New "Fasted Cardio"-Study Falsifies the Myth of Superior Long-Term (4 Week) Fat Loss on a Moderate Energy Deficit

If we go by the convincing results of the study at hand, the fasted cardio myth is obviously busted.

Sometimes the day you've been waiting for comes faster than you'd thought... no, I am not talking about a teen's eighteens birthday or Christmas (reminds me, I still have to buy a ton of presents), but rather of the recently hinted at "fasted cardio study" by Brad Jon Schoenfeld, Alan Albert Aragon, Colin D Wilborn, James W Krieger and Gul T Sonmez.

The study of which I wrote only 2 days ago in my article about the 50% increase in fatty acid oxidation in fasted vs. fed morning cardio (learn more). And it is in fact the study which may finally solve the "Is fasted cardio good for your weight loss?"-question.

In contrast to the previously discussed paper, Schoenfeld et al. who started with the common hypothesis that "performing aerobic exercise after an overnight fast accelerates the loss of body fat" (Schoenfeld. 2014), did not content themselves with measures of acute fatty acid oxidation. What they did was a study to investigate the actual changes in fat mass and fat-free mass following four weeks of volume-equated fasted versus fed aerobic exercise in young women adhering to a hypocaloric diet.

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Needless to say that this study has the potentially to give us reliable insights with respect to the previously formulated question, because their subjects, twenty healthy young female volunteers were randomly assigned to 1 of 2 experimental groups,

• a fasted training (FASTED) group that performed exercise after an overnight fast (n =10) or
• a post-prandial training (FED) group that consumed a meal prior to exercise (n =10)

not for one or two testing days, but for 4 weeks! The training itself consisted of 1 hour of steady-state aerobic exercise on a regular treadmill (0% incline) and was performed for 3 days per week for the previously mentioned total study duration of 4 weeks.

"Subjects performed a warm-up for the first 5 minutes at an intensity equating to 50% of maximal heart rate (MHR), determined by the formula 220 - age, then increased intensity to 70% MHR for the next 50 minutes, and finished with a 5 minute cool down at 50% MHR. Heart rate monitors (model F7U, Polar Electro Inc, Lake Success, NY) were used to ensure that exercise remained at the appropriate intensity." (Schoenfeld. 2014)

To ensure that (a) the subjects actually trained and they would (b) only do the prescribed standardized volume of exercise, all training sessions were supervised by research assistants who were upper level undergraduate students in exercise science and the subjects were instructed to refrain from performing any additional structured exercise for the duration of the study.

One thing to consider: I would not fully discard fasted cardio, yet. Even if the resulrs of the study are convincing. It's one study that simulates a specific scenario. In a real world scenario you will often have people, who do shorter fasted cardio sessions, extend the fast and thus reduce their overall energy intake. This is similar to breakfast skipping, which works magic if you don't compensate for the lack of energy intake in the AM (learn more). In the study at hand this "side effect" of morning cardio didn't exist, because of the standardization of the dietary intakes of the female participants. This is perfectly correct from a science perspective, but may still be a reason the real world results you or your clients see may differ from the null-result in the study at hand.

Subjects were provided with customized dietary plans designed to induce a caloric deficit. In that, their total caloric intake was calculated on the basis of the Mifflin-St. Jeor Equation, which yields adequate, but obviously not 100% precise measurements of the resting metabolic rate (max. 10% off in non-obese adults according to Frankenfield. 2005). Since the same method was used for both groups, any possible inaccuracies, due to which the real caloric deficit among the women may not be identical to the calculated one, should carry no real weight, though. And we can simply assume that all women were in the same ~500kcal/day energy deficit the researchers thought to create.

Figure 1: Nutrient composition and total energy intake of the subjects in both groups (Schoenfeld. 2014)

In addition to their regular diet, the adherence to which was monitored on a regular basis, the subjects received a meal replacement shake either

• immediately prior to exercise for the FED group or
• immediately following exercise for the FASTED group,

with this nutritional provision carried out under the supervision of a research assistant. The "Pursuit Recovery" (Dymatize Nutrition, TX) shake you could also buy at your local GNC contains 250 calories, total, and 40 g carbohydrate (from maltodextrin and organic cane sugar), 20 g protein (from whey protein isolate + added leucine), and 0.5 g fat (residues).

Let's  take a look at the results now

As you can see in Figure 2, both groups showed a significant loss of weight (P =0.0005) and fat mass (P =0.02) from baseline, but no significant between-group differences were noted in any outcome measure (which means, that all the differences you see are "random").

Figure 2: Pre- vs. Post-study body composition measures (Schoenfeld. 2014)

As Schoenfeld et al. rightly point out, their findings clearly "indicate that body composition changes associated with aerobic exercise in conjunction with a hypocaloric diet are similar regardless whether or not an individual is fasted prior to training" (Schoenfeld. 2014) - in other words, in this pretty realistic scenario (I hope nobody starves himself after a 1h morning cardio session for another 4-8h) the myth that morning cardio on an empty stomach would accelerate fat loss is thus busted.

Bottom line: The assumption that the consumption of an insulinogenic pre-workout meal as it was used in the study at hand and a subsequent reduction of fatty acid oxidation during the workout would induce a shift from fat to carbohydrate oxidation (not measured in the study at hand, but previous studies show that this is the case) and have significant effects on an individual's long-term fat loss on an energy reduced diet is thus falsified.

The study at hand shows that the 50% increase in fatty acid oxidation w/ fasted cardio does not translate into increased fat loss | more

You could still argue that it may be beneficial if there is no energy deficit involved, for example by improving glucose levels as it was reported by Van Proeyen et al. (2013) in a study with a hyper-caloric energy intake (~bulk), but that's a whole different story.

Or you could argue that there is an albeit non-significant trend for an increased loss of fat mass in the FASTED group (inter-group difference = 33%, but the latter was (a) paid dearly for by an almost 2x higher increase in lean mass loss (inter-group difference = 60%) and stands (b) in contrast to the non-significant greater reduction in abdominal fat in the FED group as it is signified by changes in waist circumference.

For the time being, the long-standing "myth" that fasted cardio would lead to a significant acceleration has thus to be considered "questionable", if you put 100% faith the statistical accuracy of the study at hand (with only 10 participants in both groups, I am inclined not to do that) even "busted". For so long, at least, until another study, maybe one with more participants (which would allow to really figure out how "significant" the difference actually was), but a similar strict standardization, will show that it works. In that case, we would have to find out could have been that made the difference - could be the sex or training status of the subjects, the extend of the caloric deficit, the total protein intake (which was comparatively low), the type of the pre-workout meal or the form of cardio training that was used... Comment on Facebook!

References:

• Frankenfield, David, Lori Roth-Yousey, and Charlene Compher. "Comparison of predictive equations for resting metabolic rate in healthy nonobese and obese adults: a systematic review." Journal of the American Dietetic Association 105.5 (2005): 775-789.
• Van Proeyen, Karen, et al. "Training in the fasted state improves glucose tolerance during fat-rich diet." The Journal of physiology 588.21 (2010): 4289-4302. 
• Schoenfeld, Brad, et al. "Body composition changes associated with fasted versus non-fasted aerobic exercise." Journal of the International Society of Sports Nutrition 11.54 (2014)

Want to Clean Up Cellular Garbage? Train Fasted! Fasted Training Boosts Cellular Housekeeping (=Autophagy) & Forms the Basis of Structural Adaptations to Exercise

Want to promote muscular and overall health? Do this after an 8h+ fast.

Exercise is a stressor. It modifies the intra and extracellular millieu, impairs the energetic status and stretches, sometimes even over-stretches the membranes. That certainly sounds as if you want to avoid it at all costs, but as nature had it, it is this eustress (good stress) that is absolutely essential for the remodeling of the muscle we are all working out for to happen - no stress no reason to adapt. It's that simple and does still have one major caveat: Too much stress and the adaptation turns into a constant and often insufficient repair process.

But who wants to "deconstruct" muscle, anyway?

Now, from the gymbro perspective the most important aspect of the training induced adaptation processes would probably be protein synthesis. And while you can actually argue that this was the case if things were just about "growing", a different picture emerges, when you look at health benefits and the actual remodeling process which does necessarily begin with "demodeling", or rather the demolution of old muscle tissue - when that's happening in a controlled self-induced (by the cell) manner, scientists call this process autophagy.

Autophagy is one of the main reasons fasting is good for you

Now, when cells "kill" themselves, they usually do that for a reason. In fact, the process of autophagy must be seen as part of the general housekeeping - a part with enormous importance, as one of the possible consequences  of its failure is cancer. Moreover, it has been demonstrated only recently that autophagy is also an essential process for muscle adaptation:

Suggested read: "If a High Fat Diet was a Pill, the Lay Press Would Celebrate it as 'Exercise in a Pill'" | read more

"Autophagy is activated in skeletal muscle by numerous catabolic stimuli such as food deprivation, denervation or sepsis. However, evidence for the necessity of basal autophagy level in the maintenance of myofibrillar integrity has counterbalanced the vision of a system only implicated in muscle wasting. Very recently, the activation of the autophagy-lysosomal pathway has emerged as an essential process for skeletal muscle adaptation after endurance training (Lira. 2013)." (Jamart. 2013)

That being said, a group of researchers from the Université catholique de Louvain in Belgium set out to study whether the two major pro-apoptotic mechanisms in our lives, i.e. working out and fasting would complement each other so that their effects add up and you get the double dose of healthy - and as you have learned today "muscle (re-)building" cell death.

Can you combine it? Yes you can!

As you can see in figure 1 the answer is clear: Yes, you can - meaning you can combine fasting and exercise and achieve an even greater activation of the autophagy-lysosomal pathway .

And what about humans? Do we have reason to believe this would not happen in human beings? Of course we do, but it is actually very unlikely that there will be major differences in the intra-muscular response to fasting. Plus, we do have human studies showing related benefits that are exclusive to fasted training, already (see "bottom line").

The data in figure 1 arose from the observations the researchers made, when they had a group of rodents perform a 90 min run at a speed of 10m/min (I did not plot the increases in markers of autophagy like Gabarapl1-II, Atg12, Lc3b, Gabarapl1 and p62/Sqstm1, simply because I don't think they are useful for you - take it for granted that those were only increased in the fasted state).

Figure 1: Comparison of selected markers of celluar and mitochondrial autophagy (mitophagy) in mice before and after 90min run in the fasted or fed state (Jamart. 2013)

 For the mice half of whom had been food deprived for 8h that's actually the normal speed of locomotion and would equal a low intensity walk/jog for a human being (about 55% of VO2max). The reason the scientists picked this protocol was that it has previously been shown to be sufficient to arrive at a plateau phase when no further increases in the accumulation of autophagosome number in different skeletal muscle groups of mice submitted to exercise running can be observed (He. 2012).

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But is this even a good thing? Now, I can already see you struggling with the idea of voluntarily inducing "catabolism" - that's stupid right? Yes, you are right, it is in fact stupid to think about autophagy this way. This is not a non-selecive process that kills valuable muscle tissue like sarcopenia, it's a necessary prerequesite for the structural integrity of your muscle (get rid of the junk, build new stuff in place) and your whole body. The ability to boost local the systemic activation of the autophagy-lysosomal pathway is thus in fact a definitive plus you don't want to miss, but don't want to overtax, either (don't do it everyday, don't do it in combination with a high caloric deficit, don't forget to refuel after the workout).

Suggested read: "3x30s High Intensity Intervals Increase mTOR & Ramp Up Marker of Protein Synthesis - Even in a Fasted State!" | read more

In 2011 van Proeyen et al. observed that training fasted does not only increase the intramuscular fatty acid oxidation in 20 healthy young volunteers, it did also and this may come as a surprise, prevent "the development exercise-induced drop in blood glucose concentration" (Van Proeyen. 2011) - the same drop in blood sugar that will make you feel exhausted and is a potential risk factor for an acceleration of the metabolic downregulation that occurs, whenever you are dieting. One year before van Proeyen et al. had already established that in times of high fat overfeeding (+30%kcal; 50% fat) only fasted training was able to increase the AMPK levels (=anti-cancer, anti-diabetic, anti-obesity effect) in young men (van Proyen. 2011).

Said study by van Proyen was by the way the first to prove 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. So, I suggest you remember it, when you wake up tomorrow and think about whether you should go for a run now or rather after filling up your belly with some delicious eggs or whatever it is that you have for breakfast.

References:

• He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q,
  Korsmeyer S, Packer M, May HI, Hill JA, Virgin HW, Gilpin C, Xiao G, Bassel-Duby
  R, Scherer PE, and Levine B. Exercise-induced BCL2-regulated autophagy is required
  for muscle glucose homeostasis. Nature481: 511-515, 2012. 
• Jamart C, Naslain D, Gilson H, Francaux M. Higher activation of autophagy in skeletal muscle of mice during endurance exercise in the fasted state. Am J Physiol Endocrinol Metab. 2013 Aug 20. [Epub ahead of print]
• Lira VA, Okutsu M, Zhang M, Greene NP, Laker RC, Breen DS, Hoehn KL, and Yan Z. Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance. FASEB J, 2013. 
• Van Proeyen K, Szlufcik K, Nielens H, Pelgrim K, Deldicque L, Hesselink M, Van Veldhoven PP, Hespel P. Training in the fasted state improves glucose tolerance during fat-rich diet. J Physiol. 2010 Nov 1;588(Pt 21):4289-302.
• Van Proeyen K, Szlufcik K, Nielens H, Ramaekers M, Hespel P. Beneficial metabolic adaptations due to endurance exercise training in the fasted state. J Appl Physiol. 2011 Jan;110(1):236-45. doi: 10.1152/japplphysiol.00907.2010. Epub 2010 Nov 4.

Well-Stocked Muscle Glycogen Stores Not Necessary For Exercise Induced Muscle Anabolic Response. Additional 5x Increment by Post(!)-Workout Whey + Cho Supplement.

Image 1: Glycogen depleted or not,
post-workout protein, preferably from a 
leucine-rich, fast digesting and nutritionally
complete source such as whey, is a must.

It is one thing that many trainees feel they perform better, train harder or have better endurance, when they (over-)"load" their muscle glycogen stores pre-workout. And as long as their need for carbohydrates is not merely imaginary, i.e. they feel sluggish and their gym performance sucks, whenever they are training on empty glycogen stores, I am quite sure that they will also make better gains. This mechanism would yet be completely different from any immediate, yet hitherto scientifically not validated, facilitative biomolecular effect of well-stocked glycogen stores on muscular hypertrophy, as it is proposed by many advocates of preworkout or even 24/7 carbohydrate (re-)feeding.

Dr. Connelly, who talked about this issue at length in the past installments of the BodyRX Show, was kind enough to remind me that back in 2007 Coffey et al. from Stuart Phillips' group at McMaster University, in Hamilton, Ontario (Canada), conducted a study that was based on an antithetical hypothesis, i.e. whether or not commencing resistance exercise with low muscle glycogen would enhance the encoding of genes implicated in muscular hypertrophy (Coffey. 2007). Yet, while there were significant differences at rest for the glycogen depleted vs. the normal leg of the subjects, both the increased GLUT4-MRNA expression, which is a sign of an increased capacity for glucose uptake, as well as the reduced expression of atrophic atrogenes (responsible for proteolysis, i.e. protein degradation) were overridden by exercise. Now, four years later Donny Camera from the University of Melbourne presented the results of a recent colloberation with the scientists from McMaster at the American College of Sports Medicine Conference in Denver, this year (Camera. 2011). The intention of this 2nd study was to elucidate the "effect of divergent glycogen content and subsequent post-exercise nutrition on anabolic signaling target p70S6 kinase during the early recovery period" after the completion of a standardized resistance training protocol.

Illustration 1: Very simplified illustration
of the role of mTOR and p90S6K
in protein synthesis.

Did you know that p70S6 kinase is a key component of the mTOR (the mammalian target of rapamycin) signaling cascade? The activation of mTOR via branched chain amino acids (leucine in particular) has been shown to increase p70S6K phosphorylation (the phosphorylation is equivalent to 'switching' it on). In a similar vein, physical exercise can activate protein synthesis via phosphorylation (activation) of p70S6K. The degree / increase / decrease of p70S6K kinase phosphorylation is thus considered a reliable indicator of the protein anabolic response to supplement and exercise protocols.

The evening before the actual experiment was conducted, the 16 resistance-trained male subjects (~23y) who participated in the study, reported to the laboratory in order to perform a single-legged cycling exercise to fatigue. In order not to upset the thusly established difference in glyocogen content between the trained (LOW) and the untrained leg (NORMAL), the subjects consumed an identical low carbohydrate meal after the workout and had to abstain from foods until the subsequent day, when they performed 5 unilateral leg press repetitions at 80% of their personal 1RM (one-repetition-max) with both their normal, as well as the glycogen depleted (LOW) leg. Muscle biopsies were taken 1h post exercise, and subjects consumed either a 0.5l post-workout shake that consisted of 20g whey + 40g maltodextrin or placebo immediately post and 2h after the exercise regimen.

Figure 1: Increase in  p70S6K phosphorylation in 16 resistance trained males after unilateral leg press exercise in normal and glycogen depleted leg relative to baseline (data adapted from Camera. 2011)

Although the muscle glycogen content increased exclusively in the nutrient (20g whey + 40g maltodextrin) group, significant increases of phosphorylation of p70S6K one of the key regulators of protein synthesis were seen in both legs of the subjects. As my plot of the restricted data I could extract from the abstract in the conference protocol (a paper obviously has not been published, yet) indicates, this increase was augmented up to 5x in the 1-4h hour post workout window in the glycogen depleted leg. While there was still a 8x increase in p70S6K phosphorylation in the glycogen-depleted leg even in the absence of post-workout nutrient repletion, post-workout nutrient (re-)feeding turned out to be necessary to illicit any increase in p70S6K phosphorylation over baseline in the normal leg.

Note that the baseline levels of the LOW and the NORMAL leg were probably different and the 8x increase could thus have lead to an absolute level of p70S6K phosphorylation that was still lower than in the NORMAL leg..

These results do not only contradict the initially raised hypothesis that well-stocked glycogen stores would be a necessary or at least facilitative prerequisite for the muscle anabolic response to exercise to take place, they also (re-)raise the question whether "training on empty" may not after all be advantageous if ...

1. the training performance is not effected by the lack of muscle glycogen and
2. the muscle anabolic response is augmented via appropriate post-workout nutrient-replenishment

Since this conjecture is yet solely based on the relative increases in phosphorylation, the scientists cite in their abstract, it is far from being a valid scientific hypothesis. We will probably have to wait for the publication of a respective paper (or ask someone who was lucky enough to attend the presentation for the absolute values; cf. "Note...", above), to get a preliminary answer on any beneficial effect exercising in a glycogen depleted state could have. In that, I would like to add that its artificial incarnation, i.e. the induction of local glycogen depletion, as it was practiced in the study at hand, has no significance with regard to the whole body (including liver) glycogen depletion some trainees experience as a result of (over-)training and no-carb (over-)dieting. In case of the latter, it does not take a rocket scientist to be able to tell that this won't have any beneficial effect on the gains people are making in the gym.

Cardio on Empty Improves Insulin Sensitivity

Doing your cardio sessions on an empty stomach (mostly first thing in the morning) may be debatable, if you are already lean and eat a clean and healthy calorie-restriced diet. If you gorge yourself of fatty high-energy foods, on the other hand, you may be happy to hear that K. Van Proeyen et al. (Proeyen. 2010) found "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".

The scientists had a group of healthy male volunteers (18-25y) consume a hyper-caloric (~+30% kcal/day) fat-rich (50% of kcal) diet for 6 weeks. Part of the subjects performed endurance exercise training (4d/week) in the fasted state (F; n=10), whilst the others ingested carbohydrates before and during the training sessions (CHO; n=10). With regard to the effects of this intervention the scientists write: 

Body weight increased in CON (+3.0±0.8 kg) and CHO (+1.4±0.4 kg) (P<0.01), but not in F (+0.7±0.4 kg, P=0.13). Compared with CON, F but not CHO enhanced whole-body glucose tolerance and Matsuda insulin sensitivity index (P<0.05). Muscle GLUT4 protein content was increased in F (+28%) compared with both CHO (P=0.05) and CON (P<0.05). Furthermore, only training in F elevated AMP-activated protein kinase α phosphorylation (+25%) as well as up-regulated fatty acid translocase/CD36 and carnitine palmitoyltransferase 1 mRNA levels compared with CON (~+30%, P<0.05).

 So, you can (almost, cf. table 1) prevent weight gain from bad diet habits by fasted state training,

Table 1: Effect of high-fat diet, alone or in conjunction with training in either the fasted
or the carbohydrate-fed state, on body weight and subcutaneous fat.

you can enhance glucose tolerance and c) you can jack up AMP-K and improve fatty acid oxidation. What are you waiting for? Get out of bed and run! If you can't drag your ass out of bed without it, pop a stimulant fat-burner, like VPX Meltdown or OxyElite, they will help to further increase fat-loss, as well.