Thymosin alpha-1

What is thymosin alpha-1?

The thymus is the organ in which the immune system’s T cells mature. Thymosin alpha-1 was isolated in 1977 from a mixture called “thymosin fraction 5” obtained from calf thymus. According to the FDA’s 2024 assessment it is a 28-amino-acid peptide acetylated at the N-terminus; its form produced chemically and having the same amino acid sequence as the natural peptide is called thymalfasin. ^[1] The EMA’s 2003 summary also states that the substance was first obtained from bovine thymus and is now produced by chemical reactions, that it acts on the immune system and that it may increase the ability of T lymphocytes to kill tumor cells. ^[3]

According to the FDA, its effect depends, at least in part, on interaction with Toll-like receptor 9 (TLR9) in dendritic cells and lymphoid precursor cells. In rodent studies it was reported to suppress tumor growth and viral infections and to reduce sepsis; however, most of these studies used equivalent doses markedly higher than those used in humans. ^[1] Its half-life in the blood after subcutaneous administration in healthy men is about 2 hours. ^[1]

Despite the similarity in name, thymosin alpha-1 is not the same substance as thymosin beta-4, which is on the doping list, and its fragment TB-500: TB-500.

In which countries is it licensed as a drug?

According to the 2003 summary of the European Medicines Agency (EMA), thymalfasin is licensed in Italy within the EU, where it is used to boost the immune response induced by influenza vaccine. The same document records that the substance was granted “orphan drug” status in 2002 for the treatment of liver cancer (hepatocellular carcinoma); the EMA states explicitly that orphan drug status is not a marketing authorization. ^[3]

The FDA’s December 2024 presentation reports, based on the 2014 annual report of the company that develops the product, that the substance is “approved” in Asia-Pacific, Latin America, Eastern Europe and the Middle East for the treatment of hepatitis B and C, as a vaccine adjuvant and as a chemotherapy adjuvant; the FDA notes that it could not independently verify all of these approvals. According to the same presentation, thymosin alpha-1 is not approved in the US, in Japan or in Europe (except Italy) and is not recognized in the European and Japanese pharmacopoeias. The FDA’s nonclinical safety summaries are based on the monograph of the product marketed outside the US under the trade name Zadaxin. ^[1]

What did the hepatitis B and hepatitis C trials find?

Hepatitis B. The 2026 Cochrane review includes 10 randomized controlled trials (1,349 adults) conducted in Bangladesh, China, Italy, Korea, Singapore and Taiwan and published between 1991 and 2018. Thymosin alpha-1 may reduce all-cause death compared with control treatments (RR 0.53; 95% CI 0.29–0.96; 3 trials, 907 people), but the certainty of this evidence is “very low.” The effect on hepatitis B-related disease is very uncertain (RR 0.86; 95% CI 0.54–1.40); it may have very little or no effect on improvement in liver tissue. Four trials were funded by industry. The authors write that, because certainty is very low, they are not sure whether thymosin alpha-1 reduces death or serious adverse effects. ^[4]

The FDA’s assessment paints a similar picture. The results of five trials with thymosin alpha-1 alone are mixed; in the only randomized, double-blind, placebo-controlled trial among them, the proportion of patients with undetectable HBV DNA 6 months after the end of treatment was 20% in the thymosin alpha-1 group and 21% in the placebo group. Its effectiveness remained uncertain when added to preferred drugs of today such as peginterferon or entecavir; the authors of one trial concluded that adding it to peginterferon was not superior to peginterferon alone. The FDA notes that the trials were small, mostly unblinded and used tests much less sensitive than today’s. ^[1]

Hepatitis C. In a double-blind trial in 109 patients in the US in 1998, adding thymosin alpha-1 to interferon, the standard treatment of the time, increased the proportion of patients whose liver enzymes returned to normal at the end of treatment (37.1% versus 16.2% with interferon alone); the sustained biochemical response remained at 14.2% and 8.1%. ^[5] In a later double-blind trial of addition to peginterferon and ribavirin, sustained viral response was 12.7% versus 10.5%. The FDA stresses that these trials were done with old treatments that have been replaced by oral antiviral drugs achieving cure rates above 90% today. ^[1]

What did the largest sepsis trial show?

According to the FDA, all previous sepsis trials were conducted in China and most were small and unblinded. ^[1] The trial that answers this question most strongly is TESTS: between 2016 and 2020, 1,106 adults diagnosed with sepsis at 22 centers in China were randomized to thymosin alpha-1 or placebo for 7 days; 1,089 people were included in the analysis. 28-day mortality was 23.4% in the thymosin alpha-1 group (127 of 542 people) and 24.1% in the placebo group (132 of 547 people). With the data correction made after publication, the hazard ratio (HR) was updated to 0.97 (95% CI 0.76–1.24); there was also no difference in 90-day mortality. No significant difference was seen in any of the secondary and safety outcomes. ^[6]

In the prespecified subgroup analyses, possible differences were seen in an unfavorable direction under age 60 (HR 1.67) and in a favorable direction in people with diabetes (HR 0.58); these are not the main result, and the authors’ conclusion is that “there is no clear evidence that thymosin alpha-1 reduces 28-day mortality.” The study was funded by two public research programs and the manufacturer of the product; some of the authors reported receiving grants or consulting fees from the manufacturer. ^[6]

A 2025 meta-analysis, which included three of the TESTS authors, calculated a reduction in 28-day mortality in 11 randomized trials (1,927 patients) (OR 0.73; 95% CI 0.59–0.90). However, the difference disappeared when only high-quality trials (OR 0.82; 95% CI 0.65–1.03) and multicenter trials were taken; the authors state that the sample size is insufficient for a definitive conclusion. ^[7]

What is the state of the evidence in COVID-19 and other uses?

COVID-19. Thymosin alpha-1 was widely used in COVID-19 treatment. In a meta-analysis pooling 9 studies (5,352 patients) in hospitalized adults, the effect of thymosin alpha-1 on death was not significant (RR 1.03; 95% CI 0.60–1.75); the authors write that the results do not support its use. In subgroup analyses, death was found to be lower in severe or critical patients (RR 0.66); this is a subgroup result and does not change the main result. ^[8] Three of the four meta-analyses the FDA reviewed found no reduction in death; most of the studies were small, retrospective and done in the early period of the pandemic. According to the FDA, the treatment guidelines of the Infectious Diseases Society of America, the NIH and the World Health Organization do not address thymosin alpha-1. ^[1] In 2020 the FDA sent a warning letter to a company selling thymosin alpha-1 online with COVID-19 claims, characterizing the product as an unapproved and misbranded drug. ^[10]

Vaccine response. The influenza vaccine studies on which the licensed use in Italy rests consist of five studies ranging from 9 to 330 people; according to the FDA, four of them measured only antibody levels rather than a clinical outcome, control groups were missing or inadequate, and the evidence is insufficient to reach a conclusion on effectiveness as a vaccine adjuvant. ^[1]

Cancer, HIV, COPD, chronic fatigue. The FDA also reviewed the studies in melanoma, liver cancer, lung cancer, HIV and COPD one by one and concluded that in each the evidence was insufficient to demonstrate effectiveness; a 488-patient melanoma trial showed no difference on the primary outcome. In chronic fatigue syndrome (ME/CFS) it found no clinical trial at all. ^[1] According to the FDA document, the substance is marketed on the internet in the US for many conditions including Lyme disease, allergy, asthma and chronic fatigue. ^[1]

What are the risks and unknowns?

According to the FDA, in most clinical trials with subcutaneous use for up to 12 months no serious adverse effect attributable to thymosin alpha-1 was seen; the most commonly reported were irritation, redness and discomfort at the injection site. ^[1] In the Cochrane review, serious adverse effects were seen less often in the thymosin alpha-1 arms (RR 0.72; 95% CI 0.53–0.99; 5 trials, 1,056 people; low certainty). ^[4]

The same FDA assessment lists the following signals: ^[1]

• Flares in liver enzymes in chronic hepatitis B patients and thyroid test (TSH) abnormalities in hepatitis C patients.
• Fatal immune-mediated anemia (hemolytic anemia) and graft failure in stem cell transplant recipients; the FDA notes concern that in patients who are deliberately immunosuppressed the substance could cause or worsen graft-versus-host disease.
• Warnings and contraindications in foreign product information for children, pregnant and breastfeeding women, people with autoimmune disease and immunosuppressed people.
• As a 28-amino-acid peptide, a risk of immune response (immunogenicity); aggregation, especially in concentrated solutions, can increase this risk. No animal carcinogenicity study was found.

General peptide risks are covered in a separate guide: Peptide side effects

FDA, WADA and Türkiye: what is the legal status?

US: no approval, recommendation against compounding

According to the FDA, there is no approved drug containing thymosin alpha-1 in the US; the FDA also draws attention to a website that promotes the substance as “FDA-approved.” ^[1] Thymosin alpha-1 had been nominated for drugs to be compounded in pharmacies and then placed in the category of “substances that may present significant safety risks” (Category 2). On the FDA’s page dated April 22, 2026, the substance is in the table of substances “withdrawn by the nominators”; on the same line the FDA writes that compounded drugs containing thymosin alpha-1 may carry a significant risk of immune response with some routes of administration and that safety information is inadequate. ^[9]

Although the nomination was withdrawn, the FDA evaluated the substance on its own discretion and recommended to the advisory committee on December 4, 2024 that it not be added to the list. ^[1] In both of the separate votes for the free base and the acetate form, the committee recommended, 4 yes to 17 no, that it not be added to the list. ^[2] This process is not about drug approval but about whether the bulk substance can be used in compounding. The meaning of the “for research purposes” label is covered in a separate guide: What does “research peptide” mean?

Sport (WADA)

The WADA list in effect from January 1, 2026 does not name thymosin alpha-1. The substance named in section S2.3 is “thymosin beta-4 and its derivatives, e.g., TB-500,” and this section is prohibited at all times. The S0 class covers only substances that no governmental health authority has approved for human therapeutic use; the classes of the list, however, give their examples with the wording “including, but not limited to.” ^[11]

Türkiye

No product with thymosin alpha-1 (thymalfasin) as the active ingredient appears on the TİTCK (Turkish Medicines and Medical Devices Agency) Licensed Human Medicinal Products List dated October 16, 2026. ^[12] Article 19 of Law No. 1262 on Pharmaceutical and Medicinal Preparations (İspençiyari ve Tıbbi Müstahzarlar Kanunu) punishes those who manufacture unlicensed preparations and those who knowingly sell, offer for sale or have them sold with imprisonment of one to five years; importing preparations made abroad without a license for commercial purposes is treated as smuggling. ^[13] Under Article 24 of Law No. 6197 on Pharmacists and Pharmacies (Eczacılar ve Eczaneler Hakkında Kanun), medicines cannot be sold on the internet or any other electronic medium. ^[14]

The general legal framework for peptides: Are peptides legal?

Evidence table: claim, population and limits

Limits of this guide

This page summarizes published human studies and the assessments of official bodies on thymosin alpha-1. It gives no dose, course, preparation, administration technique or product sourcing information. Use in the countries where it is licensed is limited by those countries’ product information and by physician decision; there is no licensed equivalent in Türkiye.