BPC-157 or Collagen: what's the difference

BPC-157 and collagen often come up in the same conversation when the subject turns to tendons, ligaments and joints. However, these are substances from different worlds: one is an experimental synthetic peptide, the other a dietary protein. The editorial team has examined how they differ in nature, mechanism, evidence and status.

Two different categories of substance

BPC-157 (body protection compound) is a synthetic pentadecapeptide, that is, a chain of 15 amino acids. Its sequence is taken from a fragment of a protein found in human gastric juice. Almost all studies of this substance come from a single research group in Zagreb led by Predrag Sikiric.

Collagen is the main structural protein of connective tissue: tendons, ligaments, cartilage, skin and bones. As a supplement, it is obtained from the skin and bones of animals or fish in the form of gelatin or hydrolysate (collagen peptides).

The fundamental difference lies in how the body «sees» them. Collagen is food: in the digestive tract it is broken down into amino acids and short peptides, which are used as building material and signalling molecules. BPC-157 is positioned as a pharmacologically active substance that affects healing processes.

Hence the different regulatory status: collagen is sold as a food product or dietary supplement, whereas BPC-157 is registered neither as a medicine nor as a supplement.

Mechanism of action of BPC-157

In preclinical studies, BPC-157 exhibited a broad spectrum of effects: accelerated healing of wounds, muscles, tendons, ligaments and the mucosa of the gastrointestinal tract. The authors attribute this primarily to stimulation of angiogenesis - the formation of new blood vessels.

Among the proposed mechanisms are an effect on the nitric oxide system, increased expression of vascular endothelial growth factor receptors (VEGFR2) and activation of the FAK-paxillin signalling pathway, which is responsible for cell migration.

Chang et al. (2011) showed in vitro that BPC-157 promotes the survival and migration of tendon fibroblasts. Earlier, Staresinic et al. (2003) described accelerated healing of a transected Achilles tendon in rats.

However, all these mechanisms have been established in cell cultures and animal models. How they are realized in the human body, and whether they are realized at all, is unknown: there are no controlled clinical studies with published results.

Mechanism of action of collagen

After taking collagen hydrolysate, not only free amino acids - glycine, proline, hydroxyproline - enter the blood, but also short peptides, notably prolyl-hydroxyproline. They are credited with a signalling role: stimulating fibroblasts and the synthesis of the extracellular matrix.

Shaw et al. (2017), in a randomized human study, showed that taking 15 g of gelatin with vitamin C about an hour before a short jumping load doubled the blood marker of collagen synthesis compared with placebo. Vitamin C is needed by the enzymes that hydroxylate proline and lysine during collagen formation.

An important nuance: collagen works in combination with mechanical load. A tendon responds to training with collagen synthesis, and the supplement only provides the substrate at the right moment.

Collagen supplements are not «medicines for tendons». Their effects are moderate and depend on dose, timing of intake and rehabilitation protocol, but they have been studied in humans and have a favourable safety profile.

Comparison of the evidence base

The greatest gap between the two substances is in the quality of evidence. For BPC-157 there are dozens of animal studies but, as Gwyer et al. (2019) note in a review on soft-tissue healing, human clinical data are practically absent.

For collagen there are randomized studies. Clark et al. (2008) observed a reduction in activity-related joint pain in athletes over 24 weeks. Praet et al. (2019) showed improved function in Achilles tendinopathy when collagen peptides were combined with eccentric exercises.

A systematic review by Khatri et al. (2021) summarized that collagen supplements can increase collagen synthesis and reduce joint pain, although the quality of individual studies varies.

So comparing the efficacy of the two substances «head to head» is incorrect: for one there are human data, for the other only animal data. Direct comparative studies of BPC-157 and collagen have not been conducted at all, so any claim of the superiority of one over the other rests on assumptions.

Status in sport and safety

BPC-157 is named directly in the WADA Prohibited List as an example of a substance in section S0, «Non-approved substances». This section covers pharmacologically active substances not approved by any health authority for human use, and applies at all times.

Collagen and gelatin are ordinary food products and have no anti-doping restrictions. The only risk for athletes is contamination of the supplement, so it is advisable to choose products with independent certification.

As for the safety of BPC-157, the main problem is uncertainty. Stimulation of angiogenesis could theoretically be undesirable in the presence of tumours, and the lack of quality control means a risk of impurities and endotoxins.

Collagen is usually well tolerated; among the adverse effects, digestive-tract discomfort has been described. People with an allergy to fish or other source materials should pay attention to the origin of the product.

• BPC-157: prohibited in sport, not approved, safety in humans not established.
• Collagen: a food product, moderate proven effects, a high safety profile.

Editorial conclusions

BPC-157 and collagen differ in everything: origin, mechanism, level of evidence and status. The first is an experimental peptide with impressive results in animals but without clinical data; the second is a dietary protein with moderate but human-confirmed effects.

For the health of tendons and joints in humans, a proven role is played by properly dosed load, rehabilitation exercises and adequate nutrition, to which collagen with vitamin C can be an addition.

Athletes should remember that BPC-157 is prohibited by WADA at all times.

We also recommend reading our materials on the results of BPC-157 studies, on collagen for joints and on what was studied for tendons - TB-500 or BPC-157.

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. 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.
3. 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.
4. Shaw G, Lee-Barthel A, Ross ML, Wang B, Baar K. Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis. Am J Clin Nutr. 2017;105(1):136–143.
5. Clark KL, Sebastianelli W, Flechsenhar KR, et al. 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Curr Med Res Opin. 2008;24(5):1485–1496.
6. Praet SFE, Purdam CR, Welvaert M, et al. Oral supplementation of specific collagen peptides combined with calf-strengthening exercises enhances function and reduces pain in Achilles tendinopathy patients. Nutrients. 2019;11(1):76.
7. Khatri M, Naughton RJ, Clifford T, Harper LD, Corr L. The effects of collagen peptide supplementation on body composition, collagen synthesis, and recovery from joint injury and exercise: a systematic review. Amino Acids. 2021;53(10):1493–1506.
8. World Anti-Doping Agency. The World Anti-Doping Code International Standard: Prohibited List. Montreal: WADA; актуальна редакція.