Thymosin alpha-1: evidence, FDA status and research

A peptide sold by wellness clinics as an immune booster. Trials show a modest effect in hepatitis B, and a large sepsis trial found none.

Sold for

Thymosin alpha-1 is sold by wellness clinics as an immune-system booster for infections, cancer support, autoimmune disease and long COVID.

Studies say

Randomized trials support a modest, delayed antiviral effect in chronic hepatitis B, a large trial found no benefit in sepsis, and there are no trials of the immune-boosting uses marketed in the US, which is why it grades B.

Why grade B. Thymosin alpha-1 has several randomized trials in chronic hepatitis B (98 and 316 patients) and a meta-analysis of five trials with 353 patients showing delayed viral suppression, which is the approved use abroad. The 1,106-patient TESTS phase 3 trial in sepsis found no mortality benefit. The general immune-boosting use it is sold for in the US has no controlled trials, so the compound grades B on its hepatitis B evidence and D on the wellness claims. ²¹³¹⁴¹⁵

FDA. Thymosin alpha-1 is not approved by the FDA for any use. It is approved as thymalfasin (Zadaxin) in more than 35 other countries for hepatitis B and C and as an immune adjuvant. In the United States it was taken off the FDA's Category 2 compounding list after its nominators withdrew it, and in December 2024 the Pharmacy Compounding Advisory Committee voted 17 to 4 against adding it to the 503A bulks list; it is sold online as a research chemical.

Written from 15 cited sources. Last refreshed 2026-10-27. Not physician reviewed.

What this means for you

What people take it for: Boosting the immune system
Can a US doctor prescribe it?: No. It is not approved and is sold as a research chemical. It is approved in over 35 other countries.
Properly tested in people?: Partly: hepatitis B trials of 98 to 316 people, none for the immune-boosting uses it is sold for.

Evidence checklist

Randomised controlled trial Randomized hepatitis B trials, sepsis trialyes
Human study over 100 people TESTS enrolled 1,106 adultsyes
More than one research group Trials in several countriesyes
Clinical outcomes, not surrogate markers Sepsis mortality: no benefityes
Human safety data beyond case reports Mild events across trialsyes

Drawn from the cited studies below. A dash means the sources give no information.

What it is

Thymosin alpha-1 is a peptide with 28 amino acids and an acetyl group at one end. Researchers first isolated it from thymosin fraction 5, a crude extract of calf thymus. It is now made synthetically. The thymus is the gland behind the breastbone where T cells mature. The synthetic drug is called thymalfasin. SciClone sells it as Zadaxin. ⁹¹⁰

Zadaxin is approved in China, Italy and several other countries for chronic hepatitis B and as a vaccine adjuvant. It never received FDA approval. US trials in hepatitis C and melanoma reached late-stage testing in the 2000s. They did not lead to a filing. In the US, it circulates through compounding pharmacies and gray-market vendors. ¹⁷

How it works

Thymosin alpha-1 acts on dendritic cells, the immune cells that show antigens to T cells. It does so through Toll-like receptor 9, a sensor that normally detects microbial DNA. In lab and mouse studies, this pushes T cells toward the Th1 response that fights viruses and fungi. It increases interferon-gamma and interleukin-2. It also boosts natural killer cell activity. The same signaling also switches on an enzyme (indoleamine 2,3-dioxygenase) that produces regulatory T cells. So the peptide can promote tolerance as well as attack. That dual behavior is why it has been tried in both infections and autoimmune settings. ⁹¹¹

What human research shows

In a 1998 randomized trial, 98 patients with chronic hepatitis B received a 26-week or 52-week course of thymosin alpha-1, or no treatment. Researchers assessed them 18 months after entry. Complete virological response means loss of hepatitis B virus DNA and e antigen. It occurred in 41 percent of the 26-week group versus 9 percent of controls. Responses kept building after treatment stopped. A Japanese randomized trial had 316 patients and compared two doses for 24 weeks. A year after therapy ended, about 23 percent had cleared e antigen. Liver enzymes had returned to normal in 36 percent. ²¹⁴

A 2001 meta-analysis pooled five randomized trials (353 patients). It found no advantage over placebo at the end of treatment. At six months there was a trend. At 12 months after stopping, the odds ratio for virological response was significant at 2.67. Liver enzyme normalization did not differ at any point. ¹³

The TESTS trial appeared in BMJ in 2025. It randomized 1,106 adults with sepsis at 22 Chinese intensive care units to thymosin alpha-1 or placebo for seven days. Twenty-eight-day mortality was 23.4 percent on thymosin alpha-1 and 24.1 percent on placebo. No secondary or safety outcome differed. A pre-specified subgroup analysis suggested possible harm in patients under 60. It suggested possible benefit in those with diabetes. The authors treated both as hypotheses, not findings. ⁴¹⁵

Study	Model	Finding
TESTS sepsis trial (BMJ 2025)	Humans, n=1,106 adults with sepsis, randomized placebo-controlled phase 3	No difference in 28-day mortality (23.4 percent versus 24.1 percent) or any secondary outcome. ¹⁵
Japanese hepatitis B trial (2005)	Humans, n=316, randomized two-dose comparison, 72-week follow-up	About 23 percent cleared hepatitis B e antigen and 36 percent normalized liver enzymes a year after a 24-week course, with mild adverse events. ¹⁴
Chien 1998 hepatitis B trial	Humans, n=98, randomized controlled	Complete virological response at 18 months in 41 percent of the 26-week treatment group versus 9 percent of untreated controls. ²
Meta-analysis of hepatitis B trials (2001)	Humans, 5 randomized trials, n=353	Virological response did not differ at end of treatment but was significantly higher 12 months after stopping (odds ratio 2.67). ¹³

Safety

Across the hepatitis B trials, adverse events were mild. Most were swings in liver enzymes. The investigators blamed these on the immune response against infected liver cells. In the 1,106-patient sepsis trial, adverse event rates were the same in both arms. Injection-site discomfort is the most common complaint in clinical use abroad. ²¹⁴¹⁵

The gaps are in the US market. Compounded or gray-market thymosin alpha-1 is not subject to the quality controls that apply to Zadaxin. No trials cover the doses or uses that wellness clinics follow. Nothing is known about long-term use in healthy people. The FDA's compounding review listed the nomination as withdrawn and not evaluated. ⁷

Questions for your clinician

Is there a controlled trial for the immune-boosting use I have in mind?
Why did the sepsis trial show no mortality benefit?
Is the product I am offered a licensed one?

Questions people ask

Where is thymosin alpha-1 approved, if anywhere?

No. It is approved as thymalfasin (Zadaxin) in over 35 countries, mainly for hepatitis B and as a vaccine adjuvant. The FDA has never approved it. Its nomination for the US compounding list was withdrawn. So pharmacies cannot legally compound it under that pathway. ¹⁷

What did the TESTS trial find?

TESTS randomized 1,106 adults with sepsis in China to seven days of thymosin alpha-1 or placebo. Mortality at 28 days was 23.4 percent versus 24.1 percent, a null result. The authors flagged subgroup signals in younger and diabetic patients. They said those need their own trials. ¹⁵

How is thymosin alpha-1 different from thymosin beta-4?

Both were isolated from calf thymus extract, and that is where the similarity ends. Thymosin alpha-1 has 28 amino acids. It is an immune modulator that acts on dendritic cells. Thymosin beta-4 has 43 amino acids and is found in nearly all cells. It binds actin and is studied for wound and heart repair. ⁸⁹¹¹

When do the effects of thymosin alpha-1 show up?

In hepatitis B, the effect is delayed. Trials and the meta-analysis found no advantage at the end of a six-month course. A significant advantage showed only 12 months after stopping, as the immune response kept building. There are no data on timing for the immune-boosting uses sold in the US. ²¹³

How well tolerated has it been in trials?

In trials, effects were mild and uncommon. These were injection-site reactions and temporary rises in liver enzymes in hepatitis B patients. The sepsis trial found adverse event rates equal to placebo. No one has studied the safety of long-term use in healthy people. ¹⁴¹⁵

Citations

Garaci 2009, Expert Opin Biol Ther: From lab to bedside, emerging clinical applications of thymosin alpha 1 pubmed.ncbi.nlm.nih.gov
Chien 1998, Hepatology: Efficacy of thymosin alpha1 in chronic hepatitis B, randomized controlled trial pubmed.ncbi.nlm.nih.gov
Wu 2013, Critical Care: Thymosin alpha1 in severe sepsis, randomized trial (ETASS) doi.org
Liu 2025, BMJ: Thymosin alpha1 for sepsis (TESTS), phase 3 trial doi.org
Iino 2005, J Viral Hepat: Thymosin alpha-1 in Japanese patients with chronic hepatitis B doi.org
2025, Front Cell Infect Microbiol: Efficacy of thymosin alpha1 for sepsis, systematic review and meta-analysis doi.org
FDA: Certain bulk drug substances for use in compounding may present significant safety risks fda.gov
Mannherz 2009, Cell Motil Cytoskeleton: The beta-thymosins, intracellular and extracellular activities pubmed.ncbi.nlm.nih.gov
Chan 2004, Expert Rev Anti Infect Ther: Thymalfasin for chronic hepatitis B pubmed.ncbi.nlm.nih.gov
Ren 2011, Microb Cell Fact: Production of N-acetylated thymosin alpha1 in E. coli pubmed.ncbi.nlm.nih.gov
Romani 2006, Blood: Thymosin alpha1 activates dendritic cell tryptophan catabolism pubmed.ncbi.nlm.nih.gov
2026, Peptides: Thymosin beta 4, an emerging therapeutic candidate for kidney diseases pubmed.ncbi.nlm.nih.gov
Chan 2001, Aliment Pharmacol Ther: Thymosin in chronic hepatitis B, meta-analysis pubmed.ncbi.nlm.nih.gov
Iino 2005, J Viral Hepat: Thymosin alpha-1 in Japanese patients with chronic hepatitis B, randomized trial pubmed.ncbi.nlm.nih.gov
Liu 2025, BMJ: Thymosin alpha1 for sepsis (TESTS), multicentre phase 3 trial pubmed.ncbi.nlm.nih.gov