Showing posts with label leucine. Show all posts
Showing posts with label leucine. Show all posts

Wednesday, November 4, 2015

No Additional Gains With PWO Protein + Leucine Shakes in Rookies? Why the "Shocking" Results of a Recent Study Don't Mean That They, Let Alone You, Cannot Benefit at All

You can't expect wonders from protein supplements... no matter, when you take them, by the way. But I wouldn't mark them down as useless - even for rookies - based on the study at hand.
When I look at the 14 year old kids who need an written permission from their mum to train at the gym buying protein tons o powders and dozens of bars from the vending machines at the gym, even I have to shake my head. Not necessarily, because they're buying those products, but rather about what they tell each other about the effects: "Yo,... recently I ate this protein bar right after my workout and I felt swole for day..."

Now, you know that I am into supplement psychology and have no doubt about the fact that said kiddo felt swole all day, but we all know that protein is in no way a supplement the muscle-building and strength advantages of which will show within hours. And with that, I have a perfect transition to today's topic: The recent study from University of Central Florida in Orlando (Boone. 2015).
You can learn more about protein intake at the waredownloadsoft

Are You Protein Wheysting?

5x More Than the FDA Allows!

More Protein ≠ More Satiety

Protein: Food or Supplement?

Protein Timing DOES Matter!

Less Fat, More Muscle!
You will probably remember the most striking result of this study in which Carleigh H. Boone and colleagues "examine[d] the short-term effect of resistance training with and without protein supplementation on changes in muscle morphology and strength in untrained young men" (Boone. 2015).

Some of you may now be wondering: Why on earth do they even test that? We have ample evidence that protein supplements are powerful muscle builders! And you are right, but as it is the case for (almost) every research question in exercise science, even the highly acclaimed benefits of pre- or post-workout protein supplementation are somewhat contested. There's the evidence that supports the benefits of peri-workout protein supplementation on exercise induced muscle gains. Unfortunately, many of these studies may have been over-interpreted. Why?

FSR ≠ more muscle. Just because the post-exercise fractional protein synthesis increases this does not mean that you will gain more muscle in the long term. Check out this SV Classic to learn why!
Well, many of the often-cited studies in rookies, like Biolo et al. (1995), Phillips et al. (1997), or Tipton et al. (1999), measured increases in acute muscle protein synthesis and markers of anabolism. Due to their short design, however, increased long-term gains could only be predict, but not detect. In my 2014 article "Study Confirms: Acute Post-Exercise Myofibrillar Protein Synthesis Is Not Correlated with Resistance Training-Induced Muscle Hypertrophy in Young Men" (read more) you have learned, though, that the assumption that significant increases in post-workout muscle protein synthesis will necessary lead to significant augmented increases in muscle size in the long run is logical. but futile.

There are studies where this is the case, e.g. Coburn et al. (2006); Hulmi et al. (2010); Walker et al. (2009); Willoughby et al. (2007) - in both, trained and untrained individuals, but as Boone et al. rightly point out, there are also studies by Antonio et al. (2000) or Hoffman et al. (2009) in which protein or amino acid supplements had no beneficial effects on muscle or strength gains in either or trained and untrained individuals. The randomized, double-blinded study Boone et al. (2015) conducted is thus by no means superfluous. It is yet no perfect either, because with a length of only our week, the scientists picked exactly the time-frame in which things, or I should say "gains" happen faster than you can measure them. Furthermore, the use o a lower body unilateral resistance training makes it very difficult to infer the effects of protein supplementation on (a) muscle morphology [cross-sectional area, muscle thickness, pennation angle], (b) lower body power output, (c) maximal dynamic strength, and (d) maximal isometric strength in other muscle groups and in response to an overall metabolically more demanding workout.
Protein Timing Does Matter! Yet Only in Trained Men. More Than 2x Higher Relative Protein Retention W/ Immedi-ate vs. 6h Post Whey Consumption in Bodybuilders vs. Rookies | read more
Why does trained vs. untrained matter? We know that the growth stimulus in response to exercise and the unused growth potential are both maximal in untrained individuals. As far as strength is concerned, they have the additional advantage of making rapid gains by learning to master the exercises properly and neurological adaptations which are for the most part responsible for the rapid strength increases in the first months of resistance training. It is thus only logical that there's evidence that rookies do in fact gain "no matter what", while advanced trainees will have to up their game by advanced training techniques, protein supplementation and as I pointed out in a 2014 article, here at the waredownloadsoft even protein timing, which appear to be pretty useless for the people who have just been picking up the bar- and dumbbells.
Since the scientists have concise dietary records (Figure 1) and used a supplementation regimen that included not just 17g of whey protein concentrate, but also 3g of cholostrum and an extra 2g of leucine (PLA was an iso-caloric amount of resistant maltodextrin) to trigger a maximal increase in protein synthesis when the shake was consumed ad-libitum (in this case whenever the subjects wanted) on non-training days and immediately after the training sessions on training days, the data is still worth discussing (also because I already mentioned it on Facebook and I don't want you to over-estimate the overall significance of the study).
Figure 1: Overview of the macronutrient (in g) composition of the subjects' diets at baseline and during the study (the value for protein include the amount of protein from the protein shake in the PRO group | Boone. 2015).
As you can see in Figure 1 the protein intake of the twenty untrained young men who were randomly assigned to either a resistance training + protein (PRO; 21.4 ± 1.9y, 75.3 ± 15.7kg) or resistance training + placebo (PLA; 22.9 ± 3.1y, 76.8 ± 14.4kg) group was almost identical at baseline (1.2g/kg) and increased from 1.2 to 1.3g/kg in the protein group (+18.2%) while it dropped to 1.0g/kg body weight in the placebo group (-17.1%).

No such differences existed with respect to the supervised resistance training programs which started with five minutes of non-fatiguing aerobic activity on a cycle ergometer at a self-selected resistance and cadence. This was followed by a specific warm-up consisting of body weight squats, alternating lunges, walking knee hugs, and glute kicks (10 each). The subsequent, actual training sessions is described as follows.
"Each training session consisted of unilateral countermovement jumps (CMJ), leg press (LP), and leg extension (LE) using the dominant leg. CMJ were performed for a total of three sets of 8 repetitions with maximal effort. The LP and LE exercises were performed for a total of three sets of 8-10 repetitions at 80% of the participant’s previously determined 1RM with 90 seconds allotted between sets and exercises. If a participant was unable to perform the minimum amount of repetitions during the first or second sets of LP or LE, weight was decreased to an intensity deemed appropriate by a certified trainer. Consequently, if the participant was able to perform all repetitions with proper form and minimal strain, weights were progressively increased during the subsequent training session at the certified trainer’s discretion" (Boone. 2015).
After twelve of these training sessions, which took place at the university’s Strength and Conditioning Lab, on three nonconsecutive days per week.
Why would it have been nice to know when the size and power gains were measured? The answer is "the pump", ... well, not exactly. It's rather the cell swelling that occurs in the hours and days after a workout. The latter may have increased the overall impression of size gains and thus reduced the significance of potential differences if there was not a interval of at least 5 better 7 days between the last workout and the measurement of the muscle sizes. Bullocks?
Working out leads to increases in water content (left) corresponding increases in muscle "size" (right) at the 10 & 20 cm measuring points of the the quads; all values expressed as relative changes (%) vs. baseline | more
No, reread my 2014 article "Cell Swelling Keeps Muscles "Pumped" For More Than 52h. Size Increases of Up to 16% After a Single Leg Workout! Plus: Changes in Tendon Water & Collagen Content" (read the full SV-Classic article)- that the data will be distorted is a proven fact, with just one study investigating the extent, though, we cannot tell if the data will always be 16% off and the difference thus practically relevant.

Another reason why I was specifically looking for information on the interval between the last training and testing sessions was the lack of increases in peak and mean power (the changes in Figure 2 are all non-significant). If we know when the testing was done, one may be able to tell if this was a result of residual fatigue or if there were in fact no power gains in any of the two groups.
I've plotted the size, strength and power gains, which were assessed on an unfortunately non-disclosed time (see box above for elaborations) in Figure 2:
Figure 2: While even the small size gain in the rect. femoris in the PRO group was stat. sign. compared to the pre-value, none of the visible differences between PRO and PLA reached stat. significance and the mean and peak power did not even change at all... well, statistically speaking (see box above for a discussion why this may be the case | Boon. 2015)
Now, it's not like there were no gains, the cross-sectional area and muscle thickness increased significantly, but the scientists observed neither statistically nor practically significant (mostly due to the large inter-individual differences, e.g. a standard deviation of +/-12% for the CSA increase of the Rectus Femoris in the PRO group).
Table 1: Changes in maximal dynamic, isometric, and specific strength following training - Values are means ± SD. * Significant change from Pre to Post (p < 0.05 | Boone. 2015).
Since the strength data in Table 1 is similarly inconclusive, there is little doubt that is - for the study at hand - 100% warranted to say that while "the current findings suggest that short-term resistance training resulted in significant increases in muscle strength and size in untrained young men", they also suggest that "[t]he addition of a post-exercise protein supplement used in the current investigation was not sufficient to enhance the effect of resistance training" (Boone. 2015).
Polydextrose and Resistant Malto-dextrin May be Useful Dieting Aids, But are They good Placebos?
So what? Don't dumb your protein supplements, yet ;-) Aside from the previously mentioned study duration and the unrealistic training regimen, there is another thing I would like to highlight to substantiate my previously voiced warning that you should not overestimate the practical significance of the study at hand: The "placebo" supplement. Usually you'll see that protein is tested against regular maltodextrin. In the study at hand, however, it was tested against resistant maltodextrin of which you, as a waredownloadsoft reader know that it has been shown to significantly curb the appetite in humans and rodents. More recently, Hira et al. (2015) calculated that only 10g of these resistant starches per day may be able to reduce the energy intake by a whopping 7%.

This puts the -9.4% reduction in energy intake in the placebo group into an altogether different light and makes me question whether the placebo was as inactive as it should be. I have to admit, though, that eventually a lower total protein intake and a lower total energy intake as it was observed in the PLA group at identical study outcomes would even substantiate the claim that additional protein is useless in rookies, but who knows which other unknown effects the 20g of the resistant maltodextrin "placebo" had ;-)

Enough of the speculations, though. Let's stick to the facts: (1) Very few of you will be in the first four weeks of their resistance training "career", (2) even fewer of you will train only one leg, and I'd hope that (3) none of you plan to train for only the next for weeks only. So, that alone would make me want to repeat the scientists' own suggestion that "more research needs to be done" while telling you to (a) keep the results of this study in mind and file them under "protein is no wonder drug", while (b) keep taking your protein supplements. There's good enough evidence to say that >90% of you are going to benefit in one area or another - and always remember whey is more than a muscle builder (learn more) | Comment on Facebook!
References:
  • Antonio, Jose, et al. "Effects of exercise training and amino-acid supplementation on body composition and physical performance in untrained women." Nutrition 16.11 (2000): 1043-1046.
  • Biolo, Gianni, et al. "Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans." American Journal of Physiology-Endocrinology And Metabolism 268.3 (1995): E514-E520.
  • Coburn, Jared W., et al. "Effects of leucine and whey protein supplementation during eight weeks of unilateral resistance training." The Journal of Strength & Conditioning Research 20.2 (2006): 284-291.
  • Boone, Carleigh H., et al. "Muscle strength and hypertrophy occur independently of protein supplementation during short-term resistance training in untrained men." Applied Physiology, Nutrition, and Metabolism ja.
  • Hira, Tohru, et al. "Resistant maltodextrin promotes fasting glucagon-like peptide-1 secretion and production together with glucose tolerance in rats." British Journal of Nutrition (2015): 1-9.
  • Hoffman, Jay R., et al. "Effect of protein-supplement timing on strength, power, and body-composition changes in resistance-trained men." International journal of sport nutrition 19.2 (2009): 172.
  • Hulmi, Juha J., Christopher M. Lockwood, and Jeffrey R. Stout. "Review Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein." Nutrition & metabolism 7 (2010): 51.
  • Phillips, Stuart M., et al. "Mixed muscle protein synthesis and breakdown after resistance exercise in humans." American Journal of Physiology-Endocrinology And Metabolism 273.1 (1997): E99-E107.
  • Walker, Thomas B., Et Al. The Influence Of 8-Weeks Of Whey Protein And Leucine Supplementation On Physical And Cognitive Performance. Air Force Research Lab Brooks Afb Tx Human Effectiveness Directorate, 2009.
  • Willoughby, D. S., J. R. Stout, and C. D. Wilborn. "Effects of resistance training and protein plus amino acid supplementation on muscle anabolism, mass, and strength." Amino acids 32.4 (2007): 467-477.
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Too Much Whey Today, Type II Diabetes Tomorrow - Human Study: Whey Reduces Muscular Glucose Uptake by 25%!

Is it really bad to drink that whey shake before you eat the bananas, strawberries and blueberries, because whey makes you insulin resistant? Sounds "bogussy" and a closer look at the questionable methodological choices of the scientists who conducted the study don't make the results sign. more credible.
In the fitness community, whey protein is the #1 on the "must have supplement" list. Multi-vitamins? Creatine? Who cares, as long as you get your 30g of whey per day, you're good... really? One of you recently send me a study that would suggest that "good" is not exactly the right word to describe the effects of whey protein on at least one out of the set of well-established parameters of optimal metabolic health: Your muscles' insulin sensitivity.

In the paper that has been published in the reputable scientific journal "Diabetes", Gordon I. Smith and colleagues describe an experiment the results of which clearly suggest that whey doesed at 0.6g/kg fat free mass has a sign. insulin-desensitizing effect in twenty-two sedentary (<1.5 hour of exercise/w) and weight-stable (<2 kg change for at least 6 months), 50-65y old postmenopausal women who participated in this acute response study.
You can learn more about protein intake at the waredownloadsoft

Are You Protein Wheysting?

5x More Than the FDA Allows!

More Protein ≠ More Satiety

Protein: Food or Supplement?

Protein Timing DOES Matter!

Less Fat, More Muscle!
Acute response? Yes, there it is, the first in a line of problems that reduces the significance of the results. After all, testing the acute response to a certain health cannot tell you anything about the long-term effects on said parameter... especially if your subject group due to being sedentary and in an age where the parameter in question is deteriorating, anyway.

But let's not be the "it's not bros, so it's not valid for bros"-guys. Let's rather take a look at (a) the procedures and (b) the results and make up our minds later. And let's first take a look at a handful of important parameters of the study design: To determine the insulin sensitivity, the scientists used two hyperinsulinemic-euglycemic clamp sessions with the subjects being randomly assigned to do the procedure with vs. without whey protein first.
If you've got brawn and brain you cannot ignore that whey is much more than a potent muscle builder | learn more
"Before each clamp procedure, subjects were instructed to adhere to their usual diet and to refrain from vigorous physical activities for three days. Subjects were admitted to the Clinical Research Unit in the late afternoon, where they consumed a standard dinner between 1800 and 1900 h, and then fasted, except for water, until the next morning. At 0600 h, a catheter was inserted into an arm vein for the infusion of a stable isotope labeled glucose tracer; catheters for blood sampling were inserted into the radial artery of the opposite arm and in retrograde fashion into the femoral vein of one leg. At ~0645 h, a primed, constant infusion of [6,6- 2 H2]glucose (priming dose: 22 µmol·kg body wt-1, infusion rate: 0.22 µmol·kg body wt-1·min-1), purchased from Cambridge Isotope Laboratories Inc. (Andover, MA), was started and 4 h later the hyperinsulinemic-euglycemic clamp procedure was initiated with two 5-minute priming doses (first 200 mU·m-2 body surface area (BSA)·min-1 then 100 mU·m-2 BSA·min-1) of human insulin (Novolin R, Novo Nordisk, Princeton, NJ); for the remaining 230 min, insulin was infused at a rate of 50 mU·m-2 BSA·min-1. Euglycemia (at blood glucose concentration ~5.6 mM) was maintained by variable rate infusion of 20% dextrose (Baxter, Deerfield, IL) enriched to 2.5% with [6,6-2H2]glucose" ().
During the "whey trials", the subjects consumed 0.6 g of whey protein (unflavored Unjury®, ProSynthesis Laboratories, Inc, Reston, VA) per kg FFM dissolved in 360 ml water or the same volume of water alone. In addition, the researchers conducted a trial in which the subjects consumed the same amount of leucine.
Whey protein alone is gluconeogetic alone to increase the amount of glyocogen in liver (left) and muscle (right) of sedentary rats even if they don't eat a single ng of sugar or carbs (Morifuji. 2005). If you ignore the proven gluconeogenic effects, you must not complain if someone calls your study results irrelevant.
To understand the full "bogus" of the study at hand, you have to understand what a hyperinsulinemic-euglycemic clamp does. And you're lucky, it's not very difficult: The whole procedure is based on acutely raising a person's insulin levels to 100 μU/ml by continuously infusing insulin. The insulin levels are then kept constant, while just enough glucose is infused to keep the plasma levels of glucose stable. Higher rates of glucose infusion during the "clamp test" thus indicate a greater effect of insulin on glucose clearance and thus higher levels of insulin sensitivity. Now the bogus in this case is that it is (a) questionable how useful it is to compare a non-caloric to a caloric (and gluconeogenic) beverage with this test and (b) to ignore that part of the proven benefits of the caloric beverage you test are based on its ability to increase the same insulin levels you're keeping stable, anyway... not to speak of its effects on satiety. What? Yeah, I call that bogus.
To figure out if any effect they would observe was induced by whey, i.e. a complex protein, or just the most-applauded whey ingredient, i.e. leucine, the scientists ran a follow-up test (1-4 weeks later) in which the subjects consumed either 0.0684 g/kg FFM of pure leucine (that's equivalent to the amount of leucine in the whey protein)  dissolved in 360 ml Kool-Aid® (Kraft 94 Foods, Inc, Northfield, IL) or the same volume of the Kool-Aid® solution alone during the clamp procedure. I don't have to tell you that this was a mistake that makes the results of this follow-up useless for comparisons to the previous trial, in which the whey protein was mixed with water - Kool-Aid is after all all-carbohydrate - with 0.9g carbohydrates per ml of junk... ah, I mean per ml of the soft-drink.
Figure 1: Clearance of glucose during the hyperinsulemic clamp for the whole body and the legs (Smith. 2015). It is noteworthy that there control vs. active treatment signalling protein response (mTOR, p-AKT, ACC, etc. - not shown in figure) did not show differences that could explain the alleged negative effects of whey on glucose uptake (see Figure 2).
This does not mean that we couldn't use the data from the leucine trial, at all, though. But let's be honest, who cares about the non-significance of the effects of a non-gluconeogenic amino acid (meaning that leucine cannot be converted to glucose by the liver) if you cannot compare them to the significant decrease in insulin-mediated glucose disposal (38.8 vs 51.9 µmol glucose per µU insulin/ml / min; P<0.01) the scientists observed in the whey condition, because the test was messed due to the use of a different and by no means "neutral" control?
Figure 2: Don't worry, while the scientists cleverly call the glucose disappearance into the legs "leg glucose uptake" it's just the product of blood flow to the legs times whole body glucose disposal and suffers from the same methodological short-come as the whole body glucose disposal that assumes that whey was non-gluconeogenic (data from Smith. 2015)
Rather than as a basis to argue that whey is bad and leucine is good, you can use the Kool-Aid glitch and the fact that leucine cannot be converted to glucose in the liver to substantiate the following hypothesis: If the scientists had accounted for the gluconeogenic glucose load from whey when they tested their allegedly sugar-free (manufacturer claim) whey protein vs. water in the previous trial, they would probably have found no significant effect of whey protein on muscular glucose uptake, because the test wouldn't have been unfairly thwarted in favor of the water control which came without the additional glucose load from the whey-induced gluconeogenesis in the liver.
Figure 3: Both, acute and chronic realistic and thus relevant studies show beneficial effects of whey on glycemia (Petersen. 2009) and insulin sensitivity (Pal. 2010) - you decide which studies to trust ;-)
Plus, even if we assume that this hypothesis wasn't true (I am pretty convinced it is), the results of the study at hand would still be an inexplicable artifice that stands in stark contrast to the well-proven multi-facetted acute and chronic beneficial effects of whey protein on glucose- and weight-management in healthy, diabetic and pre-diabetic individuals (Layman. 2004; Frid. 2005; Peterson. 2009; Akhavan. 2010; Pal. 2010) - effects of which no one ever claimed that they were mediated by acute increases in muscular insulin sensitivity, by the way; and that despite the fact that the data from Pal (Figure 3, left) clearly indicates that these benefits occur in the real world.
Dairy or eggs? Why not just mix dairy and egg protein or dairy and eggs - A similar protein mix exerts most promising effects on anabolic signalling proteins related to increased muscle mass and fat loss, as the results of a study show | read more
What's the verdict, then - true or false? True. In the unrealistic and unfair comparison Smith et al. conducted, whey protein is inferior to water with respect to its effect on the post-menopausal body's ability to clear intravenously infused glucose from the blood stream.

What is yet more important is that the overall message the study and the half-sentence "protein ingestion causes insulin resistance" (Smith. 2015) from the abstract are sending are false: In fact, the study at hand doesn't allow for any reliable conclusions with respect to either the long-term or acute real-world insulin sensitizing or desensitizing effects of whey protein, because the scientists used a method that does not account for extra glucose that is produced in the liver during the testing procedure via gluconeogenesis (I know that high insulin levels reduce gluconeogenesis, but they won't shut it off).

Against that background and in view of the existing data from dozens of practically relevant clinical trials which indicate that whey will have positive, not negative effects on glucose metabolism, it would appear foolish to cite use the study at hand to argue that the cosumption of whey protein may ruin your insulin sensitivity and "too much whey today" may turn you into a type II diabetic tomorrow | Let me know what you think on Facebook!

References:
  • Akhavan, Tina, et al. "Effect of premeal consumption of whey protein and its hydrolysate on food intake and postmeal glycemia and insulin responses in young adults." The American journal of clinical nutrition 91.4 (2010): 966-975.
  • Frid, Anders H., et al. "Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects." The American journal of clinical nutrition 82.1 (2005): 69-75.
  • Layman, Donald K., and Jamie I. Baum. "Dietary protein impact on glycemic control during weight loss." The Journal of nutrition 134.4 (2004): 968S-973S.
  • Morifuji, Masashi, et al. "Dietary whey protein increases liver and skeletal muscle glycogen levels in exercise-trained rats." British journal of nutrition 93.04 (2005): 439-445.
  • Pal, Sebely, Vanessa Ellis, and Satvinder Dhaliwal. "Effects of whey protein isolate on body composition, lipids, insulin and glucose in overweight and obese individuals." British journal of nutrition 104.05 (2010): 716-723.
  • Petersen, Brent L., et al. "A whey protein supplement decreases post-prandial glycemia." Nutr J 8.47 (2009): 1475-2891.
  • Smith, Gordon I., et al. "Protein ingestion induces muscle insulin resistance independent of leucine-mediated mTOR activation." Diabetes 64.5 (2015): 1555-1563.
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