Low Grade Metabolic Acidosis May Eat Away Your Bones and Blow Up Your Belly Via Empowering Glucocorticoids!

The way we eat and live is not just obesogenic it is also acidogenic... or is the former just a consequence of the latter? 

I've written about the nasty effects of low grade metabolic acidosis which include calcium loss and brittle bones, nitrogen / protein loss and decreased protein synthesis, impaired growth hormone and IGF-1 production and more in a 2013 SuppVersity Science Round-Up (read it).

For you, as a SuppVersity veteran who's read this and related articles, it should thus not be surprising that scientists from the German Aerospace Center in Cologne were now able to establish a new, mechanistic link between the "long-term ingestion of habitually acidifying western diets may constitute an independent risk factor for bone degradation and cardiometabolic diseases" (Buehlmeier. 2015).

As Judith Buehlmeier and her colleagues point out, we have long been aware of the ill effects of low-grade metabolic acidosis (LGMA), as induced by high dietary acid load or sodium chloride (NaCl) intake and a lack of alkaline foods and nutrients in the average Western diet. What has hitherto not been fully elucidated is the underlying mechanisms, which is not as simple as the dissolving tooth in a glass of coke would suggest.

You can learn more about bicarbonate and pH-buffers at the SuppVersity

The Hazards of Acidosis

Build Bigger Legs W/ Bicarbonate

HIIT it Hard W/ NaCHO3

Creatine + BA = Perfect Match

Bicarb Buffers Creatine

Alkalosis Boosts Muscle Activity

In their latest study, the researchers from the German Aerospace Center in Cologne and their colleagues from the Universities of Bonn and Heidelberg do now present the first convincing evidence that the previously cited catabolic / anti-anabolic effects of chronic low-grade acidosis (LGMA) are triggered by interactions of the acid–base balance with the metabolism of glucocorticoids (GC). In said, study, the researchers "aimed to investigate GC activity/metabolism under alkaline supplementation and NaCl-induced LGMA" in eight young, healthy, normal-weight men who participated in two crossover designed interventional studies.

Figure 1: Correcting a diet-induced low grade metabolic acidosis with K-bicarbonate reduces the nitrogen loss of 750mg - 1000mg per day (per 60kg BW) in post- menopausal women in a prev. study (Frassetto. 1997)

• In Study A, two 10-day high NaCl diet (32 g/d) periods were conducted, one supplemented with 90 mmol KHCO3/day.
   
• In Study B, participants received a high and a low NaCl diet (31 vs. 3 g/day), each for 14 days. During low NaCl, the diet was moderately acidified by replacement of a bicarbonate-rich mineral water (consumed during high NaCl) with a non-alkalizing drinking water. 

In repeatedly collected 24-h urine samples, potentially bioactive GCs (urinary-free cortisol / free cortisone), as well as tetrahydrocortisol (THF), 5a-THF, and tetrahydrocortisone (THE), were analyzed.

Even Low Grade Acidosis Will Increase Your Diabetes Risk | learn more!

Beware! It does not take much to mess you up! A quantitative analysis of the data from the study at hand shows that even increases of dietary acid loads in the magnitude of only 30 mEq/d, which drive the renal net acid excretion into a range that is commonly seen in people on the standard Western diet (60–70 mEq/d), suffice to affect glucocorticoid activity in ways that may ruin your bone, heart and muscle health. In that, the main offenders are grains, not meats. Grains contribute an estimated 38% to the net acid load of the avg. Westerner (Sebastian. 2002).

A brief glimpse at the glucocorticoid levels in the urine of the subjects (see Figure 2) shows that with supplementation of 90 mmol KHCO3, the marker of total adrenal GC secretion dropped (p = 0.047) and potentially bioactive-free GCs were reduced (p = 0.003).

Figure 2: aily adrenal cortisol secretion as indexed by the sum of excretion rates of the 3 major urinary glucocorticoid (GC) metabolites tetrahydrocortisol, 5a-tetrahydrocortisol, and tetrahydrocortisone (THF + aTHF + THE) as well as excretions of potentially bioactive-free GCs (UFF + UFE | Buehlmeier. 2015)

This is particularly interesting if we also take into account that in Study B, the GC secretion and potentially bioactivefree GCs did not exhibit the expected fall with NaCl-reduction as net acid excretion was raised by 30 mEq/d. In conjunction study A + B do thus underline the important role of alkalizing agents like bicarbonate or potassium - irrespective of the total intake of NaCl, of which the study at hand confirms that it is part of the problem. Its ill effects, however, appear to be mediated mainly, if not exclusively, via the acidifying effects of chloride.

Bottom line: As the authors point out, their study is the first to provide convincing evidence that the ill effects of chronic low-grade metabolic acidosis are mediated via enhanced glucocorticoid activity and secretion. In that, the pro-acidic effects of NaCl, as well as the lack of alkalizing foods and nutrients in the Western diet are the main motors of dietary induced glucocorticoid elevations.

Inactivity amplifies the ill effect of glucocorticoids on muscle loss by up to 213% (Ferrando. 1999).

These elevations are - in spite of being still in the physiological range - significant enough to compromise bone quality (Bedford. 2010; Shi. 2015), cardiometabolic health & diabetes (Prodam. 2013; Qi, 2007), and protein turnover (Frassetto. 1997 | see Figure 1; Buehlmeier. 2012), and appear to be particularly unfavorable under conditions of physical inactivity (Ferrando. 1999 | see Figure on the right). Reason enough for the authors to conclude that "[a]ccordingly, higher dietary acid loads may, in the long run, constitute an independent GC-driven musculoskeletal and cardiometabolic risk factor related with western dietary habits" (Buehlmeier. 2015) | Comment!

References:

• Bedford, Jennifer L., and Susan I. Barr. "The relationship between 24-h urinary cortisol and bone in healthy young women." International journal of behavioral medicine 17.3 (2010): 207-215.
• Buehlmeier, Judith, et al. "Alkaline salts to counteract bone resorption and protein wasting induced by high salt intake: results of a randomized controlled trial." The Journal of Clinical Endocrinology & Metabolism 97.12 (2012): 4789-4797.
• Ferrando, Arny A., et al. "Inactivity Amplifies the Catabolic Response of Skeletal Muscle to Cortisol 1." The Journal Of Clinical Endocrinology & Metabolism 84.10 (1999): 3515-3521.
• Frassetto, L., R. Curtis Morris Jr, and A. Sebastian. "Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women." The Journal of Clinical Endocrinology & Metabolism 82.1 (1997): 254-259.
• Qi, Dake, and Brian Rodrigues. "Glucocorticoids produce whole body insulin resistance with changes in cardiac metabolism." American Journal of Physiology-Endocrinology and Metabolism 292.3 (2007): E654-E667.
• Prodam, Flavia, et al. "High-end normal adrenocorticotropic hormone and cortisol levels are associated with specific cardiovascular risk factors in pediatric obesity: a cross-sectional study." BMC medicine 11.1 (2013): 44.
• Sebastian, Anthony, et al. "Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors." The American journal of clinical nutrition 76.6 (2002): 1308-1316.
• Shi, Lijie, et al. "Higher glucocorticoid secretion in the physiological range is associated with lower bone strength at the proximal radius in healthy children: importance of protein intake adjustment." Journal of Bone and Mineral Research 30.2 (2015): 240-248.

Load Carrying Cardio Doesn't Affect Muscle Protein Flux While Intra-Workout EAA Reduces Protein Breakdown and Bumps Nitrogen Balance From Zero to Plus 50µmol/kg/h

While this picture shows loaded cardio in its most beautiful form, the study investigated loaded cardio on the treadmill and compared it (for questionable reasons) to non-loaded cardio on a stationary bike and guess what: Both burn the same amount of muscle - NET: Zero!

Carrying a (heavy) load during cardio? Sounds dumb? Well, that's however, how the real world looks like. Not just soldiers who are carrying armor and a heavy backpack in the field, but also hikers will attest to the fact that doing "cardio" with a weight on your shoulders or elsewhere is more natural than running around in the park with your mobile and ear-plugs as the only load you're carrying on top of your ultra-light runners clothing.

With that being said, it is actually quite astonishing that Stefan M. Pasiakos and colleagues from the Military Nutrition Division at the US Army Research Institute of Environmental Medicine in Natick are the first to take a look at the muscle anabolic and catabolic effects of regular (unloaded) and loaded cardio training in 40 free-living healthy, physically fit (peak oxygen uptake, VO2peak 40/60 mL/ kg/ min), adults (37 males and 3 females), normal weight men and women between the ages of 18–39 years.

HIIT is the ideal complement to classic "cardio" training!

Never Train To Burn Calories!

Tabata = 14.2kcal /min ≠ Fat Loss

30s Intervals + 2:1 Work/Rec.

Making HIIT a Hit Part I/II

Making HIIT a Hit Part II/II

HIIT Ain't For Everyone

In said study, the volunteers were then randomly assigned to one of four experimental groups, each
of whom performed a single 90 min exercise bout.

• Two groups performed CE and the other two performed LC. 
• One of each of the exercise groups received EAA drinks to consume during exercise, and the other groups received control (CON) drinks. 

To determine the effects on skeletal muscle, the subjects' individual muscle protein synthesism (MPS) was assessed during exercise and recovery and whole protein turnover was determined in recovery only. What may be a bit surprising in this context is the fact that a resting MPS measure was not included in the study. The authors, however, have a good argument to neglect this, when they say that (a) the MPS responses to endurance-type exercise (i.e.,as they relate to resting MPS) are well established and that (b) their ...

"[...] intent was not to determine temporal changes in MPS within an exercise mode (with or without EAA), but to examine MPS responses between LC and CE during exercise and recovery independently" (Pasiakos. 2015).

Another thing that was just like in any other study, though, was the standardization of diet and physical activity, the scientists describe as follows:

"Volunteers completed 3 d diet and activity records at baseline, and similar to our previous work (Pasiakos. 2011), these records were used to individually prescribe 7 d lead-in diets to maintain body weight and to limit the potential confounding effect of diet on outcome measures. Compliance was confirmed by 24 h dietary recalls conducted every two days during the lead-in phase (Food Processor SQL1, version 10, ESHA Research, Salem, OR) (Table 1). Volunteers were also instructed to maintain activity levels reported at baseline for the first five days of the lead-in phase. All resistive and endurance-type activity was prohibited 48 h before data collection to minimize any potential residual effects of previous exercise on protein turnover" (Pasiakos. 2015).

The actual news is however not the dietary standardization what you are (rightly) interested in is probably the exercise protocol which is - and I will get to that in the bottom line - not ideal: While the LC, i.e. the load carriage training, was performed by walking on a treadmill while wearing a weighted vest equivalent to 30% of baseline body mass, the CE, i.e. the control endurance exercise, was non-weight bearing and performed on a cycle ergometer (Lode, BV, Netherlands), of which the scientists say that they used it to "allow for comparisons with our previous studies" (Pasiakos. 2015).

Illustration 1: Graphical overview of the study design (Pasiakos. 2015) | EAA = 10g of EAAs, CON = non-nutritious control drink; LC = load carrying cardio on a treadmill, CE = control endurance exercise on a stationary bike.

What's unquestionable a strength of the study, though, was the fact that the baseline VO2peak and associated heart rates at maximal and submaximal levels were used to establish target exercise intensities for the LC and CE trials. In addition, speed and grade for LC and power (watts) for CE were adjusted to match the absolute exercise intensity (intended oxygen uptake was 2.4 L /m) and
to elicit a similar energy cost (intended energy expenditure was 1050 kcal /90 min) between
LC and CE. Lastly, ...

"[m]atching the intensity and energy cost was done to isolate the effects of the possible differences in mechanical force and contractile properties of LC and CE from the relative intensity and energy cost of the exercise bout [and a] familiarization trial was conducted to ensure the accuracy of the exercise prescription and the ability of the volunteer to complete the prescribed exercise bout" (Pasiakos. 2015).

As previously alluded to, the intra-workout beverage the subjects consumed was either a high EAA drink (10 g EAA: 0.7 g histidine, 0.7 g isoleucine, 3.6 g leucine, 1.2 g lysine, 0.3 g methionine, 1.4 g phenylalanine, 1.0 g threonine, and 1 g valine) or an identically looking placebo drink (non-nutritive).

Figure 1: Overview of protein fluxes (synthesis vs. breakdown and oxidation) and subsequent net protein balance in the four treatment groups, i.e. loaded and control cardio with and with out EAA (Pasiakos. 2015)

Interestingly enough, the latter, i.e. the 10 grams of EAA drink that was consumed in four small doses (i.e., 350 mg of phenylalanine and 900 mg of leucine per serving), over 90 min to minimize "any isotopic dilution that may have occurred if the EAA drink was consumed as a bolus" (Pasiakos. 2015) was the only treatment that made a difference to the protein flux parameters illustrated in Figure 1. In that it is worth mentioning the tthe difference in protein oxidation alone does not fully explain the conservation of skeletal muscle protein even if we assume that all the amino acids that were oxidized during the EAA supplementation trial came from the EAA supplement. This is curious in view of the lack of effect of BCAAs on exercise (learn more) induced protein breakdown and points with a finger to other EAAs as potential motors of this effect.

Figure 1: Protein synthesis. Mixed-muscle (A), myofibrillar (B), and sarcoplasmic (C) muscle protein synthesis (MPS) during exercise and mixed-muscle (D), myofibrillar (E), and sarcoplasmic (F) MPS in recovery from a 90 min, metabolically matched load carriage (LC) or conventional endurance (CE) exercise bout, with and without (control, CON) essential amino acid (EAA) supplementation. Data are mean ± SD, n = 10 per group. †Mode main effect; LC different than CE, P < 0.05. *Drink main effect; EAA different than CON, P < 0.05 (Pasiakos. 2015).

The fact that the loading didn't make a difference in either direction, i.e. that it did neither increase nor decrease the breakdown or synthesis of muscle protein may be surprising, but it's not the only result worth mentioning before we evaluate the results in the bottom line. In addition, it should be noted:

1. The EAA-mediated decrease in muscle breakdown was complemented by both enhanced mixed-muscle and sarcoplasmic MPS during exercise.
2. During the recovery phase, the mixed muscle and sarcoplasmic protein synthesis in response to loaded cardio training were higher than they were in the control group.

Of these results, finding #2 is of most interest as it puts the alleged uselessness of loaded cardio into perspectives. Muscles do after all grow during rest and if the muscle protein synthesis during the recovery phase is increased compared to the control non-loaded exercise this clearly suggests that loaded endurance exercise is more anabolic than non-loaded endurance exercise.

Yes! You can use whey or even regular milk protein, as well and benefit. Better don't eat a steak during your workout though. Learn more in this SV Classic  "23g of Dairy Protein + 5g of Leucine Turn Cardio Sessions Into Muscle Building Workouts"

So, loaded endurance exercise is not much, but a little better? Well, in this study it appears to be as if the former was the correct conclusion to be drawn. Generalizations, however, must be made with utmost care. Especially in view of the unfair comparison of walking on a treadmill with cycling on a bike, of which you could argue that it is naturally less anabolic than walking - irrespective of whether you're carrying an extra-load or not. Thus, the researchers have weakened the generalizability of their results by making the (imho unnecessary) decision to rely on a tried and proven method, i.e. cycling, only to (as I suspect) make it easier to standardize the workload in numbers. This, however, is bogus: I mean, you all have probably worked out for say 500kcal on an exercise bike and for 500kcal on a treadmill. Now tell me: What did you feel was more exhausting and had a subjectively significantly larger impact on your metabolism? You answer probably is 'treadmill'.

Eventually, the most practically relevant information you can draw from the study at hand are thus: (A) You can do both 90 minutes of loaded cardio on the treadmill and 90 minutes of classic cardio on an exercise bike without any muscle loss (at least from the exercised muscles) even if you consume only water (see net balance = 0 in Figure 2). (B) If you bring 10g of EAA and consume them over the course of your workout you may even hop off the treadmill or bike with a few micrograms extra muscle on your legs. And (C) if you chose the treadmill and loaded cardio this will trigger a better post-workout anabolic response than the bike. How meaningful all that is - in terms of gains, I mean - will yet have to be seen in future long(er)-term studies | Comment!

References:

• Pasiakos, Stefan M., et al. "Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis." The American journal of clinical nutrition 94.3 (2011): 809-818.
• Pasiakos SM, McClung HL, Margolis LM, Murphy NE, Lin GG, Hydren JR, et al. "Human Muscle Protein Synthetic Responses during Weight-Bearing and Non-Weight-Bearing Exercise: A Comparative Study of Exercise Modes and Recovery Nutrition." PLoS ONE 10.10 (2015): Online only.

BFR Preconditioning Not Better Than Placebo? Long Rest Periods For Sustained Testosterone Increase? Train One Leg, Grow Both? - Resistance Training Update October '14

Single-legged leg presses that make both legs stronger are only one of many topics, today.

Time for an update on the latest resistance training research - just the interesting stuff, obviously ;-) What exactly? Well, let's see: We'll take a look at how long rest periods sustain the exercise induced. Then, we'll dive right into a placebo-controlled study on blood flow restriction as a means of preconditioning before resistance training, only to top things off with a study that found that training your dominant leg will also increase the leg press strength of the untrained, non-dominant limb.

Ah, and since there was some space left in the bottom line, we will acknowledge that AM vs. PM training have identical effects on power, force and hormonal response in young men and pretend to be surprised that a three-set upper-body workout is much more energetically demanding than its one-set analog. All in all, a very balanced update on the latest resistance training research, I'd say.

Read more about exercise-related studies at the SuppVersity

Tri- or Multi-Set Training for Body Recomp.?

Aug '15 Ex.Res. Upd.: Nitrate, Glycogen, and ...

Pre-Exhaustion Exhausts Your Growth Potential

Full ROM ➯ Full Gains - Form Counts!

Body Pump, Cardio & Exercise Expenditure

Study Indicates Cut the Volume Make the Gains!

• Long rest periods prolong testosterone response to bench press exercise -- From various previous SuppVersity articles you know that resistance training triggers an acute increase in testosterone. That this increase may depend on the rest between sets, though, is news. News from a recent article in the Journal of Strength and Conditioning Research.
  
  The purpose of the study was to examine the influence of rest period duration (1 vs. 3-minute between sets) on acute hormone responses to a high intensity and equal volume bench press workout (5x3 sets at 85% of the 1RM, to be specific).
  

  

  Figure 1: Mean (left) and individual (right) free testosterone levels before and after performing bench presses with 1 min or 3 min rest (Scudese. 2015).

  To this ends, Scudese et al. (2015) recruited ten resistance trained men (25.2 +/- 5.6 years; 78.2 +/- 5.7 kg; 176.7 +/- 5.4 cm; bench press relative strength: 1.3 +/- 0.1 kg/kg of body mass) and had them perform two bench press workouts separated by one week. Each workout consisted of 5 sets of 3 repetitions performed at 85% of 1-repetition maximum, with either 1 or 3-minute rest between sets. The rates of perceived exertion and serum levels of growth hormone (GH), cortisol, free and total testosterone were sampled at three different timepoints right (PRE), right after (T0) before, 15 (T15) and 30 (T30) minutes after. The results were as follows:
  • For total testosterone, both rest lengths enhanced all post-exercise verifications (T0, T15 and T30) compared to PRE, with 1-minute showing decreases on T15 and T30 compared to T0.
  • For free testosterone, both 1 and 3-minute rest protocols triggered augmentations on distinct post-exercise moments (T0 and T15 for 1-minute; T15 and T30 for 3-minute) compared to PRE.
  • Since the the cortisol values did not change throughout any post-exercise verification for either rests, the total testosterone/cortisol ratio was significantly elevated for both rests in all post-exercise moments compared to PRE.
    The growth hormone values did not change for both rest lengths.
  Now, that's exciting, right? The free testosterone levels kept increasing... well, not exactly. If you look at the data in Figure 1 right, you will notice interpersonal differences that suggest that the elevation would not have lasted for much more than those 15 extra-minutes .
  
  What's of significantly greater importance for the interpretation of the study results is yet a study by West et al. (2012) who observed that the testosterone response (both free and total) to resistance training is not associated with either strength or size gains. So what? It is very likely that the results of the study at hand are of zero practical relevance for your gains (strength- and sizewise, as West's study indicates).
• Blood flow restriction before strength training? It works - just as well as placebo! -- You will probably remember my recent article about the benefits of using blood flow restricting cuffs before a sprint workout, right (click here if not)? With the publication of the results of Moacir et al.'s (2015) latest study, we do now know that similar benefits will be seen with subsequent resistance training, too.

  

  The study at hand should make you question the results of the previously discussed study which did not have a placebo group | learn more

  "Thirteen men participated in a randomized crossover design that involved 3 separate sessions (ischemic preconditioning, placebo and control). A 12-RM load for the leg extension exercise was assessed through test and retest sessions prior to the first experimental session. The IPC session consisted of 4 cycles of 5 minutes occlusion at 220 mmHg of pressure alternated with 5 minutes of reperfusion at 0 mmHg for a total of 40 minutes. The PLACEBO session consisted of 4 cycles of 5 minutes of cuff administration at 20 mmHg of pressure alternated with 5 minutes of pseudo-reperfusion at 0 mmHg for a total of 40 minutes. 

  The occlusion and reperfusion phases were conducted alternately between the thighs, with subjects remaining seated. No ischemic pressure was applied during the control (CON) session and subjects sat passively for 40 minutes. Eight minutes following IPC, PLACEBO or CON, subjects performed three repetition maximum sets of the leg extension (2min rest between sets) with the pre-determined 12-RM load. Four minutes following the third set for each condition, blood lactate was assessed" (Moacir. 2015)

  When the researchers analyzed the results, they found that for the first set, the number of repetitions significantly increased for both the IPC (13.08 +/- 2.11; p = 0.0036) and PLACEBO (13.15 +/- 0.88; p = 0.0016) conditions, but not the CON (11.88 +/- 1.07; p > 0.99) condition.
  

  

  Figure 2: Significant increases in the number of reps (left) were observed for both the placebo and IPC group. The fatique index (right) did not differ between treatments, but the large inter-individual variety in the IPC group clearly suggests that BFR as a means of preconditioning ain't for everyone (Moacir. 2015).

  Similarly, the IPC and PLACEBO conditions resulted in significantly greater repetitions versus the CON condition on the 1st set (p=0.015; p=0.007) and 2nd set (p=0.011; p=0.019), but not the 3rd set (p=0.68; p>0.99). No significant difference (p=0.465) was found in the fatigue index and lactate concentration between conditions.
  
  As the researchers point out, their results "indicate that IPC and PLACEBO ischemic preconditioning may have small beneficial effects on repetition performance over a CON condition" (Moacir. 2015). It is thus not completely logical that they suggest "that ischemic pre-conditioning might be practiced gradually to assess tolerance and potential enhancements to exercise performance" (ibid.). What? Oh, you think your clients would notice that their blood flow is not actually impaired and the placebo effect would be lost? Right, now I understand why you should keep using it. Unfortunately that does not exclude that it is still a placebo effect which seems not unlikely in view of the larg(er) inter-individual differences in the IPC vs. any other group. Further studies are necessary... obviously!
• Train your right leg, and your left leg will become stronger, too - on leg presses, at least -- What sounds like a joke (or magic) is actually science. Science that is going to be presented in an article in a future edition of the Journal of Strength and Conditioning Research; and more precisely from a study that assessed the cross education of strength and changes in the underlying mechanisms (muscle size, activation, and hormonal response) following a 4-week unilateral resistance training (URT) program.
  
  In said study by Beyer et al. (2015), a group of nine untrained men completed a 4-week URT program on the dominant leg (DOM), while cross education was measured in the non-dominant leg (NON); and were compared to a control group (n=8, CON).

  "Unilateral isometric force (PKF), leg press (LP) and leg extension (LE) strength, muscle size (via ultrasonography) and activation (via electromyography) of the rectus femoris and vastus lateralis, and the hormonal response (testosterone, growth hormone, insulin, and insulin-like growth factor-1) were tested pre- and post-training" (Beyer. 2015).

  In all strength and size related measures, the trained group improved significantly better than CON. Significant group x time effects for PKF, LP, LE, and muscle size were observed only in the dominant leg (DOM), the non-dominant (NON = untrained leg), on the other hand, the scientist observed not just a trend, but rather an actual and statistically significant increase in leg press strength.
  

  

  Figure 3: Relative leg press and leg extension strength relative to body weight; the values above the post-bars indicate the relative difference between post and pre-test (2015).

  Whether that's related to the acute hormonal response to URT, the scientists observed, is more than questionable, after all the strength increase in the non-dominant leg didn't just occur in the absence of "detectable changes in muscle size, activation (EMG), or the acute hormonal response" it did also occur only during leg presses - if it was the result of any of the aforementioned factors one would expect to see at least something like a trend for leg extensions, as well.
  
  Against that background it should also be clear that you must not neglect one leg or arm when you train in the definitely false hope it would grow and the almost certainly false hope it would get stronger as you train your "favorite" limb. 

There's more: In view of the fact that the bottom lines to the individuals studies discussed in SuppVersity Research Overviews are always provided at the end of the respective item, I have room for mentioning two other interesting results at least briefly.

Figure 4: Energetic demands of 5x3 vs. 5x1 set upper body workout in men and women. Needless to say that the inter-group difference between 3 vs. 1 sets and the inter-group difference between men and women (not shown) were significant (Mookerjay. 2015).

Firstly, Hatfield et al.'s study of the "Effects of circadian rhythm on power, force, and hormonal response in young men" that indicates that "high force and power exercises utilizing  bench press-throws or jump squats may be performed any time of day without detrimental decreases in acute performance" (Hatfield. 2015). And secondly, Mookerjay et al.'s "[c]omparison of energy expenditure during single vs. multiple-set resistance exercise" (Mookerjay. 2015) that yielded a very obvious result which was that the multi-set protocols yield greater metabolic and cardiovascular demands than single set protocols when the number of exercises performed are the same (see Figure 4). In the study 5 upper-body exercises of either 1 or 3 sets per exercise performed in random order the gross and net energy expenditure was determined for the workout + 5 minutes of recovery. You can see the exact data in Figure 4, in case you're interested | Comment on Facebook!

References:

• Beyer, et al. "Short-Term Unilateral Resistance Training Results in Cross Education of Strength without Changes in Muscle Size, Activation, or Endocrine Response." Journal of Strength and Conditioning Research (2015): Ahead of print.
• Hatfield, et al. "Effects of circadian rhythm on power, force, and hormonal response in young men." Journal of Strength and Conditioning Research (2015): Ahead of print.
• Moacir, et al. "Ischemic preconditioning and placebo intervention improves resistance exercise performance." Journal of Strength and Conditioning Research (2015): Ahead of print.
• Scudese et al. "Long rest interval promotes durable testosterone responses in high intensity bench press." Journal of Strength and Conditioning Research (2015): Ahead of print.
• 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.

52% Reduced Fat Gain Over 4 Weeks of Overfeeding Twenty Young Men W/ 1000 kCal/Day on a High Fat (55%) Diet Due to Double Dose of a Commercial Multistrain Probiotic

Probiotics act on in the digestive tract, but their effects are still systemic.

You've read about the anti-weight gain effects of probiotic supplements in rodents before at the SuppVersity and in the SuppVersity Facebook News. Nice, yes, but will this also work in human beings? If we put faith into the predictive quality of a recent from Virginia Tech, it should.

Before we delve deeper into the study design, results and evaluation in the bottom line, I'd yet like you to know that (a) we don't know if the effects will persist for more than 4-weeks, if they will become stronger or weaker and that (b) the study was funded by VSL Pharmaceuticals (Osterberg. 2015) - both additional reasons not to confuse a single study like this with "proof" that probiotics block fat gain.

You can learn more about the gut & your health at the SuppVersity

Fiber for Female Fat Loss

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

Is Gluten Intolerance Real?

The objective of Osterberg's latest study was to "determine the effects of the probiotic, VSL#3, on body and fat mass, insulin sensitivity, and skeletal muscle substrate oxidation following 4 weeks of a high-fat diet" - in humans, and even better in 20 non-obese men (18-30 years) who participated in the study.

Learn everything about overfeeding! How do the effects of high vs. low fat, high vs. low protein and high vs. extra-high energy intake differ, what's the effect on thyroid and other important hormones and more

"All testing took place at the Human Integrative Physiology Laboratory between the hours of 5:00 and 11:00 am. Participants fasted for 12 h, did not consume caffeine or alcohol, performed no vigorous physical activity for the prior 48 h, and were free from acute illness for the prior 2 weeks.

[...]Following a 2-week eucaloric control diet, participants underwent dual X-ray absorptiometry to determine body composition, an intravenous glucose tolerance test to determine insulin sensitivity, and a skeletal muscle biopsy for measurement of in vitro substrate oxidation" (Osterberg. 2015). 

Subsequently, participants were randomized to receive either VSL#3 (2x450 billion bacteria), a dietary probiotic supplement that contains a motley mix of bacteria, i.e. Streptococcus thermophilus DSM24731, Lactobacillus acidophilus DSM24735, Lactobacillus delbrueckii ssp. bulgaricus DSM24734, Lactobacillus paracasei DSM24733, Lactobacillus plantarum DSM24730, Bifidobacterium longum DSM24736, Bifidobacterium infantis DSM24737, and Bifidobacterium breve DSM24732, or placebo daily during 4 weeks.

Figure 1: Composition (in g/day) and energy consumption (kcal/day) of the lead in and high fat diet (Osterberg. 2015).

Both, i.e. the probiotic supplement VSL#3 as well as the placebo supplement, were consumed alongside a high fat milk shake which also served to bring up the total energy intake (+1,000kcal/day) and relative contribution of fat from 8% to 55% compared to the standardized diet that was used in the 2-week lead in. Practically speaking, we are thus looking at a standardized high fat overfeeding study with or without probiotic intervention.

Figure 2: Changes in body composition in response to 4-week high fat overfeeding with or without probiotic supplementation (VSL#3, a 900 billion multi-strain probiotic) in 20 normal-weight young men (Osterberg. 2015).

A study that yielded interesting results, but results that are of questionably practical relevance. Yes, there was a statistical group effect for the changes in total body mass (0 kg vs. 0.8kg) and the total body fat mass (+1.1% vs. +2.4%).

Since there were neither significant differences in body fat% due to the lower lean mass gains in the probiotic group and considering the fact that there were no additional health effects in form improvements in insulin sensitivity or fat oxidation. Since neither of them was affected by the overfeeding, anyways, the significance of the lack of change is questionable.

Bottom line: In spite of the statistically significant weight and fat gain differences, the interpretation of the study at hand is not 100% straight forward. This may be due to the fact that within only 4 weeks other changes (esp. health relevant parameters) did not occur in either group.

While this study shows no immediate health benefits, there's evidence that gluten sensitive individuals may benefit from supplementing /w certain strains.

Furthermore, it must be said that the reduced lean mass gains in the probiotic strain and the subsequent lack of changes in body fat percentages, suggest that the amelioration of the subjects' weight gain is mediated by a mere reduction in energy-availability (this assumes that the intakes in both groups were identical to begin with). If this is the case, the supplement still has its merits: According to the questionable approximation that says that it takes 7,000kcal extra to gain 1kg of body fat, the probiotic supplementation would have compensated for 1.3 kg x 7000 kcal/kg = 9100kcal over 4 weeks and 325 kcal/ day (note this is not a scientifically accurate calculation).

Still, much more research is going to be necessary - not only to elucidate the exact mechanism, but also to find out if the effect might depend on the type of diet: A high fat diet, for example, has been shown to have significant, potentially detrimental effects on the human gut microbiome, which may be meditated by the bile acid resistance of several strains of bacteria, i.e. more fat = exuberant bile production = death to many good bacteria (David. 2014) |  Comment on Facebook!

References:

• David, Lawrence A., et al. "Diet rapidly and reproducibly alters the human gut microbiome." Nature 505.7484 (2014): 559-563.
• Osterberg, et al. "Probiotic Supplementation Attenuates Increases in Body Mass and Fat Mass During High-Fat Diet in Healthy Young Adults." Obesity (2015): Ahead of print.

Non-Adherence and Design Problems: Two Reasons Why Recent Diet Study May Fail to Show Benefits of High(er) Protein + Dairy Intakes in Overfat (>37%) Women

Don't expect weight loss wonders from high(er) protein and dairy intakes, but especially when the energy intake is not controlled both can have benefits the study at hand could not detect.

What's better a calorie reduced diet with the suggested amount of protein or one with a slightly higher amount of protein and extra low-fat dairy in it, when it comes to shedding the exuberant body fat off the hips, abs and buttocks of 104 overweight / obese (or with a body fat content of 37%+ "overfat") premenopausal women?

That's probably not exactly the way the scientists from the Utah State University, the Pennsylvania State University, the University of Illinois and the FB Technical Center (Shlisky. 2015) would phrase their research question, but in the end, their 24-week three-phase randomized weight loss intervention comes tried to answer exactly this question.

Learn more about women's weight loss & co a the SuppVersity

1g PRO per 2g CHO + Circuit T. for Women?

Is the Optimal Exercise Order Sex-Specific?

1-3mg Melatonin Shed Fat W/Out Diet & Exercise

Not Bulky! Lifting Will Make Toned & Strong.

How to Really Train Like a Woman

Sex-Differences in Fat Oxidation - Reviewed

To learn more about the impact of higher protein intakes (30% vs. 20% of total energy intakes) and the purported "magic" of diets that are high in low fat dairy (in particular yogurt), Julie D. Shlisky and her colleagues had their subjects go through a three-phase weight loss intervention with

• the JumpStart phase (weeks 0–2), being intended to kickstart the subjects' weight loss on a ~35% energy deficit, phase (2), 
• the Weightloss phase (weeks 3–12; total of 12 weeks), during which the subjects were supposed to adhere to a 1,500-1,700kcal diet which came close to a 25-30% energy deficit compared to their baseline energy intakes, and
• the Weightloss Maintenance phase, (weeks 13–24; total of 12 weeks), over the course of which the subjects had to stick to a dietitian designed "energy-balanced" diet which had still ~20% less energy than the subjects baseline diet (see Figure 4, right)

If you look at the tabular overview of what the subjects eat (I won't reprint 4 pages from the full text here) you can easily get confused and think that there were five different groups, eventually it does yet all come down to two groups, the intervention (INT) and comparison (COM) groups and their different diets during the previously explained phases of the study.

Figure 1: Macronutrient compositions of the prescribed diets in the intervention and comparison group (Shlisky. 2015).

In that, the most significant inter-group difference were (a) the macronutrient composition with 30% PRO, 25% FAT, 45% CHO in the intervention group (INT) and 16-17% PRO, 24-25% FAT, 59% CHO in the comparison group (COM).

Figure 2: Total intake (g) of carbohydrates, proteins and fats during the 12 week weight loss and maintenance phases (Shlisky. 2015)

"[w]eekly educational sessions were held for both INT and COM groups throughout the 6- month study and included lessons on basic nutrition knowledge, exchange patterns of eating, portion size and control, purchasing and preparing food and modifying recipes as well as motivational lessons on outcome expectations, selfregulation and monitoring, problem- solving, lifestyle modification, emotion eating and motivation for walking" (Shlisky. 2015) 

In addition, the subjects were told to consume 5 servings per day (with a focus on low fat yogurt) in the intervention and 3 servings of dairy (excluding yogurt) in the comparison group, as well as to finally get their behind off the couch for a total of ~8,000-10,000 steps per day (that was ~30-40 minutes of walking per day).

Thorpe et al. were able to show that high(er) protein intakes from dairy will decrease calcium loss and preserve bone mass (WB = whole body; LS = lumbar spine) while dieting. Don't fall for the "protein is bad for your bones" lie!

What does previous research tell us? If you look at previous research by Bowen (2004 & 2005), Josse (2011), Thorpe (2008) and Zemel (2004), there is significant evidence that high(er) protein intakes will augment fat loss and lean mass retention while increased dairy intakes may benefit bone mass and metabolic markers in men, women, young and old. In particular, when they are consumed alongside true exercise regimen, high(er) protein intakes have been proven have additive effects on body comp. during weight loss (8.8kg vs. 5.5kg fat loss in 16wks | Layman. 2005).

Against that background I would be very hesitant to take use the study at hand to argue that you can shed body fat just as effectively on the bogus "recommended diet" (=15-20% protein, 60% carbohydrates and 20-25% fat).

Needless to say that the novelty of the physical activity, of which I'd like to remind you that it had the same volume for both groups, must be taken into consideration when we take a look at the results of the 24-wk study:

Figure 3: Relative changes in markers of body composition after the weight loss and weight maintenance phase; all values expressed as percent difference to the respective pre-values in both groups (Shilsky. 2015).

Now, if you look at the overall effects and inter-group differences in Figure 3, three things are remarkable: Firstly, all subjects lost a significant amount of body weight and body fat without having to starve themselves or spending hours on the elliptical or treadmill. Secondly, there were no inter-group differences, which means that neither the overall increase in protein intake (see Figure 2), nor the increased intake of low-fat dairy and most prominently yogurt (effectively, the difference was only 1 serving per day, because the INT subjects failed to hit their target of five and ate only four servings per day) had beneficial effect on (a) the actual weight and more importantly fat / lean mass loss and (b) the subjects' general ability to keep the weight off during the follow up.

Figure 4: Reduction in energy expenditure (% of baseline) and total step count (activity level) of the subjects in the weight loss and weight maintenance phases of the study (Shlisky. 2015)

If we also take into account the data from Figure 3 which depicts the reduction in energy intake from baseline and the total number of steps participants in both groups took on a daily basis, we could yet conclude that the lower dairy (no yogurt) + lower protein group achieved very similar results with less efforts. There is thus no debating the scientists conclusion that

"[h]ealthy premenopausal women with excess adiposity effectively lost BW and fat mass and improved some metabolic risk factors following an ERD with approximately 20% protein and 3 svg/d of nonfat dairy intake." (Shlisky. 2015)

The increased protein or dairy (in this case mostly yogurt) intake did after all not offer significant benefits, as neither of the existing differences in Figure 3 was statistically significant.

The actual macronutrient ratio during the weight loss and maintenance phase (figure shows averages) was by no means what it was supposed to be. The women ate ~8% less protein than they were supposed to do.

So, there's no benefit to high(er) protein and dairy intakes? No, there isn't - at least in a study with such a questionable design. Did you recognize the culprit? Yes, you're right: What on earth do you expect to happen if you design a "weight maintenance phase" during which the subjects still have to consume an energy reduced diet... I mean, it is well possible that the dietitians equations said that the diet was "energy-balanced". If you compare their intake to the ad-libitum diets of the subjects (=their baseline diet), the women still consumed 18% (HP) and 27% (NP) less energy during the weight maintenance phase - this time with a significant inter-group difference in favor of the high(er) protein high(er) dairy (yogurt) group who consumed more energy during both the weight loss and maintenance phase with identical results.

I am not sure what you think, but I personally would refute any statement about the standard diet recommendation being as efficient as a high(er) protein + high(er) dairy variety based on the study at hand. The increased satiety effect, a potential increase in thermogenesis, etc. - all the purported benefits of high(er) protein intakes couldn't show due to (a) non-adherence (instead of 30%, the subjects in the intervention group consumed only 23% and 20% protein during the weight loss and maintenance phase, respectively, and were thus not far off of the 20% and 18% in the COM group) and (b) the stupid idea not to let the women eat an ad-libitum with a fixed macronutrient ratio during the weight maintenance phase. This is after all a more realistic scenario and one in which real benefits of high(er) protein can show | Comment on Facebook!

References:

• Bowen, Jane, Manny Noakes, and Peter M. Clifton. "A high dairy protein, high-calcium diet minimizes bone turnover in overweight adults during weight loss." The Journal of nutrition 134.3 (2004): 568-573.
• Bowen, J., M. Noakes, and P. M. Clifton. "Effect of calcium and dairy foods in high protein, energy-restricted diets on weight loss and metabolic parameters in overweight adults." International journal of obesity 29.8 (2005): 957-965.
• In particularly in conjunction with exercise, high(er) protein intakes have been proven have additive beneficial effects on body composition during weight loss (Layman. 2005)
• Josse, Andrea R., et al. "Increased consumption of dairy foods and protein during diet-and exercise-induced weight loss promotes fat mass loss and lean mass gain in overweight and obese premenopausal women." The Journal of nutrition 141.9 (2011): 1626-1634.
• Shlisky, Julie D., et al. "An energy‐reduced dietary pattern, including moderate protein and increased nonfat dairy intake combined with walking promotes beneficial body composition and metabolic changes in women with excess adiposity: a randomized comparative trial." Food Science & Nutrition (2015).
• Thorpe, Matthew P., et al. "A diet high in protein, dairy, and calcium attenuates bone loss over twelve months of weight loss and maintenance relative to a conventional high-carbohydrate diet in adults." The Journal of nutrition 138.6 (2008): 1096-1100.
• Zemel, Michael B., et al. "Calcium and dairy acceleration of weight and fat loss during energy restriction in obese adults." Obesity research 12.4 (2004): 582-590.