Tuesday, March 5, 2013

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. 2012).
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, 2012)
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)

  • 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 2012; 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. 2012 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.


  1. After a workout, how many grams of protein hydrolysate would you ingest? Also, how many grams of isolated l-isoleucine supplementation would you ingest? Would you also ingest casein with the protein hydrolysate and isolated l-isoleucine supplementation? If yes, how much casein?
    Thanks for any suggestions!

    1. I suggest you initially read JPs last post, calm down take a deep breath and then maybe try 10-15g of WPH; personally, I would wait for further studies on the isoleucine before buying a batch and whether the casein has to be taken spaced out from the WPH would warrant further studies. You could probably argue that it may slow down the absorption (which would not be a problem) and thus increase the chances of the dipeptide bonds being digested before they are absorbed as a whole (which could be a problem)

    2. Dr. Andro,

      I really appreciate your reply! I already purchased a batch of the isolated l-isoleucine supplementation. I was going to take 3 grams with each of my meals containing carbs. Will isolated l-isoleucine supplementation increase the release of insulin? Also, what are your thoughts on adding 3 grams of the isolated l-isoleucine supplementation to each of my meals containing carbs?

      I also purchased protein hydrolysate for after working out. If I do not eat carbs post workout and only use protein hydrolysate, will my liver just convert the protein hydrolysate to blood glucose and not use it to rebuild muscle?

      Thank you so much for your time!

  2. I'm glad you are pointing out that a study "not finding a statistically significant difference" is not the same thing as a study finding that "there is no difference." The latter actually can't possibly be shown by any study, and is pretty preposterous on philosophical grounds anyway.

    It's standard practice to report effect sizes with their std errors. I don't understand why it's not standard practice to report e.g. the range of true effect size around 0 that a study reporting a null result did not have the power to discriminate. Ugg, its hard to say that clearly, but you probly get my meaning. The sensitivity/power should ALWAYS be reported when discussing any null finding.

    1. I guess I get what you are hinting at + we should not forget that those underfunded studies oftentimes simply lack participants to achieve "statistical significance" in terms of many of the results

  3. Hey what a surprise, ANOTHER study that shows protein supplementation combined with exercise doesn't increase size or strength gains. Guess this further supports evidence previously shown by Bucci 1992, Fogelholm 1993, Fry 1993, Lambert 1993, Cambell 2007, Koopman 2009, Verdijk 2009, Verhoeven 2009, Hulmi 2010, Leenders 2011, Moore 2012, and Weinheimer 2012

  4. I think most are so stressed out about getting the details that they forget to nail what is really important, their overall training, diet, and rest.

    Forget the nuance things and focus on the big picture. I think the bottom line of Adel's post sums that up clearly.

    1. good comment, so good in fact that I had to reference it in my response to the first question by Anonymous (1) ;-)

  5. I really appreciate your reply! I already purchased a batch of the isolated l-isoleucine supplementation. I was going to take 3 grams with each of my meals containing carbs. Will isolated l-isoleucine supplementation increase the release of insulin? Also, what are your thoughts on adding 3 grams of the isolated l-isoleucine supplementation to each of my meals containing carbs?

    I also purchased protein hydrolysate for after working out. If I do not eat carbs post workout and only use protein hydrolysate, will my liver just convert the protein hydrolysate to blood glucose and not use it to rebuild muscle?

    Thank you so much for your time!

    1. I would be inclined to hear about the results of that experiment. It should actually NOT increase insulin but help with non-insulin dependent glucose uptake, BUT what you must not forget is that this only works, when your glycogen stores are still empty. Whether this makes a difference on regular meals, when you are not dieting is not sure - post workout it will (at least if you trained long / hard enough to deplete muscle glycogen)

      on the second question: I will not "only" do so, but it will do so. Why don't you have one of those yellow prepackaged carb meals they call Banana with it? Trust me, it's not going to make you fat an is above all a source of minerals your body can use

  6. Dr. Andro,
    I wake and eat 25 grams of whey, 20 grams of casein, 30 grams of carbs, and 10 grams of fat. Two to three hours later, I do 20 minutes of HITT with 30 sec active and 60-90 sec rest then I lift weights for 30 to 40 minutes with 60 sec between sets. After my workout, I wait 30 to 60 minutes to ingest either 25 grams of protein hydrolysate or whey protein with no carbs to burn more body fat after workout. Then 30 to 60 minutes later, I eat a meal with 40 grams of protein from meat, 45 grams of carbs, and 15 grams of fat. I just started adding 3 to 5 grams of isolated l-isoleucine supplementation to my meal to help with glucose uptake to my muscles. Then 3 to 4 hours later, I eat another meal 40 grams of protein from meat, 45 grams of carbs, and 15 grams of fat. I just started adding 3 to 5 grams of isolated l-isoleucine supplementation to my meal to help with glucose uptake to my muscles. Then before bed, I eat 80 grams of casein and 20 grams of fat. I just started adding 3 to 5 grams of isolated l-isoleucine supplementation to my last meal to help with protein being converted to glucose then converted glucose to uptake to my muscles.

    Would you suggest ingest the protein immediately after working out or wait 30 to 60 minutes to help burn more body fat?

    Any advice on my approach to my workout, eating, and supplementation?

    Or is too much protein being converted to glucose?

    Thanks again for your time!

    1. wait, you are eating before you work out and seriously worry about having a protein shake immediately after the workout because it could blunt fat burn? That does not make sense at all. Also, whey won't stop you from burning fat (http://ajpendo.physiology.org/content/283/3/E565.short) and you are missing out on the <40min after a workout where you can actually get all the glucose into the cell without even needing insulin to ramp up GLUT-4 expression

      2ndly you say to take the isoleucine to help protein being converted to glucose!? I thought I had said and written often enough that there is hardly anything worse than "living off" protein. Whenever your body has to get a lions share of his energy requirements from protein he will think it's starvation time and react appropriately.

      You carbophobia is totally inappropriate, I mean look at Adelfo - the main reason he is now looking better than ever is that he finally threw it overboard => http://suppversity.blogspot.de/2013/03/adelfo-cerame-11-days-out-looking-back.html

      You use the isoleucine to shuttle glucose into the muscle, the glucose you EAT in form of carbs, not the one you "create via the emergency program" from protein.

      I'd also suggest you read up on the two "carb past 6pm will make you ... lean" posts (http://suppversity.blogspot.de/2012/08/carbs-past-6pm-reloaded-circadian.html, link to the first post inside), there is no reason not to eat any carbs before bed. How's your sleep? You're sweating or peeing like crazy and never really feel you slumble deeply?

  7. All animals with small stomachs for their size search for food or hunt when they get hungry. Then, they eat. Why do they keep spending money in research when common sense gives the answer?

    The cycle is:

    (Hunger -> Exercise -> Food -> Satiety/Rest -> Hunger and so on).

    Animals with larger stomachs that process great quantities of low quality food have to east and digest through the day.