LL-37 monograph

Overview

LL-37 is the 37-amino-acid active peptide cleaved from the human cathelicidin precursor hCAP-18. It is an innate immune effector with broad antimicrobial and immunomodulatory actions, but it is not an approved bodybuilding or performance drug. Human therapeutic use is not established; most of the practical literature is preclinical, and community use is anecdotal and not a reliable basis for dosing.[^1]

Pharmacokinetics & Mechanism

• Class: Endogenous host-defense peptide (cationic antimicrobial peptide; cathelicidin family)
• Mechanism of action: LL-37 is amphipathic and cationic, so it binds microbial membranes, disrupts membrane integrity, and can also modulate host immune signaling. It can neutralize bacterial products and influence chemotaxis, cytokine signaling, wound-healing biology, and antiviral/antibacterial defense pathways. Some literature also describes intracellular signaling effects after uptake, but the exact human receptor-level mechanism is not a single established target.
• Target(s): Not a single-drug receptor target. Reported biological interactions include microbial membranes; host immune pathways involving formyl peptide receptor 2 (FPR2/FPRL1) in chemotaxis-related effects; intracellular interactions reported with receptors such as GAPDH in monocytes; and modulation of TLR/NF-κB, MAPK, and inflammasome-linked inflammatory signaling. Evidence is context-dependent and not a validated clinical target map.
• Route(s) of administration: Not well established for human therapeutic use. In research and experimental settings, LL-37 has been studied as topical/local administration, wound/skin delivery systems, and other local formulations; systemic injection use is not clinically established. Community/vendor use is anecdotal and not a standardized route.
• Onset: Not well established in humans. Local antimicrobial effects are expected to be immediate to rapid after exposure in experimental systems, but no validated human onset window exists for coaching purposes.
• Half-life: Not well established in humans. LL-37 is rapidly degraded by proteases in biological fluids; one direct human-relevant example is cleavage by bacterial HtrA that abolishes activity, and general peptide instability suggests a short effective half-life. No reliable clinical half-life for LL-37 itself was found. Extended or DAC-like variants are not established clinical standards for LL-37.
• Metabolism / clearance: Cleared mainly by proteolytic degradation rather than a defined hepatic metabolic pathway. It can be inactivated by host and bacterial proteases; the Campylobacter HtrA paper shows direct cleavage at Ile20-Val21 eliminating activity. Formal human clearance kinetics are not well established.