Thymosin α-1
Thymosin alpha-1 is a 28-amino-acid thymic peptide with immune-modulating properties, marketed as Zadaxin (thymalfasin) and approved as a prescription drug in roughly 35 countries for chronic hepatitis B/C and immune deficiency; it has been studied in human trials for sepsis, COVID-19, and vaccine adjuvant use, with mixed results and no US FDA approval.
Thymosin α-1 reconstitution calculator
Open full calculator →Typical dosing
| Goal | Range | Route | Frequency |
|---|---|---|---|
| Chronic hepatitis B (Zadaxin label — approved in ~35 countries, not the US) | 1.6 mg (900 mcg/m2); 40 mcg/kg if under 40 kg | SubQ (never IV) | 2x weekly for 6-12 months, as monotherapy or with interferon |
| Chronic hepatitis C (Zadaxin label) | 1.6 mg (900 mcg/m2); 40 mcg/kg if under 40 kg | SubQ | 2x weekly for 12 months, in combination with interferon only |
| Severe sepsis (ETASS trial regimen) | 1.6 mg | SubQ | 2x daily for 5 consecutive days, then 1x daily for 2 days |
| Sepsis (TESTS phase 3, 2025 — found no 28-day mortality benefit) | Per-dose amount not stated in the published abstract | SubQ | Every 12 hours for up to 7 days |
| Reconstitution and US status | Reconstitute with 1.0 mL of the supplied diluent immediately before use | SubQ | No FDA-approved dose exists — all of the above are non-US labels or trial protocols |
Ranges compiled from research literature — not a prescription.
How it works
Thymosin alpha-1 is a synthetic version of a peptide originally isolated from thymic tissue (thymosin fraction 5). It does not act as a direct antimicrobial or antiviral agent; instead it functions as an immune modulator. Research shows it binds Toll-like receptors (TLR2, TLR9, and others) on dendritic cells and macrophages, triggering NF-κB and MAPK signaling that drives dendritic cell maturation — upregulating MHC class I/II and costimulatory molecules (CD80, CD86) — and shifting T-cell differentiation toward Th1/cytotoxic phenotypes while also supporting regulatory T-cell balance.
Clinically, this mechanism underlies its longest-standing use: as Zadaxin, an adjuvant therapy for chronic hepatitis B and C, approved in roughly 35 countries but never by the US FDA. Multiple randomized controlled trials, including a phase III multicentre placebo-controlled study and earlier dose-ranging trials in chronic hepatitis B, reported higher rates of viral DNA clearance and ALT normalization versus control, though effect sizes were modest and inconsistent across populations and study designs.
More recent research has tested thymosin alpha-1 as an adjunct in sepsis and COVID-19, conditions marked by immune dysregulation. Earlier trials and meta-analyses (including the ETASS trial) suggested a mortality benefit in sepsis, but the largest and most rigorous trial to date — TESTS, a multicentre phase 3 RCT of 1,106 adults published in 2025 — found no clear reduction in 28-day mortality, a reminder that early promising signals in smaller trials do not always hold up. COVID-19 studies showed a similar pattern: several cohort studies and smaller RCTs reported improved lymphocyte recovery or reduced mortality in moderate-to-severe patients, but a 2022 systematic review noted substantial variability in study quality and outcomes.
Taken together, thymosin alpha-1 has more extensive human clinical trial data than most investigational peptides, largely because of its decades of international use as Zadaxin. But that same body of evidence is mixed and context-dependent — strong in some hepatitis B/C and sepsis subgroups, inconclusive in others — and it remains unapproved by the FDA for any indication in the United States.
Side effects & safety
- Generally well tolerated in clinical trials; the most common adverse effects reported are mild injection-site reactions such as redness or swelling.
- As an immune-modulating agent, it may theoretically interact with autoimmune conditions or immunosuppressive/immunostimulant medications — clinical supervision is advised.
- Not FDA-approved in the US for any indication; approved as Zadaxin (prescription) in about 35 countries for specific, medically supervised uses.
- Most long-term human safety data comes from patients with hepatitis B/C, sepsis, or cancer under clinical monitoring, not from healthy populations using it outside medical care.
- Sourcing and purity vary widely outside regulated pharmaceutical supply chains; unregulated or research-labeled material carries contamination and dosing-accuracy risks.
- Anyone considering use should consult a licensed clinician first, especially if pregnant, breastfeeding, immunocompromised, or taking other immune-active therapies.
Research
Primary sources — PubMed.
- The efficacy and safety of thymosin α1 for sepsis (TESTS): phase 3 RCT. 2025. https://pubmed.ncbi.nlm.nih.gov/39814420/
- Wu J, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS). Crit Care. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056079/
- Efficacy of thymosin α1 as immunomodulatory treatment for sepsis: systematic review of RCTs. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC5025565/
- Thymosin alpha 1 use in adult COVID-19 patients: systematic review and meta-analysis. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC9754924/
- Andreone P, et al. Thymosin alpha 1 in chronic hepatitis B: phase III multicentre RCT. J Viral Hepat. https://pubmed.ncbi.nlm.nih.gov/10607256/
- Romani L, et al. Thymosin alpha 1 activates dendritic cell TLR-mediated regulatory pathways. Blood. https://pubmed.ncbi.nlm.nih.gov/16741252/