¶ TB-500 (Thymosin Beta-4 Fragment)
Evidence: Strong for wound healing and cardiac repair in animals; clinical data is limited and primarily anecdotal for sports injuries.
Safety: Good safety profile; no significant toxicity reported in trials.
Action: Category 2 ban (FDA). No longer compoundable in the U.S.
¶ Summary / At a Glance
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 specifically refers to the active domain (amino acids 17-23: LKKTETQ) responsible for promoting actin polymerization and cell migration.
- Primary Goal: Accelerate wound healing, repair damaged tissue (muscle, tendon, ligament, heart), and reduce inflammation.
- Key Distinction: Often confused with full-length Thymosin Beta-4, TB-500 is the shorter fragment used for its systemic bioavailability and specific regenerative properties.
- Status: Widely used in sports medicine and veterinary contexts (notably horse racing) for injury recovery.
- Regulatory Warning: As of late 2023/2024, the FDA has placed Thymosin Beta-4 and its fragments (including TB-500) on the Category 2 list of bulk drug substances, prohibiting its compounding in the United States due to safety concerns and lack of clinical need.
¶ Mechanism of Action
The primary mechanisms of TB-500 revolve around its 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 actin, a protein essential for cell structure and movement.
- Sequestration: By binding to monomeric actin (G-actin), TB-500 maintains a pool of available actin monomers.
- Release: When a cell needs to migrate to an injury site, TB-500 releases these monomers, allowing for rapid polymerization into filaments (F-actin). This enables the formation of cellular protrusions (lamellipodia) necessary for cell movement, critical for wound closure and tissue regeneration[1].
¶ Angiogenesis (New Blood Vessel Formation)
TB-500 promotes 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), improving blood flow to damaged tissues[2].
¶ Anti-Inflammatory Effects
Research indicates that Tβ4 can downregulate inflammatory cytokines and reduce the infiltration of inflammatory cells at injury sites, potentially preventing excessive scar tissue formation (fibrosis)[3].
¶ 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
Phase II trials have evaluated Tβ4's efficacy in treating venous stasis ulcers and pressure ulcers, showing accelerated healing rates compared to placebo. The peptide promotes keratinocyte migration and collagen deposition[4].
¶ Cardiac Repair
GRADE: Moderate (Preclinical) / Low (Clinical)
One of the most promising applications is in ischemic heart disease. Animal studies consistently show that Tβ4 administration after a heart attack reduces infarct size and improves ventricular function by activating epicardial progenitor cells[5]. However, large-scale human trials confirming these regenerative effects are still in progress.
¶ Musculoskeletal Recovery
GRADE: Low
Despite its popularity among athletes, 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 suggest it can accelerate muscle fiber regeneration[6].
¶ Dosing and Administration
- Standard Protocol:
- Loading Phase: 2 mg to 5 mg per week (split into multiple doses, e.g., 2 mg twice a week) for 4–6 weeks to saturate tissues.
- Maintenance Phase: A lower maintenance dose of 1 mg to 2 mg per month is sometimes used thereafter for ongoing recovery support.
- Route: Subcutaneous injection is the standard method.
- Sourcing: Users must verify whether they are purchasing the full 43-amino acid Tβ4 or the shorter fragment TB-500, as potency and dosing may vary.
¶ Safety and Side Effects
- General Profile: In clinical trials, Thymosin Beta-4 has generally been well-tolerated with no significant dose-limiting toxicities reported.
- Common Reactions: Temporary lethargy or a "head rush" immediately post-injection.
- Cancer Risk: Because Tβ4 promotes angiogenesis and cell migration—processes also utilized by tumors—there is a theoretical concern that it could support the growth of existing cancers. It is generally contraindicated for individuals with active malignancy[7].
¶ Legal Status
United States (FDA)
- Compounding Ban: In late 2023, the FDA categorized Thymosin Beta-4 (TB-500) as a Category 2 bulk drug substance (Safety Concerns). This classification effectively bans the compounding of TB-500 by U.S. pharmacies. Legitimate access via telemedicine has largely ceased as of 2024/2025.
World Anti-Doping Agency (WADA)
- Prohibited: TB-500 and Thymosin Beta-4 are listed under S2. Peptide Hormones, Growth Factors, Related Substances, and Mimetics. They are banned for use by athletes at all times, both in and out of competition.
¶ References
Goldstein AL, et al. Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues. Trends Mol Med. 2005;11(9):421-429. ↩︎
Smart N, et al. Thymosin beta4 and angiogenesis: modes of action and therapeutic potential. Angiogenesis. 2007;10(4):229-241. ↩︎
Young JD, et al. Thymosin beta 4 sulfoxide is an anti-inflammatory agent. Nat Med. 1999;5(12):1424-1427. ↩︎
Guarnera G, et al. The effect of thymosin beta4 treatment of venous ulcers: a phase II study. Int Wound J. 2010;7(6):501-510. ↩︎
Srivastava D, et al. Thymosin beta4: a therapeutic peptide for the heart. Ann N Y Acad Sci. 2007. ↩︎
Spurney CF, et al. Thymosin beta4 improves cardiac function and prevents fibrosis in a mouse model of Duchenne muscular dystrophy. PLoS One. 2010. ↩︎
Moon EY, et al. Thymosin beta-4 is a novel hypoxia responsive protein. Exp Cell Res. 2010. ↩︎