Are We Whey-sting Money? Study says: No Increase in Size or Strength Gains With Peri-Workout Protein Supplements. Plus: Pegylated Whey & Leucine - Worth the Extra Bucks?

Protein, sugar or plain water - what if it would not even matter what was in his bottle, as long as he is still young, works out hard and gets his 1.2g+ protein per kg body weight from whole foods?

If this is not the first time you're here at the SuppVersity you are unquestionably aware that the effect size of the tried and proven peri-workout supplementation is totally overrated. Notwithstanding, a protein supplement and especially a fast digesting whey protein is one of the SuppVersity Suggested Staple Supplements; one of those supplements of which even I claim that 99% of the trainees can benefit. So what do we do with the results of a recently published paper by Ashley A. Walter and her colleagues from the University of Kansas Medical Center, the University of Kansas, the California State University-San Bernardino, the University of North-Carolina-Chapel Hill and the University of Central Florida?

Have we been doing it wrong, all the time?

Do we simply ignore their data, which indicates that 8 weeks of resistance training (three times per week, chest + legs) does increase muscle performance and size similarly among all groups "regardless of supplementation" (Walter. 2013). Why no? I mean let's wrap this up and simply say, the study must be flawed. No wonder, actually, after all the idea to investigate the differential effects of different forms of protein (regular vs. "bioenhanced" = pegylated* whey), different workout volumes 3 vs. 5 sets and a placebo vs. a "no supplement at all" control group looks like one of the classic mistakes science greenhorns ake. A mistake I know only all to well fro the real world university (not the SuppVersity), where overeager students of mine who try to write the "Jack of All Traits" Bachelor or Master thesis in 99% of the cases produces a garbled mess with little or no scientific value.

What is pegylation? Pegylation refers to the process of binding a molecule, like a small peptide or amino acid to polyethylene glycol in order to increase its bioavailability. It's common practice with pharmaceuticals and has already shown some promise in previous studies with pegylated creatine (e.g. Camic. 2010). Especially in the case of PEG creatine, it is however questionable, whether the higher bioavailability, which does nothing, but reduce the dosage requirements (Herda. 2008), would be worth the additional costs. My personal answer to that question clearly is "no" and the fact that these expensive products actually never had a breakthrough on the market would confirm that the marginal utility is zero (or negative ;-)

On the other hand, there is no debating that the study at hand, with its 106 healthy active male volunteers (mean age 21 years, body fat 10-25%; ~60% with aerobic training, ~40 percent with resistance training experience or both, as well as 60% performing other recreational sports regularly) and thus ~20 subjects per group is not underpowered, as you would expect and should thus in fact be able to spot differences between the 5 arms of the 8-week randomized, placebo controlled clinical trial:

• bio-enhanced whey* protein with low volume training (BWP LV , n=22)
• bio-enhanced whey protein with moderate volume training (BWP MV, n=20)

• standard whey protein with moderate volume training (SWPMV, n=22), 

• placebo with moderate volume training (PLA, n=21), 
• control (=no suppleent) with moderate volume training (CON, n=21).

The supplement itself was chocolate-flavored and ingested on both workout days and off days: one before, one after the workout or a single shake at a self-chosen timepoint on the off day. The main difference between the "bio-enhanced" and the regular whey was the addition of 5g of polyethylene glycosylated (PEG) leucine to the baseline amount of 20g of whey. The placebo contained pure maltodextrin and the control group did not receive any drink whatsoever... actually this is something I have not seen before - a neat way to answer the question: How much of the efficacy of a tried and proven staple supplement lke Whey is actually in your head, only?

Enough of the presquabble let's take a look at the results

Looking at the plots in figure 1 certainly does not look like there would not be any differences to begin with, but once you realize the "differences" are almost exclusively negligible and well within the standard deviations of the respective parameters.

Figure 1: Changes in body composition (left), strength and strength endurance (right; Walter. 2013)

There are just two things that stick out, #1 is the statistically non-significant but still obvious fat loss advantage of not supplementing at all (marked by an arrow) and the other one is the lean and total mass disadvantage of the ...

• Note: Both programs involved training chest and legs thrice a week, which should obviously be enough of a growth stimulus. If you doubt that or believe that it may even be too much, take a look at the success of the guys in the control groups.
  low volume training program , which involved an onramp up to 3 sets of 6 reps with 80% 1-RM on the bench and the leg press,compared to the

• high volume program, in the course of which the subjects performed 5 sets of 6 reps with 80% 1-RM on the bench and the leg press

This observation does in fact fit pretty well with rationale the scientists use to explain the non existence of any measurable differences between the 5 arms. "[A]midst the anabolic stimulus of resistance training." (Camic. 2013), the additional growth stimulus any amount of protein could add to the already high basal level of workout induced MPS in young men would simply be negligible (cf. Volpi. 2001; Yarasheski. 2002).

"This may partially explain why this study showed no significant effects of protein supplementation beyond the resistance training during the 8- week study period, regardless of treatment group.[...] Our primary outcome variable was muscular strength changes. While the present study indicated strength changes in all groups, the importance of a lack of additional change in the groups with protein supplementation." (Walter. 2013)

What is yet interesting is tthat not just the protein supplementation but also the ~40-45% higher volume in the "-MV"-groups (medium volume training) vs. the "-LV"-group (low volume training) did bring about significant changes in 55-59% of the resistance training volume elucidated significant differences in strength or size gain.

Suggested read "Greater & Steadier Strength Gains w/ 8 Sets of Squats." (Article I) and "Higher Volume Increases Strength Gains in Legs,  Satellite Cell Recruitment and Fiber Size in Legs & Traps." (Article II)

Unfortunately, it cannot be said if the protein supplementation did in this case create an equal playing field or not, although the researchers' statement that 

"[...] these findings suggest that when a moderate- or high-volume of resistance training is not possible, consuming protein and amino acids in conjunction with a low-volume resistance training program may be sufficient for achieving equivalent results" (Walter. 2013).

 appears to suggest just that: The fallicious believe that you can "out-supplement" suboptimal training routines. This does not necessarily mean that you got to to 5 sets of every of the X exercises you do, but if you stick to only one, you better make sure to have at least five sets esp. for legs and other large muscle groups (check out the suggested reads on the right for more information: Article I, Article II)

Apropos level playing field 

A brief glance at the data in figure 1 shows that (a) the protocol did work out as it is supposed to be and only the guys in the protein supplement groups did actually exhibit a significant increase in protein intake, and (b) that the overall protein intake on a per kg of body weight base was - quelle suprise (!) - exactly where the many ofthe latest reviews say it has to be, in order to support optimal protein synthesis in young men: in the +1.2g  range (e.g. Coleman. 2013).

Figure 2: Protein intake before (pre, no supp) and during the study period in the different arms of the study (left) and respective protein intakes relative do body weight in the different groups (right)

Without significant differences in any other of the established nutritional parameters - first and foremost the overall energy intake, the only argument left would be that consuming even more protein on a daily basis may make the difference.

The lack of MPS data is a definitive, but by no means rare downside of the study

Figure 3: Fractional  protein synthesis (FSR) in the Moore study (young participants leg curls + leg extension medium intensity, red), in which a ceiling effect occurred and the Yang study (old participants rel. light workout, blue), where the latter was absent (originally published on February 11, 2013)

If we did yet follow this rational we would have to discard 90% of the muscular protein synthesis (MPS) data from previous studies we have become so fond of. After all, 90% of the pertinent and heavily cited data is based on trials using only 20-30g of whey after a workout. And if taking the protein before and after the workout would be a problem this would only compromise the body recompositioning effect, superior strength and size gains should yet still be visible. And taking more? Well, the 40g of whey (20g pre and 20g post) used in this do actually already approach the "ceiling level" after which the marginal utility of additional protein approaches zero - at least in young trainees and after a reasonably intense workout (read up on my previous comparison and elaborations on the data from young and old individuals from studies by Moore et al. and Yang et al.; cf. figure 3).

In the end, comparisons like the former involving MPS / FSR studies like the ones by Moor et el. with the study at hand would yet require the presence of respective data for the early mid- and end-phase of the Walter study. Since this data is not present and in view of the fact that we do actually have to be as skeptic about the prognostic value of MPS data measured in the immediate vicinity of a workout as we are about the heavily scrutinized "anabolic" response to a workout (cf. yesterday's post and the suggested reads), the overall significance of the study at hand remains questionable.

As questionable, by the way, as the researchers discussion of the "practical implications". After stating for the fifth time that supplementation clearly did nothing to augment the exercise induced increase in size and strength, the researchers suddenly don't dare to speak out the only logical consequence, i.e. "there is no use in protein supplementation" and walk the eggshells instead when they state:

Acutually you could also argue that using stevia as a sweetener may benefit older trainees and people on low volume routines. I've written about its potential effect on satellite cell recruitment over a year ago, already (learn more)

"Furthermore, athletes could benefit from a  low-volume regimen in conjunction with protein supplementation while recovering from injury and completing their prescribed rehabilitation program. This may potentially speed up the recovery  process and decrease the event of post-injury complications. As active adults age, they are encouraged to maintain or increase activity. However, less is known about how older adults may respond to whey protein and leucine supplementation in conjunction with chronic resistance exercise. A lower-volume of resistance exercise plus supplementation can potentially benefit untrained or detrained individuals, similar to moderate-volume without protein supplementation.

It is also possible that older adults and elderly patients may have a higher aptitude to respond to  the anabolic effects of protein supplementation and resistance exercise. Additionally, it is possible that PEG may be more beneficial for the absorption of the amino acids in those with  difficulties digesting nutrients, rather than healthy young men that already have a high basal MPS rate." (Walter. 2013; my emphases of the conditionals and speculations)

I don't know about you, but in my mind the best term to describe aftertaste that remains after reading this "conclusion" is  "Much Ado About Nothing" ;-)

---

Bottom line: Since the above "practical implications" are probably of little use to you, let me give you mine. Forget about everything but the fact that protein synthesis may not be the best indicator of long(er) term real world strength and size gains and stick to the tried and proven. Mix 20-30g of whey (plus 10-20g casein, optional) after your workout add 1-2 bananas / or some instant oats (amount depends on whether you are trying to build muscle or cut body fat), head home, have a full meal within the next hour or so (don't freak out if it takes 61 or even 90min until you get something to eat) and - last but not least - make sure that each of your whole food meals has at least 20-30g of EAA rich whole protein in it. That's it! Easy, right?

Hydrolysates have clear advantage over EAAs (learn more). Plus, w/ the isoleucine-dipeptides they may even outperform regular whey. The study to prove that in a realistic scenario has yet to be conducted, though.

What? Oh yeah, you want to know if you should buy PEG whey? Well, I guess the results of this study speak for themselves, don't they? So even if the claims I've found in a patent by someone who goes by the telling surname "Guru" and reports a 5x higher amino acid accumulation from micronized PEG enriched whey compared to its conventional counterpart were not just the result of non-peer-reviewed   "experiments" (Ramanathan. 2010), which have been conducted for only one purpose, i.e. making the patented product shine, you probably don't have to worry that you could be missing out on this one.

If you insist on trying something different, I would rather suggest you take a look at the readily available and as of now no longer that expensive protein hydrolysates. No, not for their fast absorption, but rather for their unique small peptide structure (suggested reads: Isoleucine-dipeptides and  GLUT-4, hydrolysate vs. EAA)

References:

• Aragon AA, Schoenfeld BJ. Nutrient timing revisited: is there a post-exercise anabolic window? J Int Soc Sports Nutr. 2013 Jan 29;10(1):5.
• Camic CL, Hendrix CR, Housh TJ, Zuniga JM, Mielke M, Johnson GO, Schmidt RJ, Housh DJ. The effects of polyethylene glycosylated creatine supplementation on muscular strength and power. J Strength Cond Res. 2010 Dec;24(12):3343-51.
• Coleman, E. Protein Requirements for Athletes. Clinical Nutrition INSIGHT: September 2013; 38(9):1–3.
• Herda TJ, Beck TW, Ryan ED, Smith AE, Walter AA, Hartman MJ, Stout JR, Cramer JT. Effects of creatine monohydrate and polyethylene glycosylated creatine supplementation on muscular strength, endurance, and power output. J Strength Cond Res. 2009 May;23(3):818-26.
• Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T, Tarnopolsky MA, Phillips SM. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr. 2009 Jan;89(1):161-8.
• Ramanathan, Guru. Dietary Ingredient With Enhanced Bioavailability. United States Patent Application. Pub. No. US2010/0209558A1. August, 2010.
• Volpi E, Sheffield-Moore M, Rasmussen BB, Wolfe RR. Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. 2001; JAMA 286:1206-1212.
• Walter AA, Herda TJ, Costa PB, Ryan ED, Stout JR, Cramer JT. Muscle Performance, Size, And Safety Responses After Eight Weeks Of Resistance Training And Protein Supplementation: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. J Strength Cond Res. 2013 Feb 25.
• Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, Tarnopolsky MA, Phillips SM. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr. 2013 Nov 28;108(10):1780-8.
• Yarasheski KE, Welle S, Nair KS. Muscle protein synthesis in younger and older
  586 men. JAMA. 2002; 287:317-318.

Science Round-Up Seconds: The Latest Data on Periworkout Nutrition - Protein, Carbs, HMB & More: Is it Possible You Have Done It All Wrong?

Honestly, even if they had available back in the day, I am not sure if Arnold would have preferred a virtually carb-free whey protein isolate over his mixture of two cups of milk, 1/2 cup of dry, nonfat milk solids (the old-school version of protein powders ;-), one egg and 1/2 cup of flavored ice cream.

I must confess that after going >30min over time on yesterday's installment of the SupppVersity Science Round-Up (click here to download and listen to the podcast if you missed the live show) I have run out of "Seconds". Since the SuppVersity buttery ... ah, I mean archive, is well stocked, this is yet not real problem. I just have to go down into the basement and pick some fresh ingredients for today's installment of the Seconds.

For my liking yesterday's show was a bit "healthitarian", meaning the topics centered mostly around health issues. Now, don't get me wrong. The show was outstanding and topics such as the "egg / chicken prostate cancer connection" or the "omega-6 for heart health study", of which you would actually have to say in retrospect that it bordered murder by negligence are obviously highly relevant, but I am a fan of diversity and well aware that there may be some topics many of you may not be that interested in. So what would be more obvious than switching things up completely and preparing an "erogogenitarian" menu today?

Now, tell me: What are everyone's favorite ergogenic? Right! Those are protein powders and amino acids ranging from BCAAs and EAAs, to creatine, glutamine and more exotic but still interesting stuff like HMB. Luckily, two groups of researchers from Iran, and the UK, Australia and Spain who have submitted their papers to the Journal of Exercise Physiology and the European Journal of Experimental Biology a couple of weeks ago must obviously feel the same. And since both articles made it into the February issues of the respective journals, they are still fresh and thus qualify as ingredients for today's installment of the SuppVersity Science Round Up. So, bon appetit, then ;-)

Are carbohydrates, not protein the most important part of "anabolic" peri-workout nutrtion

(Kazemzadeh. 2013) -- I guess this will be a shocker for some of you, but the headline is not entirely provocative only. In their most recent paper, Yazer Kazemzadeh and his colleagues from the Islamic Azad University and the Hamedan University of Medical Sciences in Teheran, Iran, are actually suggesting that the

"[...] ingestion of carbohydrate during resistance exercise may be [more potent in] inhibiting the catabolic hormone (cortisol), increasing the anabolic hormone (insulin) and creating a hormonal milieu for anabolism [than] whey protein." (Kazemzadeh. 2013)

They do yet also point out that "other anabolic markers need greater investigation" (Kazemzadeh. 2013) and we all know that these "other anabolic markers" that are related to the protein-exclusive increase in protein synthesis are what makes the largest contribution to your muscle gains in the long term... at least as you provide yourself with the fuel you need to train and this is where the hormonal effects of the ~750 ml 6% CHO beverage ten out of the 20 untrained young men (age:22.3±3 y, bodymass: 74±5 kg) in the study consumed during the sets of a 75%RM strength training regimen that consisted of

• 4 exercises for lower body, which were leg presses, leg curls, leg extensions and calf raises, and
• 4 exercises for upper body, namely lat pull downs, bench presses, barbell biceps curls and supine triceps extensions

All exercises were performed for three sets of 8-10 reps to failure. With one minute rest between sets and two minute rest between the individual exercises, the total duration of the workouts was <60min and the workouts were performed in the late afternoon 16:00-18:00h to minimize the influence of natural diurnal variations of cortisol, testosterone and GH.

Figure 1: Cortisol, insulin, growth hormone and total testosterone levels before and after the workout with carbohydrate (CARB) or protein (PRO) drinks being ingested between the sets (Kazemzadeh. 2013)

As you can see from the plots in figure 1 the carbohydrate beverage, which contained a 10ml/kg of a 6% mix (=6g of carbs per 10kg body weight) of fast and slow digesting carbs from glucose (fast) and Quaker oats (slow) did a pretty decent job in establishing an allegedly optimal anabolic hormonal milieu by cranking up the GH, insulin and total testosterone levels and blunting the cortisol response.

Insulin up, cortisol down - how important is that?

The total amount of carbohydrates the CARB group in the study at hand consumed during their workouts does actually come pretty close to the 130-150g of carbs even the most sedentary slob can easily stash away in the glycogen stores of muscle and liver on a daily basis. If you want to learn more about the reaoning behind these figures, I suggest you go back to my previous post on "Carbohydrate Shortage in Paleo Land" (read the whole article).

With insulin and cortisol being the only parameters that responded significantly more favorable to the glucose load, the picture that emerges is unquestionable more conducive to protein anabolism. Based on dozens of previous studies, I can however guarantee that the actual protein synthesis rates, which were not measured in the study at hand, were higher in the whey protein arm of the study (2g protein per kg body weight).

That being said, the addition of carbs could still have had a beneficial effect on exercise recovery and ultimately  - probably only after weeks of training and in an otherwise low carb scenario - yield significantly greater increases in strength and lean muscle tissue. With the total amount of carbs well within in the <150g range and the maintenance of the GH response, of which many people claim it would be blunted by the ingestion of nutrients, in particular carbs, during or after a workout probably even without compromising your body composition (assuming that you compensate for the additional kcal in the subsequent meals).

The latter hypothesis of mine does actually make an excellent segue into the next study, so just keep on reading, if you want more ;-)

Performance enhancing supplement Cyclone first and foremost "fat enhancing"

(Cooper. 2013) -- I promised you that in the last sentence of the previous "course" of this installment of the SuppVersity Science Round-Up Seconds and here it is: Certainly somewhat surprising scientific evidence that 56g of carbs alone won't, but an isocaloric serving of the commercially available carbs + protein + creatine Cyclone will make you you fat.

Figure 2: Nutrient content of supplement and placebo (Cooper. 2013)

Now that I have got your full attention, let's take a look at the context in which these counterintuitive effects occurred. You can see the macro and, in the case of the commercial protein + mineral + amino acid combo, also the micronutrient composition of the supplements in figure 2 on the right hand side. As already mentioned, the amount of calories in the products was identical. Any differences in strength and mass gains, as well as changes in the body composition that arose in the course of the 12-week training regimen would therefore have to be attributed to differences in the macro / micronutrient composition.

If you follow your gut feeling, I guess you'd say that using a supplement full of more or less proven ergogenics while you train four times a week, following an

• upper body = bench press; bent over row; shoulder press, bicep curls, and triceps extension,
• lower body = squat, stiff leg deadlift, lunges, and dynamic upright row

split (training days: Mo, Tue, Thurs, Fri), in the course of which you perform 4 sets per exercise with 6 to 12 repetition at 65 to 80% of your one-repetition max  (2 min rest between sets) should actually produce measurably superior results to the ingestion of the meager amount of 56g of maltodextrin, right?

Figure 3: Changes in strength and body composition after 12 weeks on a upper-body, lower body split trained 2x per week on Mo & Tue, as well as Thurs & Friday (Cooper. 2013)

Right! At least that's what I had expected, as well. The results I plotted for you in figure 3 do yet speak a very different language. Ok, the overall lean mass increase of the 13 healthy already resistant trained men (23.5 ± 2.7 yrs old, body mass (BM) = 80 ± 13 kg, height = 179 ± 6 cm, body fat % ~11-18%)  was higher in the group that used the "professional" multi-component supplement. If your goal is "lean mass", however, the allegedly fattening carbohydrate drink which produced a small, but significant increase in lean mass without any accompanying fat gains, does yet suddenly look unexpectedly attractive, doesn't it (see figure 3, right)?

As far as the strength gains go, things actually don't look much different. Due to the small sample size, none of the he intergroup differences reached statistical significance and the scientists way of resorting to effect sizes instead of group averages, based on which they argue that "the lack of significance due to CYC supplementation does not mean the supplement was ineffective" (Cooper. 2013) Tells me that they were similarly surprised as I am about the outcome of this 12-week trial.

"That's impossible, so where is the design flaw, here?"

I know the above is what you are thinking now, so let's check the usual and not so usual suspects.

• 

  There are three things you need to succeed in your efforts to achieve optimal health, a decent physique and a long and active live: A plan, the guts to stick to it and change / tweak it, whenever that's necessary and - often overlooked - the right tools to measure your progress. And I can tell you a scale "body fat or not" is not among those tools (read more about goal setting, planning and stock taking).

  Diet? The subjects were "instructed to maintain the recommended dietary habits throughout the duration of the study" when necessary, specific tweaks were applied to make sure that they would hit the 1.5-2g of protein, 5-6 g of carbs and a fat intake of ~25%-30% of their daily total caloric intake. So, if we simply assume that any deviations from that regimen were similar in the two groups this cannot explain the differences.
• Body fat scales? Not a problem, because the body composition was assessed by whole body densitometry using air displacement in a Bod Pod® - whether that may have skewed the results due creatine induced water retention is yet not 100% certain. On the other hand, lower fat gains would imply even greater lean mass gains and that's not realistic given the fact that the subject's strength levels did hardly improve.
• Missing training sessions or not training with adequate intensity? Since the scientists don't mention that the training sessions were supervised, this could have been an issue. On the other hand, why would that happen only in the CARB, but not in the Cyclone group?
• Misreporting by the scientists: Actually I have now checked three times, whether it may be possible that the researchers simply messed up with the data in the tables and put the results for the CARB group in the Cyclone row and vice versa. Based on the discussion at the end of the paper this does yet not appear to be the case.

So, if all these don't apply what's left then?

• 

  The "anabolic window" turns out to be more of a barn door, which is unlocked by the key of exercise and nutrition science (learn more)

  Following the manufacturers advice instead of common practice: This is actually one the scientists came up with in their discussion. In the majority of previous studies with similar supps, the products and placebo were consumed before and after the workout. In the study at hand, they were consumed as prescribed by the manufacturer after breakfast and after the workout. Not likely that this is the reason? Well, honestly, I would agree. 
• Having way too small group sizes: This is certainly an important fact to consider. If you don't test training vs. not training having 7 subjects in the active and 6 in the placebo arm is not very likely to produce significant differences. On the other hand, this does not explain that the non-significant differences are more or less opposed to what you may have expected.

Now, even if this was all I could come up with, I would still not  suggest you give up on protein powder, creatine and your preferred carb source and switch to maltodextrin, only, as your post workout nutrition of choice! God forbid! After all I do still have an ace up my sleeve, which is

• 

  Don't worry, the 10g+ of EAA with every meal (20-30g+ of quality protein) rule of thumb to get lean and stay lean does still apply (read more). A single study won't change that overnight. And while the current carb-scare is hilarious and misplaced, carbs alone, just like protein only, don't build magnificent, athletic and healthy physiques.

  Not starting on a level playing field: If you take a brief look at the baseline body composition data there is one thing that shoul leap out. The initial body fat levels! While the Cyclone group started out with a six-pack and 11% body fat, the guys in the placebo group were running around with 18% on average and - this is even more important - a standard deviation of 10%! In other words, it's not unlikely that two or even three of the guys in the CARB group actually lost body fat, over the 12-week training period. This would nullify any fat gains in the rest of the group and yield a net increase of less than 0.1% body fat for the CARB group. Some of the guys in the cyclone group, however were in that peculiar <10% range (the standard deviation here was +/- 5.4%), where it's really hard to shed additional body fat and actually pretty easy to bounce back into your bodies comfort zone.

If that does not soothe your concerns that you could have done all wrong over the years, just take my word for it: This study is one of those highly educative outliers which are mostly SuppVersity newsworthy, because they offer a chance to practice your critical thinking skills and remind you of the value of single scientific paper.

References:

• Cooper R, Naclerio F, Larumbe-Zabala E, Chassin L, Allgrove J, Jimenez A. Effects of a Carbohydrate-Protein-Creatine Supplement on Strength Performance and Body Composition in Recreationally Trained Young Men. JEPonline 2013;16(1):72-85.  
• Kazemzadeh Y, Zafari A, Bananaeifar A, Moghadam RH, Abasrashid N, Shafabakhsh F. Comparison of whey protein and carbohydrate consumption on hormonal response after resistance exercise. European Journal of Experimental Biology. 2013; 3(1):10-15 .

Science Round-Up Seconds: Cytokine Modulating Power Cakes, Endurance & Resistance for Maximal Cardiovascular Benefit, Gluten Degrading Bacteria and Cancer Fighting Green Tea + Levitra Combo. Plus: Sirt-3 & Protein Blends

Not sure if the "Power Cakes" in the Kerasioti study looked like these, but it would sure have been appropriate, after all the poor study participants had to cycle for 3h (in total) - makes you wonder if they are WADA approved, doesn't it?

Today's installment of the SuppVersity Science Round-Up Seconds has some delicious stuff for you in stock. We will start out with an interleukin 6 & 10 modulating CRP reducing cake from Greece as an appetizer, or pre-workout, whatever you like better. When we have finished that one, the table or gym talk will center around debunking the myth that only aerobic training was good for your cardiovascular system. When even the last i**** has gotten that, it's about time to devour the delicious anti-carcinogenic and gluten destroying bacteria stew with green tea and Levitra(R), I've been cooking for ya ;-)

Before you go for the cake, however, I want to apologize that I was somewhat out of it on yesterday's show (click here to listen to the podcast). As a compensation today's Seconds have - as you can see - become pretty "nutritious" at least on a quantitative level ;-)

Looking for the perfect peri-workout meal? What about some cake?

(Kerasioti. 2013) -- It may not really sound like "high performance fuel", but in fact the protein cake a group of Greek scientists fed to their nine physically active and pretty well-conditioned male subjects (age, 28 ± 2 yr; height, 184 ± 3 cm; body fat, 11 ± 2%; body mass index, 23 ± 1 kg/m²) turned out to be much more than just performance fuel after the 2 h of continuous cycling on cycle ergometer at an intensity corresponding to 60-65% of the subjects established VO2max.

Figure 1: Interleukin 6, interleukin 10 and c-reactive protein (CRP) levels before and after the first 2h exercise bout with experimental (EXP) and placebo (PLA) cake; data expressed relative to baseline (Kerasioti. 2013).

As the data in figure 1 goes to show you, the cakes which contained a combination of 0.9g/kg carbohyrates and 0.26g/kg protein did in fact have surprisingly more beneficial effects on the rise and fall of the pro- and anti-inflammatory cytokines IL-6 and IL-10 (IL = interleukin) during the two counterbalanced trials, than the placebo, an identical cake with a different macro-nutrient ratio of 1.1g carbs and 0.1g protein per kg body weight.

Training twice a day? No problem with the power cake ;-)
 
Only four hours later the scientists shooed their subjects onto the bike again for another hour of medium intensity exercise and a 95% VO2max time-trial sprint at the end, "to determine if the cake administration affects performance" (Kerasioti. 2013). Sounds logical, right? What's confusing, though is that Kerasioti et al. don't even mention the performance effects they did or didn't observe in the second bout in the discussion of their results - so I suspect that (a) there were no differences or (b) Kerasioti et al. regard the cytokine response to the second trial as a "performance" marker and stick to that as their "effect on performance" (I don't know about you, bun in my humble opinion the latter would be an even greater flaw than leaving the non-significant information out).

Figure 2: IL-6, IL-10 and CRP response over the whole study period; expressed relative to baseline (Kerasioti. 2013)

If you add the cytokine expression in the steady state 2h trial from figure 1 to the data that was recorded after the completion of the 1h steady state + time trial cycling session four hours later and the 48h post levels of the inflammatory markers, the resulting graph exposes a very neat symmetry with an almost identical rise and fall in the expression of the short-lived cytokines and an eye-catching difference in the intermediate inflammatory response evidenced by the increase in CRP in the recovery phase of the placebo trial (just as a reminder: C-reactive protein aka CRP is the same stuff you will also see chronically elevated in diabesity and all sorts of inflammatory diseases).

A propos protein: We also talked about the benefits of protein blends with fast and slow proteins.Here is the SuppVersity article about the human study on the casein + whey combination I mentioned.

Bottom line: Compared to carbohydrates alone the combination of carbs + whey does not only offer a muscle building, but also an inflammatory edge, especially endurance athletes and anyone with a high training density will benefit from -- just like the 3g glutamine (1.5g pre, 1.5g post workout), Carl and I talked about during yesterday's installment of the SuppVersity Science Round-Up, by the way, with the only difference being that the effects of whey protein are probably mediated by it's glutathione (the master oxidant) repleting glutamylcysteine groups (Bounous. 1991), beta-lactoglobulin, lactoferrin and other anti-inflammatory compounds in whey proteins (Peng. 2009).

Cardio and weights: Your cardiovascular system loves both

(Spence. 2013) -- There is this longstanding and die hard myth that only aerobic training would be good for the heart. With the publication of a recent paper by a group of scientists from the University of Western Australia and the Liverpool John Moores University, you do now finally have something to print out, and tack it to every idiots forehead who still insists that only half-marathon running, but not resistance training could save you from cardiovascular infarction ;-)

For their 6-months experiment, the scientists recruited 23 27±5 year-old healthy male subjects who were then randomized to either either endurance (ET, n=10) or resistance training (RT, n=13) in order to evaluate the long-term effects of these training modalities on brachial, femoral and carotid artery diameter and wall thickness (IMT), as well as femoral and brachial flow-mediated (FMD) and glyceryl trinitrate (GTN) mediated dilation. Ha? Well, let's say they wanted to know how the different exercise protocols, the scientists desribe as follows,

For those of you who want to add something to their regimen that boosts the longevity sirtuin, sirt-3 Carl and I have talked about during yesterday's show, here is the HMB + Leucine study I mentioned.

"[...] the ET intervention consisted of a progressivelyoverloaded programme of walking, jogging and running, inclusive of specified training phases over the 24week period. The focus of the periodized RT programme was Olympic weightlifting with incorporated supplemental exercises (e.g. dead-lift, back squat, front squat, bench press and overhead press) to develop overall strength and technique. Relative intensities for the ET and RT interventions were monitored throughout the sessions, individualized and progressed to ensure that subjects were exercising at prescribed percentages of VO2peak and 1RM, respectively" (Spence. 2013)

would effects the structure and performance of the hearts of their subjects, who completed three 1h training sessions of the respective exercise type per week.

As even resistance training enthusiasts should have expected, the RT group did not see significant improvements in O2Peak (ET yielded +5% increase in this indicator of cardiovascular fitness). On the other hand, the endurance training had no effect on upper body strength, which increased by statistically highly significant +21% in the resistance training group. Both these improvements are yet not really newsworthy and the whole study would not have made it to the SuppVersity Science Round-Up, respectively the Seconds, if it had not been for the high-resolution ultrasound images of the heart, which revealed:

Figure 3: Changes in body composition
relative to pre values (Spence. 2013)

• Resistance training affects the brachial artery, increases brachial artery resting (+8%, P<0.05), peak FMD  and GTN-mediated (P<0.01) diameters
• Endurance training affects the femoral artery, increases resting (+3%, P<0.05), peak FMD femoral artery diameters, and improvements in the femoral FMD-to-GTN% ratio 
• Both forms of training had similar beneficial effects the carotid artery wall thickness

In summary: Despite the fact that the two training forms will have differential effects on your overall conditioning and strength, they both increase lean mass (see figure 3) and decrease the artery wall thickness of the artery which supplies your brain with oxygen (the carotid artery). And with their unique effects on the brachial artery in the upper arm (RT) and the femoral artery in the tigh (ET), they make a perfect team to protect you from cardiovascular disease and stroke.

"I'd like a Levitra(R) enhanced green tea with probiotics..." What?

The last two items from yesterday's list that did not make it into the show are actually not brand new studies. One is a comment from the Journal of Clinical Investigation and the other one is a study that has been around since 2011, already. I picked them up in the course of the week and found them news-worthy, although it is not really sure, a combination of green tea, viagra and rothia bacteria is going to prevent cancer and solve your problems with gluten or whether one or the other or a combination of all is going to kill you ;-) Anyways, here are the details:

• 

  Rothia has hitherto rather been known as a bad guy, which can, if it gets into the wrong places cause endocarditis (heart), meningitis (brain), peritonitis (an inflammation of the peritoneum, the thin tissue that lines the inner wall of the abdomen and covers most of the abdominal organs) and other infections (Photo by Nathan Reading)

  Rothia bacteria in the upper gastrointestinal tract degrade gluten (Zamakharchi. 2011) -- Back in 2011 already a group of researchers from the Boston University Henry M. Goldman School of Dental Medicine published a paper in which they describe the astonishing ability of a common gram positive bacteria called Rothia, which is also present in the oral cavity could degrade 50% of the glyiadin peptides the scientists had added to the petri dish before the they were incubated for 30min.
  
  In view of the fact that the immunogenic parts of the peptides, that cannot be cleaved by our natural digestive enzymes, it does appear like a too happy coincidence that our microbial subtenants from the oral and upper gastrointestinal tract possess the enzymatic machinery to degrade the harmful gluten peptides for us - don't you think so?
  
  One thing is for sure, the presence of a bacteria that deals with the stuff, we cannot deal with on our own in our oral cavity certainly does support what I said in the context of the "bulimia apparatus" - the digestive process with all it's downstream effects on your metabolism starts in the mouth:
  

  "During mastication (chewing) foods are mixed with whole saliva helping to accelerate the break-down by digestive enzymes during the residency time in the oral cavity. Oral microorganisms in the swallowed food bolus may or may not survive and/or continue to exert proteolytic activities during or after gastric passage. Our in vitro data with R. aeria show that its enzymes are not abolished at acidic pH values, and are optimally active under more basic pH conditions. In vivo, this could mean that during gastric passage the enzymes will neither be active nor destroyed, and that enzymatic reactivation would occur upon transfer to the duodenum." (Zamakharchi. 2011)

  Aside from the fact that they could make it into the large intestine, previous studies have already confirmed that R. mucilaginosa can even gain a foothold there (Ou. 2009), so that probiotic supplementation with Rothia mucilaginosa could in fact turn out to be a viable treatment / prevention strategy for celiac disease and other gluten related health problems.

• EGCG + PDE-5 = cancer killer (Yang. 2013) -- Cancer is like the Learnean Hydra from ancient Greek mythology (see image on the right). Whenever you cut off one of its heads it'll grow two new ones... well, i must admit the analogy isn't perfect, but it's still useful to understand why the PDE-5 inhibitor vardenafil worked wonders when it was co-administered with the green tea catechin EGCG.
  
  

  

  You really have to wonder why these ancient heroes who had the cunning to kill the Hydra did not even wear a pair of speedos, when they entered into it's watery realms ;-)

  Just like the many Greek warriors who died in their battle with the Hydra before it was finally slain by Heracles, EGCG is well capable of doing major harm to the cancer cells. Just like the snake-like beast the cancer cells have yet found a way to resist the onslaught. Obviously not by growing new heads, though, but rather by over-expressing PDE-5 in order to repress the EGCG increased cGMP activity that would otherwise initiate apoptosis, i.e. the natural self-destruction mechanism of a cell.
  
  So what could be more straight forward than using a PDE-5 inhibitor just like Iolaus, Heracles cousin, used a firebrand to scorch the neck stumps of the Hydra after each decapitation. Clever and effective, don't you think so?
  
  Well, there still is one downside: Just like the story about the Hydra is nothing but a myth, the studies Yang and Wang reference in their commentary in the latest edition of the Journal of Clinical Investigation are only in-vitro studies and whether drinking green tea and popping one of Bayer's Levitra(R) pills after the other, is going to prevent, let alone kill existing cancer, will still have to be elucidated.

That's if for today! And since I am a bit in a hurry, I will leave it up to you to check out the latest really short news on the SuppVersity Facebook wall. Contrary to the green tea + Levitra treated cancer cells, the facebook news are guaranteed to proliferate even before the official Saturday installment of On Short Notice is going to be posted in ~24h (in fact, it will first have to researched and written ;-)

References:

• Bounous G, Gold P. The biological activity of undenatured dietary whey proteins: role of glutathione. Clin Invest Med. 1991 Aug;14(4):296-309.
• Kerasioti E, Stagos D, Jamurtas A, Kiskini A, Koutedakis Y, Goutzourelas N, Pournaras S, Tsatsakis AM, Kouretas D. Anti-inflammatory effects of a special carbohydrate-whey protein cake after exhaustive cycling in humans. Food Chem Toxicol. 2013 Jan 26.  [epub ahead of print] 
• Ou G, Hedberg M, Horstedt P, Baranov V, Forsberg G, et al. Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease. Am J Gastroenterol. 2009;104:3058–3067.
• Peng X, Xiong YL, Kong B. Antioxidant activity of peptide fractions from whey protein hydrolysates as measured by electron spin resonance. Food Chemistry. 2009; 113(1):196–201. 
• Spence AL, Carter HH, Naylor LH, Green D. A prospective randomised longitudinal study involving 6-months of endurance or resistance exercise on conduit artery adaptation in humans. J Physiol. 2013 Jan 28. [Epub ahead of print] 
• Yang CS, Wang H. Cancer therapy combination: green tea and a phosphodiesterase 5 inhibitor? J Clin Invest. 2013 Jan 25:1-3. [Epub ahead of print]
• Zamakhchari M, Wei G, Dewhirst F, Lee J, Schuppan D, Oppenheim FG, Helmerhorst EJ. Identification of Rothia bacteria as gluten-degrading natural colonizers of the upper gastro-intestinal tract. PLoS One. 2011;6(9):e24455.