Intermittent Thoughts On Intermittent Fasting - Exercise (1/3): Cycling, Powerlifting and Lean Gaining ;-)

Image 1: It may be more effective than your usual "eat half as much diet", but even with intermittent fasting exercise is compulsory, not facultative.

In the last installments of this series we have analyzed the natural interplay between AMPK and mTOR, have learned that chronic over-expression of either of the two can be detrimental to the way you look, feel and perform and have scratched on the surface of how intermittent fasting and the use of AMPK and/or mTOR promoting supplements can restore and amplify the natural up and down on the AMPK/mTOR seesaw and thus promote fat loss and and gains in lean body mass - not at the same time, but cyclically. In this episode it is high time to take a closer look on how exercise, the one and only true "body recompositioning agent", plays into this.

Tell me who you are and I tell you how your body will respond to exercise.

What we already know is that the exercise induced depletion of intra-cellular ATP and the corresponding increase in ADP and AMP levels will produce profound(!) increases in AMPK phosphorylation. In a recent study on the effects of a 30s Wingate test (a sprinting test on a cycle ergometer with breaking loads equivalent to 10 and 8% of body weight for men and women), for example, scientists from Gran Canaria found increases in AMPK phosphorylation vs. baseline of +495% - 98% for the ten women in the study and +278% - 33% for the 17 (cf. figure 1)

Figure 1: Relative changes in AMPK phosphorylation in response to 30s Wingate sprint test in 17 male and ten female subjects (data calculated based on Fuentes. 2011)

As you can see there is a huge (and statistically significant) gender difference in the initial AMPK(-alpha) response to sprinting, the difference at 30min and 120min post exercise on the other hand did not reach statistical significance (p<0.05). In an aerobic exercise scenario (90min at 60%VO2max), however, Roepstorff et al. PK came up with the exact opposite results (Roepstorff. 2006):

A 198% increase (P < 0.001) was observed from rest to 90 min of exercise in men, whereas in women the exercise-induced 74% increase in αAMPK Thr¹⁷² phosphorylation was only borderline-significant.

The different fiber-composition of the male and female subjects could provide an adequate explanation for this phenomenon. With a +23% higher ratio of slow twitch type I to fast twitch type II fibers, the women in the Roepstorff study were, on a pound per pound base, more effective endurance athletes than the men. Consequently, they did not run out of fuel so fast and thusly there was no need for their bodies to ramp up AMPK by the same 198% as the bodies of the men did.

Figure 2: Fat oxidation (in kcal/kg per min) calculated based on respiratory exchange ratio in male and female participants of a 90min cycling bout at 60% of their individual VO2Max (Roepstorff. 2006)

It is important to note that despite lower AMPK activiation in the female participants of the Roepstorff study, the women (due to their high ratio of type I fibers with +25% higher capillarization) had statistically significantly higher fatty acid oxidation rates (i.e. they burnt more fat) than their male counterparts (cf. figure 2)! This goes to show you that the metabolic scene, which is set by AMPK, is not the sole determinant of substrate metabolism. In the end, the capacity of the mitochondrial furnaces decides how much energy from fat you will be able to burn. For subjects with a high amount of type I fibers whose primary objective is to actively burn additional fat calories, aerobic exercise may thus well be a viable alternative for intense HIT regimens, of which Astorino et al. have recently shown that the rate of fatty acid oxidation in recreationally active men and women is identical within the statistical margins (Astorino. 2011).

Conversely, the higher type II to type I fiber ratio of men makes them better sprinters. That and their overall larger muscle mass could have allowed them to perform the 30s sprint on the cycle ergometer without having to resort to extra-muscular energy stores, which would explain why we did not see a significant increase of AMPK immediately after sprinting. Its occurrence 30 minutes after the sprinting exercise does yet go to show that even very short exercise bouts can trigger pretty profound AMPK responses, of which I would speculate that they facilitate post-exercise glycogen repletion via "energy-repartitioning".

Why cyclists should powerlift and powerlifters should cycle

Illustration 1: Differential response of cyclists and power lifters to strength and endurance training; statistically significant increases are highlighted in green, statistically significant decreases in red (data compiled from Coffey. 2005)

With regard to the differential response to different exercise modalities we also know from a 2005 study by Coffey et al. (Coffey. 2005) that muscle from strength-  and endurance-trained individuals respond very differently to endurance (1 h cycling at 70% VO2peak) or resistance training (8 sets of 5 maximal repetitions of isokinetic leg extensions).

I've gone to all the bother of compiling the extensive data on muscle protein synthesis and related signalling proteins from the study into a single chart (cf. illustration 1), where statistically highly significant increases are highlighted in green and statistically significant decreases are highlighted in red. Thusly, you should be able to see that if the goal is to increase AMPK, cyclists have to strength train, while powerlifters will have to get into the saddle of an elliptical or ergometer.

What appears paradoxical at first, is the result of adaptation processes: Only novel and unaccustomed stimuli trigger further adaptation... and "novelty" is such a profound trigger of adaptational responses that - under the assumption that p70S6K phosphorylation is a reliable measure of the protein synthetic training response - cycling causes almost comparable increases in protein synthesis as resistance training in powerlifters, a group of athletes who are not exactly known for doing large amounts of "cardio" training.

Since this is not exactly "intermittend fasted" related, I leave it up to you to interpret the rest of the data. Before I "think on", I do yet want to caution you against getting stuck in doing the same type of exercise over and over again - there is a reason that 99% percent of the figure athletes, bodybuilders, fitness models or whatever other athletes and celebrities you think have an aesthetic body, incorporate some form of aerobic training into their regimens, as well (if you read the latest posts on HIIT training, you will be familiar that "aerobic" does not always mean steady state endurance training ;-)

Training fasted? Maybe, for athletes and performance oriented amateurs.

While the previously discussed studies showed that AMPK/mTOR responses to different exercise regimes largely depend on who you are and what type of training you have conditioned your body to, it did not answer the question that appears to be preying on everyone's mind, which is "Do I do my aerobic and or resistance training in a fasted (no food at all), semi-fasted (only protein and maybe some fat), or fed state?" Or in other words: "Do I break the fast before or after training?"

Image 2: Ramadan fasting can serve as a relatively particularly well studied "model" of intermittent fasting. You can find more information about the strengths and limitations of this model, please read Part 2 and Part 3 of this series.

A brief reminder for all who of you who missed the first installments of this series and may now wonder why I am, without further explanations, referring to studies on Ramadan fasting as if it was intermittent fasting - in essence it is! This is why I have already discussed a handful of studies that investigated the effects of Ramadan fasting on Muslim athletes, in the initial installments of this series. In that context, I have also pointed out why the Ramadan "protocol" is an acceptable model of intermittent fasting and where it deviates from what we are seeing in the dietary regimens with which Adelfo and Duong get to grips with the little fat that is still left on their athletic bodies. For more information on that I would like to refer you to Part 2 and Part 3 of this series, in particular.

If you are a competitive athlete, who follows the advice of the establishment, the answer is easy - EAT, EAT, EAT! And do not even think of fasting! On the other hand, even experts openly admit that despite the fact that it is (Maughan. 2010).

often automatically assumed that intermittent fasting will lead to decrements in exercise performance. [...t]he available evidence does not entirely support this view, but there is little or no information on the effects on elite athletes competing in challenging environments.

With respect to the lack of data, we are in the fortunate position that the Olympic Games 2012 coincide with the Ramadan period from July 21 to August 20, 2012, i.e. right in the heart of the Games. Meanwhile we do yet have to resort to the little reliable data there is and of which Maughan et al. writes in another article that it "suggests that effects of Ramadan-style fasting on exercise performance are generally small." And a pretty recent study which investigated the effects of Ramadan fasting on performance and body composition of 16 young soccer players (17.4±1.2 years, 175.4±3.6 cm, 69.6±4.3 kg and 5.1±1.3 years of training experience) corroborates this assertion.

Study shows: You can improve body composition and performance if you train intermittendly fasted, but not in a fasted state 

Alpay Güvenc from the School of Physical Education and Sports at the Akdeniz University in Antalya, Turkey, assessed body composition, hydration status, dietary intake and sleep duration of his 16 male subjects, who continued their regular pre-season soccer training during the four weeks of Ramadan, on four occasions: before Ramadan, at the beginning of Ramadan, at the end of Ramadan and 2 weeks after the end of Ramadan. The training sessions were yet postponed, so that the soccer players could have a snack or meal before they took to the field - they were thus intermittendly fasting, but not training in a fasted state!

Figure 3: Relative changes in RD: running distance, RT: running time, RV: running velocity and
RV4.0: running velocity at 4.0mmol.L-1 lactate concentration due to Ramadan fasting during the pre-season preparations in 16 male soccer players (data calculated based on Güvenc. 2011)

As figure 3 goes to show, there was an initial decline in exercise performance in the first week of Ramadan (=intermittent) fasting. In the last week of Ramadan, the maximal running distance, the running time and velocity and the RV4 (running velocity at 4.0mmol.L-1 lactate concentration) had improved - only by 3%, 3%, 1% and 2% over baseline, but nevertheless statistically significantly. Now, what may be even more interesting for professional athletes is that these beneficial effects continued well into the post-Ramadan phase - how much of this has yet to be ascribed to the training regimen (remember the soccer players were in their pre-season preparation) could only be determined if half of the kids had been Christians and had served as a non-intermittendly-fasted control.

Figure 4: Changes in total body water (TBW in L), fat free mass (FFM in kg), body fat (in kg) and  the sum of skin-fold measures (in mm) due to Ramadan fasting during the pre-season preparations in 16 male soccer players (data calculated based on Güvenc. 2011)

In a similar vein, we cannot say for sure, whether there had been comparable improvements in body composition (as evidenced by the statistical significant reduction in skinfold measures, i.e. -2.2% by week 4 of Ramadan fasting; cf. figure 4), if the players had just continued their usual pre-season training without fasting intermittendly. What we can say for sure though, is that they achieved the latter without any major changes in their overall caloric intake or macronutrient composition (cf. figure 5)
And that the fasting had no negative effects on the subjects sleep duration (~8.7h) or their hydration status. So that, it would appear that during a metabolically demanding pre-season training a non-specific intermittent fast works just / at least as good as a normal diet, as long as the athletes meet their training induced caloric demands.

Training fasted? Yes, for lean gains.

Image 3: For some "lean gains" happen only in their heads (img muscle.iuhu.org)

Now, while "exercise performance" obviously is an important variable, I assume most of you who are toying around with the idea of doing an intermittent fast, are more interested in its effect on body composition and would tolerate a dip in "exercise performance" (whatever type of exercise that may be in your case) if only those love handles finally disappeared and allowed your ever-increasing muscle mass to shine... or are you interested in the potential (largely AMPK-related) health benefits intermittent fasting has to offer in a world, where nutritional abundance is a 24/7 phaenomenon and the world "bulking" is often misinterpreted as taking advantage of the former as often as possible?

In both cases the results of a 2010 study from the Human Performance Laboratory in Leuven, Belgium (not the one in Canada!) would be relevant for you. In that study (Van Proeyen. 2010), Van Proeyen et al. had 27 healthy male volunteers consume a hypercaloric high-fat diet (∼+30% kcal/day; 50% of kcal from fat) for 6 weeks. Additionally 20 of the subjects had to participate in 4 training sessions per week (2x90min and 2x60min) consisting of cycling at 70-75% of the individual VO2Max and running at 85% of the maximal heart rate. 10 of the subjects (CHO; n=10) had yet had breakfast (~90min before training; 675 kcal, 70% carbohydrates, 15% fat, 15% protein), the rest (fasted; n= 10) reported to the lab after an overnight fast.

Figure 4: GLUT4 and AMPK expression in 10 healthy male subjects before and after 5 weeks on a hyper-caloric high-fat diet with or without (control) exercise in the fasted or fed (CHO) state  (data calculated based on Van Proeyen. 2010).

As the asterisk in figure 4 indicates, the exercise induced increase in GLUT4 (responsible for muscular glucose uptake) and AMPK expression is significant (p<0.05, i.e. chances that this is only coincidence <5%) only in the subjects which trained in a fasted state. Moreover, only the group which trained in the fasted state had neither statistically significant weight increases, nor statistically significant increases in the sum of the skinfold measurements (a relative reliable marker of body fat levels). The unexercised controls and the CHO group (training in fed state), on the other hand, gained 3kg and 1.4kg body weight (both p<0.05). Interestingly, though only the control group experienced a statistical significant increase in the sum of their skinfold measures of +15.1%! (+1.1% in fasted; +5.4% in CHO).

This study for the first time shows that fasted training is more potent than fed training to facilitate adaptations in muscle and to improve whole-body glucose tolerance and insulin sensitivity during hyper-caloric fat-rich diet. (Van Proeyen. 2010).

Obviously, we are dealing with a very different situation, when an intermittent fast is combined with a caloric deficit - yet in view of the idea to use intermittent fasting as dietary strategy on a "lean bulk", the results of the Van Proeyen study could be of great importance. Not only in view of keeping the fat gains at bay, but also with regard to potential negative health effects of deliberate overeating and subsequently compromised insulin sensitivity.

A pros pos "lean bulk", I suggest you do come back next week if you want to know more about when and what to eat right after what type of workouts in order to maximize muscle and minimize fat gains when you train intermittendly fasted. For now, I wish all of you a sunny Sunday (here it is one) and an intense week at the gym, regardless of whether you train (intermittendly) fasted or not ;-)

Intermittent Thoughts on Intermittent Fasting - The Switch: Introducing the AMPK vs. mTOR Metabolic Seesaw

Figure 1: The mTOR - AMPK "cycle" can become a vicious one, as soon as its natural balance becomes disturbed by external, mostly nutritional and/or exercise related factors. Intermittent fasting could help you restore the balance.

Before we prematurely(?) break the fast and get to the nitty gritty of the feeding window, I want to briefly recapitulate the results of the last installment, which - as it will turn out - are of particular importance in view of today's discussion, as well. It were the thoughts on the health and possibly life-extending effects of intermittent fasting in the last installment of this series that brought up the involvement of 5'-adenosine monophospate (AMP)-activated protein kinase (AMPK) in both the weight, or we should say, fat loss and possible life-extending and anti-cancer effects of (intermittent) fasting. Now, before we even delve into a more detailed discussion of its relation to its "antagonist", the mammalian target of rapamyacin (mTOR), it would appear prudent to begin today's 6th installment of the Intermittent Thoughts on Intermittent Fasting series with a brief review of AMPK's effect(s) on protein synthesis, adipose tissue metabolism and apoptosis.

We already know that both fasting and exercise trigger increases in AMPK enzyme expression, which in and out of itself acts as an intracellular sensor that registers elevated AMP/adenosie tri-phospate (ATP) and inorganic phospate(Pi)/phosphocreatine (PCr) ratios - in short, it registers when you are running out of fuel. It is thus obvious that the main function of AMPK within muscle cells is to maintain energy stores at homeostatic levels. In order to achieve that, the 5’-adenosine monophosphate (AMP)-activated protein kinase enzyme upregulates catabolic processes and downregulates anabolic processes. The (entailing) overall effects the phosphorylation, i.e. the activation, of AMPK has on your metabolism are yet more complex than this dichotomous distinction would suggest - its tissue specific effects are illustrated in figure 2:

Figure 2: Downstream effects the "activation" of AMPK has on liver, muscle, and fat tissue.

In terms of the thought-after gain/retention of lean muscle mass, you must thusly consider AMPK as one of your worst enemies - an enemy which has conclusively been shown to respond to decreasing muscle glycogen content, both at rest and during exercise (Wojtaszewski. 2003) and inhibits overload-induced hypertrophy in fast-twitch muscle fibers.

Now, it would be paradigmatically short-sighted to draw the bro-scientific conclusion that you, as a physical culturist, should do everything in your power to avoid the phosphorylation of the 5’-adenosine monophosphate (AMP)-activated protein kinase enzyme to harness the power of permanent mTOR-activation. As mentioned in the last installment, AMPK and mTOR, i.e. the mammalian target or rapamycin, are antagonist - yet not in the sense of a switch with two mutually exclusive positions, but rather like two kids on a seesaw: where one can only go up, when the other is going down.

Proteine kinase seesawing for beginners

Image 1: Seesawing ain't working if you are trying to do it with someone who does not allow AMPK to come into it's own (img perceptasmile)

There is however more to this analogy than it may appear at first sight. If you think about your childhood, did you ever try to seesaw with an adult or another kid that was much heavier than you were? I assume if you have, you will remember that this was not very funny, because it constantly disrupted the natural (and fun) rythm of up and down... if you are asking yourself now, where this stupid physicist is heading with his seesaw example, think of your counterpart on the other side of the seesaw as being a sedentary, obese, carboholic diabetic who is constantly stuffing candy, chips, burgers and French fries down his pie-hole in a futile effort to satisfy his insatiable craving for a constant supply of readily available energy. This guy will be so heavy that seesawing is absolutely impossible. The rhythmicity of the game, is yet not the only thing that is disrupted, the natural and vital rythm of anabolic and catabolic or I should say production and recycling of your opponent is broken, as well.

With the constant abundance of readily available energy and, consequently, a low AMP:ATP (~used to usable energy source) ratio, the AMPK-related phosphorylation TSC2 and RAPTOR (cf. figure 5), which in turn would inhibit mTOR activity is absent. Now, what sounds as if it was taken right from a body builders well-spray-tanned dreams, is in fact as unhealthy as it is unnatural. Not only does it block all the beneficial effects of AMPK, i.e.

• increased glucose uptake in liver and muscle,
• increased fatty acid oxidation, 
• reduced glucose and fatty acid synthesis, and
• autophagy

the presence of which in figure 1 you may not even have noticed, when you heard the dreaded word "catabolic". Of these, the latter, i.e. autophagy, may have the least cosmetic value (and some of you may even not know what exactly it is) is of paramount importance for your health - after all, these cellular degradation processes allow your body to constantly rebuild itself, to sort out degenerate cells and make good use (recycle) what would otherwise pile up in form of messy metabolic junk or - even worse - uncontrollably proliferating tissue, i.e. cancer!

AMPK vs. mTOR in energy regulation, health and disease

The seesaw analogy should have made it quite clear that not mTOR or AMPK, but mTOR and AMPK and their interplay constitute the fundamental backbone of an energy sensing and growth regulating system, we have inherited from our earliest, eukaryote ancestors. And with many (if not all) of the major health problems of the Western society being related to a profound disturbance in energy regulation, it is by no means surprising that the chronic (over-)expression of the mTOR pathway (as exemplified by our overweight seesawer from image 1) that is so characteristic of our world of nutritional abundance has recently been implicated in all sorts of...

[...] disease states, where growth is deregulated and homeostasis is compromised, namely cancer, metabolic diseases and ageing (Zoncu. 2010).

Assuming that you have read all previous installments of this series, this should make you sit up: Cancer, metabolic disease (obesity, diabetes, hyperlipidemia,...), even aging (cf. figure 3)... in the past Intermittent Thoughts you have not only read about all of these, but you have also seen that intermittent fasting, in the form of either alternate-day-fasting, or Ramadan fasting was able to ameliorate or even partly reverse all these ailments of an obesity-stricken society, which is about to drown in fructose-corn-syrup and partially hydrogenated vegetable oils.

Figure 3: The contribution of a chronic overactivation of the mTOR pathway on aging
(based on a review of the literature by Zoncu. 2010)

The fast (regardless of whether its background is a religious one or not) breaks the vicious cycle of chronic mTOR (over-)expression and allows the body to start necessary and beneficial catabolic breakdown processes to rebuild, repair and recycle what got damaged and patched together raggedly in the course of the "anabolic" phase. Now, just as even someone with the repair-skills of Bob the Builder ("I can fix it!"), would obviously - at some point - be unable to make up for the wear and tear the furnishings in his house are exposed to, the well oiled cellular repair-machinery of our bodies will also hit a wall, when all the debris is cleared and the excess energy that had been stored away in times of nutritional abundance is either running short or cannot be accessed fast enough to satisfy acute energy demands (specifically of the brain). Yet, while the latter would obviously be much more likely, when after the "magical" ~16h, after which the glucose stores in our livers begin to dwindle (cf. Intermittent Thoughts - Myth 2), the undesirable result of the energy shortage, i.e. catabolism, would always be the same.

Image 2: Do you too have a question related to AMPK, mTOR or Intermittent Fasting, in general? Don't be shy and send it in! Questions, comments and suggestions for future installments of this series can be posted either at the Suppversity Facebook wall, via Twitter or right in the comment-area at the bottom of this page.

Does mTOR make you fat? It may be of interest to some of you (I know someone asked, but forgot who - shame on me) what the effect of the "anabolic" mTOR pathway on adipose, i.e. fat, tissue is. Well, if you look at the obese seesawer in image 1, the question appears unnecessary... if we delve a little deeper into the complicated interactions that are taking place here, we will yet notice that it ain't the mTOR signal per se that is fattening, but the way it sets the stage for increased adiposity by inhibiting the expression of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) (Chakrabarti. 2010), so that stored triglycerides cannot be broken down and released into the blood stream to be subsequently burned as fuel, and, at the same time, by ramping up lipogenesis and thus increasing the lipid accumulation in white adipose tissue (and, in severe overfeeding scenarios, liver and muscle, as well). Without the presence of a chronical overabundance of energy and the consequent over-expression of mTOR in the presence of readily available substrates for fatty acid synthethase, fat storage would however not be a concern. Moreover, if the AMPK-mTOR cycle is intact, the excess energy that is not used for protein synthesis, but stored during the anabolic phase, will come handy to fuel the repair processes when (during a "fast") AMPK takes the reign.

A chronic overexpression of AMPK and consequent catabolism of metablically active tissue (muscle and organ tissue) is unquestionable as undesirable as the fattening, cancer-promoting and life-shortening effects of chronic activation of the mammalian target of rapamycin (mTOR).

Figure 4: Merely illustrative sketch of the interplay of mTOR and AMPK as a function of time [in h] with feeding / fasting periods at the indicated time points.

The sketchy graphical illustration (it should be obvious that neither the sinosodial nor the linear parts are based on actual observational data) of the interplay of AMPK and mTOR and their relation to feeding, and thus energy availability in figure 4 goes provides some clues about how the large fasting window, allows enough time for an acute, yet temporary energy shortage to occur in the course of the postprandial /-absorptive phase, where the constant influx of nutrients which keeps the anabolic mTOR pathway humming runs out and AMPK eventually takes charge, as its activation consequent to the rise in AMP:ATP ratio (=energy shortage) subsequently decativates the mTOR pathway via phosphorylation of tuberous sclerosis protein 1+2 (TSC1+TSC2, cf. figure 5) and their inhibiting effect on GTP-binding protein Rheb, which is the central governor in the regulation of growth and cell cycle progression.

Figure 5: Graphical illustration of the way growth factors, substrate availabilty (amino acids) and energy supply / shortage regulate cell growth and metabolism

The re-constructive yet eventually catabolic reign of AMPK, on the other hand, comes to an abrupt end, as soon as a nutrient-rich meal is ingested and the AMP:ATP ratio decreases. This process will obviously not be as linear as I sketched it in figure 4, but it does stand to reason that the length of the transitional period will be somewhat proportional to the speed at which the intracellular ATP levels are repleted. That being said, a tried and proven way to quickly replenish ATP stores is the ingestion of a relatively large bolus of high glycemic carbs.

Carbing up immediately post workout could help you to make the most of the feeding window

Against that background, even low-carbers may suddenly see some sense in adding a reasonable amount of simple sugar to their post-workout shake, especially if they position their feeding-window right after their training session at the gym (which would then obviously have been performed in the (semi-)fasted state). The fast acting carbohydrate would then not only replete the muscle glycogen stores, they would also allow the amino acids that come with both the post workout shake, as well as the subsequent whole-foods meal(s), and the training and nutritionally induced growth factors to do their anabolic magic by releasing the "catabolic AMPK-break" as fast as possible.

Image 3: To "carb up" after exercise simple dextrose is probably enough. It does not have to be the expensive Vitargo. And certainly not WaxyMaize, which has a profoundly reduced 4-hour glucose and insulin responses compared to maltodextrine / sucrose (Sands. 2009)

Carbohydrate timing: Did you know that a 1988 study by Ivy et al. found that there is a statistically highly significant difference in the rate of muscle glycogen storage depending on when you ingest the carbohydrates? In fact, the rate of glycogen storage was 45% slower if the carbs were ingested 2h after exercise (vs. immediately post) and the amount of glucose that was stored in the vastus lateralis muscle of the 12 healthy subjects after 70 minutes on a cycle ergometer at 65% of their individual VO2Max with two intermittent intervals at 88% of their VO2Max was ~25% greater, when the 2g/kg carbohydrate were consumed immediately post-workout. Overall, clear-cut evidence of the repartitioning effect of exercise that would support the well-known advice to "time your carbs around [for someone on an intermittent fast obviously after] workouts".

Now that we are finally approaching the enjoyable part of intermittent fasting, i.e. the feast after the fast, I got the strange feeling that it is time for me to break my own fast, since the increasingly low glucose levels in my liver appear to impact my ability to hear myself think and thus begin to compromise the quality of the Intermittent Thoughts I am committing to the blogger interface.

I would yet assume that you have ingested more than enough information on funky acronyms and modeled signaling pathways to stimulate the neuro-anabolic lEARNing pathway in your brain, so that the intellectual stimulus would ward off any non-beneficial catabolic effects of acute Intermittent Thought deprivation until the next installment will be available - this, I hope, will happen earlier than you may expect ;-)

Intermittent Thoughts on Intermittent Fasting - The Fast #2: Health & Longevity Effects of Intermittent Fasting

Image 1: Any roundworms reading this? I hope you know that by not eating enough and feeling miserable you can extend your lifespan ;-)

Thanks Caenorhabditis elegans, or "C. elegans", almost everybody who is able to read a newspaper or online magazine will have heard of the miraculous effects of calorie restriction and fasting on longevity (of this worm!). Since I assume that you possess more gray matter than this transparent nematote, you will probably have asked yourself how, or rather if these results from a worm with an average lifespan of 2-3 weeks translate to human beings,... well, all I can tell you is that leading a miserable life of lifelong dieting appears to work in non-human primates, as well (Kemnitz. 2011). Now, the obvious question is:

How does all that relate to Intermitent Thoughts on Intermittent Fasting? Obviously, none of the roundworms or rhesus monkey's followed Martin Berkhan's intermittent fasting approach, did they?

No, I have not seen pictures of abes on leangains.com, either, so I suppose they did not follow Berkhan's approach, but - and this is the likewise fascinating, as well as surprising, connection - there is scientific evidence that intermittent fasting could reproduce some of the beneficial effects of caloric reduction while avoiding a whole host of its undesirable side-effects. Reason enough for me, to devote this episode of the increasingly popular Intermittent Thoughts on Intermittent Fasting series to the non-cosmetic health effects of intermittent fasting (I know that's not as getting ripped and jacked, guys ;-)

Figure 1: Ramadan fasting leads to profound beneficial changes in inflammatory markers (left) and blood lipids (right) in 20 healthy male non-obese volunteers aged 23-39 (data calculated based on Aksungar. 2006)

We touched on one of this unsexy, yet vitally important health-benefits at the end of the last installment on the metabolic and endocrine effects of fasting, already: the beneficial effect on insulin resistance (as measured by a +44% increase in the inverse of the long-term marker of insulin resistance 1/HOMA-IR and the slight increase in QUICKI) Shariatpanahi et al. had observed in 55 ramadan fasting subjects (Shariatpanahi. 2008) for example constitutes one of these "boring side-effects", of which many dieters fail to realize that improvements in insulin sensitivity or reductions in inflammatory markers and C-reactive protein (cf. figure 1, left), as they were reported by Aksungar et al. in a 2006 study on the effects of religious "intermittent" fasting (Aksungar. 2006) facilitate weight - and more specifically - fat loss.

Image 2: Would the issue of dehydration distort the results of Ramadan studies and thus render them irrelevant for our argumentation? (photo Offline Clinic)

As in almost every episode I want to make a few brief statements regarding the "Ramadan model of intermittent fasting". I have already discussed its advantages over "over-other day" or "alternative day" fasting in the second installment of this series and I have hinted at possible problems related to the restriction of water intake within the fasting period in the third installment of the series. Now, in view of the general recommendation to drink more and more frequently to avoid dehydration (USDA), it seems prudent to verify that potential beneficial health effects of fasting are not masked by detrimental side effects of dehydration, if we - once again - want to rely on the available data on religious fasting as part of our argumentation. In a paper published in the European Journal of Clinical Nutrition in 2003, Leiper, Molla and Molla report that despite the fact that "[d]uring the daylight hours of Ramadan fasting, practising Muslims are undoubtedly dehydrating", it is neither "clear whether they are chronically hypohydrated" nor have there been any "detrimental effects on health [...] directly attribut[able] to negative water balance at the levels that may be produced during Ramadan" observed in any scientifically relevant studies (Leiper. 2003). It is thus relatively safe for us to assume that we can neglect he influence of potential dehydration in our initial analysis of respective studies.

Now, what about the longevity effects?

Image 3: The effects the calorie restriction had on the ape on the right is certainly impressive, when you compare it to his 27.6 year old age-mate on the left - would be interesting to see how an "intermittently fasted version would end up ;-) (img. from the Irish Medical Times)

With or without the beneficial effects on cardiovascular risk markers, the question still remains: "Can intermittent fasting mimic the longevity effect of calorie restriction without the constant cravings, continuous hunger and all sorts of "human" problems that won't show in studies on yeast, worms, rodents or even apes (see image 3)?"

In order to answer this question, we will first have to give a clear cut definition of what our understanding of intermittent fasting is, in this context, because, obviously, if we coupled our (intermittent) fast with a a deliberate and severe calorie restriction we would probably end up like Canto, the ape from the the longevity study in image 3 - old, but miserable. What we want, on the other hand, is an intermittent fast, where - within the feeding window - we are allowed to eat to satiety... similar to what we are seeing in religious fasting: no calorie counting and perceived (when compared to normal meal sizes) overeating.

Now, we do already know from the studies cited above (and in previous installments of this series) that one month on a dietary regimen like that provides considerable benefits as far as weight loss, insulin sensitivity, blood lipid ratios (! this is important, because we are knowledgeable enough to give a f*** about total cholesterol & co) and inflammatory markers, all of which are associated not only with an increased life-expectancy (Danaei. 2010), but, more importantly, with an increased life-quality and neurological health (Bronwen. 2006) up into the old(er) ages. From the same studies, we do yet also know that breaking the fast, and returning to our old dietary habits returns these markers to baseline (cf. post values in figure 1). What we do not know, however, is whether ...

1. intermediate improvements in correlates of health and longevity as they can be observed during intermittent periods of Ramadan (intermittent) fasting provide any, or even significant longterm health benefits, and
2. longterm (as in for years and decades) intermittent fasting would not over months or years lose its effect, or even worse, be detrimental to our overall health and thus reduce not extend our life-expectancy and/or life-quality

From rodent studies we already know that a life-long alternate-day feeding protocol increases lifespan in the absence of any caloric reduction (Goodrick. 1990; Mattson. 2000). Evidence that similar beneficial effects, at least as far as mortality from chronic disease is concerned, would occur in human beings comes from a 2007 study by Varaday and Hellerstein (Varaday. 2007), who do yet remark that (as I already pointed out) "more research is required to establish definitively the consequences of ADF [alternate day fasting]".

The circadian clock hypothesis

A finding from alternative day fasting studies that may be of paramount importance in view of the "quality of life"-aspect, is the increase in brain-derived neurotropic factor (BDNF) that has been observed in animal studies. BDNF is involved in brain development and plasticity and its (intermittent) fasting-induced elevation could explain the neuroprotective effect of respective feeding patterns (Duran. 2001). In a review of the literature, Fory and Miskin do yet remark that (Froy. 2010)

[...] BDNF could not be [directly] linked to the neuro-protective effects in the brain of calorically restricted rats, but increased levels of another neurotrophic factor, glial cell line-derived factor (GDNF), were correlated with neuro-protection of a calorically restricted primate model of Parkinson's disease. Interestingly, BDNF is also a component of the hypothalamic melanocortin pathway that controls food intake and body weight in adult mice, and it has been implicated in the regulation of energy metabolism.

After all, the scientists believe that IF exhibits part or even all of its effects by (re-)setting clock genes, a hypothesis which despite having its merits would yet lead us into theoretic considerations with little merit to our "intermittent thoughts" on the real-world outcomes of intermittent fasting, which is why I will, at this point, skip forward to the results of a 1999 study into the relation of adipose tissue size and reductions thereof to longevity.

Is it not about eating less, but just about getting leaner?

Image 4: When we are talking about the benefits of losing body fat, this obviously does not imply you have to get in Phil Heath Mr. Olympia '11 shape to live longer (photo bodybuilding.com)

In the introductory paragraphs of this installment of the Intermittent Thoughts on Intermittent Fasting series I somewhat ridiculed the idea of changing one's whole life to get "ripped and buffed", now, after revisiting some of the studies and observing the close correlation of improvements in metabolic health markers, reductions in body fat and consequent life-extending effects of (intermittent) fasting, the central question of Nir Barzilai's and Gaurav Gupta's 1999 paper Revisiting the Role Fat Mass in the Life Extension Induced by Calorie Restriction seems by no means far fetched: What if ain't inflammation and insulin resistance & co that make us fat and reduce our lives, but being fat that leaves us insulin resistant, inflammed & co and thusly reduces our life-expectancy? The answer, according to Barziilai and Gaurav, is simple (Barzilai. 1999):

In fact, all of the benefits of CR on the neuroendocrine system and those related to the improvement in glucose homeostasis can be attributed to decrease in adipose cells and their products.

Probably too simple and above all difficult to treat with a drug and thus not profitable enough to be accepted by the medical establishment. Now, if this would be the case, intermittent fasting would in fact provide the sought-after silver bullet to leading a leaner, healthier life, as both the anecdotal reports on the Net, as well as the the majority of the studies that have been cited in this, as well as the previous installments show quite conclusively that going without food for periods <24h is capable of reducing body fat stores, while preserving lean muscle (and bone) mass. But why, or better how does that work?

Intermittent fasting, fat reduction, health improvements and the cyclicality of life

Illustration 1: It probably is the magic interplay of AMPK and mTOR that produces such remarkable transformations as Duong Nguyen's. We will delve deeper into the their reciprocal interaction in the next installment of the Intermittent Thoughts on Intermittent Fasting Series

Due to its cyclic nature intermittent fasting seems to temporarily produce similar "reductions in protein synthesis" (Barrows. 1978) as the ones which have been established as the fundamental mechanisms of the life-extending effects of calorie restriction as early as in the late 1970s and of which we know today that they partly mediated by an AMPK-induced downregulation of the mTOR pathway. In that, this transient AMPK response to intermittent fasting, which most intermittent fasters further stimulate by exercising in a (semi-)fasted state, appears to be profound enough to stimulate or, according to some recent research (cf. Canto. 2010), we should probably say "sustain" the SIRT1-pathway to an extent that allows dieters to benefit from its immediate fat-mobilizing effect on white adipocytes (Picard. 2004) and its ability to maintain telomer length (and subsequent longevity, cf. Palacios. 2010) without the unwanted muscle-wasting side-effects of prolonged fasting periods.

The fasting induced AMPK expression is yet only one part of the cycle, of which we have learned in this installment that it is responsible for both, the "cosmetic" effects on body fat, which could, after all, be causative and not just corollary or even subsequent to improvements in insulin sensitivity (cf. What Comes First: Inflammation or Obesity?), lipid profiles, and the whole string of beneficial health effects which irrefutably contribute to the longevity effect of inhumane low-calorie diets. In view of the fact that another valuable Sunday afternoon is drawing to a close, the discussion of the second player in this cycle, the mammalian Target of Rapamycin, or in short mTOR, will yet have to be postponed to the next episode of the Intermittent Thoughts on Intermittent Fasting Series - so stay tuned, keep the questions and comments coming and don't forget to check back on Thursday to see what AMPK and mTOR are doing to our man at the 2012 wheelchair nationals, Adelfo Cerame!

Intermittent Thoughts on Intermittent Fasting - Myth #3: Intermittent Fasting Hampers Athletic Performance.

Image 1: Would Usain Bolt be able to compete on an intermittent fast? Or would even the performance of the fastest man in the world suffer? (photo by Erik van Leeuwen)

In the first three installments of the Intermittent Thoughts on Intermittent Fasting series, you've already learned that, just as an increase in meal frequency does not magically strip off unwanted fat-weight, a decrease in meal frequency and thus extended time without "fuel" will not automatically predispose you to obesity. In fact, the deliberate restriction to a narrow "feeding window", which obviously is the main feature of intermittent fasting, and the associated unconscious/voluntary caloric restriction and macro-nutrient modulation have been shown to induce weight loss. This appears to be specifically likely, when - like during Ramadan fasting - the "feast", i.e. the 1-2 gorgeous meals consist of nutritionally (not calorically!) dense whole foods. In the last installment, you've also learned that compared to every-other-day fasting, Ramadan fasting, with its shorter ~15h fasting periods, combined with regular (3x a week) led to a more pronounced and certainly visible -2.6% reduction in body fat in a group of 10 recreationally active study participants (Trabelsi. 2011).

Now, the purported weight loss benefits of exercising in a fasted state (in fact, the 10 men in the Trabelsi study commenced their exercise protocols about 12-14h after their last meal) have been discussed over and over, both, in the health and fitness community on the Internet, as well as in the scientific literature and the divide between proponents and opponents of doing (specifically) "cardio"-training (I stick to using the expression "cardio" to designate endurance training, although a "real" cardio regimen would consist of a bunch of high-intensity intervals) in a fasted state, appears to be widening - not closing - with the publication of each new study, review or position stand on this controversial topic. While I will try to dig deeper into the purported biochemical and endocrine mechanisms proponents and opponents on each side of the divide are putting forward in one of the next installments of the Intermittent Thoughts on Intermittent Fasting series, I decided that it would be more prudent to stick to the much less debatable results of a handful of significant studies on the effects of Ramadan fasting on the physical and mental performance in active and/or athletic study populations - after all, I assume you would concur, that it makes little sense to look closer at something of which scientists have conclusively shown that it does not work in practice... wouldn't you?

Image 2: Dehydration is a problem of Ramadan fasting that won't occur upon "intermittent fasting" regimens as they are suggested in the health and fitness community.

Note: I just want to remind everyone that, although Ramadan fasting with its 15-16h fasting periods may be a better model of the general accepted health and fitness interpretation of "intermittent fasting", the questionable (from a health perspective) water abstinence, as well as the eschewal of BCAAs, protein shakes, stimulants and other supplements "intermittent fasters" are commonly using in their endeavor to "optimize" fat loss, performance and whole body nitrogen balance, are major and potentially important differences, in light of which the overall results of thusly "optimized" intermittent fasting regimens can be expected to surpass (in a beneficial sense) those of religious fasting, especially as far as the maintenance or even improvement of athletic and cognitive performance and the retention of lean mass are concerned.

The first relevant result actually stems from the Ramadan study by Trabelsi, et al. (Trabelsi. 2011). Obviously, the subjects in his study did not feel like their empty stomachs would compromise their exercise performance. Now, though the "rate of perceived exertion" may be a frequent measure in scientific studies into the effects of specific training regimens, supplements and/or combinations of both, it is not the most reliable measure and I assume that most of you know that - especially when it comes to recreational activities like the ones Trabelsi's study participants performed - the way we feel during and after a given exercise is a notoriously unrealiable measure of "performance".

Much more reliable results come from another very recent study by Amir-Hossein Memari, et al. who investigated the effects of Ramadan fasting on body composition, calorie intake and physical performance in young female taekwondo athletes (15-27 years) who continued on their regular training regimens in the four weeks of religious fasting. 

Figure 1: Weight, BMI, waist to hip ratio (indicator of body fat) and calorie intake in female athletes who continued their regular training regimen during 4 weeks of religious fasting (data calculated based on Memari. 2011)

From the data in figure 1 it becomes immediately obvious that, contrary to the recreationally active subjects in the Trabelsi study, who obviously were free to adapt intensity, duration and type of their 3x/week athletic activity according to their fasting regimen, the body composition of the female athletes was not beneficially influenced by the "intermittent fast". On the contrary, despite (or I suspect rather due to) a pretty harsh reduction in caloric intake (absolute values -500kcal from 1658kcal/day to 1163kcal/day) over the four weeks of fasting, the ladies lost only 1.63kg of weight. In view of the fact that their waist to hip ratio increased even before the compensatory overeating in the two weeks after Ramadan (post), it stands to reason that most of the "weight loss" was in fact water-weight (remember the ladies didn't drink before sundown), so that I would venture the guess that their body-fat percentage, which unfortunately has not been measured by the scientists, will have increased during the fast, as well.

Figure 2: Measures of exercise performance in female athletes 2 weeks before (pre), during and 2 weeks after Ramadan fasting (data based on Memari. 2011)

Contrary to what you may have expected the athletes were yet able to maintain, in the first two weeks of fasting even improve their performance in agility, balance and vertical jumping tests (cf. figure 2). Given the fact, that even in the first two weeks of Ramadan, the women had reduced their already surprisingly low caloric intake (1658kcal/day) by -16%, certainly is a surprising result. If, however you remember my elaborations on the cortisol and catecholamine response to fasting from the first installment of this series and, at least for the moment, do away with the unreasonable vilification of temporary increases in cortisol that is so rampant in the bro-scientific world of bodybuilding and fitness forums, you may realize that the performance increase you are getting from your favorite stimulant or pre-workout product is the immediate result of its high caffeine, geranamine or whatever other methyl-xanthine content's ability to trigger a profound stress response. Now, the longer-term trade-offs of these short term benefits are the well-established induction of insulin-resistance, the down-regulation of the endocrine system (thyroid and sex hormone production) and the ensuing decrease in energy expenditure that are falsely ascribed to cortisol in general.

Did you know that the symptoms of low cortisol are (in parts) identical to those of high cortisol? Low energy levels, weight and particular fat gain and severe problems to get rid of excess body weight are characteristic of both constantly elevated, as well as constantly low cortisol levels.

The profound increase in "balance" after the fasting period, aside, the results of the Memari study leave no doubt that athletes on a non-supplemented intermittent-fasting regimen without tight control of the caloric intake can maintain their performance only via a profound and persistant upregulation of glucocorticoids and catecholamines that is (and the skill-related performance tests show that) not sustainable over an extended period of time. Moreover, in the long term, the combination of constantly elevated cortisol levels and the insufficient calorie intake (for an athlete) trigger all the negative adaptations that are characteristic for what I've previously described as "starvation mode", so that the fat gain (as evidenced by the +5% increase in waist-to-hip ratio) in the two weeks after the "intermittent fasting" period is the athletic counterpart to the "YoYo"-effect on starvation diets.

Evidence that even the Ramadan variation (i.e. no fluids and no supplements) of "intermittent fasting" can work for athletes comes from another 2011 study by Rabindarjeet Singh and colleagues from Malaysia and Singapore (Singh. 2011). While the scientists used "perceived" performance indices from questionnaires, their data is still convincing due to the sheer size and heterogenity of their study population (411 male and 323 female Malaysian Junior-level Muslim athletes avg. age 16.3 ± 2.6 y from various sports).

Figure 3: Effect of Ramadan fasting on perceived performance in 411 male and 323 female Malaysian Junior Level Muslim athletes (data calculated based on Singh. 2011)

Figure 3 cleary shows that, despite the fact that the number of junior-athletes who felt that fasting had a negative effect on their performance is greater, than the number of athletes who felt they would benefit from fasting, the vast majority of athletes, i.e. more than 70%, either felt no effect or were not sure - regardless of whether they participated in team, skill-based, endurance or combat sports. In that, I think it is noteworthy, that in athletes who participate in endurance sports, the number of athletes who experienced negative effects of fasting outnumbers those who felt benefits by factor x7. In combat sports (listen up weight-lifters), on the other hand, the number of athletes who consider fasting beneficial is almost identical to the number of athletes who felt that their performance decreased over the course of four weeks.

Figure 4: Effect of Ramadan fasting on perceived snack, fluid and food intake in 411 male and 323 female Malaysian Junior Level Muslim athletes (data calculated based on Singh. 2011)

General variations in athletic and thus caloric and nutritional demands, aside, the obvious differences to the Memari study may well be explained by superior or maybe just less restrictive feeding practices in the younger athletes, the majority of whom, as the data in figure 4 goes to show, managed (and were psychologically able / I am referring here to the fear of getting fat that is unfortunately pretty prominent among post-pubertal female athletes esp. if weight classes are an issue as in the taekwando athletes from the Memari study) to compensate for the lack of snacks, fluid and overall caloric intake in the fasting periods by "feasting" after sundown.

Figure 5: Perceived effects of 4 weeks of Ramadan fasting on alertness / sleepiness in Malaysian junior-athletes (data adapted from Singh. 2011)

Despite the absence of negative effects on exercise performance in the majority of the study participants, more than 66% of the young athletes felt sleepy and less alert in the course of the day and roughly 50% of them felt that their sleep quality or the duration of their sleep were affected by their fast. How all that ties back into the profound endocrine changes that are induced by modulating food and macronutrient intake and frequency (you can read up on closely related and probably even more surprising beneficial effects of eating all your carbohydrates after 6pm in a previous blogpost of mine), along with tips how to counter detrimental effects by meal-timing, macronutrient selection and supplements will be the topic of the next installments of the Intermittent Thoughts on Intermittent Fasting series, which - due to my tight time-schedule - won't be written before the coming weekend. For the time being, I want to remind you that comments, critique, suggestions and questions are always welcome and may be posted via Facebook, Twitter or in the comments area of this page.

Intermittent Thoughts on Intermittent Fasting - Myth #2: Reducing Meal Frequency to 1-2 Meals Will Make You Fat.

Image 1: It stands to reason that "reducing" your food intake to one serving of 13,780 pounds of spaghetti + 120 gallons of ruby red marinara sauce is not really what "intermittent fasting" is all about (world record of 2009 at Buca di Beppo's in Garden Grove).

In yesterday's first installment of the Intermittent Thoughts on Intermittent Fasting series, you have already learned that the idea of increasing energy expenditure and improving weight loss by increasing the number and decreasing the size of your meals is futile, because, in the longer term (>1 week), any temporarily occurring metabolic overshoot, i.e. an inappropriately (as in larger than "optimal") pronounced postprandial thermogenic response, will be leveled out by metabolic adaptation processes. This does yet not automatically exclude that the reverse, i.e. an appropriate increase in postprandial energy expenditure, would occur whenever someone, who has been eating 3-4x more or less balanced meals since he/she was a child, out of a sudden decided that it would be prudent to skip 2 or 3 of his meals and to cram his/ her whole caloric intake into 1 or 2 gorgeous meals.

So, if increasing meal frequency does not have an effect, wouldn't decreasing meal frequency, as in intermittent fasting, then be as futile? Or does decreasing meal frequency from 5-6 small meals a day to a single gorgeous feast even predispose to obesity, as you may have heard it on CNN only yesterday?

"Intuitively", yet not as in genetically programmed, but rather as a result of lifelong medial and educational indoctrination, it occurs to us only reasonable that someone, who crammed his/her whole daily calorie intake of 2.400kcal into a single meal, when his/her body is used to 3x or 4x 600-800kcal servings, would gain (fat)weight - especially if there are some of those nasty fattening carbs around the "new smarter(?) generation" of dietitians has finally identified as the root of all metabolic disease. Accordingly, you will probably not be surprised by a remark I took from a review of the effects of meal frequency on weight gain and body composition by Bellisle et al. from the year 1997 (Bellisle. 1997)...

[A] very large bolus meal with a high carbohydrate content might saturate the maximal rate of glycogen synthesis and force additional disposal via de novo lipogenesis; there is much evidence to support a hyperlipogenic effect of gorging in animal studies.

Now, while intermittent fasting obviously allows for several smaller meals within a 4-8h time window, it seems logical that the "saturation" of glycogen synthesis could nevertheless become a problem. After all, you have read about the limited ability of our bodies to "store away" excess glycogen in previous posts on the SuppVersity and will thus be familiar with the idea that, contrary to the fat storage capacity of our adipose tissue, our bodies' glucose stores, which are located primarily in muscle and liver tissue, are very limited.

"How much fat can you really gain from a single 750g carbohydrate meal?"*
* this is the answer to the question at the end of yesterday's installment of the Intermittent Thoughts on Intermittent Fasting series

Illustration 1: This is a very theoretical calcuation of what "could" happen if you ate 19 cups of cooked pasta = 750g of carbs after a glycogen depleting workout (calculations based on estimates by Acheson. 1988)

While you may have expected that the "exact" amount of carbs your body would be able to store varies with the amount of muscle you are carrying, it may surprise you that it also varies according to which source you are using (that's science, folks!). It is, however in general assumed that an average adult human being can store about 500grams of carbohydrate. Athletes on the other hand could theoretically store up to 1.0-1.1kg before the onset of de novo lipogenesis, i.e. the synthesis of fatty acids from carbohydrate substrates (Acheson. 1988).

In 1988, Acheson et al. established in a series of overfeeding studies that it takes roughly 475grams of excess carbohydrates to manufacture and store 150grams of fat (Acheson. 1988). 

You may notice that this would yield an energetic ratio of 1g of fat to 3g of carbs and thus constitutes another violation of the generally accepted oversimplified "laws of dietary thermodynamics", as they are propagated by dietitians and mainstream-media. If our bodies could inter-convert and store macronutrients as readily as people are made to believe, according to the 4kcal/9kcal energy rule, the 750g of carbs in my sample calculation in illustration 1 should translate into 111g of fat, if 500g of the carbs had previously been stored in empty glycogen stores.

Image 2: R. Feinman (photo) and Eugene Fines authored a paper on the fallacy of the "a calorie is a calorie"hypothesis

 If you are interested in a detailed discussion of the applicability of the laws of thermodynamics in a nutritional context, I suggest you start by reading Richard Feinman and Eugene Fine's 2004 paper "A calorie is a calorie" violates the second law of thermodynamics, where the two scientists discuss existent data to show that thermogenesis, alone, would be sufficient to predict metabolic a metabolic advantage of low- over high-carb diets and make a point in stating that "as a general principle, 'a calorie is a calorie' violates the second law of thermodynamics."

(Un-?)fortunately, neither carbs nor fats are built of "calories" that your body could use interchangeably and without any additional effort, so that the real world outcome of overeating is a lot more complicated than basic "carbs in vs. carbs out times 4/9" calculations - even if one discards the influence of other macro- and micro-nutrients and the temporary +35% increase in energy expenditure Acheson et al. observed in their low-fat, high-carb overfeeding studies (~4.500kcal/day).

Yet, before we are delving any deeper into a discussion of optimal macronutrient composition for lean gains, weight loss and optimal performance (we will get to that in a later part of this series, I promise), let's get back to the topic at hand and look at some of the research that may be able to explain, why anecdotal evidence clearly shows that, on a combined exercise + intermittent fasting regimen, as Martin Berkhan and others recommend it, weight gain never seems to become an issue - and that despite the fact that many of his followers claim they even had to force themselves to eat the prescribed amount of food.

Myth 2: A lower meal frequency equals (fat)weight gain

Illustration 2: Comparison of feeding schedules on "normal diet", alternate-day-fasting (ADF) and the current interpretation of intermittent fasting (IF).

Quite often, when you find explanations on why intermittent fasting would or not, the authors cite studies which employed alternate-day-fasting (ADF) regimens. It stands out of question that alternately eating a normal diet on one day and refraining from food consumption on the following day is a form of "intermittent fasting" - nevertheless a better and even more studied "model" (this is just our perspective on these studies) of non-calorically restricted intermittent fasting comes from the middle-east, where the effects of Ramadan fasting, which prohibits any food intake before sundown, have been studied for decades, now.

Although the small breakfast most of the Muslims ingest before dawn and the additional abstinence of fluid intake distinguishes Ramadan from intermittent fasting, the average period dieters remain without food (from 4am to 7pm, i.e. 15h) is comparable and, what's equally important, the length of the fasting and thus the study period (one month) is long enough to bring about measurable effects.

Image 3: After ~13h of fasting 78% of your liver glycogen stores of roughly 300mmol/kg liver tissue will be depleted; 3h left until your body will have to come up with "alternative" fuel sources.

Those of you who read the erratum on the "Glycogen-Free Muscle Growth" post a few days ago, will already be familiar with a possible explanation for the success many people have with the 16h fasting-window Berkhan and others suggest mainly based on a very practical "no muscle loss observed" argumentation (cf. Berkhan. 2010). The latter is related to the capacity and usage of your hepatic and muscular glycogen stores. While your muscle glycogen stores are "degraded to generate ATP during increased energy demand", your liver glycogen stores function as an immediate back-up system for whole body glycogen supply (Greenberg. 2006). Thus, it appears obvious that your body will have to catabolize more protein and liberate and oxidize more fat by ramping up its glucocorticoid output, as you approach the ~16,67h fasting limit, when the 300mmol/kg glycogen your liver holds in the fed state will be depleted (calculations based on a hourly glycogen depletion of 18mmol/kg as it was observed by Nilsson. 1973). Although, I will address this issue in more detail in a future installment of this series, it is also important to understand a major and potentially significant difference between "intermittent fasting" and "alternate day fasting", where the complete depletion of hepatic glycogen stores, as well as the consequent stressful switch to alternative fuel sources, the gradual progression into a catabolic state and the ensuing cortisol-related suppression of thyroid hormones and androgens are inevitable consequence (even if you lie in bed all day) of the extended (24h) fasting period and thus pave the way to what I described as "starvation mode" in the introduction of part I of this series.

One of the most recent Ramadan studies published in the Asian Journal of Sports and Medicine was conducted by Khaled Trabelsi and four colleagues of his from Tunesia, New Zealand and the US (Trabelsi. 2011). Its topicality aside, the study is also interesting because the subjects, 10 men at an average age of 26.6 years and with a BMI: 24.6kg/m² and a body fat percentage of ~19.4%, who exercised at least 3x a week, are somewhat representative of many men out there who may be considering to experiment with intermittent fasting, these days.

Figure 1: Changes in energy intake during and body composition in the course of Ramadan fasting in 10 healthy physically active (min. 3x/week) men (data calculated based on Trabelsi. 2011)

As the data in figure 3 goes to show, daytime fasting and the reduced meal frequency induced a voluntary -7% decrease in energy intake, which went hand in hand with a +6.6% increase in protein intake and brought about a slight, yet statistically significant recomposition effect, i.e. the loss of 2.6% body fat (measured by the means of a caliper) without concomitant reductions in lean body mass.

Image 4: The beneficial macronutrient modulation (+6.6% protein; less carbs and fats) the subjects from the Trabelsi study unconsciously adapted during Ramadan are probably the result of family traditions and not some sort of instinctive dietary adaptation (at least not in the short run)

In view of the fact that the voluntary, or I should say, unconscious increase in protein intake at the expense of dietary fats and carbohydrates has lately been deemed particularly beneficial in terms of losing fat and maintaining muscle weight (more on optimal macronutrient composition during intermittent fasts in a future installment of this series), it could appear as if the fasting Muslims intuitively knew about the benefits of additional amino acids! Unfortunately, the underlying reason for the increase in protein intake is probably way more profane. During Ramadan you do not snack, you abstain from the classic sweet breakfast, and all the other low protein foods. Instead, you have one or two large high quality (and in the Arabic world this still involves a healthy peace of meat) meals with your family.

When we are looking for the underlying reasons for these beneficial changes in body composition a 2005 study by Heilbronn et al. from the Pennington Biomedical Research Center comes to mind (Heilbronn. 2005). In their study 16 non-obese health men (N=8; age 34y; BMI 25.2; fat 22%) and women (N=8; 30y; BMI 22.6; fat 25%) who fasted every other day lost 4% body fat and 2.5% of their body weight within 22 days. And despite the fact that this is not the kind of intermittent fast that got Duong his "Aesthetically Muscled" physique (cf. my remarks on the role of liver glycogen stores and the 16h fasting window in one of the red info-boxes above), the subjects did not experience the dreaded decrease in resting metabolic rate (RMR) that is so commonly seen on traditional diets with a constantly reduced calorie intake.

Figure 2: Effects of 22 days of alternate day fasting  (ADF) on body composition (lean mass and fat mass in kg) in 16 non-obese, healthy subjects (data adapted from Heilbronn. 2005)

The Heilbronn study, also provides a first glimpse at one of the topics of the future installments of this series, which is the underlying mechanism by which alternative fasting could facilitate such results: a major factor probably was the -57% decrease in fasting insulin that allowed for a greater release of stored fatty acids and thus facilitated the +15 g/day increase in fat oxidation - energy which had not to be derived from the oxidation of valuable muscle (or other organ) proteins. In view of what I have said about the differences between intermittent and alternative day fasting (cf. red box), it is yet noteworthy that the subjects in the Heilbronn study did lose 1.1% of their lean mass, while the fasting Muslims in the Trabelsi study despite performing their habitual 3-times a week exercise regimen, in a fasted state between 4pm and 6pm, i.e. ~12-14h after their last and shortly prior to their next meal, maintained (+0.2% is a non-significant increase) their lean body mass. This goes to show your that exercise although it may not mandatory to avoid weight gain and derive benefits from an intermittent or alternate-day fast that is characterized by a reduced meal frequency and an increase in meal size, can help maintain (with appropriate meal-timing and supplementation as discussed in future installments of this series, maybe even build) lean body mass.

A pros pos exercise, interestingly, none of the 10 subjects who were obviously not used to exercising in the fasted state reported any changes in the rate of perceived exertion. This obviously contradicts observations the anti-fasting faction on the Internet commonly cites as one of the most important reasons not to go on an intermittent fast, for everyone for whom his/her exercise (and some even say cognitive) performance is important. In view of the fact, that, even for me, there is a life beyond the SuppVersity, I will yet have to postpone myth #3, i.e. "Intermittent Fasting Will Ruin Your Physical and Cognitive Performance" to the next installment of the Intermittent Thoughts on Intermittent Fasting series. In the mean time, feel free to leave comments, questions and suggestions as to where this series should be heading on Facebook, Twitter or in the comments area of this page.