TB-500 + Thymosin Alpha-1 Stack: Evidence, Mechanisms, and Protocol

What is TB-500, and what is thymosin alpha-1?

TB-500 is a synthetic, N-acetylated 7-amino-acid fragment of thymosin beta-4: residues 17 to 23, sequence Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH, molecular weight about 889 g/mol [1]. Full-length thymosin beta-4 is a 43-amino-acid protein found in blood, saliva, tears and wound fluid; TB-500 is neither that protein nor thymosin alpha-1 [1]. 'TB-500' is a common name rather than an official drug name, and FDA found several salts and derivatives, including different active moieties, sold under it [1]. It appears to have been first synthesized in 2003, with a veterinary preparation marketed from 2011 to boost performance in horses and greyhounds [1].

Thymosin alpha-1 is a 28-amino-acid peptide with an acetylated N-terminal end, originally isolated from thymosin fraction 5, a thymus extract [2]. Thymalfasin is the synthetic version with the same sequence; Zadaxin is the brand of the finished 1.6 mg injection sold outside the US, and it is not interchangeable with bulk powder [2]. It is described as an immune modulator that augments T-cell function, and after subcutaneous injection in healthy volunteers it peaks at about 0.7 to 2 hours and clears with a half-life of about 1.8 to 2.6 hours, with no accumulation after five daily doses [7][2].

What human evidence exists for TB-500?

None. FDA's July 2026 evaluation searched PubMed, Embase, ClinicalTrials.gov and other sources and found no article in which TB-500 was given to any person for any condition, and none of the three papers its nominator cited involved TB-500 in humans [1].

How do the two peptides differ in mechanism?

One is a fragment of an actin-binding protein; the other is an immune modulator acting on T-cell function [1][7]. The LKKTETQ stretch of thymosin beta-4 is described as the actin-binding site behind its wound-healing effects, but for TB-500 itself FDA found no in-vivo animal study of wound healing [1]. In an in-vitro scratch-wound test, TB-500 at 50 micrograms/mL did not induce wound closure in fibroblast cultures; a shorter metabolite, N-acetylated LKKTE, did show activity [1].

What do the thymosin alpha-1 trials show?

Thymosin alpha-1 has been studied in several settings, including chronic hepatitis B and vaccine responses in hemodialysis patients [3][8][9].

A 2026 Cochrane review pooled 10 randomized trials with 1,349 adults with chronic hepatitis B, published 1991 to 2018 and run in Bangladesh, China, Italy, Korea, Singapore and Taiwan, comparing thymosin alpha-1 alone or with interferon, lamivudine, entecavir or tenofovir against placebo, no treatment or the same co-treatment [3]. It found possible lower all-cause mortality (risk ratio 0.53, 95% CI 0.29 to 0.96; 3 trials, 907 people) but the certainty was very low, with little to no effect on quality of life or liver histology; the reviewers said they are not sure it helps [3].

Individual trials are modest and mixed. A double-blind placebo-controlled trial in 98 adults added thymosin alpha-1 1.6 micrograms three times weekly (n=48) or placebo (n=50) to 24 weeks of lymphoblastoid interferon; HBeAg loss at 72 weeks was 45.8% versus 28.0%, a difference of 17.8% (95% CI -1.2 to 35.3) that did not reach statistical significance (P=0.067) [10]. A 1991 pilot gave thymosin fraction 5 or thymosin alpha-1 to 7 people and placebo to 5, twice weekly for six months; serum HBV DNA cleared in 6 of 7 (86%) versus 1 of 5 (20%) (P<0.04) [11]. A 2001 pharmacy review reported a serum half-life of about 2 hours and noted that hepatitis B had been evaluated in 195 patients across four trials, with one randomized trial showing HBV DNA clearance in 40.6% after 6 months of thymosin alpha-1 and 25.6% after 12 months, versus 9.4% of untreated controls [7].

In hemodialysis patients the studies are small and preliminary. One pilot randomized 194 patients 1:1 to 1.6 mg thymosin alpha-1 subcutaneously twice weekly for 8 weeks or to no treatment; the preliminary report listed 3 deaths in the treated group versus 7 in controls and 12 COVID-19-related serious adverse events, 5 versus 7 [8]. Another pilot added Zadaxin at 3.2 or 6.4 mg to an adjuvanted pandemic H1N1 influenza vaccine in hemodialyzed patients and measured antibody responses by hemagglutination inhibition, microneutralization and single radial hemolysis [9].

Do studies of full-length thymosin beta-4 apply to TB-500?

No. Trials of the full-length protein are a different product. A phase 1 study gave 54 healthy volunteers a single intravenous dose of recombinant human thymosin beta-4 at 0.05 to 25 micrograms/kg or placebo, and 30 received 0.5, 2 or 5 micrograms/kg daily for 10 days; adverse events were mild to moderate, with no dose-limiting toxicity, no serious adverse events and no obvious accumulation [12]. A phase 2 dry-eye trial of 0.1% thymosin beta-4 drops in 72 adults found no significant difference on either primary endpoint at day 29 [13]. A smaller eye-drop trial in 9 patients (12 treated eyes, 6 vehicle eyes) reported a 35.1% reduction in ocular discomfort and a 59.1% reduction in total corneal staining versus vehicle at day 56 [14]. In 96 STEMI patients after angioplasty, infarct area at 90 days was smaller only in the subgroup that received the first dose within 8 hours (n=43); the overall difference across all 96 was not significant [15].

A retrospective chart review, not a trial, involved thymosin beta-4 alongside BPC-157: 16 patients reached by phone after intra-articular injections, 12 with BPC-157 alone and 4 with BPC-157 plus thymosin beta-4 (form not specified), where 75% of the 4 reported significant improvement versus 11 of 12 on BPC-157 alone [16]. There was no control group, no validated measurement tool, and results were recalled by patients [16].

Is there a TB-500 and thymosin alpha-1 protocol?

No dosing schedule can be established for this combination because TB-500 has no approved dose or human dosing study [1]. The nomination FDA reviewed proposed a 3 mg/mL lyophilized powder for subcutaneous or intramuscular injection, which is a proposed formulation rather than a recommended dose, and doses used in trials of recombinant full-length thymosin beta-4 do not apply to the fragment [1].

For thymosin alpha-1 there is no US-approved dose either [2]. In Italy, Zadaxin 1.6 mg is given subcutaneously or intramuscularly twice weekly for 4 weeks starting at the first vaccination, repeated from week 8 to week 12 at the second vaccination; the Italian label says it is not for children, is contraindicated in pregnancy and breastfeeding, and calls for caution in people with allergies or autoimmune disease and with other immune-modulating drugs [2].

What are the safety concerns?

For TB-500, human safety is unknown [1]. FDA's stated concern for injectable TB-500 is immunogenicity, potentially amplified by peptide aggregation and impurities, and no study of TB-500 immunogenicity or aggregation was found [1]. FDA's adverse-event database search through March 26, 2025 retrieved no TB-500 reports, and its food and supplement complaint system retrieved two cases about a blended TB-500 and BPC-157 product with no safety assessment [1]. In a separate review, a 40-year-old woman using a research-purposes-only BPC-157 plus TB-500 (5 mg/5 mg) product subcutaneously twice daily developed widespread skin hyperpigmentation and gum darkening within a week, recurring when she retried the product two weeks later; because the product held two peptides, FDA said it cannot tell whether either caused it [17].

For thymosin alpha-1, FDA's adverse-event database search of April 22, 2024 found zero reports [2]. The 2026 Cochrane review found it may have caused fewer serious adverse events than comparison treatments (risk ratio 0.72, 95% CI 0.53 to 0.99; 5 trials, 1,056 people; low-certainty evidence) and fewer non-serious events (risk ratio 0.47, 95% CI 0.27 to 0.83; very low-certainty evidence) [3]. Authors tied to the manufacturer report more than 4,400 people enrolled in trials and more than 17 million doses given after marketing with adverse experiences described as infrequent and mild; that is company-linked data [2].

What is the regulatory status in the United States?

TB-500 is not an FDA-approved drug. FDA's July 2026 review found no USP or National Formulary monograph, no FDA-approved drug containing it, no listing in the European or Japanese pharmacopeias, no approved product in Canada, Australia, the UK, Belgium, Ireland, France, Norway, Germany, Spain or Italy, and no European Medicines Agency authorization [1]. FDA's page on bulk substances that may present significant safety risks lists the LKKTETQ fragment in its nominated-but-withdrawn table, holding substances previously in the higher-risk category whose nominators withdrew; FDA's concerns remain that it has not identified any human exposure data and that injectable peptides may pose immunogenicity risk, and removal from that category was not a finding that it is safe [18]. It appears in none of the three categories on FDA's list for state-licensed pharmacies and physicians and is not on the outsourcing facility list; FDA's category 1 policy, under which it generally does not act against compounders who meet the conditions, does not cover it [19][20][21]. FDA staff proposed in July 2026 that neither the free base nor the acetate be added to the pharmacy bulks list, citing no human data and immunogenicity risk [1]. FDA's Pharmacy Compounding Advisory Committee voted in favor of adding it on July 23, 2026, against staff's recommendation, but that is advice only and not binding [5][22]. HHS's draft enforcement-discretion policy, filed October 28, 2026, names TB-500 acetate for subcutaneous or intramuscular injection and says HHS does not intend to take enforcement action against certain pharmacies and physicians if its conditions are met; the notice says it does not establish rights for any person and is not binding, and it is not an approval or a listing [22][23].

Thymosin alpha-1 is also not FDA-approved [2]. FDA's December 2024 review notes four US orphan drug designations, but orphan designation is a separate process and is not an approval [2]. It is approved as a medicine in some other countries: FDA lists Italy, where Zadaxin is authorized as an adjuvant to influenza vaccination in immunocompromised people, India for chronic hepatitis B in adults 18 or older with compensated liver disease and virus replication, and Hong Kong; the European Medicines Agency has granted only an orphan designation for hepatocellular carcinoma [2]. It sits in the same nominated-but-withdrawn table, with FDA's stated concerns about immunogenicity for certain routes and safety information it called inadequate [18]; on the outsourcing facility list it is in category 3, nominated without adequate support [19][20]. On December 4, 2024, FDA's Pharmacy Compounding Advisory Committee voted 4 yes and 17 no, with no abstentions, on both the free base and the acetate [6]. It is not one of the six peptides in HHS's October 2026 draft policy [23].

Is either peptide banned in sport?

WADA's Prohibited List names thymosin-beta4 and its derivatives, for example TB-500, in S2.3 (growth factors and growth factor modulators); it is prohibited at all times, in and out of competition, on the 2026 List and still on the 2027 List [4][24]. Thymosin alpha-1 is not named on the 2026 or 2027 List [4][24].