WHAT IS LL-37

LL-37 is the only known cathelicidin antimicrobial peptide (AMP) expressed in humans. It is derived from a larger precursor protein called hCAP18.

LL-37 is a fundamental component of the body's innate immune system (the first line of defense) and plays a pivotal role in defense against bacterial, viral, and fungal infections.

Origin and Function

 LL-37 is produced naturally by various cell types in response to infection or tissue injury, including:

• Immune Cells: Such as neutrophils and macrophages.

• Epithelial Cells: Found in the skin, airways, and gastrointestinal tract.

• Bone Marrow-Derived Cells.

LL-37 acts as both a potent antimicrobial agent and a crucial signaling molecule that regulates inflammation, tissue repair, and the overall immune response. 

WHAT DOES LL-37 DO?

LL-37 is a powerful multi-functional molecule that addresses both infection and tissue repair. It exerts its effects through multiple physiological pathways, targeting both pathogen elimination and tissue regeneration. Its actions are versatile, meaning it can be effective whether used for skin wounds, gut health, or internal immune support.

Dual Mechanism: Infection Control and Regeneration

Direct Antimicrobial Action

Its primary defense mechanism relies on its cationic charge binding strongly to the negatively charged surface of bacterial membranes.

• Membrane Disruption: This binding allows the peptide to physically penetrate the membrane, form transmembrane pores, and cause cell lysis and death.

• Broad Spectrum: It is effective against a broad spectrum of pathogens, including Gram-positive and Gram-negative bacteria, fungi, and enveloped viruses.

Immune Modulation and Tissue Repair

LL-37 has complex, context-dependent effects on the immune system, acting as a crucial signaling molecule.

• Recruit Immune Cells: It acts as a chemoattractant, recruiting neutrophils, monocytes, and T cells to the site of infection via chemokine receptors.

• Neutralize Endotoxins: It binds to bacterial products (for example, LPS or endotoxin), inhibiting their ability to activate TLR4 receptors and preventing excessive systemic inflammation (sepsis models).

• Wound Healing and Angiogenesis: LL-37 actively promotes tissue repair by:

  • Angiogenesis: Inducing the proliferation and migration of endothelial cells and increasing VEGFA expression to accelerate blood vessel formation.

  • Epithelialization: Promoting the migration and proliferation of keratinocytes for re-epithelialization during wound closure.

BENEFITS/ CLINICAL TRIALS

Unlike performance peptides that focus on muscle growth or hormonal balance, LL-37 shines in areas of immune function, infection control, and tissue recovery. Its versatility makes it appealing for athletes, biohackers, and individuals with chronic inflammation or persistent injuries. LL-37 is a key target in the development of next-generation antibiotics and regenerative therapies. 

Antibacterial, Antiviral, and Antifungal Defense

LL-37 has potent, broad-spectrum antimicrobial effects.  It can neutralize a wide range of pathogens by disrupting their membranes.

• Broad-Spectrum Anti-Infective: Highly effective against antibiotic-resistant strains (for example, MRSA) and capable of disrupting bacterial biofilms, which are difficult to treat with conventional antibiotics.

• Targeted Action: It is active against Staphylococcus aureus, E. coli, Pseudomonas, Candida, and enveloped viruses like influenza and herpes.

• Applications: Useful in skin infections, wound healing, and respiratory tract infections. It may reduce the frequency and severity of cold and flu-like illnesses.

• "LL-37 demonstrates antimicrobial activity comparable to that of conventional antibiotics while exhibiting immunomodulatory properties."

Wound Healing and Tissue Regeneration

LL-37 promotes rapid healing by stimulating cell migration, collagen synthesis, and angiogenesis (new blood vessel formation).

• Tissue Repair: Promotes rapid healing of cuts, abrasions, ulcers, and burns. Topical application of LL-37 promotes re-epithelialization and vascularization in animal models of wounds, burns, and chronic ulcers. 

• Skin Applications: Useful for acne scars, diabetic ulcers, or post-surgical wounds. It may support dermatological recovery from eczema or psoriasis. 

•  Cell Function: Enhances fibroblast function and tissue strength in healing phases. 

   

   

  Immune Regulation and Gut Health

LL-37 plays a dual role in stimulating the immune system and reducing unnecessary inflammation.

• Gut Health: LL-37 is expressed in the gastrointestinal tract, where it defends against pathogenic bacteria and supports epithelial integrity. It may help in conditions like leaky gut, IBD, or chronic bloating.  It supports gut lining repair and mucosal immune defense, and is often stacked with BPC-157 for synergistic GI recovery. 

• Immune Priming: Balances immune responses without overstimulation, enhancing overall immune readiness, especially during periods of stress, travel, or illness. 

•  Anti-Sepsis/Anti-Endotoxin: Neutralizes inflammatory damage caused by bacterial products, offering potential in models of sepsis. 

   

   

  Clinical Context and Safety Challenges

•  Formal Clinical Trials: LL-37 has not received FDA approval as a peptide antibiotic or therapeutic agent.  Clinical research is limited but ongoing, primarily in early phases 

•  Melanoma Research: Clinical trials have investigated intratumoral injections of LL-37 for the treatment of metastatic melanoma to stimulate the immune system locally. 

• Autoimmune Context: The challenge for clinical translation is balancing its benefits against its potential for cytotoxicity at high concentrations.  In conditions like Psoriasis, LL-37 is often overexpressed and can contribute to pathology by forming complexes with host DNA, triggering chronic inflammation via TLR9.

SIDE EFFECTS

LL-37 is generally well-tolerated at appropriate concentrations, but its powerful immune-modulating capabilities can cause dose-dependent side effects, particularly if misused or over-dosed. Most issues are mild, but beginners should monitor closely.

Common and Transient Side Effects

• Injection Site Reactions: LL-37 is known to cause localized burning, redness, or swelling at the injection site. This is due to its cationic charge and interaction with local immune cells.

• Flu-like Symptoms/Systemic Inflammation: Because LL-37 stimulates cytokine release and immune cell recruitment, some users report low-grade fever, fatigue, or body aches, particularly during the first few days.

  • Management: Reduce dose to 100 mcg per day and ramp slowly. Stay hydrated and support recovery with ZMT and Krill oil. Avoid stacking with other immune-stimulating agents (like GH peptides) in the first week.

• Gut Disruption: Ironically, while LL-37 can help with gut healing, too much may lead to nausea, bloating, or loose stools, especially when fasted or if gut flora is imbalanced.

  • Management: Keep doses below or equal to 200 mcg per day. Stack with probiotics and glutamine-based recovery products like POST.

Critical Risks and Safety Cautions

• Overstimulation in Autoimmune Conditions: In individuals with autoimmune diseases (for example, lupus, Hashimoto's, RA), LL-37 may aggravate symptoms due to immune activation.

  • Management: Consult with a healthcare provider before use. Consider alternative peptides like BPC-157 or TB-500, which are more anti-inflammatory and less immunostimulatory. Monitor symptom flare-ups and cycle conservatively.

• Local Toxicity: At high concentrations, its membrane-disrupting mechanism can potentially damage mammalian cells (cytotoxicity), though cell membranes are generally protected by cholesterol.

• Inflammatory Risk: Due to its role as an endogenous immune signal, improper administration or chronic high levels could theoretically lead to dysregulated inflammation or trigger autoimmune responses in susceptible individuals.

• Antibiotic Resistance: Sub-inhibitory concentrations of LL-37 have been shown to induce resistance in certain bacteria in in vitro settings, posing a risk if used improperly for infection treatment.

IS LL-37 SAFE?

LL-37 is an unapproved research peptide. Like many research peptides, it is not FDA-approved for human use, but it is not a controlled substance either. It exists in a regulatory gray zone, where it can be legally purchased for research purposes only in the U.S. and in many other countries.

Safety and Regulatory Summary

• FDA Caution: The FDA has cautioned against the use of compounded drugs containing LL-37 due to safety risks and potential complications.

• Biological Intersection: LL-37 is a potent biological signaling molecule that sits at the intersection of antimicrobial defense and autoimmune disease.

• Safety Takeaway: Due to its powerful and complex biological effects, its administration must be strictly confined to controlled research settings.

DOSAGE

Dosing protocols for LL-37 are non-standardized and highly varied, dependent on the research model and targeted effect (for EXAMPLE: topical vs. systemic vs. intratumoral). LL-37 is typically used in short cycles due to its immune-stimulating effects and potential for irritation at high doses.

Administration Methods

• Subcutaneous (SubQ): Typically administered via SubQ injection for systemic effects (immune support, gut health).

• Topical: Applied as a cream or gel for skin and wound research.

• Intratumoral: Used in oncology research.

Empirical Dosing Guidelines (SubQ)

Dosing depends on the goal—whether it's immune support, skin healing, or gut repair—but beginners should always start conservatively.

• Typical Beginner Dosage: 100–200 mcg per day, administered via subcutaneous injection.

• Frequency: Once daily, 5 days per week.

• Cycle Length: 2–4 weeks, followed by at least 2 weeks off.

• Advanced Dosing: Advanced protocols may go up to 500 mcg per day, but this is not recommended for first-time users due to potential side effects like injection site irritation or systemic immune overstimulation.

• Concentration Note: Effective antimicrobial and immunomodulatory activities are often observed in the nanomolar (nM) to micromolar (µM) concentration range. High doses are generally associated with toxicity risk.

RECONSTITUTION

LL-37 is supplied as a lyophilized (freeze-dried) powder. Proper technique is essential during reconstitution to prevent degradation and maintain the peptide's effectiveness.

Reconstitution Procedure

1. Prepare the Vials

Remove the plastic caps from both the peptide vial and the bacteriostatic water vial. Wipe the exposed rubber stoppers with a fresh alcohol pad to sterilize them.

2. Draw and Inject the Water

Use the mixing syringe to withdraw the desired volume of bacteriostatic water (BAC Water). A common volume for a 5 mg vial is 1 mL, which yields a highly concentrated solution of 5 mg/mL (5,000 mcg/mL). Gently inject the water into the vial containing the LL-37 peptide powder. Aim the water towards the side of the glass wall, not directly onto the powder, to ensure a slow, controlled flow.

3. Dissolve the Peptide 

After adding the water, remove the syringe. Do not shake the vial vigorously, as this can degrade the peptide. Instead, gently swirl or roll the vial between your hands for a few minutes until all the powder is completely dissolved into a clear solution.

Storage and Stability

• Storage Location: Once reconstituted, the solution must be stored in the refrigerator (2°C to 8°C) and kept away from light.

• Stability: The reconstituted peptide is subject to proteolytic degradation (breakdown by enzymes). It is typically stable for approximately 6 weeks under proper refrigeration, but usage within a shorter timeframe is always ideal.

WHERE TO BUY LL-37

Researchers should always vet their sources to ensure that a few key factors are present in their test subjects. With the rise in peptide popularity in recent years, many companies have created peptides that undergo little to no testing, quality standards, or regulations. As it is not regulated by the FDA, researchers must do their due diligence and look closely at the company's practices and standards. 

When selecting a supplier for LL-37, focus on transparency and quality assurance, not customer testimonials:

1. Quality Documentation: A reputable supplier must provide:
   •  Certificate of Analysis (COA): This document must be recent (corresponding to the batch/lot number purchased) and demonstrate a minimum purity of >95% via High-Performance Liquid Chromatography (HPLC) testing.
   • Mass Spectrometry (MS) Data: The COA must include mass spectrometry (MS) confirmation to verify the compound’s exact molecular weight, confirming its chemical identity.
   • Contaminant Testing: Look for reports on heavy metals, microbial load, and solvent residues (e.g., residual trifluoroacetic acid, or TFA). The presence of these contaminants can severely compromise research and introduce unknown toxicity.
2. Vendor Verification and Transparency 

   • Specialization: Prioritize vendors who specialize in the manufacturing and distribution of peptides for academic and biotechnology research, rather than general supplement vendors.

   • Manufacturing Origin: Inquire about the source of the raw materials and the manufacturing protocols. Ideal suppliers adhere to strict quality control processes.

   • Handling & Storage: The supplier must provide clear documentation on the proper storage and handling procedures for the peptide to maintain its stability and integrity.

Conclusion on Procurement: Given the high risk of contamination, mislabeling, and legal ambiguity. The use of LL-37 outside of this defined research context poses unacceptable, unquantified risks to human health.

REFERENCES

• LL-37 Patient Information.Docx, happyhormonesmd.com/wp-content/uploads/2024/12/LL-37-Patient-Information.docx.pdf. Accessed 22 Nov. 2025. 
• by, Written. “LL‑37 for Beginners: Healing, Immunity, and Dosing Guide.” Swolverine, swolverine.com/blogs/blog/ll-37-for-beginners-the-antimicrobial-peptide-with-healing-potential#:~:text=July%2022%2C%202025-,LL%E2%80%9137%20For%20Beginners:%20The%20Antimicrobial%20Peptide%20with%20Healing%20Potential,in%20gut%20and%20tissue%20healing. Accessed 22 Nov. 2025. 
• “LL-37.” National Center for Biotechnology Information. PubChem Compound Database, U.S. National Library of Medicine, pubchem.ncbi.nlm.nih.gov/compound/ll-37. Accessed 22 Nov. 2025.

• The Journal of Immunology (PubMed ID 19166322). "Structure-function $\text{Relationship}$ of the $\text{Human}$ $\text{Antimicrobial}$ $\text{Peptide}$ $\text{LL-}37$ and $\text{LL-}37$ $\text{Fragments}$ in the $\text{Modulation}$ of $\text{TLR}$ $\text{Responses}$."

• MDPI (ID 2218-273X/14/3/320). "$\text{LL-}37$: $\text{Structures}$, $\text{Antimicrobial}$ $\text{Activity}$, $\text{and}$ $\text{Influence}$ $\text{on}$ $\text{Amyloid-Related}$ $\text{Diseases}$."

• Frontiers in Pharmacology (ID 10.3389/fphar.2025.1587351). "$\text{LL-}37$ promotes angiogenesis: a potential therapeutic strategy for lower limb ischemic diseases."

• ResearchGate (ID 344279264). "Immunomodulatory Role of the $\text{Antimicrobial}$ $\text{LL-}37$ $\text{Peptide}$ in $\text{Autoimmune}$ $\text{Diseases}$ and $\text{Viral}$ $\text{Infections}$."

• UCLA Newsroom. "$\text{UCLA-led}$ $\text{study}$ $\text{could}$ $\text{point}$ to $\text{ways}$ $\text{to}$ $\text{better}$ $\text{control}$ $\text{inflammation}$ $\text{in}$ $\text{autoimmune}$ $\text{diseases}$."

• Revolution Health. "$\text{LL-}37$ $\text{Peptide}$: $\text{Immunity}$, $\text{Antimicrobial}$ $\text{Defense}$ $\&$ $\text{Inflammation}$ $\text{Support}$."