Branched Chain Amino Magic: Study Takes Another Step Towards a Better Understanding of the Anabolic & Anticatabolic Effects of BCAAs and Their Essential Cousins

Image 1: Without the other essential amino acids (EAAs), the branched chain amino acids, leucine, isoleucine and valine (BCAAs) have nothing to "build" your muscle from ;-)

Usually, I do not get very excited, when I hit upon another study into the "protein-synthetic response" that is triggered by the ingestion of branched chain amino acids (BCAAs). I mean, let's be honest... we all know that their ingestion will trigger the phosphorylation of the mammalian target of rapamycin and thusly increase protein synthesis, so why would we need another study where instead of a 17.5% increase in protein synthesis, we would see a 18.3% increase? Actually, we don't... the data Marcus Borgenvik, William Apró and Eva Blomstrand from the  Åstrand Laboratory, Swedish School of Sport and Health Sciences and the Karolinska Institutet, in Stockholm, Sweden (Borgenvik. 2011), collected goes yet well beyond what we have seen in most of the previous studies and is thus well worth an individual blogpost here at the SuppVersity.

BCCAs work! How? Little do we know...

If we are honest, we must concede that our (=the scientific) understanding of the complex processes that are triggered when "large" amounts of BCAAs hit our bloodstream, is very limited. What we know is that we can measure increases in mTOR-expression that correlate with likewise measurable increases in protein synthesis. What we do not really know is how exactly one leads to the other and where the influences of amino acid supplementation and exercise training overlap. This is even more true for the complementary side of the protein synthetic equation of which Borgenvik et al. state that

[w]hereas extensive evidence for the stimulatory effect of amino acids, either alone or in combination with exercise, on protein synthesis has been reported, their effect on protein breakdown is elusive.

In that, it is particularly confusing that "previous investigations involving ingestion of essential amino acids (EAA) in connection with resistance exercise have revealed no attenuating effect on protein breakdown", while studies which investigated the effect of BCAA or leucine in isolation, report reduction in protein degradation in subjects at rest or performing eccentric endurance exercise (MacLean. 1994). Reason enough for the Swedish scientists to recruit a group of seven healthy, recreationally active participants (5 men, 2 women; 27 (± 2) years; height 175 (± 5) cm; weight 67 (± 7) kg), put them on a standardized diet (17% protein; 25% fat; 57% carbs; ~2100kcal for women, ~2700kcal for men) for two days and, on the subsequent morning (subjects reported to the lab fasted) and after a thorough warm-up, have them perform

• 4 sets of 10 repetitions at 80% of their predetermined 1 RM, followed by another 
• 4 sets of 15 repetitions at 65% of their 1 RM of single-legged leg presses.

The subjects used the same leg on all exercises and rested ~5min after each set. Before the warm-up, during and immediately after and 15 and 45min after the exercise regimen the subjects consumed either

• 150 mL of BCAAs (2:1:1 ratio) in flavored water, or
• 150 mL flavored water alone.

The total amount of BCAAs was 85mg/kg or 5.695g for the "average" study participant. After four weeks the experiment was repeated with each participant receiving the opposite treatment.

Figure 1: Complete analysis of serum amino acid levels in the trained and untrained leg of subjects receiving BCAA or Placebo supplement before, during and after the completion of a standardized single-legged leg press exercise (data adapted from Borgenvik. 2011)

As far as the study protocol goes this is thus certainly not an extraordinary study. If you take a look at figure 1, where I deliberately plotted all the data the scientists gathered as far as serum amino acid concentrations are concerned, you will yet realize that what makes this study stand out is the sheer amount of parameters Borgenik et al. have analyzed. Similar data is also available for the amino acid concentrations in the exercised muscle and though, the scientists, who set out to investigate the effects of BCAA supplementation on protein breakdown, would probably disagree with me, here, I feel that this data actually has the most real world significance for physical culturists, like you and me.

Figure 2: Relative increase / decrease in intra-muscular BCAAs and other EAAs in BCAA supplemented subjects vs. placebo control at different time-points before, during and after single-legged leg presses (data adapted from Borgenvik. 2011)

After all, a brief glance at the effects the ingestion of ~6g of BCAA had on the respective tissue levels of leucine, isoleucine and valine (figure 2, BCAA) and the other, "missing" essental amino acids (figure 2, EAA - BCAA) should suffice to understand that though BCAAs may be the necessary to trigger protein synthesis, they are yet obviously not sufficient to "build muscle" - or how else would you explain the

pronounced reduction in the concentration of the aromatic amino acids, tyrosine and phenylalanine, in both plasma and muscle as well as muscle EAA (BCAA excluded) during the recovery period

Borgenik et al. observed in their study? The scientists at least conclude that

[s]ince tyrosine and phenylalanine are neither synthesized nor degraded in skeletal muscle, reduction in the levels of these amino acid could be indicative of an improved net muscle protein balance, i.e. an enhanced rate of synthesis and/or decreased rate of breakdown [and] could  be explained by incorporation into protein.

The accrual of muscle mass (whatever that may eventually mean, cf. yesterday's installment of the Intermittent Thoughts) thusly obviously relies on the presence of all essential amino acids and not just the "branched chained holy grail" of protein synthesis, of which the current study revealed that they (BCAA ingestion) reduced the expression of MAFbx, which regulates the protein transcription factor MyoD and the eukaryotic initiation factor-3f (eIF-3f), which, in turn is of importance in the mTOR-p70S6k signaling pathway, by 30% and 50% in the resting and exercising legs, respectively.

Figure 3: Relative (compared to placebo) mTOR and p70S6K phosphorylation in response to BCAA supplementation in exercised (EX) and non-exercised (Rest) leg at different time-points before, and after single-legged leg presses (data adapted from Borgenvik. 2011)

As figure 3 finally goes to show, we see the "usual" increases in mTOR and p70S6K phosphorylation that are commonly held responsible for the downstream increases in protein synthesis, and which were obviously more pronounced in the exercised compared to the non-exercised leg. The latter may be ascribed to what the scientists cautiously label a ...

[...] tendency for BCAA supplementation to attenuate the elevation in the level of Rheb mRNA in both resting (1.7-fold under the placebo versus 1.2-fold in the BCAA condition) and exercising muscle (2.4-fold versus 1.5-fold).

This ameliorative effect on Rheb, the low-molecular weight GTPase located immediately up-stream of mTOR, in combination with the exercise induced reductions in REDD2 expression (another negative regulator of mTOR) the scientists observed in the exercised leg are actually where we are currently at, as far as our understanding of the complex protein synthetic machinery goes. It is here at the gene-level where amino acid supplementation and its effect on Rheb and exercise and its effect on REDD synergize and facilitate those muscle gains trainees have been making for years often without any understanding of the biological underpinnings.

And though we may eventually be able to squeeze out another 5-10% more muscle mass, when we eventually get the "whole picture", I seriously doubt that even the most thorough understanding of the underlying biomolecular processes will change such basic recommendations as "take your 25g of fast digesting whey as a bolus immediately post workout" (cf. "Never Sip Your Whey!") - or what would you say?

Leucine & Phenylalanine Enriched YoYo-Diets Ameliorate Fat Gain, Protect Muscle & Maintain T4→T3 Conversion

Too little leucine & phenylalanine in O.'s diet?

Actually it is quite counter-intuitive that the "YoYo"-diets competitive boydbuilders adhere to (diet vs. bulking phase) are capable of producing such amazing physiques. I mean, when Mr. and Mrs. Average "diet down" and "bulk", the result will usually be neither aesthetic nor healthy, right?

A recent study from the University of Sao Paulo does now provide some insights into the important role the high amount of essential amino acids (leucine and phenylalanine, to be precise) in the typical bodybuilding diets may play with respect to its moderating effects on the lean muscle loss and body fat gains of Opra-esque ups and downs in body weight.

Leucine + Phenylalanine + diet and refeed = ???

I guess the details in the headline to this paragraph are not actually detailed enough to get an idea of what Donato Jr. et al did in their latest rodent study, are they? I see. I will still try to stick to the most important facts.

Contrary to the beliefs of many mostly female victims of life-long dieting, never eating to satiety is NOT going to promote a bikini body - quite the contrary (learn more)

Donato and his colleagues fed a group of adult Wistar rats diets that differed only in their amino acid make-up. Both the control and the experimental diet were based on the same synthetic standard chow (remember what you've learned about synthetic chow lately?). What was different, though was the form of protein / amino acids the scientists used to replace 8.55g of the cornstarch (per kg) of the original diet. The final diets did thus contain either...

• 8.55g of casein (control), or
• 5.45g l-leucine + 3.1g l-phenylalanine (LP)

... as replacements for the cornstarch. Since both were still isocaloric and had an identical protein content (12%) this modification would allow Donato et al. to see if the different amino acid profiles would have nay effects on the weight development of the rodents.

I guess by now you may be asking yourself about the connection to Oprah and boydbuilding diets, right? Well, the 28-day experiment actually had 2 phases a dieting and a maintenance phase. Both cycles were 14 days long. In the first one, the rodents dietary intake was cut in half, while they were allowed to eat as much as they wanted (ad-libitum feeding) in the second 14-day cycle.

YoYo or not - is that the question?

Now, what would you guess happened? I mean, remember: Both diets had an absolutely identical amount of calories and protein - so, the rodents in both groups "hit their macros", right? The logical answer - at least to an increasingly popular, but over-simplistic dietary paradigm - must be: "Nothing! Both groups will end up at an identical body composition.", right!? A brief glance at the data in figure 1 does however suffice to tell you the IIFYM prognosis was not exactly correct - at least not if we take the changes in body composition into account.

Figure 1: Effects of weight cycling with casein (control) and leucine + phenylalanine (L+P) on body composition (left), feed efficiency (=how much weight do you gain per gram of food) and weight (Donato Jr. 2013)

So what can we conclude based on the results in figure 1? Firstly, the small figure on the bottom right goes to show you that weight cylcing per se does not make you "heavy" as in "having a higher BMI than somebody who does not weight cycle". The large figure on the left, on the other hand informs us that weight cycling can cost you muscle and make you fatter - 4% fatter to be precise. Skinny fat, so to say. Notwithstanding, the data from the Donato Jr. study does also tell us that the provision of a low amount of additional leucine and phenylalanine minimized the fat gain in the bulking phase and had beneficial effects on amount of lean mass the rodents maintained and build during the 4-week study. The net result is a higher body weight in the L+P group, at an almost identical body composition.

Leucine + phenylalanine also blunt the reduction of T4 → T3 conversion

If we look closer we do yet see another related, but non-negligible advantage: The typical downregulation of the conversion of the "inactive" thyroid hormone T4 to the "active" thyroid hormone T3 in response to long-term dieting was significantly reduced by the provision of leucine and (I will just go on a limb here and say "more importantly") the neurotransmitter precursor phenylalanine.

Figure 2: Effect of weight cycling of markers of glucose and thyroid metabolism (Donato Jr. 2013)

This did yet not translate into a significant amelioration of the highly significant (>50%) deterioration of the blood glucose metabolism, and the triglyceride levels (not shown) were actually 20% lower in the casein yoyo group (CON) than in the non-weight cycled control group. From a health perspective, the addition of leucine and phenylalanine is thus "only" useful, because it will help you retain or actually build muscle mass (with the data we have, it's difficult to say which effect was the dominant one, but I'd suspect it's the anti-cabatolic one).

Bottom line: You need to be careful about mis- and over-interpreting the results of the study at hand - and that's not just because it's "only a rodent study".

If there was one "take home message" from the study at hand, I guess it would be very similar to the one from the one of the December 2012 post I borrowed this figure from: "Make sure to get at least 10g of EAA with each of your meals"... ah well, "... and avoid 'classic' YoYo dieting à la Oprah, whenever possible - of course!" ;-)

The alleged "lean mass gains" on the L+P diet come at the expense of a non-negligible increase in body fat. Overall the lean mass to fat mass ratio is thus not better than in the continuously fed rodents. And unless your beauty ideal is all about being "massive", this is not necessarily going to be an improvement to your physique.

If you take another look at figure 1 you will also see that the feed efficiency, i.e. the amount of weight you gain per kcal you consume was not reduced but increased by the addition of leucine and phenylalanine. This may be a result of the pro-insulinogenic and "anabolic" (Nuttall. 2006; Iverson. 2013), as well as the anti-cabatbolic effects of these amino acids and is thus not necessarily "bad".

It would nevertheless be highly unwarranted to believe that supplementing your diet with leucine + phenylalanine on a a "lean bulk" would yield significant advantages - this hypothesis is clearly not supported by the study at hand. The same goes for the usefulness of supplementing isolated amino acids, in this case leucine and phenylalanine, on top of a high protein diet, in general. In fact, I can refer you directly to an older article of mine that confirms that you better make sure to get the full dose of 20g+ of whole protein than trying to make up for it by adding additional aminos (learn more)

References:

• Donato, J. et al. Effects of leucine and phenylalanine supplementation during intermittent periods of food restrictionand refeeding in adult rats. Life Sciences. 2007 [epub ahead of print]
• Iverson JF, Gannon MC, Nuttall FQ. Ingestion of leucine + phenylalanine with glucose produces an additive effect on serum insulin but less than additive effect on plasma glucose. J Amino Acids.
• Nuttall FQ, Schweim KJ, Gannon MC. Effect of orally administered phenylalanine with and without glucose on insulin, glucagon and glucose concentrations. Horm Metab Res. 2006 Aug;38(8):518-23.

3.2kg of Lean Mass Over Night W/ 40g of Slow Digesting Protein 30min Before Bed!? Over One Year, a Positive Nitrogen Balance and +20% FSR Could Make It Happen!

Image 1: Babies instinctively know how to grow - mother's milk (60% whey, 40% casein, at later stages) + sleep ;-)

Tell me, does the sentence "Where Bro- and Pro-Science Unite in the Spirit of True Wisdom" ring a bell? Anyone? Well, that's what I thought. It's the mantra of the SuppVersity... unfortunately, more often than not, one "science" does not really care about the other, so that studies as the one by Peter T. Res and his colleagues from the University of Maastricht are unfortunately rather the exception than the rule (Res. 2012).

Pre-bed protein intake could be a crucial determinant of 24h protein synthesis

I guess, I won't have to tell you that bro-science has it that the most important thing to do before you go to bed (and for some hardcore "bros" even in the middle of the night) is not to brush your teeth, let alone to shower or at least wash your face, hands, feet and certain other body parts... no! The most important thing to do before you go to bed is to have a huge serving of protein - preferably a "night-time protein", like a slow-digesting casein-based protein shake with some additional fats to further slow the absorption (whether the fat will actually prolong the digestive process beyond what you will see if you ingest intact micelles, which will then be hydrolized in the gut and start clumping is anyone's guess, though). In fact, this is one of those truisms that has been repeated so often on the boards (and the ads) that you may be surprised to hear that Res et al. rightly claim that their study is the first one to investigate, whether this practice does actually povide any benefit for the professional or recreational lifter.

To this ends, the scientists recruited a group of 16 of the usual suspects, ah.. pardon "recreationally active men", which in this case means that they had a weekly physical activity level of 6.3h and 5.2h for the eight men in the protein and the seven in the placebo arm (#8 had a problem with a catheter, so that he had to be excluded), respectively. As you would expect from any study investigating the effect of dietary supplements on exercise performance and/or muscle growth, the subjects received a standardized dinner (0.04kcal/kg; 57% carbs, 13% protein, 30% fat) at the evening before the testing session, as well as "identical" (obviously the energy content was matched to the body weight of the respective individual) meals for breakfast, lunch and dinner on the day of the experiment. The overall protein content of the regular meals was 1.2g/kg body weight and should thusly at the lower end of what the "bros" would prescribe as a baseline protein intake for anyone trying to gain muscle.

Exercise protocol: Leg presses and extensions 8x8 - 45 min total

After a standardized meal at 4:45pm and a whole host of experimental procedures (most importantly to place the catheter for the multiple blood draws during the night), the participants performed 8 sets of 8 reps on a leg press and another 8 sets of 8 reps on a leg extension machine (2 sets at 55% and 65%, 6 sets at 75% of 1RM; "subjects were verbally encouraged during the test to complete the whole protocol"). Rest between sets was 2 min rest between exercises 5 min. At 9pm, ca. 15min after the exercise test, the subjects received a serving of Lucozade Sport Body Fuel and Lucozade Sport Recovery (yes, the study was supported by GlaxoSmithKline ;-), which contained 60g of carbs and 20g of whey and thusly mimics what many non-carbophobic athletes use to replete glycogen stores and ramp up protein synthesis after a workout. After a muscle biopsy at 11:30pm, the subjects received either 40g casein protein or placebo and "remained in a supine position until 0:00am" ... I lover this formulation, because it suggests that with all those catheters every subject fell asleep at exactly 0:00am after "remaining in a supine position" *rofl* - be that as it may, the scientists simply assume that their subjects had slept for 7 hours, when they woke them at 7am for the second muscle biopsy.

Figure 1: Plasma levels of essential amino acids (µmol/L) and overnight mixed muscle fractional protein synthesis rates (measured by phenylalanine tracer) in subjects after receiving 40g of slow acting protein (casein) or placebo 30min before bed (at T=0; data adapted from Res. 2012)

As you can see in figure 1 the EAA levels the scientists measured in the blood of their subjects in the course of the night was profoundly elevated in response to the protein feeding. It is thusly not surprising that the fractional protein synthesis rates the scientists calculated for the 7.5 h of overnight sleep was ~22% higher in the "pre-bed" protein group than in the subjects who received the placebo supplement (cf. figure 1; right). Yet, although this may sound much, we are talking about 0.059% vs. 0.048% fractional muscle protein synthesis per hour and thusly about a 0.011% increase, which was only "borderline significant" (meaning p = 0.05).

Figure 2: Net protein breakdown, synthesis, oxidation (all left) and balance (right) measured over night in previously exercised subjects after receiving 40g of slow acting protein (casein) or placebo 30min before bed (based on Res. 2012)

What is probably more important than the difference in fractional protein synthesis, anyways, is the overall net protein balance, which indicates that contrary to the trainees in the placebo group, the subjects who received a 40g serving of casein 30 min before they went to bed (and hopefully slept 7h ;-) did effectively "gain" muscle, or I should say, muscle protein over the course of their 7.5h nightly "fast", while the subjects in the placebo group ended up losing a minimal amount of skeletal muscle protein.

3.2kg of lean muscle mass in one ear with nothing but a protein shake before bed?!

If we take a look at the abstract numbers the scientists measured, such as an increase in whole body (!) net protein retention of ~50µmol/kg (measured in phenylalanine tracer molecules) over the course of 7.5h and do some math, this tells us that a trainee who weighs ~80kg and followed this practice over the course of one year, where we assume that he trains four times a week (i.e. 208 sessions) this would allow him to store 832mmol or (if I did not miscalculate) ~146g of the phenylalanine tracer in the 208 nights following his training sessions... does that sound much? No, it certainly does not, but we just assume that for each of those phenylalanine molecules another molecule of each of the other EAAs was stored within the muscle (since we are talking about "whole body" protein retention, other organs will get their share as well, though), and further assume that they all weigh about the same (which is obviously bullocks) the 40g of casein every night would result in a net protein gain of 3.2kg! How does that sound?

Image 2: Quark = Natural #1 casein source

Note: Fatfree asked rightly, whether there are not any natural alternatives to protein shakes and as I thought this is relevant for everyone, I decided against answering in the comment area. Personally I would suggest you watch out for either curd/quark (~10g casein per 100g) which has tons of highly bioavailable calcium etc. An alternative with lower protein content is cottage cheese. More fat, but still nice - any other cheese. A huge chunk of steak could work, but I am not sure if that is not problematic in terms of nighttime digestion, which was one of the 2ndary results of the study at hand: Casein is easily digested while we sleep.

Now while this is a pretty optimistic calculation, while we are (again) dealing with "rookies" who obviously gain like crazy, and so on and so fort, the fact that there are still 175 days, where you don't train and your body would still be able to store some protein, goes to show how important a properly timed intake of protein and with it a persistent influx of readily available amino acids is, if you want to gain muscle - and in that it does not matter if that are going to be 500g or 10kg over the course of one year. However, I beg you not to forget that you cannot live on protein alone and that it is highly questionable that by escalating the dose to say 60g or 80g the net gains would increase by 50% let alone 100%, respectively. So keep that in mind before you set up a bathtub full of protein to sleep in ;-)

References:

• Res PT, Groen B, Pennings B, Beelen M, Wallis GA, Gijsen AP, Senden JM, VAN Loon LJ. Protein Ingestion before Sleep Improves Postexercise Overnight Recovery. Med Sci Sports Exerc. 2012 Aug;44(8):1560-9.

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.