BPC-157, the Orally Available Peptide That Repairs Tendon, Muscle, Intestines, Teeth, Bone and More in Vitro & Vivo

BPC-157, the Orally Available Peptide That Repairs Tendon, Muscle, Intestines, Teeth, Bone and More in Vitro & Vivo

bone BPC 157 BPC-157 health IBS injury intestines muscle muscle damage muscle injury muscle repair peptides

BPC is not patentable, and thus not interesting for BigPharma.

In a way this article is a response to a question I got from Ryan on the Faebook Page of the SuppVersity a week ago. He asked, whether I had an article on Pentadecapeptide BPC-157, a substance of which he'd heard that it can accelerate tendon and muscle repair and work all sorts of other healing magic. Now, as a regular at the SuppVersity you may know that I didn't have an article on this agent a week age. So I decided to write one. Not just because Ryan asked, but also because of the practical significance of the healing effects of this peptide from in vitro and in vivo studies (no medical advice here!).

Unlike antioxidants with their anti-hormetic effects, BPC-157 actually promotes healing

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Studies as they were published by Brcic, et al. in the J Physiol Pharmacol  in 2009. A study in cell cultures and living rodents whose crushed muscles and transected muscle and tendons didn't heal magically, but a comparison of the animals who received  BPC 157 at a dosage of 10 µg (human equivalent 5.4 µg/kg) dissolved in saline to those who were treated with an equivalent volume of saline alone (5 ml/kg) showed a sign. accelerated response of the measured cell antigens, FVIII (involved in platelet adhesion and aggregation, present on endothelial cells of mature blood vessels) and CD34 (involved in leukocyte adhesion and endothelial cell migration during angiogenesis, present on capillary endothelial cells), as well as VEGF (Figure 1):

Figure 1: All markers of inflammation and muscle repair were sign. elevated with oral BPC-157(solid live) vs. control treatment with saline (dashed line) treatment in a model of  muscle injury (Brcic. 2009).

These observations clearly suggest an accelerated (or phase-shifted) angiogenic repair process in the crushed tissue of the lab animals. One that stands in line with other scientists like Krivic et al. (2006) had found previously that they promote...

• promote tendon & ligament healing by tendon outgrowth, cell survival, and cell migration as it was observed in a rodent model of Achilles tendon rupture (Chang. 2011), and when administered in the drinking water to rats with experimentally damaged medial collateral ligaments (Cerovecki. 2010)
• direct tendon-to-bone healing so effectivel that they may actually "successfully exchange the present reconstructive surgical methods" (Krivic. 2006), 
• counter the damaging effects of NSAIDs on the gut lining so effectively that scientists call BPC 157 "a NSAIDs antidote" one of which they say that "no other single agent has portrayed a similar array of effects" (Sikiric. 2013), 
• repair the damage that's done by inflammatory bowel disease within days of oral administration in µg or ng doses in a rodent model of IBS (Vuksic. 2007), 
• help cure perdidontitis when it is chronically administered in a rodent model of periodontitis potently enough to have scientists conclude that "BPC 157 may represent a new peptide candidate in the treatment of periodontal disease" (Keremi. 2009), 
• reverse systemic corticosteroid-impaired muscle healing, in a rodent model where it was administered with a front-load of 10µg orally once daily for 14 days to rats w/ crushed gastrocnemius muscle (Pevec. 2010 | similar benefits in a rodent study by Novinscak et al. that was published in Surgery Today in 2008), and
• bone healing in rabbits who suffered an experimental segmental bone defect before being treated with BPC-157 (Šebečić. 1999).

Cool? Well, I guess your next question is: "What's the necessary dosage?" If we use the existing rodent data as a yardstick, the answer to this question is ca. 5µg/kg body weight (Novinscak. 2008; Cerovecki. 2010). That's ~400µg per day for an 80kg man and thus roughly what you will see people on the Internet say they use.

Want to listen to me explain the study? Plus: Update! Download yesterday's installment of the SuppVersity Science-Round-Up at SuperHumanRadio.com | click here to download! On another note, after this article was originally published I received word from someone who claims to know the researchers who did the original studies and cautions against putting to much faith into their results... that is yet not the main argument for me; rather than that I am only skeptically optimistic, because no human studies have confirmed the efficacy of the compound.

Without a human study that would conform that you need that much / that much little is sufficient, it is yet impossible to provide a science-backed recommended dosage for optimal effects at minimal side effects (chronic consumption not suggested, yet | learn why).

Figure 2: Pevec et al. didn't just observe that BPC-157 blocked the ill effects of corticosteroids on muscle healing, they also found that BPC-157 alone super-charged the healing process (Pevec. 2010).

Ah, and before you ask: Yes, the peptide can be administered without a peptidase inhibitor or other agent to increase absorption and reduce breakdown, because it is a gastric juice peptide (Sikirić. 1993), or rather a part of it, namely a 15 amino acid fragment "with apparently no sequence homology with known gut peptides" the effects of which appear to be mediated "at least by the hormones of the adrenal, parathyroid, thyroid and ovarian glands" (Sikiric. 1994).

BPC-157 should stack well with GH as it potentiates its effects on tendon repair (Chang. 2014).

So why didn't my doctor prescribe this? As gastric juice peptides, BPCs - including BPC-157 - are not patentable. Therefore, they are not interesting, and thus not produced or marketed by pharma companies (so your doctor probably doesn't even know about their existence) and thus not available as FDA regulated drugs.

The lack of money one can make from this agent is probably also the reason there's still relatively little research on this compound; and I fear that this is not going to change very soon... it is thus probably more a question of money than one of time when and if we will see the human studies we need to decide if its effective+safe in man | Comment!

References:

• Brcic, L., et al. "Modulatory effect of gastric pentadecapeptide BPC 157 on angiogenesis in muscle and tendon healing." J Physiol Pharmacol 60.Suppl 7 (2009): 191-196.
• Cerovecki, Tomislav, et al. "Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat." Journal of orthopaedic research 28.9 (2010): 1155-1161.
• Chang, Chung-Hsun, et al. "The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration." Journal of Applied Physiology 110.3 (2011): 774-780.
• Chang, Chung-Hsun, et al. "Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts." Molecules 19.11 (2014): 19066-19077.
• Keremi, B., et al. "Antiinflammatory effect of BPC 157 on experimental periodontitis in rats." Journal of physiology and pharmacology 60.7 (2009): 115-122.
• Krivic, Andrija, et al. "Achilles Detachment in Rat and Stable Gastric Pentadecapeptide BPC 157: Promoted Tendon‐to‐Bone Healing and Opposed Corticosteroid Aggravation." Journal of orthopaedic research 24.5 (2006): 982-989.
• Novinscak, Tomislav, et al. "Gastric pentadecapeptide BPC 157 as an effective therapy for muscle crush injury in the rat." Surgery today 38.8 (2008): 716-725.
• Pevec, Danira, et al. "Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application." Medical Science Monitor 16.3 (2010): BR81-BR88.
• Šebečić, Božidar, et al. "Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation." Bone 24.3 (1999): 195-202.
• Sikirić, Predrag, et al. "A new gastric juice peptide, BPC. An overview of the stomach-stress-organoprotection hypothesis and beneficial effects of BPC." Journal of Physiology-Paris 87.5 (1993): 313-327.
• Sikiric, Predrag, et al. "The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesions induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H 2 receptor antagonists, dopamine promotors and gut peptides." Life sciences 54.5 (1994): PL63-PL68.
• Sikiric, Predrag, et al. "Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157." Current pharmaceutical design 19.1 (2013): 76-83.
• Vuksic, Tihomir, et al. "Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia) heals ileoileal anastomosis in the rat." Surgery today 37.9 (2007): 768-777.

HMB 'Likely' Protects 'Muscle Quality' & 'Possibly' to 'Likely' Cuts Inflammation During 23-Day Intense Military Training

HMB 'Likely' Protects 'Muscle Quality' & 'Possibly' to 'Likely' Cuts Inflammation During 23-Day Intense Military Training

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Unfortunately, the study at hand provides insufficient evidence to decide whether you should buy (free acid) HMB if you are about to participate in a military bootcamp.

The idea that HMB is the rather anticatabolic version of leucine, I've mentioned in previous articles, obviously occurred to an international group of scientists from the University of Central Florida, the Israel Defense Forces as well as associated universities, too (Hoffman. 2016).

In their recent study, the scientists examined whether HMB supplementation can attenuate muscle loss and the inflammatory response during highly intense, sustained military training. A study, of which Hoffman et al. point out, that it is "to the best of [their] knowledge" the first study to "have examined HMB supplementation in soldiers during intense military operations" (Hoffman. 2016).

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The authors examined the effect of 23-days of HMB supplementation on the immune and inflammatory response, and changes in muscle mass in combat soldiers during highly intense military training duringn which they consumed eiather with three servings (1 gram per serving) per day (at meal time | BetaTor®), or a placebo (PL) consisted of a similar amount of Litesse® polydextrose, reverse osmosis water, corn syrup, debittering agent, orange flavoring, stevia extract, citric acid, potassium sorbate, and xanthine gum powder (both sponsored by Metabolic Technologies Inc.):

• During the 23-day study period all soldiers performed the same daily protocol. 
• On days 1 – 10 soldiers were garrisoned on base and participated in the same advanced military training tasks that included combat skill development and conditioning. 
• During days 11 – 17 soldiers were released for a week of rest and recovery. Upon reporting back for duty, soldiers were then subjected to a week (days 18 – 23) of extreme training with minimal recovery. 
• On days 18 through 20, soldiers navigated 23.3 km per evening in difficult terrain carrying approximately 35 kg of equipment on their back (equating to approximately 40% of participant’s body mass). The duration of the navigational exercise lasted between 6 – 8 hours per evening. During daylight TED 
• On day 21-23, the soldiers were subjected to excessive physical training that included 90-min of intense hand-to-hand combat (krav-maga training), 60-min of endurance training and an additional 60-min of resistance training. 

As the scientists point out, the soldiers slept of only 22.5 h (3.8 ±3.0 h per night) during the six days of intense training, which including two evenings of no sleep (days 18 and 22). Blood draws and magnetic resonance imaging (MRI) measures were conducted in a single day prior to (PRE) and approximately 18-hours following the final supplement consumption (on day 24) (POST). All
blood draws and MRI measures were performed at Soroka Medical Center.

Table 1: Circulating cytokine concentrations (pg/ml) and muscle damage markers in HMB and PL in response to intense military training (Hoffman. 2016) | All data are reported as means ± SD.

Due to injuries and compliance issues, only 13 of the 27 participants were included in the final analysis (HMB = 6 and PL = 7), and even those subjects consumed only 89.3 ± 6.8% of the possible servings. I doubt, however, that the scientists didn't observe significant interactions were observed between HMB and PL for body mass (F=3.36, p=0.094) from pre (72.6 ± 7.1 kg and 70.7 ± 6.6 kg, respectively) to post (71.7 ± 6.4 kg and 71.2 ± 6.9 kg, respectively).

Why is HMB-FA supposed to be better than calcium HMB (Ca-HMB)? While some people say that the producers make false marketing claims about the bioavailability of HMB-FA, the reality is that the patent holder's claim that "BetaTOR [HMB-FA] is more rapidly absorbed so you get a higher peak and sustained concentration in the blood" (Manufacturer claim) has been proven in both, rodent (Shreeram. 2014) and human studies (Fuller. 2011). The former, however, also reveal that the bioavailability, i.e. the amount of HMB that actually hits the circulation - or, as scientists say the area under the curve (AUC) from t = 0 to t = ∞ - is actually 49%, 54%, and 27% lower (with increasing doses reducing the difference) than for Ca-HMB (Shreeram. 2014). The often-heard claim that the AUC doesn't matter as much as the speed may be in analogy to the comparison of whey vs. steaks, where the speed at which whey protein is absorbed and its leucine content enters your bloodstream is supposed to make all the difference, but is as of yet unproven.

On the other hand, the scientists observed potentially meaningful effects of HMB on markers of inflammation. More specifically, HMB ingestion, based on magnitude analysis (see Table 1 for an overview of all results), ...

• likely attenuated (78% likelihood effect) response compared with the effect of PL (a difference ± 90% CI of -38 ± 43.7 pg/ml between he Δ HMB – Δ PL)
• likely(87.2% likelihood effect) attenuated the INFγ response compared with the effect of the placebo (a difference ± 90% CI of -42 ± 47.3 pg/ml between the Δ HMB – Δ PL)
• possibly attenuated (74% likelihood effect) the IL-1ra response compared to PL (a difference ± 90% CI of -11 ± 18.9 pg/ml between the Δ HMB – Δ PL).
• possibly (74.5% likelihood effect) attenuated the IL-6 response compared to PL (a difference ± 90% CI of -6.6 ± 11.2 pg/ml between the Δ HMB – Δ PL).
• possibly attenuated (63% likelihood effect) the GM-CSF response compared with the effect of PL (a difference ± 90% CI of -8.1 ± 20.0 pg/ml between the Δ HMB – Δ PL).
• likely decreased (80.5% likelihood effect) the IL-8 response compared to PL (a difference ± 90% CI of -6.7 ± 10.0 pg/ml between the Δ HMB – Δ PL).
• very likely (92% likelihood effect) attenuated the TNF-α response compared to PL (a difference ± 90% CI of - 10.8 ± 7.2 pg/ml between the Δ HMB – Δ PL).

As the authors point out, "[t]he remaining cytokines demonstrated no significant pre and post changes between HMB and PL for IL-1b (F=0.04, p=0.84), and MCP-1(F=0.58, p=0.46) [and,  more importantly] the magnitude based inference analyses indicated that comparisons between HMB and PL on these inflammatory markers were unclear" (Hoffman. 2016).

Figure 1: There's a 77% chance the rel. increase in adductor magnus MRI muscle volume is significant (Hoffman. 2016). In view of the likely increased CK and LDH levels this could be a result of cell swelling in response to muscle damage.

Unfortunately, we have to eyeball the trend (F=4.30, p=0.062) towards HMB's effects on plasma CK with the same skepticism as the "likely", "possible" and even "very likely" effects on markers of inflammation. Ok, the fact that the increased CK levels in the HMB group were accompanied by "a likely increase (84% likelihood) in the LDH response compared to PL (a difference ± 90% CI of 53 ± 5.8 IU·L-1 between the ∆ HMB - ∆ PL)" (Hoffman. 2016), is what you'd expect in response to exercise. Usually, though, CK and LDH are considered markers of muscle damage and IIRC the scientists thought to demonstrate that HMB has a muscle protective effect.

To even complicate things, in previous studies both acute increases and chronic decreases in CK have been observed in studies by Wilson et al. (2009 | acute data) and Panton et al. (2000 | chronic data), respectively. Whether there was an increased muscle damage or whether HMB had protective effect as the "likely [...] increase muscle volume for the adductor magnus (77% likelihood [see Figure 1]) compared to PL" (Hoffman. 2016), the scientists appears to suggest, is thus impossible to say.

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Bottom line: Even though I cannot debate that the scientists' magnitude analyses provide, as they say in the conclusion, "evidence that HMB supplementation may attenuate the inflammatory response to high intense military training, and maintain muscle quality" (Hoffman. 2016). The study is seriously under-powered (remember they had 14 dropouts).

Due to the high number of dropouts, it was more or less impossible to produce significant results. In a situation like that, the use of magnitude analyses to "save" the study makes sense, but reliability of the results is even lower than "likely" and "possibly" would suggest.

So why did I discuss the study, then? Well, let's say I sense that either Metabolic Technologies Inc., who are mentioned in the acknowledgements, which also declare that the authors have "no conflict of interests to report"(Hoffman. 2016), or licensees of HMB free acid are going to cite this study in write-ups and on product packages without mentioning words like "possibly" or "likely" or any of the other problems discussed above | Comment on Facebook! 

References:

• Fuller, John C., et al. "Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt." British journal of nutrition 105.03 (2011): 367-372.
• Hoffman, Jay R., et al. "HMB attenuates the cytokine response during sustained military training." Nutrition Research (2016).
• Panton, Lynn B., et al. "Nutritional supplementation of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) during resistance training." Nutrition 16.9 (2000): 734-739.
• Shreeram, Sathyavageeswaran, et al. "The Relative Bioavailability of the Calcium Salt of β-Hydroxy-β-Methylbutyrate Is Greater Than That of the Free Fatty Acid Form in Rats." The Journal of nutrition 144.10 (2014): 1549-1555.
• Wilson, J.M., et al. "Acute and timing effects of beta-hydroxy-beta-methylbutyrate (HMB) on indirect markers of skeletal muscle damage." Nutrition & metabolism 6.1 (2009): 1.

Cacao, Delicious + Ergogenic - Performance Up and Muscle Damage Down After 7d on 21g/d of Hershey's 100% Cacao

Cacao, Delicious + Ergogenic - Performance Up and Muscle Damage Down After 7d on 21g/d of Hershey's 100% Cacao

cacao chocolate CK cooper test ergogenic ergogenics LDH muscle damage natural ergogenic performance

Hershey's 100% Cacao, soon also available at your local GNC? If you look at the results of the study at hand, it does appear likely that a regular "food item" can compete with sign. more expensive sport supplements.

From previous SuppVersity articles you know that several studies have demonstrated the protective effects of cocoa consumption, due to its anti-inflammatory and antioxidant properties. From the news and my critical evaluations of the study results, you do yet also know that (a) regular chocolate lacks most of these beneficial effects and that the effects have (b) often been hilariously exaggerated in the laypress. Furthermore, studies that probe the efficacy of cacao or high cacao chocolate on exercise performance are, unlike studies on its anti-oxidant effects (e.g. Berry. 2010; Davison. 2012), something in-between "rare" and "quasi non-existent".

In spite of its relatively small size (fifteen 15-18 year old soccer players), a recent study González-Garrido et al's latest study that examined the effect of cocoa consumption on the markers of muscle damage, oxidative stress and physical fitness in professional soccer players, is thus still worth being discussed in the SuppVersity news.

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Furthermore, the fifteen players (15-18 years old) were part of a case-control study in which the which subjects acted as their own control - a means of making the results more significant in spite of a relatively low number of subjects.

Table 1: Nutritional profile of 25g of the cocoa "supplement", Hershey's 100% cacao powder.

A study in which the researchers analyzed the biochemical parameters, markers of muscle damage and oxidative stress, and physical performance before and 24h after consuming 0.375 g/kg body mass of Hershey's 100% cacao powder in 300 mL water for 7 days.

Figure 1: Rel. changes (%) of markers of lipid and protein per-oxidation and anti-oxidant defenses (González-Garrido. 2015).

For the average study subject that was a dosage of roughly 25.1 g of cocoa per day - not exactly mass and certainly not enough to be afraid that the additional 162.5 kcal/day could have negative effects on your body composition, but obviously enough to trigger significant decreases in all the relevant markers of oxidative damage MDA + 4-HNE (lipid per-oxidation), carbonyl groups (protein per-oxidation), and improvements in all relevant markers of antioxidant defenses, i.e. GSH, TAC (increased) and thiols (decreased).

So what? Now the obvious question is: "Couldn't this impair the adaptation to exercise?" This question cannot be answered based on an acute response study, but with the acute increases in exercise performance (Cooper test, see Figure 2) and in spite of the significant reductions in CK and LDH (see Figure 2), which are usually interpreted as markers of muscle damage, this appears generally unlikely - yet not impossible.

Figure 2: Copper test (test of physical fitness | more) performance and creatine kinase (CK | more) and lactate dehydro- genase (LDH) levels after the 12-minute Cooper test before and after 7-days of supplementing with ~21g/d of 100% cacao powder (González-Garrido. 2015).

On the other hand, it is important to note that only the increased Cooper test performance (Figure 2), but none of the other markers has at least a non-significant predictive value with respect to the possible long-term effects on exercise performance - an effect that will have to be tested in future longer-term studies. A conclusion that would go beyond the scientists' statement that they "have shown the potential that cocoa consumption has on endurance performance and its role in recovery from muscle damage in athletes" (González-Garrido. 2015) would thus be unwarranted... as unwarranted as any speculations about the underlying mechanisms: yes, it is likely that the high polyphenol content of 100% cacao is what does the trick, but to prove that we'd need a low polyphenol chocolate control we don't have. If you want to benefit, though, I highly suggest to pick a 100% cacao powder with a low degree of processing | Comment!

References:

• Berry, Narelle M., et al. "Impact of cocoa flavanol consumption on blood pressure responsiveness to exercise." British Journal of Nutrition 103.10 (2010): 1480-1484.
• Davison, Glen, et al. "The effect of acute pre-exercise dark chocolate consumption on plasma antioxidant status, oxidative stress and immunoendocrine responses to prolonged exercise." European journal of nutrition 51.1 (2012): 69-79.
• González-Garrido, et al. "An association of cocoa consumption with improved physical fitness and decreased muscle damage and oxidative stress in athletes." The Journal of Sports Medicine and Physical Fitness (2015): Epub ahead of pring Dec 02, 2015.