Section 01
What it's used for
Approved for hepatitis B, not C
Thymosin alpha-1 (Zadaxin) is approved in several countries for hepatitis B; with interferon, trials show significantly better response rates than interferon alone. For hepatitis C, a trial in prior non-responders found no added benefit.
▸Clinical wording
Thymosin alpha-1 (Zadaxin) is approved in multiple countries for chronic hepatitis B, and human trials combining it with interferon show significantly higher virological, biochemical, and complete response rates than interferon alone. For chronic hepatitis C, however, a clinical trial in patients who had not responded to prior interferon/ribavirin therapy found that adding thymosin alpha-1 provided no significant adjuvant benefit.
Survival benefit varies by cancer
Added to standard cancer treatment, thymosin alpha-1 showed improved survival in liver and lung cancer trials, but the largest trial in metastatic melanoma missed statistical significance. In breast cancer, evidence is just one case report.
▸Clinical wording
Thymosin alpha-1 is used as an immune adjuvant alongside chemotherapy, radiation, and checkpoint inhibitor therapy. Clinical trials in hepatocellular carcinoma and non-small cell lung cancer report improved survival when it is added to standard treatment, but the largest randomized trial in metastatic melanoma did not reach statistical significance for a survival benefit. Evidence in breast cancer is limited to a single case report rather than clinical-trial data, so an improved-survival effect does not hold uniformly across all of these cancers.
Approved to boost vaccine response
Thymosin alpha-1 is approved in several countries as a vaccine booster, strengthening response to flu, hepatitis B and other vaccines. It appears especially useful in elderly and immune-weakened people, who often respond poorly to vaccines.
▸Clinical wording
Tα1 is approved in several countries as a vaccine adjuvant, enhancing immune response to influenza, hepatitis B, and other vaccines. It is particularly effective in elderly and immunocompromised populations who normally have suboptimal vaccine responses.
Does not raise CD4 counts directly
In HIV patients whose immune systems weren't recovering, a trial found thymosin alpha-1 did not significantly raise CD4+ counts at 24 weeks, though CD4+ percentage and immune markers did improve. It remains investigational, not proven.
▸Clinical wording
Thymosin alpha-1 has been studied for immune restoration in HIV/AIDS, post-chemotherapy immunosuppression, transplant recipients, and age-related immunosenescence. In a clinical trial in HIV immunological nonresponders, it did not significantly change absolute CD4+ cell counts at 24 weeks, though CD4+ percentage and markers of thymic output and T-cell exhaustion did improve. It is best described as an investigational immune-restorative agent rather than a treatment proven to raise CD4+ counts.
A large 2025 trial found no benefit
An earlier, smaller trial called ETASS (2013) hinted at a survival benefit in severe sepsis. But the larger, definitive TESTS trial (2025, 1106 patients) found no significant difference in 28-day deaths: 23.4% vs 24.1% (HR 0.99, P=.93).
▸Clinical wording
Thymosin alpha-1 has been studied in severe sepsis for its potential to restore immune function and prevent immunoparalysis. An earlier, smaller randomized trial (ETASS, 2013) suggested a mortality benefit, but the larger, definitive phase 3 randomized controlled trial (TESTS, n=1106, 2025) found no significant difference in 28-day mortality between thymosin alpha-1 and placebo (23.4% vs 24.1% deaths, HR 0.99, P=.93).
Used in Chinese COVID protocols
During the COVID-19 pandemic, thymosin alpha-1 was included in Chinese treatment protocols. Observational studies, not controlled trials, suggested better immune recovery and lower mortality in critically ill patients with low lymphocytes.
▸Clinical wording
During the COVID-19 pandemic, Tα1 was used in Chinese treatment protocols based on its immunomodulatory properties. Observational studies suggested improved immune reconstitution and reduced mortality in critically ill patients with lymphopenia.
Section 02
Mechanism of Action
Waking up the immune system's scouts
- It acts on sentinel cells through a receptor that senses microbial DNA (TLR9).
- Those cells mature, display captured targets better and prime T cells that have never met an antigen.
- Matured scouts make more IL-12 and interferons, tilting responses toward cell-mediated defence.
▸Clinical wording
Dendritic Cell Maturation
Tα1 acts on dendritic cells (DCs) through toll-like receptor 9 (TLR9) and intracellular signaling through MyD88 and IRF7. This promotes DC maturation, enhancing antigen presentation and the ability to prime naive T-cells. Mature DCs produce increased IL-12 and type I interferons, shifting immune responses toward Th1 (cell-mediated) dominance.
Maturing T cells and restoring their work
- Immature thymus cells are pushed toward mature helper and killer T cells.
- It raises T-cell receptor levels and the cells' proliferative response to antigens.
- It is reported to restore T-cell function in immune-suppressed states and to favour the cell-mediated arm.
▸Clinical wording
T-Cell Differentiation and Function
Tα1 promotes differentiation of immature T-cells (thymocytes) into mature, functional CD4+ helper T-cells and CD8+ cytotoxic T-cells. It upregulates T-cell receptor expression, enhances T-cell proliferative responses to antigens, and restores T-cell function in immunocompromised states. It also promotes Th1/Th2 balance by selectively enhancing Th1 responses.
Sharpening the body's cell-killing patrol
- It raises a targeting receptor (NKG2D) on natural killer cells.
- Those cells then make more of the proteins that puncture and dissolve target cells.
- This activity is described as contributing to anti-viral and anti-tumour surveillance.
▸Clinical wording
Natural Killer Cell Activation
Tα1 enhances NK cell cytotoxicity through upregulation of NKG2D receptor expression and increased production of perforin and granzymes. This enhanced NK activity contributes to anti-viral and anti-tumor immune surveillance.
Training the innate pattern detectors
- Beyond TLR9, it adjusts three further microbe-sensing receptors on immune cells.
- Better pattern recognition strengthens the fast, non-specific arm of immunity.
- The source calls it an "immune system trainer" that improves detection of diverse threats.
▸Clinical wording
Toll-Like Receptor Modulation
Beyond TLR9, Tα1 modulates TLR2, TLR3, and TLR4 signaling on immune cells, enhancing pathogen recognition and innate immune responses. It acts as an "immune system trainer," improving the ability of immune cells to detect and respond to diverse threats.
Shielding immune cells from chemical damage
- It raises three antioxidant enzymes inside immune cells.
- Those enzymes protect the cells from oxidative damage that blunts their function.
- This is described as mattering most in chronic infection and cancer, where immune cells become exhausted.
▸Clinical wording
Oxidative Stress Reduction in Immune Cells
Tα1 upregulates antioxidant enzyme expression (SOD, catalase, glutathione peroxidase) in immune cells, protecting them from oxidative damage that impairs function. This is particularly important in chronic infections and cancer, where oxidative stress contributes to immune exhaustion.
Section 03
Biological Pathways
- TLR9/MyD88/IRF7Tα1-TLR9 binding activates MyD88-dependent signaling, activating NF-κB and IRF7. NF-κB drives pro-inflammatory cytokines (TNF-α, IL-1β, IL-6); IRF7 induces type I interferons (IFN-α, IFN-β) for antiviral defense.
- JAK/STAT immune signalingCytokines induced by Tα1 (IL-12, IFN-γ) activate JAK/STAT in T-cells and NK cells. STAT1 and STAT4 drive Th1 differentiation and cytotoxic T-cell function, while STAT3 balances inflammatory responses.
- p38 MAPK stress responseTα1 activates p38 MAPK in immune cells, enhancing response to stress signals and pathogen-associated molecular patterns, and driving cytokine and chemokine expression that recruits immune cells to infection sites.
- IDO/tryptophan regulationTα1 modulates IDO expression in dendritic cells, balancing immune activation with tolerance, which may help prevent autoimmune reactions while maintaining anti-pathogen and anti-tumor responses.
Section 04
Dosage Information
Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Subcutaneous — approved label | Zadaxin label, chronic hepatitis B | 1.6 mg (900 µg/m²) twice a week for 6–12 months, alone or with interferon; 40 µg/kg under 40 kg — about 18–23 µg/kg at 70–90 kg. | Approved in over 35 countries, in none for immune support in healthy people; the FDA gave only orphan status. The label covers hepatitis B and cancer care. |
| Subcutaneous — sepsis trials | Two randomised trials in severe sepsis | 1.6 mg every 12 hours for 5 days, then daily for 2; phase 3 kept 1.6 mg every 12 hours for 7 days in 1,106 adults. | Seven times the weekly label amount. The double-blind phase 3 put 28-day deaths at 23.4% against 24.1% on placebo — it did not work in intensive care. |
| Subcutaneous — COVID-19 trials | Hospitalised COVID-19, trials 2020–2022 | 1.6 mg a day for 7 days when lymphocytes were low; a 105-patient phase 3 gave 1.6 mg twice a day, three times if severe, on days 1–7. | Small trials against a standard of care that kept changing, with mixed results; no NIH or WHO guideline lists the peptide. All of it is hospital dosing. |
| Subcutaneous — self-administration | Off-label immune support, outside any trial | The hepatitis B schedule reused unchanged: 1.6 mg twice a week, 3–4 days apart, for 12–16 weeks — about 18–23 µg/kg at 70–90 kg. | The number is borrowed, not derived: no trial has dosed thymosin alpha-1 in healthy adults for immunity, ageing or fatigue. Convenience, not evidence. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
- Protocol 01
Thymosin Alpha-1 Immune Protocol
Immune modulating peptide for chronic illness, immune deficiency, and infection recovery.
- Focus
- Immune Support
- Level
- Intermediate
- Duration
- Minimum 3 months
Section 06
Stability & Storage
Lyophilised powder
The commercial product (Zadaxin, 1.6 mg and 3.2 mg vials) is kept at 15–25 °C for up to 3 years. Research-grade powder is instead kept at −20 °C long-term.
After reconstitution
It is reconstituted with sterile water or bacteriostatic water; the resulting solution is stored at 2–8 °C and used within 14 days.
Section 07
Side Effects & Precautions
Thymosin alpha-1's safety record is based on controlled trials with over 4,400 patients, and consistently shows an adverse event rate similar to placebo, with no signal for autoimmune flare, liver toxicity, or drug interactions.
What Clinical Trials Show
Tα1 has one of the best-documented safety profiles among therapeutic peptides, with over 4,400 patients treated in controlled clinical trials. The overall adverse event rate is comparable to placebo across multiple studies.
Commonly Reported Reactions
- Injection site reactions: mild redness (erythema), pain, or hardening (induration) is the most common effect; transient and self-limiting.
- Flu-like symptoms: occasional mild fever, fatigue, or myalgia (muscle aches) can occur with the first few doses as immunity activates; usually resolve within 24 hours.
No Autoimmune Activation and No Liver Toxicity
- Despite strong immune enhancement, Tα1 has not been linked to autoimmune flares in trials; its mechanism strengthens immunity without hyperactivation.
- Tα1 has shown liver-protective properties and does not cause liver enzyme elevations, even in patients with pre-existing liver disease.
No Significant Drug Interactions
No clinically meaningful drug interactions have been identified. Tα1 is used safely in combination with interferons, antivirals, chemotherapy agents, and other immunomodulators.
Section 08
Regulatory Status
It has never received a general marketing approval from the FDA and has no centralized EU authorisation.
Approved markets
Zadaxin is registered in 35+ countries
National regulators in China, Italy, the Philippines and other countries across Asia, South America and Europe have approved thymalfasin, chiefly for chronic hepatitis B and as an adjunct to certain cancer treatments.
FDA / United States
Not approved as a drug
The FDA has never approved thymosin alpha-1 for any indication, though it holds Orphan Drug designation for hepatocellular carcinoma and DiGeorge anomaly; several INDs have been filed and US trials conducted, none leading to approval.
FDA compounding
No lawful compounding route
Thymosin alpha-1 was not on the 503A Bulks List as of 5 August 2026, and section 503A lets a pharmacy compound from a bulk substance only when it carries a USP/NF monograph, is a component of an approved drug or appears on that list. In late 2023 the FDA had assigned it to Category 2 of the interim bulk-substances list; reports of a later reclassification were not matched by any published list.
European Union
No centralized EMA approval
Thymosin alpha-1 has no EU-wide marketing authorisation; individual member states such as Italy authorise it on their own, so availability differs country to country within Europe.
WADA
Not on the Prohibited List
Thymosin alpha-1 is not named on WADA's Prohibited List. Where it is an approved medicine it is dispensed by prescription; in the United States it remains outside any approval.
Approval in one country does not carry over to another, and an announcement about a list is not the same as a published list. Regulatory status differs between jurisdictions and changes over time — check the current documents of your own regulator before relying on any of this.
Section 09
Research Studies
- [1]Modulation of human natural killer cell cytotoxic activity, lymphokine production, and interleukin 2 receptor expression by thymic hormonesSerrate SA, Schulof RS, Leondaridis L, et al. · The Journal of Immunology · 1987
- [2]Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through Toll-like receptor signalingRomani L, Bistoni F, Gaziano R, et al. · Blood · 2004
- [3]The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B: results from a randomized clinical trialIino S, Toyota J, Kumada H, et al. · Journal of Viral Hepatitis · 2005
- [4]Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and toleranceRomani L, Bistoni F, Perruccio K, et al. · Blood · 2006
- [5]Thymosin alpha1 activates the TLR9/MyD88/IRF7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivoBozza S, Gaziano R, Bonifazi P, et al. · International Immunology · 2007
- [6]Thymosin alpha1 and cancer: action on immune effector and tumor target cellsGaraci E, Pica F, Serafino A, et al. · Annals of the New York Academy of Sciences · 2012
- [7]Thymosin alpha1 based immunomodulatory therapy for sepsis: a systematic review and meta-analysisLi C, Bo L, Liu Q, Jin F. · International Journal of Infectious Diseases · 2015
- [8]Immune Modulation with Thymosin Alpha 1 TreatmentKing R, Tuthill C. · Vitamins and Hormones · 2016
- [9]Thymosin alpha-1, a natural peptide, inhibits cellular proliferation, cell migration and the level of reactive oxygen species and promotes the activity of antioxidant enzymes in human lung epithelial adenocarcinoma cell line (A549)Kharazmi-Khorassani J, Asoodeh A. · Environmental Toxicology · 2019
- [10]Thymosin alpha 1: A comprehensive review of the literatureDominari A, Hathaway D III, Pandav K, et al. · World Journal of Virology · 2020
Section 10
Frequently Asked Questions
It depends on the condition. For chronic hepatitis B, trials combining it with interferon show significantly better response rates than interferon alone, and it is approved for this in over 35 countries. For hepatitis C in prior non-responders it added no significant benefit, and the largest, most rigorous sepsis trial to date (TESTS, n=1,106) found no mortality difference versus placebo (23.4% vs 24.1% deaths) despite an earlier, smaller trial suggesting one.
This has not been measured outside specific disease trials. Hepatitis B trials ran 6 to 12 months before assessing response, and COVID-19 trials measured outcomes around day 7. There is no published timeline for how quickly it acts when used for general immune support, since that use has never been formally studied.
The approved hepatitis B schedule is 1.6 mg subcutaneously twice a week for 6 to 12 months. Sepsis and COVID-19 trials used far more frequent dosing, up to every 12 hours for several days. Off-label immune-support use typically borrows the hepatitis B schedule unchanged, though no trial has tested that regimen in healthy adults for immunity or fatigue.
Across more than 4,400 patients in controlled trials, its overall adverse event rate has been comparable to placebo. The most common effects are mild injection-site reactions and occasional flu-like symptoms — low fever, fatigue or muscle aches — mainly with the first few doses, and no autoimmune activation or liver toxicity has been reported.
It is approved as thymalfasin (Zadaxin) in over 35 countries, including China, India and South Korea, mainly for hepatitis B and as a cancer-therapy adjunct. It is not FDA-approved for any indication — only orphan-drug status for liver cancer and DiGeorge syndrome — and in the US it is sold as a research compound. It is not on the WADA prohibited list.
No, they are different peptides entirely. Thymosin alpha-1 is a 28-amino-acid immune-signaling peptide that acts on dendritic cells and T-cells; thymosin beta-4, the source of the fragment sold as TB-500, is a 43-amino-acid peptide that works mainly through actin binding in tissue repair. They share a thymus origin in name only.
It was used in Chinese treatment protocols during the pandemic, and observational studies reported improved immune reconstitution and lower mortality in critically ill patients with low lymphocyte counts. That evidence comes from observational reporting, not the kind of large randomized trial that gave a negative result for the same peptide in sepsis, so the COVID-19 signal has not been confirmed the same rigorous way.