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TB-500 + MOTS-c Stack: When to Pick One Over the Stack

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At a glance

  • TB-500 identity / N-acetylated 7-amino-acid fragment of thymosin beta-4, about 889 g/mol [2]
  • MOTS-c identity / 16-amino-acid peptide encoded in mitochondrial DNA [1][5]
  • Approved dose / none for either peptide [1][2]
  • FDA approval / neither is approved or a component of an approved drug [1][2]
  • Sport / TB-500 in WADA S2.3, MOTS-c in S4.4.1, banned at all times [6][7]
  • Draft HHS policy / names each peptide separately and lists a single active ingredient among its conditions [3][4]

What the laboratory and mouse work shows

TB-500 is a synthetic, N-acetylated seven-amino-acid fragment of thymosin beta-4 (residues 17 to 23), with a molecular weight of about 889 g/mol [2]. In an in-vitro scratch-wound test, TB-500 at 50 micrograms/mL did not close fibroblast cultures; a shorter metabolite, N-acetylated LKKTE, did show activity in vitro [2].

MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA [1][5]. In mice, 0.5 mg/kg/day intraperitoneally for 8 weeks gave about 20% lower body weight on a high-fat diet, and in one study a late-life schedule of 15 mg/kg three times weekly extended median lifespan from 912 to 970 days [1][5][8]. FDA says the molecular targets are unknown and no dose-response relationship was assessed [1].

What human data exist?

FDA's July 2026 reviews found no published study that gave TB-500 or MOTS-c to a person, and for MOTS-c the 12 papers the nominator cited were not clinical studies [1][2]. Human work has measured the body's own MOTS-c: in a randomized study of 30 healthy adults, circulating MOTS-c showed only a trend to rise after endurance exercise and was not related to fitness [9]. Exercise also raised endogenous MOTS-c expression in muscle and blood in another study, without giving the peptide [8].

Trials of full-length recombinant thymosin beta-4 exist, including an intravenous phase 1 study in 54 healthy volunteers and dry-eye drop trials, but that is a different molecule from the seven-amino-acid fragment and does not show what TB-500 does [10][11][12][2].

What the draft policy says about a blend

HHS's draft enforcement-discretion policy, filed October 28, 2026, names both peptides and says HHS does not intend to take enforcement action against certain pharmacies and physicians compounding them if conditions are met, including a single active ingredient, the acetate form, and subcutaneous or intramuscular injection [3][4]. A product combining TB-500 and MOTS-c appears not to meet the single-active-ingredient condition [3][4]. The notice says it is not binding on HHS or the public, and it is not an approval and does not place either peptide on any list [3].

FDA's Pharmacy Compounding Advisory Committee voted on July 23, 2026 in favor of adding each peptide to the pharmacy bulks list, against FDA staff's recommendation. That vote is advice only, and neither peptide is on the list [14][1][2].

Safety documented for a peptide blend

FDA warns that injectable TB-500 and MOTS-c may cause immune reactions because peptides can aggregate or contain impurities; the risk in people is unknown [1][2]. The closest documented report for a blend is a 40-year-old woman who injected a research-use BPC-157 plus TB-500 product (5 mg/5 mg) twice daily and developed widespread skin hyperpigmentation and gum darkening within a week, recurring when she tried it again; because the vial held two peptides, FDA could not tell which caused it [13].

Frequently asked questions

Is TB-500 the same as thymosin beta-4?
No. TB-500 is the N-acetylated seven-amino-acid fragment of the 43-amino-acid protein thymosin beta-4 [2]. Human trials of full-length recombinant thymosin beta-4 tested a different molecule and do not show what TB-500 does [10][11][2].
Are TB-500 and MOTS-c banned in sport?
Yes. WADA names TB-500 in S2.3 and MOTS-c in S4.4.1, and both are prohibited at all times, in and out of competition [6][7].
Does the HHS draft policy cover a TB-500 plus MOTS-c blend?
It names each peptide and lists a single active ingredient among its conditions, so a two-peptide product appears not to meet that condition [3][4]. The draft is non-binding and establishes no rights [3].

References

  1. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  2. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  3. Official web page. Official web page
  4. Official web page. Official web page
  5. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-54. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
  6. World Anti-Doping Agency. World Anti-Doping Agency
  7. World Anti-Doping Agency. World Anti-Doping Agency
  8. Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
  9. von Walden F, Fernandez-Gonzalo R, Norrbom J, Emanuelsson EB, Figueiredo VC, Gidlund EK, et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol (1985). 2021;131(3):1035-1042. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans
  10. Wang X, Liu L, Qi L, Lei C, Li P, Wang Y, et al. A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers. J Cell Mol Med. 2021;25(17):8222-8228. A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers
  11. Sosne G, Ousler GW. Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE™) model. Clin Ophthalmol. 2015;9:877-84. Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE™) model
  12. Sosne G, Dunn SP, Kim C. Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial. Cornea. 2015;34(5):491-6. Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial
  13. U.S. Food and Drug Administration. U.S. Food and Drug Administration
  14. U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee
Evidence overview for TB-500 + MOTS-c Stack: When to Pick One Over the Stack