TB-500 or BPC-157: what was studied for tendons

TB-500 and BPC-157 are the two peptides most often mentioned in the context of tendon injuries. But what exactly is known about them from the scientific literature? The editorial team has gathered the studies that specifically assessed tendons and adjacent tissues, and explains to what extent these data can be transferred to humans.

What TB-500 and BPC-157 are

BPC-157 is a synthetic peptide of 15 amino acids whose sequence derives from a gastric-juice protein. Practically all studies have been carried out by the group of Predrag Sikiric at the University of Zagreb, which in itself is an important circumstance for assessing the data.

TB-500 is the commercial name of a synthetic peptide related to thymosin β4 (Tβ4). Thymosin β4 itself is a natural protein of 43 amino acids, present in almost all cells, which binds actin and regulates cell motility. Under the name TB-500 what is usually sold is a fragment corresponding to the actin-binding region of Tβ4, or an analogue of it; the exact composition of commercial products varies.

This detail is fundamental: most scientific work has been done with full-length thymosin β4, not with the «TB-500» product. Transferring the results of one to the other must be done very carefully.

Both substances are not registered as medicines and are prohibited by WADA: BPC-157 in section S0, and thymosin β4 and its derivatives, notably TB-500, in section S2.

BPC-157 and tendons: what the experiments showed

The best-known work is Staresinic et al. (2003): in rats with a transected Achilles tendon, BPC-157 accelerated functional, biomechanical and histological recovery compared with the control. The same peptide stimulated the growth of tenocytes in vitro.

Krivic et al. (2006) studied a model of avulsion of the Achilles tendon from the bone and reported improved healing at the attachment site, as well as counteraction of the negative effect of corticosteroids on healing.

Chang et al. (2011) - one of the few works by another group - showed in a culture of rat tendon fibroblasts that BPC-157 increases cell survival under oxidative stress and their migration through activation of the FAK-paxillin pathway.

Together these works form a consistent picture at the level of animals and cells. However, the review by Gwyer et al. (2019) emphasizes: there are no clinical studies of tendon healing in humans, so efficacy in humans remains a hypothesis.

Thymosin β4 and tendons: what is known

The main body of research on thymosin β4 is devoted to other tissues. Malinda et al. (1999) showed accelerated healing of skin wounds in rats, and Bock-Marquette et al. (2004), in the journal Nature, described a protective effect on the heart muscle after infarction in mice.

The mechanism proposed for regeneration is the binding of G-actin and an effect on cell migration, angiogenesis and inflammation. Theoretically this may also apply to tendons, where the migration of fibroblasts into the injury zone is a key stage of healing.

However, there are far fewer studies specifically on tendon injury models with thymosin β4 than for BPC-157, and with the TB-500 product there are effectively none in the peer-reviewed literature. The popularity of TB-500 for tendons rests more on extrapolation and experience in equine veterinary medicine than on dedicated experiments.

The review by Goldstein et al. (2012) describes thymosin β4 as a multifunctional regenerative peptide and lists clinical programmes in ophthalmology, dermatology and cardiology, but not in the treatment of tendinopathies.

Comparison of the evidence for tendons

If we assess purely the number of dedicated works on tendons, BPC-157 has more data. However, almost all of them come from a single laboratory, and independent reproduction of results is one of the key criteria for the reliability of science.

For thymosin β4 the data are broader in scope and come from various groups, but tendons themselves have been studied little. That is, each peptide has its own weak link.

What both have in common is the absence of studies in humans with tendon injuries. Neither peptide has clinical data on dose, efficacy or safety in tendinopathy.

So to the question «what was studied for tendons» the honest answer is this: BPC-157 - in rats and in cell cultures, thymosin β4 - mainly in other tissues, TB-500 as a product - almost nowhere.

Why data in rats do not equal an effect in humans

Rat tendons differ from human ones in size, load, rate of metabolism and healing. An acute transection in a laboratory also bears little resemblance to the chronic tendinopathy that athletes most often face.

In addition, animal studies control conditions that in real life are uncontrolled: the purity of the substance, the route of administration, the uniformity of the injury. A grey-market product has no such guarantee.

The history of pharmacology contains many examples where convincing results in animals were not confirmed in clinical studies. That is why preclinical data are a reason for research, not for use.

What has an evidence base for people with tendinopathy:

• progressive loading treatment (eccentric, isometric, heavy slow exercises);
• correction of training load;
• collagen peptides with vitamin C as an adjunct;
• assessment by a doctor in the absence of improvement.

Editorial conclusions

For tendons, BPC-157 has been studied more than TB-500, but exclusively in animals and cells, mainly in a single laboratory. Thymosin β4 has a broad preclinical base in other tissues, while for the commercial TB-500 there are almost no dedicated tendon studies.

Neither peptide has clinical data on the treatment of tendon injuries in humans, both are not approved as medicines and are prohibited by WADA.

For tendon problems it is advisable to rely on methods with proven efficacy and to consult sports medicine specialists.

We also recommend reading our materials «TB-500 vs BPC-157: a comparison of study data», «BPC-157 or collagen: what's the difference» and on the status of peptides on the WADA list.

References

1. Staresinic M, Sebecic B, Patrlj L, et al. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. J Orthop Res. 2003;21(6):976–983.
2. Krivic A, Anic T, Seiwerth S, Huljev D, Sikiric P. Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: promoted tendon-to-bone healing and opposed corticosteroid aggravation. J Orthop Res. 2006;24(5):982–989.
3. Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JHS. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J Appl Physiol. 2011;110(3):774–780.
4. Gwyer D, Wragg NM, Wilson SL. Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing. Cell Tissue Res. 2019;377(2):153–159.
5. 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;12(1):37–51.
6. Malinda KM, Sidhu GS, Mani H, et al. Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999;113(3):364–368.
7. Bock-Marquette I, Saxena A, White MD, DiMaio JM, Srivastava D. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432(7016):466–472.
8. World Anti-Doping Agency. The World Anti-Doping Code International Standard: Prohibited List. Montreal: WADA; актуальна редакція.