Caffeine By Afrida: Intermittent Thoughts On Intermittent Fasting - Exercise (2/3): Opening the "Anabolic Barn Door" With the Key of Exercise and Nutrition Science!

Image 1: The "anabolic window" turns out to be more of a barn door, which is unlocked by the key of exercise and nutrition science (Random House Books)

Looking back, the main take-aways from the last installment were the dependence of exercise performance on adequate and not so much constant energy supply, as discussed in the context of the Ramadan fasting soccer players, the increased AMPK response to fasted training on a hypercaloric diet, which would suggest that things like "fasted cardio" in the morning could well have it's place in an intermittent fasting regimen even when you are bulking (in order to ward off fat gains), and, last but not least, the differential AMPK- and p70S6K protein synthetic response of cyclists and powerlifters to unaccustomed training stimuli. Accordingly, a versatile training routine that is timed in a way that allows you to train fasted or semi-fasted training, i.e. having your first easily digestible high protein meal / supplement ~30min-1h before you hit the gym, will certainly help with lean gains and muscle-sparing fat loss.

How to train if someone "just wants to look good naked"?

While the observations of the Coffey study (Coffey. 2005) did underline the importance of versatility, or, I should say constant "novelty", or at least modification of the training stimuli, they did not really provide any clues on how someone, who "just wants to look good naked" (and I assume this applies to the majority of non-athletes, today) should train to transform his formerly at best non-obese physique to the cover-model'ish look everybody is aspiring these days.

Figure 1: Study design of the Vissing study with its 10-week preconditioning phase for the strength and endurance training groups (generated based on information from Vissing. 2011)

In regard to this question, a similar, yet more recent study on non-athletes comes to mind. In the course of the latter, K. Vissing and his colleagues from Aarhus, Denmark, and Geelong, Australia, took a closer look at the response of the "AMPK/mTOR seesaw" to either endurance or strength training (Vissing. 2011) after a comparatively brief per-conditioning period of 10 weeks (cf. illustration 1) - a scenario of which we can expect more reliable results than from its "highly trained recreational athletes" counterpart from the Coffey study, where the participants have been focusing on training for their respective sport (cycling or powerlifting) for years. Accordingly, Vissing et al. expected to see that...

[...] mTORC1 signaling would be selectively activated by SE [strength training], whereas AMPK signaling would be activated by both types of exercise but to a relatively higher degree after EE [endurance exercise] compared with SE [...]

Thus, their research hypothesis was in accordance with the publicly accepted idea that only strength training builds muscle (obviously the role of mTOR-activation in this process is widely unknown in the general public), while endurance exercise would be the better form to train if one wanted to lose fat - as a diligent reader of the SuppVersity, you will obviously be aware that the reduction in adipose tissue you will hopefully observe, when you are dieting, is primarily a result of the depletion of muscular (and hepatic) ATP stores, which brings the AMPK energy emergency police on the scene which will concomitantly tell your muscles to suck up all extra (i.e. more than your brain needs) glycogen from your blood stream and kick your adipocytes' asses, so that they release some of their fatty energy reserves as metabolic firewood for your mitochondria.

I hope you remember "The 'hungry' side of neuronal AMPK activation", i.e. the differential effects of AMPK phosphorylation in reaction to energy shortage in muscle or liver tissue vs. its effects in the brain. If not, I suggest you (re-)read the respective passage in "AMPK III/III: Natural Rythmicity for Maximum Fat & Minimal Muscle Loss", as a thorough understanding of this difference if of utmost importance if you want to be able to compare and interpret the data from various studies correctly.

The Coffey study (discussed in the last installment) did however show that this assumption, i.e. both endurance, as well as strength training will always increase AMPK, does not hold true, when we are talking about highly trained athletes - neither in the cyclists nor in the powerlifters from the Coffey study did engaging in their respective discipline produce statistically significant increases in AMPK phosphorylation.

Figure 2: AMPK phosphorylation (0, 2.5, 5 and 22h post) and approximate area under the respective curces (small graph) during post-exercise recovery from single-bout exercise, conducted with an exercise mode to which the exercise subjects were accustomed through 10 weeks of prior training (data calculated based on Vissing. 2011)

Conversely, in the Vissing study, AMPK phosphorilation did transiently increase in both the strength and endurance trained groups immediately post (at 0h) exercise (cf. figure 2). However, with the subsequent drop of the phosphorylated AMPK (pAMPK) below the values of the control groups, the estimated area under the curve (AUC; I simply used weighed averages for the calculation), i.e. the absolute AMPK phosphorylation over the whole 22h post-exercise window, for which the scientists have data (cf. figure 2, right), was -12% and -17% lower in the strength training group than in the control and endurance group, respectively.

Without the AMPK elevation of an intermittent fast (or calorie reduction), it is thus unlikely that strength training alone is going to trigger significant AMPK responses.

Interestingly, the scientists state that the protein expression "of any of the reported signaling proteins" was "not altered" by the 10 weeks of pre-training, which would indicate that, contrary to years of competitive endurance exercise (cf. cyclists in illustration 1 in previous installment), 10 weeks with three weekly sessions of combined steady-state and interval exercises on stationary bikes do not blunt AMPK phosphorylation in response to 120 min of bicycle exercise at 60% of the individual VO2 max.

The induction of mTOR phosphorylation is and will remain the real strength of strength training

Likewise, the protein synthetic response (as evidenced by mTOR and p70S6K expression) did not change in response to a 10-week pre-conditioning phase comprising 30 leg workouts (3 exercises; 3-5 sets; 10 reps in the first 15 sessions, 4-6 reps in the last 15 sessions). Interestingly, and contrary to the often heard assertion that mTOR phosphorylation would be a strength training exclusive, figure 3 shows that there is still a minor, yet over the course of the post-exercise period, non-negligible increase in mTOR phosphorylation in the endurance trained subjects, whose 45min cycling session effectively blunted the mTOR dephosphorylisation the control group, who, just like all of the previously (before the preconditioning) 22 untrained healthy male subjects (79.1 kg; 182 cm; 23.3 years), fasted for the first 5h "post exercise" (their exercise consisted of sitting on the couch, doing nothing ;-).

Figure 3: mTOR phosphorylation (0, 2.5, 5 and 22h post) and approximate area under the respective curces (small graph) during post-exercise recovery from single-bout exercise, conducted with an exercise mode to which the exercise subjects were accustomed through 10 weeks of prior training (data calculated based on Vissing. 2011)

Even without looking at the data in figure 3 it should be obvious that the meager increase in mTOR phosphorylation in the endurance group cannot compete with what we see in the strength trained subjects, whose p-mTOR ( = phosphorylated mTOR) levels skyrocket in the post exercise phase, peaking at +218% (control: 56%; endurance: 130%) not immediately or maybe 1h post exercise but 5h after. Thus, the purported "anabolic window" of 1-2h after a workout turns out to be a barn door, in the real world - a barn door which is wide open right in the middle of your intermittent fasting feeding window!

Strength training = opening the "anabolic barn door"

Yet, while we do now know how to unlock the barn door, we still do not know if there ain't a way to push it open even further / faster, and how to keep it wide open for as long as possible. In this context, a study by Burd et al. from Steward Phillips group at the Department of Kinesiology of McMaster University in Hamilton, Ontario (Burd. 2011) could provide further clues into the "optimal" way(s) to push the "anabolic barn door" open, as wide as possible.

After all that has been said about the over-expression of mTOR in our current society in the previous installments, it should be said that the problem does not lie with mTOR itself, as it is not the latter which inhibits AMPK, but the energy abundance that triggers the mTOR response in our western obesity scenario. This chronic nutritionally induced suppression of AMPK is something we need to distinguish from both the training-induced increase in mTOR phosphorylation and the temporary and strategically used dietary stimuli that are so characteristic of intermittent fasting.

Figure 4: If we disregard the nutritional component, the training induced "anabolic barn door" does not only coincide with the feeding window, it would also keep you nicely "anabolic" in the course of the fasting period.

In figure 4, I have extrapolated the missing two hours to complete a 24 hour intermittent fasting period, in the course of which you would do your training session early in the morning, head towards the gym at 8:00am, change your clothes, warm up, training for about an hour and break the fast at 10:00am. Thereafter, you would have a pretty long feeding window of about 6 hours, to then begin another fast... in that, your meal pattern would differ profoundly from the one of the study subjects, because the latter had to fast for the first 5 hours post exercise, so that the mTOR response was not augmented and the study results distorted by meal ingestion (afterwards they were allowed to eat whatever they wanted until 22:00pm and had to report back for the 8:30am blood draw (mTOR still +89% elevated) on the next morning. Due to these differences it is difficult to predict how your overall (i.e. exercise + food induced) mTOR response would look like on the above regimen.

Will the "anabolic barn door" stay open in the course of the fast and thusly prevent muscle breakdown?

This is where the data from the Burd study comes into play (Burd. 2011). In their study, Bird et al. had measured the fractional protein synthesis rate in response to feeding (15g of whey protein) and feeding and exercise (unilateral leg raises) at different intensities, i.e. 90% 1RM to failure, 30% 1RM with matched work-load and 30% 1RM to failure. What they found was that

regardless of condition, rates of mixed muscle protein and sarcoplasmic protein synthesis were similarly stimulated at FED and EX-FED (Burd. 2011)

- an observation, the scientist attribute to the fact that the sarcoplasmic constituents of the muscle may be more susceptible to hydration flux, so that the results may not adequately represent the "actual" protein synthetic response.Thusly, the researchers rely in their interpretation of the data mainly on the myofibrillar protein synthesis rate (cf. figure 5).

Figure 5: Changes (% per hour) in absolute myofibrillar protein synthesis (adapted from Burd. 2011)

As you would expect and actually can see in figure 5, the latter did respond to the additional exercise stimulus. Pumping away at 30% of your 1RM max without going to failure, is yet not enough to augment the statistically hardly significant increase in fractional protein synthesis that was triggered by protein ingestion, alone. It takes some effort, or, in other words, heavy weights and training to failure to trigger elevations in AKT phosphorylation (90% 1RM to failure) or mTOR phosphorylation (30% 1RM to failure) to get that done (note: neither of the two, i.e. protein kinase B = AKT or mTOR was significantly elevated by feeding, alone).

[...] protein ingestion stimulated rates of myofibrillar protein synthesis above fasting rates by 0.016 ± 0.002%/h and the response was enhanced 24 h after resistance exercise, but only in the 90FAIL and 30FAIL conditions, by 0.038 ± 0.012 and 0.041 ± 0.010, respectively. Phosphorylation of protein kinase B on Ser473 was greater than FED at EX-FED only in 90FAIL, whereas phosphorylation of mammalian target of rapamycin on Ser2448 was significantly increased at EX-FED above FED only in the 30FAIL condition.(Burd. 2011)

Moreover, and this may be of even greater importance in the context of exercising on an intermittent fast, muscle protein synthesis stayed elevated way beyond what is usually considered the <4h "anabolic window".

Our results suggest that resistance exercise performed until failure confers a sensitizing effect on human skeletal muscle for at least 24 h that is specific to the myofibrillar protein fraction. (Burd. 2011)

While this is obviously important for everyone who wants to accrue as much muscle muss as possible, any elevations in protein synthesis will also help a dieter to keep is hardly earned muscle, because in essence our muscles are continuously build up and broken down - proteolysis, i.e. the breakdown of muscle tissue, and protein synthesis are going hand in hand and it is the ratio of one to the other, which decides whether we are in an "anabolic" (synthesis > breakdown) or catabolic (breakdown > synthesis) state. Consequently, any elevation in protein synthesis will ameliorate muscle loss - no matter how proteolytic a dieter may become during the fasting phase.

It takes >24h for the barn door to close itself - use this time to get rid of fat, not muscle

Fine, we unlocked the "anabolic barn door", it stays open for "at least 24h"... blah blah... wtf! how does all that translate from the metaphorical into the real world of intermittent fasting? Well, the answer is pretty simple, as hundreds of trainees have been practicing exactly that with extreme success over the past couple of months:

fast until min. 1h before your training
spike your protein synthesis with a protein shake (~20g of whey), EAAs (~10g) or BCAAs (~8g)
train semi-fasted and heavy
feast within a 5-8h window
repeat the same litany again

Now, the sheer size of the barn door, ahm... sorry, the long-lasting anabolic and thusly anti-catabolic effect of intense strength training should allow you to either skip or replace "3. train semi-fasted and heavy" with "3. passive or active recovery" (in that case you also do not want to ingest the protein shake / EAA / BCAA) or even some "3. semi-fasted cardio" (see notes in red box) if you feel that your conditioning or weight loss will benefit from that, every other day without running the risk of either gaining too much fat weight.

Image 2: Your "anabolic barn" is huge enough to accommodate one or two steady state, low intensity or high intensity "cardio" sessions per week.

If you want to incorporate "cardio" training into your routine, the pre-conditioning protocol from the Vissing study could actually be a very good, since diversified, regimen. In that, you would cycle between doing "standard" steady state conditioning work, longer medium-intensity interval training and short, but intense HIIT sessions. The result would be a very complete "cardio" protocol, of which the Vissing study showed that it will help you ramp up your AMPK levels pretty profoundly, even if you are only sitting on one of those cycle ergometers pedaling away jovially at 60% of your VO2 max. And in case you are now concerned about possibly shutting the barn door - look at figure 3 again, the mTOR response to this kind of exercise may not be earth-shattering, but a plus of 25% @5h post exercise is better than what you would get if you just lay around lazily, as the control group in the Vessing study did.

With these insights into why that of which you already knew that it works actually works, I conclude this week's installment of the Intermittent Thoughts and hope that I did not bore you so much that you do not come back next Sunday for another installment of this series ;-)