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TB-500 (Thymosin Beta 4) for Ultimate Healing

Updated: Jul 8, 2023

TB-500 is a synthetic analog of thymosin-beta-4 (TB4), a regenerative peptide that is natural to most animal and human cells [1].


TB4 is made of 43 amino acids and is central to the wound healing process, primarily through its modulation of cellular migration and promotion of vascular growth. It is released by platelets and macrophages upon injury to reduce inflammation, cellular damage, and risk of infection [1 ,2].


TB-500 maintains the biological activity of TB4, with both linked in clinical studies to a range of therapeutic effects. These include improved healing in multiple tissue types, as well as anti-aging and cardiovascular benefits. TB4 is under close investigation as a prospective treatment for various cardiometabolic and inflammatory diseases, such as myocardial infarction, ulcerative colitis, corneal inflammation, and renal fibrosis [2].

Research and Development


Discovered in 1981 in bovine thymus tissue, thymosin beta-4 was first studied for its immunomodulating effects as a possible treatment for immunodeficiency and autoimmune diseases. Research has subsequently widened to cover its multifunctional properties [3].


TB-500 is popular in veterinary contexts and has been banned for use as a performance-enhancing substance in horse racing. TB4, TB-500, and related substances have also been banned for sporting use in humans by the World Anti-Doping Association (WADA) and the national bodies tasked with implementing its Code [1, 4].

Nonetheless, TB-500 and TB4 have been subject to ongoing research into their potential therapeutic benefits, evidencing favorable safety profiles in both animal and human models. Novel derivatives have recently been developed to improve bioavailability and targeted therapeutic effects, to be discussed below [5].


What Does TB-500 Do?


While TB4 has been more heavily researched, researchers and clinicians consider TB-500 to be functionally identical. As such, studies on the therapeutic benefits of TB4 theoretically apply to both [1].


TB4 is noted for its anti-inflammatory, antifibrotic, and protective effects throughout the body. It upregulates vascular endothelial growth factor (VEGF) and actin to promote angiogenesis and cellular migration, both important in the healing process. In these capacities, it is of particular interest to clinicians for its ability to repair cardiac and nervous tissues following ischemic events [2, 6].


TB4 also regulates cytokine levels to dramatically reduce oxidative stress, and attenuates fibrosis to improve healing. Its anti-inflammatory properties endow it with the potential to treat hepatic, renal, and cardiac injuries, as well as inflammatory bowel disease. Through these mechanisms, TB4 and TB-500 may contribute to the overall integrity of cardiovascular and connective tissues beyond the scope of injury repair [6].


Routes of Administration


Studies on TB-500 and TB4 use in human and animal models have featured several delivery methods. The primary administration routes are parenteral, oral, nasal, and topical. When injected, subcutaneous and intramuscular are the preferred methods. Research on optimal dosage and administration methods suggests that these are subject to change based on the clinical target [7].


TB-500 Benefits | Clinical Trials and Research

Most of the current data on TB-500 is pulled from studies in animal models, although there have been a handful of TB4 clinical trials.


While further investigation on TB-500 use in humans is needed, available findings include numerous therapeutic benefits, most notably:


Wound healing


TB4 improves healing through several physiological processes, including the promotion of epithelial and stem cell migration, as well as the inhibition of apoptosis in multiple tissue types.


Among these are muscle, skin, cardiac, corneal, and nerve cells. It has been closely studied as a treatment for dermal wounds. Clinical trials in both adults and children showed that topical application of TB4 safely accelerated wound healing in venous ulcers and other chronic cutaneous lesions. Another study suggested that TB4 organized collagen fibers to reduce scarring and strengthen connective tissues [2, 6, 8].


Angiogenesis


Studies show that TB4 stimulates the formation of new blood capillaries, a process known as angiogenesis. It has been shown in rat models to upregulate vascular endothelial growth factor (VEGF) and promote endothelial differentiation, increasing capillary density in ischemic tissue. This further contributes to the healing process while facilitating disease recovery and improving cardiovascular health [2].


Anti-inflammatory properties


The anti-inflammatory action of TB4 has been observed in various organs, such as the liver, kidneys, eyes, heart, and brain. This is attributed to its regulation of inflammatory genes and cytokine levels. TB4 was shown in rat models with neuroinflammatory disease to significantly reduce inflammatory cells within the brain. Another animal study showed that TB4 reduced inflammatory factors in neonates with fetal alcohol disorder. In its anti-inflammatory capacity, TB4 is considered a potential treatment for renal and liver fibrosis, as well as ulcerative colitis [6].


Neurological health


Research indicates that TB4 has marked neurological benefits. It has been observed in animal studies to have neuroprotective and neurorestorative effects following traumatic brain and spinal cord injuries. In promoting neurovascular recovery, TB4 shows promise as a treatment for multiple sclerosis and diabetic myopathy, among other neurological diseases [2, 9].


While these are among the most significant findings on the therapeutic potentials of TB-500 and TB4, this is not an exhaustive review. Further areas of interest include improved hair growth and the treatment of metabolic disease. Additionally, TB-500 and TB4 may have global anti-aging outcomes due to their regenerative effects in multiple organ systems [2, 10].


The Heal Like Wolverine Peptide Stack – BPC 157 and TB500


You know the saying that “some things are better together” – well that goes for BPC-157. What’s been dubbed the “Wolverine Peptide Stack” by Ben Greenfield is a combination of BPC-157 and TB500 or Thymosin Beta-4. While BPC-157 upregulates the growth hormone cell receptors, TB500 improves the speed of the entire healing process.


TB-500 Safety and Side Effects


Although TB-500 and TB4 have not been formally evaluated for safety in humans, available data suggest their safety and tolerability when properly administered. Documented adverse effects and rare, transient, and mild. These include [4, 11]:


• Fatigue

• Headache

• Nausea

• Dizziness

• Blurry vision

• Changes in heart rate

• Bruising at the site of injection


Nonetheless, researchers are advised to exercise caution when administering TB-500 due to the relative lack of available information on short or long-term use in human subjects. In general, research peptides can be linked with further minor side effects, such as [12]:


• Changes in blood pressure

• Changes in appetite

• Pain at the site of injection


Adverse effects typically subside on their own and correspond with the use of low-grade peptide products. Such products, purchased from unauthorized suppliers, may be mislabeled or contain harmful contaminants.


TB-500 Dosage and Cycle


Pending regulatory approval for use in humans, TB-500 does not yet have set dosage guidelines. However, research findings offer useful insights into the safe and effective dosage of TB-500 , as follows [4]:


• Many studies involve parenteral administration, namely subcutaneous and intramuscular injection.

• Healing outcomes are often time- and dose-dependent. As such, optimal dosage and frequency may change with the therapeutic target.

• Experimental dosages in humans have included 2-5 mg administered twice weekly. Other studies feature a loading regimen that entails a higher starting dose followed by a period of lower maintenance doses.

• Trials typically do not exceed 8 weeks, and indefinite TB-500 use is not advised.

• It is recommended to start at a low dose and increase it gradually to prevent side effects.

• Dosages seen in animal studies do not scale to human subjects.

• The optimal dosage is subject to change with the weight and health of the subject.

• The best route of administration may vary according to context. For example, when used to heal dermal wounds, topical administration is shown to be the most efficient.

• Novel formulations for oral and intranasal delivery may present unique benefits.

Sample TB-500 Dosing Protocol


According to available findings, researchers may reference this TB-500 dosing protocol for healing and injury recovery.


• TB-500 Dosage: 2mg TB-500, administered once a day via subcutaneous injection

• Course Duration: 15 days

• Notes: This protocol calls for three TB-500 10mg vials for a single research subject per 15-day course. A lower maintenance dosage of 1mg daily may be applied until full or near-full recovery.


References


1. Ho EN, Kwok WH, Lau MY, Wong AS, Wan TS, Lam KK, Schiff PJ, Stewart BD. Doping control analysis of TB-500, a synthetic version of an active region of thymosin β₄, in equine urine and plasma by liquid chromatography-mass spectrometry. J Chromatogr A. 2012 Nov 23;1265:57-69. doi: 10.1016/j.chroma.2012.09.043. Epub 2012 Sep 23. PMID: 23084823.

2. Xing, Y., Ye, Y., Zuo, H., & Li, Y. (2021). Progress on the Function and Application of Thymosin β4. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.767785

3. Low TL, Hu SK, Goldstein AL (1981) 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 78: 1162–1166.

4. World Anti-Doping Agency. World Anti-Doping Code International Standard Prohibited List 2022. WADA website. January 1, 2022. Accessed Mar 2022. https://www.wada-ama.org/sites/default/files/resources/files/2022list_final_en.pdf

5. Nitta K, Shi S, Nagai T, Kanasaki M, Kitada M, Srivastava SP, Haneda M, Kanasaki K, Koya D. Oral Administration of N-Acetyl-seryl-aspartyl-lysyl-proline Ameliorates Kidney Disease in Both Type 1 and Type 2 Diabetic Mice via a Therapeutic Regimen. Biomed Res Int. 2016;2016:9172157. doi: 10.1155/2016/9172157. Epub 2016 Mar 20. PMID: 27088094; PMCID: PMC4818806.

6. Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin β4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opin Biol Ther. 2012 Jan;12(1):37-51. doi: 10.1517/14712598.2012.634793. Epub 2011 Nov 10. PMID: 22074294.

7. EP1908779B1 - thymosin beta 4 derivatives and use thereof [Internet]. Google Patents. Google; [cited 2023Feb]. Available from: https://patents.google.com/patent/EP1908779B1/en

8. Ehrlich HP, Hazard SW 3rd. Thymosin beta4 enhances repair by organizing connective tissue and preventing the appearance of myofibroblasts. Ann N Y Acad Sci. 2010 Apr;1194:118-24. doi: 10.1111/j.1749-6632.2010.05483.x. PMID: 20536458.

9. Michael Chopp & Zheng Gang Zhang (2015) Thymosin β4 as a restorative/regenerative therapy for neurological injury and neurodegenerative diseases, Expert Opinion on Biological Therapy, 15:sup1, 9-12, DOI: 10.1517/14712598.2015.1005596

10. Maar K, Hetenyi R, Maar S, Faskerti G, Hanna D, Lippai B, Takatsy A, Bock-Marquette I. Utilizing Developmentally Essential Secreted Peptides Such as Thymosin Beta-4 to Remind the Adult Organs of Their Embryonic State-New Directions in Anti-Aging Regenerative Therapies. Cells. 2021 May 28;10(6):1343. doi: 10.3390/cells10061343. PMID: 34071596; PMCID: PMC8228050.

11. Wang, X., Liu, L., Qi, L., Lei, C., Li, P., Wang, Y., Liu, C., Bai, H., Han, C., Sun, Y., & Liu, J. (2021). A first‐in‐human, randomized, double‐blind, single‐ and multiple‐dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers. Journal of Cellular and Molecular Medicine, 25(17), 8222-8228. https://doi.org/10.1111/jcmm.16693

12. Brennan, R., Wells, J. G., & Van Hout, M. C. (2014). An unhealthy glow? A review of melanotan use and associated clinical outcomes. Performance Enhancement & Health, 3(2), 78–92. doi:10.1016/j.peh.2015.06.001

13. Notice of opportunity for hearing (Nooh) manookian, Edward 8/5/16 [Internet]. U.S. Food and Drug Administration. FDA; 2016 [cited 2022Sep23]. Available from: https://www.fda.gov/regulatory-information/electronic-reading-room/notice-opportunity-hearing-nooh-manookian-edward-8516

14. Richards, N., & Hudson, I. (2016). UK medicines regulation: Responding to current challenges. British Journal of Clinical Pharmacology, 82(6), 1471-1476. https://doi.org/10.1111/bcp.13077

15. Shaer, D. A., Musaimi, O. A., & Albericio, F. (2022). 2021 FDA TIDES (Peptides and Oligonucleotides) Harvest. Pharmaceuticals, 15(2). https://doi.org/10.3390/ph15020222

16. At 7.5% CAGR, global peptide synthesis market size & share to surpass US$ 845.68 million by 2028 | peptide synthesis industry [Internet]. Bloomberg.com. Bloomberg; 2023 [cited 2023Feb]. Available from: https://www.bloomberg.com/press-releases/2023-01-31/at-7-5-cagr-global-peptide-synthesis-market-size-share-to-surpass-us-845-68-million-by-2028-peptide-synthesis-industry?utm_source=website&utm_medium=share&utm_campaign=copy

17. Eglovitch JS. FDA guidance spells out acceptance criteria for synthetic peptide andas [Internet]. Regulatory Affairs Professionals Society (RAPS). [cited 2023Feb]. Available from: https://www.raps.org/news-and-articles/news-articles/2021/5/fda-guidance-spells-out-acceptance-criteria-for-sy

18. The Federal Register [Internet]. Federal Register :: Request Access. [cited 2023Feb]. Available from: https://www.federalregister.gov/documents/2018/12/12/2018-26840/definition-of-the-term-biological-product

19. The Federal Register [Internet]. Federal Register :: Request Access. [cited 2023Feb]. Available from: https://www.federalregister.gov/documents/2021/05/14/2021-10179/evaluating-the-clinical-pharmacology-of-peptides-establishment-of-a-public-docket-request-for

20. Huang Z, Song Y, Pang Z, Zhang B, Yang H, Shi H, Chen J, Gong H, Qian J, Ge J. Targeted delivery of thymosin beta 4 to the injured myocardium using CREKA-conjugated nanoparticles. Int J Nanomedicine. 2017;12:3023-3036

https://doi.org/10.2147/IJN.S131949

21. Wang W, Jia W, Zhang C. The Role of Tβ4-POP-Ac-SDKP Axis in Organ Fibrosis. International Journal of Molecular Sciences. 2022; 23(21):13282. https://doi.org/10.3390/ijms232113282

22. Bose M, Farias Quipildor G, Ehrlich ME, Salton SR. Intranasal Peptide Therapeutics: A Promising Avenue for Overcoming the Challenges of Traditional CNS Drug Development. Cells. 2022; 11(22):3629. https://doi.org/10.3390/cells11223629

23. W. B. What is Bacteriostatic Water? [Internet]. Study.com | Take Online Courses. Earn College Credit. Research Schools, Degrees & Careers. 2022 [cited 2022Aug17]. Available from: https://study.com/academy/lesson/what-is-bacteriostatic-water-definition-uses.html

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