Important Insights into Muscle Growth: Muscle Breakdown & Protein Synthesis Balance Determines Your Muscle Gains

Important Insights into Muscle Growth: Muscle Breakdown & Protein Synthesis Balance Determines Your Muscle Gains

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MyoPS - muscle damage = gainz - It's as easy as that, but this simple equation gets complicated by decreases in both...

You will remember from previous SuppVersity articles that the assumption that an acute increase in myofibrillar protein synthesis (MyoPS) you measure after a workout would necessarily translate into "muscle gains" is oversymplistic. In fact, a correlation between muscle hypertrophy and acute MPS has been shown not to exist (learn more).

In the introduction to their latest paper, Felipe Damas et al. (2016) highlight our lack of understanding of the different mechanisms that eventually determine t he hypertrophy response to resistance training.

If you want to build muscle you have to make sure to optimize your protein intake 

Protein Timing DOES Matter!

5x More Than the FDA Allows!

Protein requ. of athletes

High EAA protein for fat loss

Fast vs. slow protein

Whey vs. Pea Protein

To investigate how muscle hypertrophy is modulated through RT, Damas et al. "measured day-to-day integrated myofibrillar protein synthesis (MyoPS) using deuterium-oxide ingestion and assessed muscle damage at the beginning (T1), at 3wk (T2), and 10wk of RT (T3)" in a study that involved ten young men (27(1) y) who had muscle biopsies (vastus lateralis) taken to measure integrated MyoPS and muscle damage (Z-band streaming and indirect parameters) before and 24h and 48h post-resistance exercise (RE) at T1, T2 and T3.

Figure 1: Experimental design. RE: resistance exercise; D2O: deuterated water; MVC: maximal voluntary isometric torque; SOR: muscle soreness; T1: 1st week of resistance training (RT); T2: 3rd week of RT; T3: last week of RT (Damas. 2016).

The analysis of the data from the subjects who had prior experience in lower limb RT, before they trained their lower limbs (bilateral 45° leg-press exercise and leg extension) for 10 weeks in the study at hand (twice a week, totaling 19 workouts), but who had not engaged in lower limb RT for at least 6 months prior to the study and did not use vitamin supplements or anti-inflammatory medications chronically were recruited, provided some interesting insights.

Figure 2: Fibre cross-sectional area (CSA) at the first week (T1), third week (T2) and tenth week (T3) of resistance training. † Significantly different (P < 0.05) from T1 and T2. Values are means (SEM | Damas. 2016)

Firstly, there's the increase in fibre cross-sectional area, which was observed to be significant only when the scientists compared the fcsa at T3 compared with T1 (P =0.017) and T2 (P = 0.027; see Figure 2) - in other words: Significant gains were made only over the latter part of the training period.

Figure 3: (A) Myofibrillar (Myo) fractional synthetic rate (FSR) at rest, 24h and 48h following a single bout of resistance exercise at the first week (T1), third week (T2) and tenth week (T3) of resistance training. * Significantly different (P < 0.05) from rest at T1. # Main acute time effect (24h significantly different (P = 0.003) from 48h independent of training phase). ‡ Main training phase effect (T1 significantly different (P < 0.03) from T2 and T3). (B) Change from baseline in the percentage of fibres that showed any Zband streaming sign following a single bout of resistance exercise at the T1, T2 and T3. ‡ Significantly different (P < 0.05) from T2 and T3. + Significantly different (P < 0.05) from T3 (Damas. 2016).

These increases in the actual muscle size gains (vs. MyoPS) are the related to the second and most important observation, which is, as the highly significant decrease in Z-Band data in Figure 3.b indicates, a result of the improved difference between muscle protein synthesis, which decreased much less than the protein breakdown the scientists approximated by the means of directly assessed muscle ultrastructure changes (Z-band streaming). In other words: the "net gains" increased over time, as the subjects accommodated to the workouts.

In the previous study by Mitchell et al. (2014) there was no correlation between MyoPS / FSR andn the actual increase in muscle size over 16 weeks.

Bottom line: One thing that is important to highlight is the training status of the subjects of whom I previously pointed out that "had not engaged in lower limb RT for at least 6 months prior to the study" (Damas. 2016). This is important, because it is probably the prerequisite for the time-effect. A time effect which is characterized by (a) slightly decreasing protein synthesis from week one to week three (and following) and highly significantly decreasing muscle damage over the first 3 weeks, over which the muscle damage due to the initially unaccustomed exercise declined progressively.

Accordingly, Damas et al. were able to confirm a correlation between MyoPS, i.e. the myofibrillar protein synthesis, and the actual muscle hypertrophy that had not been observed by Mitchell, et al. (2014 | read up on the study in my previous article) only in the latter ~70% of the study when the net muscle gains increased due to the significant decrease in protein breakdown.

That the results of this study which are in disagreement with a previous studies that found "acute increases in MyoPS aligned qualitatively with hypertrophy-related chronic RT outcomes, such as increases in muscle volume and muscle fibre CSA (fCSA)" would be "due to damage to protein structures that would require repair, and therefore a greater increase in protein synthetic response" was the point of departure for Damas et al. in the study at hand. And it is also what the data the experiment generated confirmed: "Despite the lack of correlation between initial MyoPS and muscle hypertrophy, we observed that early (T2) and later (T3) rates of MyoPS, while attenuated compared to initial (T1), were strongly correlated with muscle hypertrophy" (Damas. 2016).

Another related and likewise important important finding of the study at hand is the observation that the subjects' muscle damage, on the other hand, "which was progressively mitigated throughout RT reaching a minimal magnitude at the end of 10wk of RT, did not correlate with MyoPS or hypertrophy at any time point during RT" (Damas. 2016). Eventually, the exercise induced increase in protein synthesis may thus still be considered the determinant factors underpinning RT-induced muscle hypertrophy in - as long, at least, as we are looking at trained subjects doing exercises they have already accommodated to (within ~3 weeks) | Comment on Facebook!

References:

• Damas, Felipe, et al. "Resistance training‐induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage." The Journal of physiology (2016).
• Mitchell, Cameron J., et al. "Acute post-exercise myofibrillar protein synthesis is not correlated with resistance training-induced muscle hypertrophy in young men." PLoS One 9.2 (2014): e89431.

Not Resting Long Enough May Ruin Your Gains! 1 vs. 5 min Cut Post-Workout Increase in Protein Synthesis by 50% !

Not Resting Long Enough May Ruin Your Gains! 1 vs. 5 min Cut Post-Workout Increase in Protein Synthesis by 50% !

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Rest is not a waste of time ;-)

You may remember Schoenfeld et al's 2015 study with the telling title "Longer inter-set rest periods enhance muscle strength and hypertrophy in resistance-trained men" (Schoenfeld. 2015) and Henselmann's and Schoenfeld's previous review of "The Effect of Inter-Set Rest Intervals on Resistance Exercise-Induced Muscle Hypertrophy" stating that "the literature does not support the hypothesis that training for muscle hypertrophy requires shorter rest intervals than training for strength development or that predetermined rest intervals are preferable to auto-regulated rest periods in this regard" (Henselmann. 2004).

Eventually, it can thus not be surprising that James McKendry and colleagues write in their latest paper that "short rest (1 min) between sets of moderate-intensity, high volume resistance exercise blunts the acute muscle anabolic response compared with a longer rest period (5 min), despite a superior circulating hormonal milieu," and conclude that their "data have important implications for the development of training regimens to maximize muscle hypertrophy" (McKendry).

Want to bump up the volume? Add bicarbonate as a pH-buffer to make that possible!

The Hazards of Acidosis

Build Bigger Legs W/ Bicarbonate

HIIT it Hard W/ NaCHO3

Creatine + BA = Perfect Match

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Beta Alanine Fails to HIIT Back

What may be surprising, though, is the extent (see Figure 2) to which the post-exercise protein synthesis the researchers measured in young male subjects who habitually performed lower-limb resistance training at least once per week for ≥1 year prior to study enrollment and were deemed ‘recreationally trained’, when they had them do the same leg workout

• 4 sets of leg press and 4 sets of knee extension exercise at 75% of 1RM
• performed w/ a lifting-lowering cadence of ~1 sec in both concentric & eccentric phases, 
• without pause, until momentary muscular failure (i.e. 9-10 on the Borg CR-10 scale). 

with either five minutes or one minute of passive rest between sets and gave them 25g of whey protein isolate (MyProtein, Cheshire, UK) right after the workout to kickstart the protein synthesis.

Figure 1: Overview of the initial (Trial 1) and next morning procedures (Trial 2 | McKendry. 2016).

After having ingested the whey protein shake, the participants rested in both trials supine for 240 minutes. After those 4h, another muscle biopsy was obtained ~3cm proximal to the second biopsy to determine MPS rates over the ‘early’ phase (0-4 h) of post-exercise recovery. The data from this phase was complemented by data from a last, fourth muscle biopsy on the next morning and after consuming an identical protein shake after 10h of fasting (lunch and dinner on the day before were standardized, so that this would not mess with the results).

Figure 2: Protein synthetic (myofibrillar) and hormone response after working out with 1 vs. 5 min rest (McKendry. 2016).

Whether and to which extent the sign. difference in protein synthesis of which the scientists say that it is an 76% vs. 152% increase in the 0-4h time-window after the workout is related or even triggered by the significantly higher GH response in after the 5-min rest trial is questionable, but if you recall the seminal paper by West et al. (2012), you will certainly remember that GH and cortisol are the only hormones the levels of which after a workout show any correlation with muscle gains (see Figure 3).

Figure 3: Sign. associations between PWO hormone levels and lean mass, as well as fiber size increases (West. 2012).

With that being said, you may consider this odd, because usually the metabolically more demanding short-rest workout will yield greater GH increases (Kraemer. 1990; Goto. 2004; Bottaro. 2009) - this and the fact that the previously hinted at association exists, but the incline or, in other words, the effect on fiber size per unit increase in GH is low (too low to fully explain the 5-minute-advantage) suggest that there must be more to it than the small GH increase with 5 minutes vs. 1 minute rest.

Why do other studies not confirm this finding? I guess that depends on the study. An often-cited paper by Kraemer, et al. for example found 1 minute of rest to outperform 3 minutes hypertrophy-wise - probably because the 1-min rest protocol involved 3 sets of 8 exercises with a 10-RM load, while the 3 minute protocol involved "only" five sets of five exercises, performed with a 5-RM load, so that the two workouts were not volume equated and the study no comparison of workouts with different rest times, but rather one of hypertrophy vs. strength workouts.

Acute effect of different rest intervals between sets over the number of repetitions maximum (RM). Values expressed as RM (de Salles. 2009)

Conflicting results from other studies, e.g. Villanueva, et al. (2015) who found sign. greater muscle gains in with 1 vs. 4 minutes of rest, may be explained by differences in the study population (elderly in Villanueva, et al.) and/or the training protocol, which did not involve training to failure and thus probably didn't produce significant volume advantages for the 4-minute rest group. Eventually, volume appears to be, within sustainable limits, the most sign. determinant of the hypertrophy response to exercise, so if you do something to increase it (e.g. myoreps or real vs. volume- equated drop sets, etc.) you may still benefit. If you simply cut the rest, however, the volume suffers from not resting long enough (cf. table on the left) and this may affect your gains.

The existing differences in  anabolic signaling protein phosphorylation (e.g. p70S6KThr389, rpS6Ser240/244, 4EBP1Thr37/46, etc.) can likewise not serve as a mechanistic explanation. After all, these are the switches that trigger the growth. Saying they are responsible would be tantamount to saying that the light switch is the reason the light went out, when someone actually switched it off.

So, what is it that makes the difference? Well, in view of the results of previous studies that suggest that, ultimately, it's not hormones, not protein phosphorylation, but rather the total volume of weight that is lifted (at least unless that's so much that you do more harm than good) that determines the hypertrophy response to resistance training (Schoenfeld. 2013), we should look at a different study outcome: the total volume in kilograms (see Figure 4):

Figure 4: Set- and total volume when subjects trained with 1 vs. 5 minutes rest (McKendry. 2016).

That the sign. difference in volume on set 3 and 4, and the significant difference in total volume are actually the explanation, is obviously speculative, but at least for me it is the most likely explanation for a difference (see red box, as well).

The ineffectiveness of drop-sets in Fisher's recent study may in fact also have been a result of a lack of difference in training volume | more

Bottom line: Eventually, the study at hand only proves what we already knew - training volume is more important than metabolic stress when it comes to hypertrophy gains.

Any training regimen / modification that reduces the total volume of weight lifted may thus potentially compromise your gains... if the volume is in fact all that is to the effects of shortening rest times will obviously still have to be determined. As of now, volume is yet the best explanation for the differences or lack of differences and effects scientists observed in this and previous studies such as the recently discussed dropset study by Fisher et al. where the set-volume standardization may have blocked any sign. advantage of real-world (=add-on) dropsets | Discuss!.

References:

• Bottaro, Martim, et al. "Effects of rest duration between sets of resistance training on acute hormonal responses in trained women." Journal of science and medicine in sport 12.1 (2009): 73-78.
• de Salles, Belmiro Freitas, et al. "Rest interval between sets in strength training." Sports Medicine 39.9 (2009): 765-777.
• Goto, Kazushige, et al. "Muscular adaptations to combinations of high-and low-intensity resistance exercises." The Journal of Strength & Conditioning Research 18.4 (2004): 730-737.
• Henselmans, Menno, and Brad J. Schoenfeld. "The effect of inter-set rest intervals on resistance exercise-induced muscle hypertrophy." Sports Medicine 44.12 (2014): 1635-1643.
• Kraemer, WJ, Marchitelli, L, Gordon, SE, Harman, E, Dziados, JE, Mello, R, Frykman, P, McCurry, D, and Fleck, SJ. Hormonal and growth factor responses to high intensity resistance exercise protocols. J Appl Physiol 69: 1442-1450, 1990.
• Schoenfeld, Brad J. "Postexercise hypertrophic adaptations: a reexamination of the hormone hypothesis and its applicability to resistance training program design." The Journal of Strength & Conditioning Research 27.6 (2013): 1720-1730.
• Schoenfeld, Brad J., et al. "Longer inter-set rest periods enhance muscle strength and hypertrophy in resistance-trained men." Journal of strength and conditioning research/National Strength & Conditioning Association (2015).
• Villanueva, Matthew G., Christianne Joy Lane, and E. Todd Schroeder. "Short rest interval lengths between sets optimally enhance body composition and performance with 8 weeks of strength resistance training in older men." European journal of applied physiology 115.2 (2015): 295-308.
• West, Daniel WD, and Stuart M. Phillips. "Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training." European journal of applied physiology 112.7 (2012): 2693-2702.
• Willardson, Jeffrey M. "A Brief Review: How Much Rest between Sets?." Strength & Conditioning Journal 30.3 (2008): 44-50.

Ecdysterone Beats Popular Anabolics!? Plus 75% Muscle Size in 21 Days in Rats - More Than DHT, IGF-1, Dianabol...

Ecdysterone Beats Popular Anabolics!? Plus 75% Muscle Size in 21 Days in Rats - More Than DHT, IGF-1, Dianabol...

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Parr et al. suggest that ecdysterone should be added to the WADA list.

Actually, I didn't plan to write a SuppVersity article about an agent of which everybody says that it's a waste of money, but I have to admit that the conclusion that "ecdysterone exhibited a strong hypertrophic effect on the fiber size of rat soleus muscle that was found even stronger compared to the test compounds metandienone (dianabol), estradienedione (trenbolox), and SARM S 1, all administered in the same dose (5 mg/kg body weight, for 21 days)" (Parr. 2015) in the abstract of a recent non-sponsored (no conflict of interest, either) study from the Freie Universität Berlin intrigued me.

In the corresponding study, Parr and colleagues had tested the effects of ecdysterones on the fiber sizes of the soleus muscle (that's mainly slow twitch muscle fibers) of rodents in vivo and in vitro.

If you want to build muscle forget T-booster and optimize your protein intake 

Protein Timing DOES Matter!

5x More Than the FDA Allows!

Protein requ. of athletes

High EAA protein for fat loss

Fast vs. slow protein

Whey vs. Pea Protein

In the less relevant in vitro study, the researchers incubated C2C12 derived myotubes with the test compounds and determination of diameters of 47 myotubes per group (mean of measurements every 10–20 µm along the myotube) by fixing the cells and using photographs of the stained cells to determine the myotube diameters of 50 myotubes every 10–20 µm along the length of the myotube (further details see Parr. 2014). As the authors point out, incubation with ecdysterone showed "sign. increased myotube diameters compared to vehicle treated control cells" (Parr. 2015 | see Figure 1).

Figure 1: Myotube diameter in the in vitro study after incubation with DHT, IGF-1 or Ecdysterone (Parr. 2015).

If you compare the effects of the Ecdy treatment with those of the endogenous anabolic androgenic steroid dihydrotestosterone at the same concentration and those of the anabolic growth factor IGF-1 (concentration for comparison was 1.3 nM) it is quite impressive to see that there was an (albeit non significant) advantage for an active phytoecdysteroid the Russians have supposedly used as early as in the 1980s for doping purposes.

How does ecdysterone work? Previous studies already confirmed the beneficial effects of ecdysterone on skeletal muscle protein synthesis. As early as in the year 2000, V.N. Syrov published a paper in the Pharmeceutical Chemistry Journal in which the beneficial effects ecdysterone and related agents on rodent muscles were documented. Later on, Gorelick-Feldman et al. proposed direct or indirect stimulation of the PI3K/Akt signaling pathway as mechanism for this increased protein synthesis (Gorelick-Feldman. 2008 & 2010). In the study at hand, Parr et al conducted molecular modeling experiments which appear to confirm that the effects of ecydesterone are mediated by estrogen-receptor-β (ERβ) binding, rather than via the androgen receptor which is the target of the many of the other drugs used. 

Obviously, the effects of bathing individual cells in concentrated ecdysterone cannot serve as a reliable litmus test for the anabolic prowess of an agent bodybuilders take as an oral supplement in dosages of usually no more than 1g per day. In this respect, the concomitantly conducted experiment with intact rodents is of much greater interest. In this part of study, the authors fed male Wistar rats (n = 42, Janvier, Le-Genest St-Isle, France) either 5 mg/kg body weight of ecdysterone, metandienone, estradienedione, or the selective androgen receptor modulatar (SARM) S-1, each diluted in a solution of 20% DMSO and 80% peanut oil daily. In that, it is unfortunately not 100% quite clear if the scientists used intraperitoneal or intra-muscular injections, but the composition of the "supplement" and the fact that a previous study (Syrov. 2000) used the same dosage orally, appear to suggest that Parr et al. refer to about IP injections, which mimic oral supplementation, but have the advantage of giving rodents no chance to regurgitate the drug, when they write that the rodents "received injections". What is pretty clear, though, is that the scientists used changes in muscle fiber size of the soleus muscle of male Wistar rats as measure of the anabolic potency of their test substances.

Figure 2: Anabolic effect of ecdysterone (Ecdy) expressed as fiber size of soleus muscle in intact rats (Parr. 2015).

The results of the comparison of ecdysterone to the anabolic androgenic steroids metandienone (dianabol) and estradienedione (trenbolox) as well as the selective androgen receptor modulator S-1 are plotted in Figure 2. Quite impressive , no? And this is not an outlier study. As Parr et al point out, their study is not the first to show that "ecdysterone induces hypertrophy of muscles with a comparable or even higher potency as shown for anabolic androgenic steroids, SARMs or IGF-1", as analogous findings have been reported in the previously cited study by Syrov back in 2000. Human data, as well as data that would confirm similar effects on muscles that are predominantly fast-twitch (the soleus which was examined in the study at hand is mostly slow twitch) are yet missing. The latter is of particular interest, because estrogen treatment appears to favor a more oxidative (=more slow vs. fast twitch) fiber muscle fiber composition (Suzuki. 1985).

Hormonal Response to Exercise, Revisited: A Consequence, not a Determinant of Your Mood, Effort & Performance | learn more

Bottom line: In spite of the fact that the study provides quite convincing evidence in favor of the unexpected potency of Ecdysterone, there is a problem with dosing. While the scientists say they used 5mg/kg body weight in order "mimic the situation in athletes", the correct rodent equivalent of the aforementioned dosages of up to 1g per day would be roughly 50-75mg/kg per day and thus far more than the meager 5mg/kg the researchers used.

In other words, if they didn't accidentally give us the human equivalen dose instead of the actual rodent dose, those 1g/day some bodybuilders may be taking should be way more than you'd need to see significant increases in muscle gains and that is a problem.

Why? Well, not because I'd believe that dosages as high may have toxic side effects, but rather in view of the fact that you can hardly imagine that a drug as effective as that wouldn't be all over the place in the discussions on pertinent bulletin boards. A 2006 study by Wilborn et al. even fuels the doubts, because it found no performance or hypertrophy effects in the 15 out of 45 subject of their 8-week training study who consumed 30 mg of 20-hydroxyecdysone per day from an allegedly standardized (but not tested) extract from Suma root. An even older study by Simakin et al. (1988), however, appears to confirm the existence of potent anabolic effects of ecdysterone in humans with significant increases in lean (6-7%) and reductions in fat mass (10%) in a 3-week study on 78 highly-trained male and female subjects. In view of the conflicting evidence, I am still very skeptical whether (a) the results translate to human beings, whether (b) the growth promoting effect is maybe restricted to slow twitch fibers and thus of little use to bodybuilders and whether (c) the supplements that are already being sold actually contain ecdysterones | Comment!

References:

• Gorelick-Feldman, Jonathan, et al. "Phytoecdysteroids increase protein synthesis in skeletal muscle cells." Journal of agricultural and food chemistry 56.10 (2008): 3532-3537.
• Gorelick-Feldman, Jonathan, Wendie Cohick, and Ilya Raskin. "Ecdysteroids elicit a rapid Ca 2+ flux leading to Akt activation and increased protein synthesis in skeletal muscle cells." Steroids 75.10 (2010): 632-637.
• Parr, Maria Kristina, et al. "Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone." Molecular nutrition & food research 58.9 (2014): 1861-1872.
• Parr, M. K., et al. "Ecdysteroids: A novel class of anabolic agents?." Biology of sport 32.2 (2015): 169.
• Simakin, S. Yu. "The Combined Use of Ecdisten and the Product'Bodrost'during Training in Cyclical Types of Sport." Scientific Sports Bulletin 2 (1988).
• Suzuki, S., and T. Yamamuro. "Long-term effects of estrogen on rat skeletal muscle." Experimental neurology 87.2 (1985): 291-299.
• Syrov, V. N. "Comparative experimental investigation of the anabolic activity of phytoecdysteroids and steranabols." Pharmaceutical Chemistry Journal 34.4 (2000): 193-197.
• Wilborn, Colin D., et al. "Effects of methoxyisoflavone, ecdysterone, and sulfo-polysaccharide supplementation on training adaptations in resistance-trained males." Journal of the International Society of Sports Nutrition 3.2 (2006): 19-27.

Net Protein Retention and Dietary Protein: When It Comes to Steaks, More Helps More - By Inhibiting Protein Breakdown

Net Protein Retention and Dietary Protein: When It Comes to Steaks, More Helps More - By Inhibiting Protein Breakdown

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Want to maximize net protein retention? Order another one... another steak ;-)

In view of the WHO's recent epidemiological bogus publication, ... ah I mean their review of the epidemiological research that said that "red meat kills", it is quite surprising that the study Il-Young Kim and colleagues conducted in healthy young adults was even approved by the ethics committee of their respective research institutions. After all, the study involved measuring the whole body protein kinetics of young men and women after the consumption of ~40g (moderate protein, or MP) or, even "worse", ~70g (higher protein, HP) of protein in form of red meat (85% lean ground beef) in a regular food matrix (=as part of a normal meal | see Table 1 for an exact overview of the macronutrient content).

You can learn more about protein intake at the SuppVersity

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Whole protein kinetics? Yes, that's different from what you see in the average "whey protein builds muscle study", in which the researchers measure only the fractional protein synthesis. Kim et al. went one step further and measured the protein synthesis (PS), breakdown (PB), and net balance (NB) in their subjects, twenty-three healthy subjects [18 – 40 yrs] who were recruited from the Little Rock area using local newspaper advertisements and flyers posted around the University of Arkansas for Medical Sciences (UAMS) campus and the Little Rock area. Now, it's not like humans had a display you can use to read these variables, so eventually, they were still calculated based on the determinations of the rate of appearance (Ra) into the plasma of phenylalanine and tyrosine, and the fractional Ra of endogenous tyrosine converted from phenylalanine as in a previous study by the same team of researchers (Kim. 2015a). Since this technique is unable to distinguish between the different sites of protein breakdown.and storage, the results of the study at hand could describe increases or decreases in splachnic (=organ) protein synthesis or breakdown, too. It is thus not possible to exclude a null effect on skeletal muscle protein synthesis and breakdown based on the available data.

Whole protein kinetics, two different amounts of protein, with and without exercise

There were yet other things Kim's study had in common with many of the aforementioned "whey protein studies": The study had a run-in that was included to minimize any potential effects of the protein content of the subjects' baseline diets. The subjects ate their high or medium protein meals in the fasted state and the participants - or at least some of them - also trained. To be more specific, the subjects were randomly assigned into an exercise group (X, n=12) protocol consisting of 3 sets of 10 repetitions of bench press, lateralis pull-down, leg press, and leg extension each at 80% of 1 repetition maximum (1 RM, the maximum weight that can be lifted for one repetition) at a pace of 30 sec per set (rest interval between sets was less than 2 min, and the entire exercise bout was completed in ~45 – 50 min), or a resting group (R, n=11).

Table 1: Overview of the macronutrient intake during the 4-day run-in and the actual experiment (Kim. 2015b)

So much for the study design. Let's take a look at the results now: When the scientists analyzed the data from the 7-h stable isotope tracer infusion protocol that was used to determine the rate of protein synthesis (PS), breakdown (PB) and net protein balance (NP), they realized that...

• exercise did not significantly affect protein kinetics and blood chemistry, while 
• feeding, in general, resulted in a positive net protein balance at both levels of protein intake,

Boring? You're right. This would hardly be a 'SuppVersity newsworthy' study if the researchers had not also confirmed what most of you probably already suspected: The high protein meal lead to a significantly greater increase in net protein balance than the medium protein meal.

Figure 1: It's the decrease in protein breakdown, not the marginal increase in protein synthesis that makes the difference between the net protein balance after the high and medium protein meals (Kim. 2015b).

Interestingly enough, this increase in net protein balance was achieved primarily through a greater reduction in PB and to a lesser extent stimulation of protein synthesis (for all, p<0.0001). This is an important results, because it suggests that all previously reported ceiling effects for protein synthesis could be irrelevant when we are talking about a potential limit of protein intake beyond which you won't be able to see further beneficial effects on body composition in general and the accrual of lean mas in particular.

Figure 2: The analysis of the inter-group differences in EAAs, glucose and insulin suggest that the difference is meadiated mainly by the increase in serum EAAs and not a "side effect" of increased, highly anticatabolic (Fukagawa. 1985) insulin.

Bottom line: When it comes to interpreting the results, two things are important. Firstly, it is worth mentioning that the previously described decrease in protein breakdown was achieved in response to a greater increase in plasma EAAs (p<0.01) - not in response to increased insulin levels (inter-group differences were non-significant over time). That's important because it means that you wouldn't see the same effect by simply adding more insulinogenic carbs to the meal in order to increase the levels of one of the most powerful inhibitors of protein breakdown: insulin (Fukagawa. 1985)!

Sounds great, right? More helps more! True, there's yet (a) the previously hinted at problem that we can't tell if what the scientists measured was muscle or splachnic protein. Furthermore, the results of the study are (b) valid only if the protein comes from slow-digesting meat. From previous research, I discussed in detail back in 2013, already, we know that the ingestion of similarly high amounts of fast digesting proteins, like whey, does not inhibit, but rather trigger an increase in protein breakdown and gluconeogenesis that uses the ingested protein as a substrate. Now, that doesn't mean that using too much whey protein will cost you muscle mass. What it does mean, though, is that you'll be "Protein Wheysting" if you mistakenly believe that the results of Kim's study apply with a very slow digesting protein source apply turbo-proteins, as well.

So what's the verdict?  Don't economize on protein, but don't fool yourself to believe that with protein more is always always better. Maybe I should also remind you that when you're dieting a high protein intake can yield better results than a very high one and that's a conclusion from a metabolic ward study | Tell me and others what you think on Facebook!

References:

• Fukagawa, N. K., et al. "Insulin-mediated reduction of whole body protein breakdown. Dose-response effects on leucine metabolism in postabsorptive men." Journal of Clinical Investigation 76.6 (1985): 2306.
• Kim, Il-Young, et al. "Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults." American Journal of Physiology-Endocrinology and Metabolism 308.1 (2015): E21-E28.
• Kim, et al. "The anabolic response to a meal containing different amounts of protein is not limited by the maximal stimulation of protein synthesis in healthy young adults." Am J Physiol Endocrinol Metab (November 3, 2015b). doi:10.1152/ajpendo.00365.2015.