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).

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.

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    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.
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