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

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

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.

More HMB Free Acid Science: Now It's Also Good For High Intensity Interval Training (HIIT) Says the Latest Spon-sored Trial W/Out Calcium HMB Con-trol in Young Men & Women | more!

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

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.

Milk & Exercise a Perfect Match? A Summary of the Latest Scientific Studies on Its Ability to Sustain Muscle Growth, Protect from Muscle Damage, Binges and Dehydration

Is milk the perfect fluid replacement + anti-post-workout binge + muscle protector for gymrats, fitness junkies and professional athletes? 

It stands out of question. Compared to Coke and many of the so-called "sports-" or "energy drinks" that are in fact no much more than over-caffeinated liquid sugar bars, milk is a healthy beverage. Whether it's also a potent ergogenic though, is still intensely debated.

A recent study from the McMaster University in Hamilton, Ontaria, for example, indicates that the initial surge in post-workout protein synthesis cannot be sustained solely by the low amount of protein in regular milk (Volterman. 2015). Its inability to trigger longlasting increases in protein synthesis and thus to promote a positive whole body protein balance does yet not negate the already proven benefits milk and some of its less-known constituent (I am not talking about whey or casein!) may have for athletes and gymrats.

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You want to know what kind of advantages this may be? Well, here is a brief overview of the latest scientific evidence that is either directly or indirectly related to potential beneficial effects of milk:

• Consumption of 500 ml of milk post-exercise-induced muscle damage can limit decrements in muscle function in females, and limit increases in soreness and serum markers of muscle damage in females and males.
  
  That's not something I say, but something, scientists from the Institute of Technology in Carlow, Ireland, conclude based on their observations in 32 team sport players (male n = 16; female n = 16) who were randomly, but equally divided into four groups: male milk, male carbohydrate, female milk, and female carbohydrate. Immediately following muscle damaging exercise, participants consumed either 500 ml of milk or 500 ml of an energy-matched carbohydrate solution. Skeletal troponin I (sTnI), creatine kinase (CK), peak torque, counter movement jump height, 20 m sprint performance and passive and active soreness were recorded prior to and 24, 48 and 72 h post-exercise-induced muscle damage (EIMD).
  

  

  Figure 1: Brief overview of the most important facts (Rankin. 2015).

  What the scientists found was that the women experienced likely to very likely beneficial effect on attenuating losses in peak torque at 60°/s from baseline to 24, 48 and 72 h, and a likely beneficial effect in minimizing decrements in sprint performance and soreness over 72 h. Furthermore, the milk consumption was unlikely to have a negative effect on serum markers of damage from baseline to 48 and 72 h.
  
  For males, on the other hand, milk had an unclear effect on muscle function variables. Milk had a most likely/likely beneficial effect on limiting muscle soreness from baseline to 72 h, and a possible beneficial effect on attenuating increases in CK. The effect on sTnI was unlikely to be negative from baseline-72 h. In that, the female participants demonstrated smaller increases in sprint time, passive soreness, active soreness (non-dominant leg) and sTnI values and did thus benefit to a greater yet not significantly greater extent from the 500 ml of milk - that's a difference that could be both sex- and/or protein-specific; I mean, for a man, 500 ml of milk yield significantly less protein on a per kg body weight basis than the same 500 ml do for a woman. That's a difference that could well partly explain why women benefit more from milk vs. carbohydrates only compared to men.
• The consumption of skimmed milk following 30 min of moderate-vigorous cycling exercise reduces subsequent energy intake in female recreational exercisers.
  
  Obviously, working out will only help you shed body fat if the increased energy expenditure during the workout is not (over-)compensated by increased food intake after your workouts. Against that background the results from a recent study from the Northumbria University (Rumbold. 2015) are significant, because they indicate that 600 mL of skimmed milk have a significantly more pronounced "anti-binging" effect than 600 mL of an isocaloric orange drink when they are ingested immediately after a workout.
  

  

  Figure 2: Absolute and relative energy intake during the milk vs. orange juice trials (Rumbold. 2015).

  As the data in Figure 2 indicates the 9 female recreational exercisers (19.7 ± 1.3 years) who completed a standardized exercise regimen consisting of an VO2 peak test and 30 min of moderate-vigorous exercise (65% V̇O2peak) consumed 25.2% ± 16.6% less energy on an ad-libitum pasta meal that was served 60 minutes after the workout.
  
  If we assume that they women didn't compensate for the "missing" 25% of the energy later during the day and assuming that they did the workout 2x per week, the 169kcal per workout would yield a total fat loss of 1.9kg per 6 months - well, if the 7,000kcal deficit per 1kg of fat equation actually held ;-)
• Milk-based drinks are more effective rehydration options compared with traditional sports drinks. The additional energy, protein, and sodium in a milk-based liquid meal supplement facilitate superior fluid recovery following exercise.
  
  The aim of a recent study from the Griffith University study was to compare the rehydration potential of a carbohydrate-electrolyte beverage with several varieties of milk following exercise-induced fluid losses. Fifteen male participants (age 24.9 ± 5.5 years, height 179.3 ± 4.9 cm, body mass 75.8 ± 6.6 kg (mean ± SD)) lost 2.0% ± 0.2% body mass through intermittent cycling before consuming a different beverage on 4 separate occasions.
  
  The drinks that were tested included cow's milk (286 kJ·100 mL(-1)), soy milk (273 kJ·100 mL(-1)), a milk-based liquid meal supplement (Sustagen Sport (Nestle); 417 kJ·100 mL(-1)), and a sports drink (Powerade (Coca Cola Ltd); 129 kJ·100 mL(-1)). Beverages were consumed over 1 h in volumes equivalent to 150% of body mass loss. Body mass, blood and urine samples, and measures of gastrointestinal tolerance were obtained before and hourly for 4 h after beverage consumption.
  

  

  Figure 3: Overview of the most important study results (Desbrow. 2014).

  The results show that the net body mass at the conclusion of each trial was significantly less with Powerade (-1.37 ± 0.3 kg) than with cow's milk (-0.92 ± 0.48 kg), soy milk (-0.78 ± 0.37 kg), and Sustagen Sport (-0.48 ± 0.39 kg). Net body mass was also significantly greater for Sustagen Sport compared with cow's milk trials, but not soy milk. Upon completion of trials, the percentage of beverage retained was Sustagen Sport 65.1% ± 14.7%, soy milk 46.9% ± 19.9%, cow's milk 40.0% ± 24.9%, and Powerade 16.6% ± 16.5%.
  
  If it were not for the fact that some of the subjects were complaining over increased bloating and fullnessduring all milk trials compared with Powerade, there would thus be no reason to go for the "classic" high carb + electrolyte solutions.

Are the hormonal side effects of dairy and its cancerous consequences even worse than they're painted by the steadily growing anti-dairy lobby? Find the answer to this and related questions in a previous SuppVersity article from January 2014 | read more.

Not all that glitters white like milk is gold, though. Only recently scientists from the Tokyo Metropolitan Institute of Gerontology had to realize that milk fat globule membranes, of which previous studies have shown that they may help avoiding metabolic syndrome (Pfeuffer. 2007), do not boost the already beneficial effects of exercise on the frailty status of elderly men and women (Kim. 2015).

Just like the previously discussed disappointing results of the Volterman (2014) study, the results Kim et al. present in their latest study do not negate the existing beneficial effects on satiety / anti-binging, muscle damage and function in response to muscle damaging exercise and rehydration discussed in this article | Comment on Facebook!

References:

• Desbrow, Ben, et al. "Comparing the rehydration potential of different milk-based drinks to a carbohydrate–electrolyte beverage." Applied Physiology, Nutrition, and Metabolism 39.12 (2014): 1366-1372.
• Kim H, Suzuki T, Kim M, Kojima N, Ota N, Shimotoyodome A, Hase T, Hosoi E, Yoshida H. "Effects of Exercise and Milk Fat Globule Membrane (MFGM) Supplementation on Body Composition, Physical Function, and Hematological Parameters in Community-Dwelling Frail Japanese Women: A Randomized Double Blind, Placebo-Controlled, Follow-Up Trial." PLoS One 6;10.2 (2015):e0116256.
• Pfeuffer, M., and J. Schrezenmeir. "Milk and the metabolic syndrome." Obesity reviews 8.2 (2007): 109-118.
• Rankin P, Stevenson E, Cockburn E. "The effect of milk on the attenuation of exercise-induced muscle damage in males and females. Eur J Appl Physiol. (2015): Feb 12. [Epub ahead of print] 
• Rumbold, Penny, et al. "Milk Consumption Following Exercise Reduces Subsequent Energy Intake in Female Recreational Exercisers." Nutrients 7.1 (2015): 293-305.
• Volterman, Kimberly A., et al. "Effects of postexercise milk consumption on whole body protein balance in youth." Journal of Applied Physiology 117.10 (2014): 1165-1169.

Rhabdo & Liver Failure or Just an Intense Leg-Workout? What Your Doctor Does not Know About AST, ALT and CK - CK-Values of 10,000 IU+ Will not Necessarily Kill You

Intense training sessions will always increase ALT, AST & CK. Unfortunately doctors will never learn that in med-school.

I don't remember the exact number, but I am afraid that I have promised to write and post this article at least a dozen of times. After getting another three questions pertaining to elevated AST, ALT and CK values on the last lab report within the last two weeks, only, I think it's about time to live up to this promise and translate + update an older, German article, I've written about the very same subject several years ago (note: I decided against translating it, but will write a complete new article - with updated facts, obviously).

Let's first see what we are actually talking about. Typically you went for a routine blood work and get a call from the nurse that there was something wrong with your "liver"- or "muscle-enzymes". You are summoned into the doctor's office, where your concerned doctor is already waiting at his desk looking at you as if you were a criminal and an idiot: "Do you do steroids?"

No, creatine is not the reason your creatine kinase levels are increased?

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That's the standard questions you will hear, when you enter the office - usually with this accusing undertone that says: "There you have it, now you have to suffer the consequences". Usually, this is the moment, when your mind starts racing: "What does he want, I did never... oh, my! Maybe the wise-asses over at the FDA were right after all? Was one of the supplements I took tainted..."

*STOP!* Agonizing about what you could possibly have done wrong is not going to help you here. This is all the more true if we take into account that tit is very likely that you did not do anything wrong at all. Against that background I'd suggest you stop panicking and start reading today's SuppVersity article, which will inform you about (1) what exactly AST, ALT and CK are, (2) why your doctor is so concerned about their elevation, and (3) how you can find out if he is rightly concerned or you are in the midst of a fitness version of Much Ado About Nothing.

What exactly are AST, ALT and CK & how do you read them (in contrast to your Dr)

On the text-book level this question is easy to answer. I guess it'd be best if we started with the proper name, of which you'll see that they already give away half of the solution to the mystically ALT, AST and CK elevations and the rarely measured but often likewise elevated lactate dehydrogenase and myoglobin levels.

Table 1: Time in h before ALT, AST, etc. (➚) exceed reference, (☆) peak, (➘) are back to normal (Petterson. 2007)

• ALT - alanine transaminase
  formerly SGPT, serum glutamic-pyruvic transaminase
• AST - aspartate transaminase
  formerly SGOT, serum glutamic oxaloacetic transaminase
• CK - creatine kinase
• LD - lactate dehydrogenase
• Myoglobin - iron- and oxygen-binding protein

Instead of tackling them alphabetically, we will start with "C" as in "creatine kinase", because this muscle enzyme, every SuppVersity reader knows as a frequently used, but pretty unreliable indicator of muscle damage is - at least in my experience - the #1 reason you may receive an overanxious call from your doctor's receptionist.

Elevated CK = Intense workout ↛ rhabdomyolysis ⇆ cardiac infarction

Did you ever notice that most lab reports list two types of creatine kinase? No? Usually they are listed as CK-MM and CK-MB and denote two out of a total seven isoforms scientists and doctors who specialize in muscular disorders are regularly testing for:

• 

  Suggested Read: "Why training over the full ROM counts" | more

  CKB ➫ brain | BB-CK
• CKBE ➫ ectopic expression | n.a.
• CKM ➫ all muscle | MM-CK
• CK-MM  ➫ mostly skeletal muscle
• CK-MB ➫ mostly heart muscle
• CKMT1A, CKMT1B ➫ ubiqu. mitochondrial CK
• CKMT2 ➫  sarcomeric mitochondrial CK

For your purposes the funky mitochondrial CK values are irrelevant and testing brain CK levels is usually not necessary either. Knowing your CK-MM and CK-MB, however, can come very handy to exclude identify which muscles are affected (note: Being lovesick does not lead to elevated CK-MB levels ;-)

The CK-MM differntial diagnosis: Have you sustained a cardiac infarction?

I should have mentioned it before, but I believe you are smart enough not to take this article as an invitation to recklessly ignore your Dr's calls. The first thing you would want to do, when the doctor's receptionist is calling it to ask her for the exact CK-MM and CK-MB values.

Tip #1: Always insist on a print-out of all your lab values. The receptionist may say that she cannot pass confidential health information via the telephone, but neither she nor your doctor have the right to keep all or parts of your medical records from you. You paid for the lab report, so it's your property and the least your doctor can do, is handing you a copy or printout of the results. File the sheets in a folder for reference and make sure you never lose that folder.

Their ratio, i.e. the ratio of "skeletal specific" and "heart speficic" creatine kinase, can tell you whether it makes sense / is necessary to further investigate the presence of weak and not even noticeable cardiac infarction.

• A follow up on your heart health is indicated, if CK-MB is elevated and higher than 5% of the total CK (CK-MM) value | example: CK-MB = 200 + CK-MM = 1000

Despite the fact that the 'text-book' ratio of CK-MM to CK-MB for muscle is 99:1, the balance can be slightly off in response to intense exercise, even in the absence of cardiac damage. On the other hand, ca. 25% of the patients with acute myocardial infarctions and symptoms like chest pain, shortness of breath etc. don't even have elevated CK-MB levels, when they present in the ED (Karras. 2001).

Irrespective of all uncertainties, it is very unlikely that your heart has actually taken a beating, if you are and have always been symptom free and have a high CK-MM:CK-MB ratio. This is particularly true if you have been training in the days before the blood draw.

Figure 1: Serum creatine kinase levels (in µkat/L) of perfectly healthy young men after a single intense full-body workout (left); exercise selection (right) - all exercises were performed for 3 sets à 12 reps with 70% of the 1-RM max, the average total weight moved during a single workout was >10 metric tonnes (Petterson. 2007)

As the data in Figure 1 goes to show you, increased levels of creatine kinase in response to strenuous physical activity, such as the standardized resistance training regimen (full body, 3x12 reps on each exercise, training to failure, 60s rest between sets; total training volume in weight units 10,500kg) in a 2007 study by Petterson et al. are perfectly normal. If you look closer, you will also relize that ...

1. the creatine kinase elevations peaked 3-4 days after the workout
2. the peak values vary from 'well within range' (= within the green box) to 6x above normal

In subjects 9, 11, 12 and 15, who had CK values that peaked 158x-278x higher than the official upper reference limit for the tests Petterson et al. used (note: most labs will use IU references, where the 3.2 µkat/L from Petterson's study would equal 206IU/L), the amount of myoglobin, which is likewise an indicator of severe skeletal muscle damage, was even above the upper detection limit (2999µg/L). Without the accompanying information that the previously untrained subjects have been hitting the weights, it is thus more than likely that most doctors who are looking solely at the lab raport would assume the 15 subjects from the study at hand were suffering from borderline to full-blown Rhabdomyolysis (Greek: ῥαβδω rhabdo- striped; μυς myo- muscle; λύσις –lysis).

Tip #2: Tell your doctor, when you've been lifting before the blood draw! If your medical practitioner does not know you and your training practices you can hardly blame him for being concerned about your health, when your creatine kinase levels are 10x-200x elevated.

It goes without saying that neither the 'low -', nor the four 'high responders' in the Petterson study had to be transferred to the emergency room for impeding kidney damage in response to full-blown rhabdomyolysis and that despite the fact that their levels were - due to their low training status - much more pronounced than those of the average athlete.

If you train like an athlete you will have the creatine kinase levels of an athlete

Irrespective of the protective effects of regular exercise, even professional athletes have chronically elevated creatine kinase levels. Yet, despite the fact that a 1984 study by Jaffe et al. was by no means the first to conclude that a substantial fraction of professional athletes have elevated CK-MM and CK-MB levels (Jaffe. 1984), Vassilis Mougios' 2007 paper "Reference intervals for serum creatine kinase in athletes" was the first to present a set of scientifically verified reference intervals for creatine kinase levels in athletes (Mougios. 2007). 

Figure 2: Experimentally verified CK values in male and female athletes and calculated CK reference ranges for athletes and non-athletes (Mougious. 2014))

If you are training like an athlete, the reference values Mougious calculated based on data from 483 male athletes and 245 female athletes (aged 7–44 years; see Figure 2) are thus a much better benchmark to determine whether you should or shouldn't be concerned about the red exclamation mark on your lab report.

What you (could) have learned today: Before we are about to take a closer look at the "liver values" ALT and AST, next week, let's briefly summarize what you you could have learned today that may help you, when you're summoned to the doctors office and your doctor wants to call the ambulance to save your kidneys from the consequences of your "rhabdo":

• Elevations of >10,000IU can occur and last for days after intense workouts.
• Regular training lowers the exercise induced CK leakage from the 10,000+ range back to the 500-1,500IU range.
• Nevertheless, the CK levels of athletes will always be higher than that of sedentary controls.
• It can take up to a week for your CK levels to return to baseline. If you want to make sure that your high CK levels are caused by exercise and nothing else, you will have to take a full week (best 14-days) off, before you retest.
• If the levels don't return to "normal" when you rest and / or if you train at a frequency and intensity that leads to chronically elevated CK levels, don't ignore this problem. Try to get to the bottom of it and make sure it's not a health issue - as soon as that's done, adapt your training regimen and rewrite it from "insane" to "intense, but sensible".

Before you go, I would like to point out that your doctor is right to be concerned. Even if he knew about the effects of exercise (most doctors don't), 99% of his patients are not going to the gym and doing breathing squats for reps. For those people CK-values in the 1k+ range are a serious cause of concern. Learn more about elevated AST and ALT levels in the follow up!

Reference:

• Jaffe AS, Garfinkel BT, Ritter CS, Sobel BE. Plasma MB creatine kinase after vigorous exercise in professional athletes. Am J Cardiol. 1984 Mar 1;53(6):856-8.
• Karras DJ, Kane DL. Serum markers in the emergency department diagnosis of acute myocardial infarction. Emerg Med Clin North Am. 2001 May;19(2):321-37. Review.
• Mougios V. Reference intervals for serum creatine kinase in athletes. Br J Sports Med. 2007 Oct;41(10):674-8. Epub 2007 May 25.