Weight Loss Program for Health: anabolic

Showing posts with label anabolic. Show all posts

Arms Don't Grow Faster With Leg Training: Stuart M. Phillips Busts Ronnestad's "Hormonal Ghosts"

Image 1: Although Tom Platz had massive
arms, as well, there is little conclusive scientific
evidence that this was a result of leg training.

Usually I am offering you my thoughts and comments on the results of the studies I am presenting here at the SuppVersity. In this case however, I am going to rely on the insightful analysis of Stuart M. Phillips, head of the Department of Kinesiology, Exercise Metabolism Research Group at the McMaster University, who spotted some interesting inconsistencies in a recently published paper by Ronnestad et al. who had reported that (contrary to conclusive findings from dozens of study by Phillips and others) endogenous hormone release from leg training had a major impact on the anabolic response in the arm flexors (cf. news from March, 2nd / I plead guilty of not having seen these inconsistencies, though I must say in mitigation that back in March I only reported, not commented on studies).

As Phillips points out, Ronnestad's conclusion that training legs+arms results in bigger guns or, rather, that without training legs, your arms won't grow at all is funded in

selective reporting (considering only the site of the largest CSA), incomplete statistical analysis (not comparing the changes (in CSA between arms), and questionable MR practices (Phillips. 2011)

In his analysis of the Ronnestad study, Phillips shows conclusively that, according to Ronnestad's own figures (Phillips refers to figure 6 of the paper, in particular), the authors' statement that

only L + A [leg plus arm training—a high ‘anabolic’ hormonal exposure condition] achieved increase in the CSA at the part of the arm ﬂexors with the largest cross-sectional area (p \ 0.001), while no changes occurred in A [arm only training—a low ‘anabolic’ hormonal exposure condition]. (Ronnestad. 2011)

is not sustainable, since "examination of Fig. 6 in their paper reveals that signiﬁcant hypertrophy did occur at two sites (of 4 measured) in the A arm", i.e. the non-leg-trained arm. By means as simple as drawing a few vertical lines (cf. figure 1) Phillips is able to show that the hypertrophic response to the training stimulus was in fact identical in three out of the four measured cross sections.

Figure 1: Four horizontal lines are all it took Phillips to show that there must be something wrong with Ronnestad's data; after all, it is unlikely that section 8 of the biceps had atrophied in the course of the stud (illustration taken from Phillip's letter to the editor of the European Journal of Applied Physiology)

Phillips makes a point that, unless one assumes that - for whatever reasons - there has been a strictly localized atrophy in section 8 of the arm (cf. mismatch of pre-values in left and right graph of figure 1), the most likely explanation for the mismatch would be that "the pre- and post-training scans were not aligned at the same point along the arm". Smart-witted as Phillips is, he also observed that with the purportedly greater changes in muscle cross-sectional-area in the leg+arm condition it is strictly impossible for the muscle volume to be identical, unless "the authors believe that the A arm got longer". I would assume that you agree with me that even with eccentric muscle training this would be a rather surprising event. Consequently, this is another argument in favor of the obvious absence of measurable effects of an overall more anabolic milieu in the "arm + leg training"-condition on the hypertrophy response to strength training - or, in short, we still have no conclusive evidence that training legs before arms would make the latter grow faster.

Image 2: Make your biceps grow with the SuppVersity EMG series!

Now, if the hypertophy response was identical, it is even more surprising that the "leg+arm" group exhibited "through some inexplicable mechanism" (Phillips. 2011) an overall greater 1RM strength than the control group. Phillips, who does not refrain from pointing out that "this [was] a surprising observation that was not even alluded to in the paper", argues that this result stands in stark contrast to the "central fatigue" hypothesis Ronnestad et al. cite as an explanation for the "dampened" (Ronnestad. 2011) training loads in the "leg+arm" training group. Phillips, on the other hand, speculates that it could be a direct result of a "a superior neuromuscular adaptation" (Phillips. 2011, my emphasis), which would be the exact opposite of what Ronnestad et al. had in mind.

Even if one neglects the questionable measuring practice of Ronnestad et al., in the course of which the "scanned arm [was] stretched behind the head and centered in the middle of the machine" (Ronnestad. 2011), the absence of an "estimate of variability of the procedure they used in their lab" and the questionable reference to "similarities" to magneto resonance scans (note that Ronnestad et al. used CT scans ;-) carried out by Moss et al. (Moss. 1997), the Ronnestad study is a particularly good example for the way research hypotheses can interfere with the "objective results" of scientific studies by establishing a (often unconscious) bias towards "desired" results. Selective reporting, incomplete statistical analysis and ad-hoc explanations for differences to the findings of previous studies are the undesirable, yet completely human manifestations of this phenomenon, I want everyone of you to be aware of - even if this means that my own thoughts and conclusions, which are almost always produced under time-pressure, are about to get more critical comments in the future ;-)

Cardio, Fat and IGF-1: Study Investigates Modulatory Effect of Endurance Exercise and High Fat Meals on IGF1 Binding Protein Levels in Obese Human Subjects

Image 2: 3D structural model of the IGF1 protein (rendered by Emw)

It's probably less than 24h ago, that you read about growth hormone (GH) here, at the SuppVersity. Its increase during fasts was one of the points, I addressed in yesterday's installment of the Intermittent Thoughts on Intermittent Fasting series. In fact it has been known for quite some time now, that fasting does increase the release of the 191-amino acid, single-chain polypeptide from the anterior pituitary gland, which in turn facilitates the (mostly) desirable switch to non protein-catabolic metabolic state, where fat becomes the major energy substrate. GH's growth promoting magic, on the other hand is believed to be largely mediated by the growth hormone induced production and release of insulin like growth factor 1 (IGF-1) in the liver, as well as directly at the level of target tissues. Apart from the sheer amount of IGF that is produced, its binding to respective carrier proteins, so called insulin like growth factor binding proteins, or IGFBPs, is yet another major determinant of the half-life and more importantly the mode of interaction of the IGF peptides with their target receptors at the cell surfaces.

From previous studies into the effects of exercise on IGF-1 levels activity, we already know that trained endurance athletes exhibit higher levels of IGFBP-1 (insulin like growth factor binding protein 1) than their sedentary counterparts (Manetta. 2003). Other studies have shown that after acute (vs. chronic) bouts of aerobic exercise the levels of IGFBP-1 return to baseline within 12-24h (Nindl. 2009; Berg. 2008; Koistinen. 1996) In that, the IGF-binding effect of exercise appears to be restricted to endurance type of exercises, as a more recent study by Nindl et al.found no increase in IGFBP-1 levels in young lean women after 8 weeks of strength training (Nindl. 2010).

Image 2: Ronny Coleman's belly is recurrent topic on various bulletin boards. This image was part of a discussion on the muscular development forum. Is it s imply fat or the results of the false(?) belief in "the muscle building magic" of IGF-1? (photo by Dan Ray for MuscularDevelopment.com)

The results from the Nindl study are also important in view of the interpretation of "increased" or "reduced" endogenous (i.e. produced by the body) IGF-1 levels in terms of their purported anabolic effect on muscle tissue, as Nindl. et al. point out...

[...] increased lean mass, aerobic fitness, and upper and lower body strength resulting from an 8-wk exercise training programs can occur without concomitant increases in either circulating bioactive or immunoreactive IGF-I, as well as associated IGFBPs. In terms of reflecting positive anabolic neuromuscular outcomes, these data do not support a role for endocrine-derived IGF-I. (Nindl. 2010)

All horror stories about GH-guts aside, you may want to keep that in mind before you condemn all aerobic exercise as being anti-anabolic and pay a shitload of money for supplements that "have been shown in clinical trials" (why are you laughing? ;-) to increase IGF-1 levels.

From epidemiological studies (Heald. 2003; 2005), we also "know" (you are probably familiar with my antipathy against epidemiology) that high fat diets are associated with lower levels of IGFBP-1. It has also been implicated as more or less reliable predictor of cardiometabolic diseases in longitudinal studies (Heald. 2001). Reason enough for Prior et al. to probe the combined effect, or I should say, the interference of 6 months of potentially IGFBP-1 lowering aerobic exercise ("3 weekly sessions of 20 minutes at 50% of heart rate reserve and gradually increased to 3 weekly sessions of 40 minutes at 70% of heart rate reserve"), on the one hand, and IGFBP-1 suppressing high fat meals (84% was derived from fat, 13.7% from carbohydrates, and 2.7% from protein), on the other hand, in a group of 10 overweight (bodymass index = 28.7 ± 0.9 kg/m²), older (61± 2 years) men and women.

Figure 1: Effect of 6 month of aerobic exercise on serum free glucose, free insulin, HOMA-IR and IGFBP-1 levels in obese subjects (data calculated based on Prior. 2011).

As the data in figure 1 goes to show, the exercise regimen had profound beneficial effects on insulin sensitivity - evidenced by the increase in serum free insulin levels and HOMA-IR (considered a "reliable" long-term marker of insulin resistance). As previous research had suggested, these changes were accompanied by a major increase in IGFBP-1 (and thus presumably a decrease in IGF-1 receptor activity). The increase in IGFBP-1 was however (almost completely, cf. figure 2) 4h after the study participants consumed a single high fat meal.

Figure 2: Effect of high fat meal (84% fat, 13.7% carbohydrates, and 2.7% protein) on IGFBP-1 levels (data calculated based on Prior. 2011)

This negative effect of high fat feeding on IGFBP-1, as can be seen in figure 2, was almost identical before and after the 6-month exercise intervention, which led the scientists to conclude that despite the fact that ...

[...] aerobic exercise training has a potentially beneficial effect to increase fasting plasma IGFBP-1 concentrations in previously sedentary middle-aged to older adults [..., a]erobic exercise training did not attenuate the adverse effect of a high-fat meal on plasma IGFBP-1 concentrations

Image 3: Germany's former foreign minister Joschka Fischer is a famous "victim" of the "low-fat-marathon-style-endurance-training" fat loss myth with built in YoYo-effect - I guess you will have your own celebrities with similar impressive "transformations" ;-)

and (you probably expected this) use this as a welcome opportunity for repeating the good (I should rather say "bad") old mantra of the benefits of chronic endurance exercise and low fat dieting.... I mean, come on. Look at our (Germany's) former foreign minister, Joschka Fischer (cf. image 3) - don't we all know that low-fat cereals and marathon running are no solution.

It would be nice to see some scientists going beyond this illusive paradigm, in order to gain insights into the underlying mechanisms or, even more fundamentally, to answer the question whether high(er) levels of free IGF-1 are causative or just corollary to cardiovascular disease, cancer and all the other maladies IGF-1 is currently held responsible for and which role all the healthy low-fat grains we are supposed to eat play in the etiology of these diseases... in case that is going to happen within my life-time, you can be dead-certain (pun intended) that the SuppVersity is the place, where you will read about it first.

The Intracrine Effects of Anabolic Steroids - Metanolone Promotes Stretch-Induced Intramuscular MGF Expression

Arnold's workout regimen are known to generate a hell lot of wear and tear and actually this could be part of his success formula.

I have to admit that the increase in intra-cellular MGF production is probably not the only, but certainly a new and very important pathway by which anabolic steroids "actively" promote muscle growth. According to a recent study from the Department of Rehabilitation and Physical Medicine, Graduate School of Medical and Dental Sciences at the Kagoshima University in Japan (Ikeda. 2013) anabolic agents such as metenolone which is a naturally occuring, WADA-listed long-acting anabolic steroid with weak androgenic (testosterone or androsterone-like) properties. It is isolated from the glands of pregnant domesticated felines, and is supplied as the acetate ester for oral administration and as the enanthate ester for intramuscular injection. Adult doses for the treatment of aplastic anemia are usually in a range of 1–3 mg/kg per day (Wikipedia).

Stretch-induced muscle growth

For the rodents in the study at hand the scientists did escalate the dosage and pumped roughly 10mg/kg (this is already the human equivalent) into the critters.

Then, the right gastrocnemius muscles were stretched repeatedly by manual ankle dorsiflexion 15 times per minute for 15 min. The contralateral muscles were not stretched as a control. In the control rats (n=6), the gastrocnemius was stretched as for the treatment group, but no metenolone was injected. Twenty-four hours after the procedure, the rats were sacrificed by injection of a lethal dose of sodium pentobarbital and their medial gastrocnemius muscles removed on both sides.

Actually, I suspect the sacrifice would not have been necessary as the extraction of the MGF, or as the scientists call it the "the specific autocrine IGF-I splicing variant mechano-growth factor" is something you can measure from a muscle biopsy. So, the only argument against a human study, is probably the dosage and the general administration of anabolic steroids to human subjects.

Figure 1: Treatment effects on MGF, MyoD, Myogenin (a.u.) in rats w/w/out metenolone injection (Ikeda. 2013)

With the highly significant effects on MGF and the non-significant effects on myoD and myogenin, both of which are involved in the recruitement of new muscle nuclei from the stem cell (satellite cell) pool in the musculature, the result of the study is yet of generic nature and will almost certainly apply to humans as well.
And with the effects of MGF being related to the important strength facilitating effects of exercise and the underlying cause of the changes being a simple stretch of the musculature the results put another emphasis on the necessity of the "wear and tear" for your body to make the necessary adaptations to exercise

Figure 2: Illustration of what you should have learned, if you read all installments of the Intermittent Thoughts on Building Muscle (read summary)

So what exactly is he result of the study then? I guess the elevator pitch is: Study confirms the facilitative role in skeletal muscle restructuring / growth of anabolic steroids. If you want more details, I suggest you go back to the "Intermittent Thoughts on Building Muscle Series" and educate yourself about IGF-1, MGF, GH, testosterone, myostatin and co and their specific roles in skeletal muscle hypetrophy (see "reading assignment).

Figure 2, to the right delivers a sneak peak of what you can expect and if that's not attractive enough, I'd suggest you use the "Preliminary Conclusion - Exercise, mTOR/AKT/MAPK, IGF-1, Testosterone, Estrogen, DHT, Nutrition, Supps & Sleep" (read it) of the series as a cognitive anabolic to promote your interest ;-)

I already hinted at that in a previous paragraph, but I think it's still worth repeating in the bottom line that despite being derived in a rodent study with an "exotic" anabolic agent, there is no question that the results of the study at hand will also be relevant for chemical athletes and little evidence they would not apply to
References:

Ikeda S, Yoshida A, Matayoshi S, Tanaka N. Repetitive stretch induces c-fos and myogenin mRNA within several hours in skeletal muscle removed from rats. Arch Phys Med Rehabil. 2003 Mar;84(3):419-23.
Ikeda S et al. The Effect of Anabolic Steroid Administration on Passive Stretching-Induced Expression of Mechano-Growth Factor in Skeletal Muscle. The Scientific World Journal. 2013: Article ID 313605.

Is Resistance Training in the PM More Anabolic Than in the AM? Time of the Workout Doesn't Influence Acute Hormonal Response or Circadian Pattern of Testosterone Production

The sun is setting and you're still working out. Could this disrupt your circadian testosterone rhythm? Or is it maybe even beneficial? I mean, you could compensate the natural nadir in testosterone in the PM, right?

Testosterone, much like any other hormone, is subject to a circadian rhythm. This means that there are spikes and troughs at certain time points in the day. Now, we all know that a bout of resistance training will also have an effect on testosterone, i.e. it will lead to a measurable increase in the post-workout period, and could thus (a) amplify natural spikes and / or (b) fill natural troughs.

Against that background, it appears to be a warranted question, whether one would want to do (a) or (b), i.e. amplify a natural spike as it occur in the morning and head to the gym at 8:00AM, or whether it would make more sense to wait a until the late afternoon / evening to hit the gym at 8:00PM, when the testosterone levels are at a nadir?

You can learn more about sleep and the circadian rhythm at the SuppVersity

Sunlight, Bluelight, Backlight and Your Clock

Sunlight a La Carte: "Hack" Your Rhythm

Breaking the Fast to Synchronize the Clock

Fasting (Re-)Sets the Peripheral Clock

Vitamin A & Caffeine Set the Clock

Pre-Workout Supps Could Ruin Your Sleep

The practical question thus is: "Are athletes better off undertaking their resistance exercise in the morning or afternoon?" A question, Ardalan Shariat, Mehdi Kargarfard, Mahmoud Danaee, and Shamsul Bahri Mohd Tamrin tried to answer by determining, whether there were any significant differences in hormonal response to a standardized high intensity resistance training regimen when it was performed once in the AM, once in the PM.

The natural ups and downs get lost, when a man goes through andropause (Bremner, 1983)

To this ends, the scientists recruited 20 healthy young male recreational lifters (age 18.0± 1.3) with two years of experience in weightlifting. The subjects were randomized to to either the resistance exercise group (n=10), who completed a series of resistance exercise (3 times a week, in the afternoon, 6-7 repetitions, at 85% of 1RM for 3 weeks), or a control group (n=10), who did not exercise during the 3 weeks. The control group was installed to eliminate other effects, such as the circannial fluctuactions in testosterone levels as they were described, for example, by Reinberg et al. in 1978.

The workout was a classic full-body workout with a focus on exercises that work: Hang pulls, bench press, leg press, sated row, leg curl, shoulder press, lat pulls, knee extensions, arm curls each à 3 sets of 7 reps and sit-ups with 3 sets of 20 reps.

This is not an acute, only study! The good thing about the study at hand is that it's not testing the acute effects, but the chronic effects of resistance training on the circadian rhythm of testosterone. That's much different from the acute studies we know and of which we currently believe that they don't provide relevant information about the potential long-term effects of resistance training. This would obviously be different for a chronic change in the circadian testosterone profile - an upward shift, for example, could be anabolic, a crash, on the other hand, would almost certainly impair the strength and mass gains.

In contrast to a previous study by Kramer et al. which also lacked a control group, Shariat et al. moved the workout to the afternoon hours to mirror the training practices of the majority of trainees.

Figure 1: Circadian testosterone rhythm in response to resistance training in the PM (left; Shariat. 2014) and AM (right; Kraemer. 2001); mind the units (!) - pmol/mL on the left, pg/mL on the right!

In additon, the researchers chose a lower number of reps and correspondingly higher workout weight to "voke a larger effect on hormonal responses in comparison with Kraemer’s 2001 study."
If you look at the data in Figure 1, you will still see that the results Shariat et al. produced (left) are quite similar to those from Kraemer's 2001 study (right):

"The main finding of the present study was that an intense period of intensive resistance-oriented sport activities provides a nominal temporary effect upon the testosterone circadian rhythm that diminishes an hour after the workout, after which testosterone levels return to normal." (Shariat. 2014)

The findings obtained through both resistance exercise and control groups obviously manifest a circadian pattern in which there is a presence of higher concentrations during the morning and lower concentrations during the evening and it is under circadian patterns.

So, when do I train, now? The answer to this question is easy: Whenever you have time and feel that it works for you. There is no "best time to train" for everyone and if you have to work at 9am, what would be the use of a (if anything marginally) increased anabolism from working out at 8am if you have to stress yourself like crazy to arrive at your working place in time?

Bottom line: Overall, the study at hand confirms the results Kraemer et al. presented in their paper in the European Journal of Applied Physiology in 2001, already. As Shariat et al. point out, neither AM nor PM training will have lasting effects on the circadian rhythm of testosterone concentrations.

In view of the fact that the acute effects remain acute (at least as long as you are not overtraining, there are no chronic effects on T-levels or their rhythm) the results of the cited studies leave us with the previously mentioned insight that the interaction between exercise and free testosterone could be less important for the anabolic cascade that's triggered in response to a workout than broscience would tell us.

Reference:

Bremner, William J., Michael V. Vitiello, and Patricia N. Prinz. "Loss of Circadian Rhythmicity in Blood Testosterone Levels with Aging in Normal Men*." The Journal of Clinical Endocrinology & Metabolism 56.6 (1983): 1278-1281.
Kraemer, William J., et al. "The effect of heavy resistance exercise on the circadian rhythm of salivary testosterone in men." European journal of applied physiology 84.1-2 (2001): 13-18.
Reinberg, Alain, et al. "Circadian and circannual rhythms in plasma hormones and other variables of five healthy young human males." Acta endocrinologica 88.3 (1978): 417-427.
Shariat, Ardalan. Intensive Resistance Exercise and Circadian Salivary Testosterone Concentrations among Young Male Recreational lifters. Diss. Islamic Azad University, Roudehen, Iran. 4, 2014.

Serum & Intramuscular Testosterone, DHT and Androgen Receptor Response to High vs. Low Volume Training

Another set for another ng of testosterone? Does it work that way and is it worth it - not just on paper, but in terms of real gains?

I know that we don't know! And among the many things we don't know the influence of the post-workout elevation in the long-thought "anabolic" hormones testosterone, growth hormone, and co. is unquestionably one of my personal favorites. You've read about it, here at the SuppVersity many times and I got to tell you in advance that the absence of convincing evidence for / against its importance will become a problem in the bottom line of today's SuppVersity article dealing with the intriguing results of an experiment that has been conducted by Lukas J. Farbiak as part of his Honors Thesis (Farbiak. 2013).

"Effects of Lower- and Higher-Volume Resistance Exercise on Serum Total and Free Testosterone, Skeletal Muscle Testosterone and Dihydrotestosterone Content, and Skeletal Muscle Androgen Receptor mRNA Expression and Protein Content"

That's quite a title for a thesis right? Well, one thing's for sure: Having the words, "high, "low", "training volume", "resistance exercise", "total and free testosterone", "dihydrotestostereone", etc. all in the headline is certainly an advantage when it comes to findability of a paper - or in this case - a thesis in a database. And in fact, it was really the title of the 91 page piece that has caught my eye, a couple of days ago - what peaked my interest, though were the research hypotheses Farbiak, whose thesis was by the way overseen by Darryn Willoughby, formulated:

H1 : Following the HV [high volume] exercise bout involving both upper- and lower-body resistance exercise, a significant increase in serum testosterone will occur compared to the LV [low volume] exercise bout only involving lower-body resistance exercise.
H2 : Following the HV exercise bout involving both upper- and lower-body resistance exercise, a significant increase in muscle testosterone and DHT content will occur compared to the LV exercise bout only involving lower-body resistance exercise.
H3 : Following the HV exercise bout involving both upper- and lower-body resistance exercise, a significant increase in AR mRNA expression and protein content will occur compared to the LV exercise bout only involving lower-body resistance exercise.

I took the liberty of highlighting three things in Farbiak's hypotheses, which tell you why you want to know the outcome of the study, even if the current "state of the research" questions the significance of exercise-induced elevations of androgens in terms of their ability to elicit muscle growth.

What's special, here, is that we are not measuring serum levels exclusively, but get a much more detailed picture of the endocrine response to high vs. medium volume training.

Why would the internal androgen levels differ from those outside of the cell? The notion that this could and in fact is the case did not arise before Hammes et al. discovered that contrary to the previously heralded position that says that only free testosterone levels would matter and that the latter would be able to enter the cells via passive diffusion, the entrance of testosterone into the cell is actually governed by (attention please) megalin, a low density lipoprotein receptor (LDR) related protein. According to Hammes, SHBG can bind to megalin can internalize the SHBG + androgen pair into the cytoplasm, where the binding globulin is degraded and the steroid will be released to the cellular environment.It goes without saying that this changes the interpretation of previous data and provides a whole new perspective on the androgen - muscle interaction with the formerly "passive" bound testosterone suddenly having the ability to promote hypertrophy.

In this context the relation of free androgens, androgen receptor expression and the presence and concentration of intra-muscular may well provide first insights into why previous studies, which have predominantly relied on the determination of serum levels without even checking,

whether there were enough receptors to (this is an oversimplification) transduct the anabolic signal of workout induced increases in testosterone to the muscle cells, and
to which extent the changes in extra-cellular androgen levels correlate with the amount of testosterone and DHT that's actually in the muscle.

Now that I have your full attention let's take a look at what kind of workout program we are dealing with in the study at hand, for which the researchers recruited 10 "apparently healthy resistance trained [regular, consistent resistance training (i.e. thrice weekly) for at least 1 year prior to the onset of the study], men between the ages of 18-30" (Farbiak. 2013).

"In a randomized, cross-over design, participants visited the laboratory on 5 separate occasions in the following manner: visit 1 = entry/familiarization session, visit 2 = testing/resistance exercise session 1, visit 3 = 24 hour follow-up for session 1, visit 4 = testing/resistance exercise session 2, visit 5 = 24 hour follow-up for session 2. Relative to the testing sessions (visits 2 & 4), participants performed a resistance exercise session involving the knee extension exercise on two occasions separated by one week. One session constituted the control session and was preceded by rest and the other was preceded by the experimental session and preceded by a bout of high-volume, moderate-intensity upper-body resistance exercise using short rest periods." (Farbiak. 2013).

The dependent variables, i.e. serum free and total testosterone, intra-muscular testosterone, DHT and AR receptor mRNA, as well as protein expression were determined on all, but the initial entry/familiarization visit.

The workout itself (remember this is not a chronic resistance training study, as the one by West et al. (2012) which is - at least to my knowledge unique wrt to the real-world relevance of the data; learn more) consisted of

LV - low volume: 5 sets of 5-RM (90%-95% 1-RM) of the bilateral knee extension exercise with 3 minutes of rest between sets.
HV - high volume: Upper-body resistance exercise protocol of 4 sets of 10-RM each of the bench press, seated row, and overhead shoulder press exercises immediately prior to the knee extension protocol.
the initial load was set at 80% of the 1-RM for each participant.
if muscle fatigue/failure occurred during a set, a spotter provided assistance until the participant completed the remaining repetitions and resistance was reduced for subsequent sets

In all cases, 2 minutes of rest separated sets and exercises. All training sessions were conducted in
the Baylor Laboratories for Exercise Science & Technology (BLEST) and supervised by study personnel.

Figure 1: Sum total and free testosterone in response to high and low volume training (Farbiak. 2013)

Now, the data in figure 1 actually mirrors what we already know: The overall serum response to high volume training is more pronounced that that to playing around on a leg extension machine (which happens to be the favorite benchmark for the / I repeat myself / likewise not very useful studies on PWO protein synthesis).

"Several studies have shown that acute resistance exercise bouts elicit a testosterone response (Kraemer. 1990; Kraemer, Gordon et al., 1991; Kraemer, Hakkinen et al., 1999; Spiering, Kraemer. 2008; Roberts. 2009). Such exercise bouts shown to elicit a testosterone response need to consist of a high intensity (load) (85%-95%) of one repetition max and meet a minimum threshold, and moderate to high volume (set x number of reps x intensity). Exercises that utilize large muscle groups (i.e. power clean, squats, and dead lifts) as well as performing exercises involving large muscle groups first, with short rest periods (30-60 sec) have shown to elicit the greatest response (Kraemer, Marchitelli et al., 1990; Spiering, Kraemer et al., 2008; Vingren, Kraemer et al., 2010). [...] It is known that the testosterone response resistance exercise is highly variable (Kraemer, 1988). Thus, it is possible that after multiple years of resistance training, the initial phasic response of the hypothalamus gonadal axis (aka. testosterone axis) response elicited by resistance exercise bout un trained individuals has become blunted from habitual resistance exercise. However, it is necessary that further research be conducted to elucidate why this blunted response occurs." (Farbiak. 2013; my emphasis of the key points)

As far as the differential response of free and total testosterone is concerned the tendency for both to go hand in hand has been observed in previous studies, as well (Durand. 2003; Kraemer. 1990; Kraemer. 1991; Kraemer. 1999; Spiering. 2008; Roberts. 2009). What's "new" or let's say something we have much less reliable data on are the changes that take place within the muscle (see figure 2)

Figure 2: Intra-muscular androgen & -receptor mRNA & protein expression (Farbiak. 2013)

Interestingly, enough those potentially far more relevant changes take place on a very different time-scale. While we do see the touted increases in serum testosterone in the immediate vicinity of the workout, the corresponding intra-muscular levels are actually declining from pre to post (red vs. blue bars). As Farbiak points out, these changes were yet statistically non-significant and to thus correspond to previous results presented by Vingren & Kraemer et al. in 2008 (Kraemer. 2008). The same goes for the DHT response that did not make it past the p > 0.05 mark of statistical significance (FYI: this means the chance that this is just a statistical artifice is >5% and thus "not significant").

As far as the androgen receptor mRNA expression is concerned a often-cited (also by me, here at the SuppVersity) by Kraemer et al. observed a reduction in response to a single bout of resistance exercise, (Kraemer. 2010). The latter does actually conflict with in-vitro studies that suggested that the presence of higher testosterone levels would lead to an increased expression of androgen receptor mRNA and proteins - an observation of which Farbiak points out that it does not only stand in line with a previous study by Willoughby and Taylor (Willoughby. 2004) who observed a

"+35% and +43% increases in AR mRNA expression 48 hours after the first and third resistance exercise bouts, with a peak increase of 68% in AR mRNA expression occurring 48 hours after the second resistance exercise bout within the resistance exercise group" (Farbriak. 2013)

which was ascribed to corresponding increases in serum testosterone levels. In view of the fact that the latter were absent in Farbiak's subjects, it is not surprising that the existing increases in AR receptor mRNA in the study at hand did not reach statistical significance. Similarly, Farbiak was not able to show significant alterations in androgen receptor protein content in response to either LV or HV bouts of resistance exercise, which leaves us with pretty much of a null result and raises the question...

What do we make of this null result?

I guess the first thing would be to take a look at the underlying "mathematical" reason for the non-significance of the results... standard deviations - HUGE standard deviations, indeed. So huge that I initially thought that this must be a mistake, I mean if you have a mean pre-testosterone level of 43.59 ng/dl and a standard devition of 43.03 ng/dl, i.e. 99%, what can you expect? Now this is an extreme example, but in view of the relative small number of participants it should suffice to tell you that - maybe - we should not focus that much on statistical significance, here?

Suggested read: "Advanced Trainees Benefit from Increased Training Volume! Greater & Steadier Strength Gains with 8 Sets of Squats. Plus: Over 6 Weeks, 1 Set and 4 Sets Equally (In-)Effective." If higher volume begets higher T-responses and the latter is blunted in advanced trainees, it would appear logical that they benefit from doing more (learn more)

Schoenfeld mentioned similar effects in a whole host of pertintent studies in his excellent review of the literature on the effects of the exercise induced hormonal changes on muscle hypertrophy (I mentioned this review before, e.g. March 2, 2013; March 4, 2013). So it could simply be inter-individual variability that skewed the results. If that was the case, it is however unlikely to assume a dose-response relationship between any (serum or intramuscular) changes in androgens / androgen receptor expression and skeletal muscle hypertrophy - I mean that would imply much more pronounced differences in muscle growth in response to a workout than the real world results do indicate.

Another factor that may have influenced the results is the high training experience (>8 years) of the participants in the Farbiak study, if the initially cited hypothesis that the androgen response to exercise declines in experienced athletes turns out to be true, the non-significance of the endo- and paracrine hormonal response in the study at hand could well be "normal" and no anomaly. And if that was the case, it would suggest that the changes that were observed in previous studies, many of which were conducted on rookies, do matter - at least to a certain degree.

To use this as the only explanation for the (comparatively) exorbitant gains training noobs experience once they pick up their first dumb- and barbells would yet be shortsighted. To add it as yet one of the many confounding factors, on the other hand, would make perfect sense, as it would stand in line with the (comparably) short-term detrimental effects chronic resistance training without off-times has on the protein synthetic mTOR response to exercise (learn more about exercise induced "mTOR resistance").

Bottom line: To sum it up, while we do now have another puzzle piece, it looks as if it only made us realize that our 1,000 piece puzzle is in fact a 10,000 piece puzzle and that it will probably require more than just a handful of follow up study to investigate the numerous factors "such as age, time of day [not all trainees trained at the same time, so the circadian rhythm may be an issue, in the study at hand], and training experience" (Farbiak. 2013) of which Farbiak speculates in the discussion of his honors thesis that they may account for the observed discrepancies and inconsistencies in testosterone response to acute resistance exercise... ah, and once we've done that, we would need more studies like the one by West et al. (2012) to see the real world implications. I guess, we better issue a bond to get those finance, right?

References:

Farbiak, LJ. Effects of Lower- and Higher-Volume Resistance Exercise on Serum Total and Free Testosterone, Skeletal Muscle Testosterone and Dihydrotestosterone Content, and Skeletal Muscle Androgen Receptor mRNA Expression and Protein Content. A Thesis Submitted to the Faculty of Baylor University In Partial Fulfillment of the Requirements for the Honors Program. May 2013.
Durand RJ, Castracane VD, Hollander DB, Tryniecki JL, Bamman MM, O'Neal S, Hebert EP, Kraemer RR. Hormonal responses from concentric and eccentric muscle contractions. Med Sci Sports Exerc. 2003 Jun;35(6):937-43.
Hammes A, Andreassen TK, Spoelgen R, Raila J, Hubner N, Schulz H, Metzger J, Schweigert FJ, Luppa PB, Nykjaer A, Willnow TE. Role of endocytosis in cellular uptake of sex steroids. Cell. 2005 Sep 9;122(5):751-62.
Kraemer WJ, Marchitelli L, Gordon SE, Harman E, Dziados JE, Mello R, Frykman P, McCurry D, Fleck SJ. Hormonal and growth factor responses to heavy resistance exercise protocols. J Appl Physiol. 1990 Oct;69(4):1442-50.
Kraemer WJ, Gordon SE, Fleck SJ, Marchitelli LJ, Mello R, Dziados JE, Friedl K, Harman E, Maresh C, Fry AC. Endogenous anabolic hormonal and growth factor responses to heavy resistance exercise in males and females. Int J Sports Med. 1991 Apr;12(2):228-35.
Kraemer WJ, Häkkinen K, Newton RU, Nindl BC, Volek JS, McCormick M, Gotshalk LA, Gordon SE, Fleck SJ, Campbell WW, Putukian M, Evans WJ. Effects of heavy-resistance training on hormonal response patterns in younger vs. older men. J Appl Physiol. 1999 Sep;87(3):982-92.
Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports Med. 2005;35(4):339-61.
Roberts MD, Dalbo VJ, Hassell SE, Kerksick CM. The expression of androgen-regulated genes before and after a resistance exercise bout in younger and older men. J Strength Cond Res. 2009 Jul;23(4):1060-7.
Schoenfeld BJ. Postexercise hypertrophic adaptations: a reexamination of the hormone hypothesis and its applicability to resistance training program design. J Strength Cond Res. 2013 Jun;27(6):1720-30.
Spiering BA, Kraemer WJ, Anderson JM, Armstrong LE, Nindl BC, Volek JS, Maresh CM. Resistance exercise biology: manipulation of resistance exercise programme variables determines the responses of cellular and molecular signalling pathways. Sports Med. 2008;38(7):527-40.
Spiering BA, Kraemer WJ, Vingren JL, Ratamess NA, Anderson JM, Armstrong LE, Nindl BC, Volek JS, Häkkinen K, Maresh CM. Elevated endogenous testosterone concentrations potentiate muscle androgen receptor responses to resistance exercise. J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):195-9.
West DW, Phillips SM. Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training. Eur J Appl Physiol. 2012 Jul;112(7):2693-702.
Willoughby DS, Taylor L. Effects of sequential bouts of resistance exercise on androgen receptor expression. Med Sci Sports Exerc. 2004 Sep;36(9):1499-506.

Whey or Casein? Pre- or Post Workout Protein? Insights into Peri-Workout Nutrition from Small Scale Study in Elderly People Bring Milk Back onto the Radar

You already read it in the title of this post: The following data comes from a small scale study (Dideriksen. 2011) in elderly people. Those, who listened to my dissertation on how reliable science is (aired on Carl Lenore's Super Human Radio on Wednesday, 20 April 2011), will know that a small number of participants from what one may call a "special population", in this case 15 elderly men and nine elderly women (age 68 ± 1 years, range 61–80 years), dictates caution in view of the overall significance and reliability of the data. The results which are soon to be published in the Scandinavian Journal of Medicine & Science in Sports are nonetheless, worth to be taken note of.

Diderisken et al. had their subjects (again: 15 elderly men and 9 elderly women; age 68 ± 1 years, range 61–80 years) perform 5 sets of eight repetitions at 80% of 1 RM in both unilateral knee-extension and bilateral leg-press with 3 min of rest between sets and measured muscle myofibrillar and collagen fractional synthesis rates (FSR) by a primed continuous infusion of l-[1-¹³C]leucine using labeled proteins during a 6-h recovery period. Other than the researchers had expected the fractional protein synthesis rates did not depend on form or timing of the 0.45 g/kg LBM supplemental protein their subjects consumed.

No differences were observed in muscle myofibrillar and collagen FSR with Whey [administered post workout] compared with CasPost [casein post workout], and it did not differ between CasPre [casein pre workout] and CasPost.

This being said, secondary data on the leucine concentration does support the well-established advice to prefer whey over casein in the (non-existent) "post workout window":

The plasma leucine concentrations were increased during the entire post-exercise periods in CasPre, CasPost, and Whey compared with the basal levels. The leucine concentrations reached a peak of 227 ± 11, 282 ± 17, and 490 ± 32 μmol/L in CasPre, CasPost, and Whey, respectively. [...] The total leucine response expressed as the AUC in the time period 15–390 min after the resistance exercise bout was significantly higher in Whey compared with all the other groups (P<0.05), higher in CasPost compared with CasPre (P<0.05), and lower in Control than in the other groups (P<0.01).

This very ability of whey protein to "spike" leucine levels post workout go hand in hand with findings from previous studies (in rodents, as well as human subjects) that suggest a slight yet significant advantage of whey over casein in view of the nutritional amelioration of exercise induced muscle anabolic responses. It is yet worth mentioning that both additional casein pre-ingestion and casein (co-)ingestion post-workout could be valuable strategies to prolong the increase in total (TAA) and essential (EAA) amino acids. This hypothesis is supported by the following findings:

[...] plasma TAA concentrations were increased in CasPre (15–150 min), CasPost (30–60 min), and Whey (30–60 min) compared with the basal levels. The plasma EAA concentrations were increased in CasPre (30 min), CasPost (30–270 min), and Whey (30–60 min) compared with the basal levels.

Figure 1: Nature already invented
the perfect peri-workout drink: Milk!
(photo (cc) Chedid, Janine. 2004)

In essence the combination of a slow acting casein before workout and a mixture of fast acting whey and slow acting casein protein after workouts would maximize both total, as well as, essential amino acid levels over a time period from 15-60 and 30-270 minutes, respectively - with a whey-induced "anabolic" leucine spike in the immediate vicinity of the workout.

Well, that being said, guess who has already developed such a pre/post/peri-all-in-one-workout formula for you? Nature! The name? Milk! Milk is roughly 80% casein and 20% whey, has some additional carbs in it that will get you through your workout and is full of healthy minerals and vitamins that will help you recover even faster. Make it raw unpasteurized milk from the happy grass-fed cows of a local farmer and there will be little room for further improvements ;-)

Ursolic Acid and The Narrow Line Between Anabolism and Myotoxicity: +25% Increased Protein Accretion in In-Vitro Study, But Cell Death With 2x "Effective" Dose

Image 1: "An apple a day keeps the doctor away!" And though the ursolic acid in its peel may be part of the underlying mechanism, this does not make it a "natural anabolic", but rather another item on the list of "healthy stuff from real food"

The number of purported natural anabolics increases year by year. Against the background that most of these products are nothing but supplemental nonstarters in shiny bottles and boxes with "non-FDA approved" promises of "unparalleled muscle growth" on them, the recent release of a broad range of ursolic acid supplements must already be considered a "highlight". With a peer-reviewed rodent studies backing its anti-catabolic, pro-anabolic properties (Kunkel. 2011), it appears as if ursolic acid could be more than another potent placebo. And if we put things into perspective, in the end its potential beneficial effects on skeletal muscle hypertrophy are rather negligible compared to its previously proposed role as a therapeutic compound in various conditions such as Alzheimer’s diseases (Wilkinson. 2011), cancer (Kim. 2000; De Angel. 2010; Pinon. 2011), and diabetes (Zhang. 2006; Jayaprakasam. 2006).

More ain't more, but toxic! And even less is probably more than you can get.

Only recently, Vandré Casagrande Figueiredo and Gustavo A. Nader were able to confirm the muscle building effects in an in-vitro study using C2C12 myoblasts which were incubated with different concentrations of ursolic acid for 72h (Figueiredo. 2012).

Figure 1: Protein content and cell viability after 72h incubation with different concentrations of ursolic acid (in µM); light bars p > 0.05, statistically non-significant (data calculated based on Figueiredo. 2012)

As you can see in figure 1, this treatment lead to dose-dependent increases in protein accretion in the muscle cells. These increases reached statistical signficance only in the 10µM group (their real-world significance is even more questionable, as we don't know if similar concentrations can even be achieved by oral administration of ursolic acid).

The profound loss of protein in the higher dose groups and the subsequent decrease in cell viability, on the other hand, are statistically highly significant. Their real world significance does yet appear to be even more questionable, after all, it is rarely possible to double the serum concentration of a given substance by just ingesting twice as much. At the dosages that are present in the currently available supplements myotoxicity, as it was observed in this in-vitro study, is thusly probably not a real concern.

No reason to be afraid, but no reason to expect grandiose results, either

Image 2: These muscles were not build on ursolic acid - that's for sure.

In other words, while the study at hand did help us to elucidate the underlying mechanism of previously reported benefits under mostly atrophic (=muscle loss) conditions, its overall real-world significance in view of the negative, but also in view of the positive effects appears to be more than limited. If you also take into consideration that the scientists were able to rule out that ursolic acid exerts hyperplastic (cell proliferation) effects on skeletal muscle tissue, that its "muscle building" effects (referring to the increased protein accretion observed in the study at hant) was highly dependent on the presence of additional growth factors in the culture medium and that ursolic acid did not increase the myocyte RNA levels, it remains questionable whether the ingestion of respective (most certainly underdosed) supplements will produce any significant improvements in training and diet induced skeletal muscle hypertrophy.

In the end, the new data stand in line with the observations of Kunkel et al. who identified an increase in skeletal muscle insulin sensitivity and subsequent upregulation of the IGF-1 induced growth response as the underlying cause of the atrophy-inhibiting effects or ursolic acid. What can be said for sure, however, is that the currently available OTC supplements are in no way "muscle builders". According to the currently available research, they should rather be filed under "health supplements", along with alpha lipoic acid and the like. Now, that does obviously not exclude that the health improvements - above all the improvements in insulin sensitivity could not help you build muscle - the label "natural anabolic" does yet still appear largely misplaced.

Farmer's Walk or Squat, Tire Flip or Bench Press, Stone Lift or Seated Row - Is Strongmen Training as "Anabolic" as Classic Hypertrophy Training and Which is "Best"?

Is he (or she?) going to be muscular when he grows up, or is this kind of exercise just making him strong?

I guess we all know that the most muscular guys are not necessarily also the strongest men in the gym - but why is that the case? And moreover, how does this fit in with the notion that you'd have to use heavy weights to induce skeletal muscle hypertrophy? Yeah, I know. Many scientists believe that's nothing but "broscience" (cf. Burd. 2012) and if you look at the muscle fiber composition of a bodybuilder in this previously published article, you will see that it is by no means type II and thus "strength-specific". And let's be hones does not the advent of blood flow restricted training signify that we are about to witness a "paradigm change"? With the classic approach (heavy weight and 8-10 reps) being on the upper end of a "optimal growth continuum"?

Notwithstanding this contemporary trend towards "making light weights heavier" (let's be honest, BFR for example does exactly that), a group of researchers from the Health and Human Performance Laboratory at the Hofstra University and the Gridiron Training Facility in Hempstead, New York, did actually dare to "waste" their time on research on the opposite extreme of the heavy vs. light lifting divide.

Don't forget: The paradigm determines the research design

Before we delve further in to the methodological issues, let me briefly get one thing straight. Ghigiarelli and his colleagues firmly believe in the significance of the immediate and early endocrine response to a workout. They specifically cite the work from Stuart Phillips lab, I have been referring to numerous times times, but (and this is science, guys!) politely disagree with the conclusion that the relationship between elevated endogenous testosterone levels and hypertrophy function was non-existent or at least irrelevant, stating that...

Suggested read "Anabolic Workouts Revisited"
"[...] a much larger body of evidence supports the integral role that the acute hormonal response to RE [resistance exercise] has on muscle hypertrophy (Schoenfeld. 2010; Vingren. 2010) and its role in strength training adaptation (Hansen, 2001;Kvorning. 2006). Those in support of an endogenous testosterone response stand by the belief that RE causes an initial downregulation on AR content in the target tissue (i.e., skeletal muscle) followed by a subsequent upregulation during the recovery period, thus increasing free testosterone uptake facilitating protein synthesis." (Ghigiarelli. 2013)

It is therefore not a design flaw, when the scientists take the acute testosterone response to the workout as a measure of it anabolic potential and speculate that a strongmen-esque workout, which engages much more muscle fibers than even a compound based bodybuilding workout does, would elicit a stronger hormonal response than a "classic" hypertrophy training (additional read => the Saturdaily installment of On Short Notice) .

Real trainees, real workouts, real (?) results?

To probe their hypothesis the scientists recurited trained athletes from various athlete backgrounds. The mean age of the

tan recreational strength trainees (>4 training sessions per week, >2 years of training),
one wrestler and one football player,
two competitive bodybuilders,
one competitive powerlifter and one competitive o-lifter

was 24 years, whose mean 3-RMs , i.e. the weight the participants can maximally perform for 3 reps, were 161kg for the squat and 126kg for the bench press.

Main result: Not superior, but "similar"testosterone responses

I guess, when you read the word "similar" (which is a real quotation from the full text) in the above subheading and take a loot at the actual data in figure 1 some of you may not without good reason complain that Ghigiarelli et al. use the word "similar" pretty generously.

Figure 1: Salivary testosterone response to immediately after (post) and 30 min after work-matched classic hypertrophy, strongmen and mixed routines (Ghigiarelli. 2013)

If you look at the raw data on the left, it does after all look as if the classic hypertrophy workout with its squats, the leg presses, bench presses and seated rows was way more "anabolic" than

its strongmen counterpart that consisted of tire flips, chain drags, farmers walks, keg carries and stone lifts,

the mixed protocol which was build around tire flips, squats, chain drags, bench presses and stone lifts

when all exercises were performed for 3 sets x 10 reps with 75% of the weight the subjects could lift... and what should I say? You are right!

"Hold on! I don't see any 'similar' response!?"

What the average data in figure 1 (left) does yet not convey, are the large inter-individual differences. If you take those into account and use some statistical shenanigan to compensate for differences in the workout duration and the individual exercise intensity (whatever that may be, see Steele's recent paper on the absence of a clearcut definition of "intensity"), the superiority does turn into "a nonsignificant trend of greater testosterone release after the H protocol" (Ghigiarelli. 2013) - a trend, the researchers ascribe to the "abnormal response" they observed in response to the hypertrophy training (abnormal as compared to other studies, where the reponse hypertrophy training is usually in the 70% range, as well), which in turn would be attributable to 6 high responders with extreme spikes testosterone spikes of 165-493%.

Does true mastery of the exercise determine skeletal muscle anabolism?

Usually outliers like that are a problem, but sometimes there are cases where the exception from the rule has the greatest explanatory value and in this case, the latter may well be the case. How come? Well, the two hypothesis Ghigiarelli et al. come up with to explain the differences is simply too attractive to discard it as being irrelevant. Firstly, the scientists believe that it would be plausible that the anxiety level due to the unfamiliarity of strongman lifts may have reduced the testosterone spike.

You have no goals or don't track your results? Huge mistake (learn why)!
"This possibility is supported by previous literature examining the hormonal responses to different RE protocols in seasoned trainers (Beaven. 2008). Beaven et al. suggested that the novelty and stress of the situation are likely to be perceived based on experience. Thus, the stressors of the ST and XST sessions and the lack of familiarity of the exercises can suppress the actual physical nature of the stimulus. This psychological nature of the hormonal response in our subject pool may have caused a different response to protocols with which they were unfamiliar with or disliked." (Ghigiarelli. 2013)

Now, if you go one step further and expand on this idea by involving my mantra that training is not about moving weights from point A to point B and rephrase all that using a term Nicolas Burd et al. mentioned in their recent review in Applied Phyisology and Nutrition, in which they advance the idea that it does not really matter on which extreme of the low vs. heavy weight continuum you train, as long as your protocol elicits "high intensity contractions" (Burd. 2012), you could also argue that the subjects may have moved the weight for 3 sets of 10 when they did the farmer's walk etc., but did not to so using "high intensity contractions".

The intensity of the contraction determines the gains

Knowing the "101 of Pre Workout Protein Supplementation" can make a difference. Over all the supplement shenanigan many trainees do yet tend to overlook the basics and simply assume that as long as they move weight from A to B the use of the right powders and popping the right pills at the right times would have the largest impact on their results - big mistake!

In other words, the calculated "intensity" and the real muscular tension, i.e. the intensity of the contraction, were not identical and certainly sub-optimal for those of the trainees who have never flipped tires or carried kegs before. The bodybuilders and certainly also most of the recreational athletes may well have been so focused on the novel exercise that they could not pay any attention to the one thing that's at the bottom of skeletal muscle growth the "high intensity contraction".

Now, it is probably undebatable that the actual work that is done by the muscle and not the physical work, you would calculate by multiplying the weight (respectively the force you would apply to it in an ideal scenario) and the length of the way along which you dragged, carried or flipped it, is the physiologically relevant number here. In this context it would also be irrelevant, if the endocrine response to a workout does actually correlate with the net gains in muscle size or strength, as long as the "intensity of the contraction" did. In the end, it is thus not the weight or the exercise that determines the actual growth stimulus, but rather your ability to use a given weight in a given exercise to induce those damn high intensity contractions.

Bottom line: For 90% of the trainees out there, the first step to improve their gains would thus to improve their game. To take the true meaning of "training", of which the venerable Oxford English Dictionary says that it is "the sustained instruction and practice (given or received) in an art, profession, occupation, or procedure, with a view to proficiency in it." (OED Online. 2012). For the majority of trainees I see at the gym, it would thus be much wiser to follow Adelfo Cerame's recent advice and focus on a handful of exercises, instead of hopping from one exercise to the next, whenever a study says: Subjects, X,Y and Z gained 0.5% more mass doing farmer's walks vs. squats.

For others, it may yet be time to move on or to expand their arsenal of exercises with what Ghigiarelli et al. feel are "unique and exciting" exercises which provide "effective alternative to traditional resistance training, but require a lot of training to even master them "manipulate the specific combinations of rest intervals, loading, and volume toward [your] desired training goals" (Ghigiarelli. 2013).

References

Beaven CM, Gill ND, Cook CJ. Salivary testosterone and cortisol responses in professional rugby players after four resistance exercise protocols. J Strength Cond Res. 2008 Mar;22(2):426-32.
Burd NA, Mitchell CJ, Churchward-Venne TA, Phillips SM. Bigger weights may not beget bigger muscles: evidence from acute muscle protein synthetic responses after resistance exercise. Appl Physiol Nutr Metab. 2012 Jun;37(3):551-4. doi: 10.1139/h2012-022. Epub 2012 Apr 26.
Ghigiarelli JJ, Sell KM, Raddock JM, Taveras K. Effects of strongman training on salivary testosterone levels in a sample of trained men. J Strength Cond Res. 2013 Mar;27(3):738-47.
Hansen S, Kvorning T, Kjaer M, Sjøgaard G. The effect of short-term strength training on human skeletal muscle: the importance of physiologically elevated hormone levels. Scand J Med Sci Sports. 2001 Dec;11(6):347-54.
OED Online. "training, n.". December 2012. Oxford University Press. < http://www.oed.com/view/Entry/204425 > accessed March 04, 2013.
Kvorning T, Andersen M, Brixen K, Madsen K. Suppression of endogenous testosterone production attenuates the response to strength training: a randomized, placebo-controlled, and blinded intervention study. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1325-32.
Schoenfeld BJ The mechanisms of muscle hypertrophy and their application to resistance training.J Strength Cond Res. 2010; 24: 2857–2872.
Steele J. Intensity; in-ten-si-ty; noun. 1. Often used ambiguously within resistance training. 2. Is it time to drop the term altogether? Br J Sports Med. 2013 Feb 12.
Vingren JL, Kraemer WJ, Ratamess NA, Anderson JM, Volek JS, Maresh CM. Testosterone physiology in resistance exercise and training: the up-stream regulatory elements. Sports Med. 2010 Dec 1;40(12):1037-53.

Review Claims: CLA & Fish Oil Improve "Anabolic" Effects of Exercise - What Does the SuppVersity Sniff Test Say?

A bigger biceps and less body fat to cover your precious gains? At least for CLA this has in fact been observed in a human study (see figure 1).

About two weeks ago, I stumbled across an interesting paper that had just been published in the peer-reviewed journal Nutrients, filed it and got so much to do that I would almost have forgotten about it. When I was just thinking about which topic to address next, I did yet remember the auspicious conclusion to the abstract, which says "we can hypothesize that fat supplements may improve the anabolic effect of exercise." (Macaluso. 2013). "May" and "hypothesis", those are terms I like and since fish oil and CLA were implicated in the previous lines, I suppose you are going to like it as well. So what would be more obvious than to apply the "SuppVersity Sniff Test" (I am beginning to like this term, Carl often uses on the Science Round-Up) to this ostensibly well-researched review of the literature?

"May improve the anabolic effect of exercise"

Usually things that "may" do just that, namely "improve the anabolic effect of exercise" end up in a pricey and useless testosterone booster.

Check out the overview of the Intermittent Thoughts on Building Muscle and learn how testosterone, growth hormone, IGF-1, mTOR and the rest of the pack orchestrate skeletal muscle hypertrophy and why boosting your testosterone levels from mid will not translate into visible muscle gains (read more)

Personally, I don't know of any test booster though, which boasts that fish oil or CLA were it's main ingredients and without taking away too much of the results of this sniff test, I can already tell you that there is a good reason for why this is the case: It's even less likely to produce significant effects than the next best herb that "grows but in one place" in the Amazonian rain forest, where the CEO of company X harvests it at the hazard of his own life... ah, you know that spiel, so I don't have to repeat it here.

If you take a look at the tables the researchers provide as part of their review and have basic mathematical and reading skills, it's not difficult to count the number of which would remotely support the notion that fish or CLA supplementation have any effects at all: It's 5 out of 9 for fish oil and 4 out of 7 for CLA. Certainly reason enough to "hypothesize" a bit.

Fish oil is good for your heart, but not for your physique

In the next step we need a little more than to identify those studies with the "no effect" label from the tables and take a the ones we were left with after our initial glance at the data. If we do just that the number of studies we have to look at decreases from 9 to 4 studies, as none of the fish oil studies survives the "Sniff Test", after all, neither

They probably ain't anabolic either, but could help you to stay lean on a bulk: DHA-phospholipid, as you would find them in krill vs. common fish oil supplements (learn more).
improved cardiovascular function in the absence of increased endurance performance or recovery in football players (Buckley. 2009)

a minimal reduction in O2 cost in the absence of effects on the endurance performance in cyclists (Peoples. 2008),

improvements in VO2max in previously sedentary men a non-placebo-controlled study (Brilla. 1990)

a reduced acute phase inflammatory response in a non-randomized non-placebo controlled intervention with average Joes (Ernst. 1991)

would qualify as convincing evidence for any "anabolic effects" - in fact, even if we were talking about ergognenic effects in general, only the study by Guezennec would survive 2nd phase of the Sniff Test.

Now, what's interesting about the Guezennec study, though, is that the "beneficial" effects (a profound decrease red blood cell deformability; RCD) were hypoxia specific and could easily turn against you. After all, one of the reasons athlete "train high and compete low" (meaning they train at high altitudes with less oxygen in the air and thus hypoxic conditions to outperform the competition at sea level) is that this will increase the production of red blood cells. Now guess why that happens!? Correct! It's a result of the hemolytic effect of hypoxic training... now, what will happens if you copy the 6g /day EPA-max supplementation regimen of the 19-38 years old guys in the Guezennec study? Right, this effect will be absent. I wouldn't go so far and call this "ergolytic", but you could certainly make a point that huge amounts of EPA are - at least in this scenario - anti-ergogenic.

So what about CLA, then? Isn't that simply a fat burner

So, if even the widely hailed fish oil has little data to support its usefulness as an ergogenic supplement for athletes and aspiring physical culturists, what about CLA, then? I mean, we all know that the benefits researchers observed in human trials were miles apart from what they had expected to happen based on previous experiments in rodents (click on the image to the right to be redirected to a study, where the CLA treated ice dropped 77% body fat and did nevertheless display statistically significant increases in endurance capacity).

Adequate dosing still remains an issue

These discrepancy in terms of the body fat reducing effects of conjugated linoleic acid supplementation, as Dilzer and Park pointed out only recently, at least in parts a result of insufficient doses:

In July 2012 I wrote about what I believe is the unquestionably most impressive study on the fat burning and endurance enhancing effects of conjugated linolic acid. 77% body fat reduction - that's bordering lipodystrophy. The dosage used in this study would be roughly equivalent to 30g/day for human being and supports the notion that profound effects are only observed with amounts of CLA that have yet not been administered to humans in controlled trials (learn more)!
"Studies with mice used diets containing 0.5 w/w%* CLA, which is equivalent to about 56 g CLA/day/70 kg (Malpuech-Bruger. 2004). Most human studies used CLA doses ranging between 0.7 g and 6.8 g per day, which is lower than doses used in mice." (Dilzer. 2012)

*Addendum: Anonymous pointed out correctly, that the figures in the above quotation (which is dirertly from the FT) are inconsistent. 0.5% would be only 5.6g. I guess that's a typo in the Dilzer study, because the Malpuech-Bruger study they reference says "a daily intake of 0.70 g/kg body mass was effective in mice". (Malpuech-Bruger. 2004) - sloppily as they are, they don't say that this is already in human equivalents, though. That becomes clear in the next sentence only, which says "A value of 0.70 g/kg body mass in humans would correspond to a daily intake of 56 g of CLA." (ibid.) The July 2012 study I reference under the image to the right used a HED of ~30g (learn more), so even if the exact figures are questionable, the argument obviously still holds.

Since the same goes for studies investigating the "anabolic" effects the abstract to Macaluso et al.'s review explicitly mentions, chances are that increases in endurance performance, as they were observed in the previously mentioned rodent study (read the full story, here), were likewise species or at least dosage specific.

Is CLA "anabolic" or at least ergogenic?

If we take a look at the 7 studies the researchers included in their review (I guess you will be hard-pressed to find more than those seven, as CLA is not exactly the typical supplement researchers use as an ergogenic), we can easily exclude three of them. In these studies that were conducted on healthy young women, trained male bodybuilders and physically active men and women, supplementation with 3g, 6g and 3.9g/day of CLA did exactly nothing.

This leaves us with a set four studies to take a closer look at - three of them report improvements in body composition, two of them also observed increases in endurance performance and a single one even found "slight increases in testosterone":

Improvements in body composition were observed by Thom (2001), Colakoglu (2006) and Pinkonski (2006); all studies were placebo controlled and the participants were physically active or at least healthy men (only in the Thom study) and women who consumed 1.8, 3.6 and 5g of CLA per day.

While the former two studies by Tho and Colakoglu used exhaustive and medium intensity endurance programs, the study by Pinkonski et al. used a stardardized full-body workout with 12 exercises ranging from leg presses, bench and shoulder presses, to lat pull downs, biceps curls, and some core exercises. Each exercise was performed three times per week consisting of 3–4 sets of 4–10 repetitions at approximately 75–90% of one-repetition maximum (1RM).
Figure 1: Relative changes in body composition biceps and quadriceps size and strength parameters after 7 weeks of serious strength training with or without 5g of CLA per day (Pinkoski. 2006)
This protocol and the high number of study participants (76 men and women) and their training status - the majority had more than 2 years of weight training experience under their belts - make the results of the Pinkoski study so interesting for us. The results, on the other hand (cf. figure 1), are not exactly earth shattering, especially in view of the fact that only the fat loss and the increase in biceps size reached statistical significance and that despite a pretty high number of participants. Whether or not CLA really is "anabolic" and not "just" a mediocre fat burner has thus still to be determined.

Figure 2: Increases in cortisol (top) and testosterone (bottom) and respective increases in lean body mass in response to a 12-week hypertrophy oriented resistance training program (West. 2012)

Increases in testosterone, as Macaluso et al. observed them in 10 "physically active" male subjects (age, 27.4) in a previous study in response to 6g CLA per day, on the other hand, would probably qualify as "anabolic" if the latter had not been measure right the workouts, as part of a short 3-week study with no corresponding effects on body composition (Macaluso. 2012).

The latter should actually not come as a surprise to any seasoned SuppVersity student. After all you've learned that (1) endocrine induced changes in body composition take their time in the Intermittent Thoughts on Building Muscle, that (2) the role of testosterone levels in the normal range in the whole process is fundamentally overrated and (3) that the seminal paper by West & Phillips, on which the data in figure 2 is based, clearly refutes the notion that post-workout increases in testosterone have any impact on skeletal muscle hypertrophy.

If we also take into account that numerous rodent studies do in fact support the notion that CLA posses "ergogenic", yet not necessarily "anabolic" qualities. Macaluso et al. are certainly correct, when they conclude their paper with the scientific equivalent to "And they lived happily ever after" stating that "additional research".

Milk from pastured cows has a relatively high amounts of both, CLA and DHA + EPA. The absolute amounts are however so low that you would probably have to drink more than the notorious gallon of milk per day to see any effect - and let's be honest, even if CLA + DHA make a good fat burner, the gallon of milk certainly makes a better weight gainer ;-)

Bottom line: I guess, you'd like to hear a supplement recommendation now, right? Well, as far as ergogenic and/or anabolic effects are concerned, CLA is unquestionably the more promising fatty acid off the "two" (actually we are talking about four fatty acids, here: DHA + EPA = fish oil and cis-9,trans-11 and trans-10,cis-12 CLA). CLA's anti-PPAR-gamma effect, which is probably responsible for the reductions in insulin sensitivity and detoriations of the lipid metabolism that have been observed in numerous studies (only trans-10,cis-12 CLA), is probably not so much of a problem for lean, physically active people and the upside of the PPAR-gamma blockade is a reduced rate of fat storage....

Ah, you see I am diverting to the fat loss effects again. And if we are honest, the results of this review do actually only confirm that what you've read here at the SuppVersity roughly 3 months ago the combination of CLA + DHA could turn out to be a safe and effective fat burner (learn more), if we would finally see adequately doses, long(er) term supplementation trials in humans.

As ar as the "anabolic" nature of either of them, i.e. EPA + DHA or cis-9,trans-11 and trans-10,cis-12 CLA. The jury may still be out there, but the verdict is - at least in the case of regular fish oil almost certainly "not guilty", .. ah I mean, "not anabolic".

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