Peptides have exploded in popularity within the anti-aging space, and for good reason.
They come with promises of a strengthened immune system, rejuvenated skin and a healthier head of hair.
A great example is Thymosin Beta 4 (TB4), which can deliver these outcomes for both men and women.
But research is showing TB4 can also accelerate wound healing, repair sun-damaged skin, and protect against illnesses via enhanced production of antibodies and white blood cells.
In this article, we’ll explore the science backing Thymosin Beta 4’s health benefits and how they can boost your health from the outside-in… AND the inside-out!
What is Thymosin Beta 4?
Thymosin Beta 4 is the predominant form of thymosin, a hormone produced by the thymus gland.
One of its main modes of action is tissue regeneration.
TB4 is part of a group of proteins that helps build cells, and when it binds with actin, TB4 mobilizes and migrates stem and progenitor cells.
When you sustain an injury, it is released by the body to protect and repair the damaged tissues and cells.
This leads to a number of biological cascades:
- Angiogenesis, i.e. the formation of new blood cells
- Minimized scar formation via reduction of myofibroblasts (the cells responsible for wound healing and tissue repair)
In short, TB4 supports the protection, regeneration, and remodeling of damaged or injured tissues, essential for effective tissue repair.
Additionally, Thymosin plays a crucial role in immune health by promoting the production of T-cells and supporting B cells in developing into plasma cells, which produce antibodies.
In doing so, thymosin reduces inflammatory markers like cytokines and curbs microbial growth due to injury.
This makes TB4 a valuable treatment for colds, infections, influenza, and even deadlier diseases like HIV and AIDS.
NOTE: The synthetic version of Thymosin Beta 4, known as TB-500, has healing properties that aid in repairing damaged ligaments, tendons, muscles, heart, skin, and hair.
Benefits of Thymosin Beta 4 Peptide Therapy
Thymosin Beta 4 offers several health benefits, all of which are backed by studies in both animals and humans.
Let’s look at the evidence supporting the use of TB4 for immune system health, hair growth, healing, and more!
Immune System Health
As already stated, TB4 falls under the category of peptides that boost your immune system health.
It works by increasing the production of antibodies and white blood cells, keeping your immune system primed to fight infections while protecting you from sickness-inducing pathogens.
TB4 also works by suppressing the proinflammatory cytokine interleukin 8 (IL8) while protecting your cells from cell death (i.e. apoptosis) due to tumor necrosis factor-α.
This has been shown in a study published in the European Journal of Oral Sciences, where the use of TB4 protected participants’ gums from the oral cavity and damage caused by a mouthwash that contained carbamide peroxide and chlorhexidine digluconate:
“Thymosin beta4 (Tbeta(4)) is a naturally occurring, ubiquitous, non-toxic protein with documented wound-healing, anti-inflammatory, anti-apoptotic, and tissue-repair properties in skin, the ocular surface, and the heart.
The ability of Tbeta(4) to demonstrate similar protective properties in cells of the oral cavity was analyzed using an in vitro model of cultured human gingival fibroblasts.
Thymosin beta 4 significantly suppressed the secretion of interleukin-8 (IL-8) following stimulation with tumor necrosis factoralpha (TNF-alpha), suggesting that it may suppress the inflammatory response initiated by pro-inflammatory cytokines.
By contrast, Tbeta(4) was not effective in protecting fibroblasts from challenge with lipopolysaccharide purified from Porphyromonas gingivalis or Escherichia coli.
Thymosin beta 4 was able to protect gingival fibroblasts against the known cytotoxic effects of chlorhexidine digluconate, a mouthrinse containing chlorhexidine digluconate, and carbamide peroxide.
Additionally, Tbeta(4) was able to protect gingival fibroblasts from the apoptosis that is induced by stimulation with TNF-alpha or by exposure to chlorhexidine.
Because of its multifunctional roles in protecting cells against damage, Tbeta(4) may have significant potential for use as an oral healthcare aid with combined antimicrobial, anti-inflammatory, anti-apoptotic, and cytoprotective properties.”
In another study, TB4 was shown to modulate lymphocyte function in the human colon.
It did so by suppressing thymidine incorporation into lamina propria lymphocytes, which helped to reduce inflammation and improve immune response:
“Thymosin alpha 1 and thymosin beta 4 are two thymosin fraction 5-derived peptides with the capacity to alter a variety of immune functions in human and animal models.
In this study we investigated the effect of both thymosin alpha 1 and thymosin beta 4 on human colonic lamina propria lymphocyte (LPL) proliferation and ornithine decarboxylase (ODC) activity.
LPL from eighteen human colon specimens were cultured in the presence or absence of thymosin alpha 1 and thymosin beta 4.
We found that both peptides suppressed thymidine incorporation into LPL.
However, thymosin alpha 1 and thymosin beta 4 did not alter thymidine incorporation into phorbol ester (PDB) and calcium ionophore (ionomycin)-stimulated LPL.
Furthermore, thymosin alpha 1 and thymosin beta 4 also did not alter ODC activity in Con A-stimulated LPL.
These results suggest that both peptides alter LPL proliferation and that the mechanism for this inhibition may not involve the calcium fluxes or the ODC pathway but may involve protein kinase C.
We postulate that thymosin alpha 1 and thymosin beta 4 may participate in the modulation of the human mucosal immune system.”
Skin Health, Injury Recovery, and Wound Healing
TB4 is one of the few peptides that is simultaneously effective for skin health, injury recovery, and wound healing.
That’s why it’s one of the peptides included in my Wolverine Stack to reduce the time required to treat bodily damage.
TB4 particularly excels in accelerating cellular-level wound healing, which also makes it a must-have peptide for athletes recovering from rigorous training.
And it serves as a valuable peptide for pain management, offering relief and support for various types of pain.
In a study published in the Annals of New York Academy of Sciences, patients with corneal wounds (a difficult-to-heal wound that usually results in scarring and vision loss) experienced faster wound healing after they were given 2 drops of TB4 eye drops four times daily:
“Neurotrophic corneal defects are difficult to heal and all too often lead to scarring and vision loss. Medical management is often of limited success.
We describe the results of nine patients (ages 37–84) with chronic nonhealing neurotrophic corneal epithelial defects who were treated with thymosin beta 4 (Tβ4) sterile eye drops for 28 or 49 days with a follow-up period of 30 days.
Those with geographic defects (six patients) showed dramatic healing without clinically significant neovascularization.
Stromal thinning was observed in one patient.
Three patients with punctate epithelial defects did not have a demonstrable change in their clinical findings.
Reduced ocular irritation was reported by all patients soon after treatment initiation.
Results from these compassionate use cases indicate that Tβ4 may provide a novel, topical approach to wound healing in chronic nonhealing neurotrophic corneal ulcers.”
In another study published in Dovepress, both patients and rat models with ulcers and chronic wounds experienced faster wound repair after using Thymosin Beta 4:
“Thymosin beta 4 (Tβ4) is a peptide with 43 amino acids that is critical for repair and remodeling tissues on the skin, eye, heart, and neural system following injury.
To fully realize its utility as a treatment for disease caused by injury, the authors constructed a cost-effective novel Tβ4 dimer and demonstrated that it was better able to accelerate tissue repair than native Tβ4.
A prokaryotic vector harboring two complete Tβ4 genes with a short linker was constructed and expressed in Escherichia coli.
A pilot-scale fermentation (10 L) was performed to produce engineered bacteria and the Tβ4 dimer was purified by one-step hydrophobic interaction chromatography.
The activities of the Tβ4 dimer to promote endothelial cell proliferation, migration, and sprouting were assessed by tetramethylbenzidine (methylthiazol tetrazolium), trans-well, scratch, and tube formation assays. The ability to accelerate dermal healing was assessed in rats.
After fermentation, the Tβ4 dimer accounted for about 30% of all the bacteria proteins.
The purity of the Tβ4 dimer reached 98% after hydrophobic interaction chromatography purification.
An average of 562.4 mg/L Tβ4 dimer was acquired using a 10 L fermenter.
In each assay, the dimeric Tβ4 exhibited enhanced activities compared with native Tβ4.
Notably, the ability of the dimeric Tβ4 to promote cell migration was almost two times higher than that of Tβ4.
The rate of dermal healing in the dimeric Tβ4-treated rats was approximately 1 day faster than with native Tβ4-treated rats.
The dimeric Tβ4 exhibited enhanced activity on wound healing than native Tβ4, and the purification process was simple and cost-effective.
This data could be of significant benefit for the high pain and morbidity associated with chronic wound disease.
A better strategy to develop Tβ4 as a treatment for other diseases caused by injuries such as heart attack, neurotrophic keratitis, and multiple sclerosis was also described.”
Hair Growth
Thymosin Beta 4, a peptide for hair growth, has regenerative properties that are also applicable towards improving hair health.
A study published in the Journal of Dermatological Treatment found patients with alopecia areata — an autoimmune disorder causing hair loss — experienced reduced hair loss and new hair growth after three months of treatment with TB4:
“Alopecia areata (AA) is a non-scarring auto-immune hair disorder.
Recent researches explained the role of growth factors (GFs) in hair follicle cycling.
The main reservoir of GFs are alpha-granules of platelets and novel procedures have been implemented aimed at collecting platelet-rich plasma (PRP).
PRP has been safely implemented in many medical applications and has also been successfully used as alternative cell-based therapy for the treatment of hair growth disorders, among which also AA.
By means of a randomized double-blinded, placebo and active-controlled, parallel group study we have studied the efficacy of a cosmetic product (named TR-M-PRP plus) comprising biomimetic peptides specific for hair growth, mimicking PRP composition for the treatment of AA.
Subjects were treated for three months and evaluated, at the end of the study and after one month of follow-up, as regards hair growth using SALT score.
TR-M-PRP plus-like topic produced a statistically significant clinical improvement in SALT score after 3 months of therapy, compared to baseline.
Hair growth results further improved after 1 month of follow-up.
This clinical investigation suggests that the biotechnological designed PRP-like cosmetic could represent a valid and safer alternative to autologous PRP for the treatment of AA.”
In a separate study with rats published in The FASEB Journal, Thymosin Beta 4 helped to stimulate the active phase of the hair follicle cycle and promote stem cell migration to the base of the follicle, thereby inducing hair growth:
“Thymosin B4, a 43-amino acid polypeptide that is an important mediator of cell migration and differentiation, also promotes angiogenesis and wound healing.
Here, we report that thymosin B4 stimulates hair growth in normal rats and mice.
A specific subset of hair follicular keratinocytes in mouse skin expresses thymosin B4 in a highly coordinated manner during the hair growth cycle.
These keratinocytes originate in the hair follicle bulge region, a niche for skin stem cells.
Rat vibrissa follicale clonogenic keratinocytes, closely related, if not identical, to the bulge-residing stem cells, were isolated and their migration and differentiation increased in the presence of nanomolar concentrations of thymosin B4.
Expression and secretion of the extracellular matrix-degrading enzyme matrix metalloproteinase-2 were increased by thymosin B4.
Thus, thymosin B4, accelerates hair growth, in part, due to its effect on critical events in the active phase of the hair follicle cycle, including promoting the migration of stem cells and their immediate progeny to the base of the follicle, differentiation, and extracellular matrix remodeling.”
Additional Research on Thymosin Beta 4
While the applications below are not as well-supported as the health benefits previously discussed, they show the promising potential of Thymosin Beta 4 to tackle many other disease states.
Improves Heart Health
Although our hearts are capable of self-repair, tissue/muscle damage due to a heart attack is irreversible.
However, a growing number studies report TB4 may repair and regenerate heart damage caused by heart attacks.
In fact, stimulated vessel growth was observed in one experiment where mammals were given TB4.
The peptide also prevented heart muscle cell death while promoting heart stem cell growth, helping to regenerate heart muscle damage:
“Hypoxic heart disease is a predominant cause of disability and death worldwide.
As adult mammals are incapable of cardiac repair after infarction, the discovery of effective methods to achieve myocardial and vascular regeneration is crucial.
Efforts to use stem cells to repopulate damaged tissue are currently limited by technical considerations and restricted cell potential.
We discovered that the small, secreted peptide thymosin beta4 (Tbeta4) could be sufficiently used to inhibit myocardial cell death, stimulate vessel growth, and activate endogenous cardiac progenitors by reminding the adult heart on its embryonic program in vivo.
The initiation of epicardial thickening accompanied by increase of myocardial and epicardial progenitors with or without infarction indicate that the reactivation process is independent of injury.
Our results demonstrate Tbeta4 to be the first known molecule able to initiate simultaneous myocardial and vascular regeneration after systemic administration in vivo.”
Improves Liver Health
Thymosin Beta 4 has been shown to suppress the activation, proliferation, and migration of hepatic stellate cells.
These three biological cascades would otherwise result in liver fibrosis or scarring if left unaddressed:
“Liver fibrosis, the main characteristic of chronic liver diseases, is strongly associated with the activation of hepatic stellate cells (HSCs), which are responsible for extracellular matrix production.
As such, investigating the effective regulators controlling HSC activation provides important clues for developing therapeutics to inhibit liver fibrosis.
Thymosin beta 4 (Tβ4), a major actin-sequestering protein, is known to be involved in various cellular responses.
A growing body of evidence suggests that Tβ4 has a potential role in the pathogenesis of liver fibrosis and that it is especially associated with the activation of HSCs.
However, it remains unclear whether Tβ4 promotes or suppresses the activation of HSCs.
Herein, we review the potential role of Tβ4 in liver fibrosis by describing the effects of exogenous and endogenous Tβ4, and we discuss the possible signaling pathway regulated by Tβ4.
Exogenous Tβ4 reduces liver fibrosis by inhibiting the proliferation and migration of HSCs.
Tβ4 is expressed endogenously in the activated HSCs, but this endogenous Tβ4 displays opposite effects in HSC activation, either as an activator or an inhibitor.
Although the role of Tβ4 has not been established, it is apparent that Tβ4 influences HSC activation, suggesting that Tβ4 is a potential therapeutic target for treating liver diseases.”
Promotes Nerve Regeneration
Thymosin Beta 4 plays an important role in nerve regeneration and protection in different types of nerve injuries.
For example, the use of TB4 helped reduce inflammatory infiltrates and stimulate oligodendrogenesis (the formation of the protective covering of neurons) in mice with brain inflammation.
In turn, this helped to improve the recovery of their cognitive abilities:
“In the present study, we hypothesized that thymosin beta 4 (Tbeta4) is a potential therapy of multiple sclerosis (MS).
To test this hypothesis, SJL/J mice (n=21) were subjected to experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
EAE mice were treated with saline or Tbeta4 (6 mg/kg, n=10) every 3 days starting on the day of myelin proteolipid protein immunization for total 5 doses. Neurological function, inflammatory infiltration, oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes were measured in the brain of EAE mice.
Double immunohistochemical staining was used to detect proliferation and differentiation of OPCs.
Tbeta4 was used to treat N20.1 cells (premature oligodendrocyte cell line) in vitro, and proliferation of N20.1 cells was measured by bromodeoxyuridine (BrdU) immunostaining. Tbeta4 treatment improved functional recovery after EAE.
Inflammatory infiltrates were significantly reduced in the Tbeta4 treatment group compared to the saline groups (3.6±0.3/slide vs 5±0.5/slide, p<0.05). NG2+ OPCs (447.7±41.9/mm2 vs 195.2±31/mm2 in subventricular zone, 75.1±4.7/mm2 vs 41.7±3.2/mm2 in white matter), CNPase+ mature oligodendrocytes (267.5±10.3/mm2 vs 141.4±22.9/ mm2), BrdU+ with NG2+ OPCs (32.9±3.7/mm2 vs 17.9±3.6/mm2), BrdU+ with CNPase+ mature oligodendrocytes (18.2±1.7/mm2 vs 10.7±2.2/mm2) were significantly increased in the Tbeta4 treated mice compared to those of saline controls (p<0.05).
These data indicate that Tbeta4 treatment improved functional recovery after EAE, possibly, via reducing inflammatory infiltrates, and stimulating oligodendrogenesis.”
Improves Brain Health
Moreover, Thymosin Beta 4 is reported to protect your brain from possible injuries such as stroke and this is largely thanks to its tissue protective/regenerative properties.
Rats that had experienced ischemic strokes and were given TB4 showed improvement in their neurological functions beginning at 14 and 35 days of treatment.
The peptide boosted vessel density in the ischemic boundary and myelinated axons while promoting remyelination.
All of which also increases myelinating oligodendrocyte and oligodendrocyte progenitor cell (OPC) production:
“Male Wistar rats (n=18) were subjected to embolic middle cerebral artery occlusion (MCAo).
Tbeta4 (6 mg/kg, IP) was administered 24 h after MCAo and then every 3 days for four additional doses (n=9). Rats treated with saline were used as a control (n=9).
The adhesive-removal test (ART) and modified Neurological Severity Score (mNSS) were performed to measure functional outcome.
Rats were sacrificed 56 days after MCAo.
Immunostaining was performed with antibodies against NG-2 (chondroitin sulfate proteoglycan), CNPase (2″, 3″-cyclic nucleotide 3′-phosphodiesterase) to detect immature and mature oligodendrocytes.
Neurofilament-H (NF-H) antibodies were used to detect axons while myelinated axons were identified with Bielschowsky/Luxol (B/L) Blue staining. EBA (endothelial barrier antigen) was used for detection of mature vessels.
Ischemic rats treated with Tbeta4 demonstrated a significant overall improvement in the ART and the mNSS when compared to controls.
Significant improvement was observed beginning at 14 and 35 days, respectively.
Lesion volumes showed no significant differences between the two groups.
Treatment with Tbeta4 increased myelinated axons and increased vessel density in the ischemic boundary and augmented remyelination which was associated with an increase of oligodendrocyte progenitor cells (OPCs) and myelinating oligodendrocytes.”
How Thymosin Beta 4 Works and Proper Dosage
To recap what was stated earlier in the article: Thymosin Beta 4 binds to actin and promotes the movement and mobilization of stem/progenitor cells, both of which are crucial for new blood vessel formation and tissue regeneration.
But it can help boost immune cell numbers, reduce inflammation, and decrease scar formation by reducing myofibroblast production.
As for the proper dosage of Thyosmin Beta 4, the recommended dosing protocol is straightforward:
300 mcg to 1 mg of Thymosin Beta 4 taken once a day via subcutaneous injection
I recommend not using it than 3 months continuously; you should cycle it “on” for 6-12 weeks and then cycle “off” for 6 weeks.
Individual dosage needs will vary, so always make sure to consult with your doctor before starting the regimen.
Potential Side Effects of Thymosin Beta 4
Thymosin Beta 4 is generally safe when used as directed, although some first-time users may report some common side effects at the site of injection:
- Discomfort
- Reddening
- Pain
However, using TB4 incorrectly tends to lead to the following list of undesired outcomes:
- Dizziness
- Headache
- Lethargy
- Nausea
- Tiredness
If these symptoms persist despite proper use of TB4, talk to your doctor to adjust your dosage and lower the occurrence of unwanted side effects.
Closing Thoughts and Where to Buy Thymosin Beta 4
If you’re looking to optimize your immune system, hair health and skin health as you age, Thymosin Beta 4 is a peptide worth using.
Its anti-inflammatory and regenerative properties also offer potential benefits for your cardiovascular health, cognitive health, and liver function.
But before adding TB4 to your stack of existing peptides, consult your doctor for guidance on the correct dosage and administration to minimize potential risks.
It’s also crucial to purchase Thymosin Beta 4 from a reputable supplier like Limitless Biotech to ensure you’re getting the highest-quality product possible.
You can choose between Limitless Biotech’s Thymosin Beta-4 Peptide 10 mg (TB4 Fragment 1-4) and TB-500 Thymosin Beta 4 Fragment (17-23).
They have the best formulations of experimental compounds available, and no other vendor comes close to offering them at ultra-high levels of purity for reasonable prices.
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