Gut Inflammation (60 Capsules) (Stable BPC-157, KPV, PEA, Tributyrin) FREE Shipping

Synergy for Gut Inflammation and Gut Repair: BPC 157, KPV, PEA, and Tributyrin

BPC 157, KPV, PEA, and tributyrin are all compounds with important functions in the gastrointestinal tract. Their properties overlap, but are different enough that researching them together may provide synergistic benefits in the setting of intestinal inflammation. The next step into research of these peptides would be to determine if their combined properties might offer substantial benefit in the setting of inflammatory bowel disease and other intestinal inflammation.

To understand how these peptides work together in the gut, it is important to first understand their individual properties. Those looking to develop experimental protocols for combinations of these peptides would do well to start with the lengthy research supporting each. Overarching these include control of systemic inflammatory responses, improvement of intestinal barrier function, reduction of inflammation in adipose tissue, control of inflammatory cytokine signaling (especially TNF-alpha), and reduction in immune responses to intestinal inflammatory signals.

Each of these products is naturally occurring, making them of even great interest to inflammation researchers because they are easier to isolate and produce, offer a reduced risk/side effect profile, and can be used to explore natural inflammatory pathways and the interactions that occur between them.

What Is BPC 157 and Stable BPC157 Arginate?

BPC 157 is a synthetic derivative of the naturally occurring protein known as body protection compound (BPC). BPC was first isolated form the human gastrointestinal tract where it is known to have anti-inflammatory and healing properties. It has been investigated in phase I clinical trials for the treatment of gastrointestinal ulcers as well as tendon and muscle injuries. BPC 157 is one of the rare anti-inflammatories to also possess angiogenic properties as well.

It is important to note that not all forms of a peptide are equivalent. In the case of BPC 157, there are two forms of the peptide: an Arginate salt and an Acetate salt. Research with oral administration of standard BPC 157 (acetate salt) has shown that it tends to break down in gastric acid more than the ariginate salt form. The body’s response to this is to simply produce a lot of BPC 157 and only in the areas where it is needed. Of course, this solution is not tenable when delivering the peptide orally and so scientists set out to produce a more stable form of BPC 157 by adding additional chemical structures to the peptide that resist gastric acid but do not alter overall function. The more orally bioavailable “stable” form of BPC 157 is the arginate salt. Studies show that just 5% of BPC 157 arginate is degraded after 5 hours in gastric acid as compared to 98% of the acetate salt. By reducing the degradation of BPC 157, the arginate salt makes the peptide more effective as an orally administered compound. The enhanced oral bioavailability of the arginate salt makes it the preferred choice in BPC 157 oral research[1].

What Is KPV?

KPV is a synthetic analogue of alpha-melanocyte stimulating hormone. Made up of three amino acids, KPV is known to retain the properties of the much larger alpha-MSH protein including anti-ischemic and anti-inflammatory properties. It is under active investigation as a potential treatment for inflammatory bowel disease[2].

KPV is a potent general anti-inflammatory, but its true benefit is in its ability to reduce intestinal inflammation in mouse models of inflammatory bowel disease. Research shows that the peptide can reduce inflammatory infiltrates, MPO activity, and histological evidence of inflammation. Research in mice shows that KPV can accelerate clinical recovery and improve weight gain in the setting of IBD[3].

Research shows that KPV is a potent suppressor of TNF-alpha and that its effects can be targeted to the intestine with the proper delivery mechanism[4]. This is important because TNF-alpha is a driver of inflammation in IBD and a target of current therapeutics like infliximab (Remicade/Inflectra) and adalimumab (Humira). These medications are effective early in their use, but lose efficacy due to the formation of systemic antibodies against them over time. They also carry with them a host of substantial, if rare, side effects. The ability to target anti-TNF-alpha activity to the intestine could help to thwart these drawbacks and would also allow for higher dosing and thus better disease control.

What Is PEA?

Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide produced from a combination of palmitic acid and ethanolamine. It binds to the peroxisome proliferator-activated receptor alpha (PPAR-a) as well as to cannabinoid-like G-coupled receptors GPR55 and GPR119 to influence pain and chronic inflammation. It also inhibits cyclooxygenase-2 signaling.

Research shows that PEA influences pain perception in at least two different ways. The first, and perhaps most important way in which PEA alters pain is via its anti-inflammatory actions. These actions are mediated through the PPAR-a receptor and through effects on NF-kappaB signaling[5].

Research in mouse models shows that PEA attenuates inflammation by activating PPAR-alpha. PPAR-alpha is a nuclear receptor protein that acts as a transcription factor[6]. While originally of interest for its ability to regulate lipid metabolism in the liver, PPAR-alpha has since been found to have anti-inflammatory properties. PPAR alpha is found in liver, kidney, heart, muscle, and adipose tissue in high quantities and in many other tissues in somewhat lower quantities. A number of prescription anti-diabetic and metabolic syndrome drugs target PPAR-alpha.

The ability of PEA to alleviate pain via an alternative to PPAR-alpha stimulation has been demonstrated in mouse models. In these studies, PEA was found to bind to the cannabinoid CB2 receptor in a manner similar to the endogenous cannabinoid (endocannabinoid) anandamide. This allows PEA to alleviate the perception of pain (nociception), but this effect is limited to pain controlled by the CB2 receptor, which has no impact on thermal pain or capsaicin-induced pain[7]. Because PEA is a naturally occurring molecule, it is likely that the cannabinoid CB2 receptor is its native target along with PPAR-alpha.

PPAR-alpha and endocannabinoid action are not the only mechanisms by which PEA seems to operate though. Research in mice indicates that PEA inhibits NF-kappaB nuclear signaling in the dorsal rout ganglia of spinal nerves[8]. This results in significant reductions in cyclooxygenase-2 (COX-2) expression in the central nervous system and subsequent reductions in nerve pain and pain signaling in general. COX-2 is the target of anti-inflammatories like ibuprofen, Celebrex, and Aleve.

The properties of PEA extend beyond pain relief and reduction in inflammation. Research in mice shows that PEA has anticonvulsant activities. The effective dose is similar to that of prescription anticonvulsants, but PEA does not appear to cause neurological impairment[9]. The anti-convulsant effect of PEA is likely mediated through its actions on the CB2 receptor of the endocannabinoid system[10]. This is the same receptor that mediates PEA’s anti-nociceptive activity. Action at this receptor has been shown to attenuate neurological damage and reduce infarct size following simulated stroke in the laboratory. It is thought that CB2 activation may help to reduce inflammation in the central nervous system and that this may lead to improvements in seizure thresholds and offer neurons protection against inflammatory processes[11].

What Is Tributyrin?

Tributyrin is a triglyceride (fat) found naturally in butter. Research shows that, within the body, tributyrin is converted to butyric acid. Butyric acid has been found to have anti-proliferative effects, slowing the growth of certain cells like colon cancer cells. Research shows that this anti-proliferative effect is the result of overexpression, induced by tributyrin, of the vitamin D3 receptor[12].

Tributyrin doesn’t just reduce proliferation though. Research using human colon cancer cell lines shows that tributyrin increases rates of cellular differentiation[13], [14]. This effect is also a result of tributyrin’s impact on the vitamin D receptor. In fact, administration of vitamin D and tributyrin together enhances the efficacy of both substances and leads to significant changes in tumor cell growth and inflammation. A large body of evidence has shown, for some time now, that vitamin D is a potent anti-inflammatory vitamin. Upregulation of its receptors could have a profound anti-inflammatory effect in and of itself.

The benefits of tributyrin extend well beyond its effects on vitamin D receptors thought. It has long been known that high fiber diets are beneficial for reducing the risk of colon cancer. Following the findings of tributyrin above, scientists wondered if the benefit provided by fiber was actually a result of the fact that fiber increases the production of butyrate by bacteria that live naturally in the intestine. Research in pigs suggests that this may, in fact, be the case. The mechanism, it seems, has to do with reduced inflammation and enhanced mitochondrial function. It would appear that tributyrin decreases mRNA transcripts of tumor necrosis factor-alpha, interferon-gamma, and interleukin-6[15]. All of these are inflammatory mediators. TNF-alpha, in particular has been linked to a number of serious inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis.

The impact of tributyrin on inflammation is quite multidimensional. Research in mice suggests that butyrate may attenuate intestinal inflammation and improve intestinal barrier function via activation of transcription factor HIF-1 in intestinal cells[16]. At the same time, research in obese mice shows that tributyrin induces an anti-inflammatory state in adipose tissue by reducing TNF-alpha signaling as well as levels of certain pro-inflammatory cytokines mentioned above. The development of inflammation in fat tissue has long been thought to be a primary driver of insulin resistance and type 2 diabetes. Mice in the study who were given tributyrin support this fact by having lower body weight and improved glucose handling as a result of improved insulin responsiveness[17], [18].

There is even research showing that tributyrin can reduce the inflammatory responses of immune cells to heat stress, making it a potential treatment for heat-induced illness. Research in cows reveals tributyrin significantly reduces TNF-alpha, interleukin-1B, and interleukin-6 levels. This, in turn, inhibits the lymphocyte inflammatory response[19].

Simply put, tributyrin is a potent anti-inflammatory with specific effects on IL-1B, IL-6, and TNF-alpha. The impact that tributyrin has on these cytokines not only reduces inflammation, it improves the function of the immune system, bolsters intestinal barrier function to reduce the risk of further inflammation, and reduces the risk and severity of colon cancer.

Synergy Between BPC-157, KPV, PEA, and Tributyrin

Individually, BPC 157, PEA, tributyrin, and KPV offer substantial benefits in fighting inflammation, particularly of the GI tract. However, there is reason to believe that a combination of the four could be synergistic due to the fact that they each regulate inflammation in a different way while overlapping in some regards. Administration of all four compounds could produce enhanced effects both by target the same inflammatory systems in different ways and by targeting different inflammatory systems to provide an overall greater anti-inflammatory response.

Starting with PEA, its primary effect is to prevent inflammation from occurring at a central level by inhibiting PPAR-alpha signaling as well as cyclooxygenase-2 (COX-2) induced inflammation. The effect of PPAR-alpha inhibition is also seen at the tissue level, offering a kind of two-step approach to reducing inflammation via this pathway.

PEA also inhibits inflammation in adipose tissue, a known risk factor for insulin resistance, glucose intolerance, and intestinal inflammation. Thus, PEA inhibits inflammation in multiple ways that all benefit the GI tract either directly or indirectly. It also stimulates endocannabinoid receptors, which help to reduce pain thought not inflammation directly.

Tributyrin has several beneficial effects when it comes to gut inflammation. First, it improves intestinal barrier function via regulation of tight junctions. This can help to reduce the number of inflammatory particles that cross from the intestinal lumen (where food is) into the body. Thus, tributyrin can actually prevent gut inflammation from occurring in the first place[16].

Tributyrin has also been shown to down regulate expression of several inflammatory cytokines, especially TNF-alpha, which has been linked to serious inflammatory conditions like ulcerative colitis and Crohn’s disease[15], [17]. There is even research to suggest that the ability of tributyrin to regulate these inflammatory cytokines may have a global anti-inflammatory effect as a result of down regulating immune inflammation[19]. Like PEA, tributyrin reduces inflammation in adipose tissue and thus may help to reduce the long-term risk of insulin resistance and diabetes[18].

The Specific Case of BPC 157, KPV, PEA, and Tributyrin in Fistula Repair

Fistulas are simply abnormal passageways between two organs that do not normally connect. A good example is the perianal fistula that connects the colon to the skin around the anus and leads to abnormal drainage and potential infection. Fistulas are common in inflammatory diseases of the GI tract, such as Crohn’s disease and ulcerative colitis. They are also notoriously difficult to treat and can affect individuals who suffer from them for years or even a lifetime.

Both KPV and BPC 157 have shown a great deal of promise in improving fistula healing, a specific case of wound healing. BPC 157 has been shown in rat studies to improve healing of GI fistulas by accelerating the rate of repair and leading to more frequent closure of the fistula.

Often times, fistula healing can be boosted by the direct injection of TNF-alpha inhibitors, like Humira, directly into the fistula. This is an expensive and difficult process that is not without side effects. KPV and tributyrin may offer an alternative by delivering TNF-alpha suppression directly to the GI tract without the need for invasive injections. Combined with BPC 157, this could result in a dramatic increase in fistula healing. By boosting tight junction function, tributyrin could slow the progression of fistulas and even reverse the process.

A Summary of Gut Inflammation

It is often said that all health starts in the gut. Whether this is perfectly accurate or not, there is no arguing that the GI tract is an important component of nutrition, immune function, and overall health. The compounds discussed above have a multitude of anti-inflammatory effects on the gut that, when combined, are likely to provide synergistic benefits in gut inflammation. PEA provides a kind of global protection by reducing both systemic and tissue inflammation. This is then built upon by KPV and tributyrin, which reduce inflammatory signaling from cytokines like TNF-alpha and improve tight junction functionality. BPC 157 provides the final benefit by boosting rates of wound healing and tissue repair without triggering any additional inflammatory response. These natural compounds work synergistically to help to establish a low-inflammation state in the GI tract to allowing healing and optimal functioning.

BPC 157, KPV, Tributyrin, and PEA exhibits minimal side effects and good oral bioavailability in mice. Per kg dosage in mice does not scale to humans. BPC 157, KPV, Tributyrin, and PEA for sale at Peptide Sciences is limited to educational and scientific research only, not for human consumption. Only buy BPC 157, KPV, Tributyrin, and PEA if you are a licensed researcher.

Storage Instructions:

All of our products are manufactured using the Lyophilization (Freeze Drying) process, which ensures that our products remain 100% stable for shipping 3-4 months reconstituted (mixed with bacteriostatic water) to maintain stability. After reconstitution, the peptides will remain stable for up to 30 days.

Lyophilization is a unique dehydration process, also known as cryodesiccation, where the peptides are frozen and then subjected to low pressure. This causes the water in the peptide vial to sublimate directly from solid to gas, leaving behind a stable, crystalline white structure known as lyophilized peptide. The puffy white powder can be stored at room temperature until you're ready to reconstitute it with bacteriostatic water.

Once peptides have been received, it is imperative that they are kept cold and away from light. If the peptides will be used immediately, or in the next several days, weeks or months, short-term refrigeration under 4C (39F) is generally acceptable. Lyophilized peptides are usually stable at room temperatures for several weeks or more, so if they will be utilized within weeks or months such storage is typically adequate.

However, for longer term storage (several months to years) it is more preferable to store peptides in a freezer at -80C (-112F). When storing peptides for months or even years, freezing is optimal in order to preserve the peptide’s stability.