebo while lower concentrations did.
- Whether either wound-healing finding would replicate in a larger trial — both are small, single-country studies.
- What the melanoma trial actually found, since no results have been published despite its 2020 completion.
- Whether LL-37 has any tested effect for the general antimicrobial and skincare uses it's marketed for.
- What an unregulated topical or cosmetic product's actual LL-37 content and stability are, compared with the pharmaceutical-grade material used in trials.
Important limitations
- Both wound-healing trials were small (34 and 40 people) and run in single countries, limiting generalizability.
- The non-linear, unexplained dose-response in the leg-ulcer trial complicates any assumption that more LL-37 works better, or at all.
- The melanoma trial enrolled only 4 of a planned 36 participants and never published results, so it adds no usable evidence.
- The human trials are small, investigator-initiated academic studies, not part of a company's approval-seeking development program, so there is no larger confirmatory trial underway.
- None of the trial evidence covers the general skincare or antimicrobial uses LL-37 is marketed for today.
Regulatory status
LL-37 has never been approved as a medicine anywhere. The human trials that exist are small, investigator-initiated academic studies rather than part of a company's approval-seeking development program.
Primary research sources
- Grönberg A, et al., "Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial"
- Wound Repair and Regeneration 2014; PMID 25041740, DOI 10.1111/wrr.12211
- Miranda E, et al., "Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial"
- Archives of Dermatological Research 2023; PMID 37480520, DOI 10.1007/s00403-023-02657-8
- "Efficacy of LL-37 Cream on Aerobic Bacteria Colonization Pattern, Inflammation Response, and Healing Rate of Diabetic Foot Ulcers"
- ClinicalTrials.gov NCT04098562, n=40, Jakarta, Indonesia, completed 2020, results published ()
- "Induction of Antitumor Response in Melanoma Patients Using the Antimicrobial Peptide LL37"
- ClinicalTrials.gov NCT02225366, Phase 1/2, MD Anderson Cancer Center/NCI. Planned up to 36 participants, only 4 treated. Completed 2020; no published results located
Full evidence entry (complete data, registry records, dosing evidence)
At a glance
- Also known as
- LL-37, Cathelicidin antimicrobial peptide (CAMP), hCAP18/LL-37
- Class
- Endogenous 37-amino-acid cathelicidin antimicrobial peptide
- Derived from
- The active C-terminal fragment cleaved from hCAP18, the human cathelicidin precursor protein naturally produced by neutrophils and epithelial tissue, including skin
- Registered human trials
- 2
- …with published results
- 2 published on ClinicalTrials.gov-registered trials, plus one additional small first-in-man trial published without a located ClinicalTrials.gov record
- Largest human trial
- 40 patients with diabetic foot ulcers (randomized, double-blind, placebo-controlled, 2020-2021)
- Studied for
- venous leg ulcers, diabetic foot ulcers, melanoma (intratumoral, oncology dose-finding), general wound healing and antimicrobial use (widely marketed, largely untested in trials)
- Dosing evidence
- Doses used in trialsTwo small randomized trials have tested specific topical concentrations of LL-37 on chronic wounds, with an unusual pattern where a lower concentration outperformed a higher one; no dose has been established for any other use, including the general skincare and antimicrobial claims it is marketed for.
- Regulatory status
- Never approved as a medicine anywhere. The human trials that exist are small, investigator-initiated academic studies rather than part of a company's approval-seeking development program.
What it is
LL-37 is not a foreign or purely synthetic peptide — it's the active fragment of cathelicidin, an antimicrobial protein the human body already produces in neutrophils (a type of white blood cell) and in skin and other epithelial tissue as part of innate immune defense. The name comes from its structure: it starts with two leucine (L) residues and is 37 amino acids long. Synthetic versions made for research and topical products are copies of this same sequence.
It has never been approved as a medicine. The human research on it comes from small, investigator-initiated academic trials rather than a pharmaceutical company's approval-track development program — a different, thinner evidence pipeline than most other drug candidates follow.
What the studies actually found
LL-37 has an unusual position in this library: genuine small randomized, placebo-controlled human trials exist, but only for a narrow use — topical treatment of chronic skin wounds.
The first, a "first-in-man" trial in 34 people with hard-to-heal venous leg ulcers, tested three different topical concentrations of LL-37 (0.5, 1.6, and 3.2 mg/mL) against placebo. Healing rate was roughly six times faster than placebo at the lowest concentration and about three times faster at the middle concentration — but the highest concentration performed no better than placebo, an unusual, non-linear dose-response pattern the study authors did not fully explain (Grönberg et al., 2014, Wound Repair and Regeneration).
A second randomized, double-blind trial in 40 people with diabetic foot ulcers tested a single topical concentration (0.5 mg/mL) against placebo cream, applied twice weekly for four weeks alongside standard wound care. The LL-37 group showed consistently greater improvement in a wound-granulation measure at every timepoint checked, but no significant difference from placebo in levels of two inflammatory markers or in bacterial colonization of the wound (Miranda et al., 2023, Archives of Dermatological Research).
Separately, a small Phase 1/2 trial at MD Anderson Cancer Center tested LL-37 injected directly into melanoma tumors, aiming to find a tolerable dose and see whether it could provoke an antitumor immune response. The trial was designed for up to 36 participants across several dose levels, but registry records show only 4 were ultimately treated before the study closed in 2020; no published results describing what was found have been located.
What exists in humans
Two genuine interventional trials of LL-37 are registered on ClinicalTrials.gov: the diabetic foot ulcer trial and the melanoma dose-finding trial described above. The venous leg ulcer trial was published in 2014, but no corresponding ClinicalTrials.gov record was located — which may reflect registration in a different registry, or trial timing relative to registration requirements.
Beyond these interventional studies, a large separate body of research measures LL-37 as a biomarker — in saliva, gum fluid, or skin — in conditions like periodontitis, rosacea, and vitamin D status, without administering LL-37 as a treatment. Those studies say something about the body's own LL-37 production; they are not evidence about giving LL-37 as a drug.
What doses have been studied in humans
The two chronic-wound trials tested specific topical concentrations directly: 0.5, 1.6, and 3.2 mg/mL in the venous-leg-ulcer trial (twice-weekly application, 4-week treatment phase, 34 people), and 0.5 mg/mL in the diabetic-foot-ulcer trial (twice-weekly, 4 weeks, 40 people). Both were applied topically to the wound itself under close clinical supervision, not taken systemically.
Notably, the leg-ulcer trial's result was not a simple "more is better" pattern — the lowest concentration tested outperformed the highest. That complicates any assumption that a higher concentration of a marketed LL-37 product would work better, or at all.
The melanoma trial tested LL-37 by direct intratumoral injection at escalating dose levels, a route and context with no relevance to any topical or systemic wellness use.
None of this dosing evidence applies to LL-37 as sold in general skincare, antimicrobial, or wellness products, which are not the same controlled formulations used in these trials and have not been tested at any dose for those uses.
What remains unknown
- Why the highest concentration tested for venous leg ulcers performed no better than placebo, while
lower concentrations did
- Whether either wound-healing finding would replicate in a larger trial — both are small,
single-country studies
- What the melanoma trial actually found, since no results have been published despite the trial's 2020
completion
- Whether LL-37 has any tested effect for the general antimicrobial and skincare uses it's marketed for
- What an unregulated topical or cosmetic product's actual LL-37 content and stability are, compared
with the pharmaceutical-grade material used in trials
Registry and study records
- Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial
- PubMed · Grönberg et al., 2014, Wound Repair and Regeneration. n=34; first-in-man; 0.5 and 1.6 mg/mL outperformed placebo, 3.2 mg/mL did not. DOI: 10.1111/wrr.12211
- Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial
- PubMed · Miranda et al., 2023, Archives of Dermatological Research. n=40; 0.5 mg/mL cream improved granulation index at every timepoint; no significant effect on inflammatory markers or bacterial colonization. DOI: 10.1007/s00403-023-02657-8
- Efficacy of LL-37 Cream on Aerobic Bacteria Colonization Pattern, Inflammation Response, and Healing Rate of Diabetic Foot Ulcers
- ClinicalTrials.gov NCT04098562 · n=40, Jakarta, Indonesia, completed 2020, results published (PMID 37480520)
- Induction of Antitumor Response in Melanoma Patients Using the Antimicrobial Peptide LL37
- ClinicalTrials.gov NCT02225366 · Phase 1/2 intratumoral dose-finding, MD Anderson Cancer Center / NCI. Planned up to 36 participants; only 4 treated. Completed 2020; no published results located
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Evidence last reviewed: September 2026. Peptide Proof reports what studies found. We do not give medical advice, dosing guidance, or treatment recommendations.