TB-500 vs BPC-157: a comparison of study data

A paradoxical situation has developed around TB-500 and BPC-157: much is written about them, but few analyze the studies themselves. The editorial team approached the topic as a reviewer: who conducted the experiments, which models were used, what was measured and what data there are on humans.

How to assess peptide studies

The strength of evidence depends not on the number of publications but on their design. The weakest level is studies in cell cultures, then experiments in animals, then clinical studies in humans of various phases and, finally, systematic reviews of randomized studies.

Several criteria matter for assessment: whether the results were reproduced by independent groups, whether there was blinded assessment of outcomes, how closely the model resembles a real clinical situation, whether adverse effects were reported.

Another aspect is which substance exactly was studied. For BPC-157 this is relatively unambiguous, but for TB-500 it is not, since most work is devoted to full-length thymosin β4.

Below we apply these criteria to both peptides and see at which stage of development each of them is.

BPC-157: a large body of data from a single laboratory

The number of publications on BPC-157 is significant: effects on the gastrointestinal tract, tendons, ligaments, muscles, bones, nervous system and blood vessels have been described. Among the works on the musculoskeletal system are Staresinic et al. (2003) on the Achilles tendon and Krivic et al. (2006) on healing at the tendon-to-bone attachment site.

The main methodological issue is independence. The overwhelming majority of studies have been carried out by the Sikiric group. The work by Chang et al. (2011) from Taiwan is one of the few examples of independent confirmation, but it too was carried out on cells.

The review by Gwyer et al. (2019) acknowledges the consistently positive preclinical results, but emphasizes the absence of clinical studies and the need for independent verification.

There are no results of controlled clinical studies of BPC-157 in peer-reviewed journals. Information about early clinical studies in inflammatory bowel disease is mentioned in reviews, but the full published data are insufficient for conclusions.

Thymosin β4: a broader scientific base, a different substance

Thymosin β4 has been studied for several decades by various groups around the world. Its role has been shown in wound healing (Malinda et al., 1999), recovery of the heart muscle after infarction in mice (Bock-Marquette et al., 2004), and in the processes of inflammation and angiogenesis.

Unlike BPC-157, a clinical safety study in humans has been published for thymosin β4. Ruff et al. (2010) reported a randomized placebo-controlled study of intravenous Tβ4 in healthy volunteers, in which no serious tolerability problems were found.

The review by Goldstein et al. (2012) describes clinical programmes in ophthalmology (eye drops for corneal damage), dermatology and cardiology. However, none of them had ended in drug approval at the time of the review.

A key caveat: all these data concern the full-length protein of pharmaceutical quality. Commercial TB-500 is a shorter synthetic peptide for which there are no clinical data of its own.

Comparative data table

The table shows that the comparison «TB-500 versus BPC-157» actually has three components: two peptides with different bodies of data and a commercial product only partly related to one of them.

In terms of the breadth and independence of studies, thymosin β4 looks more solid, but its data cannot be automatically attributed to TB-500. BPC-157 has more dedicated works on the musculoskeletal system, but their independent verification is limited.

In both cases, the gap between the laboratory and the clinic remains insurmountable at the current level of knowledge.

In practice, this means that neither substance can be considered a proven means of treating injuries in humans.

Safety and gaps in knowledge

The absence of reports of side effects in animal studies does not mean safety for humans. Long-term studies of toxicity, carcinogenicity and effects on reproductive function are not presented in the publicly available literature for these peptides.

Both substances affect the processes of cell migration and angiogenesis. These are mechanisms useful for healing, but potentially undesirable in the presence of tumours, so the theoretical oncological risk can be neither confirmed nor ruled out.

A separate risk is grey-market products of unknown purity, dosage and sterility. For injectable substances this directly threatens infectious complications.

The main gaps that future studies should close:

1. independent reproduction of BPC-157 data;
2. randomized clinical studies in tendon injuries;
3. long-term safety data;
4. studies of the very molecules sold as TB-500.

Editorial conclusions

The comparison of data shows: BPC-157 has a significant but predominantly «single-laboratory» preclinical body of work; thymosin β4 has a broader base from various groups and Phase I safety data; TB-500 as a product has almost no data of its own.

For neither substance has efficacy in injuries in humans been proven, and both are prohibited by WADA - BPC-157 in section S0, TB-500 in section S2.

Critical reading of studies helps distinguish a promising hypothesis from a proven treatment - and in this case we are dealing precisely with hypotheses.

We also recommend reading our materials «TB-500 or BPC-157: what was studied for tendons», on the long-term risks of BPC-157 and on how to tell a quality peptide from a counterfeit.

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. Ruff D, Crockford D, Girardi G, Zhang Y. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Ann N Y Acad Sci. 2010;1194:223–229.