A to Z Guide on the Wound Healing TB-500
TB-500 peptide, also known as Thymosin beta 4, or TB-4, has been shown to help in the healing process after injury, especially brain and neurological injury. Other TB-500 research has shown it helps with wound healing and hair growth.
Wound healing is a natural yet complex process where the destroyed or damaged tissues in a human body are replaced by the newly produced tissue with the help of the tissue regenerative proteins. One such naturally occurring regenerative protein is Thymosin beta 4. This is a naturally occurring protein found in large quantities in the platelet cells. It is regenerative in nature and helps restore the damaged tissues.
TB-500 peptide is the synthetic version of the otherwise naturally occurring protein Thymosin beta 4. TB-500 peptide has the same properties as Thymosin beta 4, and helps induce angiogenesis, elevate the wound healing process, and possess other properties including increased metastatic potential of tumor cells and hair growth.
TB-500 peptide, which is synthetic in nature, mimics the properties of the natural regenerative hormones found in the body.
Apart from being highly soluble in water and light in weight, TB500 is a 43 amino acid containing peptide found in abundance in the wound fluid that comprises multiple blood platelets. This peptide also has anti-inflammatory properties and can escalate wound healing and repair in brain, spinal cord, and heart, in addition to skin repair (1).
Having extremely low molecular weight, the peptide easily travels throughout the body due to which it can promote healing at a faster rate than usual.
Thymosin and TB-500 History
Prof. Allan Goldstein first discovered thymosin protein in 1964 and its great impact on the human immune system.
Until 1964, the thymus gland was considered as simply an existing body organ without any function. However, soon after the experiment, it was discovered that thymus gland is the source of body T-cells, a type of white blood cells and releases thymosin proteins, which are critical for a healthy immune system.
During these years when thymosin was first discovered, Prof. Goldstein worked with a company to commercialize two types of thymosin: thymosin alpha 1 (which elevates human immune system) and thymosin beta 4 (which elevates wound repair and healing). Since then, there have been several research and clinical studies that have advanced the potential health benefits of these peptides (2).
TB-500 Mode of Action
The healing effects of TB-500 are largely due to its ability to upregulate the level of actin protein in the human body.
What makes TB-500 increase the levels of actin?
TB-500 peptide, also known as thymosin β(4), comprises a distinct peptide segment (17)LKKTETQ(23) which acts as the active site responsible for actin binding, cell migration and wound healing (4).
Below is the amino acid sequence of TB-500 –
Thymosin-beta (4) biologic description – image of amino acid sequence [Image source: NIH.gov]
Actins are involved in a sequence of wound healing events including acute inflammation, collagen deposition and contraction and remodeling. By promoting the levels of actin in the body, TB 500 induces the tissue repair processes which eventually leads to wound healing (3).
Moreover, given that TB 500 has low molecular weight and is highly soluble in nature, it makes the peptide extremely versatile and mobile, with the ability to travel long distances within the human body. Owing to this characteristic, TB500 can easily flow any distance in the body, identify the wound area and stimulate the healing process. This makes it unique and does not necessarily require it to be administered at the site of the wound itself.
TB 500 Benefits
Below are the main advantages or benefits of TB 500 peptide:
- Elevate wound healing and tissue repair
- Reduce inflammation, as it promotes fast healing
- Boost repair of connective tissue injuries, i.e. healing tendons and ligaments
- Promote dermal or skin healing
- Relieve pain
- Elevate growth of hair
A number of research and clinical studies have proven the remarkable effects of using TB-500 peptide including structuring novel blood vessels, muscle tissue fibers, cell migration and blood cells. It is because of this unique ability of TB 500, that studies have been conducted to further understand the ability of this compound to heal heart tissues for athletes suffering from a condition called ventricular hypertrophy. This is further discussed in detail in this article.
Research studies on animals have shown the TB-500 has the ability to promote stem cell development, as well as stem cell differentiation and migration in the hair follicles. By doing so, TB-500 promotes and speeds up the hair growth process. These studies are described in detail below in this article.
TB-500 Research and Clinical Studies
Early Research and Discovery
In 1964, Dr. Goldstein, then a postdoctoral student, and his professor Abraham White conducted research that mainly focused on the thymus gland and its functionality. They isolated the small proteins secreted by thymus gland, located below the breast bone and above the heart – which is when they discovered how powerful the thymosin (thymus proteins) are in maintaining the immunity system of the human body. Until then, it was accepted that children with rare immune deficiency diseases eventually develop multiple infections and die early in life; but during the study it was discovered that it is because their thymus gland was not functioning and releasing these proteins, which led them to immune deficiency in the first place (2).
After extensive safety and pre-clinical studies, Dr. Goldstein received approval from the U.S Food and Drug Administration (FDA) to conduct clinical trials on humans.
In 1974, a 5-year-old girl named Heather, who was critically ill, became the first patient to receive thymosin. The peptide turned out to be her savior, successfully increasing the number of her T white blood cells, which in turn increased her immunity (2).
TB-500 Effect on Acute Wounds
In 1999, a research study was carried out where fully wounded rats were administered with TB-500 via topical or intraperitoneal routes of administration. Four days after the application, it was noticed that the TB-500 peptide treated rats showed a 41% increase in re-epithelialization that the rats treated with saline. Seven days after the treatment, the TB-500 wounds were contracted by at least 11% more than the saline treated wounds.
Upon analysis, it was concluded that TB500 induces angiogenesis and collagen deposition which increases the wound healing rate. The process was stimulated 2 to 3 folds when as little as 10 pg of the peptide was applied. The study proved TB500 as a potent wound healing medication with many potential uses of the compound (5).
TB-500 Effect on Chronic Wounds
Chronic non-healing wounds had become a global problem with no medication able to promote or expedite the healing process.
Research studies were carried out on normal rats and mice, diabetic mice, aged mice, and steroid treated rats. All these animals, suffering from full-thickness punch wounds, were treated with TB-500 peptide. It was discovered that TB-500 accelerated the wound healing process in all animals, regardless of their pre-existing conditions.
Furthermore, phase 2 clinical trials were also conducted on individuals suffering from stasis and pressure ulcers. It was noticed that TB-500 was able to accelerate the healing process by as much as one month. TB-500 would promote stem cell mobilization and inhibit inflammation and infection – which would work to smoothen and elevate the healing process (6).
Heart Protection Abilities
Pulmonary hypertension is a progressive heart (cardio) disease where the pulmonary arteries restrict the blood ejection by the right ventricle. This results in increased pulmonary vascular resistance and pressure causing ventricular failure of the heart.
Initial studies were carried out on mice suffering from pulmonary hypertension, induced by monocrotaline (MCT), to understand the full potential of TB-500 in such health related issues.
It was discovered that TB-500 specifically targets the Notch3-Col 3A-CTGF gene axis in MCT-treated mice, which results in decreasing the right ventricular hypertrophy by a significant amount. While further clinical studies are still underway, this study opened a new chapter of potentially using TB-500 as a vasculo-protective agent for the treatment of Pulmonary hypertension and ventricular failure (7).
Hair Growth Effect
In 2003, studies were carried out on mice to examine the role of TB-500 in hair growth. Upon treatment with TB-500, it was determined via histological examination of the mouse skin cells, that the peptide increased the number of hair shafts and hair follicles, thereby inducing hair growth.
Upon real-time PCR and western blotting techniques, changes in the expression of m-RNA cells were noticed between the TB500 treated and control treated mice. The m-RNA and protein levels were elevated in TB-500 treated mice, which could have played a major role in inducing hair growth. This study proved that TB-500 may have potential use in the treatment of hair growth problems in adults (8).
TB-500 Side Effects
Based on multiple research studies conducted, it has been evident that the peptide is usually highly tolerated and does not show any major side effects.
Below listed are the common side effects reported with most of the peptides. The incidence of these side effects occurring with TB-500 are extremely rare, if at all reported.
- Dry mouth
- Flu-like symptoms
- Fatigue, temporary tiredness
There have been conflicting research studies about TB-500 potentially causing cancer. It was discovered that cancer patients have a large number of thymosin proteins built up in the carcinogenic tissues compared to usual. At first, doctors interpreted this as thymosin potentially causing cancer.
However, recent studies have shown that since thymosin is largely responsible to produce white blood cells, thymosin would naturally be in a higher proportion to boost the release of white blood cells and increase immunity. Thymosin was then considered as a potential indicator of carcinogenic cells, rather than cancer causing agents (11).
Is TB-500 Banned in Sports?
It is suspected that TB-500 is used as a doping agent in sports, and is hence banned by the World Anti-Doping Agency (WADA). (9)
TB-500 was originally extensively used in race horses to prevent wounds which may occur during the sport. Over time it was suspected that due to proven desirable results, the peptide may have been used by many athletes, which is otherwise not allowed.
Studies have shown that post administration, traces of the peptide can be detected in the plasma and urine sample via high-performance liquid chromatography (HPLC) and mass spectrometry (MS) methods. These methods can easily identify the compound’s metabolites, N-terminal acetylated 17-23 fragments of TB-500 (Ac-LKKTETQ), which would confirm the use of this agent (10).
TB-500 Powder and Reconstitution
The peptide is generally available in powder form. The lyophilized powder of TB-500 must be reconstituted with 0.9% sodium chloride, sodium chloride acting as the bacteriostatic solvent agent.
Recommended Dosage of TB-500
Clinical studies have been conducted where TB-500 was administered in the dose ranging from 1mg to 10mg per day from anywhere between 56 to 84 days (12), (13).
TB-500 is usually administered in the tapering dose format. During the first one to two weeks, full dose is taken as per the range indicated above. This is then lowered accordingly which is called the maintenance dose.
However, considering the nature of the peptide, as well as considering unique medical history for each individual, it is best recommended to seek medical advice prior to use to ensure the best results.
When is the best time to take TB-500?
There is no fixed or best time as such to take the peptide, however, it is recommended to use TB-500 at the same time to maintain consistency and for best results.
TB-500 Storage Recommendation
The reconstituted TB-500 mixture must not be stored at room temperature or in areas exposed to high sunlight. To ensure best results and sustain efficacy, it is recommended to store the product away from direct sunlight and refrigerated at low temperatures.
TB-500 peptide is a 43-amino acid containing peptide proven to demonstrate excellent results in wound healing, tissue repair and increased immune system. Recent studies have also shown TB-500 peptide to induce hair growth upon administration.
All research and clinical studies of this peptide have demonstrated a highly safe, efficacious, and non-toxic drug profile with little to no side effects. It must always be taken into consideration that this peptide is still under clinical trials and is prohibited for use by WADA athletes.
Should you consider doing research with TB-500, consider all the above evidence, and seek medical advice for a tailored prescription based on an individual profile.
1. Kleinman HK, Sosne G. Thymosin β4 Promotes Dermal Healing. Vitam Horm. 2016;102:251-75. doi: 10.1016/bs.vh.2016.04.005. Epub 2016 May 24.
2. Julia Parmley, A Life-Saving Discovery, January 04, 2010.
3. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008 May 15;453(7193):314-21. doi: 10.1038/nature07039. PMID: 18480812.
4. 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.
5. Katherine M. Malinda et.al, Thymosin β4 Accelerates Wound Healing, Journal of Investigative Dermatology, Volume 113, Issue 3, 1999, Pages 364-368, ISSN 0022-202X.
6. Treadwell T, Kleinman HK, Crockford D, Hardy MA, Guarnera GT, Goldstein AL. The regenerative peptide thymosin β4 accelerates the rate of dermal healing in preclinical animal models and in patients. Ann N Y Acad Sci. 2012 Oct.
7. Wei C, Kim IK, Li L, Wu L, Gupta S. Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy. PLoS One. 2014 Nov 20;9(11):e110598.
8. Gao, Xy., Hou, F., Zhang, Zp. et al. Role of thymosin beta 4 in hair growth. Mol Genet Genomics 291, 1639–1646 (2016).
9. List of all prohibited substances by WADA – https://www.wada-ama.org/en/
10. Esposito S, et al. 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. Drug Test Analysis. 2012 Sep.
11. Piao Z, Hong CS, Jung MR, Choi C, Park YK. Thymosin β4 induces invasion and migration of human colorectal cancer cells through the ILK/AKT/β-catenin signaling pathway. Biochem Biophys Res Commun. 2014 Sep 26;452(3):858-64.
12. Study of Thymosin Beta 4 in Patients with Pressure Ulcers https://www.clinicaltrials.gov/ct2/show/NCT00382174
13. A Phase 2 study of the effect of Thymosin Beta 4 on Wound Healing in Patients https://www.clinicaltrials.gov/ct2/show/NCT00311766
TB-500 Continued Research
For an overall TB-500 peptide review and its potential healing benefits, especially with tendon and ligament injuries, read our recent TB-500 Review, Benefits, Side Effects blog post.
NOTE: These products are intended for laboratory research use only. TB-500 for sale is not for personal use. Please review and adhere to our Terms and Conditions before ordering.
Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.