Post-Workout Chlorogenic Acid / Caffeine Supplementation - For Good or For Worse? Plus: Glycogen Synthesis & Why A Post-Workout May Be a Better Idea Than You'd Think

"Done,... where is my post-workout coffee?" - Post workout caffeine / chlorogenic acid - good or bad idea?

I know it's kind of late to post an article like this months after the ISSN conference, but I recently hit on an overview of the poster presentations and noticed that I did actually miss a couple of interesting studies. Don't worry, I won't be addressing a couple of them in the weeks to come in some detail.

Not all are really news-worthy, but aside from today's item on caffeine and chlorogenic acid, there were also posters on nutrient timing, different forms of protein, commercially available supplements and other stuff that's all classic "SuppVersity fodder"?

Chlorogenic acid? Isn't that Ozzy's green coffee bean stuff? You are correct, but could actually read about it here at the SuppVersityway before it was on Dr. Oz. Plus, I still believe that there is something wrong with the corresponding study and do still have to meet someone who has successfully lost weight by just adding some GCB to the diet, which is effectively what Ozzy and the study promised | learn more

Caffeine and chlorogenic acid? Right, that sounds like green coffee bean extract, but in the case of Jason R Beam et al.'s study, we are dealing with an artificial stack of

• 5mg/kg body weight of caffeine plus 75 g of dextrose (CAF), 
• 5 mg/kg body weight of chlorogenic acid plus 75 g of dextrose (CGA), or 
• 5 mg/body weight of dextrose plus 75 g dextrose (PLA)

the 10 moderately to highly trained study participants consumed after 30-minutes of  high intensity cycling at 60% of peak power output (~90% HR max).

Figure 1:

As you can see in Figure 1, we do see quite extra-ordinary effects of the administration of both caffeine and chlorogenic acid on post-workout glucose metabolism. The changes in the area under the cure (2h AUC) do yet overestimate the real-world difference between the glucose curves (not shown), which have a slightly higher spike immediately after the ingestion.

"Ok, no caffeine after a workout - right!?"

In the case of caffeine that was to be expected, it has after all been shown to decrease the insulin-induced glucose uptake (Graham. 2001). The fact that the glycemic response was - within the statistically probable margins - still identical, is simply the result that the stimulation of glucose uptake and hepatic, as well as muscular glucose storage is not really necessary as long at the glycogen stores are low. Accordingly, a 2004 study by Battram et al. was unable to show any effect of caffeine ingestion on proglycogen and macroglycogen resynthesis after a workout (Battram. 2004).

Figure 2: Skeletal muscle glycogen content (mmol/kg dw) immediately after exercise 0. 1, 4h after cycling to volitional fatigue (70% Vo2Peak) w/ or w/out coingestion of 8mg/kg BW (+ 1g/kg glucose) after the workout - left; corresponding levels of pCAMK and p-Akt (arbitrary units) 1h and 4h after the workout, right (Pederson. 2009).

As you can see in Figure 2 the net amount of glucose that ends up in the musculature after exhaustive (if you don't deplete the stores this effect won't be there) exercise was in fact favorably affected by the congestion of 8mg/kg caffeine and 1g/kg glucose in with caffeine in the 7 endurance-trained cyclists and triathletes in a study by Pedersen et al. from 2009. The exact underlying mechanisms of this beneficial effects, as well as dose response relationships do yet still have to be determined, but Pederson et al. speculate that it may a result of the increased activation of p-AKT:

You think you've heard about p-Akt before, but are not sure where? Well, chances are it was here at the SuppVersity, yet probably in a different context, i.e. as part of the Intermittent Thoughts on Building Muscle | read more

"The increase [in p-AKT] tended to be higher after the ingestion of caffeine with CHO after both 1 and4hof recovery, but failed to reach statistical significance. Akt seems to regulate glucose uptake by phosphorylating and inhibiting the Rab-GTPase-activating protein AS160. Thus it is tempting to speculate on the role of Akt in glucose transport given that the Akt substrate AS160 has been identified as an important regulator of GLUT4 traffic.

We have recently shown that AS160 is phosphorylated in human skeletal muscle after endurance exercise with concomitant phosphorylation of Akt (7), providing correlative evidence to suggest AS160 is an exercise-responsive protein with a role in glucose uptake." (Pederson. 2009)

If we discard potential negative effects of the caffeine-induced CNS activation on post-exercise nervous system recovery, and take into account that the elevated glucose + insulin AUC Beam observed in the experiments for his dissertation and ISSN conference poster are negligible, the preliminary bottom line for post-workout caffeine intake would be: "If glycogen resynthesis is what you are looking for, do it!"

"What about the effects of chlorogenic acid. Shouldn't the exact opposite happen?"

Now that we've searched for explanations of the effects of caffeine on post-workout glycemia we are still left with the astonishing increase in the two-hour glucose area under the curve, i.e. total glycemia, Beam observed in the glucose + chlorogenic arm of his study.

Figure 3: Insulin (AUC) for each subject during the placebo, caffeine, and chlorogenic acid trials (Beam. 2013)

If you take a closer look at the data to the right, you won't get a mechanistic explanation of the underyling reasons, but you will at least get an idea of what statistical significance means and why we are talking about it in almost every study analysis, even if it does not equate physiological significance.

In this particular case the 2 outliers, subject 1 and subject 6 do not simply "ruin" the statistical significance, they are actually the (almost) only reason that insulin response is not virtually identical to the placebo trial.

As far as potential negative consequences of the post-workout consumption of cholorgenic acid goes, you do thus not have to be worried, whether it is actually a good idea to use a supplement that's meant to increase the activity of AMPK in a phase, when the latter is already maximized, is however questionable. In the best case, the additional benefits will be minimal, in the worst case it  CGA will ruin the glucose repartitioning effects of the workout by increasing AMPK and thus glucose uptake in the fat cells (Alonso-Castro. 2008).

If you actually have problems with insulin resistance / glucose uptake (which is not the case for 90%+ of the people who buy corresponding supps), I suggest you check out this list of useful anti-diabetes agents.

Bottom line: I would assume that you will not have expected that, but based on the results of the study at hand and the review of previous literature the effects of caffeine and chlorogenic acid on post-workout glycemia are most likely negligible.

If you still insist on supplementing with one or the other immediately after a workout, though, there would be a rationale to use caffeine. The use of chlorogenic acid, green coffee bean extracts or any other highly advertised and for physical culturist 100% useless "nutrient repartitioning agents", would be at least non-sensical, in view of the potential negative effect on the true nutrient repartitioning effects, even potentially downright counterproductive.

References:

• Alonso-Castro, A. J., Miranda-Torres, A. C., González-Chávez, M. M., & Salazar-Olivo, L. A. (2008). Cecropia obtusifolia Bertol and its active compound, chlorogenic acid, stimulate 2-NBD glucose uptake in both insulin-sensitive and insulin-resistant 3T3 adipocytes. Journal of ethnopharmacology, 120(3), 458-464. 
• Beam, J. (2013). The effect of post-exercise caffeine and chlorogenic acid supplementation on blood glucose disposal and insulin sensitivity.
• Battram, D. S., Shearer, J., Robinson, D., & Graham, T. E. (2004). Caffeine ingestion does not impede the resynthesis of proglycogen and macroglycogen after prolonged exercise and carbohydrate supplementation in humans. Journal of Applied Physiology, 96(3), 943-950.
• Pedersen, D. J., Lessard, S. J., Coffey, V. G., Churchley, E. G., Wootton, A. M., Ng, T., ... & Hawley, J. A. (2008). High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine. Journal of Applied Physiology, 105(1), 7-13.

Never(!) Sip Your Whey, If You Want to Kickstart Protein Synthesis. Over 60% Reduction in 1-5h Post Workout Protein Synthesis if You "Pulse" Your PWO Shake.

Image 1: The whey isolate used in the study - I guess as a scientists you just take whatever you get sponsored ;-) All jokes aside, any other whey isolate will do just as fine.

We all know, leucine is the magic amino acid that tells your muscles to ramp up protein synthesis. We also know that whey protein, which is made from the globular proteins the manufacturers isolate from the milky by-product of cheese production, is "the whey to go" if you do not want to ingest your leucine as a free-form amino acid or as part of a BCAA or EAA free-form amino acid blend. After all, whey is not only particularly rich in leucine (~14-15%), but also highly digestible. Well, at least this is what you are told to believe by the supplement industry... but how do we know that it is really the "speed" that makes a difference? After all, in all existing studies which compare whey to "slow digesting" proteins the absorption speed is not the only independent variable. Moreover, a recent study by Reitelseder et al. on the effects of post-exercise supplementation with 0.2g/kg body weight whey vs. casein could not find significant differences in the post-exercise protein synthetic response - and that despite the fact that whey is faster digested and does contain ~5% more leucine (Reitelseder. 2011).

A cleverly designed experiment that was (how else could it be ;-) conducted by Stuart Phillips' Exercise Metabolism Research Group at the Department of Kinesiology and Neurology at McMasters University in Hamilton, Canada, could hold the answer to the question, whether the speed with which the amino acids from your post-workout protein shake hit your body actually matters (West. 2011). Instead of using caserin or another slow-digesting protein source as control, Daniel W.D. West and his colleagues effectively eliminated all other possibly interfering variables, such as the exact amino acid composition, the carbohydrate and fat or vitamin and mineral content of the control beverage, by simply comparing the protein synthetic response to strength training (8 sets of 8-10 reps at 10RM on the bilateral leg extension machine) in 8 healthy men after bolus or pulsed (10x2.5g every 20min) ingestion of 25g of whey protein.

Figure 1: Mean serum blood concentration  (nmol/ml) of essential amino acids after bolus (red) or pulsed (blue) ingestion of 25g whey protein; * significantly (p<0.05) greater than pulse, # significantly (p<0.05) greater than bolus (data adapted from West. 2011)

While, obviously, the areas under the curve were identical for both the total essential amino acid (EAA), as well as the leucine serum levels in both groups, only the bolus ingestion of 25g of whey protein caused a significant spike (+122% over baseline, +45% over pulse) of total EAA and leucine levels about 60min post ingestion (cf. figure 1, the graph for leucine looks virtually identical). Conversely, there was a transient increase (+66% over baseline, +33% over bolus ingestion) in both serum EAA and leucine content 180min at the end of the pulsed ingestion.

Figure 2: Relative increases in mTOR phosphorylation (left) and myofibrillar fractional muscle protein synthesis rates (right) over fasted baseline after bolus or pulsed ingestion of 25g of whey protein (data adapted from West. 2011)

As the relative increases in myofibrillar fractional muscle protein synthesis rates (FSR over fasted baseline) in figure 2 (right) go to show, the spike and not the total amount of EAA/leucine over a given time period (as measured by the area under the curve) is what kicks the muscle protein synthetic machinery into gear. Even with the lower serum EAA levels at the ~3h (=180min) mark, both protein synthesis as well as mTOR-phosphorylation (figure 2, left) were still higher in the group who consumed their 25g of whey in a single bolus. So, even if your whey tastes so good that you feel like it would be a sheer waste to gulp it down all at once, you better ignore those moral objections if you want to make the most of your post-workout nutrition ;-)

Exercise the one and only "nutrient partitioner"

These results are obviously important, in that they substantiate the current practice of "getting your fast digested protein in right after exercise", what I personally did yet find even more revealing is the following remark that can be found in the extensive discussion of the results:

An intriguing and important divergence between our findings and reports in which aminoacidemia resulted in only a transient rise in MPS with infusion of amino acids or with amino acid consumption is that our results were postexercise. It appears that a unique aspect of resistance exercise is to selectively sustain elevated synthetic rates of myofibrillar proteins after protein consumption. In contrast to the effects of protein consumption alone at rest, the current results and our earlier work showed that the highest rates of MPS were observed at 3–5 h postexercise when aminoacidemia had subsided.

So, what am I preaching in each and every post? There is only one "nutrient repartitioner" which works: EXERCISE. Now, get your ass to the gym and save the money the supp companies want you to spent on dubious supplements which - even if they worked - don't give you any advantage over what you can accomplish with exercise alone for a container full of tasty whey protein isolate (which ought to be ingested in bolus portions of 25g, of course ;-).

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)

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 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.

Post-Workout Glycogen Repletion - The Role of Protein, Leucine, Phenylalanine and Insulin. Plus: Protein & Carbs How Much do You Actually Need After a Workout?

Pascal Behrenbruch, German decathlete and one of those athletes whose performance during a meet will certainly depend on "optimal" glycogen repletion between the different sports.

Within the past couple of weeks I have often talked (on the Science Round-Up) and written (here at the SuppVersity) about the importance of glycogen repletion to maintain optimal exercise performance and stave off the metabolic downregulation that's a characteristic of the nasty combination of overtraining and undereating. The recent post on the anti-plateau effect of sucrose should actually have made it quite clear: Even when you are "just" dieting, you should make it a priority to satisfy your body's desire to have an adequate reserve of glucose in the muscle and more importantly the liver.

But what does that mean? Do you really have to guzzle gallons of sugar water (aka weight gainers) after a workout? Certainly not.

The notion that you need to flood your skeletal muscle tissue with sugar right after the workout and that even showering before you do so would compromise your training success and put you at danger of losing muscle is simply hilarious.

That being said, the results of the latest study from the Institute of Sport at the Carnegie Faculty of the Leeds Metropolitan University in the UK is probably of greater importance to professional athletes like triathletes, decathletes, cyclists, etc. After all, they are the ones for whom immediate glycogen repletion can make the difference between victory and defeat. On the other hand, this does not mean that there wasn't something to be learned from the data Detko et al. gathered by the means of 13C magnetic resonance spectroscopy - after all, they took a different approach to the problem and did - instead of modifying the carbohydrate source - try to elucidate how the addition of protein would influence the restoration of muscle and liver glycogen in the immediate vicinity of a workout (Detko. 2013).

Is there even such a thing as an "optimal PWO glycogen replenisher"?

The quest for the optimal PWO carbohydrate source has long been a quest for the highest GI carbohydrate. Until the low carb craze hit home, the mainstay paradigm of figure, bodybuilding and performance athletes was "the higher the GI, the faster the uptake, the greater the gylcogen (re-)synthesis, the better the results". From a scientific perspective, it has has yet long been refuted that the GI and thus the insulin response a given carbohydrate would elicit was the only determinant of its practical value as a muscle (let alone liver) glycogen replenisher.

Did you know that there is a catalytic dose of ~40g of fructose per day (=6 normal size bananas) that will improve your glucose metabolism? (learn more)

One of my favorite and in fact comparably recent studies that demonstrates the fallacy of using the glycemic index as a gauge for post-workout glycogen replenishment is the 2008 study by Wallis et al. In a well-controlled experiment, the researchers were able to show that a post-workout drink that contained 2:1 glucose to fructose ratio was on par with pure glucose in its ability to replenish the depleted muscle and liver glycogen, when it was consumed right after a standardized glycogen depleting exercise bout (Wallis. 2008). Obviously, this result stands in stark conflict with the "glycemic index (GI) hypothesis". After all, the falsely dreaded fructose, the demon of Dr. Lustig's worst nightmares, has a GI of <20 and thus the lowest glycemic index of all natural sugars.

If the "GI hypothesis" was accurate, fructose should therefore be by far the worst choice for an athlete who wants to replete his / her glycogen stores as fast as possible. That this is not the case, goes to show you that things are - once again - much more complex, than the widely accepted, but overtly simplistic "rules of thumb" would suggest.

Why is the glycemic index a bad avisor, when it comes to PWO glycogen replenishment?

Before we head on to the new data the Detko study has to offer, let's briefly take a look at why the glycemic index does not qualify as a compass to guide us on our quest for the perfect post-workout carbohdydrate source. Don't worry, I am trying to cut myself short, just listing the four most important caveats:

• 

  Table 1: It's rarely talked about, but especially endurance athletes will also benefit from increased intramuscular lipid stores. Therefore the overview of the intramuscular glycogen and lipid storage rates from a 2003 paper by Jacques Décombaz could come especially handy to the marathoners among the SuppVersity readers (Décombaz. 2003)

  Non-insulin-dependent glucose uptake: In the first 30-60min after a workout, for example the GI, i.e. the ability of a given carbohydrate source to trigger an insulin release is negligible, simply because the non-insulin dependent uptake of glucose into the muscle is already maxed out.

• Organ specificity: Contrary to the skeletal muscle tissue, the liver has a is downright dotty about fructose; and the more fructose it takes up, processes it and turns it into glycogen (see pathway, here), the more glucose will remain for your muscles to feast on.

• Ceiling effects: The amount of glycogen your muscles can synthesize is limited to approximately 9–10mmol/kg wet weight (WW). This rate can be sustained by the intake of 1.2g of carbohydrates per kg of body weight - more cannot end up in your muscle, regardless what kind of useless nutrient partitioner the company rep in disguise on your favorite bulletin board may have persuaded you to buy.

• 

  Figure 1: Muscle glycogen content 2h into the recovery period (left) and rise and fall of glucose concentrations after the ingestion of a low and high molecular weight starch immediately after a standardized glycogen depleting exercise bout (Gunnar. 2012)

  Molecular weight and absorption dynamics: While it is obvious that the latter should have a major effect they should (a) interact with the glycemic index (faster appearance in the blood = greater insulin response in healthy individuals) and (b) warrant the use of carbohydrate blends (after all, you don't want to run out, after the intitial spike, right). From my use of the conditional in the previous paragraph you may however already have realized that this assumption is not unambiguously supported by the currently available literature which does support the faster transit times, but not necessarily the purported downstream effects on the repletion of the glycogen stores in exercised muscles.
  In his 2012 thesis, Frances Gunnar from the University of Nottingham, for example, demonstrated that the much praised high molecular weight starch Vitargo(TM) did not yield produce greater increases in post-workout glycogen resynthesis than a low molecular weight counterpart (Gunnar. 2012). On the other hand, we have seminal papers such as the Y2k paper by Piehl et al. that are usually cited in this context (Piehl. 2000) and in which solutions with high molecular carbohydrate sources yielded greater rates of skeletal muscle re-synthesis.

I guess these were more than enough, "on the other hands" as Carl Lenore likes to call these lengthy departures of mine on the weekly SuppVersity Science Round-Up on the Super Human Radio Network from time to time. So let's now finally get to the study at hand.

Protein and galactose? What's that got to do with PWO glycogen repletion?

As I already hinted at in the introduction, the experiment Detko et al. conducted was not designed to compare carbohydrate solution A with carbohydrate solution B. The idea was rather to elucidate whether and by which mechanisms the addition of protein to the a standardized post-workout carbohydrate solution could accelerate the PWO glycogen repletion even further. Accordingly the test solutions the scientists prepared from commercially available raw materials contained either

• maltodextrin + galactose - 0.9 g/kg body mass (BM) maltodextrin + 0.3g/kg BM galactose, or
• maltodextrin + glactose + protein + leicine + phenylalanine - 0.5g/kg maltodectrine, 0.3g/kg galactose, 0.2g/kg whey and 0.1g/kg of each leucine and phenylalanine

As subjects, the scientists selected a total of seven recreationally, yet highly trained male cyclists who had been training for least 10h per week over the least 5 years (mean age: 33y, body weight: 79kg, VO2Max: 58 ml/kg per min).

It would have been more promising to use isoleucine instead of leucine and phenylalanine as "additives" to boost glucose uptake (click here to learn why)

Why would the scientists use galactose, leucine and phenylalanine? According to previous research the combination of maltodextrin + galactose has a slight, but significant advantage over the glucose + fructose combination mentioned earlier in this article. Practically it's unlikely that it will make a significant difference, anyways. After all, the important thing here is that fructose and galactose are preferred glycogen sources of the liver, which is thus not going to "steal" the glucose from the maltodextrin which is supposed to end up in the glycogen stores of the musculature - not the live (Decombaz. 2011).

The addition of leucine and phenylalanine, on the other hand, was supposed to increase the insulin response and thus help to shuttle the glucose into the cells. Needless to say that this is not necessarily a good idea and actually based on the same fallacious notion that insulin would be the main determinant of the rate of glucose replenishment after a workout, right?

In order to prevent differences in the baseline diet to interfere with the study outcome, the participants were not only asked to reproduce their nutrient intake in the days prior to the two testing sessions, they were also provided with standardized meals. which containing 150 g CHO, 67 g PRO and 22 g fat  and had to be consumed on the evening before the tests which consisted of

• 45min of steady state cycling at 70% VO2max,
• 6x1min sprints at 120% of the VO2max (2min recovery at 50% VO2max) and 
• 45min of steady state cycling at 70% VO2max

The steady 2nd state part of the intervention was meant to "further promote [the] depletion of glycogen in type I fibres" and to elicit a "reduction of plasma lactate concentrations at the end of the glycogen-depleting exercise".

"Ok, I got it, what about the supps and the results?"

During the trial the subjects were free to consume as much water as they wanted. Blood samples were drawn at the start, 45min after the intervention and every 30min during the 4h recovery period. The crucial part of the study, the supplementation, took place immediately after the first vastus lateralis scan. The drinks were ingested in a single 400ml bolus and 6 smaller 150ml portions every 30 min (see figure 2, left - small bottles).

Figure 2: Outline of the experimental design (left) and glycogen repletion rates - calculated based on averages for all subjects over the full course of the 4h post-workout window (Detko. 2013)

As you can see in figure 2, the averaged glucose repletion rates were virtually identical with a non-significant, but visible advantage for the muscular glycogen with higher carbohydrate and no protein intake. The result clearly refutes the researchers initial hypothesis that

"[...] the post-exercise ingestion of MD and GAL with PRO and AA would enhance liver and muscle glycogen repletion compared with an isoenergetic MD–GAL formulation." (Detko. 2013)

What's particularly intriguing about this result is that it manifested despite the fact that the large spike in insulin, the researchers had expected in response to the addition of whey and the pro-insulinogenic amino acids leucine and phenylalanine to the mix (see figure 3).

Figure 3: Blood glucose and insulin levels in the post-workout period (my markups in Detko. 2013)

In conjunction with the data about the glucose concentration, which did not crash in response to the insulin spike (this should happen if the equation "more insulin = more glucose uptake = faster glycogen replenishment held) this just confirms that the effects of the carbohydrate, protein and amino acid induced insulin spikes have little to no effect on the rate post-workout glycogen re-synthesis. While previous research suggests that a threshold limit must be maintained to keep the influx of glucose constant after the initial ~30min, this threshold is so low that any special "tactics" to increase the insulinogenic effect of post workout-nutrition appears to be a waste of time.

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Bottom line: If we follow the Taubsian mantra that insulin is the root cause of all disease, the necessary conclusion we'd have to take away from the results of this study is that you better avoid having protein in your post-workout nutrition and rather resort to carbohydrates alone... just kiddin' ;-) We obviously all know about the benefits the ingestion of a fast digesting protein in the vicinity of workout has on protein synthesis. Simply skipping on the protein fraction of your post-workout shake is therefore not really an option. After all, the transient increase in insulin, as useless as it may be, is probably not going to kill you.

That being said, this is study #2 within no more than a week that questions the usefulness of adding leucine as a free-form amino acid to your supplement stash (compare "Leucine Supplementation Exemplifies Potential Downsides of Non-Specific Insulin Sensitizers"). With ~30g of whey you should have enough readily available amino acids (including leucine!) to kickstart protein synthesis, anywa - plus: contrary to the average study participant in this and similar experiments, you are not going to fast for the next 4h, so that the protein from your next full meal is going to help you keep the plasma amino acid levels steady (Tip: If you cannot have a full meal, afterwards add 20g of casein to the shake).

What happens if you eat 194 bananas in 3 weeks? You will get fit and sick, right? No, false. What actually happens is a reduction in body fat (read more)

With your protein needs taken care of, the only other thing you'll need are some carbohydrates to satisfy your bodies desire to refill its glyocogen stores. Preferably, those carbs come at a ratio of 2g of muscle substrate (=glucose or precursors) to 1g of liver substrate (=fructose or galactose). A banana, a food I have previously recommended as a post workout carbohydrate source, would provide you with 5g of free glucose and 5g of free fructose (per 100g). It does however also contain 5g of starch, 2g of sucrose and 2.5g of fiber, so that you would end up with a 2:1 ratio of glucose (+starch) to fructose and thus "right in the zone" (if you really need to replete your glycogen levels as fast as possible, you will have to resort to non-whole food sources, though).

With 32g of carbs a single large banana (~140g) would get you up to a 1:1 ratio of protein and carbs and thus to the lower end of what I would consider a rational post-workout nutrient mix. If you (a) don't follow that up with a real meal, when you are back from the gym, it is probably smart to double the amount of minimal carbs. While this would be the bare minimum, your diet (low or high carb), the respective carbohydrate allowance (limited to X g of carbs per day), your current goals (cutting or bulking, perfromance of body composition changes) and obviously your individual "carb tolerance" (rule of thumb: the leaner the better) dictate how much you can our rather should add to that to see optimal results. And as the results of the study actually underline, only very few of the SuppVersity readers will have to go past the 1g/kg body weight margin, as long as this is not their only carbohydrate containing meal of the day.

References:

• Décombaz J. Nutrition and recovery of muscle energy stores after exercise. Schweizerische Zeitschrift für Sportmedizin und Sporttraumatologie. 2003; 51 (1): 31–38.
• Décombaz J, Jentjens R, Ith M, Scheurer E, Buehler T, Jeukendrup A, Boesch C. Fructose and galactose enhance postexercise human liver glycogen synthesis. Med Sci Sports Exerc. 2011 Oct;43(10):1964-71.
• Detko E, O'Hara JP, Thelwall PE, Smith FE, Jakovljevic DG, King RF, Trenell MI. Liver and muscle glycogen repletion using 13C magnetic resonance spectroscopy following ingestion of maltodextrin, galactose, protein and amino acids. Br J Nutr. 2013 Feb 6:1-8.
• Gunnar, F. The effects of a high molecular weight glucose polymer on muscle metabolism and exercise performance in humans. Thesis submitted to the University of Nottingham. July 2012. 
• Piehl Aulin K, Söderlund K, Hultman E. Muscle glycogen resynthesis rate in humans after supplementation of drinks containing carbohydrates with low and high molecular masses. Eur J Appl Physiol. 2000 Mar;81(4):346-51.
• Wallis GA, Hulston CJ, Mann CH, Roper HP, Tipton KD, Jeukendrup AE. Postexercise muscle glycogen synthesis with combined glucose and fructose ingestion. Med Sci Sports Exerc. 2008 Oct;40(10):1789-94.