How Does BPC-157 Work?

How Does BPC 157 Work?

BPC 157 is a derivative of a natural protein called body protection compound (BPC). BPC was first isolated from the digestive system where it plays an important role in protecting the stomach lining from stomach acid. Research has since revealed that the healing properties of BPC 157 extend well beyond the gut. The peptide has been shown to boost wound healing in a variety of tissues, increase the rate of blood vessel growth, improve blood clotting, and enhance the immune system.

To understand how BPC 157 can have such wide-ranging effects, it is necessary to start at the most basic level of its activity to see how its properties build upon one another to create an excellent healing peptide.

How Does BPC 157 Work in Blood Vessels?

Research shows that BPC 157 works in two different ways in blood vessels. First, it helps blood vessels to relax so that blood flows more easily through them. It does this by increasing concentrations of a natural compound called nitric oxide. Nitric oxide is critical to not just maintaining blood pressure, but to maintaining the health of the endothelial cells that line blood vessels. [12]

The second way that BPC 157 works in blood vessels is by directly stimulating the growth of endothelial cells[1], [2]. Thus, BPC 157 appears to increase endothelial cell growth in two ways. First, by boosting nitic oxide production in blood vessels and, second, via stimulation of a growth factor known as VEGF that causes endothelial cells to grow and divide. These findings indicate that BPC 157 likely causes changes in DNA expression patterns that are favorable to blood vessel growth and health.

How Does BPC 157 Work to Prevent Clots?

Recent research has suggested that BPC 157 might be useful in the treatment of COVID-19. It turns out that BPC 157 can prevent clots in both arteries and veins, making it potentially useful in the severe clotting that sometimes accompanies COVID-19 infection and other disease conditions. BPC 157 prevents clots, at least in part, by increasing nitric oxide concentration. Nitric oxide prevents platelets (special blood cells) from sticking together to form the first stages of a clot.

BPC 157 doesn’t just prevent clots though; it also prevents excessive bleeding. BPC 157 helps to normalize the coagulation system and help to prevent extremes on both ends. It appears that BPC 157 acts via several vascular pathways including those mentioned above (VEGF and nitric oxide) as well as FAK. FAK stands for focal adhesion kinase and it is a protein that determines how cells stick together. It is important in the process of clotting as well as in a variety of normal and pathological processes. Evidence suggests BPC 157 has a direct effect on FAK expression.

How Does BPC 157 Work in Wound Repair?

Based on its actions in blood vessels, at least part of the reason that BPC 157 is able to speed wound healing is because it helps to restore blood flow to damaged tissues. This is true whether BPC 157 is working in the stomach, the heart, tendons, or skin. Research shows that BPC 157 also increases the rate of vascular running, which refers to blood vessels growing toward an area of injury[3]. So, not only does it increase blood flow through existing vessels, BPC 157 also encourages new vessels to grow toward areas of injury and inflammation.

Its benefits on blood vessel growth are not the only reason that BPC 157 improves wound healing though. Research shows that the peptide increases the rate at which fibroblasts move into damaged tissue. Fibroblasts are the cells that generate extracellular matrix, which is a critical component for getting wound healing started[1].

BPC 157 is so effective in improving rates of wound repair that it has been investigated in fistula healing. Like tendons, discussed below, fistulas are notoriously difficult to treat. The average fistula takes more than two and a half years to heal, even with everything that modern medicine has to throw at wound repair. With BPC 157, rates of healing in animal models are reduced to less than a month[4].

How Does BPC 157 Work in Tendon Healing?

Tendons and ligaments are notoriously difficult to treat and heal because of their limited blood supply. An anemic blood supply prevents fibroblasts and cells of the immune system from reaching the site of injury in numbers great enough to have a rapid beneficial effect. Even with surgery, tendon healing is a slow and often unsuccessful process.

Animal models of tendon, ligament, and even bone injury suggest that BPC 157 has substantial positive benefits. Studies of the healing tissues show increased levels of bFGF, EFG, and VEGF following the administration of BPC 157. This means that BPC 157 is either directly or indirectly increases levels of hormones and growth factors necessary for directing cells to the site of injury. The higher the levels of these growth factors, the faster wounds heal[5].

There is also good evidence from benchtop experiments in cell culture showing that BPC 157 dramatically increases the numbers of GH receptors on tendons[6]. Growth hormone is well known for its ability to speed wound healing, increase musculoskeletal development, and boost immune function. The benefit of BPC 157 is that it increases numbers of GH receptors, rather than increasing GH levels. This provides the benefits of concentrated GH action at the injured tendon without the side effects that come with raising GH levels throughout the body.

How Does BPC 157 Work to Change DNA Expression?

All of the research conducted so far indicates that BPC 157 possibly activates EGR1, NAB2, FAK-paxillin, and JAK-2 pathways to alter DNA expression patterns[7]. In other words, BPC 157 changes how are DNA works to benefit wound healing, blood clotting, and more. Each of the pathways that BPC 157 is thought to change plays an important role in cell proliferation or immune function as follows.

• EGR1 – EGR1 is a DNA transcription regulator found in the brain. Its job is to turn genes on and off. Research shows that EGR1 is important in fibroblast activity, neuron growth, and ovarian function. There is plenty of evidence to show that BPC 157 is active in the brain where it possibly works through EGR1 to increase neuron development.

• NAB2 – NAB2 is associated with EGR1 and helps fine-tune DNA to, ultimately, make certain proteins more or less active. The list of proteins that NAB2 affects is extensive.

• FAK-paxillin – As mentioned earlier, FAK is important in cell adhesion. Paxillin is too. Together, these proteins help to determine whether cells stick together or remain separate. BPC 157 likely acts on these proteins to help modulate blood clotting and cell movement.

• JAK-2 – JAK-2 and the related JAK-STAT pathway are critical for cell division and immune system function. These pathways help to communicate to the DNA what is going on outside the cell. BPC 157 likely uses these pathways to signal to the DNA that growth, cell division, and cell specialization are needed. This leads to more cells and more specialized cells for an immune response, wound repair, and more.

BPC 157 and Cancer

There is a great deal of confusion surrounding the topic of BPC 157 because of the suggestion that this peptide can cause cancer. It does not. The argument is that because BPC 157 stimulates VEGF secretion and increased VEGF secretion is linked to more aggressive cancer because it supplies blood vessels to tumor cells, then BPC 157 must therefore cause cancer. This line of inference, a form of reasoning by correlation rather than from rational biological mechanisms and solid research, is incorrect.

First, VEGF actually increases in response to decreased oxygen levels (hypoxia), not cell growth. In the case of cancer, as tumors begin to grow, they cause hypoxia in their environment. The body responds to this by secreting VEGF to bring more blood vessels to the area. Thus, VEGF secretion around tumors is not pathological, but rather the body’s normal response to a lack of oxygen. Simply put, VEGF secretion does not cause cancer growth, cancer growth causes VEGF secretion.

The suggested connection between BPC 157 and increased tumor growth becomes even more absurd when one considers that BPC 157 is a homeostatic molecule. That is to say, BPC 157 favors balance in everything from blood vessel growth to inflammatory responses. This latter fact is important as tumor growth is accompanied by increases in inflammatory cytokines like tumor necrosis factor-alpha, interleukin-6, and more. Research shows that BPC 157 directly counters increases in these inflammatory cytokines and thus helps to thwart some of the pathways that lead to cancer growth[8].

In fact, a recent paper looking at the growth of melanoma and the role of BPC 157 has found that BPC 157 actually inhibits cell growth and VEGF signaling in skin cancer cells[9]. Again, this is in keeping with the role of BPC 157 as a homeostatic regulator. It favors restoring balance, not necessarily growth. In the case of injury, when tissue is damaged and oxygen is depleted, the balance shifts toward growth. But in the case of overgrowth, as seen in cancer, the balance shifts toward quiescence.

So, what is the bottom line? The bottom line is that while BPC 157 increases VEGF in wound healing, it does not universally increase VEGF in all tissues, only in the area of injury. This is because BPC 157 favors homeostasis above all else. Cancer arises as a result of DNA damage and gene mutations, not from blood vessel growth and certainly not from homeostasis. Remember, BPC is a natural compound found in the human GI tract.

A Note on BPC 157 Varieties

BPC 157 can be found in two different versions referred to as arginate and acetate salts. These essentially refer to modifications to BPC 157 made to protect it during transport and storage. Acetate salts are easier to produce and thus cost less, but they are less stable during transport and storage. Arginate salts are more expensive to produce, but last much longer.

The benefit of an arginate salt is not limited to storage and transport either. Research shows that arginate salts are more resistant to gastric acid and that only 10% of a given dose will be degraded after 5 hours in stomach acid. This is as compared to the acetate salt, of which 98% is gone after just a few hours in stomach acid[10]. This feature makes arginate salts more beneficial for research looking at the effects of orally (by mouth) administered BPC 157. A long-lasting version of BPC 157 not only bypasses stomach acid intact, it allows for lower doses of the peptide to be used. Thus, it may be the case that the lower dosage required of an arginate salt more than offsets its increased production cost.

How Does BPC 157 Work Overall?

BPC 157 is still under active investigation to understand precisely how it works. What is clear at this point is that the peptide actively modulates the levels of several growth factors and signaling hormones to stabilize blood vessel growth, immune function, and tissue repair. This coordinated activity suggests that BPC 157 alters DNA expression patterns in ways that help to improve the tissue environment to optimize injury repair.

One thing that is clear is that many of the benefits that BPC 157 confers can be attributed in some way to its ability to increase nitric oxide. Sections above explored how nitric oxide increases blood flow and reduces blood clotting, but the molecule has other benefits as well. In the diagram below, you can see that nitric oxide also lowers bad (LDL) cholesterol, reduces the formation of coronary artery plaques that lead to heart attach and stroke, fights against free radicals, and more. The increase in nitic oxide may explain why BPC 157 is beneficial for the immune system as well, though that is less certain than the benefits outlined in the diagram. [12]

According to Dr. Rudolf Rucman of the University of Zagreb, BPC 157 plays a role in helping the body to reestablish homeostasis. In other words, the peptide helps the body to return to baseline following an injury. This is in keeping with BPC 157 being a modulator of DNA expression patterns. Though it has yet to be fully explored, it seems reasonable to think that BPC 157 works at the most fundamental level of our biology, gene expression, to optimize the ability of the body to respond to stress and injury.

Resources

[1]T. Huang et al., “Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro,” Drug Des. Devel. Ther., vol. 9, pp. 2485–2499, 2015, doi: 10.2147/DDDT.S82030.

[2]S. A. Deek, “BPC 157 as Potential Treatment for COVID-19,” Med. Hypotheses, vol. 158, p. 110736, Jan. 2022, doi: 10.1016/j.mehy.2021.110736.

[3]P. Sikiric et al., “Novel Cytoprotective Mediator, Stable Gastric Pentadecapeptide BPC 157. Vascular Recruitment and Gastrointestinal Tract Healing,” Curr. Pharm. Des., vol. 24, no. 18, pp. 1990–2001, 2018, doi: 10.2174/1381612824666180608101119.

[4]M. Baric et al., “Stable gastric pentadecapeptide BPC 157 heals rectovaginal fistula in rats,” Life Sci., vol. 148, pp. 63–70, Mar. 2016, doi: 10.1016/j.lfs.2016.02.029.

[5]S. Seiwerth et al., “BPC 157 and Standard Angiogenic Growth Factors. Gastrointestinal Tract Healing, Lessons from Tendon, Ligament, Muscle and Bone Healing,” Curr. Pharm. Des., vol. 24, no. 18, pp. 1972–1989, 2018, doi: 10.2174/1381612824666180712110447.

[6]C.-H. Chang, W.-C. Tsai, Y.-H. Hsu, and J.-H. S. Pang, “Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts,” Mol. Basel Switz., vol. 19, no. 11, Art. no. 11, Nov. 2014, doi: 10.3390/molecules191119066.

[7]P. Sikiric et al., “Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications,” Curr. Neuropharmacol., vol. 14, no. 8, Art. no. 8, Nov. 2016, doi: 10.2174/1570159X13666160502153022.

[8]P. Sikiric et al., “Stable Gastric Pentadecapeptide BPC 157, Robert’s Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye’s Stress Coping Response: Progress, Achievements, and the Future,” Gut Liver, vol. 14, no. 2, pp. 153–167, Mar. 2020, doi: 10.5009/gnl18490.

[9]S. Radeljak, S. Seiwerth, and P. Sikiric, “BPC 157 inhibits cell growth and VEGF signalling via the MAPK kinase pathway in the human melanoma cell line,” Melanoma Res., vol. 14, pp. A14–A15, Aug. 2004, doi: 10.1097/00008390-200408000-00050.

[10]R. Rucman, “Stable pentadecapeptide salts, a process for preparation thereof, a use thereof in the manufacture of pharmaceutical preparations and a use thereof in therapy,” US9850282B2, Dec. 26, 2017 Accessed: Jul. 23, 2020. [Online]. Available: https://patents.google.com/patent/US9850282B2/en

[11] “Wake Forest University Publishes Mechanism of Action Reseach.” H-Wave, 5 Oct. 2009, www.h-wave.com/blog/wake-forest-university-publishes-moa-reseach/.

[12] “Figure 3 the Physiological Roles of Nitric Oxide on Endothelial Function.” ResearchGate, www.researchgate.net/figure/The-physiological-roles-of-nitric-oxide-on-endothelial-function_fig1_267335644.

Product available for research use only: