Intermittent Fasting And Fast Twitch Muscle Fiber Atrophy – Part II

Intermittent Fasting And Fast Twitch Muscle Fiber Atrophy – Part II

Why would any individual concerned with fitness, performance, appearance, and health voluntarily choose to not eat?  Obviously because by not eating they expect to be able to positively impact one or several of those dimensions ( fitness, appearance, health etc. ) without doing overt harm to the others.  Recently, however, several studies have been published linking short term starvation with increased autophagy in fast twitch muscle fibers.  If this is true, then it is of significant concern because fast twitch muscle fibers are the ones that exhibit the highest capacity for hypertrophy, as well as the fibers recruited when maximal force output is called for.  These studies are especially worrisome because they suggest that metabolically speaking, fast twitch muscle fibers seem to be considered highly expendable, even more so than their slow twitch brethren.  Let’s take a look at one such study, brought to my attention by reader Rachid, that makes precisely these claims to see what we can find out, because if these findings are accurate, then we would have to seriously reevaluate our rationale for fasting.   Ogata et al. Fasting-related autophagic response in slow- and fast-twitch skeletal muscle. This study investigated regulation of autophagy in slow-twitch soleus and fast-twitch plantaris muscles in fasting-related atrophy.  Male Fischer-344 rats were subjected to fasting for 1, 2, or 3 days. Greater weight loss was observed in plantaris muscle than in soleus muscle in response to fasting.  . . .  These findings suggest that preferential atrophy of fast-twitch muscle is associated with induction of autophagy during fasting and that differences in autophagy regulation are attributable to differential signal regulation in soleus and plantaris muscle.   After reading this abstract, I would not fault you if you came away with the impression that these researchers determined that rat metabolism sacrifices fast twitch muscle fiber in lieu of slow twitch fiber under fasting conditions.  After all, “preferential atrophy of fast-twitch muscle” is pretty difficult to misinterpret, and the word “atrophy” itself is ominous.  My dictionary tells me that atrophy means to waste away, typically due to degeneration of cells.  It sounds, on the face of it, like bad news all around.   B y now, though, if you’ve read some of my previous posts, you should have come away with the realization that the devil is always in the details, and far more often than should be the case, paper abstracts are downright misleading.  So, let’s look at some of those details and see whether we can exorcise some devils.    Going straight to the meat of the matter,  the results section of the paper, here is what we find:   Ogata et al. Fasting-related autophagic response in slow- and fast-twitch skeletal muscle. Body weight declined in a fasting duration-dependent manner, and F-3d rats were 31% lighter than control rats.  Compared with control muscle, absolute soleus muscle weight was not changed in the F-1d or F-2d groups, but it decreased significantly by 10% in the F-3d group. In contrast, notable plantaris muscle loss was observed with fasting. Weight loss was 11% in F-1d, 19% in F-2d, and 23% in F-3d rats relative to control rats. Total protein content was not changed by fasting in either muscle type.   By my count, there are two bombshells in that paragraph.  See if you can spot them.  I’ll wait … on the internet, we have infinite time.  Click on the bombshells below to reveal them when you are ready.   Bombshell One F-3d rats were 31% lighter than control rats.     Once you collect your jaw from the floor, ponder what in the world must have been going on in these rats to make them a full 1/3 lighter than their unfasted companions after a mere three days of food deprivation.  But, before you go down that speculation rabbit hole,  you might want to decide whether that really matters to you because, frankly, you do not need to know a single thing about metabolism in order to understand that this simply is not the way that things work in human beings.   I will freely admit that the first time I read that number, I had to go to the results table because I fully expected that it was a typographical error that had slipped by the editors.  But, no, the computation is correct:     Note that the F-3d 31% weight loss computation is the result of taking the 98g post weight of these rats and comparing it to the control rats post weight of 142g.  If you actually compare the pre and post weights for all of the groups, the control group gained 4% body mass (!!), the 1 day fasted group lost 14%, the 2 day fasted group...

Intermittent Fasting, Autophagy, and mTOR – Part I

Intermittent Fasting, Autophagy, and mTOR – Part I

Rob, a reader from Ireland, pointed me to a worrying post regarding the potentially negative aspects of intermittent fasting and asked about my opinon of it.  Ok, I’m being generous here by throwing in the modifier potentially, because the post’s author definitely holds the viewpoint that fasting will kill you … I’m paraphrasing here and exaggerating a bit for effect, but not much since the actual quote from the posts’s conclusion is:   John Kiefer The research consistently shows that the only thing IF brings to the table for athletes is detriment. IF shuts off the very anabolic processes on which we rely for improving performance. IF manages to drive beneficial metabolic processes into destructive cellular chaos. In the research, IF consistently demonstrates that is no better than an average for fat loss or muscle gain and it decreases athletic performance.   It has been said that extraordinary claims require extraordinary evidence, so, without further ado, let’s dive in to the “proof” of Kiefer’s pudding.   If you Can’t Dazzle Them With Brilliance, Baffle Them With Bullsh*t   Try as I might, I can’t follow Kiefer’s argument, mostly because I find it muddled and contradictory.  Things start off on the wrong foot when he asks the reader to suspend all disbelief and “imagine a purely destructive process that’s critical for building the very thing it destroys.”  Call me pedantic,  limited, or lacking in imagination, but to me a purely destructive process only destroys, it doesn’t build.  If it destroys and builds, then it’s not purely destructive, but rather, complex, subtle, and nuanced.   If you are in a charitable mood, you might be tempted to let Kiefer off the hook and chalk all of this up to enthusiastic overstatement – maybe he didn’t really mean that autophagy is purely catabolic.  Except that apparently, he really does mean it as he repeats this mantra throughout his post : “by definition and function, autophagy destroys tissue, making it purely catabolic.”  Not to nitpick, but even if we were to concede that autophagy is purely catabolic (it isn’t), autophagy does not destroy tissue.  Autophagy is active at the cellular level, while tissues are collections of cells.  This is a very important distinction for reasons that will become apparent later, I raise this issue here to point out that Kiefer might be a bit sloppy in either his understanding, or explanations, or both.   This stance on autophagy as purely catabolic is especially surprising when you realize that in his citations, Kiefer refers to a paper by Masiero et al. entitled “Autophagy is required to maintain muscle mass.”  I understand that Kiefer is a busy man as he is trying to build his nutritional conselling business, and he may not have had the time to read the full paper, or maybe even the abstract.  But I would hope that he at least had the time to read the title!  Trying to characterize something that plays a critical role in maintaining muscle mass as purely catabolic smacks of expending a lot of effort in pounding a square peg into a round hole.   But why is Kiefer doing this?  After all, he’s not dumb, far from it, as he tells us himself, “he’s smart as f*ck.”  Mostly, he’s trying really hard to create an association in your mind between autophagy and pure catabolism so that in the subsequent discussion, whenever you see the word autophagy, he would ideally like you to picture your body melting into a puddle of catabolic goo.  Because if he can sell you this purely catabolic disease, he can then sell you his cure, and it will only cost you $89.  The last thing Kiefer wants is for you to think of autophagy as complex, subtle, nuanced, and worst of all, tightly regulated:   Weidberg et al. (2011) Biogenesis and Cargo Selectivity of Autophagosomes More recent research has altered the original view of autophagy as a nonselective process by revealing the existence of molecules involved in selectivity of autophagosome cargos. …  Autophagy is tightly regulated to prevent its unbalanced activation, which may cause damage to cells. Studies have identified at least two signaling complexes that participate in the fine-tuning of autophagic activity under conditions of stress and other physiological circumstances in which autophagy is needed.   Selective autophagy includes a pathway for targeting specific hydrolase proteins ( the Cvt pathway ), one for processing protein aggregates (aggrephagy), another for processing ribosomes (ribophagy), yet another one for mitochondria (mitophagy), as well as pexophagy, a pathway for specifically targeting peroxisomes.  That is certainly a lot of pretty specific pathways.  As Shakespeare might have said, “if autophagy be the...