Extra Protein = Only Marginal Extra-Gains, No Special Effect on Muscle Architecture | Plus: Blend Beats Whey, Again

No, the message of this article is not that protein shakes don't work. It is that your (hopefully) tasty 20g of serving of whey is not going to build slabs of extra muscle.
You all know studies which show that protein supplementation during resistance exercise training enhances muscle hypertrophy. As a SuppVersity reader, you will yet also be aware of the numerous studies which indicate that extra-protein (before or after workouts) can be wasted if the baseline protein intake of the subjects amounts to 1.2-1.5g/kg protein, already (cf Table 1).

For some of you, this is yet probably not the only surprise this article holds. The large-scale clinical trial by Reidy, et al. did after all also confirm that protein blends may yield slightly better results than everyone's beloved whey protein.
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In their large-scale clinical trial (cf. Reidy 2016a,b), the scientists from Texas broadened the scope of their analysis of the effects of a 12-week resistance training program from mere changes in body composition to measures of individual and myofiber-specific cross-sectional area increases, satellite cell numbers and the extent to which the muscle domains multiplied by myonuclear addition (that's important for continuous gains).
Figure 1: CONSORT (Consolidated Standards of Reporting Trials) diagram of study recruitment, enrollment, randomization follow-up, and analysis (from Reidy 2016b).
To this ends, Reidy et al. recruited 70 subjects (of which 58 completed the study;  the participants were healthy and recreationally active but were not engaged in any regular exercise-training program in form of <2 sessions high-intensity aerobic or resistance exercise/wk at the time of enrollment) who participated in a supervised whole body progressive resistance training program thrice a week for 12 weeks. With a habitual protein intake of ~1.3g/kg body weight, all subjects were "in the zone", i.e. within the perimeter of which previous studies show that it's enough to reduce, if not nullify the benefits of post-workout protein supplementation.
Figure 2: Schematic of the resistance exercise training protocol (Reidy. 2016b)
All subjects underwent the same standardized resistance training program (see Figure 2): All exercise training sessions were performed under supervision and on non-consecutive days, 3 times weekly, with 4 rest days per week.
"RET was performed at an intensity of 60-80% of 1-repetition maximum (1-RM) and consisted of 3-4 sets of 8-10 repetitions performed to technical failure during the last set for each exercise.  In week 1, 3 sessions were conducted at 3 sets of 10 repetitions at 60% 1-RM.  In weeks 1-8, 2 sessions per week were performed at an intensity of 70% 1-RM, where 3 sets of 10 repetitions were the last set was performed to momentary muscular failure.  Each session consisted of whole body resistance exercise that lasted ~60-70 min. To reduce the risk of injury and overtraining, one additional training session per week was conducted at 3 sets of 10 repetitions at 60% 1RM with the goal of not reaching momentary muscular failure.  These sessions took place immediately before and after the 1-RM training days.  In weeks 9-12, 2 sessions per week were performed at an intensity of 80% 1-RM, where 4 sets of 8 repetitions were performed to momentary muscular failure. The 3rd session was performed at an intensity of 60% 1-RM as indicated earlier.   Each session consisted of whole body resistance exercise that lasted ~70-90 min. Resistance exercises included flat and incline chest press; leg press, curl and extension; seated pull-downs and rows; calf raises; and abdominal exercises.  Participants rested for 1-2 minutes between exercises and individuals sets.  1-RM was directly tested on the chest press, leg press and knee extension" (Reidy 2016b).  
Participants were allowed to maintain their recreational physical activity but instructed not to do any other strength training outside of the study. To allow for unforeseen life events, participants were given 13 weeks following the familiarization period to complete 36 exercise sessions. This allowed for 100% exercise compliance.
Table 1: Summary of all protein supplement studies with a placebo group directly assessing muscle mass during RET in young adults (Reidy 2017).
Are DXA-measured lean mass gains in this and other studies misleading? As Reidy et al. point out in the discussion of the results, you'd need ~62 to ~140 participants "to find a statistical effect of protein supplementation on whole body lean mass or fat-free mass" - most of the existing trials don't have that many subjects (cf. Reidy 2016a,b). In addition, Reidy's very own study shows that despite an (almost) statistically significant increase in lean mass, an increase in local muscle hypertrophy, as measured by ultrasound in the legs, could not be established. In fact, the increase in lean mass the DEXA scan detected could have occurred everywhere and it's by no means certain that it took place in those areas of the upper body and arms where you want your gains to become visible.
On top of their habitually "high" protein intake (101-108g/day and 102-113g/day in the protein blend and whey group, respectively), all subjects were randomized to receive either one out of two daily 22g protein supplements containing ...
  • a soy-dairy protein blend (PB, N=22) - 25% soy protein isolate, 25% whey protein isolate, and 50% sodium caseinate,2.00 g leucine from the three protein sources
  • a whey protein isolate (WP, N=15) - 100% whey protein isolate, 2.31g leucine from whey 
... or an isocaloric maltodextrin and otherwise identical placebo (MDP, N=17) supplement. In view of the results, it may be worth noting that this left the subjects in the placebo group (MDP), who also had the lowest dietary protein intake (95g/day), with ~30g protein less those in the other groups.
Figure 3: While the scientists recorded sign. increases in muscle thickness in the subjects' vastus intermedius, these changes, however, were - within statistical margins - identical for all trials (Reidy 2016b).
Nevertheless, there were no significant differences in either of the main research outcomes, i.e. the lean mass (DXA data), vastus lateralis myofiber-type-specific cross-sectional-area, satellite cell content and myonuclear addition, which were assessed pre and post-resistance training. A closer analysis of the data reveals:
  • Table 2: Total energy and macronutrient intake during the study (from Reidy 2016b, which is the large clinical of which the study at hand is a subset)
    the soy-blend with its fast-to-slow digesting mix of 25% soy protein isolate, 25% whey protein isolate, and 50% sodium caseinate yielded the most sign. gains in lean body mass (p = 0.057 for PB), 
  • adding protein, in general, i.e. pooling the results from PB and WP to PRO, increased the statistical sign. of the lean mass benefit to p = 0.050 (no sign. difference to MPB, still),
  • despite the previously hinted at advantage of the blend, significant inter-group differences for soy-blend vs. whey were not observed for any of the parameters
Very similar observations had been made in the 2016(b) paper on this large-scale clinical trial, in which the scientists didn't find significant treatment effects (see TRT in Figure 4) of either of the protein supplements on DXA measures increases in lean body mass or lean arm mass.
Figure 4: Upon closer scrutiny, the lean mass data reveals a non-sign. advantage for the protein blend (Reidy 2016b).
Against that background, it will probably not surprise you that, again on a treatment basis (no pooling of the two protein groups), no differences were reported for the separately measured leg muscle hypertrophy and vastus lateralis myofiber-type-specific cross-sectional-area (P<0.05 | not shown in any figure) in the latest follow-up (Reidy 2017).
But what about the "more helps more" studies by Antonio et al.? I have to admit that I cannot fully explain why Jose Antonio and colleagues saw much more significant increases in muscle gains in their often-cited study. It could be that this is a methodological issue Reidy et al. address in their discussion of the results with the increases in total lean mass measured by DXA being sign. more pronounced than the actual changes in muscle cross-sectional area (compare box in the bottom line of this article), which were not measured in the 2014 study by Antonio et al. On the other hand, it is likewise possible that it's simply a question of the amount of protein that's supplemented. In the three-year-old study that was enough to bump the subject's protein intake to 4.4g/kg body weight. Anyway... Antonio's observations do not refute the conclusion that a single protein shake won't do the muscle-building magic you're promised on the labels of the bazillion of different protein products on the market.
Similarly, no treatment effects, i.e. effects due to a certain protein powder, were detected for the albeit highly significant training-induced changes in myosin heavy chain I and II myofiber satellite cell content and myonuclei content (P<0.05).
Figure 5: Change in the relative frequency of larger vastus lateralis MHC II myofibers. Protein blend (PB) or whey protein (WP) or maltodextrin placebo (MDP). Data are mean ± SEM. TRT, treatment (Reidy 2017).
Only when the scientists pooled the results of the two protein groups, they found a non-significant and very modest effect of protein supplementation on the increase in MHC I satellite cell content, isokinetic torque and a slight expansion of a greater proportion of larger MHC II fibers over placebo after resistance exercise training - a "benefit" that is nothing like those you'd expect if you read the grandiose promises in the shiny advertisements of the supplement industry.
Brainwashed by shiny ads, people tend to overesti-mate the benefits of protein supps: Reidy et al. make a valid point, when they write that "[c]ontrary to popu-lar dogma, it is not unusual to observe no effect of protein supplements, in particular, whey protein, over placebo on lean mass or myofiber CSA." The authors further point out that they "are aware of only 3 studies demonstra-ting greater changes in vastus lateralis myofiber CSA and 2 studies with magnetic resonance imaging (MRI) comparing protein versus carbohydrate placebo supp-lementation during RET" (Redy 2017). Similarly dis-appointing are the results of most studies that investiga-ted the vastus lateralis myofi-ber CSA in protein supple-mented subjects on protein-adequate diets. And that's no leg-specific result, as Reidy et al. highlight: "Studies utili-zing MRI of the biceps or la-tissimus dorsi and ultrasound of the thigh muscles have clearly shown the same pattern" (Reidy 2017). A simple measuring tape may thus indeed yield more relevant results than DEXA.
So what does all that tell me? Well, I guess the first thing you have to admit to yourself is that you're expecting whey... ah, I mean, way too much from your protein powder. As Reidy et al. point out "[p]rotein supplementation during resistance training has [only] a modest effect on whole body lean mass as compared to exercise training without protein supplementation" - especially if you have a relatively high (1.2g/kg or more) baseline protein intake.

Furthermore, the study, or rather the set of papers on this uniquely large clinical trial, should remind you of the potential benefits of protein blends. Why? Well, previous studies suggest that the combination of fast and slow proteins will provide for a more sustained and eventually more anabolic state of hyperamino-acidemia compared to fast-digesting proteins like whey protein isolate, alone. That this benefit was only small in the study at hand could be a mere result of the fact that a truly slow digesting source was missing from the protein blend (sodium caseinate contains no intact micelles and is digested much faster than micellar casein).

All that doesn't render protein supplements useless, but it emphasizes that protein is mostly the fuel for hypertrophy - not more, but also not less. Its provision can increase the storage of muscle protein but it will, as the large-scale clinical trial at hand has shown quite conclusively, not "enhance resistance exercise-induced increases in myofiber hypertrophy, satellite cell content or myonuclear addition in young healthy men" (Reidy 2017), significantly. Is that surprising? Well at least for the structural parameters it isn't as discussed in the "Intermittent Thoughts on Building Muscle" (see conclusion + article overview) the latter are not directly affected by mTOR and other signaling proteins an increased protein intake would affect. And if you still believed that the post-workout shake of yours would add another inch to your biceps every two weeks, you cannot be helped, anyway | Comment!
  • Antonio, Jose, et al. "The effects of consuming a high protein diet (4.4 g/kg/d) on body composition in resistance-trained individuals." Journal of the International Society of Sports Nutrition 11.1 (2014): 19.
  • Reidy, Paul T., et al. "Protein supplementation has minimal effects on muscle adaptations during resistance exercise training in young men: A double-blind randomized clinical trial." The Journal of nutrition 146.9 (2016a): 1660-1669.
  • Reidy, Paul T., and Blake B. Rasmussen. "Role of ingested amino acids and protein in the promotion of resistance exercise–induced muscle protein anabolism." The Journal of nutrition (2016b): jn203208.
  • Reidy, Paul T., et al. "Protein Supplementation Does Not Affect Myogenic Adaptations to Resistance Training." Medicine & Science in Sports & Exercise (2017).
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