Thymosin alpha-1
Also known as Thymalfasin, Tα1, Zadaxin, TA-1
Synthetic 28-amino-acid thymus peptide, registered in dozens of countries for chronic hepatitis B and C.
At a glance
- Category
- Immune & longevity
- Status
- approved drug
- Route
- subcutaneous
- Half-life
- approximately 2 hours in serum (human, subcutaneous)
- Onset
- immunological parameters within days; clinical effect in hepatitis only after months
- Molecular weight
- approximately 3108 g/mol
- Sequence
- Ac-SDAAVDTSSEITTKDLKEKKEVVEEAEN (N-terminally acetylated, 28 amino acids)
Registered as thymalfasin (brand name Zadaxin) in more than 35 countries for the treatment of hepatitis B and C and as an immune stimulant and adjuvant 7 — the countries commonly named include Italy, China, Singapore, Mexico and several other South-East Asian and Latin American markets, though PeptideX has not been able to open a regulator's own register confirming that country list, and it is reproduced here from a review rather than from a marketing authorisation. What is verifiable is the negative: it is not approved by the FDA and holds no central EMA marketing authorisation, so in the US and the EU it is an unapproved drug 7. The material sold online as a 'research peptide' falls outside any pharmaceutical registration.
Doping status: Not listed by WADA (unlike thymosin beta-4)
Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.
Mechanism of action
Thymosin alpha-1 is the acetylated N-terminal fragment of prothymosin alpha and is produced naturally by thymic epithelium. It promotes the differentiation and maturation of T lymphocytes and shifts the immune response towards a Th1 profile, with increases in interferon gamma and interleukin-2.
The main known receptor interaction runs via Toll-like receptor 9 (and to a lesser extent TLR2) on dendritic cells and monocytes, leading to maturation of dendritic cells and antigen presentation. Increased NK cell activity has also been described.
The effect is modulatory and context-dependent: with a suppressed immune system the response is amplified, whereas in sepsis models damping of excessive inflammation has been described. Why the agent would work in both directions has not been fully elucidated mechanistically.
What the research shows
Of all the agents in this category, thymosin alpha-1 has by far the strongest dossier: dozens of randomised trials, a registered indication in dozens of countries and decades of safety data. At the same time the evidence is not unambiguous — the largest placebo-controlled phase III trial in the US missed its primary endpoint 1, and the agent does not appear in the EASL or AASLD guidelines for hepatitis B. For the popular applications outside hepatitis (general 'immune support', ageing, chronic fatigue) there is hardly any controlled evidence.
Research in humans
Several randomised trials in chronic hepatitis B using 1.6 mg twice weekly for 6 months showed a higher sustained response than untreated controls, with effects that peaked only 6-12 months after stopping. A Japanese randomised trial reported around 36% ALT normalisation in the 1.6 mg group after 72 weeks 3. A US phase III trial (Mutchnick et al., 97 patients), however, found no statistically significant advantage over placebo (14% versus 4% complete response) and the authors explicitly concluded that their results did not confirm earlier positive findings 1. Combination studies with lamivudine and with peginterferon showed better HBeAg seroconversion than monotherapy in meta-analyses 5. The agent has further been studied as a vaccine adjuvant in dialysis patients and older people, and during COVID-19 in observational and small randomised studies with mixed outcomes.
Animal and lab research
Animal models consistently show restoration of T cell counts after thymectomy, chemotherapy or irradiation, and a survival benefit in sepsis models. These models are built around immunosuppression and say little about use in people with a normally functioning immune system.
Caveats. Many positive studies were conducted in Asia, in part with small numbers, short follow-up and no placebo group. A large share of the research was funded or initiated by the manufacturer. Heterogeneity between studies is considerable and the most rigorously designed Western trial was negative 1. For unregistered applications such as ageing, autoimmune disease or Lyme there is no controlled evidence.
What it is used for
- Chronic hepatitis B and C (the registered indication in the countries where it is authorised) 7
- Adjuvant to hepatitis B and influenza vaccination in older people and dialysis patients
- Supportive treatment in sepsis and in chemotherapy-induced immunosuppression (investigational)
- Hepatocellular carcinoma and melanoma as adjunctive treatment (investigational)
- Off-registration: general 'immune support', chronic infections, ageing — without controlled evidence
Dosing
- 1.6 mg twice weekly for 6-12 months is the dose from the approved product information and from the phase III trials 1; it is not simply transferable to other indications.
- The approved product information gives a weight-based dose for patients under 40 kg: 40 mcg/kg, rather than the flat 1.6 mg. The 900 mcg/m² in the line above is the label's own body-surface-area equivalent of the 1.6 mg adult dose, not a separate dose to calculate and administer.
- In sepsis, a more intensive schedule was used in the Chinese ETASS trial: 1.6 mg subcutaneously twice daily for five consecutive days, then once daily for two days — a seven-day course in 361 intensive care patients, not an ongoing regimen 6.
- Doses circulating in user protocols for 'immune support' (for example 450-1600 mcg daily or every other day in courses of a few weeks) do not come from validated clinical studies.
- Dose adjustment in renal impairment has not been systematically studied.
These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.
Protocols
Chronic hepatitis B (thymalfasin, Zadaxin schedule)
published trial| 6 months | 1.6 mg (900 mcg per m2 body surface area) by subcutaneous injection, twice weekly |
|---|---|
| After the last dose | no treatment; response is assessed months later, not at the end of dosing |
1.6 mg twice weekly is also the registered thymalfasin dose in the countries where Zadaxin holds an authorisation. The 900 mcg/m² in the step above is the label's own body-surface-area equivalent of that same 1.6 mg, not a second dose; the label's only genuinely separate figure is 40 mcg/kg for patients under 40 kg. It is specific to chronic viral hepatitis and does not transfer to general immune support. The Chinese ETASS sepsis trial used a far more intensive and much shorter schedule: 1.6 mg twice daily for five days, then once daily for two.
Grey-market 'immune support' use (user-reported)
user protocol — not validatedSource: The pattern repeated across peptide, longevity and post-viral-illness forums together with research-chemical vendor labelling
This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.
| Most commonly reported amount | 450 mcg to 1.6 mg subcutaneously, daily or every other day |
|---|---|
| Reported course length | runs of a few weeks, sometimes repeated seasonally or at the onset of an infection |
The registered schedule is 1.6 mg twice weekly for six to twelve months in chronic hepatitis B, where the response is judged months after dosing stops. The circulating use is different in both purpose and rhythm: general 'immune support', longevity and post-viral recovery — none of it tested — with research-chemical powder self-injected daily or every other day in short courses of a few weeks. Reported amounts run from roughly 450 mcg to the 1.6 mg trial dose, and the frequency does not settle. The trial safety profile was favourable, close to placebo, but that was in supervised hepatitis patients; it says nothing about repeated self-dosing of unverified powder for an untested indication, and the near-absence of reported problems from an unmonitored population is not evidence that there are none.
Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.
Reconstitution
- Vial sizes
- 1.6 mg, 5 mg, 10 mg
- Solvent
- The registered product is supplied with sterile water for injection (1 ml per 1.6 mg vial). For unregistered powder, bacteriostatic water (0.9% benzyl alcohol) is used in practice.
- Storage
- Powder of the registered product: 2-8 °C. Use immediately after reconstitution; the registered product contains no preservative. Liquid reconstituted with bacteriostatic water is in practice kept at 2-8 °C and used within a few weeks.
Worked example
1.6 mg vial + 1 ml diluent = 1.6 mg/ml; the entire contents is a single dose. With a 5 mg vial + 2.5 ml water = 2 mg/ml; 1.6 mg then corresponds to 0.8 ml (80 units on a U100 insulin syringe).
Do not shake — let the diluent run down the wall of the vial and swirl gently. The solution should be clear and colourless.
Work it out for Thymosin alpha-1
Safety
Side effects
- Local injection site reaction: redness, swelling, discomfort (most frequently reported)
- Transient fatigue or malaise
- Rare: temporary rise in ALT during treatment of hepatitis, possibly reflecting an immune response against infected liver cells
- Rare: rash, muscle pain
- The side effect profile is regarded as favourable; in randomised trials the number of adverse events generally did not differ substantially from placebo 1
Do not use if
- Hypersensitivity to thymosin alpha-1 or any of the excipients
- Organ transplant recipients and others deliberately using immunosuppression — immune stimulation may promote rejection
- Active autoimmune disease: theoretical risk of exacerbation, not systematically studied
- Pregnancy and breastfeeding: insufficient data
Interactions
May counteract the action of immunosuppressants (ciclosporin, tacrolimus, corticosteroids). It is frequently combined in studies with (peg)interferon, ribavirin and lamivudine without reported pharmacokinetic interactions. Further interactions have not been systematically studied.
Common questions
What is thymosin alpha-1 used for?
Is thymosin alpha-1 the same as TB-500 or thymosin beta-4?
Is thymosin alpha-1 legal and banned in sport?
Sources
- Thymosin alpha1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled studyJournal of Viral Hepatitis, 1999
- Thymalfasin for the treatment of chronic hepatitis BReview, 2004
- The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trialRandomized clinical trial, 2005
- Comparison of the efficacy of thymosin alpha-1 and interferon alpha in the treatment of chronic hepatitis B: a meta-analysisMeta-analysis, 2007
- Treatment with lamivudine versus lamivudine and thymosin alpha-1 for e antigen-positive chronic hepatitis B patients: a meta-analysisMeta-analysis, 2009
- The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trialCritical Care, 2013 - 361 patients; source of the twice-daily sepsis schedule
- From lab to bedside: emerging clinical applications of thymosin alpha 1Expert Opinion on Biological Therapy, 2009 - Goldstein and Goldstein; states approval in over 35 countries for hepatitis B and C and as an immune stimulant and adjuvant. Note that the senior author discovered the compound and has a commercial interest in it