No Advantage of Bolus Ingestion of EAAs in Young Men!? Cereal Bread Not Better for Weight Control. Saturated Fat & the Heart. Plus: Serine for Your Weekend Alcohol Binge!

The "muscle full effect" indicates you don't have to consume 4 scoops at once.

With the publication of the latest issue of The Journal of Nutrition came a handful of interesting scientific papers I will briefly introduce in today's SuppVersity Nutrition Science Update.

The corresponding studies deal with the link of saturated fat to heart disease (Puaschitz. 2014), the effects of proteinogenic amino acid serine (one of the non-essential amino acids) on homocysteine metabolism in a rodent model of alcoholic fatty liver disease (Sim. 2014).

And when we're through with those, we will take a closer look at the effects of cereal enriched breads on the appetite ratings and postprandial glucose, insulin, and gastrointestinal hormone responses related to hunger and satiety in healthy men and women (Gonzalez-Anton. 2014), and the "muscle full effect", or rather limits to maximal protein synthesis in man (Mitchell. 2014).

Read more short news here at the SuppVersity

Obesity Research Upd. Nov. '14

Exercise Res. Upd. Nov '12(1)

Exercise Res. Upd. Nov '12(2)

Nutrition Res. Update Nov. '14

Weight Loss Tricks & More

Reductive Stress, Iron & the Military

• Saturated fat and your heart - Right from the Haukeland University Hospital in Norway comes a new study that investigated the associations between self-reported dietary SFA intake and risk of subsequent coronary events and mortality in patients with coronary artery disease (CAD).
  
  The study included patients who participated in the Western Norway B-Vitamin Intervention Trial and completed a 169-item semiquantitative food-frequency questionnaire after coronary angiography - 2412 patients, total, 81% men, 19% women with a mean age of 61.7 y.
  After a median follow-up of 4.8 y, a total of 292 (12%) patients experienced at least one major coronary event during follow-up.  And while a gigh intake of SFAs was associated with a number of risk factors at baseline, "there were no significant associations between SFA intake and risk of coronary events [age- and sex-adjusted HR (95% CI) was 0.85 (0.61, 1.18) for the upper vs. lower SFA quartile] or any secondary endpoint. Estimates were not appreciably changed after multivariate adjustments" (Puaschitz. 2014).
  

  

  Figure 1: Hazard ratios according to % saturated fat intake of total energy intake compared to minimal saturated fat intake (HR = 100%) in 2412 subjects (Puaschitz. 2014).

  In other words, if you ask researchers from Northern Europe, their answer to the question, whether our high intake of saturated fats is the reason we are dying prematurely from heart disease is "no". This stand in line with a recent review of the current evidence by O'Keffee et al. who point highlight that the different results (which often depend on the country, where the studies are conducted) may be attributable to the fact that "not all SFA are created equal and the food sources of SFA". Accordingly the researchers from the King's College in London, the Luke’s/Roosevelt Hospital, the New York Nutrition Obesity Research Centre and the Columbia University in New York recommend that "individual characteristics of the SFA, such as chain length, should be considered in dietary recommendations" (O’Keeffe. 2014)... and I would like to add: In every future study, as well.
  
  I mean, this and the foods from which the subjects in the study at hand got the majority of their saturated fat intake may well be the reason that there was a statistically significant correlation between high fat intakes and the occurernce of coronary artery disease (remember: all participants had CAD, already) in the cohort Western Norway B-Vitamin Intervention Trial.
• L-Serine as super-supplement for binge drinkers? At least in rodents the provision of 200mg/kg body weight (for humans this would be ~1.2-1.5g/day) serine in the diet led to an attenuation of alcohol-induced increases in serum homocysteine and hepatic triglyceride (TG) concentrations (>5-fold in the control mice) by 60.0% and 47.5%, respectively.
  

  

  Figure 2: Liver triglyceride levels, serum ALT and serum homocysteine levels in control mice (C) and "binge drinking mice" (EV) with and without 20mg/kg (ES20) and 200mg/kg (ES200) serine in their diets (Sim. 2014)

  Moreover, in the chronic ethanol study, l-serine also decreased hepatic neutral lipid accumulation by 63.3% compared with the ethanol group and ramped up the glutathione and S-adenosylmethionine content of the liver by 94.0% and 30.6%, respectively.
  
  If we assume that serine is only half as powerful, when it is given to humans, I would recommend you drink your Vodka Red Bull with serine in the future ;-)
• Super-satiating cereal enriched breads - I guess "super-satuating" is an exaggeration, but there is no doubt that the addition of variety of cereal flours (wheat, oat, and spelt) and 22% dried fruits (figs, apricots, raisins, and prunes) to regular bread lead to a significant improvement of appetite control by reducing hunger and enhancing satiety in 30 healthy adults (17 men and 13 women) aged 19–32 y with body mass index of 19.2–28.5 who participated in an experiment that was conducted at the University of Granada in Spain (Gonzalez-Anton. 2014).
  

  

  Figure 3: The hormonal changes would indicate increased satiety, the subjects reported increased satiety, but their 4h energy intake was identical in both condition (Gonzalez-Anton. 2014)

  Whether the decrease in prospective consumption and increased satiety is enough to have long-term benefits on weight control is yet questionable, because the subsequent ad libitum energy intake in a 4 h period after the ingestion of the "enriched" bread did not differ from that in the control condition, even though the postprandial blood glucose, insulin, ghrelin, were lower and the pancreatic polypeptide AUC (an indicator of satiety) was higher than with the control bread.
  
  Speaking of insulin: In view of the fact that the latter actually is a satiety hormone and its release is closely related to glucagon-like peptide (GLP) 1 and gastric inhibitory polypeptide (GIP) where the AUC (areas under the curve) were lowered as well, it's eventually maybe not too surprising that the "enriched" bread was not better than the regular one.
• Muscle full? What's limiting protein Synthesis? Scientists from the Clinical, Metabolic, and Molecular Physiology, MRC–Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research at the University of Nottingham and the Royal Derby Hospital in the United Kingdom recently determined the effect of Bolus (=all the aminos at once) vs. Spread EAA feeding in young men, hypothesizing that muscle-full is regulated by a dose-, not delivery profile–, dependent mechanism; and what they found was surprising for us - not for the researchers, though:

  

  Figure 4: Even though the study was conducted in young men, the overall dosage of 15g may potentially have had an effect on the outcome. On the other hand: If you "overdose" it would actually be more likely for spread protein ingestion to have superior effects. Against that background the "low" dose of "only" 15g of pure EAAs is not an argument that would falsify the results of the study at hand (Mitchell. 2014)

  "Despite distinct plasma and muscle profiles, Bolus feeding provided no anabolic advantage over Spread feeding (or vice versa); these findings are in keeping with our hypothesis of there being an intrinsic muscle-full state in young men at rest.
  
  Bolus feeding led to rapid aminoacidemia with a brisk upstroke and high peak plasma EAA and leucine concentrations. Spread feeding, by comparison, resulted in lower, later peak concentrations. Despite this, identical MPS responses were observed, even with the same latency (of ~90 min) and amplitude.
  
  Furthermore, with both feeding strategies, basal MPS was observed 180 min after consumption of either Bolus or the initial Spread doses. This preceded the peak Spread plasma EAAs, in keeping with the onset of a muscle-full state.

  As the scientists point out, their results do thus "suggest that, in healthy young men, it is dose dependent mechanisms that regulate the size of the anabolic response to feeding and that this response" and that this dose-dependent anabolic response "is not perturbed by later arriving, lower-amplitude aminoacidemia." The researchers also highlight hat it would seem "vital to have such a mechanism in place"; because of the "stability of muscle mass from year to year in healthy younger populations" (Mitchell. 2014). Eventually, the differences may well be explained by the existence of three distinct phases in the postprandial period, the scientists argue:
  

  

  Figure 5: Absolute changes in FSR from fasted (2120 to 0 min) to fed (0 to 240 min) (A), actual FSRs (B) and plasma EAA and insulin concentrations, phospho- 4EBP1 Thr65/70 and muscle protein synthetic rates, normalized to their own data spans shown on the same axis (C and D) in young men after consumption of 15 g of mixed-EAA meals by Bolus or Spread treatment. The black arrows represent ingestion of 15 g EAAs once, and the gray arrows represent ingestion of 3.75 g EAAs 4 times (Mitchell. 2014)

  "After the onset of essential aminoacidemia, a latent period exists when a significant negative arteriovenous EAA balance is detectable (Mitchell. 2013) but incorporation of EAAs into newly synthesized myofibrillar proteins is not. The existence of a similar latent period in response to Bolus and Spread EAA ingestion suggests that providing time for adequate intracellular EAA accumulation, even with rapid aminoacidemia with Bolus, is crucial before MPS can be ‘‘switched on.’’ After this latent period, a transient stimulation in MPS, lasting ;90 min (Bohé. 2001), occurs before the onset of the muscle-full state restores basal MPS despite sustained, near-peak postprandial EAA availability" (Mitchell. 2014).

  Put simply, it takes long enough for the muscle protein synthesis to gain full speed to incorporate all the amino acids the healthy subjects received in 4x45min boluses.
  
  Practically speaking this does not necessarily mean that you should give up your previous protein feeding strategies. With intact proteins, of which you know that they are more than the sum of their EAA parts (see "Whey Beyond Brawn"), studies by Moore et al. (2012 | learn more) and Burke et al. (2012 | learn more) yielded different results... albeit with less frequent biopsies that were taken across the postprandial period and thus a lower temporal resolution that does not exclude that said studies simply overlooked the dose-dependency of the muscle-full effect Mitchell et al. demonstrate in the study at hand.

10+ Things You Probably Didn't Know Whey Protein | more

So what are the take home messages from today's research update? I guess the one you will be most interested in, is the related to the Mitchell study which indicates that protein timing and / or the importance of bolus ingestions may previously have been overrated - at least in the short run. We should not forget, after all, that this is a result that would stand in line with Alan Aragon's & Brad Schoenfeld's recent review (Aragon. 2014  on nutrient timing which found a significant effect for the amount of protein people consume, but no evidence of the purported importance of protein timing.

This is yet not the only myth that is tumbling. The idea of heart disease triggering saturated fats and the notion that you could make bread a superfood by adding cereals and dried fruits did not get away unscathed either. With the impressive effects of serine in the rodent study by Sim et al. (2014), we do have another myth to bother with - one of which I would like to remind you that it has to remain a myth until the results have been confirmed in human beings | Comment on Facebook!

References:

• Aragon, Alan Albert, and Brad Jon Schoenfeld. "Nutrient timing revisited: is there a post-exercise anabolic window." J Int Soc Sports Nutr 10.1 (2013): 5.
• Bohé, Julien, et al. "Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids." The Journal of physiology 532.2 (2001): 575-579.
• Burke LM, Hawley JA, Ross ML, Moore DR, Phillips SM, Slater GR, Stellingwerff T, Tipton KD, Garnham AP, Coffey VG. Preexercise aminoacidemia and muscle protein synthesis after resistance exercise. Med Sci Sports Exerc. 2012 Oct;44(10):1968-77.
• O’Keeffe, Majella, and Marie-Pierre St-Onge. "Saturated Fat and Cardiovascular Disease: A Review of Current Evidence." Current Cardiovascular Risk Reports 7.2 (2013): 154-162. 
• Mitchell, William Kyle, et al. "Development of a new Sonovue™ contrast‐enhanced ultrasound approach reveals temporal and age‐related features of muscle microvascular responses to feeding." Physiological reports 1.5 (2013). 
• Mitchell, William Kyle et al. "A Dose- rather than Delivery Profile–Dependent Mechanism Regulates the ‘‘Muscle-Full’’ Effect in Response to Oral Essential Amino Acid Intake in Young Men."J. Nutr. February 1, 2015
• Moore DR, Areta J, Coffey VG, Stellingwerff T, Phillips SM, Burke LM, Cléroux M, Godin JP, Hawley JA. Daytime pattern of post-exercise protein intake affects whole-body protein turnover in resistance-trained males. Nutr Metab (Lond). 2012 Oct 16;9(1):91.
• Puaschitz et al. "Dietary Intake of Saturated Fat Is Not Associated with Risk of Coronary Events or Mortality in Patients with Established Coronary Artery Disease." J. Nutr. February 1, 2015 jn.114.203505
• Sim, et al. "l-Serine Supplementation Attenuates Alcoholic Fatty Liver by Enhancing Homocysteine Metabolism in Mice and Rats." J. Nutr. February 1, 2015 jn.114.199711.

Carbs, Leucine and Muscle Protein Synthesis: Eukaryotic Elongation Factor 2 Emerges as a New Player in a Game Where AMPK not mTOR is the Captain of the Team

Image 1: AMPK, not mTOR turns out to be the caption of the team

If you, do not only read my blogposts, here at the SuppVersity, but also follow some of the nutrition-related episodes on Carl Lenore's Super Human Radio, or Dr. Connelly's BodyRX show, you probably won't be a stranger to the amino acid "Leucine" and the name "Dr. Layne Norton", will probably remind you of the fact that, contrary to public believe, successful bodybuilders don't have to be dump meatheads. If, now, you have also listened to the latest episode of the BodyRX show, chances are, you do even remember Dr. Norton ;-) mention that his group at the University of Illinois recently did another study into the effects of amino acid supplementation... now, you tell me: Where is the place to read about the results of studies like that first? Yeah, of course, the SuppVersity is the place to go ;-)

In their study, Gabriel J. Wilson and his colleagues from the Division of Nutritional Sciences at the University of Illinois investigated the effects of leucine and/or carbohydrate supplementation on postprandial muscle protein synthesis in 34 Mmle Sprague-Dawley rats (Wilson. 2011). The animals were provided with a baseline diet providing 20% protein, 50% carbohydrates and 30% fat. In order to model human eating habits, the animals were trained to consume their food in three meals per day: 4g at "breakfast" (7:00am) and "lunch" (1:00pm) and a large dinner of 6g of their chow at 6:00pm. To reduce body fat accumulation those 12g of chow contained only 80% of the rats ad libitum caloric intake, which according to results from a 1983 study by Glore and Layman does not reduce the development of lean tissue in weanling rats (Glore. 1983).

On the day of the experiments, the rats received their usual 4g "breakfast" after a 12h fast (this was the rats customary food deprivation phase from 7pm to 7am) and 135min later, when the the post-prandial muscle protein synthesis was abating (it returned to normal 180 min after the meal), a 5ml oral gavage of either carbohydrates (CHO; 1.35g glucose + 1.35g succrose = 2x more than "breakfast"), leucine (Leu; 270mg l-leucine = 4x more than "breakfast"), carbohydrates + leucine (LC; 1.18g glucose + 1.18g succrose + 270mg leucine), or water (control). According to the scientists, ...

[t]he amounts and timing of the supplements were based on our previous research that produced maximal leucine- and insulin-induced stimulations of translation initiation and MPS 45 min after oral gavage.

Or, in other words, with the 135min delay the increase in muscle protein synthesis (MPS) from the supplement should begin exactly when the initial increase in MPS would otherwise have returned to normal, i.e. at 180min post "breakfast".

Figure 1: Postprandial changes in muscle protein synthesis (MPS expressed relative to daily MPS) 0min, 90min and 180min post ingestion of a 4g meal and following supplementation with water (control), carbohydrate (CHO), leucine (Leu), or leucine + carbohydrate 135min after the ingestion of the meal (data adapted from Wilson. 2011)

As the data in figure 1 goes to show, the "strategy" of Wilson, Norton & Co worked out pretty well. Just when the muscle protein synthesis would usually have returned baseline, i.e. at the post 180min mark, supplementation with carbohydrate, leucine and leucine + carbohydrate, ramped it right back up - in the case of the leucine + carbohydrate supplement, even to the same level where it had peaked 90 minutes after the rats hat ingested their 4g "breakfast". In view of the fact that the inter-group difference were not statistically significant, carbohydrate, leucine and a combination of both must be considered equally effective in keeping muscle protein synthesis elevated. Interestingly, though, the leucine (only) supplement did this in the absence of elevated insulin levels, which could be particularly interesting for those of you, who want to avoid insulins potentially (I want to emphasis that insulin is not per se fattening, but facilitates storage of excess energy as glycogen in muscle, but also as fat in adipose tissue) obesogenic effects.

Eukaryotic elongation factor 2 (eEF2), a new player in the game

The low insulin levels in the leucine only group, and the absence of changes in essential amino acid plasma levels and phosphorylation of p70S6K1, all of which could be responsible for the increase in muscle protein synthesis, raise the question what, if neither of these, could have triggered the renewed increase in muscle protein synthesis. The scientists' answer to this question is called eEF2, one of the eukaryotic elongation factors, which has only recently been implicated by Breen et al. (Breen. 2011) as a downstream factor in muscle protein synthesis (i.e. p70S6K1 would suppress eEF2). The results of Wilson et al. falsify this assumption and and establish eEF2, respectively its degree of phosphorylation as an independent factor in muscle protein synthesis; a factor that showed an inverse relationship (r = -0.5; p < 0.05) with MPS, which means that for every 2% decline in eEF2 there was a 1% increase in muscle protein synthesis across all treatment groups in the Wilson study.

Figure 2: Postprandial changes in AMPK activity (relative to fasted state) 0min, 90min and 180min post ingestion of a 4g meal and following supplementation with water (control), carbohydrate (CHO), leucine (Leu), or leucine + carbohydrate 135min after the ingestion of the meal (data adapted from Wilson. 2011)

Now, interestingly, the underlying key determinant of all these processes appears to be the good old AMPK energy-sensing mechanism, you learned about in the last installment of the Intermittent Thoughts Series:

[...] the incongruity between MPS and mTORC1 signaling at 180 min after the meal does not reflect a refractory period or decreased sensitivity to anabolic stimuli, but rather, an increase in AMPK activity and a decrease in translation elongation activity.

Or, in other words, it is the decrease in AMPK (cf. figure 2) after supplementation, which "allows" for a reduction in eEF2 phosphorylation and thus another increase in muscle protein synthesis.

If you think that this is all too complicated, never mind - with a huge portion of whey and, if you will, added BCAAs and/or some fast acting carbs, i.e. the tried and proven post-workout nutrition, you cannot fail, no matter which funky proteins and genes are behind the muscle-anabolic effect of this bodybuilding classic ;-)

Maximal Protein Synthesis in the Elderly: How Much Protein Does it Take? Another Study to Suggest More is Better!

Maximal protein synthesis requires protein, but how much exactly you need will depend on your age - the older you are the more PWO protein you'll need.

Scientists from the University of Auckland were fed up with the lack of information about the differential response in protein synthesis in response to the ingestion of various amounts of protein. Accordingly, Randall F. D’Souza et al. conducted a study to characterize the changes in intramuscular levels of EAAs and BCAAs and the expression of the "protein pump" p70S6K at Thr389, a marker of protein synthesis, in response to resistance exercise and graded ingestion of whey protein in older men.

As a regular SuppVersity reader you will probably already think: "Where is the actual measurement of the fractional protein synthesis?" The unfortunate answer: It's not there.

You can learn more about protein intake at the SuppVersity

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Previous research had show that the ingestion of graded amounts of high-quality protein such as whey after resistance will maximize with "only" 20g of egg protein (Moore. 2009) or whey (Witard. 2014) in young men. Multiple studies in older adults (>60 years), on the other hand, suggest that they exhibit a lower anabolic signaling and MPS response to protein feeding, resistance exercise, and the combination of feeding and exercise when compared to young men (Cuthbertson. 2005; Fry. 2011; Burd. 2013). Scientists call this phenomenon age-related "anabolic resistance" (Yang. 2012b).

Figure 1: In contrast to the fractional protein synthesis in the elderly, which increases with increasing amounts of protein, the FSR of young men shows a ceiling effect at 20g+ whey protein (Yang. 2012a; Moore. 2009)

As you can see in Figure 1 from a 2012 study by Yang, the same 20g of extra-whey (total dose 40g) that was useless in young men, lead to a significant increase in protein anabolism in elderly men. Compared to young men, the MPS response to feeding 40 g of protein was yet still slightly lower in older vs. count men (Yang. 2012a; Churchward Venne. 2013b).

What is particularly relevant for the study at hand, and the previously criticized absence of actual MPS measurements is the fact that deficits in feeding induced p70S6K phosphorylation may at least partially underpin anabolic resistance in aged skeletal muscle (Cuthbertson. 2005), which is why measuring the p70S6K phosphorylation in older human subjects (mean age 71 years) in response to the graded ingestion of whey protein after a leg workout consisting of three sets of 8–10 repetitions of bilateral barbell smith rack squat, 45°leg press, and seated knee extensions at 80% of the subjects' predetermined 1R is not as irrelevant at it may initially have seemed.

Workout + supplements, that's the "whey to go" ;-)

The exercises were performed in a circuit manner with 1 min rest between each exercise and 3 min rest between subsequent sets, the exercise protocol took approximately 20 min to complete. Following completion of the exercise protocol, subjects were immediately provided with a fixed-volume (350 mL) beverage, containing a flavored noncaloric placebo, or oneof the four doses of whey protein concentrate (10 g, 20 g, 30 g, or 40 g).

Figure 2: Intramuscular amino acids. This figure is a heat map which shows groups means fold changes from the resting fasted condition. Green represents a decrease in amino acid content, white represents no change, and red represents an increase in amino acid content (D’Souza. 2014)

Subjects were instructed to ingest the beverage within 2 min and were required to ingest the total volume provided. Following consumption of the supplements, subjects rested in a supine position throughout the 4 h of post-exercise recovery with additional muscle biopsy samples collected at 2 and 4 h post exercise.

Figure 3: Higher protein intake = higher increase in p70S6K phosphorylation (left graph). This increase is linearly associated with intramuscular leucine levels (right graph | both from D’Souza. 2014)

As you can see in Figure 3, there was a similar dose-dependent increase in p70S6K as it was observed previously for MPS in skeletal muscle of elderly subjects by Yang et al. (2012b). In fact, the fold change in the phosphorylation of p70S6K (Thr389) at 2 h post exercise was correlated with the dose of whey protein consumed (r =0.51,P<001) and was found to be significantly correlated with intramuscular leucine content (r =0.32,P=0.026).

Moreover, the intramuscular BCAAs, and leucine in particular, appear to be important regulators of anabolic signaling in aged human muscle during post-exercise recovery via reversal of exercise-induced declines in intramuscular BCAAs.

Suggested Read: "Protein Timing Does Matter! Yet Only in Trained Men. More Than 2x Higher Relative Protein Retention W/ Immediate vs. 6h Post Whey Consumption in Bodybuilders vs. Rookies" | read more.

Bottom line: In the absence of a young control group and actual muscle protein synthesis (MPS) measurement, the study at hand cannot finally answer the question, whether older men require higher amounts of protein than young ones to achieve maximal increases in post-workout protein synthesis, but it is at least another piece of evidence that "more helps more" - at least in the elderly.

As mentioned in other recent posts, there are yet still many confounding variables that would have to be controlled and modified as well to answer the important (?) question: "How much protein does it take to achieve maximal post-workout protein synthesis?" Which confounding factors that would be? Well, what about the training experience? The baseline muscle mass? The protein content of the diet? And so on and so forth || Comment on Facebook!

References:

• Burd, N. A., S. H. Gorissen, and L. J. van Loon. 2013.  Anabolic resistance of muscle protein synthesis with aging. Exerc. Sport Sci. Rev. 41:169–173.
• Churchward-Venne, T. A., N. A. Burd, C. J. Mitchell, D. W. West, A. Philp, G. R. Marcotte, et al. 2012. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J. Physiol. 590:2751–2765.
• D'Souza, Randall F., et al. 2014. Dose‐dependent increases in p70S6K phosphorylation and intramuscular branched‐chain amino acids in older men following resistance exercise and protein intake. Physiological Reports 2.8: e12112.
• Churchward-Venne, T. A., L. Breen, and S. M. Phillips. 2013a. Alterations in human muscle protein metabolism with aging: protein and exercise as countermeasures to offset sarcopenia. BioFactors 40:199–205.
• Churchward-Venne, T. A., C. H. Murphy, T. M. Longland, and S. M. Phillips. 2013b. Role of protein and amino acids in promoting lean mass accretion with resistance exercise
  and attenuating lean mass loss during energy deficit in humans. Amino Acids 45:231–240.
• Churchward-Venne, T. A., L. Breen, D. M. Di Donato, A. J. Hector, C. J. Mitchell, D. R. Moore, et al. 2014. Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial.
  Am. J. Clin. Nutr. 99:276–286.
• Cuthbertson, D., K. Smith, J. Babraj, G. Leese, T. Waddell, P. Atherton, et al. 2005. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J. 19:422–424.
• Moore, D. R., M. J. Robinson, J. L. Fry, J. E. Tang, E. I. Glover, S. B. Wilkinson, et al. 2009. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am. J. Clin. Nutr. 89:161–168.
• West, D. W., and K. Baar. 2013. May the Force move you: TSC-ing the mechanical activation of mTOR. J. Physiol. 591:4369–4370.
• West, D. W., N. A. Burd, J. E. Tang, D. R. Moore, A. W. Staples, A. M. Holwerda, et al. 2009a. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors. J. Appl. Physiol. 108:60–67 .
• West, D. W., G. W. Kujbida, D. R. Moore, P. Atherton, N. A. Burd, J. P. Padzik, et al. 2009b. Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men. J. Physiol. 587:5239–5247.
• Witard, O. C., S. R. Jackman, L. Breen, K. Smith, A. Selby, and K. D. Tipton. 2014. Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. Am. J. Clin. Nutr. 99:86–95
• Yang, Y., L. Breen, N. A. Burd, A. J. Hector, T. A. Churchward-Venne, A. R. Josse, et al. 2012a. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br. J. Nutr. 108:1780–1788.
• Yang, Y., T. A. Churchward-Venne, N. A. Burd, L. Breen, M. A. Tarnopolsky, and S. M. Phillips. 2012b. Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men. Nutr. Metab. 9:57.

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

I've heard rumors about people who get pumped, just to look pumped ;-)

I guess many of you will already have read Brad J. Schoenfeld's and Bret Contreras' latest review on "the pump"? I know for sure that Jakob read it, because he messaged me on December 29 that is was available for download over at the website of the Strength and Conditioning Journal. What he could not know, though was that I had already downloaded and read the article, when Brad and Bret, who are unquestionable two of the go-to resources for everyone who wants to learn something about the science of "getting big, lean and strong" posted the link on Facebook on December 28 (go to the original post). This link will take you to a downloadable ~2000 word paper in the conclusion of which you will find the following statement:

"[...] it is likely that exercise centered on achieving a “pump” through higher repetition sets combined with shorter rest periods also provides a potent hypertrophic stimulus that is synergistic to heavy compound lifting." (my emphasis in Schoenfeld. 2013)

In view of the fact that this excerpt summarizes the main information the paper provides excellently, I am not going to ruminate Brad's & Bret's overview of the few studies that allow for relevant and at least to some extend reliable conclusions about the real-world effects of the pump and its significance for someone whose main interest is in building size, not strength (just read the review, if you want the details).

There is something about the pump the review doesn't discuss, though

Don't worry, it's not as if Brad and Bret had overlooked the latest paper M.S Kristiansen and his colleagues from the Institute of Sports Medicine, the Section of Sports Science at the Universities of Copenhagen and Aarhus. Rather than that, the paper with the intriguing title "Concomitant changes in cross-sectional area and water content inskeletal muscle after resistance exercise" had (a) not even been published, when they the two were doing the research for their review and is (b) as we are going to see not 100% relevant to the question, whether the pump does or doesn't promote muscle growth.

Collagen loss and (super-)compensation occur in the early and late phase of the post-exercise period. If you don't want to risk injury or chronic overuse, you better remember this whenever you're working on a new workout schedule.

Does exercise also influence the water content of the tendons? In contrast to its effects on the intra-muscular water content the 3-EX regimen in the study at hand lead to "a decrease in the CSA of the central part of the PT [patella tendon]" within the first 52 h post exercise. "A concomitant increase in the water content of the tendon could not be demonstrated, though." (Kristiansen. 2013). Based on the absence of an overall decrease in water content, Kristiansen et al. speculate that previously observed decreases in tendon size (Miller. 2005; Tardioli. 2012) could have been brought up by a net loss of collagen during the early restructuring processes after heavy workouts.

Since the rate of collagen synthesis is negligible within the first 36h after exercise "the breakdown of the tissue driven by catabolic processes [...] may exceed the synthesis" that peaks after 72 h, "if multiple training sessions are too close to one another" (Kristiansen. 2013). The consequences? Acute injuries and / or chronic overuse.

Suggested Read: "Why training over the full ROM counts" | more

Now you may be asking yourselves why the results Kristiansen et al. are about to present in one of the upcoming issues of the Scandinavian Journal of Medicine & Science in Sport still made it into the SuppVersity News, if they don't provide any new insights into the contribution of the pump to skeletal muscle hypertrophy. The answer is simple: They do tell us something that puts a huge "?" behind the results of a whole host of studies on skeletal muscle hypertrophy. Something the average "disco pumper", i.e. a person who works out a couple of hours before he hits the Saturday night life to make sure that his muscles are big and full, knew for years: Your muscle size remains significantly elevated for hours even after comparatively low volume workouts.

What the average disco pumper probably didn't know, though....

... is that the water-induced cell-swelling peaks not 4h after the workout, but actually 52h after the last workout. That's probably good news for everyone who hates being wiped from the afternoon workout, when he is trying to get off with the girls on the dance floor. For the average scientist, on the other hand, that's seriously bad news. He or she has after all made a habit of ignoring the difference between muscle gains and water gains in his / her studies, whenever the measured muscle circumferences support his / her research hypothesis. In other words, until now nobody actually payed attention to the fact that what he / she measured on day 1 after the last workout of an 8 week study may be influenced to a large extend by the last and to a minimal extend by all previous workouts. It's thus totally correct that Kristiansen et al. demand that ...

"[...] post-training changes in CSA [cross sectional area] should be interpreted with caution, as they may adhere to exercise-induced water retention resulting from the last exercise bout." (Kristiansen. 2013)

In view of the fact that few researchers have hitherto exercised the said "necessary caution", it  appears to be more or less certain that a non-negligible proportion of the currently available data on skeletal muscle hypertrophy in training noobs such as Kristiansen et al.'s  ten healthy untrained study participants would have to be revised or at least tested.

Figure 1: 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 (Kristiansen. 2013)

What's good though, is that it appears reasonable to assume that the cell swelling will be particularly pronounced, when the muscle is exposed to a new training stimulus (just like the DOMS, by the way; learn more) . This, in turn, would mean that the Kristiansen's one (1EX) and three (3EX) training day intervention  consisting of ...

• 2 min recovery between sets, 5 min between exercises
• verbal encouragement during all sessions
• total workout time ca. 45min

• 5 min warm up on a cycle ergometer
• 1x warm up set (5 reps; 50-60% 1RM) for the randomly selected working leg
• 5 sets of single-legged leg presses and knee extensions per workout
• 10 reps at an intensity of 10RM per set

... would probably have different effects in trained and highly trained individuals. Data form one of the few studies with "non-rookie" (aka "recreationally active") subjects does therefore have a much lower chance of having a measuring bias than data from studies with strength training novices. For those, the results of the Kristiansen study could mean that the real-world hypertrophy effects have been largely overestimated.

Figure 2: Schematic depictions and actual axial scan of the M. Quadriceps (Kristiansen. 2013)

Not convinced? Well, you cannot tell me that you actually believe that a single leg workout will increase the actual muscle size in the "teardrop zone" of the quads (see anatomical chart at the top in figure 2) of any trainee - rookie or not - by 16%, right (see figure 1)? I see no one is shaking his / her head.... well, then what do you think: How many researchers waited for a 3 full days or better a whole week after the last workout before they sent their subjects to the magnetic resonance imaging (MRI) device to obtain axial scans such as the one in Figure 2?

I have to admit that I haven't been paying much attention to the time-lag between the last workout and the MRI or measuring tape "powered" assessment of the post-intervention muscle circumference, but I am still convinced that it will be very difficult to find any study, where the post-values were taken more than 54h after the workout.

We must not forget, though that (1) the cellular hydration state is among the fundamental determinants of protein catabolism in health and disease (Häussinger. 1993), that (2) Basco et al. were able to show that the AQP4-dependent water transport into the muscle supports both, muscle contractile activity and metabolic changes that occur in fast-twitch skeletal muscle during prolonged exercise (Basco. 2013), and that (3) Brad & Brent's review clearly suggests that the exercise induced cell swelling has a facilitative role in skeletal muscle hypertrophy.

Bottom line: If we also take into account that the vast majority of studies will use the 10cm point (see figure 2, left) to quantify the increase in muscle size, it is well possible that the average resistance training study could have overestimated the hypertrophy effect of the corresponding training (and supplementation!) regimen in novice or "recreationally trained" study participants.

In view of the fact, that very few of the studies had a duration of only three training sessions (1-2 weeks) and against the background that the multiple training sessions in studies with durations of 2-12 weeks will accustom the muscle to the previously novel stimulus, I would yet not go so far as to say that the results of the average study could be up to 10% off... I do, on the other hand, have my doubts that all the hitherto reported increases in muscle size would retain a p-value of p < 0.05 and would thus have to be considered as "statistically significant", if the CSA measurements had been taken 7days+ after the last training session.

References:

• Basco, D., Blaauw, B., Pisani, F., Sparaneo, A., Nicchia, G. P., Mola, M. G., ... & Frigeri, A. (2013). AQP4-Dependent Water Transport Plays a Functional Role in Exercise-Induced Skeletal Muscle Adaptations. PloS one, 8(3), e58712. 
• Miller, B. F., Olesen, J. L., Hansen, M., Døssing, S., Crameri, R. M., Welling, R. J., ... & Rennie, M. J. (2005). Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise. The Journal of physiology, 567(3), 1021-1033.
• Schoenfeld, B. J., & Contreras, B. (2013). The Muscle Pump: Potential Mechanisms and Applications for Enhancing Hypertrophic Adaptations. Strength & Conditioning Journal. 
• Tardioli, A., Malliaras, P., & Maffulli, N. (2012). Immediate and short-term effects of exercise on tendon structure: biochemical, biomechanical and imaging responses. British medical bulletin, 103(1), 169-202.

Study Confirms: Acute Post-Exercise Myofibrillar Protein Synthesis Is Not Correlated with Resistance Training-Induced Muscle Hypertrophy in Young Men

FSR ≠ more muscle = no news for ya!

For the average SuppVersity reader the sentence "Acute Post-Exercise Myofibrillar Protein Synthesis Is Not Correlated with Resistance Training-Induced Muscle Hypertrophy in Young Men" is not just the title of a recent paper in the open access journal PLOS|ONE, it's also the experimental verification of a claim I've made in almost all my articles about the acute effects of certain training modalities and/or supplements on myofibrillar protein synthesis and the corresponding increases in muscle size some people appear to expect from a 2h-long 10% increase in fractional protein synthesis (learn more).

And yes, practically speaking these findings imply that we have to question the real world significance of all the neat studies on the "superior muscle building effects" of whey protein, BCAAs and even more so leucine, in which the authors base their recommendations on acute increases in post-exercise protein synthesis.

Don't worry, you have not been "wheysting" your money: While there is a paucity of data to confirm the long(er) term muscle building effects of isolated amino acids (EAA, BCAA and leucine), there is plenty of data from 6-12 week human trials to support the pro-anabolic effects of whey protein. What we don't have, though is evidence to support the notion that the long-term muscle building effects are as superior to those of other protein sources (e.g. casein) as the increases in acute protein synthesis would suggest.

In the corresponding experiment that was funded by the National Science and Engineering Research Council (NSERC) of Canada Cameron J. Mitchell et al. determined whether the acute myofibrillar protein synthesis measured acutely in training-naive subjects after their first bout of resistance exercise with protein consumption would correlate with the actual increase in muscle size after 16 weeks of resistance training.

Suggested read: "Protein Intake & Muscle Catabolism: Fasting Gnaws on Your Muscle Tissue and Abundance Causes Wastefulness " | more

Before the actual experiment began, the subjects, healthy young recreationally active normal-weight men (177 cm; body mass index = 26.4 kg/m²; men age 22 years) without previous strength training experience, underwent a magnetic resonance imagining (MRI) scans of their right thigh to determine muscle volume, a dual, energy x-ray absorptiometry (DXA) scan to assess whole body fat and bone-free mass (lean mass) and standardized strength tests to determine their maximal isotonic strength (often labeled the 1RM) for all training exercises.

After all baseline measurements (including baseline muscle protein synthesis) were recorded, the subjects completed 16 weeks of RT while ingesting a protein rich beverage (30g of the same whey protein of which Burd et al. showed in 2012 that it elicits a higher increase in MPS than casein) immediately after their exercise session and with breakfast on non-training days.

"Briefly, participants trained four times weekly with two upper and two lower body workouts. Lower body exercises are described above in the acute exercise session. Upper body exercises consisted of chest press, shoulder press, seated row, lat pulldown, bicep curl and tricep extension. The program was progressive in linear manner moving from 3 sets of 12 repetitions to 4 sets of 6  repetitions. At the end of the training period, MRI, DXA scans and strength testing were repeated." (Mitchell. 2014)

If you look at the above description of the workout (and supplementation regimen) you will probably agree that this is pretty much what the majority of resistance physique oriented gym-goers do.

Figure 1: Myofibrillar fractional protein synthesis rate (left) measured acutely after a single workout and changes in muscle volume (%) over the whole 16-week study period as a function of the 1-6h post-workout FSR (Mitchell. 2014).

People who hope that the often reported increases in fractional protein synthesis would pay off and yield increased net muscle gains and thus exactly what Mitchell et al. did not observe in their study, which could not establish the corresponding correlation between the actute increase in post-workout fractional protein synthesis (Figure 1, left) and the chronic change in muscle volume (Figure 1, right).

Figure 2: Changes in muscle volume (%) expressed relative to acute increases in 4E-BP (Mitchell. 2014).

If anything, it was the expression of the Eukaryotic translation initiation factor 4E-binding protein 1 aka 4E-BP1 one of the motors of protein synthesis, but not the increase in myofibrillar fractional protein synthesis that looked as if it could have any predictive value with respect to the increase in muscle volume, the young men experienced in the course of the 16-week training period.

After thinking about the implications of these findings for a minute, I do yet have to admit that the assumption that this would refute the previously invoked recommendations completely, is probably premature.

SuppVersity Suggested Read: "Protein Wheysting?! No Significant Increase in PWO Protein Synthesis W/ 40g vs. 20g Whey, But 100% Higher Insulin, 340% More Urea & 52x Higher Oxidative Amino Acid "Loss" | more

"Though shalt not make quantitative predictions about long(er) term muscle gains based on acute FSR measurements!" - This statement is unquestionably correct. It's something I have written about before and it's a statement that is supported (if not confirmed) by the data of the study at hand.

The statement "though shalt not make qualitative predictions about long(er) term muscle gains based on acute FSR measurements", on the other hand, would yet be unwarranted and is probably incorrect. We do after all have more than enough evidence that increases in post-workout protein synthesis will (sooner or later) result increases in muscle size. The fact that we cannot predict the extent of long(er) term hypertophy effects based on measuring acute changes in FSR does not imply that these changes would not matter at all. It does only mean that we have to be careful about overestimating the real-world effects of differences in protein synthesis between training modalities and supplements, even if they are statistically significant in the hours after a workout.

Reference:

• Burd, Nicholas A., et al. "Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men." British Journal of Nutrition 108.06 (2012): 958-962.

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.

Exercise Quickie: HIIT as 24h+ Muscle Builder for the Elderly | Caffeine Without Ergogenic Effects on Biceps Curls

Caffeine won't do the "last rep" for ya.

Time for a brief review of the latest exercise and supplementation science in the SuppVersity Short News. You can see an overview of all previous articles in an RSS feed here.

This time you can take a look at the surprisingly lasting pro-anabolic effects of HIIT as measured by skeletal muscle protein synthesis in the elderly and the similarly surprising finding that caffeine - even if it's consumed in significant doses before a workout - will not have you curl an extra pound on either barbell or dumbbell curls.

Read more short news at the SuppVersity

Exercise Research Uptake Nov '14 1/2

Exercise Research Uptake Nov '14 2/2

Weight Loss Supplements Exposed

Exercise Supplementation Quickie

Exercise Research Uptake Jan 12, 2015

Read the Latest Ex. Science Update

• 27% increase in protein synthesis even 24h after HIIT exercise in the elderly - Resistance exercise (RE) and aerobic exercise are recommended for older adults for fitness and strength. High-intensity interval exercise (HIIT) is an understudied but potent potential alternative to aerobic exercise. A recent study from the McMaster University aimed to determine how each mode of exercise affected the integrated day-to-day response of muscle protein synthesis.
  
  To do so, they recruited 22 sedentary men (mean age = 22; 67±4 years; body mass index: 27.0±2.6 kg m- 2 [mean ± SEM]) who were randomly assigned to perform resistance training, aerobic exercise, or HIIT. The participants consumed a stable isotope tracer (D2O) for 9 days. Daily saliva samples were taken to measure tracer incorporation in body water. Muscle biopsies were obtained on Days 5-8 of D2O consumption to measure tracer incorporation into muscle at rest, 24 hours, and 48 hours following each exercise bout: RE (3 × 10 repetitions: leg extensor and press, 95% 10RM), HIIT (10 × 1 minute, 95% maximal heart rate [HRmax]), or aerobic exercise (30 minutes, 55%-60% HRmax).
  

  

  Figure 1: Myofirillar (left) and sarcoplasmic (right) protein fractional synthesis rate (FSR) at baseline and postexercise. Data are means ± SEM. Bars bearing different letters are signifiantly different within each exercise group | AE = aerobic exercise; HIIT = high-intensity interval exercise; RE = resistance exercise (Bell. 2015).

  What the scientists found is quite surprising: While resistance training showed, as it was expected, the greatest increase in fractional protein synthesis immediately, post workout, only the HIIT protocol lead do significant increases in sarcoplasmic protein fractional synthetic rate 24-hour postexercise (2.30±0.34% d- 1 vs 1.83±0.21% d- 1).
  
  That does not mean that HIIT is the better muscle builder, though. Specifically in view of the fact that it's the myofibrilar, not the sarcoplasmic protein synthesis rate that bunks with aging (Balagopal. 1997), the higher myofibrilar post-workout protein synthesis after the relatively low volume resistance training session is more important than the long-lasting elevation of the protein influx into the sarcoplasma, a muscle protein fraction that is involved in the anaerobic ATP production, intracellular transport, and several other enzyme functions. 
• Stronger biceps with caffeine? No, ... at least during insometric contractions the administration of 5 mg/kg and 10 mg/kg caffeine does not have ergogenic effects on the elbow flexors.
  That's at least what the latest study from the University of Kansas shows. In their 13 recreationally trained male subjects, the ingestion of the aforementioned amounts of caffeine in form of of a caffeineated drink did not lead to significant increases in any of the relevant performance markers.
  

  

  Figure 2: Caffeine did not have significant ergogenic effects; at least the rate of torque development did increase, though (Trevino. 2015).

  In contrast to previous research which has indicated that under certain conditions, caffeine may increase muscle force production during anaerobic activities (3,6,15,17). The results of our study revealed that caffeine did not significantly affect peak torque during the maximal isometric contractions. As Trevino et al. point out, this finding may result from a variety of factors:

  

  Figure 3: In contrast to the study at hand a study by Beck et al. found significant increases in bench press performance in slightly better trained subjects (Beck. 2006).

  "Past equivocal findings with caffeine ingestion and anaerobic performance may have resulted from the type of muscle action and exercise performed, caffeine dose used, muscle group tested, or training status of the subjects. Our protocol used a single-joint isometric exercise to test the effects of caffeine doses of 5 and 10 mg/kg of body mass on maximal strength of the elbow flexors in resistance trained males (participating in at least 2 training sessions per week). Beck et al. (2006) reported that a 201 mg dose of caffeine significantly increased bench press 1RM in resistance trained males (participating in at least 4 training sessions/week). 

  Because significant results were found with a caffeine dose less than ours (average absolute doses in the current study were 426.7 and 853.4 mg for the 0 and 5 mg/ kg body mass conditions, respectively), it seems that the exercise test and training status may have led to different findings between the studies" (Trevino. 2015).

  Next to the training status and the lack of familiarity with performing maximal muscle contrations (the subjects in Beck et al. (2006) trained 4 times per week, the ones in the study at hand only two times), the exercise may play a role as well. The bench press is after all a multi-joint exercise requiring dynamic involvement of the pectoralis major, deltoid, and triceps. The biceps curl, on the other hand is the classic single-joint exercise, where the CNS activating effect of caffeine may simply offer less benefits than on bench presses, squats and other multi-joint exercises. The same may be true for comparisons of large and small muscle groups and could explain why Astorino et al. (2010), Jacobson, et al. (1992) and Kalmar et al. (1999) found beneficial effect of caffeine on the leg extension performance of their subjects, while Trevino et al. were not able to detect ergogenic effects for the small elbow flexors.

The Latest on Caffeine, Exercise, Fat & Weight Loss - Increased Performance, Energy Expenditure (6%) & Fatty Acid Oxidation (27%) vs. Decreased Sleep Quality & Burnout | Learn how caffeine can benefit your exercise performance and energy expenditure and how much caffeine is too much caffeine in a recent SuppVersity article.

Bottom line: Let me make this clear. Neither of the two studies refutes any of the given truths of strength training and muscle building. The Bell study does in fact confirm that resistance training triggers the most pronounced increases in skeletal muscle protein synthesis - the fact that HIIT may have longer lasting overall effects, specifically in the sarcoplasmic protein fraction, is nice, but its practical relevance is highly questionable.

Similarly, the study by Trevino et al. which shows minimal, but non-significant beneficial effects of caffeine on the elbow flexors does not negate the many previously established beneficial effects of caffeine supplements on exercise performance. What it does, however, is to remind us that it is not possible to transfer the results obtained in one group of trainees on one particular muscle group 1:1 to another group of trainees and/or another muscle group | Comment on Facebook!

References

• Astorino, Todd A., et al. "Effect of two doses of caffeine on muscular function during isokinetic exercise." Medicine and science in sports and exercise 42.12 (2010): 2205-2210.
• Balagopal, P., et al. "Effects of aging on in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans." American Journal of Physiology-Endocrinology And Metabolism 273.4 (1997): E790-E800.
• Beck, Travis W., et al. "The acute effects of a caffeine-containing supplement on strength, muscular endurance, and anaerobic capabilities." The Journal of Strength & Conditioning Research 20.3 (2006): 506-510.
• Bell et al. "Day-to-Day Changes in Muscle Protein Synthesis in Recovery From Resistance, Aerobic, and High-Intensity Interval Exercise in Older Men." J Gerontol A Biol Sci Med Sci (2015). 
• Jacobson, B. H., et al. "Effect of caffeine on maximal strength and power in élite male athletes." British journal of sports medicine 26.4 (1992): 276-280.
• Kalmar, J. M., and E. Cafarelli. "Effects of caffeine on neuromuscular function." Journal of Applied Physiology 87.2 (1999): 801-808.
• Trevino, Michael A., et al. "Acute Effects of Caffeine on Strength and Muscle Activation of the Elbow Flexors." The Journal of Strength & Conditioning Research 29.2 (2015): 513-520.