LL-37

LL-37 is the only cathelicidin antimicrobial peptide produced by the human body, functioning as a critical component of the innate immune system with broad-spectrum activity against bacteria, viruses, fungi, and parasites. It has gained significant popularity among biohackers, longevity enthusiasts, and individuals seeking enhanced immune support, wound healing, and anti-inflammatory benefits. LL-37 is typically administered via subcutaneous injection at doses ranging from 50–200 mcg daily, with protocols generally spanning 4–8 weeks depending on individual goals and response.

What Is LL-37?

LL-37 is a 37-amino acid peptide derived from the C-terminal end of the human cathelicidin antimicrobial peptide (hCAP18). The name "LL-37" refers to its 37 residues and the two leucine (L) amino acids at its N-terminus. It is naturally produced by neutrophils, epithelial cells, macrophages, and various other cell types throughout the body, serving as a first-line defense mechanism against invading pathogens.

What makes LL-37 unique among peptides is its multifunctional nature. Unlike many antimicrobial agents that serve a single purpose, LL-37 exhibits antimicrobial, immunomodulatory, anti-inflammatory, and wound-healing properties simultaneously. Its amphipathic, alpha-helical structure allows it to interact with and disrupt microbial membranes while also modulating host immune responses.

The primary human-use benefits of LL-37 include:

• Broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria
• Antiviral properties against various viral pathogens
• Enhanced wound healing and tissue regeneration
• Immunomodulation and inflammation regulation
• Potential gut health support through maintaining intestinal homeostasis

How It Works

Membrane Disruption

LL-37's primary antimicrobial mechanism involves direct interaction with microbial membranes. The peptide's cationic (positively charged) and amphipathic nature allows it to bind to negatively charged bacterial membranes. Upon binding, LL-37 inserts into the lipid bilayer, causing membrane destabilization, pore formation, and ultimately cell death. This mechanism makes it difficult for pathogens to develop resistance, as it would require fundamental changes to membrane composition.

Immunomodulation

Beyond direct antimicrobial action, LL-37 serves as a powerful immunomodulator. It can act as both a pro-inflammatory and anti-inflammatory agent depending on the physiological context. The peptide influences immune cell recruitment, cytokine production, and the activation of various immune pathways. It has been shown to neutralize lipopolysaccharide (LPS)-induced inflammatory responses, providing protection against excessive inflammation.

Wound Healing Promotion

LL-37 promotes wound healing through multiple pathways. It stimulates keratinocyte migration and proliferation, enhances angiogenesis (new blood vessel formation), and promotes re-epithelialization of damaged tissue. Clinical research has demonstrated that LL-37 treatment significantly accelerates healing in chronic wounds, with healing rates up to six times higher than placebo in venous leg ulcer studies.

Biofilm Disruption

LL-37 demonstrates activity against bacterial biofilms, which are notoriously difficult to treat with conventional antibiotics. The peptide can penetrate biofilm matrices and kill bacteria in both planktonic (free-floating) and biofilm states, making it valuable for addressing persistent infections.

Dosage Protocols

Dosing protocols for LL-37 vary based on the intended application and individual response. Based on available research and clinical practice patterns:

Starting dose: 50–100 mcg daily via subcutaneous injection

Maintenance dose: 100–200 mcg daily

Advanced protocols: Some practitioners utilize doses up to 300 mcg daily for acute immune challenges

Cycle duration: Typical protocols run 4–8 weeks, followed by a break period of equal length

Cycling guidelines: Due to the immunomodulatory nature of LL-37, cycling is generally recommended to prevent potential desensitization of immune pathways. A common approach is 4 weeks on, 4 weeks off, though some users employ 8-week cycles with 4-week breaks.

Clinical trials investigating wound healing used topical applications at concentrations of 0.5–1.6 mg/mL applied twice weekly, with the lower doses showing superior efficacy.

How to Use

LL-37 is most commonly administered via subcutaneous injection, though topical and oral formulations have been investigated in research settings.

Subcutaneous injection: The preferred method for systemic effects. Inject into fatty tissue areas such as the abdomen, thigh, or upper arm. Rotate injection sites to prevent tissue irritation.

Injection technique:

1. Clean the injection site with an alcohol swab
2. Pinch a fold of skin
3. Insert the needle at a 45-degree angle
4. Inject slowly and steadily
5. Remove needle and apply gentle pressure

Timing: Many users administer LL-37 in the morning on an empty stomach, though timing can be adjusted based on individual preference and response.

Topical application: For localized wound healing, LL-37 can be applied directly to affected areas. Research protocols have used twice-weekly applications.

Results Timeline

Individual responses to LL-37 vary, but general timelines based on user reports and research include:

Week 1–2: Initial immune system modulation may begin. Some users report improved energy and reduced frequency of minor infections.

Week 2–4: More noticeable effects on immune function and wound healing. Those using LL-37 for chronic wounds may observe accelerated healing.

Week 4–8: Full benefits typically manifest, including sustained immune support and completion of wound healing processes. Clinical trials demonstrated significant wound area reduction (50–68%) within 4 weeks of treatment.

Long-term: Continued cycling may provide ongoing immune support and maintenance of benefits.

Research Evidence

LL-37 has been extensively studied in both preclinical and clinical settings:

A randomized, placebo-controlled clinical trial involving 34 participants with venous leg ulcers demonstrated that topical LL-37 treatment was safe and effective. The 0.5 mg/mL dose group showed healing rates approximately six times higher than placebo, with mean ulcer area decreasing by 68%.

Research published in the Journal of Medical Virology evaluated oral LL-37 against viral infections, finding that early initiation of treatment was a critical factor for clinical outcomes.

Studies have demonstrated LL-37's effectiveness against both extra- and intracellular bacterial infections, with activity comparable to conventional antibiotics in certain contexts.

A clinical trial (NCT02225366) has investigated intratumoral injections of LL-37 for melanoma, exploring its potential anticancer applications.

Research on gut health indicates that LL-37 helps maintain intestinal homeostasis and augments intestinal wound healing and barrier function.

Stacking

LL-37 is sometimes combined with other peptides to enhance overall effects:

Thymosin Alpha-1: Both peptides support immune function through complementary mechanisms. This combination may provide enhanced immune modulation.

BPC-157: For wound healing and tissue repair, combining LL-37's antimicrobial and healing properties with BPC-157's regenerative effects may offer synergistic benefits.

Thymosin Beta-4 (TB-500): Another tissue repair peptide that may complement LL-37's wound healing properties.

When stacking, it is advisable to start with lower doses of each compound and monitor response carefully before adjusting.

Reconstitution & Storage

Reconstitution:
LL-37 typically comes as a lyophilized (freeze-dried) powder requiring reconstitution before use.

1. Use bacteriostatic water (BAC water) for reconstitution—this contains 0.9% benzyl alcohol, which helps preserve the solution
2. For a 5 mg vial, add 2.5 mL of bacteriostatic water to achieve a concentration of 2 mg/mL
3. Direct the water stream against the vial wall, not directly onto the powder
4. Gently swirl—do not shake vigorously—to dissolve
5. Allow 15–30 minutes for complete dissolution

Storage:

• Lyophilized (unreconstituted) powder: Store frozen or refrigerated; stable for extended periods
• Reconstituted solution: Refrigerate at 2–8°C (36–46°F)
• Reconstituted peptides remain stable for approximately 4 weeks when properly refrigerated
• Avoid repeated freeze-thaw cycles
• Protect from light
• Do not use if solution appears cloudy or contains particles

Side Effects

LL-37 has demonstrated a favorable safety profile in clinical trials, though potential side effects should be considered:

Common/mild:

• Injection site reactions (redness, swelling, mild pain)
• Temporary skin irritation with topical use

Potential concerns from research:

• At higher concentrations, LL-37 may exhibit cytotoxicity to human cells at levels similar to those required for antimicrobial activity
• Long-term or excessive administration has been associated with skin changes including erythema (redness) and telangiectasia in animal studies
• Nonclinical research suggests potential effects on male fertility, though human data is limited
• May interact with heparin and potentially influence coagulation

The clinical trial on venous leg ulcers reported no safety concerns regarding local or systemic adverse events at therapeutic doses.

Legal Status & FDA

LL-37 is not FDA-approved for human therapeutic use. The FDA has categorized LL-37 (cathelicidin LL-37) as a "Category 2" bulk drug substance, indicating that the agency lacks sufficient safety-related information to determine whether the drug would cause harm when administered to humans.

This classification means that compounding pharmacies face restrictions on producing LL-37 for human use under Section 503A of the Federal Food, Drug, and Cosmetic Act.

LL-37 remains available for research purposes and may be obtained through certain channels, but it is not commercially available as an approved medication. Clinical trials continue to investigate its therapeutic potential.

Sports & WADA Status

LL-37 is not specifically named on the World Anti-Doping Agency (WADA) Prohibited List. However, athletes should exercise caution. WADA's prohibited list includes broad categories of peptide hormones and growth factors, and the list explicitly states that it includes substances "not limited to" those specifically named.

While LL-37's primary functions are antimicrobial and immunomodulatory rather than performance-enhancing in the traditional sense, its wound-healing and recovery-promoting properties could theoretically fall under scrutiny. Athletes subject to anti-doping regulations should consult with their governing bodies and anti-doping authorities before using any peptide.

Conclusion

LL-37 represents a fascinating intersection of natural human biology and therapeutic potential. As the only human cathelicidin, it plays essential roles in innate immunity, wound healing, and inflammation regulation. Clinical research has demonstrated its safety and efficacy in specific applications, particularly wound healing, while ongoing studies continue to explore its broader therapeutic potential.

For those choosing to use LL-37, understanding proper dosing, administration, and storage is essential for maximizing benefits while minimizing risks. As with any non-approved compound, users should approach with appropriate caution, ideally under medical supervision, and stay informed about evolving research and regulatory developments.

FAQ

What is LL-37 used for?
LL-37 is primarily used for immune support, wound healing acceleration, antimicrobial defense, and anti-inflammatory effects. It has been studied for treating chronic wounds, infections, and potentially cancer.

How long does it take for LL-37 to work?
Initial effects may be noticed within 1–2 weeks, with more significant benefits typically appearing by weeks 4–8. Wound healing studies showed substantial improvement within 4 weeks of treatment.

Is LL-37 safe?
Clinical trials have demonstrated that LL-37 is safe and well-tolerated at therapeutic doses, with no significant local or systemic adverse events reported. However, long-term safety data in humans is limited.

Can LL-37 be taken orally?
While most protocols use subcutaneous injection, oral LL-37 has been investigated in research settings. Oral administration may have different bioavailability and efficacy compared to injection.

How should LL-37 be stored after reconstitution?
Reconstituted LL-37 should be refrigerated at 2–8°C (36–46°F) and used within approximately 4 weeks. Avoid repeated freeze-thaw cycles and protect from light.

Does LL-37 require a prescription?
LL-37 is not FDA-approved and is not available as a prescription medication in the United States. It may be obtained through research chemical suppliers or certain compounding pharmacies where permitted.

Can LL-37 be combined with other peptides?
Yes, LL-37 is sometimes stacked with other peptides such as Thymosin Alpha-1, BPC-157, or TB-500 for complementary effects. Start with lower doses when combining compounds.

Is LL-37 banned in sports?
LL-37 is not specifically named on the WADA Prohibited List, but athletes should consult with anti-doping authorities before use, as peptides may fall under broader prohibited categories.

References

1. 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. https://pubmed.ncbi.nlm.nih.gov/25041740/
2. Dürr UH, et al. "LL-37, the only human member of the cathelicidin family of antimicrobial peptides." Biochimica et Biophysica Acta. 2006. https://www.sciencedirect.com/science/article/pii/S000527360600126X
3. Vandamme D, et al. "A comprehensive summary of LL-37, the factotum human cathelicidin peptide." Cellular Immunology. 2012. https://pmc.ncbi.nlm.nih.gov/articles/PMC1497871/
4. Xhindoli D, et al. "The human cathelicidin LL-37 — A pore-forming antibacterial peptide and host-cell modulator." Biochimica et Biophysica Acta. 2016. https://iubmb.onlinelibrary.wiley.com/doi/10.1002/biof.1225
5. "Antimicrobial Peptides of the Cathelicidin Family: Focus on LL-37." MDPI International Journal of Molecular Sciences. 2025. https://www.mdpi.com/1422-0067/26/16/8103
6. Barańska-Rybak W, et al. "Activities of LL-37, a Cathelin-Associated Antimicrobial Peptide." Antimicrobial Agents and Chemotherapy. 1998. https://journals.asm.org/doi/10.1128/aac.42.9.2206
7. "Cationic Antimicrobial Peptide LL-37 Is Effective against both Extra- and Intracellular Staphylococcus aureus." Antimicrobial Agents and Chemotherapy. 2012. https://journals.asm.org/doi/10.1128/aac.01650-12
8. ClinicalTrials.gov. "Intratumoral Injections of LL37 for Melanoma." NCT02225366. https://clinicaltrials.gov/study/NCT02225366
9. FDA. "Certain Bulk Drug Substances for Use in Compounding May Present Significant Safety Risks." https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
10. WADA. "The Prohibited List." https://www.wada-ama.org/en/prohibited-list
11. Fabisiak A, et al. "LL-37: Cathelicidin-related antimicrobial peptide with pleiotropic activity." Pharmacological Reports. 2016. https://link.springer.com/article/10.1007/s43440-020-00190-3
12. "Long-Term Administration of LL-37 Can Induce Irreversible Rosacea-Like Skin Lesions." Current Issues in Molecular Biology. 2023. https://www.mdpi.com/1467-3045/45/4/177