Overview
"TB-500" and "thymosin beta-4" are often used as if they were the same thing. They are not, and the difference matters for reading the research.
Thymosin beta-4 is a naturally occurring protein of 43 amino acids, found in many cell types, that binds actin, a structural protein cells use to move and change shape (Low 1981). Nearly all of the published research, including the animal wound and heart studies and the small human trials, used full-length thymosin beta-4.
TB-500 is a trade name that first appeared on a veterinary preparation. Doping control labs that analyzed it found the key ingredient to be a short synthetic peptide, LKKTETQ with an acetyl group added at one end, which corresponds to amino acids 17 to 23 of thymosin beta-4 (Esposito 2012; Ho 2012). This region is described as the actin-binding site linked to cell migration. What any given product sold as TB-500 contains depends on the supplier.
The practical point: findings for the full protein cannot be assumed to apply to the seven amino acid fragment, which has almost no published efficacy research of its own.
Research history
Thymosin beta-4 was isolated from calf thymus tissue by Allan Goldstein's group, and its complete amino acid sequence was published in 1981 (Low 1981). It was first studied as a possible thymic hormone involved in immune cell maturation. Researchers later recognized it as a major actin-sequestering molecule present far beyond the thymus.
Interest shifted toward tissue repair in the late 1990s, when a National Institutes of Health team reported faster wound closure in rats (Malinda 1999). In 2004 a Nature paper reported that thymosin beta-4 supported heart cell survival and function after induced heart attacks in mice (Bock-Marquette 2004). A company, RegeneRx, then took full-length thymosin beta-4 into human trials for skin wounds and eye conditions (Goldstein 2012).
The TB-500 name belongs to a separate thread. It emerged in horse racing, where laboratories developed tests for the acetylated fragment in equine urine and plasma (Ho 2012).
What published studies have examined
Cell and animal studies (full-length thymosin beta-4)
In a rat full-thickness wound model, thymosin beta-4 applied to the skin or given into the abdomen increased re-epithelialization compared with saline, along with more collagen deposition and new blood vessel growth (Malinda 1999). In cell assays it stimulated keratinocyte migration.
In mice, researchers reported that thymosin beta-4 formed a complex with integrin-linked kinase, activated the survival kinase Akt, and was associated with improved heart function after coronary artery ligation (Bock-Marquette 2004). Reviews from researchers closely involved with its development describe further animal work in the eye, heart and brain (Goldstein 2012).
Human trials (full-length thymosin beta-4)
- Phase 1 safety. A randomized, placebo-controlled study in healthy volunteers, four cohorts of 10, gave intravenous synthetic thymosin beta-4 as single and repeated daily doses for 14 days. Adverse events were infrequent and mild or moderate, with no dose-limiting toxicity (Ruff 2010).
- Dry eye. A phase 2 randomized, double-masked trial of thymosin beta-4 eye drops enrolled nine patients with severe dry eye and reported improvements in some sign and symptom scores versus vehicle (Sosne 2015). The authors described it as a small trial.
The TB-500 fragment
Published work on the acetylated fragment itself is mainly analytical: synthesis, identification and detection methods for doping control (Esposito 2012; Ho 2012). We found no controlled human trial of TB-500.
Open questions
- Fragment versus protein. Whether the seven amino acid fragment reproduces the effects reported for full-length thymosin beta-4 has not been established in controlled studies.
- Trial depth. The human data for the full protein come from small trials, several with authors connected to the company developing it. None has led to an approved product.
- Long-term safety. Thymosin beta-4 influences cell migration and blood vessel growth, and long-term safety data in people are lacking.
- Product identity. Materials labeled TB-500 are not standardized. Our guide to what makes a peptide research grade explains how identity and purity are documented.
For a related recovery compound with a similar gap between animal work and human data, see our review of BPC-157 research.
Sources
- Low TL, Hu SK, Goldstein AL. Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations. Proc Natl Acad Sci U S A. 1981;78(2):1162-1166. doi.org/10.1073/pnas.78.2.1162
- Malinda KM, Sidhu GS, Mani H, et al. Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999;113(3):364-368. doi.org/10.1046/j.1523-1747.1999.00708.x
- Bock-Marquette I, Saxena A, White MD, Dimaio JM, Srivastava D. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432(7016):466-472. doi.org/10.1038/nature03000
- Ruff D, Crockford D, Girardi G, Zhang Y. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Ann N Y Acad Sci. 2010;1194:223-229. doi.org/10.1111/j.1749-6632.2010.05474.x
- Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin beta4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opin Biol Ther. 2012;12(1):37-51. doi.org/10.1517/14712598.2012.634793
- Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P. Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Drug Test Anal. 2012;4(9):733-738. doi.org/10.1002/dta.1402
- Ho EN, Kwok WH, Lau MY, et al. Doping control analysis of TB-500, a synthetic version of an active region of thymosin beta4, in equine urine and plasma by liquid chromatography-mass spectrometry. J Chromatogr A. 2012;1265:57-69. doi.org/10.1016/j.chroma.2012.09.043
- Sosne G, Dunn SP, Kim C. Thymosin beta4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial. Cornea. 2015;34(5):491-496. doi.org/10.1097/ICO.0000000000000379
Frequently asked questions
Is TB-500 the same as thymosin beta-4?
No. Thymosin beta-4 is a 43 amino acid protein, while analyses of TB-500 identified a synthetic seven amino acid fragment of it, acetylated LKKTETQ. Most published research used the full-length protein, not the fragment.
Is TB-500 FDA approved?
No. Neither TB-500 nor thymosin beta-4 is approved by the FDA. The FDA previously listed the fragment it calls TB-500 in Category 2 of its compounding review, citing potential safety risks; that nomination was later withdrawn, which is not the same as an approval.
Is TB-500 banned in sport?
Yes. The World Anti-Doping Agency prohibits thymosin beta-4 and its derivatives, naming TB-500 as an example, at all times. Horse racing laboratories have also developed specific tests for it.
Has thymosin beta-4 been tested in humans?
Yes, in small trials of the full-length protein, including a phase 1 safety study in healthy volunteers and a phase 2 dry eye trial with nine patients. These trials are small and do not establish benefit for any condition.
Peptrend.Health is an educational publication. Content on this site is for informational and research purposes only and is not medical advice, and it is not a substitute for guidance from a qualified professional. Products referenced from Prime Core Dynamics are sold for laboratory research use only and are not intended for human consumption.