Carb Back-Loading and the Circadian Regulation of Metabolism

Carb Back-Loading (CBL) redux, part I

Step 1: eat little in the morning (maybe some fat+protein; definitely no carb)
Step 2: exercise in the afternoon/evening
Step 3: eat the carbs, all of them.  Preferably high glycemic carbs.
Other: no dietary fat post-workout; protein periodically throughout the day.

What makes CBL different from its predecessors is the stress on the timing – exercise and carbs in the evening.  John Berardi’s “Massive Eating” dietary guidelines are similar: protein+fat meals all day except pre- and post-workout, which are protein+carb meals.  Martin Berkan’s “LeanGains” is fasting most of the time (including pre-workout), exercise in the afternoon, then a big post-workout meal (quite similar to CBL).  My only tweak, as discussed below (and previously here and here), would be a pre- rather than post-workout meal [in some contexts].

There’s a summary of this blog post at the bottom… it might be helpful to read that first (see: “Tl;dr:”).  Also, please note that much of this post is about the fringe of theoretically optimizing nutrient partitioning, like improving from 85 to 90%, or 40 to 45%, not 40 to 90%…  I’m not that deluded.

My initial take, in general, is that this book is loaded with gems about nutrition, exercise, biochemistry, and physiology.  It’s also very readable and has a lot of good recommendations.  In this post, I want to discuss one specific aspect of CBL: tissue-specific circadian regulation of metabolism.


nutrient timing


The following quote is from an article by John Keifer, author of Carb Back-Loading and The Carb Nite Solution

Under the Hood: How Carb Back-Loading Works

Emphasis mine: “We have, however, discovered something useful about the relationship between insulin sensitivity and the time of day. In the morning, cells with GLUT4* react more strongly to insulin than in the evening [6-8]. Think of this as a mini life-cycle that’s reset each night… The same things happen, just on a shorter time scale: we wake up insulin sensitive, and go to bed somewhat insulin resistant.

The circadian rhythm of insulin sensitivity—high in the morning, lower at night—is the main reason why most diet experts recommend eating carbs first thing in the morning, then tapering them off as the day wears on. If all you care about is growing—both fat and muscle, that is—I’d agree with this strategy. If you want to get leaner, though…”

*“cells with GLUT4” refers to both muscle and adipose, although there are some important differences in how circadian rhythmicity impacts the effect of insulin on metabolism in these two tissues.


Disclaimer #1: you have to buy or at least understand the insulin hypothesis of adipose tissue growth to appreciate CBL.

Disclaimer #2: a summary of recent studies comparing ingesting the majority of calories in the morning vs. evening is summarized here (and more below).  In brief, a large body of evidence suggests that skipping breakfast and eating a big dinner may not be the most optimal pattern of calorie distribution.  It’s very nuanced, however, to say the least.

CBL Redux, part II

We know exercise induces skeletal muscle glucose uptake independent from insulin – that’s one of the reasons why it helps glycemic control in diabetics… but according to CBL, insulin sensitivity is higher in the AM, so PM exercise provides a relatively greater boost in insulin sensitivity, selectively in skeletal muscle.  In essence, carbs after a morning workout may be more “fattening” than those after an evening workout.  And CBL stresses that high GI carbs and subsequent quick & dirty insulin spike are necessary for muscle growth (let’s just go with that for now, although I have my share of reservations).

Saad and colleagues did one of the most straight forward studies on this – they measured glucose and insulin levels following an identical mixed meal administered for breakfast, lunch, and dinner (Saad et al., 2012).

The meal: 10 kcal/kg; 55% carb, 15% protein, 30% fat.

The effect: glycemic excursion was the smallest after breakfast, although this was due to increased insulin secretion (seemingly in contrast to CBL theory, which states that “In the morning, cells with GLUT4 react more strongly to insulin than in the evening” …although an earlier study by Gibson suggested both mechanisms may be at play).

After dinner, on the other hand, the glycemic excursion was higher (not necessarily due to insulin resistance, but to lower insulin secretion).

Saad insulin and glucose

The “PM glucose intolerance” phenomenon is relatively consistent in a variety of experimental paradigms (see also Tato 1991,  Dos Santos 2006Morgan 2012, and Gibbs 2013).

Regarding the validity of CBL, does it matter if glucose clearance is enhanced via increased insulin sensitivity or increased insulin secretion?

Why it might not matter(pro-CBL): slamming carbs in the evening post-workout was supposed to be safe because of circadian insulin resistance in muscle and adipose, but exercise reverses this selectively in muscle, so fat tissue will resist growth in the face of a huge surge in insulin.  In this context, lower insulin secretion in the evening could accomplish the same thing.

Why it might matter (not pro-CBL): CBL assumes “insulin sensitivity” means the same thing in muscle and adipose.  However, “insulin sensitivity” is most frequently assessed by measuring blood glucose levels after an oral glucose load (eg, OGTT).  And adipose has a very small role in clearing this glucose… maybe 2-3% ends up in adipose whereas the vast majority goes to skeletal muscle.  In adipose tissue, we’re more concerned with insulin’s effects on fatty acid uptake, lipolysis, etc.; ie, adipose growth.

There was slightly less insulin secreted after dinner relative to breakfast (AUC: 5133 vs. 4858); however, the response of adipose tissue to even very low levels of insulin is swift and robust.  In other words, adipose growth is maximally stimulated at low levels of insulin, such that the small reduction in insulin noted after dinner may have no meaningful impact.

Why it might not matter (pro-CBL): Kiefer cites 3 papers to support the claim, “after resistance training, storing body fat is nearly impossible for up to an hour” (Krzentowski et al., 1982, Bird et al., 2006, and Folch et al., 2001).  On face value, I buy this up to the degree of exercise-induced increase in sympathetic nervous system signaling (increased lipolysis, decreased insulin, etc.).  Further, if this is true, then it partially attenuates the selective circadian advantage of doing this at night.

Why it might matter (not pro-CBL): one of the reasons CBL recommends high glycemic carbs is for a quick & dirty insulin spike, so insulin is elevated to stimulate muscle growth during this hour when “storing body fat is nearly impossible.”  However, as seen in the figure above, insulin peaks at 60 minutes and is still quite high until at least 3 hours…  Furthermore, the Krzentowski paper showed that exercise further delays the insulin response, pushing it farther outside of this post-workout window.  I’ve said in the past, and still maintain that the safest time to “slam carbs,” if you so choose, is pre-workout, because exercise attenuates the insulin response and favors nutrient partitioning.  This would also keep the insulin spike more closely contained within the [theoretical] post-workout hour of adipose growth-resistance.

Part 2. 

Thus far, CBL’s recommendation to slam carbs post-workout (or preferably pre-workout) may be useful.  Kiefer also promotes exercising in the fasted state to maximize fat burning, and while this may be true, it could come at the expense of lean mass (which could be potentially offset, to a degree, by a small protein-rich meal).  Also, I suspect the difference in grams of fat burned above baseline during exercise in the fasted vs. fed state is small (ie, not orders of magnitude).

The theory of CBL “timing” remains on the docket.

What we need are data on circadian fluctuations in the sensitivity of adipose tissue to insulin… WHICH WE HAVE.

Insulin tolerance test: jab a few healthy people with 0.05 uU/kg insulin in the AM or PM, and see what happens (Gibson et al., 1975).  In agreement with the aforementioned studies, insulin caused a greater reduction in glucose in the AM than in the PM (48% vs. 34%).  However, adipose is more sensitive to insulin at night than in the morning.  Insulin suppressed free fatty acids by 47% in the morning but by 64% in the evening.

This was repeated by Morgan and colleagues, who showed that the rate of decline in fatty acids was significantly faster in the PM than in the AM after an insulin injection (491 vs. 149 uM/15 min).

Glucose tolerance test: 50 grams of glucose administered in the PM caused a significantly greater reduction in free fatty acids than in the AM (75% vs. 65%) (Zimmet et al., 1994).

Meal tolerance test (similar to Saad): free fatty acids were lower for ~9 hours after an evening meal compared to an identical morning meal (Sacks et al., 1999).  Also, beta-hydroxybutyrate, a ketone body and marker of elevated fat oxidation, bounced back to a significantly greater degree after the morning meal than after the evening meal (these conditions were controlled for physical activity and pre-meal fasting duration).

Circadian regulation of metabolism: if we think about insulin sensitivity in terms of what it means on a tissue-specific level, then muscle is more sensitive in the morning and adipose is more sensitive in the evening… ergo, a very crude oversimplification of a revised model might go something like this: carbs in the morning are less fattening (due to lower adipose insulin sensitivity) and more muscle-building (due to higher muscle insulin sensitivity) than carbs in the evening.  On the flipside, carbs at night are more fattening because insulin sensitivity is increased in adipose and reduced in muscle.  Thus, an alternative way to think about CBL’s original timing philosophy might be “damage control” …if dessert is your priority, then you need to exercise.  (yeah yeah I know, this doesn’t really work so well.)

Disclaimer #3: I don’t think the differences are going to be quantitatively more important than, for example, “adherence.”  That is, if sleep quality is high (a necessary pre-requisite) and your diet is in check, then exercising at the wrong time won’t screw up your progress… sleep and diet just seem more important than exercise timing, imo.

Part 3.

As mentioned above, there is a large body of evidence suggesting that for the casual dieter, consuming the bulk of the total food intake earlier in the day may be more effective for weight loss and body composition.  Tissue-specific circadian metabolism agrees.  Inconvenient, perhaps, but these data cannot be overlooked.

However, in at least one study (Sofer’s Israeli cop study) limiting carbs to dinner on a hypocaloric weight loss diet was better than spreading them evenly throughout the day (it’s admittedly not a perfect comparison)… those assigned to eat carbs only with dinner experienced a greater improvement in body composition – they lost more body fat and less muscle (+1!)… although this may have been somewhat confounded because the dinnerCarb group had more fat mass to begin with, and this condition is known to favor greater fat loss on a given energy deficit.

And this study, which Joseph Agu included in his review of CBL (Keim et al., 1997):  70% of the food was given in either the AM or PM.  The results showed that while the AM group lost more weight, they lost more muscle and less fat than the PM group (-1!).  HOWEVER, the researchers bollixed the crossover. *ugh*  That is, there was no washout period.  This is a grievous error and an insult to the crossover study design.

See also Martin Berkham’s review of AM vs PM eating here, and Layne Norton’s review of ‘carbs at night’ here.

Conclusion and my “opinion”

I love the basic premise of CBL – using exercise to selectively improve muscle glucose uptake at a time when insulin sensitivity is low, to improve the relative safety of carb-loading… however, adipose is exquisitely sensitive to insulin, and this only seems to increase as the day goes on (in contrast to muscle, which goes in the other direction).  That said, Kiefer’s definitely not an idiot… there are some flaws in the studies which support CBL (eg, Sofer and Keim), and some potential setbacks with the circadian aspect of it… for example, melatonin seems to enhance insulin’s anabolic effects on adipose; so a high carb meal in the evening runs the risk of a big overlap in insulin, melatonin, and an extended period of physical inactivity (when you’re sleeping)…

Furthermore, as mentioned above, regardless of when exercise is performed, you’ll still get the benefits of exercise-induced muscle glucose uptake (possibly more so in the evening), but there seems to be no selective advantages of mega-carb-loading at night [or ever, some might argue]…

Will CBL work?  Sure, for some, especially because of “convenience” (which I suspect is definitely not what the author wants to hear) – skipping breakfast, late afternoon exercise session, big dinner… easy peasy!  But the reverse may be equally effective: peri-exercise is the ‘safest’ time to carb-load… but it’s not clear [to me] that doing this in the evening has any body recompositioning advantage over the morning, biologically speaking, circadian proper.

There might other benefits, however.  For example, anecdotally, some people report being able to lift heavier weights in the afternoon than in the early morning.  That could very well be true, and might be very important in certain contexts.

All in all, CBL a pretty good book, and covers much more than what I reviewed here, which is mainly just one minor point: the circadian aspect of tissue-specific insulin sensitivity.  I’m not a huge proponent of carb-loading (back, front, or otherwise) (would prefer to see a higher protein:carb ratio for body composition), but it seems as though CBL would work just as well, if not better (in theory), if everything was shifted to earlier in the day.  Am I missing something?  Postprandial glucose clearance is a surrogate for muscle not adipose insulin sensitivity.  The studies on adipose insulin sensitivity show that it is relatively higher in the evening, so this may not be the best time to slam ze carbs.


Original CBL model:
AM: high insulin sensitivity; carbs now = muscle & fat growth, exercise may only offset fat growth due to improved nutrition partitioning.
PM: low insulin sensitivity; carbs now = exercise necessary to improve muscle insulin sensitivity leading to muscle but not fat growth.

New proposed model, incorporating the circadian regulation of metabolism in adipose tissue:
AM: high muscle insulin sensitivity, low adipose insulin sensitivity; carbs now are OK, and exercise is better (but not necessary, unless goal is muscle growth)…?
PM: insulin sensitivity low in muscle, high in adipose insulin; carb-loading now requires exercise to increase muscle insulin sensitivity and offset the high adipose insulin sensitivity by improving nutrient partitioning.


calories proper

Follow-up: Carb Back-Loading, take II

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  • Chris

    Jack Kruse talks about the leptin-melanocortin pathway in his CT series. You might as well get some insight from there…

    besides the fact that carb intake is very dependent on the circadian rhythm, it is also season dependent and location dependent, imho.

    there are way too many variables to include in the equation but you can make it simpler:

    become keto-adapted (usually takes a lot of time), become cold adapted, and then you wont need carbs to support your cravings and your workouts. may seem pseudo-science, but there are tons of examples proving it…though I may wanna look at those disproving it and debate them…

    either way, nice post Bill

    • William Lagakos

      Thanks, Chris (do you prefer “Cristi?”)

      The issue of leptin signaling frequently comes up when people talk about carb re-feeds, but CBL is a different beast altogether. CBL is carb-loading after every exercise session, which means no ketosis (if you exercise regularly)…

      Also, I tend to agree (and have speculated before) that a similar goal may be achievable with adequate ketoadaptation, but would likely require high[er] protein intake…

      • Chris

        I dont think it does require higher protein if you’re cold adapted because proteins behave thermoplatically, as I tend to believe what Jack mentions here

        I also find it not valid in my day to day experiments…there have been weeks when I drastically reduced caloric intake due to CT, reduced protein intake and was able to exercise quite intensive – both heavy lifting and HIIT…of course, this is n=1, but I truly believe we can behave very differently if we cold adapt.

        • William Lagakos

          “was able to exercise quite intensive – both heavy lifting and HIIT”

          that’s a good point. I think ‘higher protein’ is more of a long-term investment; it doesn’t provide immediate fuel for exercise per se, but rather works toward building/maintaining lean mass.

          • Thomas Hemming Larsen

            That’s a very good way of phrasing it. You should use that in a future post.

        • Jack Kruse

          Insulin has different pharmacokinetics by temperature. It simply does not do what most think it does in cold whether. Ling’s experiments on frog muscles were crazy good and smart and reproducible SO much of what we believe about biochemistry is totally gone once you realize how just temperature changes insulin physiology. Then when you realize that temperature changes directly scale to the level of electrons and protons…….you begin to see a new scale of cycles you missed. And that cycle is critical in understanding how a cell really works.

          • Jack Kruse

            The law of mass equivalence scales everywhere in the universe. Few realize it.
            How electrons work in mitochondria, which are derived from food seems to offend the “common sense of biology.” I find this concept to be a very good thing because the the principles of relativity, quantum mechanics and quantum vortices in black holes also offend biology. This is the way nature works in us, and across the whole universe. I have said this here and many times before……..mitochondria are nothing more than dealers in electrons and protons. It is time you all begin to bring your scale of understanding to the quantum level.

          • William Lagakos

            the use of resonance energy transfer assays to measure certain aspects of protein-lipid interactions is a testament that this isn’t “nuts”


          • Ash Simmonds

            Funny thing – we only find black holes by looking for something we can’t see.

            I mentioned this years ago, but I think the appearance of a DAF-2 gene – or the equivalent thereof – will be apparent in humans sometime in the next 10-20 years.

          • Ash Simmonds

            >Insulin has different pharmacokinetics by temperature. It simply does not do what most think it does in cold whether. Ling’s experiments on frog muscles were crazy good and smart and reproducible–

            That’s real interesting, except frogs are ectothermic.

            Even with half our lives dunked in ice baths with bulletproof nipples hoping to achieve cold thermogenetic zen our species will never get close to the ho-hum chillax a frog is able to maintain.

            Sure, hormones and biochemistry are completely different under radically different thermal conditions, but what the hell can I do about that as an endotherm?

          • Jack Kruse

            The key Ash is what an electron does to a protein. It ionizes it to change its function. That is why the movement of electrons can take 20 amino acids and 23,000 genes made from those amino acids and make millions of different proteins. The addition or subtraction of said electrons determines the proteins final chemistry by bending it and shaping it to give it is function. This is the beauty of thermodynamic compliant design. It is the quantum mechanism that all life uses to function. When you realize this you see how insulin function changes as the environment of electrons around it changes. Nature is the driver of nurture. The building blocks are the template we alter with the information from the environment. This is why circadian biology determines the function of how a mitochondria can and can’t work.

          • Ash Simmonds

            Yar, insulin function and thermodynamism is all great in theory, as yet I’m unable to reduce my core temperature much below a bleu steak, so practical me sticks to stuff about my biology I can actually influence.

          • Jack Kruse

            Well Ash let me make it more digestible for you. Thermodynamism is a universal physical law. Insulin is a protein moves electrons around in certain proteins and affects the hydrogen bonding network in water. At you current level of understanding this won’t make an impact upon you yet, hence why you mock these ideas using a bleu steak analogy. Now consider this: Cations, like K+, may induce strong cooperative hydrogen-bonding around proteins like insulin due to the polarization of water O-H by cation-lone pair interactions. This is why potassium, K+ is considered water’s glue in a cell. It acts as chaotrope to increase the amount of hydrogen bonding in intracellular water. This allows water to maximally transmit energy and information flows over its hydrogen bonding network. This is the basis of water’s memory that Noble Laureate Luc Montagnier has found in his experiments. Gilbert Ling was the first person to realize the importance of cations actions to making water act coherently with proteins. The more hydrogen bonding is present in water the more useful water becomes to help “sense” the environment it is in. When you marry this ability with that of DHA and collagen you building a very sensitive electromagnetic antenna to sense the native EMF’s on Earth for life to organize around. This is why circadian biology dictates everything. The movement of these cations is what causes water to alter its molecular structure by altering hydrogen bonding networks. This changes its ability to carry energy and information directly, and alters its physiologic abilities.

            The effect is reinforced by additional polarization effects and the resonant intermolecular transfer of O-H vibrational energy, mediated by dipole-dipole interactions and the hydrogen bonds. Reorientation of one molecule induces corresponding motions in the neighbors. This is why the information in my blogs OSF 3-5 information about polarization changes should begin to resonant now. When polarization changes in water or proteins it means tissues have lost their ability to sense information and energy from the environment. This is how we fundamentally lose our circadian signaling.

            Thus solute molecules dissolved in water can actually ‘sense’ these changes. They do it by reacting to the effect each other’s solubility in this water. This directly changes the hydrogen bonding network angles. When halogens are in water they also reduce the hydrogen bonding network. The smaller atomic mass halogens like Fluorine, Chlorine, and Bromine reduce water’s dielectric constant. Halogens act as ionic kosmotropes and they lower hydrogen bonding networks and they also lower the size of the exclusion zone in water possible within a cell. The biggest halogen is iodine. It has a beneficial effect on the Exclusion Zone of water, and its hydrogen bonding network. Iodine also protects DHA from oxidation in neural synapses. It has an atomic mass of 127. Spectroscopic studies of the hydrogen-bonded structure of water around the halide ions F-, Cl-, Br- and I- indicates that the total extent of aqueous hydrogen bonding increases with increasing ionic size. So the experimental data matches the beliefs you find in my theories. Ling’s data in frog’s muscle where the first time ever science got these clues and they still do not understand its massive importance.

          • Ash Simmonds

            Digestibility and mockery aren’t the issue here, I don’t pretend to get half of this yet, but I am much more interested in it than I am of the abstractions we end up with.

            However you’re missing my point there, it’s great to have a bunch of information but just like in the stuff I’m keen on such as theoretical physics there comes a point of what’s actionable, and what’s simply interesting in the case of “it is what it is”.

            I’ve read through the response twice and what I get makes sense, the other stuff pushes an expansion bubble in my brain that will tick away for a while for me to come back to.

            But in the end as I said from the start with the frog – what does that mean for us? What on earth can we do for modifying our insulin signalling thermodynamically, short of a transfusion with lizards?

            Great thought experiment, but otherwise pointless. Not saying don’t continue, but I’m half thoughtful theory and half practical, so when I say “what’s good about this?” I’m wondering if there’s any reality-based application for the information. It’s kinda why I gave up “quantum” physics in my early 20’s – that shit never got me laid.

          • Jack Kruse

            Ash nature is actionable. Its good water, DHA and paying attention to circadian biology. How hard is that? Today modern science truths are dead wrong. They remain in place because they have power not wisdom. With everyone speaking different languages in science, the truth is almost impossible to agree upon. I have chosen quantum language because it is the language of nature and not modern science. The truth is actionable and powerful when you realize her messages. Yet believing in the existence of truth is the only thing that keeps us from devolving into warfare on many of these issues. Because without the existence of truth, the person who is most powerful becomes the person who is right. Today’s scientific truths permit a temporary stability. Today’s chronic diseases make you realize our current truths are in fact temporary. Here is our irony: Man is the only creature intelligent enough to think themself to death. In order to pursue greatness we first have to understand where our source of greatness lies. It is in the quality of our thoughts. The truth only irritates those it enlightens. We must pursue these thoughts. I try never to be irritated by the truth but to engage with enthusiasm and good cheer in the pursuit of authentic knowledge and genuine wisdom. I don’t care what the truth turns out to be, I want to know the truth. I have no fears or reservations of where nature’s truths may lead me. Competence is a function of individuals, not their degrees or the certificates they hold.

          • Ash Simmonds

            My water is either spring/mineral or whatever comes in the bottle with fermented grapes. :p (I don’t know if that does anything to activate/EZify the stuff)

            Up to a third of my food is fatty fish, wild/unadulterated when I can, and shellfish/oysters as often as I can.

            My circadian biology goes through periods of zen and abuse. Last year I spent living in a shack on the beach with nothing to do but wander the earth and ocean barefoot – between spirited country drives in an exotic sports car – then sit by a fire for an hour or two after dark.

            This year however I’m back in a cramped high-rise apartment in the CBD, researching/writing way too much often to 4am – I can definitely feel the difference in exposure to an ELF/EMF laden concrete jungle full of busy-ness, zen is difficult to achieve in these circumstances, agitation seems to be the default feeling around here, so I slog away sacrificing short-term circadia to the net benefit of a 2015 that heralds a return to sand in the toes and crackling fire in the night.

            “Truth” is a fluid concept, at best a misnomer.

          • Jack Kruse

            Here is our irony: Man is the only creature intelligent enough to think themself to death. In order to pursue greatness we first have to understand where our source of greatness lies. It is in the quality of our thoughts. The truth only irritates those it enlightens. We must pursue these thoughts. I try never to be irritated by the truth but to engage with enthusiasm and good cheer in the pursuit of authentic knowledge and genuine wisdom. I don’t care what the truth turns out to be, I want to know the truth. I have no fears or reservations of where nature’s truths may lead me.

          • Ash Simmonds

            That’s basically my “it is what it is” philosophy.

            I want to understand as much about a given subject as per it sparks my interest, but at a given point the ROI on knowledge without practical application no longer propels the feedback loop.

        • Ash Simmonds

          CT has it’s place, but I fail to see how being “cold adapted” has much resonance on overall performance.

          I’ve proven to myself that the less caloric load over the previous 24-36 hours I’ve had the better I am at extended physical performance. But reduced energy intake is only something you can do for specific limited periods – unless you’re mad!

          Higher protein is neither here nor there. Protein should NEVER be an energy source, it’s role is structural, and those “weird” problems people get on high protein/low fat diets are pretty easy to see in this context. Over-eating protein is like giving a cement truck heaps of sand and metal but no fuel to mix it.

          Source: I used to be a cement mixer guy.

    • Jack Kruse

      The missing piece is how WAT, BAT and muscle’s circadian cycle yoke to mitochondrial circadian changes. When they are yoke well you can get great benefits from IFing or CBL, but this is not where most patients find themselves. Most people today, even the fit one’s have blue light toxicity. This alter’s the delta psi on the inner mitochondrial membrane and directly alters the cytochrome’s yoking to the tissues. This is where it gets difficult for people to follow. I think I shared this video with Bill in the past and Peter of Hyperlipid also picked up on this. Here is the link showing the complexity by Dr Doug Mitchell: The circadian cycle determines the epigenetic switch position. It is very hard to change unless you first correct the circadian mismatch. Anyone who has travelled east far enough can attest to the effect of jet lag. This is a short term phenomena of how environmental changes directly impact mitochondrial energy dynamics. Inside a cell there are hundreds of thousands of interaction on going constantly and our CM are peppered with receptors which also have a circadian cycle. All are designed to work within our normal cycles. When they do not, the result is an excess of positive charge from ROS and RNS. Both of these signals to an excess active change programs in mitochondria incorrectly from how they should work. These chemical reaction are going on constantly below our awareness. Because we do not perceive these staggering speeds in spaces too small to comprehend there is nothing else we can compare it to in our experience. This is because chemistry is taught and understood on the wrong scale. At the quantum level, activity is taking place at speeds that make chemical reactions seem lethargic and they happen in spaces that make a cell feel cavernous. This is the scale where chemistry gives way to physics. This is where people begin to think I am nuts. I am not. I see the phase transition tied to energy. Physics is the study of the very small subatomic world and the very fast, (186,000 mph) speed of light. On one hand, chemistry deals with biology and provides the explanations for the processes of life. On its other hand it mingles with physics and finds explanations for chemical phenomena in the fundamental processes and particles in our universe. Remember electrons give all chemicals their unique chemical properties. Same thing is true of proteins. Today scientists and clinicians are not following chemistry to the level of physics. This is what happens in a mitochondria. I do and I am. Since they do not follow it how can they be sure they are not missing the most important and fundamental aspects of what is going on in any cell? They cant. Their experiments can not measure what they do not know what to look for. The video above shows you there is a lot about mitochondria scientists are clueless about. We can only find answers to the questions we CHOOSE to ask. Today scientist believe that biochemistry and genetics is all there is too understanding the cell and that is all they will consider studying. Quantum biology is the domain of mitochondria and circadian biology. You must understand that to ask the RIGHT questions. This is why biochemistry will solve nothing. Bill, Peter and me are the few who are beginning to look deeper than biochemistry.

      • Jack Kruse

        Consider the Human Genome Project. It is a parts list for the human body. Now that we have this parts list in detail it does not tell you what the pieces are or how to combine them into anything useful for life in a cell. What joins them and controls them is tied to another scale. That scale is the quantum one. Remember 98% of our DNA is viral retrotransposon’s we used to call junk. Now we know this junk contains the owner’s manual of the part list. Yet, today cancer and obesity researcher’s remain focused on the part list for answers and not the junk which is controlled by the electromagnetic force. Why? They don’t study what they they do not know.

        • Jack Kruse

          There is another teleologic problem. chemistry and biology believe you can measure anything in an experiment. In the quantum scale you can not. Why? The uncertainity principle. Subatomic particles are so small and so fast that many were considered not to be a structure of matter. They were not considered material things. and the concepts of measurement and observations, two words used often in biology and chemistry, take on new special meanings in the quantum scale.

          • Jack Kruse

            Things a mitochondria do happen on a quantum scale. This means electrons from food can acts as particles or probability waves. It also means there is no cause or effect because you can not know all the variables of electrons at any one time. Electrons carry charge, power, and information. When you observe one aspect of the electron you can only guess things about the other two. The Pauli exclusion principle shows this queer effect. The double slit experiment does too. The de Broglie-Bohm pilot waves also explain this queer phenomena. Biochemists do not understand how to tie this to biochemistry because they are looking at things on the wrong scales. QED says that just the act of measuring and observing electrons alters and drains their energies. This means you can never truly know anything. Very counterintuitive to most until you understand what a mitochondria does. It takes electrons and controls their movements in cytochromes, MINOS and water to tell specifically what all three parts of the electron contain and we use that to build a zero entropy system. DHA is the only lipid that can capture electrons well so it must make up most of the CM in humans for mitochondria to be able to this. This is why carbs electrons enter cyto one and tie to the NADH levels. Fats and proteins enter at FADh2. This separates food electrons based upon the added photon power from long light cycles. The spin is controlled by the proteins in the cytochromes to affect their bond angel rotations and this is coded by changes in quantum time through the mitochondrial cytochromes. The 3 D molecular arrays is what determines the proton signals a cytochrome gives. This is where ROS and RNS signals begin.

          • Jack Kruse

            People think this is nuts until they look at what makes up a protons and realize that is component quarks when summed together fall far short of the mass of a proton. What makes up the difference to get a protons mass? Energy does. That energy is what the mitochondria takes full advantage of. This is why measurements done macroscopically never see the energy drain that occurs……..with all subatomic particles. Mitochondria and photosynthetic antenna however can account for these changes in energy to make life go. Until we get Bill’s and my colleagues to think about creating experiments to scale to this level we are living a lie. Time links to mass, energy, and both tie to DHA. No one seems to see it yet, but you must if you want to really change things in this modern world for patients. Researchers and clinicians do not realize that the use of carbohydrates out of season and blue light toxicity are the major factors in destroying mitochondrial signaling in our modern world. Both tie to alterations in circadian coupling in cytochrome proteins. This alters quantum timing. This time is so fast no one thinks it matters. It does to the proper cytochrome physiologic function. When timing is off, we lose power to our environment. When this happens masses increase and chaos ensues and protons increase and electrons decrease in a mitochondria. Food and exercise react to these changes they do not cause nor can they reverse these quantum 3 D molecular changes. The idea that an ‘imperfect hypothesis’ must be wrong, I have no time for any longer. Every early version of a good idea needs modifying. The best hypothesis is the one that is strengthened by nature, instead of undermined by its inevitable modifications. To borrow a metaphor from astronomy, we are still at the Copernican epicycle stage in modern biochemistry, but that’s better than being on a flat earth at the center of the cosmos, which is where ancestral health and modern medicine are today.

          • Chris

            I really need to get my head stuck into “Life at cell level and below”. I know you recommended the book. I’m still reading and pondering upon Hameroff’s: Ultimate Computing…

            Jack, those who think you’re crazy, they are crazy…You are way ahead of our time, same as Hameroff was back in the 80s and still is today.

          • Jack Kruse

            People who are way out in front are often looked at as nuts until people realize what we are saying and then look at the science already published that supports the craziness. It is there. Bill has tapped some of it. There is a lot more to do.

          • This Old Housewife

            +1. I used to read Aubrey DeGray’s stuff until he started watering it down with “everyday common man” stuff. Apparently, the British government asked him to start writing about how regular people can lengthen their lives, and to avoid writing about the science-fiction-type stuff. Science fiction gave us the WATERBED (Heinlein), Star Trek gave us the cell phone (I’m still waiting for the stun setting), and NASA gave us Velcro, the Tempurpedic mattress, Tang, the Bloom Box, and god knows what all else.

            My husband’s a SF collector, and can rattle off which author gave us the idea for what.

          • Jack Kruse
        • William Lagakos

          I attended a talk about a polymorphism which markedly increases the lifespan of C.elegans – the worms lived *significantly* longer. During the Q&A session, someone asked about the specific mutation, and the speaker told us it was in the “Junk DNA.”


          • Ash Simmonds

            Oh, I mentioned upstream that I’ve talked about that years ago – I can probably speak more intelligently on the subject now, but it’s still a good overview for others:


            I also keep track of anything to do with negligble senesence etc, I’ll be expanding my stuff on this soon enough:


          • rs711

            Only 1.5% of our genome codes for proteins. Expect mutations to occur mostly outside that 1.5%.

            What really clinched it for me in terms of grasping the complexity, was knowing just how far a chromatin loop could join 2 distant DNA sequences to get promoters & regulators closer to one another…it puts the whole information genome into perspective, showing you the seemingly limitless combinations that can occur – even with only a tiny bit of our genome actually coding for proteins. That figure is deceptive. Basically, we don’t need more because our mix-&-match capacity is what confers us adaptability but is also what makes understanding genetics so damn difficult.

          • William Lagakos

            it’s very deceptive! Eg, a protein can have different functions in different contexts, cell types, etc… so should it count as more than one protein? (what if one version is glycosylated, another palmitoylated, another differentially spliced, etc…)

          • rs711

            It’s easier to understand if you leave the 1-gene-1-protein paradigm behind. Rather, it’s more like a ‘repository’ of ‘minimum starting parts’ which can then be modified to a dazzling extent: in post-transcritional & post-translational mods, splicing, frameshifting, missense mutations etc.

            I’m not sure when & where exactly the glycosylation & palmitoylation occurs (& for which protein specifically) but nonetheless this cannot happen to early on in gene expression. It’ll depend on transport-partners, substrate availability and so on…

            This is where I prefer to start thinking of things as information..rather than as ‘lego blocks’, as the common analogies would frame it.

            Since quantum mechanics looks at a distribution of probabilities (information) then maybe this is where the link can start to form…

          • Jack Kruse

            Life is not built for our comfort of understanding. She weaves her web using the 4 forces of nature. It is ourt job to see that magic. It is all physics and the movement of charged particles in mitochondria.

        • rs711

          “Junk” (nuclear) DNA is just scientists sucking at naming things. It is not junk, its function is simply unknown. Speculations: Junk DNA may well be a ‘spacer’ element which provides ‘order’ to the information parsing network, that is the feedback signals modulating chromatin & activity and in turn the expression of DNA.

          Is there a specific, well-controlled experiment you can point me to showing how this understood biochemical interplay is being governed by EMFs? I ask because I am studying both “Molecular Biology of the Cell, 5th Edition – Alberts & Johnson et al. (2007)” & “Human Molecular Genetics, 4th Edition – Strachan & Reid (2011)” do not even allude to this yet (as expected).

          PS: I watched that entire lecture when posted on Peter’s blog. It brings support to single-electron events without explicitly invoking the need for quantum-biology (yet).

          • Jack Kruse

            This is what I have on my office laptop. Dr. Vlail Kaznacheyev, Director of the Institute for Clinical and Experimental Medicine in Novosibirsk, showed that a virus can be transmitted from one culture plate to another using ultraviolet light. Thus, information is being carried with photons that have been “structured” in one culture plate to another culture plate. Some Russian scientists believe that this effect is being carried out by “torsion” energy.
            • Dr. Dzang Kangeng in China showed that light passed through a duck into 500 chicken eggs resulted in chicks in which 80% had flat bills, 90% had eyes moved to a position similar to ducks and 25% had webbing between their toes. Their offspring remained partial duck, partial chicken.

            • Dr. Gariaev directed green laser light through salamander eggs and then through frog eggs. Salamanders hatched from the frog eggs. He has coined the term “wave genetics”.

            • Nobel Laureate virologist, Dr. Luc Montagnier (who shared the prize for discovering the HIV virus) discovered the apparent ability of DNA fragments to “regenerate” themselves using an electromagnetic field. Two separate tubes were placed in a copper coil and subjected to an electromagnetic field of 7 hertz. One tube had a DNA fragment and the other tube just had pure water. After 16 hours, the tubes were subjected to the polymerase chain reaction (PCR) to create replicants of the DNA (the standard technique that enzymatically makes many copies of DNA to enable measurement of DNA that is originally in a small quantity). The DNA was found in the tube with just pure water. The hypothesis is that the DNA structure is preserved and amplified through quantum coherence in the water tube and the PCR process mistakes it for the DNA itself. His work is published in Nature in 2012-13.

            In order to gain some understanding of the mechanism involved and to see how consciousness plays into the effects, one can look at the work of Dr. Fritz-Albert Popp at the International Institute of Biophysics in Germany. The hypothesis: DNA interacts strongly with coherent laser light and affects the NH…O and NH…H hydrogen bonds. Biophotons from all parts of the body are coherent (not random) and thus can allow communication. Machinery of each cell coordinates its activities by exchanging biophotons with other cells. Organization occurs cooperatively using a pattern supplied by the DNA. The DNA acts like a photon store and will raise the energy levels of molecules, preparing them for a chemical reaction. Consciousness may affect the non-local field (like a torsion/bioenergy field) which affect DNA which affect biophotons release which affect chemical reactions such as protein synthesis.

          • rs711

            Thank you for pointing me to starting material. I will look through it more thoroughly at some point (time permitting!).

            Just from the description of the experiments I can already see that methodology and controls would need to be of such a high standard that I even wonder if we have this ability yet…? This is where I usually call on help from physics &/or chemist friends.

            Furthermore, let’s say those experiments show exactly what you say they show – they’re still ‘proof of concept’ at best. Extrapolating effects to biochemistry as we know it would need lots more experiments (decades & decades & decades)…if we were to do this confidently & less speculatively, that is..

            Never say never…this is exciting!
            Again, thanks for your patience with those of us who aren’t quite physics/chemistry literate.

          • Jack Kruse

   Just so you know physics experiments already can do these controls………biochemistry does not realize it yet because they do not read their journals as I do

          • Jack Kruse

            And to show you just how much science has missed: Consider now biology is just realizing what I been saying and yet they still miss the key issue: If a bacteria do this and we ultimately evolved from them how do we twist this ability in us in our mitochondria?

          • Jack Kruse

            And along the lines of Fritz Popp work and Montagnier’s recent work a Russian scientists performed and reported an experiment many find hard to believe and it has not been reproduced as yet: Dr. Peter Gariaev, Director of Wave Genetics in Russia, performed an amazing experiment. When DNA, under vacuum, is exposed to a mild laser light, a sensitive photomultiplier instrument can pick up the signals from the DNA. When the DNA is removed from the container that held the DNA, the photomultiplier still picks up a structured photon presence and does so for about 30 days (the “phantom DNA effect”). Standard science says this cannot occur. Since it did occur and is reported, the DNA has structured the photons in this space, i.e., established a pattern in the field. This experiment gives us insight on the mechanism of messaging using DNA. I think it needs to be reproduced first.

      • William Lagakos

        “It is very hard to change unless you first correct the circadian mismatch.”
        +1! I believe this is true, in a variety of contexts.

  • Jeff Rothschild

    Good stuff! Regarding morning carbs, wouldn’t it be better to further divide this between fruit and starch? Liver glycogen stores should be fairly low in the AM, while muscle glycogen should still be topped off. Having something high in fructose should go towards filling liver glycogen and not raise insulin too much, as opposed to having a bowl of potatoes which don’t really need to be taken up into the muscles since their stores are full from last night’s carb binge at dinner. Am I off on this?

    • William Lagakos

      Hi Jeff, thanks!

      For the sake of this blog post, I was trying to play by the rules set forth in CBL… which would’ve meant, from a biochemically extremist perspective (“no fun”), no fruit OR starch, but rather only straight dextrose (highest glycemic index)… in this context, I don’t think filling glycogen stores is really the end goal; it’s just a byproduct of the carb-loading done to spike insulin levels, which provides the anabolic stimulus to muscle.

      That said, low liver glycogen favors increased reliance on fat & fat-derived fuels [in this context]… so you may not really want to intentionally “top-off” liver glycogen…

      • Ben

        I wonder how liver glycogen utilization varies given the context of a high fat diet? My guess is that there is a glycogen sparring effect that results from lowered fatty oxidation costs. Alternately, it probably becomes more important to keep glycogen topped off once you hit a certain body fat percentage as the propensity to mobilize fat decreases (becomes more costly.)
        Personally, I am naturally lean, I don’t work out much, and I carb load almost every night. I have had some notable improvements in energy during the first half of the day. Not sure if this is sustainable or if my results would be better through augmenting some variable. However, I do suspect that having a well stocked liver glycogen reserve holds it all together.

        • William Lagakos

          a lot of interesting points!

          “I wonder how liver glycogen utilization varies given the context of a high fat diet?”

          A few [~dependent/independent?] variables here: liver glycogen is lower on a low carb diet, but can be replenished with high protein meals. And I think I agree, liver glycogen “spared” with a high fat diet.

          “Alternately, it probably becomes more important to keep glycogen topped off once you hit a certain body fat percentage as the propensity to mobilize fat decreases.”

          I actually don’t think this is physiological; body fat would have to be extremely low, maybe even pathologically low…

          That said, I don’t really put a high value on *full* liver glycogen; when it gets low, gluconeogenesis takes over (I also don’t view gluconeogenesis as a pathological or problematic process).

          • Ben

            Hmmm, I still suspect that there is some sort of mechanistic
            regulation of fat mobilization that has somewhat of a continuous relationship
            with the total amount of body fat stored, as opposed to a sort of binary
            condition in which fat is mobilized at a relatively constant rate until it is nearly

            Generally, I think that it is more unwieldy to try to
            maintain inefficient metabolic states like ketosis or even gluconeogenesis in
            people who are already lean. I think the result is that you wildly oscillate in
            your energy levels. For lack of a better phrase, I think metabolism “slows.”
            Like it can’t produce as much energy from a given amount of metabolic substrate,
            and more substrate can’t be mobilized to make up the difference. Of course
            genetic adaptation through enzyamatic upregulation reduces inefficiency, but I
            think there is still something of an ebb and flow that is unavoidable. From a
            biological perspective, it makes sense that the body would first allow lower
            energy and hunger in an effort to encourage food acquisition.

            “liver glycogen is lower on a low carb diet, but can be replenished with high protein meals.”
            This makes me think that the the people like Dave Asprey who regard nutritional ketosis as a panacea, are encouraging unnecessarily difficult diets. Shouldn’t gluconegenesis be easier and less volatile than nutritional ketosis?

          • William Lagakos

            for just “shooting from the hip,” you make some pretty good speculations!

            Nutritional ketosis isn’t a universal panacea, but it has it’s place… very effective in some cases of intractable epilepsy. And it seems to spontaneously normalize appetite in obese populations.

            But yeah, fairly restrictive, and many benefits can be had with a fairly low carb “paleo” template.

            “Shouldn’t gluconegenesis be easier and less volatile than nutritional ketosis?”

            I’m not really sure what you mean here; they go hand-in-hand, and I don’t really view gluconeogenesis as difficult or problematic…

          • Ash Simmonds

            This is where there’s some major disconnect, *SOMEWHERE* out there people are “learning” about ketogenesis and gluconeogenesis but are being told it’s some super volitile and difficult process – like you need SWAT training and to wear a bomb disposal suit to even consider it.

            I think 90% of the whole online arguments with this stuff would evaporate if GNG especially wasn’t so badly misrepresented/misunderstood.

          • William Lagakos

            This isn’t the first time “GNG=bad” has come across my radar, but it’s like a myth or something – no one can point me to where it started. Even the people that believe “GNG=bad” don’t know why.

          • Thomas Hemming Larsen

            Its because of the ketone love some people have (Jimmy Moore). Peter Attia has also mentioned several times that too much protein will lower your ketones because of GNG but he has never said its a dangerous process. Some people equate the level of ketones to general health.

          • William Lagakos

            I don’t think protein is the bad guy, either!


          • Thomas Hemming Larsen

            Haha, Bill. I could accuse you of many things but thinking protein is bad would be the absolutely last one! 😛

            On a serious note. I’m sincerely happy that you’ve somewhat convinced me to eat more protein. It has definitely improved my satiety and I’ve been able to put on some muscle. And, dare I say, lean out a little.

          • Ben

            Assuming a diet that is not deficient in calories and low carb, can’t this state be accomplished within a spectrum of protein to fat, thus gluconeogenesis to ketosis? My thought was that gluconeogenesis(beyond initial accusation) is comfortable given a high enough protein intake. On the other hand if one is shooting for ketosis they are intentionally limiting protein. So in the latter case, if something goes wrong and you don’t produce enough ketones then you’re stuck because you also don’t have enough readily available protein for gluconeogenesis. So that was my basis for thinking that ketosis is more unweildy than regular low carb.

          • Ash Simmonds

            GNG is *demand driven*. You don’t just willy-nilly glucate your body just because a few years ago Jimmy Moore said “excess protein is like chocolate cake”.

            GNG doesn’t even require significant exogenous amino acids – the glycerol backbone plus other precursors from triglyceride oxidation (fat burnin’) is plenty enough to supply a vast majority. The amount of protein you rip from your body is ridiculously tiny, and only used as a substrate precursor for GNG in EXTREME circumstances like actual starvation – ie bodyfat below critical levels.

            Ketogenesis is only really suppressed a little because of any insulinogenic properties of whatever you ate/did/injected.

            I see almost no scenario where there aren’t enough (or too many) and/or glucose/ketones to do their job outside of a seriously fckd up metabolism – in which case that person is probably already dead.

            Ketogenesis isn’t “unweildy” – it’s the default state in the absence of carbohydrates.

            It’s like calling sobriety unweildy – you can only achieve it by not consuming ethanol.

          • William Lagakos

            ^^^ what he said.

            “GNG is *demand driven*.”

            Ben, this is a good way to look at it.

            1) ultra-high protein meals don’t cause hyperglycemia

            2) you can inject mice with loads of gluconeogenic precursors and blood glucose doesn’t budge (personal observation).

            3) I would only disagree with the quantitative aspect of it: the contribution of amino acids to gluconeogenesis is greater than glycerol and lactate (cite Cahill & Westman)…

          • Ben

            “Ketogenesis isn’t “unweildy” – it’s the default state in the absence of carbohydrates.””
            In describing ketosis as unweildy, I wasn’t implying that you won’t produce ketones, that ketosis is a binary state, or that it is bad. I was refering to the variation in the subjectivity of how that metabolic shift affects one’s energy level. From my own experience, I think that there are variables that affect how ketosis and low carb make you feel. I think that there can be variations in metabolism that affect the amount of energy that you are producing given that the body is in a low carb state and that the body has adjusted through GNG and ketone production.

          • William Lagakos

            …a spectrum: ketosis reduces the need for gluconeogenesis because many tissues reduce glucose consumption in favor of ketones.

            “So in the latter case, if something goes wrong and you don’t produce enough ketones then you’re stuck because you also don’t have enough readily available protein for gluconeogenesis.”

            This doesn’t happen: if not enough dietary protein is available; 1) there’s still plenty of glycerol and lactate; and 2) the body will seamlessly transition to skeletal muscle amino acids (which is more a function of starvation as opposed to level of dietary carbs)…

          • Ben

            I remember hearing John Kiefer mention that low-carb can down regulate hormones over time, and that pattern can be mitigated through insulin spikes. So, is it possible that while the body seamlessly adapts to low-carb, downregulated hormones affect these adaptations as a feeling of lower energy levels?
            Thanks for answering these questions.

          • William Lagakos

            I think you hit the nail on it’s head in your reply to Ash (above):

            “I was referring to the variation in the subjectivity of how that metabolic shift affects one’s energy level.”

            There are a lot of variables involved in “the perception of energy levels,” and diet alone is likely a very small piece of the puzzle.

            Also, to my understanding, Kiefer generally recommends a ketogenic diet with periodic carb re-feeds to aid performance in high-intensity, heavy resistance exercise… not necessarily “energy levels,” which he also says are high in glycogen-depleted, low carb states (I don’t think this goes against what you said, just doesn’t address it directly).

            My personal opinion is that if one experiences “perception of low energy levels” on low carb, it could just as likely be due to inadequate total calorie intake; this is a common symptom of a big energy deficit.

  • Thomas Hemming Larsen

    Kiefer wrote CBL for serious, big powerlifters, they can get away with a different load of carbs (maybe even benefit from them). Recently he has been promoting clean carbs a lot more.
    What you say about protein makes a lot of sense. I guess there is also a case for spreading out protein (beside pre-workout) throughout the day to have those amino acids in your body to help build muscle all the time. I just think that having no protein at breakfast is a bad idea, even when having some pre-workout. So is it really just a low carb, moderate protein diet we should do without spiking one or the other at any time of day? Even though protein is very satiating I’m still trying to find out if you should try to go beyond your hunger for muscle gains. I just find it ‘unnatural’ too eat much more than 100g/day but I’m not sure that’s enough.
    I think almost everyone agrees that carbs should be taken peri-workout

    • William Lagakos

      “Recently he has been promoting clean carbs a lot more.”

      Good riddance. In the book, he writes “Pizza, French fries, donuts, sandwiches, icecream, whatever…” which made me realize that he didn’t have a good understanding about how those foods would work in the CBL protocol… high sugar + high fat = super-long insulin surge (would extend *well* beyond the one-hour post-workout window).

      • Thomas Hemming Larsen

        He has said on several recent podcasts that you want very high, short insulin spikes. He also mentioned the ill effects of a long, drawn out insulin surge.

        This is exactly why you need to get on his podcast! 😛

        • William Lagakos

          Hahaha, yeah, we’d have a lot to talk about!

          Which podcasts? I’ve never heard him talk about CBL; my only primary resources were his book and that one article he wrote.

          • Thomas Hemming Larsen

            Oh man, then you’re way behind :)

   is his current website. Under ‘Around the web’ is the ones he has been on. That’s the biggest problem with CBL, the outdated information. Kiefer has also backtracked almost completely on caffeine, is now (very) pro-saturated fat etc. He is working on CBL 2.0 to update all of this.

            Philip aka the bjj caveman has written a couple of posts on notes from the podcasts. Then you can pick and choose what might interest you.


            On a side note, I’ve started working with Jef Fry from on a CBL protocol. After reading this I think I’ll try to focus more on protein instead of just slamming ze carbs :)

          • William Lagakos

            Oh boy. I’ve got some homework to do!

          • Thomas Hemming Larsen

            Yep, sometimes I’d wish I lived in ignorant bliss.
            I guess the study on elite gymnasts also makes a case for that carbs aren’t necessary. A higher pro:carb ratio is better.
            Btw, wouldn’t you also agree with that protein intake should be emphasised (maybe even kept constant on all days) on non-training days on a resistance training program?

          • William Lagakos

            “Btw, wouldn’t you also agree with that protein intake should be emphasised (maybe even kept constant on all days) on non-training days on a resistance training program?”

            yup. If anything, the effects of dietary protein on body comp will reflect the average intake of the past few weeks.

        • johnnyv

          Very high, short insulin spikes?
          Sounds like a job for whey protein rather than glucose then :)

          • Thomas Hemming Larsen

            Probably, it must be up to Kiefer to answer those questions :)

          • Noname

            Depends on form of whey and individual body response to that form.

          • William Lagakos

            Spiking insulin with glucose seems like a major ‘missed opportunity’ if it’s not coupled with protein intake.

            a higher protein:carb ratio during the refeed will likely give better long-term results, imo… maybe this will make it into CBL 2.0 :)

    • William Lagakos

      As to the protein question, YMMV. If muscle gains and body recomposition is the goal, then I would tend to aim for the higher side (again, it’s hard to assign an exact number to this). And yeah, probably best to include protein-foods with every meal because otherwise, it might be difficult to hit your daily goal without having a super-high protein meal… and I wouldn’t guess that 1 or 2 really high protein meals are better than 3 or 4 moderate protein meals… super high protein meals can upregulate amino acid oxidation, urea cycle, etc.

  • Danny Lennon

    A very interesting and well put together post Bill. I’m going to give this another read and trawl through some of those links. Plenty of thought provoking points.

    • William Lagakos

      Thanks, Danny. I’ve been meaning to dive into Kiefer’s work for a while now.

      • Danny Lennon

        As you alluded to earlier it will be interesting to see what changes/paradigm shifts Kiefer introduces when he releases the updated CBL.

        This post has been extremely useful in highlighting that although “proponents” of CBL are certainly not making things up and I’m sure are getting great results, the exact reasons/mechanisms responsible for this could be slightly different to Kiefer’s original hypothesis.

        Although I certainly do feel he is on to something and is a smart dude for sure.

        • Thomas Hemming Larsen

          I think Bill makes some good points in laying out the foundation is good but there could be further tweaks to enhance results further.

          • Danny Lennon

            For sure.

  • John Pierce

    Bill, so glad to see you post about this. Very much enjoyed the content. I enjoy Keifer’s weekly podcasts and would love to hear you on his program. I employed his “carbnight” protocol over the spring with some positive body composition changes. 10 days ketoadaptation followed by a carbnite (after 4pm post workout) which for me mainly consisted of pastries and pasta. I made myself so uncomfortable that i was looking forward to my low carb lifestyle. Still thought it was effective even though I knew i was over indulging. Keep up the great work!

    • William Lagakos

      Thanks, John. As per Thomas’s advice, I downloaded a few recent podcasts with Kiefer. I’m interested to see how CBL has evolved in the past 3 years.

      To the best of my understanding, carb-loading is once every 1-2 weeks with Carb Nite, but could be every day with CBL… very different metabolic scenarios!

      • Thomas Hemming Larsen

        Carb Nite is once/week.
        I’ve always understood CBL as it was only something to do after a heavy workout. I weight train 3 times/week so I do CBL 3 times/week (although my ‘high’ carb meals are something like two potatoes). The backloads on CBL are shorter and not as junky as CNS, as a general rule of thumb.

        • William Lagakos

          Hahaha yeah, you understand CBL better than Kiefer! Two potatoes will provide the insulin spike described by CBL *much* better than pizza, ice cream, etc.

          But two potatoes won’t sell books :(

          • Thomas Hemming Larsen

            Hehe, I’m not sure about that :)

            A powerlifter looking to set a world record might need it/get away with it because they are looking for maximal performance while still recognising the benefits of carb restriction.

            On the other end there is me who is a recovering anorexic with a body that is probably still stressed. I’ve tried getting anxiety attacks while I was squatting and getting almost suicidal at certain points after I’ve started lifting heavy. That might be due to not eating enough in general. I’m around 6-7% body fat and I more and more believe that ketosis is different for me than for someone at 25% body fat. Adding more carbs to my diet is maybe a good idea and I would go as far as saying that the days after the handful of days I’ve had a piece of cake is where I’ve felt the best for a couple of years.
            There is a time and place for everything including carbs and training.

            Again, you’re texting while leg pressing you should not be doing CBL in any form.

            Yeah, it annoys me that he has to do this marketing scheme. I have a feeling that it will be better for CBL 2.0 though.

          • William Lagakos

            1. I agree that ketosis is likely very different for you than for an obese or weight-reduced patient.

            2. “…is where I’ve felt the best for a couple of years.” I think you found your answer!

          • Thomas Hemming Larsen

            Don’t get me wrong, I don’t advise slamming cherry turnovers every day even in my case. Just saying that context matters regardless of its ketosis, CBL, vegan etc.
            I do believe that at some point in can be good to have an ice cream/cake to give your body an injection of nitrous oxide. You can’t do it all the time because it will ruin your engine but at the right time it can be beneficial.

            Speaking of which, I had a body composition scan today and its just deja vu compared to one month ago. I’m seriously contemplating that n=1 overfeeding study after seeing the numbers :)

            Anyway, I’m rambling. You must have more important things to do than reading my comments. This is just something very dear to my heart :)

          • William Lagakos

            Hahaha, I always enjoy your “rambling”

            those are some interesting points about cortisol & dietary fat… site of cortisol synthesis / regeneration may be important, too.

          • Thomas Hemming Larsen

            Its the same with downregulation of thyroid hormone which some studies (also n=1) show while others don’t. It depends on people’s context.

            I think its just easier for me to have this downregulation than someone who is obese.

  • This Old Housewife

    I’ve been conducting an N=1 experiment on my husband in regard to Carb Night and CBL–as you may remember, in the past, I used the cold potato salad weekly, because he couldn’t tolerate it two nights in a row. This experiment has been to VARY the carb source, feed each night for dinner (5:00 p.m. ET), and look at FBG the next morning (approx. 4:00 a.m.).

    So far, he hasn’t gone over 100 FBG the last few days, but it has been climbing: the potato salad did the best (night 1), followed by a stir-fry with radishes (night 2), and then a taco salad (night 3). Tonight, we’re repeating the potato salad (for night 4).

    I have found that broccoli and cauliflower don’t do so well for him unless they’re paired with Miracle Noodles.

    If this wonderful and surprising tolerance of carbs keeps up, we may come off keto and start including more veggies (and potato salad) with dinner each night.

    My own FBG this morning (4:45 a.m.) was 89. If this all works out, I may have cured our physiological insulin resistance, and maybe we can return to Paleo eating.

    • William Lagakos

      “as you may remember”

      it’d be easier to remember if you didn’t change your handle! 😉

      but yes, I remember.

      “I have found that broccoli and cauliflower don’t do so well for him unless they’re paired with Miracle Noodles–probably from the Omega-3 content of the veggies.”

      Does this happen with other omega-3 foods?

      • This Old Housewife

        I had to change it–NSA intercepted my e-mail, so I had to go change all my accounts, and open up a new e-mail addy–had to dump Wenchypoo too. As for it happening with other Omega-3 foods, yes, it happens with ALL, as well as all opioid painkillers and NSAIDS.

    • This Old Housewife

      Night #4–potato salad repeat didn’t go so well the next morning (at 102 FBG). But he didn’t eat until 7 instead of 5 like usual–he came home and passed out instead (back-to-back meetings all day). We’ll go another week with the experiment and see what else happens.

      It may be that he ABSOLUTELY needs 12 hours between meals to clear the blood sugar to normal levels.

  • This Old Housewife

    the safest time to “slam carbs,” if you so choose, is pre-workout, because exercise attenuates the insulin response and favors nutrient partitioning.

    I’ve read on body-building sites that muscle is the best sugar-sink–is this why?

    • William Lagakos


      “maybe 2-3% [of a glucose load] ends up in adipose whereas the vast majority goes to skeletal muscle.”

      Even more will go to skeletal muscle if it’s ingested pre-workout due to changes in blood flow, contraction-induced glucose uptake, etc…

      • Noname

        I thought somewhere (CBL or CN) it was mentioned that there can be sugar issues for people who lift hard in the 5pm window (most of those folks have had relatively small amounts of food to that point of the day). They are also using ketones as a primary energy source. How that factors into the utilization of carb stores / ketones etc as the session starts I have to leave to the experts, though it works well enough for me that I’m happy with it but willing to consider ways to improve it.

  • William Lagakos

    Exercise at night impairs the cortisol awakening response and results in elevated levels of cortisol in the evening.

  • William Lagakos

    “Protein for lunch & carbs for dinner” vs. “Carbs for lunch & protein for dinner”

    both groups lost weight, but “carbs for dinner” lost significantly more lean mass.

    • Thomas Hemming Larsen

      Interesting how body composition was better with carbs at lunch but glucose homeostasis and DIT was worse than carbs for dinner.

      I know Kiefer would question this study because it involved obese people which he would claim are metabolically different than healthy/lean people.
      I don’t know if that is right or wrong.

      • William Lagakos

        the differences between the groups in this study were pretty small… also, no exercise intervention, which seems to be a necessary pre-requisite to accomodate CBL’s PM carbs (Shhhh).

        I’m collecting as many ‘point-counterpoint’ studies on macronutrient timing that I can find. They’re very nuanced.

        • Thomas Hemming Larsen


          Sure. That’s what I really like about you – you’re not married to any particular view but rather to finding ‘the truth’.
          There are just so many confounding factors in any study.

      • William Lagakos

        “I know Kiefer would question this study because it involved obese people which he would claim are metabolically different than healthy/lean people.”

        oh boy…

        Out of all the [chronic] macronutrient timing studies available, all of the ones cited in favor of CBL include overweight/obese patients. Therefore, can’t discount studies that don’t favor CBL simply because patients are overweight/obese.

        on another note, the only studies with healthy people are the acute feeding studies (eg, meal or glucose tolerance tests, etc.)

        …but it seems like nuances in study design have more of an impact on the results than patient population…

        • Thomas Hemming Larsen

          I know, I know. I’m complicating things again :)

          That said, I don’t want to put words in Kiefer’s mouth, its he’s protocol so he should explain it.

          This is so all over the place. There are so many confounding factors.

          CBL is all about timing because it assumes that you have most other things in place. If you don’t sleep enough, have a crappy diet, stressful job etc. then I’m sure there are more important issues to deal with.

          Some people say only three meals/day. Kiefer doesn’t really care about that, its about the macros and timing. I think there is a hierachy of importance (like here ) – where exactly all things fit I’m not sure.

          I’m telling you, that podcast should clear up some things! I really hope that you’ll challenge Kiefer on everything!

    • Noname

      I thought CBL / CN were ketogenic systems? Its going to be very difficult to get apples to apples double blind studies that are going to absolutely define Kiefer’s system. At the end of the day it either works for people or it doesn’t. I haven’t heard many people say it is a complete fraud, though you seem to want us to infer as much.

      I think sometimes
      you’re missing the point here. 1) Ketogenic living? 2) If yes, then how do you
      prefer to train? Do you have to lift / HIIT to increase HDL? 3) If yes to
      2) then do you need carb cycling to perform 2)? 4) If so how do you do carb

      The answer to 4 is
      highly dependent on lifestyle. Frankly there is probably no implementation that
      doesn’t interfere with “ketogenic living while strength / HIIT
      training”. This can be because of the interplay between high insulin carbs
      and protein fat meals and the “one hour window” assumption (very
      minor issue IMHO if you are training at 5pm or later.. probably a bigger deal
      as it impacts #1 if you train morning or mid day… but I haven’t read CBL
      about the morning regime), or it can because of any number of other issues. But
      the bottom line is that concentrating on the timing issue (#4), is missing the
      larger benefits. Lots of areas that the community will be interested in but
      timing issue… who really cares? I burn fat all day (getting down to best
      waist I’ve had since my teens) and I’m hitting PRs all the time at night and
      I’m 47.

      If I were you I’d look at ketogenic carb cycling methodologies, study there fundamental differences compare contrast then use your intellect to “on balance” suggest which you would recommend to a family member bent on ketogenic, heavy lifting and HIIT. Put some rationale behind your choice. Then look at the double blind studies. My guess is there are few very relevant to ketogenic, heavy lifting and HIIT, but would be interesting to see how your intuition and deep dive contrasted.

      Kiefer is an entrepreneur / innovator with a system that works for many. Strangely it is a system that works for fat and high performers, but nonetheless both groups are open minded about other systems / aspects of other systems that might help to achieve their goals

      Seems like this is just an attack on Kiefer by another “double blind number monkey”. We get that the establishment folks don’t like Kiefer. We also get that Kiefer’s system works for many of us. Establishment versus innovation / entrepreneur in the 2014 US medical / system food delivery system. History will judge establishment as failure here as genetics, information, and innovation are about to help many, many people despite what the establishment’s double blind male oriented studies have to say about it. How bout using that body of knowledge for good instead of just attacking someone who is in the trenches every day trying to work this out? Would love to hear that you have taken on 10-20 clients, so that you get a little more intimately connected to the real world. You could use a little humility.


  • William Lagakos

    the Sofer study:

    intervention group: carbs only with dinner

    control group: carbs spread evenly throughout the day

    Had the control group been “carbs only with breakfast,” then maybe we could conclude restricting carbs to dinner is superior to breakfast. BUT since the control group was *multiple* meals, we can perhaps more appropriately conclude: restricting carbs to ONE meal per day is better than MULTIPLE meals… the difference is that now, the conclusion doesn’t exclude the possibility that restricting carbs to breakfast may be superior to dinner. This would also be in agreement with many of the studies cited here:

  • ‘Mash (Thomas Herbert)

    Will, just added this article to my link bundle. You might find some other discussion in there useful. John Kiefer’s Carb Back-Loading.

    • William Lagakos

      Hi Thomas,
      Cool, thanks. I’ll definitely check out that link.

      • Thomas Hemming Larsen

        I think that’s another point which is lost in the book (or maybe I’m extrapolating my own thinking). I do the back-load as low fat as possible. I don’t think its a good idea with high fat and high carb after training whereas low fat, high carb ban be beneficial. Just my thoughts.

        • William Lagakos

          the original CBL protocol said you want a high quick insulin spike and then went on to recommend pizza and ice cream…

          high fat foods attenuate the height of an insulin spike while prolonging the duration… it goes against both principles.

          • Thomas Hemming Larsen

            Yes, but I reserve the right to my own interpretation/execution :)
            I remember one podcast where he said that it was about getting a spike rather than a big AUC.

            I know you’re doing a podcast with Kiefer but when are we doing a skype call to talk all this through!?

            On a serious note, please please, challenge Kiefer on all of these points.

          • William Lagakos

            “I remember one podcast where he said that it was about getting a spike rather than a big AUC.”

            that’s what I meant by “quick & dirty,” and it’s what’s said in the book:

            1) high peak level of insulin spike: to maximize protein anabolism

            2) short duration of insulin spike: to keep it inside the 1-hr post-workout window of adipose “hypertrophy-resistance”

          • Thomas Hemming Larsen

            Yeah, I agree. I don’t think a huge, greasy is the food for the job.
            Today I had 250g of potato as my back-load.

          • William Lagakos

            the recording is scheduled for Sunday.

            what’s your email address?

          • Thomas Hemming Larsen

            Just sent you a mail to drlagakos gmail.

          • Thomas Hemming Larsen


            This is from 2011 but there are some good points regarding how powerlifters ‘have’ to eat a lot. Listening to it CBL makes more sense than what it has recently been promoted as.

  • Bill Lagakos

    Exercise timing: most studies show we’re “strongest” in the afternoon, but this isn’t permanent. Ie, if you consistently train in the morning, then the AM-PM strength differential fades.

    Yes, carbs should ideally be consumed peri-workout. Agreed :-)

    I’m aware of the carb-serotonin link, but carbs in the evening don’t bode well for metabolic homeostasis. See here for more:… that post also covers the lean active person vs. diabetic patient issue.

    • Børge Fagerli

      Agreed, consistency (both in meal timing and workout timing) is the most important.

      Some good studies there, I just go from my own experiences and a lot of the clients I work with – eating a huge breakfast will make most people fall asleep by lunchtime. Example – staying at a hotel and indulging in the buffet, me and my girlfriend could barely stay awake when we came back to our room. From a practical standpoint it doesn’t seem very productive, but from a body composition standpoint – maybe it is worth getting used to (or just going a little easier on the carbs and/or having an early workout right after breakfast)?

    • Børge Fagerli

      “Yes, carbs should ideally be consumed peri-workout. Agreed :-)”

      Do you also think that fats should be consumed peri-workout to support anabolism?

      Or – when looking at enzymatic activity (higher in muscle vs fat) and lower insulin sensitivity in fat cells early in the day, more (most?) fats for breakfast?

      • Bill Lagakos

        Based on the circadian regulation of insulin sensitivity in muscle & adipose, most of *everything* should be in the morning.

  • Bill Lagakos

    those are some very specific recommendations!

    “Evolutionary speaking, it just seems more natural that man would hunt and gather during the day only snacking lightly, then feasting when night falls”

    I understand this line of thinking, but think it might not apply so well in modern times. Most studies show consuming more calories later in the day are preferentially partitioned into fat, and evolutionarily this may have been advantageous (thrifty, etc.). Nowadays, we don’t need to bulk up our fat stores to prepare for a famine, so eating a lot at night makes less sense. What do you think?

    • Børge Fagerli

      Yeah, I can get my nerd on with the best of them 😀 Just trying to synthesize the existing research (some of it which you made me aware of here) into some practical ideas. After reading some more here, I understand that you like higher fat/ketogenic diets, so you might not agree with the higher carbs here…but for high-intensity exercise and hypertrophy/strength I am rather fond of it (although Jacob Wilson has done some interesting research on ketosis and muscle gain/fat loss) :)

      The reason for having more foods for the final meal is primarily to support anabolism from the workout, but I also wonder if you can get away with more with a feeding window which doesn’t really extend too far into the evening (such as in some of the studies)?

      Evolution set Neolithic man up for survival and not for getting as lean and muscular as possible, so yeah – I guess we might have to do a few things opposite of what our biological drive is telling us (eating a lot of calories in the evening).

      If I could be so bold as to ask you “optimize” my training day example according to your own preferences, what would it look like?

      • Bill Lagakos

        High intensity exercise and the bulk of calories in the evening = damage control. The body doesn’t partition nutrients well in the evening, so exercise is necessary to help out.

        High intensity exercise and the bulk of calories in the morning = optimal.

        Exercise timing is secondary to meal timing. The body partitions nutrients better in the morning; and I think it’s better to exercise around mealtimes…

        downside? inconvenience.
        If you can’t adhere to “optimal,” best at least do “damage control,” which is clearly better than just doing “damage” 😛

        • Børge Fagerli

          Ok, so according to this an “optimal” (obviously not practical) pattern would be:

          M1: 0g C, 40g P, 0g F
          Workout (and perhaps some carbs+whey pre-WO)
          M2: 250g C, 40g P, 100g F
          M3: 0g C, 70g P, 0g F


          Or would you spread out fats between M1 and M2?

          So far into your blog posts and books, it looks like you favor a low-carb/keto approach, so maybe what you would consider optimal is:

          M1: 0g C, 40g P, 100g F
          M2: 50g C, 40g P, 100g F
          M3: 0g C, 70g P, 0g F


          Sorry for being a pain in the ass, but I am all about practicality and examples, and this is somewhat missing in the book and blog posts.

          • Bill Lagakos

            Holy crap do you eat “food?!!” lol jk :-)

            those are just some VERY specific numbers. I take a more holistic 30,000-foot view of meal & macro timing: 1) eat more food earlier in the day; 2) exercise close to mealtime; and 3) if taking carbs, do it peri-workout.

          • Børge Fagerli

            lol yeah, I know – didn’t mean to put you on the spot there, I am just trying to turn see if I understand you correctly.

            So the optimal would be working out as early as possible and then eating close to that, I get that…but for someone training around 1-2PM the first example above was more “practical” where you can have some carbs for breakfast, some fats for the final meal – whereas this would be more “optimal”, so to speak:

            M1: 0g carbs, 30g protein, 100g fats
            M2: 250g carbs, 40g protein, 0g fats
            M3: 0g carbs, 80g protein, 0g fats


            btw – did you change your stance on pre-workout nutrition after being on the Kiefer podcast? I.e. would you avoid carbs pre-workout to increase sympathetic drive and empty glycogen?

          • Bill Lagakos

            I don’t think there’s a clear winner: pre- or post-workout nutrition, as long as the “pre” is immediately prior to exercising.

            As to the numbers game, again, I don’t even know what something like this “M3: 0g carbs, 80g protein, 0g fats” would look like! I would never condone such a meal :-)

            But I see what your getting at. Theoretically, if I were to partake in this numbers game, I’d spread out the fats and carbs, but keep most of the carbs peri-workout.
            There shouldn’t be any meals with 0 grams of a macronutrient…

          • Børge Fagerli

            Yeah, I find that it is highly individual and depends on workout intensity and volume. More high rep work moving quickly, and some tend to do better with some fruit/fruit juice immediately pre- and during the workout…

            Again – it is obviously unrealistic to have 0g of either macro, so the numbers game was simply to understand your recommendations wrt nutrient timing (especially fats vs. carbs). To reiterate the example from my very first post in this thread, this is what it would realistically look like:

            – Waking 6-7AM

            – Breakfast 8-10AM: 30-40g of carbs, 30g of protein, 40-50g of fat

            – Workout noon-1PM (or earlier)

            – Second meal 1-2PM: 160-180g of carbs, 30-50g of protein, 30-40g of fat

            – Final meal around 6-7PM: 30-40g of carbs, 60-80g of protein, 10-20g of fat

            …I appreciate your patience 😉

            Have you heard of the ketogenic research Jacob Wilson has done at Tampa U with advanced lifters?

            Better fat loss, equivalent muscle gain (after carbing up at the end of the study)…

            Preliminary data is also showing that a fat+protein breakfast increases fat oxidation over 24hrs vs having a high carb breakfast/low fat breakfast.

          • Bill Lagakos

            I pretty much never recommend a high carb breakfast…

            “Preliminary data is also showing that a fat+protein breakfast increases fat oxidation over 24hrs vs having a high carb breakfast/low fat breakfast.”

  • Børge Fagerli

    This is a rodent study, and Jacob Wilson’s preliminary data seems to show the same applies to humans, concluding that fats at the beginning of the day – but not carbs – increase fat oxidation and metabolic flexibility.

    Quotes: “For example, consumption of a high carbohydrate diet during the beginning of the active phase impairs metabolic plasticity. Furthermore, consumption of a calorically dense, high fat diet at the end of the active phase leads to accelerated weight gain, increased adiposity, glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hyperleptinemia (i.e., the cardiometabolic syndrome). ”

    “In addition, consumption of a high carbohydrate meal at the beginning of the active/awake phase results in a profound metabolic inflexibility, again independent of daily total or fat-derived calories”


    • Bill Lagakos


      “beginning of the active phase” for rodents is lights off. The circadian regulation of insulin sensitivity is at least partly mediated by the light-entrainable oscillator, not activity levels per se. So lights off for rodents = lights off for humans.

  • omctc

    How about those of us who sleep better if we eat the bulk of the carbs (50g) at dinner?

  • omctc

    Hi Bill. Did you see this paper:

    • Bill Lagakos

      Yes. The control group was 3 carb meals per day. Therefore, it showed that restricting carbs to one meal per day was better than three.

      If the control group was carbs with breakfast only, then it would’ve been able to test if AM or PM was better.

  • Daniel


    “AM: high muscle insulin sensitivity, low adipose insulin sensitivity; carbs now are OK, and exercise is better (but not necessary, unless goal is muscle growth)…?”

    Would like your opinion regarding exercise in the morning. Ive been training around 2pm last year or so and is thinking about switching that into morning instead.

    Im normally eating 50-75g protein(trying to reset my circadian rythm since i sleep(bought glasses who will arrive soon) very bad etc) within 30 mins of waking up and then going for work. If I were to exercise before work it wouldnt really be possible taking down all that protein… Would prolly make me puke during training. How would you suggest I should do? Take in a small amount of whey protein when I wake up before going to gym and then take in rest+carbs after workout?

    • Bill Lagakos

      a smaller meal should be fine… don’t want to be puking in the gym!