Thymosin Beta-4 Fragment Capsule
Also known as: TB-4 fragment 17-23, Ac-LKKTETQ, Thymosin beta-4 fragment (LKKTETQ)
Evidence: Anecdotal
Overview
Oral capsule formulation of a Thymosin Beta-4 active fragment sold for recovery; short peptides are poorly absorbed from the gut and no human data support this route.
An oral capsule of Ac-LKKTETQ, the actin-binding fragment (residues 17 to 23) of thymosin beta-4 and the peptide found in products sold as TB-500 (Esposito 2012). Every healing result behind it comes from injected or topical dosing in animals, or from the full-length protein in humans: the fragment matched the parent protein for endothelial migration and aortic sprouting at about 50 nM and for dermal repair in aged mice (Philp 2003a; Philp 2003b). No published study has measured absorption, plasma levels or efficacy of an oral capsule of this fragment in any species, and a 2024 study found it rapidly degraded in serum (Rahaman 2024). Short unprotected peptides are degraded by gastric acid and gut peptidases, so oral delivery of related peptides has needed nanoparticle or hydrogel carriers. FDA reports no human exposure data for this substance by any route.
Benefits
Marketed for recovery and tissue repair; oral efficacy unproven
Dosing reference
- Research dose
- 750 mcg to 1.5 mg daily: vendor and community range, no published human dose and no oral study of this peptide in any species
- Range
- 750 to 1500 mcg, 1x daily
Oral capsule of Ac-LKKTETQ. No published study has dosed this peptide orally in any species, so neither the dose nor the route has support; animal results used injection or topical application.
Mechanism
The product is the heptapeptide Ac-LKKTETQ, which carries the G-actin-binding motif of thymosin beta-4. In endothelial migration and chick aortic-arch sprouting assays the motif was necessary and sufficient for the angiogenic activity of the parent protein and matched it at about 50 nM (Philp 2003a), and it promoted dermal repair in aged mice (Philp 2003b). Activities mapped to other parts of thymosin beta-4 do not belong to it: the cell-survival and antifibrotic actions attributed to Ac-SDKP come from the N-terminal end of the protein (Sosne 2010; Cavasin 2006). Nothing is known about what reaches the circulation after oral dosing, so the mechanism as sold is unestablished.
Evidence
Anecdotal: no peer-reviewed data
- Commercial TB-500 material was shown by mass spectrometry to contain the N-terminally acetylated 17-23 fragment of thymosin beta-4, Ac-LKKTETQ (Esposito et al., 2012)
- The seven-residue actin-binding motif was necessary and sufficient for the angiogenic activity of thymosin beta-4 in endothelial migration and aortic-arch sprouting assays at about 50 nM (Philp et al., 2003)
- The synthetic LKKTETQ peptide promoted dermal wound repair in aged mice comparably to full-length thymosin beta-4; dosing was topical or intraperitoneal, not oral (Philp et al., 2003)
- Ac-SDKP, the separate N-terminal fragment this record previously named, has its own cardiac and antifibrotic literature and is not the peptide sold here (Cavasin, 2006)
- Ac-LKKTETQ was rapidly metabolized in human serum and in rats, and only the metabolite Ac-LKKTE showed significant wound-healing activity in fibroblasts (Rahaman et al., 2024)
- Human-trial status: no trial of this fragment by any route, and no study of oral dosing in any species. FDA states it has identified no human exposure data for the LKKTETQ fragment
References
- 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. Esposito S, Deventer K, Goeman J, Van der Eycken J, Van Eenoo P, Drug Testing and Analysis, 2012
- The actin binding site on thymosin beta4 promotes angiogenesis. Philp D, Huff T, Gho YS, Hannappel E, Kleinman HK, FASEB Journal, 2003
- Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Philp D, Badamchian M, Scheremeta B, et al., Wound Repair and Regeneration, 2003
- Biological activities of thymosin beta4 defined by active sites in short peptide sequences. Sosne G, Qiu P, Goldstein AL, Wheater M, FASEB Journal, 2010
- Therapeutic potential of thymosin-beta4 and its derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in cardiac healing after infarction. Cavasin MA, American Journal of Cardiovascular Drugs, 2006
- Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro. Rahaman KA, Muresan AR, Min H, et al., Journal of Chromatography B, 2024
Side effects
No human safety data exists and oral bioavailability of the fragment is unproven. Injectable thymosin beta-4 is associated with injection-site irritation and transient fatigue. Because the parent molecule promotes angiogenesis, use with active or suspected malignancy is theoretically inadvisable.
Storage
- Storage
- Room temperature
- Lyophilized
- 12+ months
Pharmacology
- Half-life
- Not measured. Rapidly degraded in human serum and in rats, with Ac-LKK detectable in rat urine to 72 h (Rahaman 2024)
- Molecular weight
- 889.02 Da
- Sequence
- Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln (Ac-LKKTETQ, 7 aa; residues 17 to 23 of thymosin beta-4)