# LL-37 - Canonical: https://residue.info/c/ll-37/ - Also called: Cathelicidin LL-37, hCAP18 (precursor), CAMP - Evidence grade: B (Randomized human trials). Two randomized, placebo-controlled trials of topical LL-37 in venous leg ulcers: a 34-patient first-in-man trial was positive at lower doses; a 148-patient phase IIb trial missed its primary analysis. - Status: Not FDA-approved · FDA compounding nomination withdrawn - PubChem CID: 16198951 - Updated: 2026-10-19 · Reviewed by: Residue Editorial Team LL-37 is the human cathelicidin, an antimicrobial peptide with immunomodulatory and pro-angiogenic properties [1]. Topical LL-37 improved healing of venous leg ulcers at lower doses in a 34-patient randomized trial [2], but a 148-patient phase IIb trial found no overall benefit [3]. It is not FDA-approved, and FDA records nonclinical safety concerns [4]. ## Key findings - First-in-man RCT (34 patients): healing-rate constants roughly six- and threefold higher than placebo at 0.5 and 1.6 mg/mL; 3.2 mg/mL did no better than placebo [2]. (anchor: https://residue.info/c/ll-37/#kf-pmid-25041740) - HEAL LL-37 phase IIb (148 patients): no significant improvement in healing in the full population; benefit appeared only in a post hoc subgroup with large wounds [3]. (anchor: https://residue.info/c/ll-37/#kf-pmid-34687253) - Both doses were well tolerated in both trials [2][3]. (anchor: https://residue.info/c/ll-37/#kf-pmid-25041740-2) - In 19 patients with leg ulcers, serum LL-37, but not vitamin D, correlated with healing rate [1]. (anchor: https://residue.info/c/ll-37/#kf-pmid-27663530) - FDA lists cathelicidin LL-37 among withdrawn compounding nominations, citing nonclinical findings of detrimental effects on male reproduction and possible protumorigenic effects in some tissues [4]. (anchor: https://residue.info/c/ll-37/#kf-fda-cat2) ## Effects by system - Venous leg ulcers (topical) (grade B): Positive dose-response in a 34-patient RCT [2]; no overall benefit in a 148-patient phase IIb RCT [3]. (anchor: https://residue.info/c/ll-37/#effect-venous-leg-ulcers-topical) - Stability in wounds (grade D): Fairly resistant to breakdown in chronic-wound fluid ex vivo [5]. (anchor: https://residue.info/c/ll-37/#effect-stability-in-wounds) - Natural levels (grade D): Serum level correlated with ulcer healing in 19 patients (observational) [1]. (anchor: https://residue.info/c/ll-37/#effect-natural-levels) ## What is LL-37? LL-37 is the human cathelicidin, a small antimicrobial peptide that also has immunomodulatory and pro-angiogenic properties, so it may promote wound healing; its expression is controlled by factors including vitamin D [1]. PubChem lists the 37-residue sequence beginning LLGDFFRKSK, formula C205H340N60O53 [6]. It is strongly expressed at the edge of acute wounds but only weakly in chronic wounds [5]. ## How is LL-37 thought to work? As a host-defense peptide it is antimicrobial, and it also acts on inflammation and blood-vessel growth [1]. A concern for topical use was that enzymes in chronic wounds would destroy it. In the lab, trypsin degraded it completely but matrix metalloproteinase-9 did not, and it resisted breakdown in fluid from non-healing ulcers for up to 24 hours [5]. ## What have studies found? **First-in-man trial.** Thirty-four people with hard-to-heal venous leg ulcers had a 3-week placebo run-in, then 4 weeks of randomized, double-blind treatment twice weekly. Healing rates were about six times placebo at 0.5 mg/mL and three times at 1.6 mg/mL, with mean ulcer area falling 68% and 50%; 3.2 mg/mL was no better than placebo [2]. **Phase IIb.** HEAL LL-37 randomized 148 patients (mean age 67.6, median ulcer duration 20.3 months) to 0.5 or 1.6 mg/mL or placebo with compression. It found no significant improvement in healing overall. A post hoc analysis suggested benefit in wounds of at least 10 cm², which would need a new, adequately powered trial [3]. **Registered trials.** Many ClinicalTrials.gov records measure natural LL-37 levels rather than give the peptide [7]. FDA lists "Cathelicidin LL-37" among substances whose compounding nominations were withdrawn. It notes immunogenicity risk, impurity and characterization complexities, a lack of safety information in humans, and nonclinical findings suggesting detrimental effects on male reproduction and that it can be protumorigenic in some tissues [4]. Drugs@FDA returned no application. ## What is still unknown? - **Whether it helps large ulcers**, the subgroup flagged post hoc [3]. - **Any injected use.** The trials we found were topical [2][3]. ## Frequently asked questions **Is LL-37 FDA-approved?** No. FDA lists 'Cathelicidin LL-37' among withdrawn compounding nominations and says it lacks sufficient safety information to know whether it would cause harm in humans [4]. **Does LL-37 help wounds heal?** The evidence is mixed. A 34-patient trial found faster ulcer healing at lower doses [2]; the larger 148-patient trial found no overall benefit [3]. **What is LL-37?** It is the human cathelicidin, an antimicrobial peptide that also has immunomodulatory and pro-angiogenic effects; its production is influenced by vitamin D [1]. PubChem lists it as a 37-residue peptide [6]. **What are the safety concerns with LL-37?** The ulcer trials reported it was well tolerated [2][3]. FDA notes immunogenicity risk and nonclinical findings of harm to male reproduction and protumorigenic effects in some tissues [4]. ## Sources [1] LL-37 but Not 25-Hydroxy-Vitamin D Serum Level Correlates with Healing of Venous Leg Ulcers. Krejner A et al. Arch Immunol Ther Exp (Warsz). 2017. https://pubmed.ncbi.nlm.nih.gov/27663530/ [2] Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Grönberg A et al. Wound Repair Regen. 2014. https://pubmed.ncbi.nlm.nih.gov/25041740/ [3] Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial. Mahlapuu M et al. Wound Repair Regen. 2021. https://pubmed.ncbi.nlm.nih.gov/34687253/ [4] Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks [5] Stability of the cathelicidin peptide LL-37 in a non-healing wound environment. Grönberg A et al. Acta Derm Venereol. 2011. https://pubmed.ncbi.nlm.nih.gov/21547341/ [6] PubChem compound record: LL-37. C205H340N60O53 · MW 4493 g/mol. https://pubchem.ncbi.nlm.nih.gov/compound/16198951 [7] ClinicalTrials.gov registry search: LL-37. 20 registered studies at fetch. https://clinicaltrials.gov/search?intr=LL-37 --- From Residue. Research and education only; not medical advice. Quote with attribution and a link to the canonical page.