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LL-37 vs thymosin alpha-1

Last updated: October 3, 2026 · 5 min read · By the Grey Peptides Editorial Board

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Grey Peptides
Grey Peptides Editorial Board
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Key takeaways
  • Thymosin alpha-1 is an approved drug in more than 35 countries, though not in the US, with randomised trials in hepatitis and a large sepsis trial that found no survival benefit.
  • LL-37 is the body's own antimicrobial peptide. It has been tested only as a topical treatment for leg and foot ulcers, and its larger leg-ulcer trial missed its main goal.
  • Neither has been shown to 'boost immunity' in healthy people, and injectable LL-37 is due before an FDA committee by February 2027.

Side by side

LL-37 Low and thymosin alpha-1 High sit at opposite ends of our evidence scale. The table is read from our encyclopedia entries.

FieldLL-37Thymosin α1
Encyclopedia entryLL-37 Full entryThymosin α1 Full entry
Molecule classPeptidePeptide
CategoryHealing & RecoveryImmune
FDA statusResearch ChemicalNot FDA Approved
Approved elsewhereNone recorded~35 countries, not the US
Evidence gradeLowHigh
Half-lifeUndetermined≈ 2 hours
FormulaC205H340N60O53C129H215N33O55
Molecular weight4,493.3 g/mol3,108.3 g/mol
WADA 2026Prohibited (S0 catch-all)Unsettled (S0 may apply)
WADA 2027Prohibited (S0 catch-all)Unsettled (S0 may apply)
In one lineThe only human cathelicidin — an antimicrobial peptide with direct activity against bacteria, fungi, viruses, and biofilms, with additional roles in wound healing and immune signaling.A thymic peptide approved as Zadaxin in about 35 countries; its hepatitis trials were mixed, and its largest trial, in 1,106 sepsis patients, found no effect on death.
MechanismDirect antimicrobial activity via membrane disruption of gram-positive and gram-negative bacteria, fungi, and enveloped viruses. Modulates macrophage polarization, neutralizes LPS, promotes keratinocyte migration, and stimulates angiogenesis via FPRL1 receptor activation. Abnormally elevated in rosacea and some psoriasis phenotypes (pathogenic at high local concentrations).Modulates both innate and adaptive immunity. Activates TLR2 and TLR9 on dendritic cells and monocytes, driving NF-κB activation and production of IL-12, TNF-α, and IL-6. Promotes dendritic cell maturation, T-cell differentiation (particularly Th1), and enhances NK cell cytotoxicity. Restores immune function in immunocompromised states (hepatitis B/C, sepsis, post-chemotherapy) and enhances vaccine responses in elderly and hemodialysis populations.
Sources in the entry1117
Study cards1115
Dosage pageNoneDosage page

What each is

Thymosin alpha-1 is a 28-amino-acid peptide first isolated from the thymus, the gland where T cells mature. Made synthetically as thymalfasin and sold as Zadaxin, it is approved in more than 35 countries, including Italy and China, for chronic hepatitis B and other uses; it is not approved in the US, where it has orphan drug designations 1.

LL-37 is the active form of human cathelicidin, a 37-amino-acid antimicrobial peptide made by skin, gut, urinary tract and immune cells. It kills bacteria directly and signals to the immune system; cells lining the urinary tract release it on contact with bacteria 2. It is not approved anywhere 1.

Thymosin alpha-1's evidence

Thymosin alpha-1 has been tested in randomised trials for decades. In chronic hepatitis B, 98 patients given it for 26 weeks had a complete virological response at 18 months of 40.6%, against 9.4% untreated 3, and added to interferon it increased loss of a key viral marker at 72 weeks (45.8% against 28.0%) 4. In hepatitis C, it improved biochemical response when added to interferon 5.

The largest trial was negative. In 2025, a trial across 22 Chinese centres randomised 1,106 adults with sepsis to thymosin alpha-1 or placebo for seven days; 28-day mortality was 23.4% against 24.1%, no meaningful difference 6. Smaller studies in COVID-19 and HIV found no significant benefit on their main measures 7 8. One trial in haemodialysis patients found better antibody responses to an H1N1 vaccine when thymosin alpha-1 was added 9.

LL-37's evidence

LL-37's human trials are topical. In a small double-blind study of 34 people with hard-to-heal venous leg ulcers, the two lower doses of topical LL-37 healed ulcers faster than placebo 10. The larger follow-up, HEAL LL-37, randomised 148 patients, and across the full population LL-37 did not meet its primary endpoint 11. A trial in mildly infected diabetic foot ulcers in Jakarta found improved granulation with an LL-37 cream 12, and a recombinant bacterium delivering LL-37 by mouth was tested in 238 adults hospitalised with COVID-19 13.

LL-37 also has a darker side in research: excess, abnormally processed cathelicidin is implicated in rosacea 14, and in breast cancer tissue its precursor tracked markers of aggressive disease and LL-37 amplified growth signalling 15. An antimicrobial peptide is not automatically safe to inject.

Regulatory and sport status

Neither is FDA-approved. Injectable LL-37 is one of the five peptides FDA plans to take to a second Pharmacy Compounding Advisory Committee meeting before the end of February 2027; our article on the second PCAC five covers it. Thymosin alpha-1 nominations for compounding were withdrawn, so it cannot be compounded in the US either 1. Check our WADA status page for the sport status of each.

'Immune boosting' claims

Both peptides are marketed online to 'boost immunity' in healthy people. Neither has been tested for that. Thymosin alpha-1's trials are in people with specific diseases, mostly chronic hepatitis, and its largest trial, in sepsis, was negative 6. LL-37's trials are topical treatments for chronic wounds 11. Stimulating the immune system is not a free benefit; it can worsen autoimmune and inflammatory conditions.

How the differences add up (as of October 3, 2026)

Thymosin alpha-1 is a real drug abroad, with positive hepatitis trials and a clearly negative sepsis trial, and no US approval. LL-37 is an endogenous antimicrobial peptide with small topical wound trials, one of which missed its main goal, and unresolved safety questions for injection. If you are considering either, the questions are what condition it is for, what the trials in that condition show, and where the product comes from.

Frequently asked questions

Is thymosin alpha-1 FDA-approved?

No. It is approved as Zadaxin (thymalfasin) in more than 35 countries for chronic hepatitis B and other uses, but not in the US.

Does LL-37 work?

It has been tested as a topical treatment for chronic ulcers. A small trial was positive, but the larger 148-patient trial missed its primary endpoint. It has not been tested as an injection.

Which is better for immunity?

Neither has been tested for boosting immunity in healthy people. Thymosin alpha-1's largest trial, in 1,106 people with sepsis, found no survival benefit.

Sources

  1. Grey Peptides dataset records for LL-37 and thymosin alpha-1 (approval and status text, WADA status, half-life and studied doses as sourced on each entry); read October 3, 2026.
  2. Chromek, M., et al. (2006). The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med, 12(6), 636-41. PMID: 16751768
  3. Chien, R. N., et al. (1998). Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology, 27(5), 1383-7. PMID: 9581695
  4. Lim, S. G., et al. (2006). A randomized, placebo-controlled trial of thymosin-alpha1 and lymphoblastoid interferon for HBeAg-positive chronic hepatitis B. Antivir Ther, 11(2), 245-53. PMID: 16640105
  5. Sherman, K. E., et al. (1998). Combination therapy with thymosin alpha1 and interferon for the treatment of chronic hepatitis C infection: a randomized, placebo-controlled double-blind trial. Hepatology, 27(4), 1128-35. PMID: 9537454
  6. Wu, J., et al. (2025). The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ, 388, e082583. PMID: 39814420
  7. Shehadeh, F., et al. (2023). A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection. J Infect Dis, 227(2), 226-235. PMID: 36056913
  8. Chen, C., et al. (2024). Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV. BMC Infect Dis, 24(1), 97. PMID: 38233816
  9. Carraro, G., et al. (2012). Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study. Vaccine, 30(6), 1170-80. PMID: 22178096
  10. Grönberg, A., et al. (2014). 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, 22(5), 613-21. PMID: 25041740
  11. Mahlapuu, M., et al. (2021). Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial. Wound Repair Regen, 29(6), 938-950. PMID: 34687253
  12. Miranda, E., et al. (2023). Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial. Arch Dermatol Res, 315(9), 2623-2633. PMID: 37480520
  13. Zhao, Y., et al. (2023). 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, 95(8), e29035. PMID: 37605995
  14. Yamasaki, K., et al. (2007). Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med, 13(8), 975-80. PMID: 17676051
  15. Weber, G., et al. (2009). Human antimicrobial protein hCAP18/LL-37 promotes a metastatic phenotype in breast cancer. Breast Cancer Res, 11(1), R6. PMID: 19183447

Educational information, not medical advice. Each dose in this guide names its source, an approved label or a published study. 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.

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