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.

You can learn more about chocolate and cacao at the SuppVersity

Chocolicious Statin 4 Women

Real Cacao Delicious + More

The Chocolate Diet for Women

Cacao for the Gut Microbiome

Cacao as Anti-Cancer "Drug"?

Don't Fall for Chocolate Myths

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.

Is Hydrolized Whey, the New Way to Go? 12 Week Human Study Suggests: Yes, If Your Goal is to Ward Off Oxidative Damage. No, If You Want to Build Muscle & Lose Fat

The typical soccer player is no longer a stick on muscular legs, these days. The sport has changed and so have the physiques of the players.

I guess ever since I published the article "The Glucose Repartioning Effects of Isoleucine: Falsely Underappreciated BCAA and Its Dipeptides Maximize GLUT-4 Expression and Ramp Up Muscular Glucose Uptake" (read it) that discussed the beneficial effect of the small isoleucine peptides in hydrolized whey on glucose metabolism, some of you may have been wondering, whether theh previously sneered at even more insulinogenic fast-digesting, bad-tasting, highly-processed whey protein hydrolysates (WPHs) may not be an alternative, if not the better alternative to whey concentrates or isolates.

Personally, I have always favored the "whole" over its individual parts, but the evidence that there is something special about WPH is accumulating.

"So what kind of new evidence is accumulating here?"

That being said, the latest evidence that would support this notion comes from the Universidade Estadual de Campinas in São Paulo, Brazil (Lollo. 2013). Where Pablo Christiano B. Lollo et al. investigated the effects the provision of whey protein (WP), hydrolysed whey protein (WPH), or a non-protein placebo (maltodextrin, MALTO) would exert on selected biochemical, anthropometric and performance parameters in 24 soccer player over the course of 12 weeks.

The iso-caloric supplements which contained 0.5g of protein (or placebo) per kg of body mass had to be before and after each training session, as well as on rest days (i.e. on Monday). The overall protein intake was relatively low (typical of a sport with a clear endurance focus) and was designed so that the protein of the diet plus that of the supplement would represent 15% of the total daily caloric intake. Both, the diets, as well as the sleep and training schedule were standardized. The intensity and training volume were identical for all individuals having plaing the same position (e.g. striker, defender, etc.). And the amino acid content of the two whey supplements was identical, so that the only difference between the WP and the WPH group was the chain-length of the proteins and peptides in the drinks they ingested.

Figure 1: Changes in markers of exercise induced damage (left) and body composition changes (in %) over the course of the 12-week study period (Lollo. 2013)

As you can see in figure 1 this minute difference was yet enough to result in significantly different responses to the protein supplement in the WPH and WP groups.Only, in the former, i.e. the whey protein hydeolysate group did the scientists observe significant decreases in the muscle damage indicators, creatine kinase (-42%) and lactate dehydrogenase (-30%). The minimal changes in the whey protein group, on the other hand, were not superior to the maltodextrin control.

"The foremost features of this investigation were greater than 40% and 30% decrease in CK and LDH, respectively, obtained after 12 weeks of supplementation with the hydrolysed whey protein. This outcome contrasted even more with the increase of CK, which was approximately  +35% obtained by supplementing with maltodextrin alone." (Lollo. 2013)

As you would expect there were no apparent adverse effects observed in either of the groups whose total total protein intake remained below 2.3 g/kg per day. The renal function and protein metabolism parameters, uric acid and creatinine remained within the physiological limits of normality in all groups. 

WPH the whey for elite athletes? 

In their discussion of the results, Lollo et al. make an interesting point, when they compare their observations to those in previously conducted studies and state:

Right from the archives: "Looking at Fast, Slow & Total Protein Intake. More Than 2g/kg Protein = Madness?" (read more)

"Since studies of the effects of protein supplementation have normally been carried out with non-athlete volunteers in acute experiments (Bolster et al., 2005; Pennings et al., 2011; Tipton & Ferrando, 2008), it was interesting to note that the data collected from elite athletes engaged in a real championship pointed to hydrolysed whey protein being the only form of supplement that effectively diminished the levels of muscle damage biomarkers.

Those results could be understood in light of the high antioxidant capacity of the hydrolysate." (Lollo. 2013)

If that could be confirmed for other elite athletes and highly trained gymrats, as well, the question I raised in the headline of this article may well be answered affirmatively: "Yes, for elite athletes with a high training workload, hydrolized whey proteins may in fact be the better way to go."

If you take a closer look at the data in figure 1 (right hand side), you will have to concede that this could well be a question of the kind of athlete we are looking at. A bodybuilder for example would fare better with regular whey. While soccer training is an allegedly bad model for bodybuilding, the way in which regular whey has the most favorable effects on body composition, i.e. a statistically significant 3.4% increase in muscle mass and non-significant 6% decrease in fat mass, is something I personally would not ignore (on a side note, you did see that the fat loss maxed out and reached statistical significance with the pure maltodextrose, right?). 

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Metabolic ward study shows: Higher than RDA protein intake turns weight loss into a fat loss diet, yet still it's not the more the better (learn more)

Bottom line: Despite or maybe even due to its high anti-oxidant prowess whey hydrolysate may not be the ideal protein for the average gymrat trying to build muscle, lose fat and improve his overall body composition. Allegedly, a study in soccer players and above all one with only 24 subjects is certainly not a reliable gauge, but why would you quit using what has worked for you before, if the evidence that the alternative may be good, but not exactly conducive to your primary goals?

Moreover, let's not forget, if you are simply trying to pack in some additional protein into your diet, price and taste are certainly things you want to consider, as well. And let's face it the taste and mouth-feel of the few true hydrolysates out there (most supplement producers mix various forms of whey and will still sneak a "hydro" into the name) are not exactly what you would expect from something you'd consume as a "liquid snack", right?

References: 

• Bolster DR, Pikosky MA, Gaine PC, Martin W, Wolfe RR, Tipton KD, Maclean D, Maresh CM, Rodriguez NR. Dietary protein intake impacts human skeletal muscle protein fractional synthetic rates after endurance exercise. Am J Physiol Endocrinol Metab. 2005 Oct;289(4):E678-83.
• Lollo PBC, et al. Hydrolysed whey protein reduces muscle damage markers in Brazilian elite soccer players compared with whey protein and maltodextrin. A twelve-week inchampionship intervention. International Dairy Journal. August 2013 [epub ahead of print]
• Tipton KD, Ferrando AA. Improving muscle mass: response of muscle metabolism to exercise, nutrition and anabolic agents. Essays Biochem. 2008;44:85-98.
• Pennings B, Koopman R, Beelen M, Senden JM, Saris WH, van Loon LJ. Exercising before protein intake allows for greater use of dietary protein-derived amino acids for de novo muscle protein synthesis in both young and elderly men. Am J Clin Nutr. 2011 Feb;93(2):322-31.

2-3g of β-hydroxy-β-methylbutyrate (HMB) Slam the Brake on Muscle Damage and Hit the Gas Paddle on Muscle Growth, Race Performance & Fat Loss in Elite Canoeists

With their intense strength + endurance training in the pre-contest phase canoeists may be among those athletes who benefit most from the muscle protectant anti-catabolic advantage of HMB.

It's funny how the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) disappeared into oblivion in the early 2000s, only to rise like Phoenix from the ashes, now that the 21st century is in its teenage years (Thomson. 2009; Wilson. 2013a,b) From previous SuppVersity news (read more about HMB), you know that β-hydroxy-β-methylbutyrate has slightly less pronounced anabolic, yet better anti-catabolic effects than its precursor leucine. You may also remember that many of the studies with beneficial outcome have been conducted on elderly or sick subjects (e.g. May. 2002; Vukovich. 2001) and that these studies showed (more or less across the board) favorable effects that could not be replicated in younger and/or trained subjects (e.g. Slater. 2001).

Now, despite the fact that it seems logical that HMB would have a greater "muscle building effect" for those of us who are - due to their age or other confounding factors - more prone to muscle protein catabolism than for someone like a competing elite canoeist in the strength phase of his seasonal training cycle - or, without further beating around the bush, the average 78.5kg, 11% body fat male participant of a study, the results of which have recently been published in the online edition of the Journal of Exercise Physiology (Ferreira. 2013).   

"Old school", but neither out-of-date nor "for the oldies only"

To "determine whether HMB supplementation at 37.5 mg·kg/d during intense endurance training affects markers of catabolism, body composition, and sports performance in kayak athletes’ high performance sprints" (Ferreira. 2013), the scientists from the Laboratory Cell Metabolism (LABMETAB) and the Laboratory Motor Behavior at the Federal University of Parana in Curiba, Brazil, randomized their 20 subjects to receive either a placebo (n = 6) or the active treatment dose of 37.5 mg·kg (2.5-3.0g; depending on body weight) "classic" powdered calcium HMB per day during the six strength training weeks of their prep. To minimize any non-supplementation-related influences, ...

HMB & leucine could also help you shed fat & live longer (learn more)

"[a]ll meals were kept under strict control by the nutritionist. None of the subjects was allowed the use of creatine and/or beta-agonists for at least 8 wks prior to the study. [Furthermore, a]ll subjects (i.e., athletes) were instructed to not ingest other dietary supplements with ergogenic effects during the study." (Ferreiara. 2013)

As the data in figure 1 goes to show you, the use of the supplement, which was to be taken in three seperate doses equally spread across the day (morning, afternoon, and evening), had statistical significant effects on the the results of the subjects’ training sessions.

Training like the "pros": Frequent high volume training

The workloads of the latter had been individualized and averaged ~ 6 hr/wk of resistance training (1 to 3 sets of 2 to 8 repetitions at intensities ranging from 80 to 95% of 1 RM) on Monday, Wednesday, and Friday plus 10 hr//wk of specific sprint technique training in the boat. Overall, the subjects were thus training two times a day for a total of 11 training sessions a week (bear that in mind, because it will be important in the bottom line). All trainings sessions ha been conducted under the supervision of certified coaches by CBC and subjects who missed a training session were required to make them up in accordance with the procedures of the study.

Figure 1: Relative changes in body composition, blood lipids, race performance, creatine kinase (CK), lactate dihydrogenase and creatinine (Ferreira. 2013)

 All subjects underwent monthly testing of venous blood samples, body composition analysis, and specific testing for performance in the water (boat) in the course of which the scientists observed that the paddlers in the HMB group showed...

• significantly more pronounced improvements in body composition than the subjects who had been randomized to the placebo group (-10.26% reduction in body fat % vs. +0.21% in the placebo group), and
• likewise highly significant -34.4% decreases in the skeletal muscle specific iso-form of the "muscle damage gauge" creatine kinase (CK-MM; -34.44% vs. + 40.42% in the placebo and
• pronounced reductions in lactate dehydrogenase (LDH; -20.92% vs. -1% in the placebo group), as well as

Moreover, the race-times of the participants in the active arm of the study improved by 2%, while the elite paddlers who consumed the placebo supplement increased their race-performance by only 1%

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The green dots on the left and right of the blue myonuclei are satellite cells that thrive on high(er) volume routines (learn more)

Bottom line: The overall image that emerges is clear. β-Hydroxy-β-Melthylbutyrate (HMB) works! And the improvements the Brazilian researchers observed in their 20 highly trained subjects were so pronounced that there is no debating with their conclusion that the "improvement in strength and development of muscular hypertrophy [may help] not only athletes but the general population".

For us, all devoted trainees who are well-versed in the previous literature on HMB, the most important conclusion to be drawn is yet that the early Y2K "muscle builder of the elderly" works for everyone, if - an this is the hypothetical part of the conclusion - the training regimen is intense enough to generate similar muscle damage as the relatively low volume, medium intensity resistance training protocols that were used in previous studies with older and mostly untrained subjects (e.g. Baier. 2009).

Whether training twice a day and 10+ times a week is the way to go for everyone, does still remain questionable. After all, the fundamental rule that you cannot 'out-supplement' insufficient regeneration is still valid (learn more). This is particularly true in view of the fact that the majority of trainees is not as well-conditioned as the elite athletes in the study at hand. This does yet also mean that they will suffer similar eustress from lower volume / intensity / density workouts and could still benefit from 2-3g of HMB... I am yet still waiting for study to investigate how significant this effect is, when the subjects already use a pre-/post workout protein supplementation strategy as outlined in yesterday's post, but alas - this is no research request program.

References:

• Baier S, Johannsen D, Abumrad N, Rathmacher JA, Nissen S, Flakoll P. Year-long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of beta-hydroxy-beta-methylbutyrate (HMB), L-arginine, and L-lysine. JPEN J Parenter Enteral Nutr. 2009 Jan-Feb;33(1):71-82. 
• Ferreira HR, Rodacki ALF, Gill P, Tanhoffer R, Filho JF, Cláudio L.The Effects of Supplementation of β-Hydroxy-β-Melthylbutyrate on Inflammatory Markers in High Performance Athletes. Journal of Exercise Physiology. 2013; 2:53-63.
• May PE, Barber A, D'Olimpio JT, Hourihane A, Abumrad NN. Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Am J Surg. 2002 Apr;183(4):471-9.
• Slater G, Jenkins D, Logan P, Lee H, Vukovich M, Rathmacher JA, Hahn AG. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation does not affect changes in strength or body composition during resistance training in trained men. Int J Sport Nutr Exerc Metab. 2001 Sep;11(3):384-96. 
• Slater GJ, Jenkins D. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation and the promotion of muscle growth and strength. Sports Med. 2000 Aug;30(2):105-16. 
• Thomson JS, Watson PE, Rowlands DS. Effects of nine weeks of beta-hydroxy-beta- methylbutyrate supplementation on strength and body composition in resistance trained men. J Strength Cond Res. 2009 May;23(3):827-35. 
• Vukovich MD, Stubbs NB, Bohlken RM. Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. J Nutr. 2001 Jul;131(7):2049-52.
• Wilson JM, Lowery RP, Joy JM, Walters JA, Baier SM, Fuller JC, Stout JR, Norton LE, Sikorski EM, Wilson SM, Duncan NM, Zanchi NE, Rathmacher J. β-Hydroxy-β-methylbutyrate free acid reduces markers of exercise-induced muscle damage and improves recovery in resistance-trained men. Br J Nutr. 2013a Jan 3:1-7.
• Wilson JM, Fitschen PJ, Campbell B, Wilson GJ, Zanchi N, Taylor L, Wilborn C, Kalman DS, Stout JR, Hoffman JR, Ziegenfuss TN, Lopez HL, Kreider RB, Smith-Ryan AE, Antonio J. International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB). J Int Soc Sports Nutr. 2013b Feb 2;10(1):6.

HMB Supplementation: Pre- or Pre- and Post-Workout? Anti- or Pro-Inflammatory? MA Thesis Offers Food for Thought

Supplement facts: "Is as potent as the weak androgen Oxmethalone aka Anavar!" If that's how you advertise an expensive dietary supplement that tastes like poison, you better make sure your product delivers. For HMB the supplement companies must have overlooked that their clientele is in no way similar to the elderly subjects from their references with their protein deficient diets... the result? An epic fail for both the consumers who felt ripped off and the producers who probably expected this to be a long-term investment!

HMB was once hailed to be as effective as a "weak" androgen such as Anavar. No wonder that dozens of consumers were pretty  disappointed, when they added it on top of their already protein and, at that times more or less coincidentally, leucine-laden diets and saw... nothing. Well, at least no gains that would even remotely remind anyone of Oxymetholone. With no costumer being interest to pay the extra bucks for the (at that time still) very expensive product, it was no wonder that the leucine metabolite β-Hydroxy β-methylbutyric acid (HMB) disappeared from the market relatively quickly.

I bet, the fact that it tastes like poison did not really help either. after all it is downright impossible to add an effective amount of HMB into a powdered supplement, if you do not want to totally ruin the taste of the product.

As a SuppVersity reader you will yet be aware that HMB is still no epic fail (read all older posts on HMB). Its marginal utility, however, is exactly that: Marginal -- at least when someone is taking it on top of tons of leucine rich protein powders, BCAAs and whatever else.

HMB is not useless and there appears to be much we have to learn about it

Despite the fact that it is very unlikely that taking HMB will turn you into a second Phil Health within weeks, its hitherto not fully understood beneficial effects on body fat, its effects on GH and IGF-1 as well as open questions that are related to our own bodies ability to produce HMB from leucine and whether this conversion mediated some of the benefits of the #1 among the BCAAs (=leucine) clearly indicate that there remains a lot to learn about Dr. Steven L. Nissen's 1996 discovery (Nissen. 1996).

One of those things we still have... or I should say had to learn pertains the effect of HMB on the exercise induced expression of inflammatory cytokines, which turned out to be totally different from what Paul Raymond Vulcan, a student who has recently submitted his Master Thesis on the "Role of β-hydroxy-β-methylbutyrate (HMB) on inflammation after eccentric exercise" at the Iowa State University probably expected, when he recruited the 16 female and 16 male, untrained volunteers (mean age 3±0.30y, mean weight 67.5±0.9kg, and mean hight 172.2±0.7cm) for his study.

'Extend your legs' till they burn ;-)

The study consisted of a single exercise + supplementation trial in the course of which the participants underwent the following supplementation regimen:

A note on the supplementation protocol: The way Volcan describes the protocol is at least "suboptimal". If I am getting it correctly (mostly by looking at a graphical outline) the participants in the pre/post trial received HMB not just on day 0, but also on day 1, day 2, day 3 and day 4 - always with lunch and dinner.

"Experimental groups received supplement in one of the following manners: placebo pre- & post-exercise (CON), HMB pre-exercise (PRE) in either a calcium salt form or a free acid gel, HMB pre- & post-exercise (PRE/POST) in either a calcium salt form or a free acid gel.Supplements were given in a double-blind protocol so that investigators were also blind to the contents of the supplements throughout the study.  Originally, the study called for 5 treatment groups with a separation of calcium salt groups from the free acid gel groups. Due to sample sizes, groups receiving the same quantity of HMB were consolidated for statistical reasons." (Volcan. 2012)

While it is certainly somewhat disappointing that we don't have a comparison of the salt and the gel variant of HMB (you will see the first gels hit the market, very soon, believe me),  this is understandable given the small sample size. What is yet a clear greenhorn mistake, however, is that Volcan does not disclose the amount of HMB salt the participants received. He states that the gel syringes contained 3ml but since I have no clue what else (besides HMB) is in the gel, I cannot tell you how much HMB the groups actually received (let alone calculate the equivalent in term of calcium-hmb).

Standard protocol, surprising results

Aside from this lapse the general protocol of the study looks pretty solid. The original challenge on day 0, which consisted of 3 sets of 50 eccentric leg extensions (both legs, 0° to 90°, 60°/sec; 3s per rep, 2 min rest between sets), was preceded and followed by a combination of

• urine collection, 
• muscle soreness test, 
• leg circumference measurements, 
• blood collection and a 
• strength test

which took place on day 0 (before the exercise protocol), 24h, 48h, 72h and 96h post. And I guess you could say "fortunately", the analysis of the respective data yielded not exactly what Volcan had expected. Firstly many expected effects did not occur (at least not if you consider only statistical significant inter-group effects), e.g. there were no differences for markers of muscle damage:

• creatine kinase (CK) 
• lactate dehydrogenase (LDH) and 
• 3-methyl histidine (3-MH)

Some did however show a trend (which did not reach statistical significance due to the small sample size) and / or did reach statistical significance at a certain time point only:

• 

  Figure 1: Peak performance force (in N) on the days after the leg extensions (based on Volcan. 2012). As you can see it's not like there had not been any effects, but with the small sample size few made it over the p < 0.05 hurdle, or put simply were "statistically significant".

  creatine kinase (CK) showed a non-statistically significant reduction in PRE/POST, while it was identical in PRE and CON (1593 IU compared to 3514 IU and 4068 IU; this is a candidate that would almost certainly have reached statistical significance with a larger number of participants, because the CK response shows high inter-individual variability)
• the decrease in right leg peak force was about 16% in the CON group compared to 9% and 7% in the PRE and PRE/POST groups, respectively
• the muscle soreness was also not significantly different between groups
• the difference in the loss of peak force was only significant on day two when the peak performance in the control group dropped significantly (see figure 1)

So far the somewhat disheartening but not actually novel part of the study. With the data in figure 2, however we are actually approaching the real news part of today's post:

Figure 2: Makers of inflammation (IL-1 and TNF-alpha) after 3x50 leg extension on the test day, as well as 24h, 48h, 72h and 96h post (based on Vulcan. 2012)

Take a close look and don't be fooled like I was, when I initially looked at the results and almost automatically assumed that there was a reduction in TNF-alpha and IL-1 in the group that recevived the most HMB (I must say I had only the poor black and white graphs from the original study and not the full-service pack you get, here at the SuppVersity, though ;-)

"I mean, good things reduce inflammation, right?"

Wrong, at least in the case of HMB, which certainly is a good thing, this is not the case. HMB does not reduce inflammation and that despite the fact that it works like a charm for those people of whom we are told that inflammation was the last thing they would need, namely the elderly. And still it appears as if the increased inflammatory response to the muscle damaging exercise on day 0 could actually be part of how HMB works. Volcan realizes that and states:

Just in case you don't want to believe that inflammation could play a beneficial role in the regeneration and even the subsequent super-compensation process at the end of which both your muscle strength and muscle size will go up, I suggest you read the respective installment of the Intermittent Thoughts

"The results of TNF-α and IL-1ra support the theory that inflammation is affected by HMB. In  both cases the CON group experienced a decline in serum concentration and the dip was reduced or limited by supplementation of HMB.  These results could be interpreted as an increase in the inflammatory response following HMB supplementation [...] This suggests that HMB creates a greater inflammatory response which may improve recovery of damaged tissue. When exactly this occurs and how, whether direct or indirect, is not evident from this study. We already kno that proteolysis is affected by HMB and it is also possible that inflammatory cytokines are mediating an optimal recovery." (my emphases in Volcan. 2012)

Edited: While this sounds like an excellent hypothesis there is one thing Volcan has overlooked (and me too, at least initially, thus the update). The current scientific evidence suggest that the IL-1 receptor is like a multifaceted chimera. Or put simply, in its conventional form it will accept IL-1 and thus have exert pro-inflammatory downstream effects. IL-1-RA, which is the variant Volcan measured here, actually does the opposite, though: IL-1-RA blocks the inflammatory effects of IL-1 (Arend. 1997).

In the end, this does not really change my previous assertion that "You need to go beyond the 'all inflammation is bad' paradigm and see 'inflammation', or what we usually refer to as inflammation as what it really is, namely a per se physiological reaction of our bodies that can be good, appropriate and highly desirable or bad, misplaced and highly detrimental depending on the circumstances." It just adds another level of complexity to that statement. And this added dimension can actually explain why HMB works in the elderly, but does not work (at least not to the same degree in young people). Old people have high IL-1 (the pro-inflammatory varieties), young and healthy people don't, so blocking IL-1 signaling will have more pronounced effect in the older ones of you than in the young chaps, who will probably fare quite well with nothing but a leucine rich protein shake.

References:

• Arend WP. Interleukin 1 receptor antagonist. A new member of the interleukin 1 family. J Clin Invest. 1991 Nov;88(5):1445-51.
• Nissen SR, Sharp M, Ray JA, Rathmacher D, Rice JC, Fuller Jr, Connelly AS, Abumrad N: Effect of leucine metabolite beta -hydroxy-beta -methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol 1996, 81:2095-2104.
• Volcan PR. Role of β-Hydroxy-β-methylbutyrate (HMB) on inflammation after eccentric exercise. Graduate Theses and Dissertations. 2012; paper 12501.

High and Low Dose BCAA Supplementation Have Minimal, Non-Significant Effects on Markers of Muscle Damage 24h and 48h Post Heavy Resistance Training

Image 1: Cover of the September issue of the International Journal of Wrestling Science - don't tell me you don't have a subscription, yet!

I don't know about you, but I feel that it's quite interesting to look at the highly heterogeneous dosage suggestions on the labels of the ever-increasing number of BCAA supplements on the market. Interestingly, almost every producer claims in his "non FDA-approved" statements that his supplement contains "scientifically supported" or "clinically validated" amounts of branch-chained amino acids in the "optimal" (whatever that may be) ratio of 2:1:1, 3:1:1, 4:1:1, 8:1:1, ... and all the other variations that appear to be limited only by the patent applications and lawyers of the financially more potent players in the business. From a scientific perspective, however, this "optimal" amount has still to be elucidated - at least to my knowledge, no respectable scientist has yet claimed to have found the "optimal" amount and composition of free form amino acids for a given subgroup of athletes, let alone strength athletes, bodybuilders or figure competitors, in general.

At this point I would like to add that no respectable scientist would ever dare to make the claim that he or she has found the "optimal free form amino acid supplement" for all, or even a significantly large group of athletes, unless he or she would be interested in losing his reputation as a "respectable scientist" ;-)

In a recently published study scientists from the Department of Physical education and Sports Science University of Tabriz in Tabriz, Iran, set out to establish whether there is at least a significant difference between the effects of ~15g (210mg/kg) or 33g (450mg/kg) of branched chain-amino acids taken before and after the completion of an intense resistance training regimen comprised of 7 exercises à 3 sets of 10 repetitions (Amirsasan. 2011). Yet, despite the fact, that even the "low dose" of 15g of BCAAs (in the customary 2:1:1 ratio, i.e. 7.5g of leucine + 3.75g of iso-leucine + 3.7g of valine) was about 1.5x higher than what I have seen as "suggested dosing" or "serving size" on very high-dosed commercial supplements, the effects of this amino acid overkill were "sobering", to say the least.

Figure 1: Effects of "low" (210mg/kg) and "high" (450mg/kg) dose BCAA supplement on enzymatic markers of muscle damage relative to pre-values in the placebo group (data calculated based on Amirsasan. 2011)

As the data in figure 1 goes to show both the "low" as well as the "high" (or should I say "overkill" ;-) dose of pre- and post-workout BCAAs had only marginal, and certainly statistically non-significant effects on creatine kinase (overall - CK; muscle specific - CK MB) and lactate dehydrogenase activity, both established indicators of (exercise-induced) muscle damage.

Comparison of results between groups in mean and amplitude changes of serum indexes of cell damage (CK-LDH-CKMB), 24 and 48 hours after the exercise performance showed no significant difference between the 3 groups. In other words, different amounts of BCAA did not significantly affect the serum cell injury indexes (CK-LDH-CKMB), 24 and 48 hours after the heavy resistance activity.

These results are interesting, because they contradict previous findings by Sharp et al. who reported "significantly reduced" creatine kinase levels with BCAA supplementation in likewise previously strength-trained athletes on a similarly intense (8 exercises; 3x 6-8 repetitions) resistance training protocol (Sharp. 2010), as well as the results of studies in endurance athletes and previously untrained subjects, where the provision of BCAAs decreased creatine kinase and lactate dehydrogenase enzyme expression, across-the-board (Greer. 2007; Koba. 2007; Matsumoto. 2009).

"To supplement or not?" This question may arise if you have a look at the data from this study. Thor, in a comment to this posts poses the question whether his "personal experience" that "having the fast digesting aminos seemed to increase [his] ability to have a more successful work out" is, after all "only in [his] head" and while I cannot say for sure how much of it may be the result a placebo-effect in his case, I can provide you with the results of a 2011 study by Greer et al. who found no increases in exercise performance despite reduced perceived rates of exertion with BCAA supplementation after a 90-minute cycling bout (Greer. 2011). These results seem to confirm the "central fatigue hypothesis" according to which BCAAs exert their beneficial effects agains (perceived) fatigue via modulation of the availability of the serotonin precursor tryptophan. In a 2007 review of the literature, Meeusen and Watson do yet conclude that the "nutritional manipulation of these systems [neurotransmitter] through the provision of amino acids has proven largely unsuccessful" (Meeusen. 2007)... All that does not take away from the established beneficial effects of chronic low-dose BCAA (in particular, leucine) supplementation on endurance performance and strength adaptations to exercise (e.g. Crowe. 2006; Matsumoto. 2009). In the respective studies, dosages in the 1.5-3.0g/day range have yet been sufficient, to elicit these beneficial effects - and that in subject groups that are not particularly well-known for their exorbitantly high protein intakes ;-)

Image 2: When bought in bulk and without the addition of a ton of fancy extras BCAAs have become reasonably priced - whether they are a "necessary" part of your supplement regimen may yet depend on your dietary protein intake.

Probably - this would at least be my first guess - the outcome of these studies was not so much affected by the actual study protocol, but rather by the habitual dietary protein intake of their subjects. With endurance athletes (Koba. 2007; Matsumoto. 2009),  recreationally active (Sharp. 2010) and untrained (Greer. 2007) we usually see much lower dietary protein intake than with professional wrestlers, which prompts me to repeat my previously stated skepticism towards the usefulness of large boluses of additional free form amino acids in a group of athletes whose habitual dietary protein intake is way beyond the 1.5g/kg level, anyway... but hey, that's just the opinion of a brainy physicist; so if your brawny guru says you need those 150g of BCAAs on top of your 5x50g whey protein shakes and your 3 pound of lean meat - go for it!

No Influence of Rest Between Sets on Creatine Kinase and Lactate Levels

Probably, you would assume that the reduction of rest in between sets from 3 minutes to 60 seconds would have an effect if not on creatine kinase, then at least on lactate levels. A recent study published in The Journal of Strength and Conditioning Research refutes this common-sense assumption (Machado. 2010):

Each session consisted of 4 sets of 10 repetitions with 10 repetition maximum loads for the chest press, pullover, biceps curl, triceps extension, leg extension, and prone leg curl. The sessions differed only in the length of the rest interval between sets and exercises, specifically: 60, 90, 120, 180 seconds. Serum CK and LDH were significantly (p < 0.05) elevated 24-72 hours after each session, with no significant differences between rest intervals (p = 0.94 and p = 0.99, respectively). The mechanical stress imposed by the 4 resistance exercise sessions invoked similar damage to the muscle fibers independent of the rest interval between sets.

Since the exact relation between markers of muscle damage, hypertrophy and strength gains have yet to be established, it is as of yet impossible to derive concrete training advice from these findings. In other words, this does not mean that resting times do not make a difference in view of the eventual training results. Shorter rest periods, for example have been associated with increased growth hormone response and an overall more pronounced anabolic stimulus.

Whey Protein Isolate Increases Strength Gains over Carbohydrate Control

Regular readers of the SuppVersity, won't be surprised to hear that Cooke et al. (Cooke. 2010) found that supplementing a group of 17 previously untrained participants (23 +/- 5 yr, 180 +/- 6 cm, 80 +/- 11 kg) with a) whey protein isolate (WPH; n=9) or b) carbohydrate (CHO; n=8) at 1.5 g/kg.bw/day supplement (~30 g consumed immediately, and then once with breakfast, lunch, in the afternoon and after the evening meal) for 14 days resulted in a significant positive effect on exercise recovery and plasma creatine kinase and lactate dehydrogenase (LDH) levels:

Figure 1: Strength development in a) whey and b) carbohydrate groups. (Cooke. 2010)

Isometric knee extension strength was significantly higher following WPH supplementation 3 (P<0.05) and 7 (P<0.01) days into recovery from exercise-induced muscle damage compared to CHO supplementation. In addition, strong tendencies for higher isokinetic forces (extension and flexion) were observed during the recovery period following WPH supplementation, with knee extension strength being significantly greater (P<0.05) after 7 days recovery. Plasma LDH levels tended to be lower (P=0.06) in the WPH supplemented group during recovery.

The exercise regimen, and this is particularly interesting, was pretty intense and mirrored basically what the experienced gymrat would be doing to put some mass on his skinny legs. It was a unilateral eccentric  contraction-based resistance exercise session, consisting of 4 sets of  10 repetitions at 120% of maximum voluntary contraction on the leg  press, leg extension and leg flexion exercise machine.

So, what are you wheyting for? Go heavy, but don't forget to drink your whey isolate, because that's the whey to get stronger ;o)