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At the moment it is by no means clear which type of athlete / gymrat would benefit from milk fat globule membrane supplementation and which wouldn't. It's after all well possible that the effects Soga et al. observed in rookies wouldn't occur in adv. trainees or professional athletes.

After the study on nucleotide supplements the Satako Soga's latest paper on the dietary supplementation with milk fat globule membrane is #2 on the list of studies with promising new ergogenics in less than a month. In view of the fact that the last year has been devoid of any true innovations, this is a welcome diversion from writing about whey (or other protein powders), creatine, beta alanine and baking soda, as well as the occasional study on HMB for me.

In spite of the fact that this is a follow up on previous rodent studies from the same researchers, I must warn you not to to expect too much of MFGMs, yet. More data and studies with more realistic resistance training + supplementation protocols from independent labs are warranted before MFGMs may eventually appear next to the previously mentioned top dogs on a list of "waredownloadsoft Recommended Supplements".
But hey, let's keep the skepticism for the bottom line and take a look at what the scientists from the Kao Corporation did with their fourteen Japanese subjects. The men, who were aged 31–48 years and did not participate in regular strength training before the study, took 1 g of the  structural membranes of milk which are usually covering the triglyceride globules that are dispersed as emulsified bodies in milk or 1g of an identically looking whole milk powder as a placebo in tablet form for 4-weeks (composition see Table 1).

Table 1: Composition of MFGM and whole milk powder (Soga. 2015)

"On the exercise training enforcement days [i.e. the days on which the subjects were required to train], the subjects were instructed to take the tablet within 1 h before training. On the other days, the subjects were instructed to consume the tablet at the time of their choice during their daily routines.

The MFGM was prepared from buttermilk by filtering and centrifugation. The MFGM and whole milk powder compositions were analyzed at Japan Food Research Laboratories (Tokyo, Japan)" (Soga. 2015).

The exercise routine the subjects from both groups had to follow consisted of two workouts per week. The workouts had to be performed on nonconsecutive days for 4 weeks using StrengthErgo 240 stationary cycling exercise machines (Mitsubishi Electric Corporation, Tokyo, Japan). On these machines, the subjects completed 3 sets of 15 % maximal voluntary contraction (MVC) cycle exercises for 60 s and 7 sets of 20 % MVC cycle exercises for 40 s at 50 rpm.
Physical function tests and surface electromyography (EMG) were conducted at baseline and at the end of the study period. In addition, some hemotological parameters were tested of which - surprise - the data in Figure 1 tells you that MFGMs have a small, but statistically significant "EPO-effect" and are thus capable of raising both the red blood cell and hemoglobin content - an effect that has been observed in rodents too (Haramizu. 2014b) and may be ascribed to the incorporation of MFGM phospholipids into red blood cells which would in turn be less vulnerable to exercise-related or other stressors. Whatever the reason for these changes may be, they are certainly in line with the previously mentioned (see red box) increase in fatty acid oxidation during endurance exercise that may be facilitated by an RBC and hemoglogin related increase in oxygen transport.

Figure 1: The significant increase in red blood cell and hemoglogin content could explain the previously observed increases in endurance performance and fatty acid oxidation in Haramizu et al. (2014a). The buffered decrease in white blood cell may not be statistically significant, but may still indicate beneficial effects on the immune system (Soga. 2015).

Both the increase in RBC and hemoglobin, as well as the buffering of the albeit non-significant decline in white blood cells in the placebo group, which may be a response to the exercise-induced stress and evidence of an immune-boosting effect of MFGM supplementation during any potentially exercise induced immune suppression, do yet need further investigation before they can be explained mechanistically.

No further research is needed, though, to state that all other blood markers. These included AST + ALT (liver health), glucose and triglycerides + cholesterol, neither of which was affected by the supplement. The latter cannot be said of the increase in leg extension strength before and after the intervention and the EMG activity which showed highly significant inter-group differences.
In fact, the differences in Figure 2 are pronounced enough to ask the question: Were they induced by the supplementation alone or did the pathetic training regimen have an effect here, as well? As I am going to point out in the bottom line one paragraph below, we will need studies with more realistic training programs to answer this question in a way that's relevant for trainees like you and me. In the mean time, however, there is no debating "that the daily intake of 1 g MFGM combined with regular, twice weekly exercise improved skeletal muscle strength (leg extension) in middle-aged adults, despite a lack of change in muscle mass" (Soga. 2015).

Figure 2: The MFGM supplementation lead to significant increases in leg extension strength, of which the increase in EMG activity (likewise sign.) suggests that they were mediated by neuronal changes (Soga. 2015).

The same goes for the increase in RMS of surface EMG, which indicates that the dietary provision of MFGM increased the average (RMS = root mean square) motor unit activity during muscle contraction and may thus mechanistically explain why the subjects got stronger even though they didn't make substantial gains in muscle mass: The supplement helped them to "make the most" of the muscle they had. This hypothesis is in line with results from rodent studies which

"[...] revealed that dietary MFGM combined with regular exercise improved muscle strength in adult mice primarily by stimulating the pathway involving “nervous system development” in the skeletal muscle (Haramizu. 2014b). This pathway includes functional annotations such as formation of synapses, growth of neurites, or development of NMJ. Dietary MFGM combined with exercise increased skeletal muscle expression of docking protein-7 (Dok-7) and muscle-specific receptor tyrosine kinase in mice, both of which play a critical role in NMJ [neuromuscular junction] formation. Defects in NMJ function causes muscle weakness in neuromuscular disorders, and Dok-7 gene therapy improves NMJ formation and rescues the motor activity" (Soga. 2015).

And still, even at the risk that I may sound like a broken record, I have to repeat that without future research it is impossible to tell (a) whether the assumptions we've made about the increase in red blood cell count are accurate and, maybe even more importantly, (b) who, i.e. which type of athlete, will benefit most from using MFGM supplements.
References:

• Cano-Ruiz, M. E., and R. L. Richter. "Effect of homogenization pressure on the milk fat globule membrane proteins." Journal of Dairy Science 80.11 (1997): 2732-2739.
• Haramizu, Satoshi, et al. "Dietary milk fat globule membrane improves endurance capacity in mice." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 307.8 (2014): R1009-R1017.
• Haramizu, Satoshi, et al. "Habitual exercise plus dietary supplementation with milk fat globule membrane improves muscle function deficits via neuromuscular development in senescence-accelerated mice." SpringerPlus 3 (2014): 339.
• Kim, Hunkyung, et al. "Effects of Exercise and Milk Fat Globule Membrane (MFGM) Supplementation on Body Composition, Physical Function, and Hematological Parameters in Community-Dwelling Frail Japanese Women: A Randomized Double Blind, Placebo-Controlled, Follow-Up Trial." PloS one 6.10.2 (2015): e0116256.
• Lemonnier, Lori A., et al. "Sphingomyelin in the suppression of colon tumors: prevention versus intervention." Archives of Biochemistry and Biophysics 419.2 (2003): 129-138.
• Riccio, Paolo. "The proteins of the milk fat globule membrane in the balance." Trends in food science & technology 15.9 (2004): 458-461.
• Singh, Harjinder. "The milk fat globule membrane—A biophysical system for food applications." Current Opinion in Colloid & Interface Science 11.2 (2006): 154-163.
• Snow, D. R., et al. "Membrane-rich milk fat diet provides protection against gastrointestinal leakiness in mice treated with lipopolysaccharide." Journal of dairy science 94.5 (2011): 2201-2212.
• Soga, Satoko, Noriyasu Ota, and Akira Shimotoyodome. "Dietary milk fat globule membrane supplementation combined with regular exercise improves skeletal muscle strength in healthy adults: a randomized double-blind, placebo-controlled, crossover trial." Nutrition Journal 14.1 (2015): 85.
• Spitsberg, V. L. "Invited review: Bovine milk fat globule membrane as a potential nutraceutical." Journal of dairy science 88.7 (2005): 2289-2294.
• Timby, Niklas, et al. "Neurodevelopment, nutrition, and growth until 12 mo of age in infants fed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial." The American journal of clinical nutrition 99.4 (2014a): 860-868.
• Timby, Niklas, et al. "Cardiovascular risk markers until 12 mo of age in infants fed a formula supplemented with bovine milk fat globule membranes." Pediatric research 76.4 (2014b): 394-400.

Synephrine, arginine, citrulline - Which pre-workout ensures that you're "on fire"?

As I pointed out previously, my initial idea to cherry pick only the most interesting study results that were presented in form of of poster presentations at the Twelfth International Society of Sports Nutrition (ISSN) Conference and Expo in 2015 didn't work out. The number of interesting studies is is simply too much for a single waredownloadsoft article to discuss them all.

Accordingly, I am now posting the 2nd serving of what is going to be a multi-part series of articles with brief discussions of the most significant results of the >20 studies and short references to those that didn't make the waredownloadsoft cut in this, previous and future installments of this series for one reason or another.

• Synephrine More Ergogenic Than Thermogenic? There was not just one, but two poster presentations and a full paper that has been published only days ago on synephrine containing supplements at the ISSN meeting and on the ISSN website, respectively. Synephrine? Yes, that's the supplemental non-starter, ah... I mean allegedly powerful fat burner from orange peels. The one with promising fat loss results in rodents, but discouraging results in practice.
  
  Luckily, the studies that were presented in form of posters by scientists from the Texas A&M University (Jung. 2015 & Dalton. 2015) at the ISSN meeting did not deal with synephrine as fat burner. Rather than that, Jung et al. and Dalton et al. took a look at the short- and long-term safety of synephrine as a pre-workout. A pre-workout that contained either 3g beta alanine, 2g creatine nitrate, 2g arginine AKG, 300mg N-acetyl tyrosine, 270mg caffeine, and 15mg Mucuna pruriens, alone (PLA) or the same baseline ingredients and synephrine.
  

  Figure 1: Number of reps on sets 1-3 & 4-6 in the control and treatment conditions (Ratamess. 2015)

  Now, the fact that some synephrine in your preworkout won't kill you is not really exciting. I have to admit that. What is exciting... at least sort of, though is the fact that the questionable thermogenic turned out to be an effective ergogenic in the already published and thematically related study by Ratamess and colleagues (Ratamess. 2015). A study that shows that p-synephrine of which previous studies indicate that it is a potent, but highly selective β-3 adrenoreceptor may nor be the best fat burner (the good old ephedrine was a pan-receptor activator and clenbuterol & co target the β-3 receptor, maybe that's also why the fat loss results are rather disappointing) , but at least an underestimated ergogenic.

• As the data in Figure 1 goes to show you, the p-synephrine supplement, which was administered to twelve healthy, college-aged men at a dosage of 100mg either alone (S) or in conjunction with 100 mg caffeine (SCF) for three days. On the day on which the subjects participated in a standardized resistance exercise protocol consisting of 6 sets of squats for up to 10 repetitions per set using 80 % of their one repetition-maximum (1RM) with 2 min of rest in between sets, the supplement was ingested 45 minutes before the workout. In comparison to the placebo treatment synephrine alone triggered a significant increase in total repetitions and volume load. When synephrine was combined with 200 mg of caffeine, it also increased the mean power and velocity of squat performance. What did not change in response to either synephrine alone or caffeine and synephrine, though, were the blood lactate levels or the rate of perceived (RPE) exertion the subjects reported on the usual visual analogue scales.
  
  For me personally, that's a surprising result. For the scientists it "indicate[s that] supplementation with S and SCF can enhance local muscle endurance during resistance exercise" (Ratamess. 2015); and I have to admit: They are right. One thing you should keep in mind, though, is that unlike caffeine, where you often see reductions in RPE and thus an effect you will feel, synephrine will - even if it works - do its purported "magic" more subtly.
• The Latest on "Pump Supplements" - Creatine, Arginine, Citrulline, Nitrates -- To make sure that this series is not turning into a 12-part article, I will address the results of Moon's, Suzuki's and Vogel's results in one item (since Moon's paper basically summarizes the results of studies by Falcone and Joy, I won't discuss those separately) .
  
  

  Figure 2: Increases in blood flow volume (BFV) 33 minutes after the ingestion of 1.87g of RC, 3.67g of CP (citrulline content 1.87g), 1.87g of RA, or 3.07g of AP (arginine content 1.87g) before 3 sets of 15 arm curls (Moon. 2015).

  Moon et al.'s comparison of citrulline's and arginine's ability to increase the exercise-induced vasodilation and blood flow yielded unsurprising results that confirm that citrulline-based ingredients are more effective than arginine-based ingredients for modulating vasodilation and blood flow. Now that alone wouldn't be news-worthy if the scientists had not tested the effects of both, rawe L-citrulline (RC) and raw L-arginine (RA) and, citrulline and arginine bound to a whey peptide (CP and AP, respectively).
  
  I guess I am not going to surprise you, when I tell you that regular arginine was the worst vasodilator in this quartet. What is more surprising, though, is the extent to which the peptide bonding increased the vasodilating effects of regular citrulline and even arginine. With the the former producing 2x higher increases in vessel diameter and 9% higher increases in blood glow volume than regular citrulline (let's not even mention regular arginine | see Figure 2) the effects are pronounced enough to be potentially "feelable" and "visible" during a workout.
  
  

  Citrulline & Glutathione - GSH Amplifies & Prolongs CIT's NO Boosting Effects During + After Biceps Workout | learn more.

  Against that background I would be curious to see, whether the likewise recently reported performance enhancing effects of citrulline Suzuki et al.'s observed in twenty two well-trained young men who consumed 2.4 g / day of L-citrulline or placebo for 7 days and they took 2.4 g of L-citrulline or placebo 1 hour before 4 km cycling time trial on day 8 would be enhanced by bonding citrulline to whey peptides.
  
  I mean, if citrulline-whey-peptides appear to offer the same effects citrulline does, but at a higher efficacy, their beneficial effect on cycling time trial performance of which the Suzuki et al. argue that it was mediated by an up-regulation of plasma NO availability should be superior to that of raw citrulline, as well, right?
  
  And now that we are already talking about what really matters, i.e. performance enhancements, not increases in blood flow, it would also be interesting to see a follow up on the last "pump supplement" study to be mentioned in this installment of the ISSN Research Review: A study by Vogel et al.'s on the vasolidating effects of an arginine-nitrate based pre-workout supplements that shows significant increases in brachial artery diameter. Increases that are quantitatively similar to those Moon et al. observed for citrulline-whey-peptides in the previously discussed study. That does not mean, though that they are equally effective, though. To be able to say that we would need a study in which both agents are compared head-to-head. Unless this study is done and a follow up on Vogel's study proves that the increases in blood flow will actually produce significant performance gains, the only thing I can say about arginine nitrate is: It's interesting, but with respect to its ergogenic effects more studies have to be done.

References:

• Allison, D. B., et al. "Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain?." International journal of obesity 29.4 (2005): 443-446.
• Bouza, Brooke, et al. "Exercise and calorie information on menus is not enough to improve food choices in Hispanic adults." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P3.
• Dalton, R., et al. "Safety and efficacy of a pre-wrkout dietary supplement with and without synephrine." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P5.
• Falcone, Paul H., et al. "Acute hemodynamic effects of L-arginine, arginine nitrate, and arginine peptide on exercise-induced vasodilation and blood flow in healthy men." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P10.
• Joy, Jordan M., et al. "A comparison of raw citrulline and citrulline peptide for increasing exercise-induced vasodilation and blood flow." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P18.
• Jung, Y. P., et al. "Effects of 8 weeks pre-workout dietary supplement ingestion with and without synephrine on blood chemistry panel." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P4.
• Moon, Jordan R., et al. "A comparison of citrulline and arginine for increasing exercise-induced vasolidation and blood flow." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P6.
• O'Connor, A., et al. "Short-term powdered tart cherry supplementation encircling an acute endurance challenge potentially increases running performance and attenuates post-race markers of inflammation." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P7.
• Suzuki, Takashi, et al. "Oral L-citrulline supplementation enhances cycling time trial performance in healthy well-trained males." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P52.
• Vogel, Roxanne M., et al. "Acute hemodynamic effects of a multi-ingredient performance supplement on brachial artery vasodilation and blood flow volume following elbow flexion exercise in healthy young men." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P28.

Nucleotides are building blocks of our DNA and RNA and - as preliminary evi- dence suggests - ergogenic supplements for athletes on intense workout routines. In that, "intense" is the key word, 'cause normally our bodies can produce enough nucleotides on their own.

Nucleotides? Yeah, this are the small subunits, of nucleic acids like DNA and RNA. They are essential to nearly all biological processes including DNA and RNA synthesis, coenzyme synthesis, energy metabolism, cellular signaling and protein homeostasis and can be produced by our bodies "on demand" via de novo synthesis. Just like some of the non-essential amino acids which may become essential under certain circumstances, though, our bodies' own nucleotide production facility are often incapable of meeting the needs of rapidly proliferating tissues.

As Sterczala et al. (2015) point out in the introduction to their latest paper in the Journal of Strength and Conditioning Research, a salvage pathway is therefore required to synthesize nucleotides from exogenous sources (Gil. 2002).
As such, dietary nucleotides are necessary to maintain immune function, tissue growth and cellular repair. Sounds familiar? Yeah, all of those functions are affected by exercise, which can (at least temporarily) significantly increase one's nucleotide demands to levels that cannot be supplied by endogenous (=the body's own) synthesis, alone. A recent study which shows that the blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis even suggest that this may be one of the reasons old muscle won't grow (Kirby. 2015). Consequently, there has been a growing interest in the potentiaL implications of exogenous nucleotide supplementation on exercise-induced immune
responses.

"Aside from increases in salivary immunoglobulins, McNaughton et al. (2006 & 2007) have observed a decreased cortisol response to exercise, which would partially explain the reduced immunosuppression. Animal models have observed similarly attenuated cortisol responses to stressful stimuli (Palermo. 2013, Tahmasebi-Kohyani. 2012). Given the roles of cortisol in gluconeogenesis and glycogenolysis, a reduced cortisol response may indicate a reduction in the metabolic stress of the exercise bout as a result of nucleotide supplementation. In the days following stressful exercise, [chronically (!) | see red box to learn why this is important] elevated cortisol levels could impair recovery, as cortisol can increase protein degradation and inhibit protein synthesis (Hickson. 1993; Kraemer. 2005)" (Sterczala. 2015). 

So, while we don't want to block the cortisol response to exercise altogether (here's why), Sterczala et al. are right: Attenuating or controlling it may quite beneficial. Especially if this attenuation occurs in the days after the exercise-stressor, when you want your cortisol levels to return to normal. Unfortunately, Ostojic et al. (2012 & 2013) and McNaughton et al. (2006 & 2007) who have already demonstrated the beneficial effects of nucleotide supplementation following acute exercise, did not control for the immune and cortisol response during the recovery period after the exercise stimulus. In addition, their studies involved cycling and running exercises which are, as Sterczala et al. rightly point out, "quite different in terms of muscle recruitment and metabolic demands when compared to heavy resistance exercise" (Sterczala. 2015). Therefore, the effects of nucleotide supplementation on the response patterns to resistance exercise are currently unknown and thus the perfect research object for a new study - Sterczala et al.'s new study.
Said study used a double blinded, cross-over, within subject design, with ten young men and ten women participating in the acute heavy resistance exercise protocol (AHREP) following a loading period with either a nucleotide supplement or placebo supplementation phase.

Do you remember that protease supple- mentation (e.g. 1,000mg Bromelain) has recently been shown to have ergogenic effects in athletes, too?

"The nuBound® (Nu Science Laboratories, Inc., Boston, MA [the sponsor of the study]) supplement contains dietary nucleotides, which are extracted from yeast (saccharomyces cerevisiae). During the supplement treatment cycle, subjects took two capsules of nuBound® daily, one upon waking, and one following exercise. The two capsules (1000mg) contained 278mg of dietary nucleotides, 375mg amino acids (l-glutamine, l-methionine, l-lysine), riboflavin (4.5mg), folate (400mcg), biotin (188mg) and pantothenic acid (12mcg). Other ingredients included fructo-oligosaccharides (chicory root), inositol and sodium citrate.

During the placebo cycle, subjects followed a dosing schedule identical to the supplement cycle. The placebo capsules were identical in size, shape and color to the nucleotide supplement but contained only lactose and magnesium stearate. During the first treatment cycle, subjects recorded their daily dietary intake on a diet log. The log was then used to help subjects replicate their diet during the second treatment cycle. Subjects also replicated their activity protocol during the study for each cycle" (Sterczala. 2015)."

Each cycle (placebo - PL; nucleiotides - NT) began with a two week loading phase in which subjects took the supplement while maintaining their normal exercise routines. At the beginning of the third week, an acute heavy resistance exercise protocol (AHREP) was completed. To assess the effects on recovery, subjects reported to the laboratory 24, 48 and 72 hrs following the AHREP for additional blood draws and performance testing. Before and after the the acute heavy resistance exercise protocol (AHREP), and at 24, 48, and 72 hrs thereafter, blood samples were analyzed for cortisol, myeloperoxidase, and absolute neutrophil, lymphocyte and monocyte counts. Creatine kinase was analyzed pre-AHREP and at 24, 48, and 72 hrs post-AHREP. Performance measures, including peak back squat isometric force and peak countermovement jump power were also analyzed.

Figure 1: Effects of nucleotide (NT) and placebo supplement (PL) preload for two weeks on cortisol (~stress) and creatine kinase (~muscle damage) response to exercise (Sterczala. 2015).

As you can see in Figure 1 the nucleotide supplementation resulted in significant (P ≤ 0.05) decreases in observed cortisol and MPO acutely following the AHREP, as well as significantly lower CK values at 24 hrs post. The AHREP significantly affected leukocyte counts, however, no treatment effects were observed (which is in contrast to previous studies, but in view of the disconnect between this markers and practically relevant immune outcomes, like the susceptibility to infection, irrelevant).

Figure 2: While the improved cortisol and CK are nice to see, only the accelerated force recovery in the isometric back-squat test may actually be practically relevant for athletes (Sterczala. 2015).

What is significantly more important than any of these markers of muscle stress, muscle damage or immune function is the fact that the the nucleotide supplement increased the peak force in the back squat isometric force test (albeit not the power during counter-movement jumps) immediately post AHREP and at 24 hrs and 48 hrs (see Figure 2). After all, changes like these, and not improvements in markers of whatever are what really matters for athletes.
References:

• Gil, A. "Modulation of the immune response mediated by dietary nucleotides." European Journal of Clinical Nutrition 56 (2002): S1-4.
• Hickson, et al. "Exercise and inhibition of glucocorticoid-induced muscle atrophy." Exercise and sport sciences reviews 21.1 (1993): 135-168.
• Kraemer, William J., and Nicholas A. Ratamess. "Hormonal responses and adaptations to resistance exercise and training." Sports Medicine 35.4 (2005): 339-361.
• Kirby, et al. "Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis." Journal of Applied Physiology 119.4 (2015).
• Mc Naughton, L., D. J. Bentley, and P. Koeppel. "The effects of a nucleotide supplement on salivary IgA and cortisol after moderate endurance exercise." Journal of sports medicine and physical fitness 46.1 (2006): 84.
• Mc Naughton, Lars, David Bentley, and Peter Koeppel. "The effects of a nucleotide supplement on the immune and metabolic response to short term, high intensity exercise performance in trained male subjects." Journal of sports medicine and physical fitness 47.1 (2007): 112.
• Ostojic, Sergej M., and Milos Obrenovic. "Sublingual nucleotides and immune response to exercise." J. Int. Soc. Sports Nutr 9 (2012): 31.
• Ostojic, Sergej M., Kemal Idrizovic, and Marko D. Stojanovic. "Sublingual Nucleotides Prolong Run Time to Exhaustion in Young Physically Active Men." Nutrients 5.11 (2013): 4776-4785.
• Palermo, Francesco Alessandro, et al. "Effects of dietary nucleotides on acute stress response and cannabinoid receptor 1 mRNAs in sole, Solea solea." Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 164.3 (2013): 477-482.
• Sterczala, et al. " The Physiological Effects of Nucleotide Supplementation on Resistance Exercise Stress in Men and Women." Journal of Strength and Conditioning Research (2015): Publish 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.

Chicken legs, old man? Must have been too much antioxidants ;-)

If this is not your first waredownloadsoft article, you may have read about the potential negative effects of (high dose) anti-oxidant supplementation in previous waredownloadsoft articles about, or touching on the effects of hormesis, i.e. the beneficial effects of "good oxidative stress". Up to now I have yet often said that it is possible that this effect occurs mostly in people who can handle stress pretty well and thus have to hammer it to trigger a measurable adaptive response.

The elderly subjects in the latest study from the University of Agder in Norway (Bjornson. 2015), however, don't exactly belong to the group of people I was thinking about, when I phrased this hypothesis.

Table 1: Overview of the exercises the scientists did. The exercises were identical to a previous study in young individuals and the workout was designed to give large metabolic stress (i.e., oxidative stress) and the intention was to stimulate as much muscle growth as possible (Bjornson. 2015)

"The 12-week strength training program had an undulating periodized profile (Jiménez, 2009). The protocol included three full-body sessions per week, emphasizing free weight exercises where all the major muscle groups were included. Two of the sessions each week were “moderate” (8–10 rep, with 1 min rest between sets), and one varied between “heavy” (3–5 rep, with 2 min rest between sets) and “light” (13–15 rep, with 45 s rest between sets)” every second week. [...]  

The number of sets per exercise was increased progressively from 1 to 4 sets during the first 10 weeks, and then reduced with one set each of the last 2 weeks of the intervention (tapering). 

The participants conducted one additional “warm-up” set at 50% of their target weight in each exercise before the main sets started. The last set of each exercise was performed with maximal number of repetition, and if the number of repetitions exceeded the sessions target repetitions, the load was adjusted for the next week’s sessions. Two experienced instructors supervised all strength training sessions and the loads were weekly adjusted" (Bjornson. 2015 | my emphases).

Ashwaghanda may be for gymrats, too.

Ashwaganda is one of the supplements that has been around forever. While this would suggest that it works, the relatively low number of people who actually use it suggests otherwise and scientific evidence in form of peer-reviewed, non-sponsored studies that would allow us to draw a reliable conclusion with regard to its usefulness for athletes is rare... Well, actually there are only four studies on Withania somnifera, which is also known as Indian Ginseng or Winter Cherry, of which you could say that they are at least relevant to the topic - even though none of them was conducted in resistance trained / training individuals.
There's a study by Raut, et al. that evaluated the "tolerability, safety, and activity of Ashwagandha (Withania Somnifera) in healthy volunteers" from 2012; a study by Sandhu, et al. in which the researchers probed the "effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults" and found an increase in velocity [+3%], relative power [+9%] and VO2 max [+7%] in response to 500mg/day for 8 weeks; a study by Choudhary et al. (2015) which found both, increases in VO2max and quality of life of 50 "athletic" individuals in response to a commercial Ashwaghanda product that goes by the cryptic acronym KSM-66 Ashwagandha; as well as a study by Shenoy, et al. (2012) which found 11%, 16% 16% and 2% increases in time to exhaustion, VO2, metabolic equivalents (METs) and respiratory exchange ratio (RER), respectively (note: the benefits were sign. lower in female study participants, see Table 1), in response to the same amount, i.e. 500 mg/day, of an aqueous root extract of Ashwagandha that has been used by Sandhu et al. two years before.

Table 1: Mean percentage (%) difference of pre-post readings of forty male and female elite (elite here refers to the participation of the athlete in at least state-level events) Indian cyclists in response to 8 weeks on 500 mg of standardized aqueous root extract, which was obtained in the form of capsules from Dabur India Limited (Sandhu. 2012).

With that being I should mention that several studies suggest that your source of Ashwaghanda may well determine its effects. So, any current and future contradictions in the literature may be related to the level of desirable and undesirable "active ingredients" in the tested extracts. Patel, et al., for example, report that 50% of the samples they analyzed in 2015 contained mercury (Hg) at levels "above the permissible limit". Reason enough for the researchers to conclude that the "consumption of drug (Ashwagandha) obtained from polluted areas may cause accumulated side effect as well as the toxic effect of the heavy metals, respectively" (Patel. 2015). In view of the fact that I assume that Wankhede et al. used an (a) heavy-metal free and (b) truly standardized extract with actual steroidal lactones (withanolides, withaferins), saponins and alkaloids like isopelletierine and anaferine in it, in their recent

"prospective, double-blind, placebo-controlled parallel group study to measure the possible effects of ashwagandha extract on muscle strength/size, muscle recovery, testosterone level and body fat percentage" (Wankhede. 2015)

in young men who participated in a standardized resistance training regimen, it is thus not totally impossible that the next best Ashwaghanda product from the internet will produce significantly different results. I guess you should keep that in mind if you plan to go shopping after reading this article. The product Wankhede, et al. used, by the way, was provided by Shri Kartikeya Pharma and Ixoreal BioMed and happened to be the same KSM-66 high-concentration root extract Choudhary et al. used in their likewise very recent study.

Figure 1: Overview of the study design as it is visualized in Wankhede et al. (2015)

I don't want to waste your precious time with speculations, though. Let's talk about Wankhede's recent study, on 57 men (18-50 years), who were randomly allocated to either the treatment group, in which the subjects consumed 300 mg of ashwagandha root extract twice daily, or the control group, which received identically looking starch placebo capsules.
Both, the subjects who received the active treatment in form of 2x300 mg/day Ashwagandha, as well as those who received the placebo treatment, underwent identical 8-week resistance training programs; programs, the scientists describe as follows:

"The resistance training program consisted of sets of exercises over major muscle groups in both the upper body and the lower body. [...] Each subject in both groups was asked to come to a training session every other day, with one rest day pe week, for three days per week. Every session began with a warm up consisting of five minutes of low-intensity aerobic exercise. The subjects were instructed to perform, for each set as many repetitions as they could until failure. The subjects were asked to go through the full range of motion and were demonstrated the proper technique for safe and effective weight lifting" (Wankhede. 2015).

The workouts were periodized with increasing number of sets from 1-2 to 3. More specifically, the subjects performed barbell squats, the leg extensions, seated leg curls, machine chest presses, barbell chest presses, seated machine rows, one-arm dumbbel rows, machine biceps curls, dumbbel biceps curls, cable triceps press-downs, dumbbell shoulder presses, and the straight-arm pull-downs in the first two weeks and barbell squat (3 sets) the leg extension (3 sets), the leg curl (2 sets), one chest exercise (flat, incline or decline press or fly, cable cross over, 3 sets), one back exercise (rows, pull up, pull down or seated cable row, 3 sets), another chest exercise (3 sets) another back exercise (3 sets), one biceps exercise or one triceps exercise (curls or extensions, 3 sets), and one shoulder exercise (raises or presses, 3 sets) for the rest of the 8-week study.

Figure 2: Absolute increases in thigh, arm and chest size and reduction in body fat (%) over the course of the 8-week study; the figures above the bars denote the inter-group difference in %, * denotes significant differences (Wankhede. 2015).

Significant inter-group differences were found for almost all of the measured variables: the size increases in the arms and chest, the change in body fat (remember, those are only BIA values), serum testosterone, and CK (remember, this is not a very reliable marker of exercise recovery), as well as the strength increase on the bench press and leg extension machine (1RM, each) differed significantly not just from pre- to post, but also from the supplement to the placebo group (see Figure 2, Figure 3).

Figure 3: Changes in 1RM (kg) strength and testosterone (ng/dL) over the course of the 8-week study; the figures above the bars denote the inter-group difference in %, * denotes significant differences (Wankhede. 2015).

Against that background it seems certainly warranted that Wankhede et al. postulate that their study "confirms previous data regarding the adaptogenic properties of ashwagandha" and it also clearly "suggests it [Ashwaghanda supplementation] might be a useful adjunct to strength training" (Wankhede. 2015). The authors are yet also right, when they point out that their study has...

"[...] the following limitations which should lead us to interpret the findings with some caution: the subjects are untrained and moderately young, the sample size of 50 is not large and the study period is of duration only 8 weeks" (Wankhede. 2015)

Accordingly, Wankhede et al. rightly demand that further "[r]esearch studying the possible beneficial effects of ashwagandha needs to be conducted", research that spans "longer periods of time" and includes "different populations including females and older adults of both genders" (Wankhede. 2015). In this regard, I would like to remind you that the previously discussed results Shenoy et al. published three years ago, in which the sex of the participants had a major impact on the study outcome, make studies comparing male to female resistance trainees particularly appealing - from a science perspective, obviously ;-)
References:

• Choudhary, Bakhtiar, A. Shetty, and Deepak G. Langade. "Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults." AYU (An international quarterly journal of research in Ayurveda) 36.1 (2015): 63.
• Kyle, Ursula G., et al. "Bioelectrical impedance analysis—part II: utilization in clinical practice." Clinical nutrition 23.6 (2004): 1430-1453.
• Patel, Dhaval, Harisha C. Rudrappa, and Proshanta Majumder. "A comparative pharmacognostical, physicochemical, and heavy metal analysis on Ashwagandha root obtained from natural and polluted sources." International Journal of Green Pharmacy 9.1 (2015): 14.
• Raut, Ashwinikumar A., et al. "Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania Somnifera) in healthy volunteers." Journal of Ayurveda and Integrative Medicine 3.3 (2012): 111.
• Sandhu, Jaspal Singh, et al. "Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults." International journal of Ayurveda research 1.3 (2010): 144.
• Shenoy, Shweta, et al. "Effects of eight-week supplementation of Ashwagandha on cardiorespiratory endurance in elite Indian cyclists." Journal of Ayurveda and integrative medicine 3.4 (2012): 209.
• Wankhede, Sachin, et al. "Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial." Journal of the International Society of Sports Nutrition 12.1 (2015): 43.
• 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.