March 13

More on the thermodynamics of weight loss


Okay.  I said I was through with Anthony Colpo, but now I’m going to quote from him once again.  What gives?

What gives is that I’m stuck in the airport in Seattle – my flight to Chicago is delayed for almost four hours because of bad weather in the Windy City.  I figured I would use this time to stick up a quick post about thermodynamics and provide a long quote from Robert McLeod, who writes Entropy Production, a physics (sort of) blog.  As you can see below, he pretty much trashes Bray and other nutritional researchers who blithely use the 1st Law of Thermodynamics to prove the old a-calorie-is-a-calorie notion.  To show the way the average nutritional writer looks at this law, I needed to find a quote.  As it works out, the only thing I have with me is Anthony’s book The Fat Loss Bible, which just happens to have the perfect quote.  So, sorry AC, I’m not really trying to pick on you.  And you certainly aren’t the only nutritional writer who thinks this way – you’re just the only one who has a quote handy I can use.

The First Law of Thermodynamics states that energy can neither be created nor destroyed. It can only be converted from one form to another. In other words, energy just doesn’t just magically disappear; it must be converted to something else. In the case of any excess calories you ingest, they will be stored as fat, used to accommodate an increase in lean tissue mass, or dissipated as heat through thermogenesis. Manipulating the proportion of protein, fat and carbohydrate you eat each day will not excuse you from the Law of Thermodynamics.

This is the way just about all nutritional scientists and writers look at the First Law.  Let’s take a look at how a physicist sees it.  Robert McLeod wrote a long post a while back reviewing Gary Taubes’ Good Calories, Bad Calories.  Near the end of the post, he discusses the energy balance equation and one of our old friends, Dr. George Bray, who gave Gary’s book a bad review in an obesity journal.  (I posted on this same review a couple of times here and here.)

Here’s what he says:

I was somewhat confused to see this [a nutritional description of the energy balance equation] Surely the nutritional scientists did not not really believe this, right? I mean, any idiot undergraduate students knows that the 1st Law is only useful in a closed system, and humans live on the planet Earth, not in an insulated box. Right?

Enter a rebuttal by G. Bray in the journal Obesity Reviews. Bray is a to be a major obesity researcher and one of the 2nd tier villains in the book. Taubes relates a story of Bray excising a section of a British report on obesity, where Bray removed the material pertaining to the relationship between insulin and obesity. He clearly has editorial support to make his case. Bray is one of the second-tier villains in Taubes’ book. Taubes has a footnote (p. 421), which suggests that Bray actively suppressed the carbohydrate-insulin hypothesis.

“According to Novin, when he wrote up his presentation for the conference proceedings Bray removed the last four pages, all of which were on the link between carbohydrates, insulin, hunger, and weight gain. “I couldn’t believe he would make that kind of arbitrary decision,” Novin said.”

Unfortunately, to a physicist this energy balance hypothesis looks like a silly hand-waving exercise, not a serious argument. Frankly I was flabbergasted when I first read this article. This conservation of energy argument is on the same scientific level as the ridiculous “drink cold water to lose weight” idiocy. A human organism is:

  1. Not in thermal equilibrium with their environment. Last time I checked I have a body temperature around 38 °C and spend most of my time in 21 °C rooms.
  2. Capable of significant mass flows (e.g. respiration).
  3. Capable of sequestering entropy (e.g. protein synthesis).

Is wearing a sweater fattening (by insulating you from your environment)? Here’s a quote from the rebuttal,

“Let me make my position very clear. Obesity is the result of a prolonged small positive energy surplus with fat storage as the result. An energy deficit produces weight loss and tips the balance in the opposite direction from overeating.”

According Bray’s thermodynamics argument, wearing sweaters makes you fat. This illustrates the greatest fallacy of trying to apply the 1st Law to a human: it makes the implication that living organisms consume kilocalories for the purpose of generating heat rather than perform useful work (i.e. breathing, contracting cardio and skeletal muscle, generating nervous action pulses, etc.). In reality heat is the waste product of basal metabolism. The first law does not distinguish between different types of energy. Heat, work are all equal under the First Law of Thermodynamics.

Applying the 1st Law to living organisms is Proof by Tautology. Yes, 1 + 1 = 2, but this tells us absolutely nothing about the underlying mechanics. The 1st Law does not (I repeat N-O-T) tell us whether you store excess energy in the form of fat, or bleed it off into the atmosphere by dilating blood vessels next to the skin, sweating, etc. To do so would require an accounting of entropy.

What would a semi-rigorous description of the thermodynamics of a human organism look like? Look at the title strip on the top of the page. See that equation in the background?

[The above is the background of the header of Robert McLeod’s blog]

This type of equation would be a bare starting point for energy balance in a complex system like a living organism. Good luck actually accounting for all the terms. Those Σs are sums.

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  1. A very fine post indeed by Robert. I’ve probably linked up to that a dozen times in various posts since he wrote it.

    Glad you’re aware of it. The Internet is truly an amazing resource.

    Safe flight, Doc.

    1. I read it when it first came out, but never really had a place to put it. Since I had some time on my hands and the Colpo quote available, I decided to devote a small post on it.

      We actually boarded a little ahead of our original delayed time. Writing this on my iPhone from seat #1B with a much-needed Bloody Mary at hand. Ain’t technology grand?

      And, BTW, thanks for doing the legwork to answer Stein; I just couldn’t bring myself to go through that paper again.

  2. Hi Dr. Eades,

    How is the weather in Seattle? Nice, I hope.

    I read the entire blog post by Robert McLeod from which you gathered the quoted information. He has some very interesting things to say in addition to the parts that you quoted. I found this part particularly interesting:

    “Prior to my introduction to the world of low-carbohydrate diet, I hadn’t paid too much attention to nutritional science. I worked on biophysics, where I formed the opinion that medical science was mostly garbage. This isn’t largely the fault of the scientists involved; there’s little opportunity for adequate learning though experience of repeated experiments and the systems involved are extraordinarily complex. As a physicist, if I get an correlation coefficient, R2 < 0.9997 in an experiment, I would consider that a poor result. A nutritional researcher working with human patients cannot even dream of achieving the degree of control or characterization I can, and their data are overloaded with spurious noise.

    Researchers in the soft sciences typically do not have sufficient math skills to understand the statistical methods that are they are using to evaluate their data. I've lost track of how many times I've seen evaluations of the mean and standard deviation for distributions that are clearly not normal (also known as Gaussian). Don't even get me started on p-values. More importantly, very few medical studies attempt to test a single hypothesis. Far too many studies will compare apples to bananas, rather than apples to no apples, or they'll compare apples, oranges, and bananas to no fruit. Making conclusions from such messily designed experiments is rife with the potential for misinterpretation. Drug studies are often an exception."

    What are we to think about that set of assertions? What do you think we should do after Mr. McLeod tosses out non-drug medical research?


    Michael Miller

    1. That’s why nutritional science is called a ‘soft’ science. You can’t do anything with the same degree of accuracy you can in a physics lab. Humans (and animals) are too different. You just have to do the best you can with what you’ve got. I do agree about the statistical analysis – most ‘soft’ scientists don’t have a clue.

      1. Right, as Einstein said, “All experiments are flawed, including my own, Trying to bolster your view by pointing out the flaws in your opponent’s experiments is a fool’s errand.”

      2. As a social scientist, I’m thrilled when I get an R-square value of .312 – the fact is that social science has to deal with far more spuriousness and a plethora of possible causes, while the hard sciences can isolate and focus on one particular cause. There’s also the issue, for social science, that it’s both impossible and unethical to perform experiments on human beings the way that, say, a biologist would perform an experiment in a lab on mice or rats or rabbits, or a chemist would perform an experiment in a lab with various chemicals, which limits us mostly to observational studies. For a social scientist, finding out that (for example) you can explain 31.2% of the variance in employment rates by racial or gender differences is a huge finding.

        However, if nutrition science is going to claim that it is science, it has to look at and report the results honestly, even if it doesn’t like what those results say about its hypotheses. Otherwise, it’s not science but woo-woo.

      1. Yes I did!

        Nice shirt!

        Did they strand you on the tarmac and offer you 4 potato chips and 1/2 cup of water like they did to that flight in New York?


        1. No, thank God. They let us sit in the terminal until time to go. We got on and left. And had an uneventful flight.

  3. How long will you be in Chicago?

    It always makes me cringe when television nutrition ‘experts’ continually shout out the first law and ignore the second. They bash Taubes and tell people they’re lazy gluttons, period.

    Technology really is grand. Where would we be if this kind of information were suppressed?

    Chris Masterjohn wrote a great little piece, “Why the State Hates Cholesterol” back in August:

    I’m absolutely convinced they want us sick, fat, dumb, poor, and powerless.

    Brilliant blogs, lately…keep it up!

    1. We’re not going to be here even 48 hours. Just stopped in quickly to drop by the big international housewares show. Will leave mid-afternoon Monday.

      Nice Masterjohn piece.

    1. Me too — even with 240mg desiccated thyroid I’m still cold — and wonder if the severe chills starting after low carb for type II diabetes have any connection (also effexor lists chills as a side effect — but permanent chills? after quitting effexor?)

  4. McLeod’s opinion on this makes a heck of a lot of sense to me. College-level physics 101 was a tough course for me, and many years ago.


  5. As the great Robert Heinlein said:

    “Never try to teach a pig to sing; it wastes your time and it annoys the pig.”

    The calorie-is-a-calorie folks have a 6th grade science class understanding of thermodynamics, something like claiming to understand gravity because what goes up must come down.

    I watched Robert McCleod try to explain this over at Lyle McDonald’s site many months ago. The psychotic response from Lyle’s merry band of circlejerkers was entertaining but cured me of any desire to weigh in.

    Luckily, you are made of sterner stuff… 😉

    1. You have certainly characterized that group correctly. I can’t believe Robert actually went there thinking he would be dealing with rational people.

  6. Your background in engineering serves well here. I vaguely remember studying entropy and enthalpy in engineering school over 30 years ago, but your point about entropy is well taken in the living organism context. We certainly aren’t closed systems. And we certainly are extremely complicated systems that are very difficult to accurately study using reductionist science. Seems like the more I learn about health science, the less I feel I know 🙂

  7. That was an excellent explanation of the fallacy of applying the First law of Thermodynamics to the subject of nutrition.

  8. I recently encountered another supposed expert commenting away on my blog about how I “clearly didn’t know what I was talking about” in poo-poohing the energy in vs energy out theory of weight loss. When will people get their head out of the sand long enough to recognise that perhaps there’s a reason the old theories don’t work, and that maybe it’s okay to admit you were wrong and be open to research that actually makes sense.
    Thanks for another great post Dr E.

  9. The concept of closed systems and when and how to apply the first law continues to elude many. Thanks for the taking the time to post.

    On another note, I saw this and thought it worth pointing out, because it seems medical professionals and patients look to medication to reduce risk factors associated with type 2 diabetes.

    IMO using medication to control lipids, weight and insulin makes no sense except in extreme circumstances. Controlling the diet is simpler and ultimately much less costly and more effective than medication in controlling type 2 diabetes and the health risks that stem from it..

    1. I agree with you about diet vs medications. Too many people just want a pill, however. And way too many physicians are willing to indulge them. There are always consequences when taking almost any kind of drug, but most people just don’t seem to care.

  10. I don’t mean to waste your valuable comment space and your time by heaping praise, but I can’t get enough of your musings and the directions they send me. I looked up Karl Popper and spent an enjoyable spell and intellectual exercise going over his very cool ideas of what constitutes a ‘good hypothesis’. I too read ‘Fooled by Randomness’ by Nassim N. Taleb and his other book ‘The Black Swan’. They, Popper and Taleb, and you are Low-carb, high-fat food for thought! But I’m writing one more time in defense of ‘low-carb and thermo’. My husband said my following explanation finally made sense to him. I’ve been firing off quite a few to try to get my point across that a low-carb, high-fat diet can’t violate any laws of thermo. (Neither can a low-fat, high-carb diet, but the superficial results are VERY different). HUMANS ARE NOT FURNACES. If the dietary fat we consumed was merely used to heat us and we were a closed system, then eating fat would make us obese. Dietary fat mostly goes towards maintaining our big fatty ‘higher’ brains. There is a portion that goes towards heating us and our metabolism for sure. We can grow new interneuronal, interglial connections and improve our brains (and our THOUGHTS) throughout our lives and that requires dietary FAT!. Low-fat diets degrade the brain. What’s truly scary (or remarkable) is that humans can subsist on low-fat, high-carb diets. I had an insight about what might be a manifestation and illustration of a human who is able to live (but not thrive) on a high-carb, low-fat brain-degrading diet. It appears to me there is probably a hierarchy. On a sub-optima low-fatl diet, the body and the lower (reptilian) brain are served first because the whole organism can survive this way. Then the higher (thinking brain) is degraded to serve the survival of the human. Does this make any sense? The integrity of the higher brain is actually sacrificed on a poor diet to the rest of the brain and body. You don’t need to think at a genius level to live but you do need to continue to breathe and circulate blood.
    An 83 year-old relative of mine who has eaten bread, corn oil, and partially vegetarian all her adult life is physically healthy but has short term memory loss (dementia). I think her higher brain is disassembling to serve the rest of her, and even though we have her eating more fat and meat and have banished frankenstein vegetable oils from her diet forevermore, the damage may be irreversible.

  11. In my own profession (chemical engineering) I’ve seen many, many well-educated and experienced engineers tripped up by thinking compliance with the FLOT is all that matters while completely forgetting about the SLOT. And, yes, they dont even get the FLOT part right to begin with.

    PP and PPLP since October 2009. 213 lbs to 178 and holding. BP 130/80 to 123/74 and still falling.

    Still grateful,

    1. Since I was a civil engineer and not a chemical engineer, I’m clueless as to what FLOT and SLOT are. Please enlighten.

      Glad to hear you’re doing so well on PP.

      1. A fellow ChemE stepping in..

        FLOT = First Law of Thermodynamics (You can’t win…)
        SLOT = Second Law of Thermodynmaics (You can’t break even)
        TLOT = Third Law of Thermodynamics (You can’t quit the game)

        Loved the post. PP since January 4th, down 20+lbs, and I think I might have self diagnosed a reaction to glutten (not intolerance, just a reaction…)

        Thanks, Dr. Mike. I love reading this stuff.

  12. I think we’ve established from your recent blog posts that you can prove/disprove just about anything using theories.

    How about doing something practical like getting yourself a Bodybugg/GoWear Fit & using it?

    1. OK, Niggee, this is twice with this idiocy. Any more get deleted. Unless, of course, there is some deeper meaning that eludes me.

        1. You placed the same comment in two different places without any context. If I took it wrong, you have my profound apology. I guess there was a deeper meaning that eluded me.

          1. I think Nigel is suggesting that you [or someone] use a Bodybugg under different dietary conditions and see if there is a larger energy expenditure on LC/High Fat, thereby putting MA to a non-theoretical test. Interesting if Bodybugg was accurate, but it’s not, especially on the expenditure side. 24 Hour Fitness pedals these to their clientele, and I end up seeing a lot of the reports. I can testify beyond doubt that the expenditure side [at the very least] is highly inaccurate.

          2. That’s correct. I posted a link in my post in the other blog explaining about the Bodybugg/GoWear Fit but thought that it had vanished into cyberspace.
            Tell me more about the inaccuracies. There are known errors e.g. under-reporting due to static cycling, over-reporting due to tennis, say and under-reporting due to low body temperature caused by hypothyroidism.

          3. Sorry about that. I was a little impatient and wasn’t sure whether or not my comment in the other blog post would appear. I couldn’t see it awaiting moderation.

          4. @Nigel re: Bodybugg

            It’s been a couple of years since I read their validity data, so this is from memory. I believe they developed their metric of energy expenditure from what I believe are three measurements: surface skin temp, an accelerometer and I think galvanic skin response. I also seem to remember that their validity study vs. indirect calorimetry was small and I think everybody did the same kind of exercise, like treadmill or bicycle ergometry; no other activities of daily living or even sleep. There are typically practical variances that occur when a small lab study is generalized to real life. There are also well documented inaccuracies with accelerometers.

            But for me, the main issue was what was in the reports. I’ll give you two of my favorites: a female was given 700 kcals for a very modest 30 min walk in which she was swinging her arms. This wasn’t anywhere in the universe of a power walk per relative heart rate. This was closer to a stroll. Another female was given similar energy expenditure credit for the 30 times per day that she walked 30 feet to her deck to have a smoke. I’m uncertain that someone extremely adapted to nicotine has that kind of a metabolic boost from it. I don’t know how many calories one typically burns in sleep, and maybe it’s quite a lot, but I was usually surprised by the amount of expenditure for muscle activity that was given during sleep [and no, there was no hanky panky].

            When you factor in things like known inaccuracies as you reported, inaccuracies with accelerometers, the accuracy [?] of surface skin temp as a measure of metabolic rate, your inaccuracies can get quite large. If the MA of LC/HF is in the range of a couple of hundred calories as suggested, you’re unlikely to catch it using this device.

            It’s a classic calories in/calories out method. I’m pretty sure the energy input is off by a good amount also as it utilizes the USDA data base, and at least the last time I looked at one, the user could not input unique foods not in the data base. Serving sizes are challenging for people who are not trained to eyeball servings, and even if you’re good at it, it’s often off enough not only to completely miss a test of MA, but to miss a reliable test of energy input in general.

            I usually see these when someone comes to me to lose weight, completely frustrated because their Bodybugg tells them they’re eating 1200 kcals and expending 3500 and they’re not losing weight [ok, maybe that’s a little exaggerated but not much].

            The efficacy of using galvanic skin response to determine energy expenditure was always something I meant to research and never did, so I went out quickly while writing this to find something on it. I came to this during the hunt, not on glavanic skin response, but on the devices themselves:


  13. I’d never previously read Dr. Bray’s critique of GCBC. Thank you for posting it. I’m so stoked now that I know that due to doubly labeled water technology, we now know that obesity is caused by fat people having even poorer measuring skills than lean.

    Of the many things I was surprised to read, the comment that there is no convincing evidence that carbohydrates are producing type 2 diabetes made me go, “Whaaa??” Then why are my diabetic clients on flexible insulin therapy or oral agents instructed to calculate their medication per their carbohydrate intake? Diabetics don’t count their protein or fat grams, they count their carbs. For me, there is pragmatic observation of association, and then there is intellectualized giving-you-a-hard-time-because-technically-I-can, which I think makes up a large part of his critique.

    Well, no point in going on because for me, the review just worsened as the pages progressed, on many topics large and small.

    Thank you for continuing your excellent and accessible posts on this important topic of energy balance. I circulate these writings widely, to people who’s health really depends on grasping the area of most usefulness, and who have spent decades often continuing to lose health because apparently they don’t know how to measure.

    Oh, I wonder if AC has a response up to your final post. Must go look.

    1. It looks as if AC has cut and ran. His first critique is gone as is his entire website. The last time he got a caning like this at my hands he vanished for about a year. I’m sure he’ll be back.

      I hope he does return. He’s a smart guy who has a lot to offer. He’s just got to learn to do it civilly and that he’s not infallible.

        1. Yep, he’s back up. His entire site was down for a few days, though. I guess he was just migrating it or something. I’m glad to see him back.

    2. Hi LC. Thanks for your reply of March 20th. There’s no “Reply” to click on at the end of that message, so I’m replying to you here.

      I know that the BB/GWF is inaccurate for exercises where the arms aren’t moving enough (cycling) or where the arms are moving too much or where body temperature is abnormally low. I thought that it was otherwise fairly accurate.

      It was just a thought, as Metabolic Wards are hard to come by!

  14. This is off topic, but could you post a list of your favorite books from last year? Your last list (from 2008, I think) was a great resource. (My wife enjoyed Mistakes Were Made . . . so much she just ordered TEN copies to give to friends.)

    1. Just did post the 2009 Bestseller list. You were the inspiration for it.

      I thought I had already done it, and when I went to look for it to give you the link, I discovered it didn’t exist.

      Thanks for the prod.

  15. Dr. Eades-I am newly diagnosed with IBD, I hve been VLC for about 6 month. Do you think that I can reduced my inflammation with diet alone? Thanks

  16. Hey Dr. E,

    I came to your site from Robb Wolf’s blog, and have recently read “Protein Power.” Pretty different from the Zone, and I think it makes a bit more sense (eating 4 blocks of spinach and broccoli is overwhelmingly difficult). Anyway, I had a question in reference to one of your recommendations for limiting arachidonic acid consumption (an issue that both you and Dr. Sears agree on, although Dr. Sears seems a little more concerned with it). You say to limit red meat and eggs and to trim the fat from cuts of red meat, and you allude to the diet high in grains that these animals are typically force-fed in factory farms. I was wondering if you think that applies to free range chicken eggs (especially ones that are high in DHA from a diet high in flax seed) and pasture raised beef/bison, or if this more natural diet reduces the risk of AA. I’m not particularly reactive to AA (from what I’ve noticed) but I am still young (26) and follow a pretty strict paleolithic dietary model, with intermittent fasting (12-16 hours a day). I know that you were less than convinced on the IF regimen, but I also wondered if your hesitation was more due to implementation rather than effectiveness or if you just think that it’s an individual issue more than one that can be applied as broadly as the low-carb recommendation.

    Sorry that these topics don’t have much to do with this post, but I’ve just recently come across your site and have searched through the archives reading as much as I can to catch up. Thanks for the hard work you put into the site.

    1. Actually, I’ve changed my mind on the whole arachadonic acid issue. I don’t think it makes a lot of difference as long as one is on a low-carb diet. There is a great paper by Volek on this subject that I need to post on.

      And I’ve gone back the other way on the IF issue. I think it works, but I think it’s pretty difficult for most people to implement. What works better for me is to go long periods without eating here and there. It gives the liver a rest while still allowing normal schedules to be maintained.

      1. Could you more closely define what you mean by:
        “go long periods without eating here and there” ???

  17. Dr Mike, I am back. I have been missing for a while, hope you didnt miss me too much! I have gained 30 pounds being off low carb. I developed IBS and it was horrific. I somehow contributed it to low carb at least partially. But it was stress related. I am taking metoprolol and it takes away all constipation issues. So I am back on induction low carb and it is no picknick. I feel like my mind and my body dont know each other. But I am staying optimistic, even though it is not easy. The only difference between an optimist and a pessimist is that an optimist is an illinformed optimist.

    Do you know of any tricks to ease into the low carb full force for people like me who cant do it half way? I Some people like to wean off carbs gradually, I cant. Its easier for me to jump into frozen water without stretching or warming up. I was just wondering if you know any supplements I can take to help me with this transition. Thanks!

    1. Sad to say, but the only advice I can give you is to suck up and do it.

      The Metabosol might help if you haven’t tried that.

      Maybe some other readers will have suggestions.

  18. Off topic, but just a note to point out that the links don’t work in the bar below your logo (well, the skulls and blog name). After multiple attempts, I finally noticed that there are (new?) links, that work, in a bar above the logo. So looks like you just need to delete the ones below.

  19. I’m afraid I’ve figured out leptin. Great thing for a social-anxiety type to do. Peter at Hyperlipid helped. People actually showed up and gave me hell, for talking so much. Nobody else seemed to know what was going on.

    The case for leptin as a regulator of glutamate.

    My first clue that leptin might be a regulator of glutamate metabolism came from this study;


    Protein appetite is increased after central leptin-induced fat

    Leptin reduces body fat selectively, sparing body protein. Accordingly, during chronic leptin administration, food intake is suppressed, and body weight is reduced until body fat is depleted. Body weight then stabilizes at this fat-depleted nadir, while food intake returns to normal caloric levels, presumably in defense of energy and nutritional homeostasis. This model of leptin treatment offers the opportunity to examine controls of food intake that are independent of leptin’s actions, and provides a window for examining the nature of feeding controls in a “fatless” animal. Here we evaluate macronutrient selection during this fat-depleted phase of leptin treatment. Adult, male Sprague-Dawley rats were maintained on standard pelleted rodent chow and given daily lateral ventricular injections of leptin or vehicle solution until body weight reached the nadir point and food intake returned to normal levels. Injections were then continued for 8 days, during which rats self-selected their daily diet from separate sources of carbohydrate, protein, and fat. Macronutrient choice differed profoundly in leptin and control rats. Leptin rats exhibited a dramatic increase in protein intake, whereas controls exhibited a strong carbohydrate preference. Fat intake did not differ between groups at any time during the 8-day test.

    Leptin seems to decrease appetite in rats only until fat mass is depleted. After that, appetite returns, and is similar in calories to non-leptin treated animals, but food preference changes to protein from carbohydrate in comparison to control rats. This suggests that rather than regulating calories, it regulates appetite for protein. In a similar way, insulin infusions will increase the appetite for glucose.

    Now, glucose tastes sweet, so I wondered if there was a particular taste associated with leptin. I was looking for a protein taste, so umami seemed like a likely possibility. And umami is specific to glutamate.

    So I needed a study showing the secretion of leptin in reaction to proteins. And I found it in this;


    Regulation of leptin secretion from white adipocytes by insulin, glycolytic
    substrates, and amino acids

    The aim of the present study was to determine the respective roles of energy substrates and insulin on leptin secretion from white adipocytes. Cells secreted leptin in the absence of glucose or other substrates, and addition of glucose (5 mM) increased this secretion. Insulin doubled leptin secretion in the presence of glucose (5 mM), but not in its absence. High concentrations of glucose (up to 25 mM) did not significantly enhance leptin secretion over that elicited by 5 mM glucose. Similar results were obtained when glucose was replaced by pyruvate or fructose (both 5 mM). L-Glycine or L-alanine mimicked the effect of glucose on basal leptin secretion but completely prevented stimulation by insulin. On the other hand, insulin stimulated leptin secretion when glucose was replaced by L-aspartate, L-valine, L-methionine, or L-phenylalanine, but not by L-leucine (all 5 mM). Interestingly, these five amino acids potently increased basal and insulin-stimulated leptin secretion in
    the presence of glucose.

    Unexpectedly, L-glutamate acutely stimulated leptin secretion in the absence of glucose or insulin.

    Finally, nonmetabolizable analogs of glucose or amino acids were without effects on leptin secretion. These results suggest that 1) energy substrates are necessary to maintain basal leptin secretion constant, 2) high availability of glycolysis substrates is not sufficient to enhance leptin secretion but is necessary for its stimulation by insulin, 3) amino acid precursors of tricarboxylic acid cycle intermediates potently stimulate basal leptin secretion per se, with insulin having an additive effect, and 4) substrates need to be metabolized to increase leptin secretion.


    Even though the flavour is glutamate, I kept thinking glutamic acid, it finally sank in properly today.

    Various proteins stimulate leptin secretion in the presence of insulin or glucose. But only glutamate was found to stimulate leptin in their absence. This makes glutamate an excellent candidate for the protein regulated by leptin. The effect of other proteins on leptin secretion is likely an artifact of their interaction with glutamate, under the influence of insulin.

    Glutamate metabolites feed into the krebs cycle at several points. Fat cannot be metabolized for energy without this cycle, which explains the apparent control by leptin of appetite which disappears once fat is depleted. This is clearly true. Not a theory, just an observation.

    Poorly-regulated glutamate causes excitotoxicity in the brain, killing neurons. This is a protein needing careful regulation. The idea that disregulation of leptin/glutamate metabolism is involved in some neuro-degenerative disorders seems obvious. True by definition, even. They’ve even found that leptin activates glutamate receptors, without making the connection. There are also plenty of glutamate receptors in the gut.

  20. Oh well. In for a dime, in for a dollar.

    My work on leptin raised an obvious possibility. There are five tastes, umami, sweet, bitter, and sour. Leptin goes with glutamate, umami. Insulin with sweet, obviously.

    Are there other hormones corresponding to flavours? That might give a clue to their function in the human body.

    After a while it occurred to me that Amylin, which is the peptide that accumulates in amyloid plaque in the pancreas of people with type 2 diabetes, and in the brain of people with alzheimers, appears to sensitize people to leptin. Dr Bernstein gives amylin to some of his patients in order to decrease appetite for glucose.

    Now, does that sound familiar? So although amylin isn’t technically a hormone, it seemed a likely candidate for a third taste related hormone-like substance.

    This Stephanie Steneff article gave me the information that I needed.


    However, amyloid-beta has the unique capability of stimulating the production of an enzyme, lactate dehydrogenase, which promotes the breakdown of pyruvate (the product of anaerobic glucose metabolism) into lactate, through an anaerobic fermentation process, with the further production of a substantial amount of ATP.

    I thought lactic acid was the significance of sour because of this. But then I realized that since amylin facilitates pyruvic acid breakdown into lactate, it must be secreted instead in response to the presence of pyruvic acid.

    Once you look at it that way, something becomes obvious. The beta cell secretes insulin in response to glucose. It does this for the same reason that a yeast cell does; to get and use glucose. Beta cells are so bad at this that they provide enough insulin to service the needs of the entire human body.

    Following this line of reasoning, it makes sense that excessive amounts of amylin would be produced or secreted when large amounts of pyruvic acid are present. The amylin facilitates the use of pyruvic acid for energy.

    So the amyloid plaque in type 2 diabetes and alzheimer’s starts to look like the signature of a bloom effect. Large amounts of glucose must have been broken down to pyruvic acid, spurring excess amylin production. The cells aren’t intelligent; just like yeast cells, they have no idea that the high levels of pyruvic acid aren’t forever, so they overproduce in anticipation.

    Now, this is important; why would large amounts of pyruvic acid form? One possibility is that a local energy crisis has occurred, forcing cells to turn to the fermentation of glucose for a quick source of energy. This would lead to large amounts of pyruvic acid in the area.

    What would cause the cells to turn to glucose fermentation? In cancer cells, it has been suggested that a local lack of oxygen might cause this. This makes obvious sense, fermentation is anaerobic.

    Another possibility occurred to me, again thanks to Stephanie Stennef’s article. You can’t ferment fat; a local lack of free fatty acids might cause the excess fermentation of glucose that leads to pyruvic acid formation and high-gear amylin release.

    Animals that burn more fat for energy vs sugar live longer, this crosses many animal species. Niacin, vitamin D, and a low carb diet done properly can raise adiponectin levels. Adiponectin lowers glucose production in the liver.

    What lowers glucose production? Our old friend physiological insulin resistance. When free fatty acids (particularly palmitic acid) enter the cell and feed into the Kreb’s cycle, cellular energy needs are met and the need for glucose is reduced. So free fatty acids should make the fermentation of glucose to pyruvic acid less necessary and therfore less likely.

    So it seems likely that when blood levels of free fatty acids are low, the probability of cells needing to turn to glucose fermentation to meet their energy needs becomes much lower. This has obvious implications to the development of cancer.

    That leads to thinking about what happens besides cancer when levels of free fatty acids are low. If a yeast-like bloom can occur when free fatty acids are not present, (fat acting as a control-rod of glucose and glutamate metabolism is another way to look at physiological insulin resistance), then tissues that are in greater than usual need of energy should be more susceptible to damage.

    Tissues that are healing. Adiponectin decreases the risk of heart disease and atherosclerosis. Most of the nutrients that Dr Davis advocates to reverse plaque increase adiponectin levels. A local energy crisis could explain improperly healing arteries. More free fatty acids, lessened likelihood of a disrupted energy supply.

    A problem in this is that Type II diabetics often have higher than usual levels of free fatty acids in their blood. But they also often have compromised, undersized mitochondria; this could force them to turn to glucose when energy needs are high.

    Once you’re thinking lack of energy, compromised repair you think; cavities, bone loss, sarcopenia or muscle loss.

    All of the western diseases showed up together. It makes sense that they might have a common cause.

  21. So it seems likely that when blood levels of free fatty acids are low, the probability of cells needing to turn to glucose fermentation to meet their energy needs becomes much lower. This has obvious implications to the development of cancer.

    Obviously, I meant to say when free fatty acids are high.

  22. Re the links, you wrote, “I just checked, and they work fine for me.”
    Thanks for checking! For me they don’t work from Firefox–and I’m pretty sure they used to. But I just checked and they work just fine from AOL. Sorry to bother you …


    1. Weird. I use Firefox and they work fine for me.

      No problem about the bother. I like it when readers inform me of things that don’t work.

  23. I’ll get you those studies, but first you might want to take a look at this;

    “This response to amino acids was decreased by 60% when glutamine was omitted. Insulin release by SUR1–/– islets was also stimulated by a ramp of glutamine alone.

    In normal islets, methionine sulfoximine, a glutamine synthetase inhibitor, suppressed insulin release in response to a glucose ramp.

    High glucose doubled glutamine levels of islets.”

    Glutamine has been found to induce “insulin resistance” in fat cells.

    Muscle cell glutamine production is increased by insulin.

    Suppressing glutamine synthesis suppresses insulin release in response to glucose.

    Insulin regulates glucose indirectly. Glutamine production decreases availability of glutamate, which reduces availability of glutamate-derived metabolites necessary to mitochondrial respiration. Less fat is fed into the kreb’s cycle, increasing the cell’s dependence on fermentation of glucose for energy, which increases the demand for glucose. Remember how exercise can increase glucose uptake without increased insulin? This is apparently why. And they did the study in 2004.

    For proper symmetry, I guess it will be necessary that leptin increases the production of glutamate.

    No wonder insulin is anabolic. It spares proteins from mitochondrial respiration (krebs cycle)

    “Methionine sulfoximine inhibition of glucose stimulated insulin secretion was associated with accumulation of glutamate and aspartate.”

    I should say that insulin is expressed by the beta cells in reaction to glutamine to facilitate its uptake. Insulin will increase the demand for glutamine in any cell. If pre-made glutamine is not present, the demand for glutamine will be served by the synthesis of glutamine from glutamate. Sometimes I talk right around my main point.

    Still believe in black swans, Dr Mike?

  24. It strikes me now that amylin probably increases the demand for lactate, since it increases its production from pyruvic acid. This means that the pyruvic acid ïnduced excess production of amylin is false; amylin must be secreted in reaction to the presence of lactate.

    In the movie THE WIZ, Michael Jackson plays the down and out scarecrow. WHen he meets Dorothy (Diana Ross) he sings a song. Some of the lyrics are ‘you can’t win’, ‘you can’t break even’, ‘you can’t get out of the game’. I saw this movie in the early 80’s (before I took thermo). I rented it recently to watch it with my daughter and I just about fell down laughing when this song came on. It’s priceless.

  26. Many thanks to Suzie for the FLOT (you cant win) and SLOT (you can only lose) definitions. A slight correction: I’ve gone from 203 lbs to 178, but what’s 10 lbs between friends?

    Speaking of IF:

    Just today I had the medical profession’s 50th birthday present: a screening colonoscopy. The 36-hour fast was a piece of cake! Well, low-carb ‘cake’, anyway. No surprise there; I’m on PP/PPLP maintenance. Even AFTER the ‘scoping, I didnt feel particularly hungry. Just for grins, I watched my BP while fasting and it was typically 106/68 [!]


  27. Thanks for your insightful breakdown of thermodynamics. It was like being in Chemistry class all over again, and much needed at that! I always forget about the whole ‘controlled system’ aspect of the first law.

    On another note,
    I have run across a study that seems to have confounded me and my comparatively limited nutritional knowledge compared to others. Every once in a while this happens as I find something that i just cannot seem to find where the high protein/low carb angle fits in.

    Here is the study in a nutshell (I can cut and paste the entire text from my subscription service, but didn’t know if that would be too long for this comment form): subjects were fed 5 different macronutrient distributions:
    -50g glucose (50g cho)
    -white bread bagel (49g cho; 7g pro; 2.5g fat)
    -peanuts (6g cho; 8g pro; 14g fat)
    -solid protein bar (3g cho; 29g pro; 6g fat;)
    -liquid protein drink (2g cho; 15g pro; 4g fat)

    blood samples were taken and glucose and insulin levels were measured after each trial to determine the relative levels of glucose in the blood at established times and the resulting levels of insulin in the blood post-absorption.

    As you can guess, the meal of peanuts elicited no insulin response, however, the bottom line that confuses me in the results of the study was that the high protein containing bar and liquid protein drink were shown to raise insulin comparable to the consumption of the 50g glucose, as insulin release is stimulated by protein.

    I know that insulin does play a role in protein uptake and storage for cells, but what I can’t seem to understand here is that a low-carb diet should keep insulin from elevating, thereby also regulating fat storage and cholesterol synthesis, but if high protein consumption occurs, which is purported to increase insulin to the same levels as carbs, then where is the advantage?

    I know that I must be missing something and I would be happy to post or email the entire study if its not too much trouble for you to read through…

    thanks in advance.

  28. Dr. Eades,
    Can you suggest any further reading about the effects of a high fat diet and reduction of insulin resistance without the use of medication. If it is Protein Power, then say no more. It’s on my list.

    1. Protein Power is a good start. You could also read The Protein Power LifePlan and/or Gary Taubes’ Good Calories, Bad Calories.

  29. I appear to be on Colpo’s mailing list and received his latest. As for most natural and man-made disasters, it was hard not to look. He agrees that:
    “There is indeed a tiny diet-induced thermogenic metabolic advantage for high-carb diets, but it’s too small to make any noticeable difference in weight loss.” This is the same argument that Buchholz and Schoeller made. I assume he means ‘low-carb’ but isn’t that the end on it? Is it possible that they don’t know the difference between theoretical and experimental. The case is exactly the opposite of the evolution of the steam engine which, in its earliest implementation, was highly inefficient. If we’d taken the approach of these guys, we would stop trying to perfect it and there would be no industrial revolution and this message would be delivered by hand after weeks across country on horseback. The world according to Colpo and Schoeller. Apologies if everybody is tired of this.

  30. Oh my goodness! Here is another video of half-arsed advice!

    Holly Robinson-Peete has a child with autism, and on a Larry King show, shared the fact that her child does better without wheat. And then she gives us this advice–I guess she really isn’t putting the pieces together–it doesn’t matter if cereals are “whole” they still do damage! I know, I know she’s reading a script–it still has her face and reputation attached to it!

    “Myths” #1,3,4 are not at all dealt with, the advice is still wrong.

    #1 is about eating whole grain–not good for many of us.

    #3 is about aerobic exercise, or “cardio” being necessary for heart health–not true! For a good explanation of this, go to

    and click on the videos. There is a nine part explanation of real exercise.

    #4 recommends light weights and high reps of you are a woman afraid of being “cut”! It’s not going to happen if you are not genetically designed for it. I am a 5’2″ woman who can now leg press 572 lbs, pull down 200 lbs, plus more on other machines and I am not “cut”–it’s not in my genes! Light weights and high reps are a complete waste of time and lead to sore joints–not stronger muscles.

    “Body by Science” the book by Dr McGuff offers the same philosophy of exercise as Fred Hahn’s “The Slow Burn Fitness Revolution.” Both explain what has been called super slow or high intensity exercise.

    I now exercise on seven MedX machines for 16 minutes, ONCE PER WEEK.

    I’ve lost two dress sizes. I can now bound up stairs like a teenager. I got up from a plane seat after a five hour flight like nothing happened. I stood in line for an hour and a half for that same flight without leg or back pain.(I love LAX-/snark)

    Anybody who hasn’t tried this ought to find the nearest super slow trainer ASAP and try it out. No wonder the Drs. Eades recommend this type of exercise.

    Okay, rant over.

    1. There is much misinformation out there, that’s for sure. Glad you’ve done so well with the slow-burn kind of exercise. As far as I’m concerned, it is the only way to go. Great results without spending your life in the gym.

  31. I’m a chemical physicist who spends a lot of time thinking about thermodynamics. I was having a discussion with another physicist friend of mine about the whole Energy In/Energy Out argument, and I didn’t get through to him until I wrote out the equations. Rather than going through all of the entropy accounting discussed in the OP, I just did a simple thermodynamic analysis. I wrote it up and my wife put it up as a guest post on her blog, so if you want to read it, go ahead. It’s nothing new to this crowd, but I wanted to get the simplest correct statement written down so that I could use it as arguments with other physicists.

  32. Dr Eades

    Would the thermogenic process underlying protein breakdown explain night sweats. On very low carb days (well under 30gms) if I have eaten quite large amounts of protein in particular I suffer extreme night sweats. The low carb intake would suggest to me this is not reactive hypoglycemia – and also this generally happens about 2-3am, a good 6 hours or more after eating. Is it the body’s way of burning off the excess calories have eaten in protein? interestingly on the odd day i have eaten more carbs than I should – no night sweats occur.

    Or is this happening because to my shame I dipped into anorexic tendencies for a tear or two – (despite managing to maintain muscle through exercise and eating minimal protein i weighed under 100lbs, low carb however got m back on the right track as it freed up my obsessive restriction). I now weigh around 110 (5ft 4) and am happy to maintain at this – but the night sweats remain disruptive. Your thoughts would be much appreciated – is excess protein the cause?

    Ps finding your articles have been a godsend, and has really helped on my road to requiring a somewhat normal attitude to nutrition.

  33. Hi , Dr Eades.

    Anthony Colpo et al, are examples of nonscientists taking an idea from science and running with it in strange directions.

    Let’s review The First Law of Thermodynamics :

    Energy can be transformed ( changed from one form to another) , but cannot be destroyed.

    Matter of course is just energy in a particular form.

    So, the total energy in the universe is fixed, and has been fixed since the Big Bang according to classic physics. And if you can establish an energy – impermeable subset of the universe, then the amount of energy in that subset will be fixed. ( That’s much harder to do than it sounds.)

    The law is considered valid, but of late, some questions have surfaced. How does vacuum energy ft into that picture? Some theoreticians think that in the vacuum of subatomic particles, strange particles are coming into existence and vanishing spontaneously all the time. The nature of subatomic particles is of interest: they may just be “vibrating strongs of folded space-time”. Which suggests the conditions under which space -time is folded might not be unique to the Big Bang.

    The First Law might only apply under certain conditions, and not others in other words. Then there’s the huge question of Dark Energy, which appears to be accelerating the universe’s expansion. We don;t know what it is, or how it maty illuminate the First Law.

    Then there’s the idea that our universe is just part of a larger multidimensional structure; we have no luck explaining physical observations with only 4 dimensions, and if there are more, we have to think about how energy and matter – or something else- in other spaces might influence the universe we can observe.

    How any of thi splays into obesity is not a question real physicists are addressing. This is just another case of nonscientists ( Anthony Colpo et al) latching onto an idea from science and running with it in strange directions.

    The First Law does not “prove” the caloric hypothesis because a human being is not a closed system. Matter and energy from the environment escape back to it. The question of how much of what is ingested is packed away in fat cells as opposed to used to power physiological processes or eliminated as waste matter and energy is not answered by the First Law. The First Law demands that no matter or energy be created, or destroyed, and in sum, as far as we can tell , none is, but that ‘s the end of the First Law’s reach.

    And it might not even reach that far. Much remains to be learned about energy and matter, and we’ve reason to suspect that the First Law may be a special case, applying only under certain circumstances. It’s even possible the entire law may be discrded, eventually.

    Sometimes to understand a system, it’s necessary to look at extremes.

    Here’s an extreme for you. In the devlopment of Type II diabetes, insulin resistance goes up. Many Type II diabetics experience a strange phase where appetite rises ( due to cells refusing to accept food, so they’re actually starving), and there food intake goes up in response, but they lose weight, and sometimes quite rapidly. In fact, rapid unexplained weight loss is one of he first things physicians ask patients about when diagnosing Type II diabetes. These patients can be ingesting 4,000 or 5,000 calories and still be shedding weight.

    That is impossible according to the caloric hypothesis. But then again, lots of things we observe about weight are impossible under the caloric hypothesis: drugs causing weight gain with absolutely no change in food consumption, thin rats gaining weight when intestinal flora from obese rats is transfused into them ( and no change in food consumption), site – specific differences in fat cell behavior ( lypodystrophy, male-female site – specific differences, etc.) Those are only some examples.

    The caloric hypothesis us dead. Too bad there are so many people around like ( Anthony Colpo et al) who don’t know it yet.

    Gary Taubes has very valid criticisms of the complete failure of dieting for the successful long term treatment of obesity.

    Linda Bacon Ph.D. is another person to look into Dr Eades, as well as Matt Metzgar’s blog which has new articles on obesity. I encourage all on here to look into them and even make Anthony aware of them.

    If there is one thing crystal clear in the scientific literature it is that dieting does not work. It just raises your bodyfat setpoint trying to protect you from future dieting. People who pimp caloric deprivation give out horrible advice. I hope Anthony sees he is being just like he cholesterol theory proponents on this issue. I hope he comes around, but probably won’t.


    Take care , Dr. Eades. 🙂


  34. Hi Dr. Mike,

    I have been following your blog for quite a while now. It has truly been a lifesaver. I’ve been eating low carb for a few months now (to lose weight) and wanted to try and understand the mechanics behind it – your posts are superior to all other ‘explanations’ out there.

    I hope this is in an appropriate section, but I would greatly appreciate your help. Hopefully it will be a bit of a challenge for you! Quick bit of background; I’m a 23 year old post-grad student living in Aus, at a healthy BMI of 23 (but I’m very very tall, so that never seems to have been a good indication). I have lost 10kg eating low carb, and am ALMOST there… 3kg to go! I religiously count carbs (even the ‘negligible’ ones in cheese, lettuce etc.) AND calories and have been tracking my weight loss. I have calculated my BMR using the Harris Benedict equation and ‘predicted’ daily losses accordingly. For the most part, my weight loss corresponded quite well with the predicted values. I have been restricting to around 1300cal per day (my BMR is approx. 1800 and I have accounted for a decreasing BMR due to decreasing body mass by calculating a daily BMR based on body weight). I have also made sure I eat around 100g protein a day to prevent/minimise muscle loss.

    Recently, I have hit a stall. My weight has remained the same for the past 3-4 weeks, despite eating only 1300cal/day and <20g carbs. I have tried everything to break through… I introduced exercise (cardio), I had a large calorie day etc. Nothing has worked. I am at the point of giving up. Low carb has freed me from a severe binge eating disorder I struggled with… I can feel that creeping up again because the results are not there! The math says I should have lost… the reality is quite the opposite.

    Could you please shed some light on this? Is there some kind of explanation? Most sites blame 'starvation mode' for stalls… But after reading your posts, I understand it is not that simple.

    I would deeply appreciate ANY help/explanation/advice you could offer.


  35. I have no background in chemistry, well i did have 2 subjects but that was not interesting to me. Anyway, i agree with thermodynamics by the simple body compensatory mechanism. when we feel cold our thermoregulatory center will produce heat thus increasing blood flow into the surface of the skin to counteract cold. Since heat is produce by metabolism then the stored fats will be used by the body. How about outside body heat application? Im wondering if sauna and steam bath will do same effects?

  36. well, chemistry doesn’t interest me much but the argument on how body compensate to maintain equilibrium like when the body is in low temperature or feel cold. The thermoregulating center will produce heat maybe by burning the fats and producing brain chemicals to aid this process. The heat will spread to the surface of the body to insulate the body from cold. I’m not sure how much kilocalories will burn in this process but i think its better than warming yourself from outside in with a sweater.

  37. I’m surprised you’re quoting Anthony Colpo at all because he sure has a lot of negative things to say about you. To me he seems more like a deranged stalker than anyone who is worthy of getting into a discussion with.

  38. I’ve just read Taubes’ GCBC which brought me to read the Bray review and Taubes’ rebuttal.

    I have a couple comments – first Bray cited himself numerous times – check the end of his review, I’m not anal enough to count them, but could only snicker when I noticed.

    And “bray” is a noise …. er..donkeys make….

    Dr. Eades – thank you so much for your tireless work and wisdom – you’ve helped me enormously.

  39. Dr. Eades,

    I’m sorry but was this article stating that from a physicist’s point of view that cold or heat does not affect the body’s metabolism? The quote seems to sound like it’s ridiculous to think that wearing a sweater will cause you to burn less calorie, but if it helps keep you warm them it most certainly does. You’ve spoken in the past of uncoupling proteins and one of their main jobs is to heat the body (mainly UCP-1). Clearly being cold causes you to increase metabolism.

    If you want any real world examples look at Michael Phelps who consume 10,000 calories a day and maintains his weight. If you do the math you’ll realize it’s impossible for him to burn that many calories through activity or normal metabolism. The fact of the matter is that the 4 hours he spends training all take place in water, which is highly thermoconductive. The same can be seen for people who climb Everest. They have trouble maintaining body weight and end up losing weight far faster than their activity and intake would dictate. It’s due to the cold.

    There are plenty of real world examples of people using cold to more than double their weight loss. Hell the entire purpose of brown adipose tissue is solely to produce heat (and yes, research is showing is does exist in adults).

    Sorry if I misunderstood this article and you agree with me, but from the sound of it I’m pretty sure you don’t agree. I’d like to hear your thoughts on it though.

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