Glucose Disposal

Glucose Disposal

A while ago, I got involved in a discussion in the comments section of the “Does Dairy Make You Fat?” post as to whether the conclusion I reached was defensible based on the data.  In so doing, it became apparent that the crux of the discussion was relating to an understanding of the metabolic control of glucose disposal, and rather than continue and make the case buried in the comments for that post, I decided to bring the topic here in the spotlight!   Glucose disposal is the flip side of the insulin sensitivity coin, meaning that glucose disposal is a measurement of the efficiency of insulin action, or how quickly and to what extent tissues take up glucose from plasma. If you are insulin sensitive, that is another way of saying that you have a high rate of glucose disposal, a low rate of glucose disposal and you are insulin insensitive.   If you are a researcher and you actually want to quantify insulin sensitivity, then you must do so in terms of glucose disposal rates, and when it comes to measuring that, the gold standard is a procedure known as the euglycemic hyperinsulinemic clamp technique, or ECT. Despite the somewhat imposing name, it is a fairly straightforward process to understand, and in fact, that tongue twisting name pretty much tells you exactly what you need to do, assuming you have some familiarity with Greek. In Greek, the prefix eu means good or normal, and the prefix hyper means over or excessive. Applying those definitions, the euglycemic hyperinsulinemic clamp will attempt to maintain normal (eu) glycemia in the face of excessive (hyper) insulinemia.   In practice, the ECT entails getting a subject that is willing to have intravenous drips applied, and then infusing them with significantly higher than fasting baseline levels of insulin ( hyperinsulinemia ) and maintaining ( clamping ) their insulin levels there. Now, if this were all that were to be done, then you would very quickly produce a hypoglycemic coma in your subjects, and this is something that ethics committees tend to frown upon. Accordingly, what you do concurrent with your insulin administration, is also clamp glucose by supplying it intravenously in amounts necessary to maintain it at the fasting level of your subjects ( euglycemia ). You need to take regular blood samples to determine just how much glucose is needed in order to do that. You keep this up for 120 minutes and the total amount of glucose that you had to administer is a measure of how much glucose tissues took up in response to your artificially induced insulin signalling.   Or, to put in other words, if you want to determine the rate at which the drain in your sink removes water, but you cannot, for whatever reason, measure that directly, then you can still infer this rate by adjusting the taps so that the water level in the basin stays constant. By measuring the volume of water that you need to add to the basin you have an indirect measure of the drain rate   What would an ECT look like from the perspective of someone inspecting the collected data?   You would see something rather unusual in physiological terms.  In general, insulin lags blood glucose, which means that you generally observe an elevation in blood glucose levels, and shortly thereafter, insulin levels rise to stimulate absorption of this excess glucose.  For an ECT, however, you would see a consistently elevated plasma insulin level, well over fasted baseline and, moreover, a thoroughly unresponsive glucose level, holding steady at fasted or near fasted levels as researchers dutifully made sure to administer additional glucose to ensure that this was the case.  Or, to save me 1000 words or so, something like this:       On the face of it, this graph shows us the mother of all insulin resistance.  Complete and utter failure of insulin to budge blood sugar levels.  This is insulin’s Waterloo, its crushing defeat!  Of course, we know that appearances are deceiving because the above graph is an idealized representation of an ECT.  I generated that diagram from the definition of the ECT.  So, let’s take a look at some experimentally derived data:       Note the characteristic lack of glucose response, and the elevated insulin levels.  The data, therefore, looks quite close to what we would theoretically expect, but there is just one thing that you might not expect, and that is that the graph above does not represent the results of an ECT, but rather it is the data from this table that we’ve seen before in the dairy post:...

Return To Sender

Return To Sender

Update: as of 09:56 I believe that I have fixed my issues with the contact page.  If you’ve tried contacting me within the last few days, you might want to try again.  The proof of the pudding is in the mailing!   As part of the growing pains of switching hosting providers, I’ve been having some problems with my contact page.  Essentially, due to a misconfiguration somewhere, whenever someone submits a message via the contact page, their email address is replaced with my own, which means that I have no way to reply.  So, while I try to suss out what is going on, I am going to decommission the contact form, and instead ask you to write to me directly at pablo <dot> klopper <at> cogitoergoedo <dot> com.   If you’ve tried contacting me recently, this is why you haven’t heard back from me.  I’ve probably received your message, but the only option I have is to reply to you publicly, via the site.  Here are two questions that I received recently:   Hi, I’ve been researching intermittent fasting pretty exhaustively over the past year and a half. I recently came across your MDA posts and you seem extremely knowledgeable on the subject. I have a question regarding my own experience. For the past two months I have been using one meal a day, and I also follow the supplementation guidelines listed in Perfect Health Diet. I’ve lost ten pounds, but it stalled. I read on Critical Mas that my metabolism could have down regulated. So, I’ve started eating a small breakfast/lunch, combined with one twenty-four hour fast each week, and no real weight change. I read the forty-hour fast research on MDA and was wondering if that might be beneficial due to the HGH of a fasted night (and the twenty four hour fast isn’t a fasted night because I eat dinner). Any idea what’s happening with me and why my weight loss has stalled. Body fat is around 16%, weight is 210, height 6’1. Thanks for your time.     Hey Pablo, Came across your IF articles on MDA, caught the link to your site here. First off, great job and thanks for your work. I have been doing the 8/16 protocol for over a year now (skip breakfast) and have had great success. I am in pretty good shape but noticed your once a week re-boot of a 40 hour fast and was curious if this is something I should incorporate. I know, I know, give it a shot and see if it works for me. But was curious as to the “reboot”. Is this kind of a house cleaning thing? I plan on condensing my eating window as well. Thanks! Well, gentlemen ( I’m assuming that the second question is also from a male ), I just want you to know that I’m working on a reply to both of you, because the answer will apply equally to both situations.  I hope to have that up shortly, although, just to let you know, you are in the queue behind a couple of other posts.  ...

Intermittent Fasting and Reactive Hypoglycemia

As you may know from reading through the blog, or maybe from my posts on Mark’s Daily Apple, I practice my own version of intermittent fasting which in a nutshell consists of eating a single daily meal, and going weekly without food for two consecutive days.  There is a lot of science and thought behind this, and one of these days I will finally get around to repatriating my posts from MDA.  In the meantime, if you are interested, you can read what I’ve had to say here, here, and here.   What I find extremely interesting is that if you go and read through the responses in those very long discussion threads I’ve linked above, you will invariably come across several accounts similar to this one:   It’s taken me a LONG LONG time to be able to just have one meal a day. I used to do it as a child/teenager without a second thought, but in my 30s I found myself hungry and shaky and feeling sick if I didn’t eat, like, right NOW! There was no way I could do intermittent fasting… I was an absolute carbohydrate addict! Becoming Primal didn’t help either – in the beginning – I still suffered if I skipped meals. I don’t think I was eating enough, and I often felt sick and shaky. And even though I was eating clean, I think the years of abuse from bad food choices and alcohol took a long time to rectify. I’ve been Primal for a long time, and it’s been a LONG journey for me to be able to go now, as I do, on just one meal a day (dinner). I’m happy to say that the hypoglycemia episodes are much less often, and it doesn’t bother me now to go longer without food. I’d say it took me over a year, approx, to get to this stage. And I still think I’d struggle to go 40 hours! (Even though I hope to be able to, one day.)   Anecdotally, it seems to me that there is a sub-segment of the population that probably suffers from some derangement of glucagon metabolism, or perhaps there is an underlying problem with hepatic glycogen metabolism, I’m still not sure as to what the underlying cause may be, so I’m basically speculating.  It also  seems that women are more prone to this.  A friend of mine after talking with me about my approach decide to do as I do ( did ) not as I said, so, rather than work her way up to a single meal, and then gradually to 48 hours of fasting, she decided to jump in with both feet … no eating for an entire weekend ( which was how I went about it way back in the day ).  She went through a whole slew of these symptoms, including becoming very disoriented and confused due to what was apparently very low blood sugar.  It also took a couple of days of reverting to her normal eating patterns to get back to her normal self.  Needless to say, she has given up on fasting entirely.   My cousin’s wife is also prone to this.  She is a truly wonderful person, except when she hasn’t eaten for about 3 hours, at which point, she turns into Mrs. Hyde!   I would love to get a better idea of what is going on, and to that end, I’ve included a small survey at the bottom of this page so if you happen to have had an experience similar to this, I would like to hear from you.  Ideally, if you’ve been fasting without any of these issues, you would be kind enough to take the survey as well, because I would also like to get some idea of the overall incidence rate.   The survey should appear below, but as I’m using a free service, I’m getting what I paid for, which means that periodically, it can take quite some time for the actual survey to appear.  Please give it some time. Also, please note that because this is a ‘free’ service, once you submit your responses, they will serve up an ad in the survey window. Please feel free to ignore it. Beyond clicking on submit, there is no other action for you to take, and certainly no requirement to signup for anything ( the one ad I keep seeing is actually for the survey service itself, and it keeps trying to get users to register )  ...

The More Things Change

The More Things Change

On the face of it, it may not look like much has been going on around here, but that’s not entirely true.  While most people probably spent the better part of January trying to come up with a plan to achieve their New Year’s resolutions, I was mostly concerned with what to do about a notice I received from my web hosting provider:     So it turns out that my machine was compromised, became part of a botnet, and for some inscrutable reason was being used in a DDoS attack against some Brazilian targets!  While this might be interesting were it not happening to my web server, not only was I unwittingly a participant in internet hooliganism, but this also had the effect of knocking my web server down periodically, and thereby causing great consternation to both my readers ( thanks mom ).   I could have dedicated my time to resurrecting the site by razing the previous server and rebuilding / reinstalling the OS, reinstalling my blogging platform, and migrating my data ( i.e. posts and so on ).  But, this provided me with an excellent opportunity to examine the costs associated with running this website.  Some poking about revealed that I could have hosting for approximately 1/10th the cost of what I spend with Amazon.  Since I had to rebuild the site irrespective of whether I remained with Amazon Web Services or switched providers, the monetary incentive became persuasive, not to mention not needing to worry about reinstalling the underlying OS.   I have nothing bad at all to say about AWS, but the cost for me was the deciding factor, so I went instead with Dreamhost, and migrated all the site data there.  This took some time, and as an additional consequence, I may have botched some things along the way, so if you notice anything strange, please drop me a note.  One intentional change that you may observe is that I’ve disabled site registrations.  I had been toying with the idea of having a members’ forum area, but that’s still in a half baked state.  Meanwhile, I did observe obvious bot registrations sporadically, so I’d rather not have that avenue open for scripts to potentially exploit while I decide whether I will go ahead with forums.   Hopefully, with this administrivia out of the way, we can get back to the business of posting!   Featured Image Macrophage engulfing bacteria as part of the host immune response....

Yes, Virginia, a Calorie is Just a Calorie – Part I

That’s because a calorie is simply a defined unit of measure: a measure of heat. So, just as all meters, ounces, and hectares are fully fungible amongst members of their class with each being indistinguishable from another, so it is with calories. More specifically, when referring to calories in the context of food, every calorie in the world represents the amount of energy required to warm one gram of air-free water from 14.5 °C to 15.5 °C at standard atmospheric pressure.  If that were all there was to the story, then we could move on, but unfortunately, our work is not done yet because there exists an entire school of thought out there that extrapolates from this equivalence and pushes the thermo-chemical calorie into territory where it was never meant to go.   When people say that “a calorie is just a calorie”, they aren’t alluding to the above definition. Rather, what they mean is that the macronutrient source of a given calorie is irrelevant. Whether you derive 2000 kCal of energy from fats, protein, carbohydrates, or some admixture of the three, from the point of view of your metabolism, all possible combinations will be fully equivalent, assuming you maintain the same overall net caloric intake. This common understanding is far more interesting, principally because unlike the thermochemical definition in which the equivalence is tautologically true, the common view of caloric effects on metabolism is controversial, and that has made several authors quite a tidy sum as they argue for or against the premise.  Those arguing for full caloric equivalence go about it in a manner something like this:   chocotaco369 on Marks Daily Apple Let’s take two drinks: a 32oz coffee with 400 calories worth of sugar in it and a 32oz coffee with 400 calories worth of emulsified coconut oil. Both are consumed while said office worker is sitting on their butt in addition to all the normal calories they eat throughout a day. Which is worse?   While fairly typical of the breed, as far as arguments go, this isn’t much of one.  I expect that you have seen some variant of this sort of assertion and the very fact that it is repeated so often and from so many varied sources lends it the air of credibility.  As a proof technique, this is known as proof by repeated assertion – just hammer the point until resistance collapses.  It is also helpful if you can have multiple, hopefully seemingly unrelated, sources do the same hammering of the point.  Rote learning works like this.  You wind up “knowing” things without giving a thought to the derivation or underlying logic supporting those things, which is precisely the problem :  by virtue of the frequency of repetition of such arguments espousing the equivalence of calories, most of us have become inured to the glaring and unwarranted leaps in logic contained at their core.   It is quite remarkable that the exemplar we have above consists of only three sentences and by my count contains no less than eight fallacies!  That is an impressive error density, even the biblical apocalypse makes do with a mere four horsemen, and if this were the error density Olympics, I’d say we were looking at a gold medalist. Notwithstanding that, allow me to re-frame the assertions to explicitly reveal the contained error virtuosity: Restatement with explicit equivalence Let’s take two drinks: a 32oz coffee with an amount of sugar in it that would produce 400 kilocalories of heat when completely combusted in a bomb calorimeter and a 32oz coffee with an amount of coconut oil in it that would produce 400 kilocalories of heat when completely combusted in a bomb calorimeter. Both are consumed while said office worker is sitting on their butt in addition to all the normal calories they eat throughout a day. Which is worse?   With that done, I am hoping that the problem becomes readily apparent : you are not even remotely like a bomb calorimeter … which leads us nicely to the first fallacy.   Fallacy 1 : Heat of combustion is equivalent to biological energy metabolism   Some of you may have been wondering about that definition of a calorie given earlier, specifically wondering why it is given in terms of raising the temperature of water.  This is the end result of how the process of calorimetry is performed, and to help us understand that process, we can take a lesson from NASA.   On January 17, 1967, at 1:00 PM, EST, astronauts “Gus” Grissom, Edward White II, and Roger Chaffee entered the Apollo 1 command module for a launch simulation test...

Enough Calories?

Enough Calories?

Far too frequently, when someone finds out that I advocate eating a single meal a day, the question is posed as to how one can possibly get their daily complement of calories in a single meal? The question never fails to take me aback, although by now, I really should be used to it. After a bit of back and forth with the questioner, the problem is always revealed to be implicit assumptions as to what caloric intake one ought to strive for, with the questioner always pegging caloric intake much higher than I would. Who Are You, and Why Are You Fasting? Given the reach of the internet, for all I know, this blog may be quite popular with the canine crowd. Be that as it may, when I write posts relating to fasting, I have a fairly clear picture in my mind about my target audience, and my foundational assumption is that it isn’t comprised of dogs, but, rather, mostly real people.   Along with their assumed humanity, I also assume that the person seeking to fast is generally healthy.  Despite the fact that there has been considerable research that supports the notion that fasting is beneficial for some pathological conditions like cancer, in general, I’m going to assume that you do not have any serious medical conditions that would serve to complicate things.   Further, at least when it comes to pegging daily caloric intake on the high side, I’m going to assume that you are male … sorry ladies. Women in general tend to err on the side of eating too little.  All told, then, the basic assumption is that you probably are a relatively healthy male. That’s a good starting point, but I also make assumptions about which one of these guys you are:   [Show slideshow]   I‘m fairly confident asserting that you’re probably not the guy in the picture on the right, that is, you are not an athlete. Now this is probably a good thing, because the guy in that picture is Michael Phelps, and he reportedly eats 12,000 kCal while he is in training. Take a moment to let that number sink in, and realize that he eats almost an entire week’s worth of calories in one day ( based on the US RDA assumed 2000 kCal daily caloric intake ) Now, if, by some incredibly, outlandishly, outrageously small probability, you are Michael Phelps, I am very flattered that you read my blog, but please for God’s sake do not attempt to eat all that food in one meal. You won’t be able to do it, even with your prodigious talents, and you will probably undergo a not insignificant amount of pain and gastro-intestinal distress. Furthermore, as attested to by your tremendous success in the pool, you, your coaches, nutritionists, and the rest of your team obviously know what you are doing. If it ain’t broke…   In keeping with the “ain’t broke” philosophy, I am also pretty confident that you are not the guy in the middle picture, single digit body fat guy. If you , by some chance, are in that category, again, you probably don’t need me to tell you how to go about your body re-composition goals.   So that leaves us with the guy on the left. The average male, looking at 20+ % body fat, and with no real direction or plan for getting rid of it.  You probably want to get yourself to look more like the single digit body fat guy, but you don’t really think that is a realistic goal, but at the very least you’d like to drop some of the fat.  The particular guy in this picture got that way by eating six meals a day, training with weights with a push/pull/legs split three times a week, and eating PROTEIN at every meal, making darn sure to hit 3000 – 3500 kCals per day so as not to “lose lean mass!!”.  At 6′ tall, 225 lbs., and 38 years old, things were not looking good. Now, I came to  this remarkable degree of clarity about the average male because that picture on the left, that’s me in 2006. That was also me as recently as 2008, but, due to vanity reasons, I was not particularly willing to subject myself to shirtless pictures, so I don’t have them to post.   And there you have it, I’m generally assuming that you are close to the average guy end of the spectrum, and if I am near to the mark, then I suggest that what you fundamentally need to do is to decide whether your approach...

Every Meal Counts

Every Meal Counts

Whether you follow the 8 hour diet, Fast 5, Lean Gains, or my own intermittent fasting protocol, you will have noticed that the principal difference comes down to the concept of an eating window.  Simply put, each protocol specifies an interval during which no food is taken, and a subsequent interval during which meals are permitted, the eating window.  In the 8 hour diet, this window is unsurprisingly 8 hours, Lean Gains is also an 8 hour protocol, Fast-5 gives you five hours in which to eat, and as for me, I actually don’t have a window, but rather advocate eating a single daily meal.   To the extent that intermittent fasting works at all, it does so by limiting the number of meals one takes in a given day.  In general, calorie counting doesn’t play a large role.  In fact, to listen to the gushing authors of “The 8 Hour Diet” we can : The 8 Hour Diet David Zinczenko Forget all the standard advice about cutting calories … forget willpower … forget counting calories.  Forget everything you’ve ever heard about weight loss and just do this: Eat whatever you want, as much as you want, but only eat during an 8-hour period each day.”   I think this is grossly overstating the case for intermittent fasting and landing squarely into the Heisendiet category.  Nevertheless, if we give Mr. Zinczenko the benefit of the doubt and assume that the diet works as advertised on the tin, then it is remarkable to think that these weight loss effects are brought about by changing the conventional 12 hour eating window ( from say 7:00 AM to 7:00 PM ) into an 8 hour one.  Of course, all meals come with attendant satiety, so for practical purposes, there is a limit to how short an inter-meal interval can be, assuming that you are in the habit of not eating unless you are hungry.  In practice, when you remove one third of the time that one has available for eating, the net result is the elimination of one of the conventional daily meals, most likely the meal the we culturally know as “breakfast.”  With this realization, even Mr. Zinczenko’s diet is reliant upon meal elimination.   More generally, the only reason to claim that your diet has an X hour eating window is precisely because you intend to have the adherents to your protocol eat at least twice.  Your average person will at least eat at time T, the beginning of the eating window, and then at a minimum at time T + X, the end of the eating window.  There may also be other meals or snacks in between.  As a result, eating windows are conducive to “meal frequency creep”, in fact, this aspect is pretty much baked-in to the diet from the outset.   But, if the secret sauce for all IF approaches lies in the reduction of meals, then it follows that the minimum number of meals that one can have in a given day and still eat is one.  This is the intuition behind my recommendation to only eat a single meal.  This is the only way to maximize the strategy of meal frequency reduction.   The intuition regarding meal frequency is also consistent with our understanding of metabolism.  In order for a meal to be assimilated it needs to alter your hormonal profile to convey the assimilation message to tissues at large.  This is principally done via the action of insulin, the metabolic acute energy status signal.  Accordingly, all meals, save those consisting exclusively of fat, will cause an increase in plasma insulin, which will in turn prompt systemic nutrient uptake.   More specifically, insulin will increase the activity of adipose lipoprotein lipase, suppress adipose hormone sensitive lipase, decrease the activity of muscular lipoprotein lipase ( this is an isozyme of adipose LPL with a different sequence of amino acids, but which catalyzes the same chemical reaction, hence the opposite response to insulin  relative to adipose LPL ), as well as induce translocation of the GLUT4 transporters to cell membranes.  The net effect of this is to cause muscles to switch from using lipids as an energy substrate to oxidizing and storing carbohydrate, as well as to cause adipose cells to go into fat storage mode.   Our working hypothesis, then, is that by limiting the meal generated insulin spike to a single episode, we will maximize the amount of time we spend oxidizing adipose tissue.  It would be nice if we could find some data to either confirm or refute our hypothesis.  It is actually surprisingly difficult to find studies in the...