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Evidence: LowPeptideResearch ChemicalAntimicrobialWound trialsDouble-edged

LL-37

The body's own antimicrobial peptide, tested on wounds, never as an injection

LL-37 is the only cathelicidin antimicrobial peptide humans make, and one of the few research peptides with randomised trials. Applied to chronic leg ulcers it helped in a small trial but missed its endpoint in a larger one. It also drives rosacea inflammation and promoted breast cancer metastasis in mice, and no carded study tested injecting it.

Overview

What is it?

LL-37 is the only cathelicidin antimicrobial peptide humans make: a 37-amino-acid peptide that becomes active when it is cut from the end of its inactive precursor, hCAP18. It is present in every human organ studied, highest in the gut and brain, and epithelial cells release it quickly on contact with bacteria. A 2012 review called it a factotum because it does so much: it kills bacteria, fungi and viruses, recruits immune cells, and promotes wound healing and new blood vessels.

It is also one of the few research peptides with modern randomised trials, as a topical wound treatment. In a first-in-human study in 34 people with hard-to-heal venous leg ulcers, the two lower doses healed ulcers several times faster than placebo. The larger phase IIb trial in 148 patients found no significant benefit overall, only a post hoc signal in large wounds. A 2023 trial in diabetic foot ulcers reported better granulation tissue with an LL-37 cream.

The same biology cuts both ways. Excess, abnormally processed cathelicidin drives the skin inflammation of rosacea. LL-37 made human brain immune cells release inflammatory signals, and in breast cancer its precursor tracked lymph-node metastases while LL-37 itself made cancer cells more mobile and promoted metastases in mice. An antimicrobial that also stirs inflammation and cell migration is not a molecule to inject casually.

Injected LL-37, the way it is usually sold, was not tested in any carded study; the trials used solutions on wounds, a cream and an oral bacterial delivery system. In the US its nomination was withdrawn from Category 2 in April 2026, and it is slated for review by the Pharmacy Compounding Advisory Committee by the end of February 2027, with no date set. Until FDA decides, pharmacies cannot compound it (as of September 26, 2026).

37
amino acids
cut from the precursor hCAP18
68%
smaller ulcers, lowest dose
first trial, 34 patients
148
patients in phase IIb
no benefit overall
Feb 2027
PCAC review deadline
no date set
Science

Mechanism of Action

LL-37 is part of the innate immune system, and most of what is known describes what the body's own peptide does rather than what a dose from a vial does. The four actions below are documented in the carded studies, and several are double-edged.

⚙

Killing microbes

The 2012 review describes antibacterial, antifungal and antiviral activity, and the urinary-tract study shows it at work: epithelium secreted LL-37 on contact with bacteria, mice lacking the peptide were less protected, and E. coli strains more resistant to it caused more severe infections. Bacterial resistance is already documented, which matters for any plan to use it as a drug.

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Wound repair

According to the review, LL-37 promotes wound healing and new blood vessel growth. Topical LL-37 improved healing of venous leg ulcers at low doses in a small trial and improved granulation in diabetic foot ulcers. The highest dose tested, 3.2 mg/mL, did no better than placebo, and the larger ulcer trial missed its main endpoint.

◈

Immune signalling

LL-37 recruits immune cells and modulates immune responses. In cultured human microglia and astrocytes it triggered release of IL-1β, IL-6, IL-8 and CCL-2 through p38 MAP kinase and NF-κB, and abnormally processed cathelicidin drives rosacea inflammation in skin. The signalling that helps fight infection can cause inflammation where it is not wanted.

○

Cell migration and cancer

In breast cancer cells, LL-37 amplified ErbB2 growth signalling, increased migration and produced a dispersed, metastatic-looking colony shape, and overexpressing its precursor promoted metastases in mice. The review also notes emerging evidence of a role in cancer. For anyone with a cancer history, this is the most important line on the page.

Evidence

Published Research

About 54 papers in our evidence set concern LL-37, and they fall into two groups: studies of the body's own peptide in infection, skin, gut and cancer, and a handful of trials of LL-37 as a treatment. The eleven cards below cover both, and each says which kind it is. None tested injecting it, which is how it is usually sold.

Human2014

Venous leg ulcers: first-in-human trial

Thirty-four people with hard-to-heal venous leg ulcers had a three-week placebo run-in, then four weeks of twice-weekly topical LL-37 at 0.5, 1.6 or 3.2 mg/mL or placebo, double-blind. The two lower doses healed about six and three times faster than placebo (P = 0.003 and 0.088) and shrank ulcers by 68% and 50%; the highest dose did no better than placebo. There were no local or systemic safety concerns.

PMID: 25041740
Human2021

Phase IIb: no benefit overall

The larger follow-up, HEAL LL-37, randomised 148 patients with hard-to-heal venous leg ulcers to topical LL-37 at 0.5 or 1.6 mg/mL or placebo, alongside compression, double-blind. Across the full population LL-37 did not significantly improve healing. A post hoc analysis found benefits in patients with wounds of at least 10 cm², a subgroup result that needs its own trial. The drug was well tolerated at both strengths.

PMID: 34687253
Human2023

Diabetic foot ulcers: better granulation

In a randomised double-blind trial in Jakarta, patients with mildly infected diabetic foot ulcers applied LL-37 or placebo cream twice a week for four weeks. The granulation index rose more with LL-37 at every weekly check (P = 0.031, 0.009, 0.006 and 0.037), and the authors conclude it enhanced healing. It did not lower IL-1α or TNF-α or reduce bacterial colonisation. The abstract does not give patient numbers.

PMID: 37480520
Human2023

Oral recombinant LL-37 in COVID-19

A recombinant Lactococcus lactis that delivers LL-37 by mouth was tested in 238 adults hospitalised with the Omicron BA.5.1.3 variant, in an open-label, randomised, placebo-controlled single-centre study. Started by day six, it shortened the time to a negative viral test to 9.8 days, against 14.0 with placebo, and no severe adverse events were seen. The open-label design limits how far the result can be trusted.

PMID: 37605995
Animal2007

Too much cathelicidin drives rosacea

People with rosacea had abnormally high cathelicidin in their facial skin, processed into different peptide fragments than in healthy skin because of excess stratum corneum tryptic enzyme. Injecting the rosacea-type cathelicidin peptides into mouse skin increased inflammation, and the role of cathelicidin was confirmed in mice lacking its gene. For a peptide sold as a skin and healing aid, more is not always better.

PMID: 17676051
Animal2009

Breast cancer: a metastasis signal

In 109 primary breast cancers, hCAP18, LL-37's precursor, tracked ERBB2 expression and lymph-node metastases in oestrogen-receptor-positive tumours. LL-37 amplified growth signalling through ErbB2, stimulated migration of breast cancer cells and gave their colonies a dispersed, more metastatic shape; overexpressing hCAP18 in a low-malignancy line promoted metastases in immunodeficient mice.

PMID: 19183447
Animal2006

The urinary tract's own antibiotic

Epithelial cells lining the human and mouse urinary tract rapidly produced and secreted cathelicidin on contact with bacteria, and in people LL-37 was released into urine. Mice lacking the peptide were less protected against infection, and clinical E. coli strains more resistant to LL-37 caused more severe urinary infections. It shows why LL-37 is considered a key part of the body's own defence, not what injecting it does.

PMID: 16751768
Animal2023

Heat stroke in rats

Rats were heated at 42 °C to induce heat stroke, which damages the gut barrier and triggers system-wide inflammation. Cathelicidin LL-37 attenuated intestinal injury, systemic inflammation and nitrosative stress, and improved multiple organ dysfunction, clotting problems and survival, with human intestinal cell lines used to probe the mechanism. It is an emergency-medicine lead in rodents; the abstract gives no doses.

PMID: 36958193
In Vitro2015

Inflammation in human brain cells

hCAP18 and LL-37 were found in every human organ examined, highest in the gut and brain. Added to cultured human microglia and astrocytes, LL-37 triggered release of the inflammatory cytokines IL-1β and IL-6 and the chemokines IL-8 and CCL-2, along with material toxic to neuron-like SH-SY5Y cells, through p38 MAP kinase and NF-κB. Removing LL-37 with an antibody blocked the effect.

PMID: 25686659
Human2010

Tuberculosis: LL-37 and vitamin D

In stored serum from 95 patients with pulmonary tuberculosis, 86% had insufficient vitamin D. Mean LL-37 was 49.5 ng/mL, and higher levels went with positive sputum smears and being more than 10% underweight. Vitamin D status did not correlate with serum LL-37, despite laboratory evidence that vitamin D switches the peptide on. The authors call for prospective studies before using LL-37 as a biomarker.

PMID: 20610636
Review2012

The factotum peptide, reviewed

This review describes cathelicidins as an exceptional class of antimicrobial peptides and LL-37 as the human member: antibacterial, antifungal and antiviral, chemotactic and immune-modulating, able to promote wound healing and angiogenesis and to modulate apoptosis. It also notes emerging evidence of a role in cancer. It maps what LL-37 does in the body rather than making the case for using it as a drug.

PMID: 23246832
Dosing

Dosing Data

The human trials used LL-37 on the skin or by mouth, not by injection. The venous leg ulcer trials applied solutions of 0.5 to 3.2 mg/mL, twice a week in the first trial, where the lowest concentration worked best. The COVID-19 trial used a recombinant bacterium that delivers LL-37 in the gut. The community figure in our dataset, 100–500 µg injected under the skin, has no trial behind it.

Not a recommendation. The trial doses are topical and oral, the injected community dose is untested, and LL-37 has pro-inflammatory and pro-metastatic effects in laboratory studies.
ProtocolDoseFrequencyDurationRoute
Leg ulcer, phase I/II Human studyPMID 250417400.5–3.2 mg/mL2× weekly4 weeksTopical
Leg ulcer, phase IIb Human studyPMID 346872530.5 or 1.6 mg/mLNot in abstractNot in abstractTopical
Diabetic foot ulcer Human studyPMID 37480520Cream (strength not given)2× weekly4 weeksTopical
Community (dataset) Community-reported100–500 µgDaily or alternate daysNot definedSubcutaneous

Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.

Reconstitution maths, without the guesswork
Community doses are quoted in micrograms or milligrams, while insulin syringes are marked in units. The reconstitution calculator converts between them for any vial size and volume of water, so the arithmetic is done for you rather than in your head.
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Safety

Side Effects & Contraindications

Reported Side Effects

The wound trials reported LL-37 as safe and well tolerated on the skin, and the oral COVID-19 trial saw no severe adverse events. None of that tells us what injecting it does, and the laboratory findings add risks the trials were not designed to detect.

● Topical use in leg ulcers: no local or systemic safety concerns in either trial
● Oral recombinant LL-37: no severe adverse events during hospital stay and follow-up
● Injected LL-37: no safety data in any carded study
● Inflammation: LL-37 triggered inflammatory signals in human brain immune cells in culture
● Unregulated product: contamination, the wrong peptide or the wrong amount in the vial

Contraindications & Cautions

These cautions come from what LL-37 does in the body and in laboratory studies, not from harm observed in the trials.

● Current or past cancer, especially breast cancer: LL-37 promoted migration and metastasis in breast cancer models
● Rosacea or inflammatory skin disease: abnormally processed cathelicidin drives rosacea inflammation
● Inflammatory conditions: it triggered inflammatory signalling in human glial cells and in skin
● Pregnancy and breastfeeding: no data on this page
● Competitive athletes: check the sport row of the legal table before use
● Anyone expecting the wound-trial results from injections: those trials applied it to the wound
Questions

Frequently Asked Questions

?Is LL-37 made by the body?

Yes. It is the only cathelicidin antimicrobial peptide in humans, cut from its inactive precursor hCAP18, and it is found in every organ studied, most of all in the gut and brain. Epithelial cells release it when they meet bacteria, and it is part of the body's first-line defence.

?Does LL-37 heal wounds?

Topically, possibly, in some wounds. A first trial in 34 people with venous leg ulcers found the two lower doses healed ulcers several times faster than placebo, but a 148-patient phase IIb trial found no overall benefit. A diabetic foot ulcer trial reported better granulation tissue. None of this involved injection.

?Can LL-37 treat infections?

It kills microbes as part of the body's own defences, and an oral recombinant form shortened the time to a negative COVID-19 test in one open-label trial. But bacteria can resist it: E. coli strains more resistant to LL-37 caused more severe urinary infections. No carded study tested injected LL-37 for infection.

?Is LL-37 safe?

On the skin and by mouth, the trials reported no safety concerns. Injected, it has not been tested in any carded study. Laboratory and animal studies raise two specific concerns: it drives inflammation in some tissues, including rosacea skin and brain immune cells, and it promoted breast cancer cell migration and metastasis in mice.

?Can a US pharmacy compound LL-37?

Not as of September 26, 2026. Its nomination was withdrawn from Category 2 in April 2026, and it is slated for review by FDA's Pharmacy Compounding Advisory Committee by the end of February 2027, with no date set. Until FDA decides, no list allows a pharmacy to compound it.

?Does vitamin D raise LL-37?

Laboratory studies show vitamin D metabolites switch on the gene for LL-37, but in 95 patients with tuberculosis, blood vitamin D did not correlate with serum LL-37. Whether vitamin D supplements meaningfully raise LL-37 in people is not settled by the evidence here.

Bibliography

References

  1. [pubmed] 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 Regen, 2014;22(5):613-21. PMID: 25041740.
  2. [pubmed] Mahlapuu M, et al. "Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial." Wound Repair Regen, 2021;29(6):938-950. PMID: 34687253.
  3. [pubmed] Miranda E, et al. "Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial." Arch Dermatol Res, 2023;315(9):2623-2633. PMID: 37480520.
  4. [pubmed] Zhao Y, et al. "Efficacy and safety of Oral LL-37 against the Omicron BA.5.1.3 variant of SARS-COV-2: A randomized trial." J Med Virol, 2023;95(8):e29035. PMID: 37605995.
  5. [pubmed] Yamasaki K, et al. "Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea." Nat Med, 2007;13(8):975-80. PMID: 17676051.
  6. [pubmed] Weber G, et al. "Human antimicrobial protein hCAP18/LL-37 promotes a metastatic phenotype in breast cancer." Breast Cancer Res, 2009;11(1):R6. PMID: 19183447.
  7. [pubmed] Chromek M, et al. "The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection." Nat Med, 2006;12(6):636-41. PMID: 16751768.
  8. [pubmed] Shih CC, et al. "Antimicrobial peptide cathelicidin LL-37 preserves intestinal barrier and organ function in rats with heat stroke." Biomed Pharmacother, 2023;161:114565. PMID: 36958193.
  9. [pubmed] Lee M, et al. "Human antimicrobial peptide LL-37 induces glial-mediated neuroinflammation." Biochem Pharmacol, 2015;94(2):130-41. PMID: 25686659.
  10. [pubmed] Yamshchikov AV, et al. "Vitamin D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis." Am J Clin Nutr, 2010;92(3):603-11. PMID: 20610636.
  11. [pubmed] Vandamme D, et al. "A comprehensive summary of LL-37, the factotum human cathelicidin peptide." Cell Immunol, 2012;280(1):22-35. PMID: 23246832.

Sources & Citations

Every citation on this page is PubMed-indexed and has been checked against its record. Several cards describe the body's own LL-37 rather than LL-37 given as a treatment, and each card says which. Grey Peptides sells nothing and links to no vendor.

Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.

Last reviewed: 2026-09-26