Intermittent Fasting, Part 3: Go Eat Yourself

Rocky Balboa learned a tough lesson in Rocky III: sometimes destruction is needed for future growth. Nobody wants to go through the devastation, so why not always just grow? If we limit that destruction to the detritus, then the new room created by cleaning out the garbage lets us build back stronger and bigger.

Now imagine a purely destructive process that’s critical for building the very thing it destroys. It’s counterintuitive, to say the least, and the fact that such a process exists in the case of fast-twitch muscle forced me to take longer than planned writing this third installment about intermittent fasting (IF). I didn’t anticipate how advanced our understanding of certain biomolecular processes has become.

Cliff’s Notes: Autophagy

Conceptually, the idea of eating oneself conjures various mental images. In some cases, it seems like a horrible thing, but in others, it’s quite sought after. For example, gnawing on your hand isn’t the best thing in the world, but losing fat is. When you lose body fat, the body literally eats itself, a process called autophagy.

By definition and function, autophagy destroys tissue, making it purely catabolic. As damaged and unused material builds up within a cell, it gets sick and can die. So it needs to get cleaned up: autophagy to the rescue.

Several authors give an excellent review of the basics—which aren’t so basic and I recommend this paper[1]. Relevant to our discussion there are two types, macroautophagy (Macro) and chaperon mediated autophagy (CMA). (There is a third type, microautophagy, but it’s poorly studied and, therefore, poorly understood[2,3].)

To be brief, autophagy is a reaction to either starvation or internal cellular damage; fasting triggers both on different time scales. Macro is fast-acting and short-lived whereas CMA takes a little time to kick in. Each type cleans detritus from the innards of the cells, removing the junk for healthier cell function or recycling components for tissue repair when you’re starving—literally.

Who Cares?

Autophagy, as I hinted above, keeps cells healthy by keeping them cleaned out. Think about it this way, how good do you feel when you’re constipated? Not very. Cells feel the same. Stuff builds up inside and needs to be cleaned.

Nowhere is this clearer than in skeletal muscle tissue. When autophagy is chronically suppressed (or knocked-out), chunks of non-functional protein accumulate, mitochondria (the cell’s power plant) develop bad mutations, and oxidative stress runs rampant. If autophagy fails, these conditions cause muscle fiber breakdown[4]—your muscles fall apart from the inside out and there’s really not much you can do about it.

Also, in times of nutritional deficit, like starvation, fasting or even rapid energy depletion such as happens with sustained exhaustive activity like CrossFit, autophagy actually helps to slow and protect against muscle loss[5, 6].

Autophagy is ex-lax for your cells.

Take note: autophagy is also part of the destructive process. In most tissues, Macro activates within a few hours of nutrient deprivation and only lasts a few hours. In fast-twitch muscle, however, the process can just keep going[7].

When this happens, the body is recycling chunks of protein in the muscle for use in repairing larger structures as they suffer damage[5, 6]. Autophagy helps preserve lean tissue by destroying fast-twitch muscle for spare parts. When you withhold food for a few hours or more, your muscles become a salvage yard. Obviously, muscular autophagy can only sustain muscle mass for so long until it runs out of junk material and starts destroying the entire muscle fiber. Autophagy is one of the main pathways of skeletal muscle breakdown[28].

Skeletal muscle is not the only tissue whose cells get filled with junk and could use a bit of spring cleaning from time to time. The cells of the nervous system, particularly brain neurons, become healthier, more robust and able to form new connections better, a process called neuroplasticity[8-10], when autophagy is routinely stimulated. Autophagy, literally, makes you smarter.

There’s also mounting evidence that the benefits of calorie restriction on muscle quality later in life and the benefits of exercise depend on properly activated autophagic pathways[31-33].

Autophagy is pretty damn important for skeletal muscle health, but so is how we regulate it.

Triggering the Hunger

We can trigger the first type of autophagy, Macro, with simple fasting. As I mentioned before, fasting triggers Macro within a few hours. Key point: macroautophagy is transient in nearly all tissues except fast twitch muscle[7, 11]. The body stops autophagic tissue destruction after only a few hours of initiation except in fast-twitch muscle. Bursts of Macro never last very long and need to be continually re-stimulated by eating, then fasting.

CMA, the other type of interesting autophagy, isn’t triggered directly by starvation. It’s regulated by ketone build up[1, 12]. If you’re in ketogenesis, autophagy is keeping your cells healthy and happy by cleaning out the gunk. Any type of ketogenic diet – Anabolic Diet, Atkins Prep Phase, Carb Nite, Carb Back-Loading, South Beach Induction Phase, various IF protocols, low-carb Paleo plans – all activate the chaperon mediated autophagy. Spiking free fatty acid levels—which can be done with MCT or coconut oil—also cause a strong increase in ketone production[23-25].

Being ravenous is destructive (and no, she’s not pregnant).


Don’t be ravenous

Autophagy is pure catabolism. We don’t want to it run unchecked. It’s not that tough and we can actually throttle autophagy or shut it off.

I talk about mTOR a lot, but that’s because it connects almost every muscular growth and degradation process. In this case, mTOR activation isn’t a direct regulator of autophagy, but it does, in most instances correlate with autophagy activation[13-15]. If mTOR is being stimulated, Macro activity is low; if not, Macro is high. Macro is always off when mTOR is getting a strong growth signal.

This isn’t the same as mTOR being shut-off which allows for degradation by autophagy[39-42]. It only means that unless a nutrient or system directly activates mTOR then Macro can function. For instance, mTOR can allow growth at night, but Macro can still clean cells. This is why the 12 hour window of fasting is the critical period—at this point, processes can inhibit the mTOR pathway and allow Macro to destroy our muscles.

Chaperon mediated autophagy (CMA) is different. Ketone-activated autophagy (CMA) functions independent of mTOR activation[34-38]. In other words, we can keep CMA going without sacrificing muscle. The nice thing here is that with energy influx (i.e. we eat something), we get the health benefits of autophagy and avoid the signals that trigger tissue breakdown. We also gain protection from skeletal muscle breakdown through ketone buildup[26].

Shut It Down, Shut the Field Down!*

Sometimes, we absolutely want to shut autophagy down to the fullest extent possible in fast twitch muscle, like after resistance training. Autophagy is suppressed during resistance training, but the buildup of reactive oxygen species (ROS, also known as free radicals), if left too long, triggers a strong autophagic response that can tear down muscle[16, 17]. The ROS buildup is hormetic: a little bit triggers growth factors, too much triggers destruction[18].

We can combat this destruction on several fronts. Amino acids can be highly suppressive to autophagy and in muscle, it requires both leucine and phenylalanine to shut autophagy down completely[2]. It turns out that autophagy is the only catabolic trigger that we can shut off with nutrients after resistance training[19].

(*If you don’t get the movie reference, don’t worry, it’s a geek thing from the movie Real Genius.)

What About IF?

This post might not seem to fit with IF, in that it just covers autophagy, but IF now claims magical autophagic properties, playing on the ignorance of the health and fitness community, and even some of the less informed experts. IF does trigger autophagy[12], but as you can see, none of the them from LeanGains to Eat-Stop-Eat do so optimally and anything recommending 24 hour fasts or longer is triggering catabolic processes specifically in fast-twitch muscle fiber. You may not notice this effect immediately, or at all, if you carry only a minimum of muscle, but if you’re pushing the envelop or shooting for maximum hypertrophy, fasting is not doing you any favors.

Macroautophagy stays on for 24 hours or longer only in fast-twitch muscle if we don’t eat. You know fast-twitch muscle: the stuff we all work so hard for. Autophagy stimulated by prolonged fasting is destructive; it’s passed the point of beneficial. Prolonged fasting triggers autophagy to deteriorate muscle tissue faster than severing the nerve to the muscle[29, 30]. Unacceptable after all the hard work we put into building it.

The only thing IF does for autophagy is to drive it into destructive ranges for fast-twitch muscle.

I know that people say these things work, but they’re usually sitting at 22% body fat or higher and dropping to 16% or so for men. That’s not tough and it’s established that body fat levels dictate muscle loss during weight loss-via calorie reduction—the fatter you are, the less muscle you’ll lose[20, 21]. And as was shown previously in this series, IF protocols perform identically to standard calorie reduction when it comes to body composition changes[22].

Ideal Autophagy for Muscle Growth

The ideal way to manipulate autophagy would be to allow fasts long enough to trigger macroautophagy without down-regulating the mTOR pathway, which can occur within 12 hours of fasting. At this point, eat something. If we spike free fatty-acid levels, or keeps them sustained, then the body continues producing ketones, which are the sole regulator of chaperon-mediated autophagy. This procedure has several cerebral benefits and not only will it avoid the atrophy of fast twitch muscle, but ketones protect muscle tissue from degradation.

The perfect diet? No, but compared with IF, it’s pretty damn close.

Then, when it comes time to train, your sympathetic nervous system—the one that controls fight-or-flight response, adrenaline and all that good stuff—is primed for action with bigger adrenaline pulses, faster response and stronger activation (see The Hulk Factor). The heightened burst of adrenaline also fights proteolysis[27], or muscle tissue breakdown.

This can only occur if insulin levels have been kept low all day and you’ve been eating something—otherwise, the long-lived fast can trigger adrenaline release before the workout and destroy the advantage.

At this point in the day, we’ve optimized performance, preserved muscle mass and allowed beneficial autophagy to run its course. Train. After the session, spark growth as rapidly and potently as possible by spiking insulin levels, providing raw materials for growth and shutting down the one catabolic component we have control over: destructive autophagy.

Once the frenzy is over, it’s time for bed where we’ve made sure our food choice cleared as quickly as possible to allow macroautophagy to work through the night.

IF is Nutrition’s Apollo Creed

In the first Rocky, Apollo Creed was the unchallenged boxing champion of the imaginary pugilistic world and after reading a horrible article by an IF author describing enhanced muscle mass through autophagy, I realized that Intermittent Fasting (IF) is Apollo’s dietary equivalent.

With no real challengers, IF has emerged as a champion, and in its own right, IF is a champion of diet—against average diets. It is a little better, if only because it triggers a therapeutic clean-up process at the cellular level and for most people it’s easy.

But now, I’m challenging. 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.

Rocky Balboa, the unknown underdog, went toe-to-toe with the champ. No clear victor appeared after the first match—the champ winning by default—but Apollo kept accepting challenges and we know how that story ends: Rocky beat the crap out of him.


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  • AdamReid

    Great article. Well worth the wait. As a former LG follower, the amount of new, relevant information you post on a regular basis is refreshing.

    This article in particular really cleared up questions I had personally regarding why CBL seems so much more “muscle friendly” as opposed to LG and other IF methods.

    In the CBL book you reference CBL as “IF Evolved”…in my opinion there is no comparison.

    I.F. may be CBL’s distant cousin, who rarely comes to family gatherings for fear that the other relatives will spend the entire evening gloating over CBL’s accomplishments and scientific knowledge, which only makes IF exponentially jealous.

    Sorry IF. CBL for the win…

  • Brandon Christ

    So we do get the same benefits from autophagy that Josh Whiton speaks of by doing CBL? Like the anti-aging stuff?

    • dhnaomi

      The answer is “probably”. Kiefer’s really keen on getting Whiton back for another conversation.

  • Fred

    Awesome stuff, as always, Kiefer.

    Just as a hypothetical, can we safely get up, have the anabolic activator, and not eat until 12 hours after that, backload, and not go catabolic? Not that you would recommend this protocol

    • DHKiefer

      I would say, hesitantly, yes.

      • Fred

        Thanks Kiefer, just wanted to know if the option was open.

        Also, would there be any value to using R-Alpha lipoic acid during any phase of the day, on CBL. Perhaps to enhance ketosis during the day, or assist in nutrient partitioning at night?

  • PropaneFitness

    So I would be right in thinking that we can keep the negative processes at bay with something as simple as MCT oil and whey isolate at strategic times. In keeping with the idea of backloading calories and carbs would it be sufficient to say consume servings of whey isolate and MCTs (10g/1tbsp respectively) in a 3-4 hour cadence during the day or is there some inherent benefit to consuming larger quantities of calories from solid foods?

    • Jable1066

      This is what I’d like to know too. From what I understand some benefits of the larger meals pre-training are:

      1. More energy for your workout and to include less fat in your backload. If you’re eating 150-200g of fat per day but you’ve only pulsed with 40g pre-workout, that is a lot of fat to have with your backloads which may blunt the insulin response.
      2. Having little fat and protein earlier in the day will do little to keep you satiated. When it comes to backloading later on you may go way overboard.
      3. Lastly, my backloading window is generally only 3-4 hours long after I’ve trained. It’s simply easier to fit a few 100g’s of carbs, moderate fat and protein than it is to include the entire days worth of macros more or less in this small window. I’d personally end up getting too full and wouldn’t be able to hit my daily totals.

      Most importantly, psychologically I need to eat a meal at some point before I work out. In some cases, pulsing with only 10g, 5g (protein, fat) shakes every few hours would mean in roughly a 20 hour window I’d of had 3-4 tiny shakes. The idea is unappealing and doesn’t have much longevity.

      Also, another important thing to consider is veggies. If you’re pulsing throughout the day with no solid meals, you will have had no vegetables and consequently, no fibre. You want to minimise fibre intake during a backload so if you’re not eating veggies post workout and only pulsing sans veggies pre workout… When are you getting your fibre?

      Just my thoughts gathered from the book and forum, which have absolutely no scientific reasoning.

      • dhnaomi

        Your numbered points aren’t really applicable to everyone across the board and are also highly dependent on what you do on other days.

        If you eat a lot of fat and protein on your off days (a “surplus” if you’re counting calories), you may not feel any need for significant intake pre-workout, and you could feel entirely satiated just doing the micro-shakes, with plenty of energy for the workout. That’s both observation and personal experience talking.

        Most people also have quite reasonable digestive lives consuming vegetables on a “when it makes sense” basis, meaning not necessarily at the same time / same meals every day.

        We need to get away from this “daily diet” way of thinking, ESPECIALLY when it comes to Carb Back-Loading, where the rhythm falls around training times.

        You don’t need “a whole day’s worth of macros” every day. Some days you will eat more. Some days you will eat less.

        • Jable1066

          Thanks for clearing some of that up!

          My intention wasn’t to give a reply that applies to every one across the board, nor did I say it did. I’m pretty sure that would be different for everyone.

          Likewise I didn’t say that you needed a whole days worth of macros every day… Just that in my experience, it’s easier to hit that particular days total of, say carbs for example, if food is spread out through the day.

    • DHKiefer

      We’re on the cusp of a new dieting paradigm and I can’t answer this succinctly or concretely. All meal frequency studies that I know of have been conducted with mixed meal feedings, so extracting carbs might be a game changer and give advantages, but it might not. As far as autophagy is concerned, there are no hard numbers as to the ratio of Macro to CMA for greatest cellular benefit. I would surmise that if your goal is to activate as much Macro as possible, you’d want more like 4 to 5 hour boosts or possibly longer. Ideal for Macro autophagy might be, wake, nutrient influx, 3pm nutrient influx, train, refeed. In general, though CMA takes time to kick in, so this pattern may limit CMA. This is a field where much research is needed for optimization protocols.

      • PropaneFitness

        Really interesting, thank you for the response. Given that a precise approach for autophagy is currently uncertain, with what we know about the “fasted state” would a sensible approach for body-composition be to similar to what you outlined? Namely, an influx of nutrients at a similar cadence (perhaps more frequently) with the goal of maintaining ketogenesis and elevating FFA levels? Using only small amounts of Isolate and MCTs until training, use workout nutrition as per the CBL book and then backload as usual after. The intention being to maintain an “underfed” state to perhaps amplify the metabolic effects of the backload?

  • AciD

    Ok, Kiefer – IF comunity talks about AMPK that replaces fucntions of mTOR while it’s downregulated. Can you say anything about this?

    2nd question:
    e.g. I finish eating at 9.00p.m. than on 9 or 10 a.m. I have coffe + coconut oil, nothing more.
    Than start eating at 1p.m. Is that optimal for fat loss? I’m about 11% and Try to keep my food as clean as possible [I mean White rice and french fries instead of turnovers, haha] I’ll try to get down with my BF as low as possible. Also I AM counting calories, just because I want to shred, and it’s optimal that way [I think…].


    • DHKiefer

      1. Can you verify they mean AMPK and not Akt. If so, I’ll look into the proposition, though I doubt it holds much water. The Akt route could, as it’s possible to stimulate Akt which can trump mTOR activation, but you can’t do it fasting, which again, refutes their claims. Akt is highly sensitive to energy flux. Like I said, if they do mean AMPK, I’ll have to look into it deeper.

      2. Yes. And counting calories can help give you a reference point for long-term trending, just keep in mind that precision from day-to-day isn’t as important as weekly trends.

      • AciD

        They do mean AMPK, I was just quoting one of the followers, so I think it’s worth refering to this argument.

  • fearless

    After reading this last installment i’ve made up my mind that i’ll stop any kind of IF.

    The question i have now is what to do?! i’m 225lbs and over 20% BF but my goals are strength and then physique improvement (in that order with heavy emphasis on the first). Should i be looking at CBL or am i too fat? I also only train with weights twice a week if that makes a difference….

    • Russell Yazbeck

      CBL is not for you at 20% BF. CBL will ONLY work with heavy resistance training.

      Sounds like you should try Carb-Nite. It will work even without heavy resistance training.

      • dhnaomi

        >CBL is not for you at 20% BF

        Why do you believe that?

      • fearless

        I do theavy resistance training twice a week.

    • dhnaomi

      You can easily build lots of strength on CBL while dropping fat. The variant of CBL you would follow is called “Strength Accumulation” — it’s a path laid out in the book.

      But even guys following the “Density Bulking” protocol, which prioritizes lean mass gains (and strength of course), will see good consistent fat loss when starting from 20+% body fat.

      You might want to check out the Shockwave Protocol pamphlet (free) to learn a couple of different styles of putting Kiefer’s diets to work specifically for building strength.

      • fearless

        dhnaomi – does the CBL book mention how to tailor the above 2 mentioned protocols to twice a week training? the reason i ask is because the shockwave protocol has 4-5 days training involved.

        Just to empahsise, im more interested in bringing my squat, bench and deadlift up than anything else. physique improvements would be a very welcome added bonus…judging by what i’ve read, this is something CBL can do.

        • dhnaomi

          The Shockwave Protocol is designed as “modules” that you can stack together on a single day, if you like. It’s up to you how you combine them, but it’s obviously best if you train mostly unrelated muscle groups on the same day, e.g. don’t squat on the same day you deadlift, naturally.

          So yes, you could do it in 2 days, and you could toss out the sections you didn’t feel like doing, too. It’s worth trying this training style even if you’re not following the pamphlet to the letter — this system is a precursor to a training package (called Shockwave Protocols) Kiefer’s putting together that is ALL ABOUT working within people’s individual constraints.

          The CBL book should make it clear how to configure your diet for 2 days a week training, but if you have any questions about that once you’ve dug into the book, you’re welcome to ask away in the CBL Members-only section of the DH Forum.

  • Peter

    Kiefer…I know you discuss how devastating prolonged fasting is in regards to catabolism of muscular cells..however, this is a moot point. Energy balance at the end of the day can’t really be trumped. As long as the energy balance is in surplus at the end of the day…overall you will have built more tissue than lost assuming you are training too (therefore, it’s not all fat). If your theories were entirely could basically say “oh yea..if you don’t eat for 24 hours and then gorge yourself in absolute excess at the end of the doesn’t won’t gain anything because fasting magically trumps the fact that your 1000kcal over your energy needs” …

    • Gl;itch.e

      Read the first part of this series if you have not.

    • DHKiefer

      The point is not moot. Unless you think taking 1 step back for every 2 forward is smarter than perpetual forward motion. Me, I prefer to gain at the maximum possible rate rather than at half-speed.

      • Leonardo Solis

        Kiefer, I am curious about one thing you mentioned in one of the biojacked episodes, regarding the body capacity to store protein in the organs, wich serve as primary amino acid reserve normally prefered over muscle tissue. I am really interested in lerning more about that, Can you reference some research papers dealing with such matter? Thanks in advance

      • Marc Theiler

        Why did you reply to Peter? Please, only reserve your replies for those that put forth at least a small amount of effort.

  • Steven Acerra

    Holy cherry-picking, batman. Just sayin’

    • dhnaomi

      This article was more than a month in the making, because Kiefer kept finding more and more research that modified his initial assumptions about how autophagy worked. Every week I asked him if he was about to post IF #3, and he’d say, “it’s more complicated than I thought.”

      If you have some new research to bring to our attention, by all means, reveal it here.

      Otherwise, asserting “cherry-picking” is just as bad as saying, “well I don’t believe it” and refusing to say a word after that. Unconstructive.

      • Steven Acerra

        OK, Well for instance, how about this study showing mTOR activated after 24 hrs of fasting?
        There’s more…

        • DHKiefer

          Thanks for providing the references Steven. I’m always happy for exposure to new research, or reading papers I’ve seen before.

          As to your first reference, that was mTOR activation in the fed state for 24 hours, not after 24 hours of fasting. Simply because they use the word “fasting” (“the fasted state” is the exact phrase), they’re not talking about a 24 hour fast (actually they mean first thing in the morning after waking).

          And the author in the second abstract you posted states: “Acute [12-72 hours] starvation produces profound cardiovascular and metabolic changes which are not explained by the accompanying hormonal changes.”

          In your final reference, the researchers only look at one set of skeletal muscle regulator genes, and ignores the autophagy-related genes such as LC3 or Gabarap.

          I wouldn’t say you’re “cherry picking” in your refutation only that you don’t have the breadth of knowledge wide enough to interpret the papers on which you base your assumptions and to put them in context with the 100’s of thousands articles that exist.

          I spend time exploring these topics to optimize my own protocols not to dismiss anything in particular. As a matter of fact, after doing this research, I learned I made some non-optimal suggestions in CBL which I will correct in the next version.

          I appreciate the references. Thanks again.

          • gmarceau

            Probably premature, but any idea when you would release an update to the book?

          • DHKiefer

            There will be a major upgrade this summer with the release of the hard cover edition. The electronic version will be supplemented with audio material, supplemental guides, optimized recipes and more meal plans.

          • Lefty

            In the meantime maybe a big article with some practical tips for optimization of CNS & CBL? There must be alot of juicy stuff that isn’t in the books 😀

          • dhnaomi

            That’s really the purpose that the DH forums serve. But you’re right, a round-up of useful practical application tips would be great.

          • Steven Acerra

            Good call on the first study – however, the point is that resistance exercise will stimulate mTOR regardless of eating status:
            Measurements taken “At ∼06.00 h after an overnight fast” We can say that this is roughly 14-16 hrs fasted and we see a rise in protein synthesis.

          • Steven Acerra

            Also, I don’t remember you declaring the fact that the ramadan studies are looking at dehydrated subjects. For which may play a role in RMR.
            Furthermore – there are obviously studies that show short term fasting does not have (or may have a beneficial effect) on RMR. And it should be clarified that simply losing weight from lean body mass will decrease RMR.

          • DHKiefer

            I am aware that Ramadan subjects are not as hydrated as non-fasting peers, but there has been no research to verify an assertion that the level of hydration experienced is metabolically detrimental (if you have some I’d like to see it, because that’s a topic I want to hit eventually). Also, your point about Ramadan and the Soeter’s study is moot (specifically dehydration possibly effecting RMR) because it was not performed on Ramadan-fasting subjects. It seems to me you’re making assumptions on disparate pieces and not paying attention to the actual work or implications.

            And thanks for this study, as I did not have it in my collection. But it only supports the Soeter paper, fat oxidation may have increased after 3 weeks, but insulin levels were lower (correlating with decreased carb utilization). It also confirms my statement that the results of IF are no better than standard protocols and don’t compare to ketogenic protocols in the literature. Each papar you provide only supports my original premise: IF is not a performance based diet.

            Now we have the case that AFD may not decrease REE. This does not however address the facts of this article which is that IF has detrimental effects on performance gains. For example, subjects trained fed in the study you sited…when they train fasted, Akt is down regulated (just as it is in exhausted type training regimines like CrossFit) as I referenced in part 2.

            You seem to be pulling specific articles for refutation rather than placing them in the context of everything presented here. It’s like having a jilted girlfriend tell all her friends her side of the story and they believe it without hearing the boyfriend’s version. And vice-versa. Only after considering both versions can you come to some semblance of the truth. I think you’re coming for a one-sided position. And now that I actually wrote a book, you’re assuming I do the same.

            I’ve read way too much research on this matter to be convinced that IF is metabolically superior in anyway to my protocols–either Carb Nite or Carb Back-Loading (which means several other diets would be superior as well) or even to standard weight-loss protocols other than it’s ability to trigger some autophagic mechanisms and life-extension gene upregulation (like downregulating mTOR and simulating SIRT1 activity).

            But I’m happy to have you post more information and I’ll probably edit a few sections of this series for precision in light of a couple of pieces of research you’ve presented (and use the others to optimize CBL and CN, as they seem more applicable to refining fed-state protocols).

            Do you have a site? You obviously seem well versed in IF research, at least supporting material.

          • Steven Acerra

            No site. No bias. No profit motif. Just a student.

            As far as the ex-grilfriend analogy – hardly! A main proponent of IF is Martin from leangains – from communications i’ve had with him – I don’t think i’d think very highly of him on a personal level. It wouldn’t break my heart if yours or any other program is ‘better’ than IF.

            My main issues with this series is the implication that IF will make your muscles fall off – this is how I interpreted the material you’ve presented.

            If the debate is what is optimal – i’m willing to listen. But I think the mTOR idea is insignificant – the idea that we need mTOR revving 24/7 to secure muscle from falling off is unsubstantiated imo. And from what I understand, mTOR is sensitive to food and resistance training – and even if it were downregualated (which i’m sure it would be with no exercise), If we’re training at 10 am, eating for a few hours, we can then fast for 16 hrs – fasting would have no effect on mTOR within that 24 hr time-frame.

            I think the RMR issue is irrelevant as well – at worst – it stops you from eating an extra bagel a day, at best short term fasting increases metabolism – esp., in that most people fasting are using caffeine and that should make up the difference anyway.

          • Steven Acerra
          • DHKiefer

            Thanks again Steven. I hope you realize the above links still don’t support that idea that losing muscle mass a priori implies RMR MUST go down independent of any and all factors. I hate to tell you, but you’ll never be able to prove that especially with weight loss studies in which the weight loss protocols also have a tendency to decrease thermogenic processes and hormones.

            This series has definitely sparked an in interest going through the research. It’d be awesome if you continued and created a synthesis that would be helpful to others.

            You should start a blog. Your facebook page isn’t really getting the attention it deserves.

          • Luke

            Very enjoyable conversation to read.

          • alexb

            If you’re not convinced that IF, or even longer term fasting, is superior to those other diets you mentioned….than you haven’t tried it. At least not for a substantial amount of time. It takes a very very long time to readjust one’s physiology back to the beginning, where it belongs. We’re talking about erasing countless generations of epi genetic changes from which we all suffer from…even our most elite athletes. They are simply “elite” in relation to the rest of us, but they are “nothing” compared to what we were capable 10’s of thousands of years ago. Don’t you find it fascinating that when our bodies want us to go get food, ie hunt or scavenge or whatever, as the result of detecting the fasted state……it shuts down testosterone production and releases a menagerie of other hormones and chemicals of which GH is only one of? Let’s be clear what that means….when the body wants us to be primed for an athletic endeavor, be mean and nasty, it turns off the Test. And this process happens at around teh 18-24 hour mark.
            You have your data I understand that, but you have to understand where that data comes from and how compromised the subjects truly are.

          • DHKiefer

            Also, “it should be clarified that simply losing weight from lean mass will decrease RMR.” Can you present evidence of this statement? By making it, you pretty much are saying that hormones, such as T3 have absolutely no effect on metabolic rate, which is an absurd assertion. That doesn’t mean metabolic rate can’t decrease with a loss in muscle mass, it’s not a priori true.

            And keep in mind that this is all text without inflection and I don’t mean to sound as harsh as the responses read.

          • DHKiefer

            I honestly appreciate the criticism. My goal is to be as right as possible.

            As to the ~6.00 after an overnight fast, I think you’re extrapolating the author’s procedure, because, as I could see, there was no mention of being fasted at the sampling time that occurred 6 hours after waking. I wasn’t sure. It might be prudent to contact the authors. Regardless, this does not contradict any research I’ve presented showing that mTOR activity starts decreasing within 12 hours of fasting. It may not reach a nadir, but that does not mean it’s always peaked.

            The study I cited in the first part of the series (and second) clearly showed a propensity for a lowered metabolic over the study period. You’ll notice the authors explored the rate of metabolism of different substrates. At rest, the body clearly burned less carbohydrate. The implications of this are wide and ties with other research you presented showing profound hormonal effects of short-term fasting. I see nothing inconsistent.

          • Marc Theiler

            Steven, thanks a lot for posting those references, this is the exact post/reply exchange that is actually constructive. This is a perfect example of an opportunity where everyone learns something. If you have a counter-point or a varying perspective, attempt to articulate those critical points the best you can and hopefully with cited research sources as to why you have come to that position. So when it comes time to refute and debate the relating party can then address the critical nature and possibly show error or his own cognitive erroring. I grow fucking tired of these clueless dipshits that reply with noncritical babble – it’s a waste of all of our time.

            Thanks again Kiefer – had to take a break from the action for a bit – busy bro. Super great read.

  • dhanna

    I’m just happy that you got CrossFit into the article. 😀

  • Ryan B

    I posted a comment on the autophagy biojacked article, but it was a little late and I didn’t get a response.

    I hope you don’t mind me posting here, but I’m still very curious; I heard you mention in the autophagy biojacked radio show that the metabolic fate of cbl is affected by the use of ace k. Can you elaborate on the negative implications of using ace k, whether it be in pre workout supps, protein, etc… Thanks a lot for everything. I really enjoy the biojacked series thus far!

    • DHKiefer

      Yeah, ace-k in the low-carb phase of the day (or low-carb phase of any diet) can trigger insulin release. There are no good numbers on the quantity it takes to do so in humans, only that ace-k is distinctly an insulin secretagogue. I’ve noticed over the last decade with myself and others that sticking points can be alleviated simply by removing all products with ace-k, which are usually beverages. Even replacing them with non-ace-k alternatives allowed progress.

      • Ryan B

        Wow! That makes sense and I’ll definitely keep that in mind for myself. Thanks a lot!

      • Yannis

        Kiefer, I appreciate your work and well-spoken researchers such as yourself make a big difference in our lives. As for the Leangains arguments, I would really not discount M. Berkhan’s arguments since he also knows his stuff, is very strong and looks incredibly fit. Is there any link where I can see results on your body? I very rarely take advice from people that do not look better than me. 😉 Thanks!

  • Lefty

    Hey Kiefer, how much would you have to eat to shutdown the macroautophagy? I guess an am accelerator shake wouldn’t be enough, would it? Great article by the way.

    • DHKiefer

      That’s a very good question. The AM accelerator should not, but by the time you wake, as best I could find in the research, Macro should already be off.

  • ColdsnapBryan

    Kiefer – Hi, thank you for posting this series. I see you mention ketones and carb-backloading my question is; Will someone on the carb-backloading pass the ketone urine test? Probably might depend on what day it is in their diet program, like if they carb-backloaded the night before they might not pass the morning of.

    • dhnaomi

      Even people in ketogenesis often fail the ketone urine test. Ketosis shows you are OVERproducing ketones, meaning generating more than you need. People who have been in ketogenesis for a while generally don’t overproduce, and therefore you wouldn’t see any ketones in urine.

  • Adam SmithUSA

    It is time for Lean “lose your muscle” gains, and Eat-Stop “you won’t be able to bench heavy during this period” Eat to move out of the way.

    Kiefer is here, bringing the science and he has a clear goal for this diet. This diet will continue to evolve develop and be simplified.

    Although many argue that it cannot be followed unless you have liberal amounts of time, I think that it can be followed and implemented with ease. Most people are working 9-5 whether they are students or have jobs, and most people have carb dense meals at the end of the day (well in USA, maybe not so much…..carbs with every single meal, and every snack..)

    Ultimately Kiefer bring your work to the mainstream! :

    1. Lower Book Costs.
    2. Make a simplified Book for a larger audience

    • dhnaomi

      That’s an odd argument, needing liberal amounts of time? CBL (to me) feels like the easiest and least “extra work” diet, second only to Carb Nite in terms of its simplicity, with the advantage over Carb Nite that it’s *socially* easier.

      I think you’re right about the need for a simpler, less expensive product. It’s on the horizon.

  • Meni Troupakis

    I discovered back loading from a thread on a forum, and I absolutely love the articles here, and the podcasts. DH is my most visited lifting/nutrition site now. Waiting for the software.

  • Graforlock

    1. ok, so first of all, more recent studies shown that mTOR signalling DOES NOT equal growth.

    absolutely no correlation of muscle growth with mTOR signalling; there is something else, and we dont even know about it yet, and this thing down the stream maintains prothein synthesis, but just as i said, it is yet to be known.

    2. secondly, if you are on a caloric surplus, mTOR is mainly activated, no matter what, thats due to the fat synthesis , protein synthesis and huge amounts of food, AMPK will not be signalled a fuck but during the exercise, when AMPK is always going on.

    3. thirdly, bullshit is that you burn your muscle during the, even 18-20 hour fast, there is absolutely NO PROOF, that AMPK signalling for such a short time will freakin do anything to the muscles.

    here are numerous proofs, and one that is the most important, that AMPK lowers protein synthesis by 70% IT DOES NOT, HOWEVER, SHUT IT DOWN FFS.

    more interesting is that fasted NOR NOT , weight training improves prothein synthesis by 140-150%, so you do the math.

    • DHKiefer

      Thanks Graforlock for the citations, they’re good information.
      Unfortunately, they are pretty much moot in this conversation. Nowhere did I say you’d have net proteolysis or shutdown growth. You slow and limit pathways as they begin to wain and shutdown.

      And I don’t know if you read your first reference, but you may need to explain how it shows that mTOR activation does not equal growth, as in all situations, mTOR was activated which equals growth, not to mention even a brief search for papers on mTOR and muscle hypertrohpy produce a treasure trove of papers relating mTOR activation to growth. Not that it is essential, but it can promote growth and, as a nexus for many up- and down-stream regulators, mTOR still remains one of the most important indicators of anabolism of which we know. Your citation even supports the correlation and elucidates potential down-stream targets of mTOR. I am glad the article cited at least mentions mTOR, but, alas, it says nothing to support your statement.

      And I don’t think AMPK was mentioned in the series at all (unless you misread Akt as AMPK), but thanks for your comment all the same. It’s enlightening.

      Yes, it is possible to activate muscle protein synthesis while fasted, but less so depending on the length of time fasted. There is evidence that muscle protein synthesis is blunted with longer duration fasts, as I covered in this series.

      The math is simple: irritation + irrelevant citations = useless commentary. Math done.

      Thanks again. It was a pleasure.

  • Graforlock

    addendum to 1. i meant of course, exercise induced mTOR is irrelevant and does not correlate with muscle growth AT ALL.

  • graforlock

    DHKiefer: the research about weight training is not per se, about mTOR signalling, but it finds out several things, for instance the ‘anabolic’

    signalling of Akt and mTOR was better in on of the groups, lasting twice as much as the other one, however its speculable that you can built more muscle

    in 20-50 rep range than in 5-15, the study shows otherwise relying on mTOR and Akt activation. That is why there has to be something else that manages

    prothein synthesis, because nearly every study that took the subject of reps for muscle growth, indicated that the biggest LBM gains were at 6-12 range.

    It doesnt really matter how often you activate mTOR, and the less the better, AMPK doesnt shut down muscle protein synthesis in such a short period of

    time as even 20-24 hours, and one can really get great results by AMPK advantages. Moreover, mTOR shuts down after approximately 3 hours after a

    meal, when there are still many aminoacids in the bloodstream. Even if leucine signals prothein synthesis the actual process of muscle growth is shut

    down by something else, which we do not know about exactly. Constant mTOR activation leads to fat synthesis, why not minimize it to when body needs it? Being extreme; if you eat once a day , body will absorb as much as it needs, and your body composition may improve, just as in Stote study on Intermittent Fasting group vs three meal group:

    AMPK magic does all the work.

    As for myself, i have had humongously good results with IF diet. unlike with anything else, the same goes with my friends which compete in bodybuilding,

    what they saw is better vascularization, minimal muscle loss, and maximum fat mobilization.

    An objective review of research supporting many IF thesis:

    • DHKiefer

      As for your one scientific article cited (, I don’t think the study supports fasting as a means to muscle growth, only fat loss and mimics research previously cited on the ability of back-loading carbohydrates and also on back-loading calories to elicit greater fat loss, except in those studies where the participants eat through the beginning of the day, either extremely light calorie loads or ultra-low carb, they actually lost far more fat than the other group.

      These results, taken with the paper you cited here (notice they ate their single meal in the early evening, the optimum “back-loading” time) reveal that there’s nothing special about IF. What’s special is back-loading calories and carbs. Your citation actually supports the case for back-loading over IF when taken in context of the body of current research.

      One study in vacuum cannot be “proof” of anything, especially a pilot study. I think it’s great work, but it supports CBL more than IF and gives no insight into the anabolic or anti-anabolic properties of either.

      I’m not saying anywhere that IF is impossible to use for certain tasks. The whole point of this series, recognized by the astute reader, is that IF cannot perform as well as protocols designed for performance. Give me any athlete currently using IF, and I will improve their performance in a fortnight with CBL.

      Thanks again for presenting some citations. They will be added in context to the contents of CBL as added support.

      • graforlock

        I dont know in what way does this study support CBL more, if people during the Stote trial were fasting for 23 hours on daily bases.

        I may give you one athlete who does intermittent fasting at a high level of powerlifting:

        Chriss Duffin of USP Labs.

        IF is relatively new thing but it’s been tested a bit BUT, here’s training fasted and performance among athletes:

        elite judokas
        fasted endurance training
        glucose tolerance et cetera

        also, heres the analysis of one of these studies

        As for pefrormance,personally, me and my friends noticed improved strength and endurance while training fasted. literally strength goes through the roof, i am active and very angry during the fast, very masculine if you ask, its blunted with the first bite of the food. I would consider this as ‘on drugs’ , feels much like some stimulant, but i enjoy it especially that i myslef train both judo and rugby at amateur level, and really enjoy this diet.

        But training fasted isnt the only way to go, i see ABSOLUTELY NO problem in eating pre workout meal, after a 16 hour or so fast.

        • graforlock

          again, sent too soon, and forgot to correct some misspellings or grammar. somehow, i cant edit it now. sorry

        • DHKiefer

          I’m familiar with the first study, notice the author warns against the performance decrements noted with the Ramadan fast.

          Your second test running first thing after an overnight fast, not and IF protocol and the others, again, only mimic what we know happens when you subtract carbs from the diet. None of these, in anyway, say that IF is a superior protocol even to a ketogenic diet.

          And putting a link to leangains for an implied “unbiased” look at research into IF is inane since LeanGains is strictly an IF platform. is not a platform for anything other than the best protocols possible based on science and experience with hundreds of people.

          And referencing a single elite athlete to compare to anyone is, again, not applicable. You’d have to do a comparison and get him to try CBL for example and see if he performs better. His unique genetic makeup allowing him to be elite doesn’t help the rest of us. If he’s down to try CBL, I’d be happy to provide instruction and book to him.

          I appreciate your tenacity, but you’re not providing relevant information to show IF is superior to anything other than the standard American diet–and that’s a no-brainer.

          And don’t worry about the typos. Do me a favor and dig into the details of CBL before posting again. I think it will prove enlightening even if, in the end, you decide it’s not for you.

          • graforlock

            i would , if CBL wasnt that darn expensive, of course. i wouldnt call LG bias at all.

            if stuff works, it works, why change it. i lift only for a year and a half , IF most of the time, i do rugby, judo and powerlifting all amateur of course, my squat is 170kg, deads are 225, bench is 140 kilos, i wouldnt say that it affects my performance at all, because i tried regular diet and i know it doesnt matter, only thing different is that i dont get fat now.

            i know that CBL is still based on some short fasting and im not against it, but i sense fighting the IF without a real and sufficient proof is not

            why IF isnt that popular in sports? because its relatively new to the sports, i mean like one or two years, so its hard to expact that it will conquer the diet market if regular eating based on 6 meals a day has been here since 60s.

  • graforlock

    sorry for the text formatting.

    • DHKiefer

      It is a bit odd…but no worries. It reads well enough.

  • Mike T Nelson

    Thanks for the post and all the time and research that went into it. I always like to read a wide variety of inputs since I learn something new every time.

    Question, I now you stated that prolonged fasting is catabolic to fast twitch muscle fiber, but I can’t find a reference for it. The 2 studies referenced were in denervated muscle (29,30) and mostly on mitchondria effects. I agree that cutting the nerve to a muscle will result in atrophy in short course, but missing how this is related to fasting.

    Not trying to hop on here and sound like a dink, just trying to understand!
    Mike T Nelson PhD(c)

    • abdi

      No answer.

  • Fred

    I have a question regarding the use of Leucine. If we are getting plenty of leucine from fish or red meat, is there still a reason to include it in my post wo shake? I ask this because we are including it with our food, or po shake and not seperate. Does the leucine in fish or beef sike insulin, like adding it to our po shake.

  • UofF bullshit

    Kiefer, how can we be expected to even believe you when you are so full of bullshit in your bio.

    The Graduate Catalog states that the minimum number of credits necessary to obtain a Ph.D. is 90 credits after a Bachelors of Science Degree (B.S.). As physics students usually gain credits at the rate of 24 credits a year, this means that a Ph.D. can be obtained in less than four years.

    You’re saying you completed your prelim, 90 hours of course work, did your oral and written qualifying exam, and all your research and wrote it up in a year.

    Who was your PI – I’ll walk over to the department next week and talk to them about your genius.

    • Andy Watkins

      The bio said he became a Ph.D. candidate in a year, not that he received the degree in only a year. That’s still a remarkable acceleration–most science programs have quals scheduled for sometime around your second year winter or spring–but hardly unheard of.

  • bender

    If I understand, most of your issues with IF come with a claim that they cause muscle loss. Most of the evidence you’ve cited for this is derived from acute studies looking at fasting for brief periods over a single instance. Still, longer duration studies (such as ) suggest that IF doesn’t cause any muscle loss problems. Wouldn’t this suggest that, say, upon refeeding, the “loss” of muscle is met with an increased anabolic rebound? Or perhaps not that exact mechanism, but that in the long-term, fasts in the 16-24 hour range aren’t problematic for reducing fat mass while preserving lean body mass, which is what most people are actually concerned with?

  • Fing Duck

    Brad Pilon is 178lbs and opts for 24 hr fasts. Martin Berkan is 190lbs and opts for 16 hr fasts. Kiefer is 230lbs and opts for 12-14 hr fasts.
    Am I alone in seeing a trend here?
    Pick a body type that you want and follow that program.
    I do CBL on training days, ESE on alone days or work days and LG on family days.
    This isn’t WWIII you don’t have to chose a side. Do all of them at the same time. Why not.

  • Fing Duck

    What’s the minimum amount of fat and protein grams someone has to eat to keep the anabolic processes going and how often?
    It sounds to me that if someone were to eat 2 eggs at the 12 hour mark (overnight fast) and then 2 more 4 hours later then your CBL meal about 4 hours later you got the best of the IF world and CBL also.
    If you need a goal weight as an example pick 200 lbs and 10% bf and appearance oriented, not performance.

  • Pingback: Intermittent Fasting, Autophagy, and mTOR – Part I | Cogito Ergo Edo()

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  • Al

    Is part 4 available yet?

  • Gabriel

    So, i REALLY cant register my email adress here, which sucks. I will have to ask a question here. I have been training and eating with a bodybuilding mind set for years, and once i found about IF it worked for me much better then eating every 2 hours ( specially the no breakfast which i got from you, and the fasted training) but how would you suggest a diet for bodybuilding in your methods? And the 12 hours schedule of eat and fast? and off course, the fasted training which i love.

  • Ian

    I can’t believe that I’ve just found your website. Thank you for doing what you’re doing, Kiefer. You’ve just won over another science student interested in promoting the truth of health and fitness, through scientific and logical rigor. I have a feeling I’ll be rooting around your site for quite some time. lol

  • Duncan Jones

    Oh bull pippies. The supposed “autophagy” of fast twitch muscle that occurs in IF is merely a temporary recycling of amino acids that comprise glycogen synthase and other enzymes implicated in glycogen synthesis. These are metabolized when there’s no pressing need or ability to make glycogen from glucose because there isn’t much of the latter floating around the blood stream temporarily. Refeed after the fast and voila–the “autophagy” is reversed tout de suite! Independently of this fact, just reality-test your contention. If humans were so frail that they literally fell apart every time they fasted (i.e., they didn’t have food available for a spell), they wouldn’t have survived as a species to write silly posts like this. Careful, or I’ll sic Lyle and Martin on you–and they really know what they’re talking about.

    • Raty

      Interested in Kiefer’s reply.

  • IFworks

    haha Leangains 16/8 works best! For me and for so much other people!
    Muscle gains and fat loss even in advanced lean individuals.

  • Amir

    Hi Kiefer,
    Thanks for all your information….I have been reading your stuff, watching videos, articles etc. for a while now.

    I have a question which I see you have technically addressed with not going over 12 hours of fast. Problem I have found is that while doing carb back loading I am failing to even be the slightest bit hungry until after my workout the next day (say 6pm)…. I consume a strong coffee with MCT oil pre workout just for that boost say 4pm.

    Firstly, do you think that I should force some fat consumption, even MCT oil or cream earlier on in the day to prevent my fast going over 12 hours? It seems I may be smashing too many carbs and/or not training hard enough. Would doing backloading with only consumption of food being the post workout carb up be counter-productive in the goal of nutrient partitioning? I am conscious that my body would begin to forget what fat is and where fat should be sent and carbs/protein to be sent.

    Sorry if this makes no sense whatsoever.