¶ TB-500 (Thymosin Beta-4 Fragment)
¶ Overview
TB-500 is a synthetic peptide fragment of the naturally occurring protein Thymosin Beta-4 (Tβ4). While Tβ4 is a 43-amino acid protein found in high concentrations in platelets and white blood cells, TB-500 typically refers to the synthetic version of the active domain (amino acids 17-23: LKKTETQ) or sometimes the full protein itself, depending on the context and vendor [1][2].
Thymosin Beta-4 plays a fundamental role in cell structure and motility by regulating the polymerization of actin, a protein essential for muscle contraction, cell division, and cell migration [3]. The peptide has garnered significant attention in regenerative medicine and longevity communities for its potential to accelerate wound healing, reduce inflammation, and promote the repair of damaged tissues, including heart muscle, skin, and connective tissue [4].
In clinical settings, Tβ4 has been investigated for the treatment of corneal injuries, dry eye syndrome, and cardiac damage following myocardial infarction [5]. In the performance and longevity space, TB-500 is widely utilized for its purported ability to speed up recovery from muscle strains, tendonitis, and ligament injuries, although human clinical data for these specific musculoskeletal applications remains limited compared to animal models [6].
¶ Mechanism of Action
The primary mechanisms of TB-500 and Thymosin Beta-4 revolve around their interaction with the cellular cytoskeleton and modulation of the inflammatory response.
¶ Actin Sequestration and Cell Migration
The core function of Tβ4 is its ability to bind to monomeric actin (G-actin) in a 1:1 complex. This "sequestration" prevents actin from polymerizing into filaments (F-actin) prematurely, maintaining a pool of available actin monomers [7]. When a cell needs to migrate—such as during wound repair or tissue regeneration—Tβ4 releases these monomers, allowing for rapid polymerization and the formation of cellular protrusions (lamellipodia) necessary for cell movement [8]. This process is critical for the migration of keratinocytes and endothelial cells to the site of injury.
¶ Angiogenesis (New Blood Vessel Formation)
Tβ4 has been shown to promote angiogenesis, the formation of new blood vessels from pre-existing ones. It stimulates the migration of endothelial cells and increases the expression of vascular endothelial growth factor (VEGF) [9]. Enhanced blood flow is a key factor in tissue repair, delivering oxygen and nutrients to damaged areas.
¶ Anti-Inflammatory and Anti-Fibrotic Effects
Research indicates that Tβ4 can downregulate inflammatory cytokines and reduce the infiltration of inflammatory cells at injury sites [10]. Furthermore, it appears to modulate the transition of fibroblasts to myofibroblasts, potentially reducing excessive scar tissue formation (fibrosis) while still promoting structural integrity [11]. This anti-fibrotic property is particularly valuable in cardiac repair, where scar tissue can impair heart function.
¶ Cell Survival and Apoptosis Inhibition
Tβ4 has demonstrated cytoprotective effects, reducing apoptosis (programmed cell death) in cells under stress. In models of myocardial infarction, Tβ4 treatment significantly reduced the loss of cardiomyocytes, preserving heart function [12].
¶ Evidence and Research Status
The research landscape for Thymosin Beta-4 is robust in preclinical models, with a growing number of human clinical trials.
¶ Wound Healing and Skin Repair
GRADE: Moderate
Tβ4 has been extensively studied for cutaneous wound healing. Phase II trials have evaluated its efficacy in treating venous stasis ulcers and pressure ulcers, showing accelerated healing rates compared to placebo [13]. The peptide promotes keratinocyte migration and collagen deposition, essential for closing chronic wounds.
¶ Cardiac Repair
GRADE: Moderate (Preclinical) / Low (Clinical)
One of the most promising applications of Tβ4 is in the treatment of ischemic heart disease. Animal studies have consistently shown that Tβ4 administration after a heart attack reduces infarct size and improves ventricular function [14]. It activates epicardial progenitor cells, encouraging them to differentiate into cardiomyocytes and vascular cells [15]. However, large-scale human trials confirming these regenerative effects are still in progress or have shown mixed results regarding functional outcomes.
¶ Musculoskeletal Recovery (Muscle and Tendon)
GRADE: Low
Despite its popularity among athletes and biohackers, direct human evidence for TB-500 in treating sports injuries (muscle tears, tendonitis) is sparse. The rationale is based on its mechanism of actin regulation and anecdotal reports of rapid recovery. Animal models of muscle injury suggest that Tβ4 can accelerate muscle fiber regeneration and reduce inflammation [16], but rigorous human trials specifically for sports-related soft tissue injuries are lacking.
¶ Neuroprotection
GRADE: Very Low
Emerging research suggests Tβ4 may have neuroprotective properties. In animal models of stroke and traumatic brain injury (TBI), Tβ4 treatment reduced neuronal damage and improved functional recovery [17]. The mechanisms likely involve oligodendrocyte differentiation and remyelination, as well as anti-inflammatory effects in the brain [18].
¶ Safety Considerations
¶ General Safety Profile
In clinical trials, Thymosin Beta-4 has generally been well-tolerated. A Phase I study in healthy volunteers found no dose-limiting toxicities or serious adverse events with intravenous administration [19]. Common side effects reported in anecdotal logs include temporary lethargy or a "head rush" immediately post-injection.
¶ Cancer Risk and Angiogenesis
Because Tβ4 promotes angiogenesis and cell migration—processes also utilized by cancer cells for tumor growth and metastasis—there is a theoretical concern regarding its use in individuals with active malignancies [20]. While Tβ4 itself is not carcinogenic, it could potentially support the growth of existing tumors by increasing blood supply. Therefore, it is generally contraindicated for individuals with a history of cancer.
¶ WADA and Sports Regulations
TB-500 and Thymosin Beta-4 are classified as prohibited substances by the World Anti-Doping Agency (WADA) under the category of "Peptide Hormones, Growth Factors, Related Substances, and Mimetics" (S2) [21]. Athletes subject to anti-doping testing should be aware that use of this peptide is banned both in and out of competition.
¶ Practical Notes
¶ Dosage and Administration
Note: The following information is based on research protocols and anecdotal user reports, not medical advice.
- Formulation: TB-500 is typically supplied as a lyophilized (freeze-dried) powder requiring reconstitution with bacteriostatic water.
- Route: Subcutaneous injection is the most common method of administration.
- Protocols:
- Loading Phase: Users often employ a loading phase of 2–5 mg per week (split into multiple doses) for 4–6 weeks to saturate tissues [22].
- Maintenance Phase: A lower maintenance dose of 1–2 mg per month is sometimes used thereafter.
- Stability: Once reconstituted, the peptide should be refrigerated and used within a few weeks to maintain potency.
¶ Sourcing and Purity
The distinction between the full Tβ4 protein and the TB-500 fragment is often blurred in the grey market. Users should verify whether they are purchasing the full 43-amino acid sequence or the shorter fragment, as potency and dosing may vary. High-purity (>98%) peptides are recommended to minimize the risk of immunological reactions to contaminants.
¶ References
Goldstein AL, et al. Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues. Trends Mol Med. 2005;11(9):421-429. https://pubmed.ncbi.nlm.nih.gov/16125526/ ↩︎
Huff T, et al. β-Thymosins, small acidic peptides with multiple functions. Int J Biochem Cell Biol. 2001;33(3):205-220. https://pubmed.ncbi.nlm.nih.gov/11248578/ ↩︎
Safer D, et al. Thymosin beta 4 sequesters the majority of G-actin in resting human platelets. J Biol Chem. 1991;266(6):4029-4032. https://pubmed.ncbi.nlm.nih.gov/1995652/ ↩︎
Philp D, et al. Thymosin beta4 promotes angiogenesis, wound healing, and hair growth. Mech Ageing Dev. 2004;125(2):113-115. https://pubmed.ncbi.nlm.nih.gov/15051110/ ↩︎
Sosne G, et al. Thymosin beta 4: a novel corneal wound healing and anti-inflammatory agent. Clin Ophthalmol. 2007;1(3):201-207. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701135/ ↩︎
Treadwell T, et al. Thymosin beta4: a potential novel therapy for the treatment of chronic cutaneous wounds. Wounds. 2012;24(1):6-13. https://pubmed.ncbi.nlm.nih.gov/25874742/ ↩︎
Dedova IV, et al. Thymosin beta4 induces a conformational change in actin monomers. Biophys J. 2006;90(3):985-992. https://pubmed.ncbi.nlm.nih.gov/16299076/ ↩︎
Smart N, et al. Thymosin beta4 and angiogenesis: modes of action and therapeutic potential. Angiogenesis. 2007;10(4):229-241. https://pubmed.ncbi.nlm.nih.gov/17684705/ ↩︎
Cha HJ, et al. Thymosin beta4 promotes angiogenesis and tumor metastasis by upregulating VEGF expression. Biochim Biophys Acta. 2010;1803(2):281-288. https://pubmed.ncbi.nlm.nih.gov/19932134/ ↩︎
Young JD, et al. Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids. Nat Med. 1999;5(12):1424-1427. https://pubmed.ncbi.nlm.nih.gov/10581086/ ↩︎
Bock-Marquette I, et al. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432(7016):466-472. https://pubmed.ncbi.nlm.nih.gov/15565145/ ↩︎
Hinkel R, et al. Thymosin beta4-mediated protection of the ischemic heart. Curr Pharm Des. 2010;16(35):3912-3920. https://pubmed.ncbi.nlm.nih.gov/21128898/ ↩︎
Guarnera G, et al. The effect of thymosin beta4 treatment of venous ulcers: a phase II, randomized, multicenter, placebo-controlled study. Int Wound J. 2010;7(6):501-510. https://pubmed.ncbi.nlm.nih.gov/20840510/ ↩︎
Srivastava D, et al. Thymosin beta4: a therapeutic peptide for the heart. Ann N Y Acad Sci. 2007;1112:161-170. https://pubmed.ncbi.nlm.nih.gov/17483206/ ↩︎
Smart N, et al. De novo cardiomyocytes from within the activated adult heart after injury. Nature. 2011;474(7353):640-644. https://pubmed.ncbi.nlm.nih.gov/21654746/ ↩︎
Spurney CF, et al. Thymosin beta4 improves cardiac function and prevents fibrosis in a mouse model of Duchenne muscular dystrophy. PLoS One. 2010;5(5):e10820. https://pubmed.ncbi.nlm.nih.gov/20520830/ ↩︎
Morris DC, et al. Thymosin beta4 improves functional neurological outcome in a rat model of embolic stroke. Neuroscience. 2010;169(2):674-682. https://pubmed.ncbi.nlm.nih.gov/20538036/ ↩︎
Chopp M, et al. Thymosin beta4 as a restorative/regenerative therapy for neurological injury and neurodegenerative diseases. Expert Opin Biol Ther. 2015;15(sup1):S9-S12. https://pubmed.ncbi.nlm.nih.gov/26095861/ ↩︎
Ruff D, et al. 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. https://pubmed.ncbi.nlm.nih.gov/20536472/ ↩︎
Moon EY, et al. Thymosin beta-4 is a novel hypoxia responsive protein. Exp Cell Res. 2010;316(16):2614-2624. https://pubmed.ncbi.nlm.nih.gov/20599952/ ↩︎
World Anti-Doping Agency. Prohibited List. 2024. https://www.wada-ama.org/en/prohibited-list ↩︎
Kleinman HK, et al. Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues. Trends Mol Med. 2005;11(9):421-429. https://pubmed.ncbi.nlm.nih.gov/16125526/ ↩︎