Thermodynamics and the metabolic advantage

There are a lot of disagreeable  jobs out there.  Dealing with Anthony Colpo is one of them.  Trying to make sense of thermodynamics is another.  Whereas dealing with AC is kind of like the job pictured at the left – distasteful but fairly simple – delving into the workings of the laws of thermodynamics is intellectually challenging but far from easy.  Problem is, it appears kind of easy, and everyone, it seems, fancies himself to be an expert.  (How many people have we heard blather on about how a calorie is a calorie is a calorie, thinking they are accurately stating the 1st law of thermodynamics?) But the truth is that the more you study thermodynamics and the more you seem to learn, the less you really understand.

I’ve had a family medical emergency that’s been occupying my time for the past week so I haven’t really had the consolidated time I’ve needed to finish off Part II of the AC book critique, but I haven’t forgotten about it.  I should have it up in a day or two.

Until then, I’ll give you a little thermodynamics to chew on so you, too, can see that it is far from simple.

A commenter wrote the following in response to Part I of the AC critique:

Dear Dr. Eades,

I read the Feinman-Fine second-law article you cited above with interest, but found a mistake in the Figure 2 plot and the corresponding text. I didn’t notice any erratum either.

The figures in section “Efficiency and thermogenesis” should add up to 1825.5 kcal effective yield and not to the 1848 kcal given.
They seem to have interchanged the thermogenesis percentages of CHO (7%) and lipids (2.5%) in their calculation. The error source was perhaps the order in which they list the numbers: first percentages for F, C, and P from Jequier’s review, and then the diet C:F:P = 55:30:15. Go figure.

Nevertheless, it doesn’t affect the main result about metabolic advantage, weakens it a bit, though.

This came in while I was in the throes of dealing with the family problems, so I didn’t take the time to go back, pull the paper, figure out what the commenter was talking about and put my two cents worth in.  I simply posted it as it was.

Thankfully, Dr. Feinman saw it and wrote a response on another website.  I asked for permission, which he gave, to put it up here.

1. The approach taken by many that the idea of metabolic advantage has to be consistent with thermodynamics is correct.  However, one has to understand and apply thermodynamics correctly, especially as it is used in bioenergetics.

2. People who get involved in this discussion have not followed the approach in biochemistry texts and traditional bioenergetics but have not explained why that approach is wrong.  In the traditional approach from bioenergetics, for example, one usually looks at the Gibbs Free Energy, G rather than the internal energy, E.  (G includes the effect of entropy from the second law).

3. What Figure 1 of the paper shows is that metabolic advantage must exist between systems that rely to different degrees on gluconeogenesis.  You learn this in biochemistry: it costs you 6 ATP to obtain glucose from GNG but, of course nothing if you start with glucose.  So, there is a built in metabolic advantage.  Not could be.  Not debatable.  It is there.  Period.  That is an absolute biochemical fact.  So just as people thought metabolic advantage was excluded by the “laws” of thermodynamics (by which they meant the first law), “a calorie is a calorie” is excluded by the combined first and second law.  (To try to use the first law in the absence of the second law is like, actually exactly like, using gravity without considering friction).

4. Now whether you measure it [the metabolic advantage] in any particular experiment, whether the effect is great, whether it is compensated for by other processes (in low fat diets you make fatty acids which costs many ATP although the net effect may be to increase fat storage) is a different question than whether it is there or whether you want to ignore it.

5. Most of the time, as in Leibel’s experiment with the hospital patient, there is calorie balance but Leibel’s group have also done experiments with catch-up fat where there is not energy balance.  But, again, application of the theory is different than what the theory says must be true.  We have made the point that thermodynamics predicts a difference between high and low carbohydrate diets.  It when it is not found that has to be explained.  (The explanation lies in the specific homeostatic mechanisms of biological systems, not in physical law).

6. I personally believe a) Volek’s studies show the effect because the level of experimental error necessary to account for differences would be too large and, more important b) given the potential benefit in palpable metabolic advantage it would be worthwhile to try to find the conditions in which it can be seen and that this would be time better spent than in trying to disprove it with incompletely understood thermodynamics.

7. The other reason for looking for how the theory could be seen in a real weight loss experiment, is that it occurs unambiguously in numerous other biological systems: hypo- or hyper-thyroid conditions, catch-up fat in humans and animal models, animal knock-out or over-expression experiments.

8. I generally don’t pull rank on anybody and I don’t know that there is special criteria for being a scientist but you do have to understand the difference between an effect that is absolutely dictated by physical science (e.g. general theory of relativity) and the difficulty in demonstrating it experimentally (waiting for a solar eclipse and winding up with unreadable photographic plates).

9. Along these lines, like most chemists (or maybe most everybody), I have always found thermodynamics difficult and I am willing to learn from anybody who has an insight.  However…

10. I grew up in Brooklyn so I am capable of a dialogue in the style favored by Colpo and Lyle McDonald but I mostly outgrew it and don’t want to debate at that level.

11.  Relevant ideas to ponder:  I once challenged Colpo to give me a definition of the nutritional calorie (because this makes clear what the issue is), that is, not the definition of the physical calorie (raises a gram of water 1 degree C ) but what we mean when we say carbohydrate has 4 kcal/g.  His answer suggested that he had undergone spontaneous combustion but anybody else can answer the question.  The other question is that in bioenergetics we talk about calories as the free energy, G, which is a potential, analogous to gravitational potential.  When you throw the boulder off the cliff its potential energy is converted to kinetic energy and then goes to zero when it hits the bottom.  Where does the energy go?  The delta G (energy of reaction) for hydrolysis of a peptide bond is about 2 kcal.  When it reaches equilibrium (amino acids) the energy is zero.  In other words, thermodynamics talks about dissipation of energy, not conservation.  How is that possible?  Where does the energy go? 

Hope this helps.

Richard David Feinman
Professor of Cell BiologyTher
SUNY Downstate Medical Center

As a bit of lagniappe, here is a short video Dr. Feinman created on thermodynamics and irreversibility:


Richard Nikoley over at Free the Animal posted his take on the latest Colpo meltdown. As a part of his post, Richard dug out and put up one of my responses to a commenter from a post I wrote a couple of years ago. I had completely forgotten about it, but since it applies to the situation discussed above, I’m reprinting the comment by Ryan and my response below.  A hat tip to Richard for ferreting this out:

I have a question that may be related to this.

On several low carb forums right now, there is a debate going on about what happens to the extra fat calories if carbs are kept extra low so that insulin is kept low. Some say it will be stored as fat anyway, others say it will be burned as heat and still others say it will be excreted. One member even did near-zero carbs and very high fat for a week (4500 calories instead of a normal 2500, with an average of about 80-90 g of protein). He lost a pound off of his already lean physique.

So, where does that extra fat go? Is it excreted? The detractors say that fat is completely digested before reaching the colon but I am not sure. If it is excreted, could you go ultra high fat, zero carb for a week or so and get the same detox results as the cosmic pizza grease?

Hi Ryan–

Your comment raises an interesting question. Where does all the excess energy go?

I’ve had a number of patients and countless letters from readers who have had the same experience. They consume a ton of fat, but don’t gain weight…or even, as with the guy you described, lose a little. Mostly the letters we get are from people who complain that they are following our diet to the letter, yet not losing weight. When we investigate, we find that in virtually every case these people are consuming huge numbers of calories as primarily fat. We always ask them if it doesn’t strike them as strange that they’re eating as much as they are, yet not gaining.

In order to lose weight, one must create a caloric deficit. This can be done in a number of ways. People can burn more calories by increasing exercise; they can eat fewer calories; or they can increase their metabolic rate. Or they can do any combination of the above.

Most people going on a low-carb diet decrease their caloric intake. A low-carb diet is satiating, so most people eat much less than they think they are eating even though the foods they’re consuming are pretty high in fat. Some people, however, can eat a whole lot on a low-carb diet, and, can in fact, eat so much that they don’t create the caloric deficit and don’t lose weight. But the interesting thing is that they don’t gain weight either. They pretty much stay the same. They are eating huge numbers of calories and not gaining, so where do the calories go?

First, I don’t think they go out in the bowel. If they did, people would have cosmic pizza grease stools whenever they ate a lot of fat over a period of time, and they don’t. And a number of studies have shown that increasing fat in the diet doesn’t increase fat in the stool.

Eating a very-low-carbohydrate diet ensures that insulin levels stay low. Unless insulin levels are up, it’s almost impossible to store fat in the fat cells. With high insulin levels fat travels into the fat cell; with low insulin levels fat travels out. So, it’s pretty safe to say that the fat isn’t stored. So what happens to it?

The body requires about 200 grams of glucose per day to function properly. About 70 grams of this glucose can be replaced by ketone bodies, leaving around 130 grams that the body has to come up with, which it does by converting protein to glucose and by using some of the glycerol backbone of the triglyceride molecule (the form in which fat is stored) for glucose. If one eats carbs, the carbs are absorbed as glucose and it doesn’t take much energy for the body to come up with its 200 gram requirement; if, however, one isn’t eating any carbohydrates, the body has to spend energy to convert the protein and trigylceride to glucose. That’s one reason that the caloric requirements go up on a low-carb diet.

The other reason is that the body increases futile cycling. What are futile cycles? Futile cycles are what give us our body temperature of 98.6 degrees. Futile cycles are just what the name implies: a cycle that requires energy yet accomplishes nothing. It operates much like you would if you took rocks from one pile and piled them in another, then took them from that pile and piled them back where they were to start with. A lot of work would have been expended with no net end result.

The body has many systems that can cycle this way, and all of them require energy. Look up the malate-aspartate shuttle; that’s one that often cycles futilely.

Another way the body dumps calories is through the inner mitochondrial membrane. This gets a little complicated, but I’ll try to simplify it as much as possible. The body doesn’t use fat or glucose directly as fuel. These substances can be thought of as crude oil. You can’t burn crude oil in your car, but you can burn gasoline. The crude oil is converted via the refining process into the gasoline you can burn. It’s the same with fat, protein and glucose–they must be converted into the ‘gasoline’ for the body, which is a substance called adenosine triphosphate (ATP). How does this conversion take place? That’s the complicated part.

ATP is made from adenosine diphosphate (ADP) in an enzymatic structure called ATP synthase, which is a sort of turbine-like structure that is driven by the electromotive force created by the osmotic and electrical difference between the two sides of the inner mitochondrial membrane. One one side of the membrane are many more protons than on the other side. The turbine-like ATP synthase spans the membrane, and as the protons rush through from the high proton side to the low proton side (much like water rushing through a turbine in a dam from the high-water side to the low-water side) the turbine converts ADP to ATP.

The energy required to get the protons heavily concentrated on one side so that they will rush through the turbine comes from the food we eat. Food is ultimately broken down to high-energy electrons. These electrons are released into a series of complex molecules along the inner mitochondrial membrane. Each complex passes the electrons to the next in line (much like a bucket brigade), and at each pass along the way, the electrons give off energy. This energy is used to pump protons across the membrane to create the membrane electromotive force that drives the turbines. The electrons are handed off from one complex to the other until at the end of the chain they are attached to oxygen to form water. (If one of these electrons being passed along the chain of complexes somehow escapes before it reaches the end, it becomes a free radical. This is where most free radicals come from.)

There are two parts to the whole process. The process of converting ADP to ATP is called phosphorylation and the process of the electrons ultimately attaching to oxygen is called oxidation. The combined process is called oxidative phosphorylation. It is referred to as ‘uncoupling’ when, for whatever reason, the oxidation process doesn’t lead to the phosphorylation process. Anything that causes this uncoupling is called an ‘uncoupling agent.’

You can see that the whole process requires some means of regulation. If not, then the electromotive force (called the protonmotive force, since it’s an unequal concentration of protons causing the force) can build up to too great a level. If one overconsumes food and doesn’t need the ATP, then the protonmotive force would build up and not be discharged through the turbines because the body doesn’t need the ATP. The body has accounted for this problem with pores through the inner mitochondrial membrane where protons can drift through as the concentration builds too high and by proteins called uncoupling proteins that actually pump the protons back across. So we expend food energy to pump protons one way, then more energy to pump them back.

One of the things that happens on a high fat diet is that the body makes more uncoupling proteins. So, with carbs low and fat high, the body compensates, not by ditching fat in the stool, but by increasing futile cycling and by increasing the numbers of uncoupling proteins and even increasing the porosity of the inner mitochondrial membrane so that the protons that required energy to be moved across the membrane are then moved back. So, ultimately, just like the rocks in my example above, the protons are taken from one pile and moved to another then moved back to the original pile, requiring a lot of energy expenditure with nothing really accomplished.

This is probably all as clear as mud, but it is what happens to the excess calories on a low-carb, high-fat diet.



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127 thoughts on “Thermodynamics and the metabolic advantage

  1. At the end of the day ATP is the crunch factor.
    How did it get there?
    What does it need to get there?

    Burning stuff in a bomb calorimeter tells us
    not very much about animal metabolism.

    Glucose, amino acids, fats are utilised (including excretion) in many ways in any organism.

    Using calories as a measure is about as accurate as using
    a tape measure made of elastic.

  2. Haven’t Buchholz and Schoeller already answered this.

    .”We thank Manninen and Feinman and Fine for their interest in our review, “Is a Calorie a Calorie?” (1). These 2 letters correctly point out that there are indeed some differences between the energetics of human metabolism and the measures of heat release of nutrients in a bomb calorimeter. We agree with the known concept that the metabolic route through which carbon flows to carbon dioxide, the concentrations of substrates, as well as entropy can all slightly alter the efficiency of ATP production in humans (2). This concept, however, does not automatically mean that these differences constitute a quantitatively plausible mechanism that would explain the differences in weight loss observed with a high-protein, energy-restricted diet relative to a low-fat, energy-restricted diet.

    Rather than relying on a theoretical treatment of metabolic efficiencies, as did Feinman and Fine, we reviewed studies in which known experimental diets were fed to subjects under laboratory conditions to test whether energy expenditure was actually higher with a low-carbohydrate diet than with a high-fat diet. In studies in which protein intake was held constant and fat was substituted for carbohydrate, the difference in 24-h energy expenditure between the high-carbohydrate and high-fat diets was not different from zero (: –19 ± 54 kcal/d). However, as clearly stated in our review, when the protein intake was not held constant but rather increased from 15% to 30–35% of energy, 24-h energy expenditure did increase. We determined, however, that the increase would be only 41 kcal/d for a 1500-kcal/d energy-restricted diet. This would only increase weight loss by 0.04 kg/wk, or 0.44 kg over a 12-wk course of weight-loss treatment. It should be noted that this is less than the 95 kcal/d calculated theoretically by Feinman and Fine, and it has the advantage of being based on experimental data. Thus, we do not disagree with Feinman and Fine from the perspective of pure thermodynamics; in fact, we presented evidence at the whole-body level that supports their point. However, we found the experimentally measured differences in 24-h energy expenditure, between subjects who followed a high-protein diet compared with those who followed a high-carbohydrate diet, to be too small to satisfactorily account for the differences in weight loss observed after 12 wk of treatment with these 2 diets. Thus, this is not a plausible mechanism to account for the observed increased weight loss. The experimental data on energy expenditure provide evidence of only a minimal metabolic advantage for low-carbohydrate diets.”

    As you can see it is the protein content of the diet that can make up a minimal metabolic advantage not the fat content.

    Given indentical amounts of protein, a high carbohydrate diet will actually have a metabolic advantage compared to a low carbohydrate diet because of the higher TEF of the carbs.

    • There are other carefully-controlled studies showing a higher-fat diet drives greater weight loss than does a high-protein diet. I’ll be posting on this study in Part II coming up soon.

      • Hi Dr. Eades,

        I hope you can give me some insight into a major problem I have. I think that all you have written in this blog may apply but I have to admit to a bit of trouble comprehending it all ~ even though I’m an RN!

        Back in ’03, I had a panniculectomy. When I had it done I was at my goal weight. I have since gained about 40-50 lbs. Since I no longer have my lower abdomen, the fat seems to me to be even more concetrated in what abdomen I do have. And, I am having a terrible time losing weight. I have followed your 6 week Cure plan w/ some benefit but found it hard to stay on.

        Do you have any thoughts as to what I could do to get this weight off? I’m concerned about the belly fat, for obvious reasons. My thighs are the other place the weight has gone. Never had big thighs before. I’m 61 and have a desk/phone job as a nurse so my day is rather sedentary except for my walks.

        Thanks for any help you can give me,
        Connie Sullivan

        • People who have liposuction have the same problem. Excess fat has to go somewhere, and if it doesn’t have the regular places it goes, it goes somewhere else.

          • Yes, I realize that. I was just hoping you might have some thoughts about the best way to get rid of the belly fat given that it seems to be so much more difficult to get rid of. Does it mean I just have to be more persistent and patient or could there be something additional I could be doing? I’m also prediabetic. Thanks again,

          • This response reminds me of a question I’ve had for awhile. A bit ago you posted a study that showed that as children we grow more fat cells if weight is gained versus adults’ fat cells growing larger. If one is having difficulty losing weight because fat was gained as a child and there are too many fat cells, is it possible that liposuction is a solution to that problem and a way of resetting a fat point. For example, if those fat cells are no longer there, they wouldn’t be able to be metabolically active in the body, influencing/secreting hormones, or would the body still detect the loss and try to compensate accordingly?

      • I’ve seen a few of those studies, but I haven’t found any that tested bodyfat % – have you seen any?

        Perhaps the higher protein diets lead to some muscle gain which offset the net weight lost…

    • Buchholz and Schoeller’s paper has as its main point that metabolic advantage exists but doesn’t exist. “we do not disagree with Feinman and Fine from the perspective of pure thermodynamics (exists) …; in fact, we presented evidence that supports their point (exists). However, we found …energy expenditure…to be too small (doesn’t exist) to satisfactorily account for the differences in weight loss (exists) . Thus, this is not a plausible mechanism (doesn’t exist) to account for the observed increased weight loss (what is “this” thermodynamics?) The experimental data …provide evidence of only a minimal metabolic advantage for low-carbohydrate diets (doesn’t exist).”
      I just don’t know what these authors are saying. TEF is only one source of total heat and it is the inefficiency of metabolic processes that requires greater calories (greater protein utilization) to maintain blood glucose. If you think the perfect experiment hasn’t been done to demonstrate it, you should think of how to do it because the physical laws are on your side.

  3. Maybe there’s something wrong with me, but I’m not terribly concerned about whether some dietary approach or another has a metabolic advantage. What I’m concerned about is whether I’m gaining or losing weight.

    If diet A allows me to eat an additional 200 calories a day but it makes me so hungry that I eat an additional 500 calories a day, then who cares about the metabolic advantage.

    What I like about LC diets is that when I stick to them I’m not hungry and my blood sugar stays level. If I can eat an additional small square of cheese, well that’s nice, but it’s not why I’m on the diet.

    As noted, thermodynamics is complex and requires a lot of assumptions and definitions (closed system vs open system, standard temperature and pressure, etc.). When someone tells me that a calorie is a calorie because of thermodynamics, I just tell them they don’t really understand thermodynamics and then turn the conversation to something they can understand, like the Academy Awards.

    I hope your family member is better.

    • Your comment probably makes more sense than anything else in this post. Weight loss without hunger is what it’s really all about.

      My family member is on the mend. Thanks for asking.

      • The big question then is why is low-carb better at controlling hunger? I believe this is specifically because more fat is released to the lean tissues and less of the weight lost comes from lean tissue itself. This is of incredible importance, and is also probably one reason why guys like me or Colpo had great initial results on low-carb initially as body fat was lost (in my case, I actually lost body fat and spontaneously grew tons of muscle without any exercise at all). At a certain level of leanness though you can no longer tap into body fat and a low-carb diet starts to turn south, triggering many hypometabolic symptoms like irritability, constipation, muscle cramps, and so forth.

        Low-carb will remain the best reducing diet as far as I’m concerned. But people need to understand when to use it, when to lose it, and why you can’t abuse it. Even Atkins knew full well that his diet was not appropriate for long-term use.

        • I think you’re putting words in Dr.Atkins’ mouth. I’m not so sure – at least based on my limited conversations with him – that he did believe the diet wasn’t appropriate for long-term use. I certainly don’t feel that way. I’ve been on a low-carb diet for at least 25 years and it hasn’t seem to have done me any harm.

      • Weight loss without hunger, eh? :) That is literally the title of the “general overview of low carb”-style book me and my writing partner wrote in a different language in 2004. 😉 Subtitled “- with a carb conscious diet”.

        I was once asked about the metabolic advantage, I pretty much said it’s mostly a red herring, and I still think so. Much ado about nothing THAT significant really, sure it is there, but to be honest, I’d rather not waste energy even in that sense and thus do not see any real reason to aim for it.

        Satiety and hunger management, and energy usage partitioning, now THAT is significant. And it is there that low-carb shines especially. Oh and the plethora of side-effects resulting in improved health isn’t that bad either. 😉

    • Gretchen, I just saw djinn agreeing with you, rather more verbosely, over at the PaNu forum “anthony colpo on eade’s mad”. Michael is right, of course.

    • Gretchen, I absolutely agree. I like to consider the science, but where the rubber meets the road is how well I tolerate a particular diet for my health needs. I lost to goal on low-fat w/exercise, but was miserable, and my triglycerides remained above 300. With a family history of diabetes II and no heart disease, my doc suggested that LC made more sense to lower TGL. Weight loss wasn’t even on the horizon, but I’ve lost in excess of 30 pounds, dropped into the “overweight” BMI, and have TGL of 106 now. Plus, and this is the really important part, I love bacon.

      Protein consumption may have a lot to do with the satiety factor; there are studies I blogged about where primates were observed to eat until they satisfied their protein requirements, regardless of how much food they had to eat to do it (see for one of the articles on the study).

      So I’m not sure that its the fat or the protein that satisfies our hunger, but either way, its good news for bacon.

    • I couldn’t agree more! That’s the thing that is so frustrating about people who see no difference in where calories come from. As if a calorie from a spoon of sugar takes the same amount of work to digest as does one from a bite of steak. Seems odd to me.

      My wife has been successful in staying on-plan on a low-carb diet for over two years, with very good weight loss over that time, and *no* sense of deprivation. She eats the foods she loves, is almost never hungry, and can enjoy a restaurant meal when she wants.

      And she’s always failed on low-calorie, low-fat diets.

    • Gretchen: I agree. Fast weight loss without starving … also better diabetic/glucose numbers. What concerns me is becoming hypothyroid with severe incapacitating chills.

  4. All the metabolic pathways are hard to glance at in a single look. I’ve got great books on the subject here and since I’m a software developer, I think I’m going to create a “complete” metabolic pathways simulator. You will be able to intake matter in the system and see what happens. I would make all the “known” pathways configurable so that we can include future knowledge and add new pathways.

    Anyone thinks this would be a good idea?



    • I think it would be a great idea. But extremely difficult to do accurately. A number of researchers have already created metabolic models that do what you are contemplating. Some even use these in place of actual animal or human research. They plug in the various diets and see what gets cranked out in the end.

    • It is not sufficient to know what is connected to what. You have to know the kinetic (rate) constants and other mathematical parameters of the system to know if they actually go. As Mike says, there are metabolic models and they provide information but not at the level of what to eat.

      • Thank you Dr. Feinman. This is a bit disheartening, but you probably saved me lots of time. I realize now that even if we were to take this into account in the simulation, the running time would be much too long to be of any real use for such a big system as the human body.


    • Wow, I feel like I’m back in grad school with all the good thinkers that post here, and the combination of Drs Eades and Feinman’s comments are like being back in a graduate current topics seminar [and no, for the likes of Colpo, MSMS[BS], AA and whomever, I’m not kissin’ ass, I just appreciate a really good analysis].

      As for the metabolic stimulator software, it is such a great idea but hard to manage because the state characteristics of any Ss are really going to determine what fuel they use for any given demand, and especially if the model is further challenged by exercise. What metabolic pathways will be stimulated are different given if the person is a young fit, young overweight, metabolic syndrome and fit, full-out diabetes etc, and to what degree any subject fits a criteria. It’s really hard [impossible?] to dial that stuff in and be accurate.

      As an aside, I believe this is a similar argument AA/MSMS[BS] is having about Lustig’s problem with fructose: maybe it’s not such a problem for everyone, like young fit athletes, and you can’t make a generalization because of state characteristics of the individual. Ok, but why get ugly and demeaning?

      So glad Dr. Feinman mentioned Dr. Volek’s studies. I have thought that some of these fitness guys involved in these various pissing contests should zip their testosterone back up and go read Volek.

  5. “…increasing the porosity of the inner mitochondrial membrane so that the protons that required energy to be moved across the membrane are then moved back.”.

    Does this mean that this futile cycle wastes energy on movement instead of on creating heat?


  6. I agree with Gretchen..the best aspect of a low carb diet is the lack of hunger. Thanks for taking the time to explain cellular processes so clearly. I’m always trying to learn more, and my biochemistry books just aren’t that readable.

  7. I thought that the greater weight loss was already evidence of a metabolic advantage. Granted, some of it is water, but that’s irrelevant at this point. In fact, what if the greater weight loss was only due to greater water loss? Then there would be no measurable energy difference since water contains zero calories. However, there would be a measurable mass difference, which is what we already see with the greater weight loss. After all, we are made of about 70-80% water and if there should be a substantial change in weight, it would come from the greatest part of our body, not the smallest part.

    On the other hand, if there is a change in fat mass, then there are two ways it can be measured. If it is spent, then we can measure its energy output. If it is merely discarded without being oxidized, then we can measure its mass. Like above, we can already measure its mass since it shows up on the scale, even if it doesn’t actually show up in the stools or sweat or breath.

    However, I’m with Feinman on this one, if we can measure the mass difference using a scale but can’t measure the mass by direct observation (i.e. stools, sweat, breath, heat, etc), then where is that mass going?

  8. First off, fabulous stuff. I will have to read it ten more times to understand it better, but this post seems a super compilation of notes and explanations of contributors to the metabolic advantage. A tremendous contribution to my (our collective) understanding of nutritional bio-processes.

    Thank you.

    It seems that we are witnessing the birth of a clearer understanding/definition of bio-efficiency as it relates to nutrition. Or perhaps is it simply my relatively recent introduction to the topic that make it all seem so revelatory.

    We typically learn the formalisms of work and efficiency in freshman physics, mostly as is is applied to simple physical machines. Biochemists are exposed to the energetics of bio processes. The bio-processes seem much richer in complexity nuance to me. Toss cultural, individual and genetic variation into the mix and you have a splendidly confusing and encyclopedic volume of knowledge to manage.

    Is it any wonder that people want to cling to the simplistic notion that a calorie is a calorie, and ignore the second law as it applies to bio systems? Trying to understand the energetics around cellular metabolism is too much like, well, work.

  9. Studies show that very little fat gets excreted in stools. That doesn’t necessarily mean the nearly all fat energy gets absorbed into the bloodstream. Gut microbes consume both fat and carbohydrate calories as they multiply releasing about 5 calories of heat energy for each gram (dry weight) of dead microbes in the feces. If the estimated wet weight of feces were pegged at 320 grams and 75 percent of that is water, the dry weight of microbes would be one eighth of that or 40 grams.

    That calculates out to 200 calories of heat energy released into the digestive tract as food is digested and absorbed. This heat diffuses into the body an may be regarded as part of the body’s temperature regulating mechanism.

    In overfeeding studies, subjects frequently complain of being overheated shortly after the meal is ingested. Since air is swallowed along with food and aerobic bacteria reside in the stomach, it’s quite possible that considerable fermentation takes place in the stomach with concurrent heat release during this early stage of digestion.

    Researchers generally attribute extra heat generated during overfeeding to increased metabolic activity. There may be so. However, It is important not to overlook the heat energy generated by gut microbes. 200 calories is not a trivial amount.

    It would be nice if someone would test this hypothesis.

  10. Good to see you back, Dr. Eades. Apropo of nothing, did I ever mention that you saved my life? I know, that’s good news and bad news. It kind of dampens my normal(?) tendencies when commenting here…….. Perhaps a good thing? Hope all is well.

  11. The Feinman-Fine article isn’t particularly compelling.
    The energy lost as heat doesn’t magically go away — it heats the surrounding system, i.e. the body. Given that maintaining body heat is a major portion of energy expenditures, it stands to reason that the 100 kcal/day metabolic effect that they describe may simply come out of the calorie budget for maintaining body heat meaning no overall metabolic advantage.

  12. “There are other carefully-controlled studies showing a higher-fat diet drives greater weight loss than does a high-protein diet. I’ll be posting on this study in Part II coming up soon.”

    Ok, other “carefully-controlled” studies.

    And suddenly it’s only one study your’e going to post about?

    Hope then it’s not the study of Charlotte Young “Effect on body composition and other parameters in obese young men of carbohydrate level of reduction diet” or some other like that one.

    One question. I don’t understand why there’s so much talk about the energy dissipating through gluconeogensis, a process that only will be relevant the first week or so on a low carbohydrate diet before the adaptions to ketosis will occur. If the process of gluconeogenesis should continue there would be no need for the body to adapt to ketosis since there would be a lot of glucose available.

    Hence, gluconeogenesis will not contribute to any energy dissipating process on a low carbohydrate diet.

    Compared to a “normal” diet or a diet with moderate/high intake of protein where it always will be a high rate of gluconeogenesis due to the fact that the body is actually using glucose for it’s energy needs.

    “The major fate of dietary amino acids in the Western diet appears to be gluconeogenesis (26, 71) and has been recently estimated to account for up to 60% of endogenous glucose production (23), while others estimate 47 to 60% (72-74). In one study a relatively high protein diet, (1.87 ± 0.26 g ∙ kg-1 ∙ d-1), was shown to elevate gluconeogenesis by 40% (62). Thus gluconeogenesis should be viewed as
    a normal prandial process, not one limited to fasting periods (71)”
    A Review of Issues of Dietary Protein Intake in Humans
    International Journal of Sport Nutrition and Exercise Metabolism, 2006, 16, 129-152

    • I’m limiting myself to posting about the specific studies Colpo has used in his book to make his point. I’m not dredging up every study known to man or the post would go on forever. This is a critique of his book and his information, not a post arguing my point of view.

      After adaptation, ketones can replace anywhere from 50-70 grams of glucose. The body still needs to produce glucose, so gluconeogenesis continues.

      • Of course gluconeogenesis continues (it’s always present) but there will be a great reduction. After prolonged starvation (low carb diet) there will not be that much glucose produced as you and others suggests (total 200g-(50g-70g)=150g-130g), at least not from amino acids.

        The true value is just over 80g of glucose (including glycerol, lactate, pyruvate and amino acids) produced once keto-adapted and that’s when your’e eating zero carbs. It will be even lower glucose production(gluconeogenesis) on a low carb diet because those often don’t contain zero grams carbs.

        So you can’t have gluconeogenesis as an “excuse” for dissapating more energy on a low carb diet because gluconeogenesis is always present even in a “normal” diet and even greater on diet that contains more protein even if it’s not a low carb dietm because that is how the body will utilize amino acids for energy.

        “The present study has demonstrated that there is a
        reduction in the total amount of glucose produced during
        prolonged starvation. The estimated hepatic-renal glucose
        production calculated from the limited flow data was 86 g/24 hr. The liver contributes approximately 55% and the kidney 45% of the total. The estimated glucose quivalent is 83 g/24 hr calculated from the measured hepatic-renal uptake of lactate, pyruvate, glycerol, and a-amino nitrogen from arterial blood. About onehalf of the glucose formed, as discussed above, is derived from recycled lactate and pyruvate. The remaining glucose, derived from glycerol released from triglycerides and amino acids mobilized from proteins, can be terminally combusted to C02. The central nervous system, deriving the major proportion of its energy from /8-hydroxybutyrate and acetoacetate (32 and 6 g/day, respectively) (8), continues to utilize the major part of this glucose, about 42 g/day (8).”

        Liver and Kidney Metabolism during Prolonged Starvation
        The Journal of Clinical Investigation Volume 48 1969

        • Doing some catch up reading here..Funny thing Stein.. Not sure how any sane, reasonable person could call my diet (a very low carb one) “starvation”.. I eat very very well and am very very healthy and fit.. It’s fun (but sad) watching you run in circles in your logic.

  13. One more thing. A high fat diet will only increse UCP2 and UCP3 and those UCP:s will not increase metabolic rate and even if they should you would be able to measure that increase in energy expenditure in a controlled study. Strange that this increase in metabolic rate then never has been measured in any controlled study yeat.

    “Hesselink et al. (2) have studied the capacity of UCP3 to act as an uncoupler in human skeletal muscle following a diet-induced increase in UCP3 expression. Healthy male volunteers expressed 44% more UCP3 protein in skeletal muscle while consuming a high-fat diet than while consuming a low-fat diet. The investigators assessed mitochondrial function in vivo by measuring phosphocreatine resynthesis following anoxic muscle contractions. To permit rapid bursts of muscle contraction, high-energy phosphate bonds are stored as phosphocreatine, which is formed by transfer of phosphate from ATP to creatine catalyzed by creatine kinase. The rate of phosphocreatine resynthesis reflects ATP synthetic rates via mitochondrial F1F0-ATPase, which in turn is affected by the extent of mitochondrial uncoupling. The authors observed similar time courses of phosphocreatine repletion in the high-fat and low-fat fed subgroups, indicating that the physiological upregulation of UCP3 with high-fat feeding did not affect the mitochondrial proton leak in vivo. The authors also found that relative amounts of free carnitine and acylcarnitine were similar in both subgroups, verifying that there were no differences in substrate availability (at least from long-chain fatty acids). The authors were able to reject their initial hypothesis and conclude that UCP 3 does not act as a mitochondrial uncoupler in human muscle under these physiological conditions.”

    “Third, the authors studied human beings. While transgenic mice experiments have been highly prized by first-line biomedical journals, experiments involving human physiology have been relatively undervalued in my opinion. Particularly in the area of energy expenditure, it is problematic to extrapolate data in transgenic mice to human physiology since adult humans do not have brown fat and heat production per kg body weight is much lower in humans than in rodents. This lesson was learned in the case of leptin, which exerts major effects on body temperature in rodents, while this physiological action is markedly attenuated or lacking in humans (13, 14). The observations of Hesselink et al. (2) are not only directly relevant to human physiology, but constitute some of the strongest data in any system addressing the basic biochemical role of UCP3 as an uncoupler. On balance, the paper seems to prove the old adage that, if you want to understand human physiology, sometimes you just have to study humans.”

    The role of uncoupling protein 3 in human physiology
    J. Clin. Invest. 111(4): 438-441 (2003). doi:10.1172/JCI17835.

    “In summary, the present study demonstrated that upregulation of UCP3 by a physiological intervention (HF feeding) did not affect the postexercise rate of PCr resynthesis and thereby mitochondrial coupling when flux through the F0-F1-ATPase was likely to have been close to maximal. It is concluded that the primary role of UCP3 in human skeletal muscle is not mitochondrial uncoupling”

    Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo
    J. Clin. Invest. 111(4): 479-486 (2003). doi:10.1172/JCI16653

    • I am familiar with this paper. The diets used, although different in macronutrient composition, were designed to meet, but not exceed, the subjects energy needs. One wouldn’t expect such diets, irrespective of macronutrient composition, to stimulate UCP production or increased uncoupling.

      • You are familiar with this paper(s) but anyhow you states that one wouldn’t expect diets designed to meet energy needs to stimulate UCP production.

        And yet the studie shows a stimulation in UCP production with high fat feeding from a diet that meets energy needs. It’s just that that those UCP:s stimulated are not involved in increasing metabolic rate but do have other functions such as preventing lipotoxicity.

        “The HF diet increased UCP3 protein content by approximately 44% compared with the LF diet. However, this HF diet–induced increase in UCP3 expression was not associated with any changes in the rate of muscle PCr resynthesis during conditions of maximal flux through oxidative phosphorylation. Muscle acetylcarnitine, free-creatine, and lactate concentrations during recovery were unaffected by the HF diet. Taken together, our findings demonstrate that increasing muscle UCP3 expression does not diminish the rate of PCr resynthesis, allowing us to conclude that the primary role of UCP3 in humans is not uncoupling.”

        Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo
        J. Clin. Invest. 111(4): 479-486 (2003). doi:10.1172/JCI16653.

        Another one

        “CONCLUSION: UCP2 and UCP3 mRNAs are upregulated by a high-fat diet. This upregulation is more pronounced in humans with high proportions of type IIA fibers, suggesting a role for UCPs in lipid utilization.”

        Fiber type dependent upregulation of human skeletal muscle UCP2 and UCP3 mRNA expression by high-fat diet.
        Int J Obes Relat Metab Disord. 2001 Apr;25(4):449-56

        Where is the evidence from where you can draw the conclusions that high fat overfeeding will increase UCP:s responsible for increased metabolic rate. That should then be increased production of UCP 1 that could be found in BAT. BAT that you can find in a really significant amount in a fullgrown human being……

        “The hypothesis presented here is that UCP3 is an important player in the export of fatty acid anions from muscle and BAT mitochondria and that it is a component of fatty acid oxidation. The two individual players in this pathway are known, that is, UCP3 to export fatty acid anions and an acyl CoA thioesterase to hydrolyze acyl CoA. The association of increased UCP3 expression in muscle and BAT at times when fatty acid oxidation predominates has also been noted before. The present hypothesis puts these hitherto disparate observations into a coherent story that provides a logical function for UCP3 in fatty acid oxidation in muscle and BAT. This role is not that of an uncoupler under physiological conditions.
        It is likely that other UCPs may play a similar role in other tissues under other circumstances, for example in liver, in brain, or in -cells of pancreatic islets. It is possible
        that no UCP, other than UCP1 in BAT, acts as an uncoupler
        under physiological circumstances. The name given to these carrier proteins of unknown function was based on structural homology with the long-known BAT UCP1. This
        name has focused most research on these proteins, now
        reported in almost 500 publications, on the possibility of
        their having a thermogenic function and hence a potential
        role in energy balance and obesity. It may now be time to
        give them another, less misleading, name, such as mitochondrial carrier proteins (MCPs), without specifying the
        substance they carry or their function until these have been

        Physiological Role of UCP3 May Be Export of
        Fatty Acids from Mitochondria When Fatty Acid
        Oxidation Predominates: An Hypothesis
        E.B.M. 2001, Vol 226:78–84

        “The uncoupling protein-1 (UCP1) homologues UCP2 and UCP3 are able to uncouple ATP production from mitochondrial respiration, thereby dissipating energy as heat and affecting energy metabolism efficiency. In contrast to UCP1, which plays an important role in adaptive thermogenesis, UCP2 and UCP3 do not have a primary role in the regulation of energy metabolism. UCP2, which is expressed in a wide variety of tissues, including white adipose tissue, skeletal muscle and tissues of the immune system, has been suggested to affect the production of reactive oxygen species. UCP2 has also been suggested to regulate the [ATP]/[ADP] ratio and was recently shown to influence insulin secretion in the beta-cells of the pancreas. UCP3, in contrast, is expressed predominantly in skeletal muscle and has been associated with whole-body energy metabolism. However, the primary function of UCP3 is not the regulation of energy metabolism”

        UCP2 and UCP3 in muscle controlling body metabolism.
        J Exp Biol. 2002 Aug;205(Pt 15):2275-85

  14. Low carb diets tend to cause an increase in ketosis. Many of these ketone bodies are lost in expiration and in the urine and this represents a caloric loss to the individual.

      • Diabetic ketoacidosis does not occur in normal, healthy people. To mention it in this context dissuades a low-carb diet, in my opinion. Could you please provide numbers to support your statement?

        • I don’t know what you’re looking for here, but the levels of ketones in the blood during dietary induced ketoses are a tiny fraction of those in the blood during diabetic ketoacidosis. The latter is a dangerous pathological condition whereas the former is a normal part of metabolism.

          • In statistical mechanics, entropy is essentially a measure of the number of ways in which a system may be arranged, often taken to be a measure of “disorder” (the higher the entropy, the higher the disorder). This definition describes the entropy as a measure of the number of possible microscopic configurations of the individual atoms and molecules of the system (microstates) which would give rise to the observed macroscopic state (macrostate) of the system.

            By corollary, the excretion of ketones in urine by a normal, healthy human eating a low-carbohydrate diet indicates a body at higher entropy through the additional processes (microstates) necessary to utilize fat and protein for energy. The unseen metabolic advantage produced by the microstates is confirmed through the observable weight loss or zero weight gain despite higher caloric consumption (macrostate).

            Is this a sound conclusion?

  15. Mike
    You may have blogged about this before, if so maybe you could point me to the relevant blog.
    I’ve been on an adequate-protein high-fat low-carb diet for about 8 months now. I keep coming across comments that low-carb diets work in the short term but are metabolic suicide long term. The criticisms are (1) a low ingestion of carbs keeps insulin low but over time affects glucose metabolism / reduces insulin sensitivity (if true this is obviously undesirable); (2) our body is forced to tear down in order to build up elsewhere (futile cycling?); (3) staying in ketosis long term drives the metabolic rate down.
    I wonder if these things are only a problem when a person is no longer obese and starts getting close to the bottom of the healthy weight range.

    • 1. When you don’t eat (many) carbs, your body (which doesn’t like to waste energy producing things it doesn’t need) stops producing carb-metabolizing enzymes. So if you then suddenly eat a lot of carbs, you may test diabetic even if you’re not. The extreme example of this is “starvation diabetes.” This is why they ask people to eat 200 g of carbs a day before a glucose tolerance test. As far as I know, this situation is reversible if you switch back to a high-carb diet.

      2. As I understand it, insulin resistance is the body’s way of channeling glucose to the tissues that need it most. When you’re not eating carbs, or if you’re starving (the ultimate LC diet), the body uses insulin resistance to make sure that what glucose is there will go to the brain before it’s taken up by muscles. Again, as far as I know, this is reversible.

      3. Futile cycling is just what we want when we are trying to lose weight. So what’s the problem?

      4. Any diet, LC or low-fat or low-calorie, will drive the metabolic rate down.

  16. I also find it a bit funny that this has dragged out for so long. Colpo and McDonald hate the idea of a metabolic advantage, hate it. Yet whether or not it exists it is clear that most every variable that has been implicated in unnatural morbidity and mortality (strokes, myocardial infarctions, etc.) improve on a proper low carbohydrate diet. Funny they are also overzealous training freaks too, which is about as natural as blue poo. I think thats why they want their carbs. Whether they can move without pain when they are older is up in the air at this point. I’m sure they can kick my ass though, which means umm absolutely nothing in the real world.

    Anyway to wrap this up, I know that Mike would never bring this up, but there are ways to increase futile cycling measurably to reduce weight. There is a chemical called 2,4 dinitrophenol which is an ionophore that was a diet aid in the 30’s. Basically it allows the protons to leak back through the mitochondrial membrane reducing the proton motive force and causing increased thermogenesis. You can lose weight real fast. Unfortunately if you overdose you die from hyperthermia. So there is that one problem…

  17. This fantastic post really does attempt to answer I know many of us have wondered about.

    The only thing that doesn’t resonate with my experience (or the experience of many others on low carb diets) is that if anything thermogenesis is LOWER on a low carb diet than a higher carb one.

    I sense this physically as well as seeing it reflected on the thermometer when I take my daily temps.

    This even happens when I’m losing fat so it makes me wonder just how much uncoupling is truly responsible for the fantastic effects of the low carb diet.

    Have others noted lower body temps on low carbs? Even, as I have experienced, while losing fat?

    • As Colpo has said and as I have written many times, low-carb diets make most people spontaneously restrict calories. The diets are satiating so that even when people eat until full, they eat fewer calories than they did before following a low-carb diet. As I’ve written many, many times, this spontaneous caloric restriction is a big part of the engine that drives weight loss on low-carb diets. Low-calorie diets make us run a little cooler, which is probably what is happening to you.

  18. Thanks for the great post. I’m definitely tracking this, as I have been a bit skeptical about the metabolic advantage of LC diets (sounds nice, but I’ve been looking for scientific evidence before accepting it as true — so this post is a big help).

    Keep them coming! We’re hungry (no pun intended) for factual information…

  19. I did an overfeeding study on myself a while back. It was zero carb,almost entirely muscle meats and suet. I averaged 4800 calories for 14 days with 80% of calories coming from fat and gained 8 pounds. Important to note was that one week prior I had just gone zero carb coming from a high-carb vacation and had lost about 8 pounds – probably mainly water and glycogen.

    But, I had another 2 month venture with zero carb that just ended and noticed my weight went up and down almost precisely with calorie content.

    I think the TEF can account for a good bit of the calorie difference since I believe all amino acids will convert to glucose/fat (10-11 ATP to complete) after the body has utilized its daily protein requirements which I don’t think are that high (80-100g).

    Also, as the poster above mentioned, its vitally important to measure energy content of any excrement when doing these trials.

  20. Here’s another bit to throw into the mix: your gut cells like to eat butyrate. In fact it is their favorite food. They don’t get it much, or enough, on the typical diet, because if you ingest butyrate it is digested before it reaches the gut (and it smells horrid: you probably wouldn’t eat it voluntarily). However, if you eat certain kinds of fiber that have a specific “digestion mode”, then bacteria can eat the fiber and produce butyrate, which nourishes the gut cells.

    Now, fat can be broken down into butyrate too. So what if: when you eat “too much” fat, the extra is not absorbed in the upper gut. It is eaten by bacteria in the lower gut, which keeps the bacteria happy and also produces butyrate. Which makes the gut cells happy, but they don’t produce fat: they just get healthier. Extra gut cells slough off all the time, and wouldn’t show up as “undigested fat” in tests.

    I personally think that the whole “gut health” thing has a lot to do with obesity and insulin too: if the gut cells aren’t working right, they can allow iron overload, and THAT really messes with insulin levels.

    Dr. Eades, I think you are one of the few people to touch on the connection between iron levels and metabolic syndrome, but I haven’t seen much research on WHY iron levels would go up when the body is trying so hard to regulate iron uptake. Incorrectly functioning gut tissue would do it though, I think.

      • Indeed; I came to the protein power diet as a way to moderate the inflammatory effects of chronic Hep C, including reducing the fibrosis risk; but the iron factor means that red meat needs restricting (and other factors make vegetable protein attractive – it tends to be higher in “inessential” amino acids like arginine, plus lignans and isoflavones like genistein have marked antifibrotic effects).
        I recommend Dounglas Kell’s paper Iron Behaving Badly on Scientific Commons.

        A question; does the proton pore effect have anything to do with osmolytes like taurine and betaine?

    • I have to agree with you. From where I’m coming from poor gut health is a major scource of endotoxins; these stress the liver and poor liver function (and, of course, inadequate protein) reduces synthesis of proteins that carry away excess iron – so it is stored in the liver or enters circulation virtually unbound, causing metabolic havoc.
      It’s amazing the conditions that respond to probiotics; food allergies, but also hayfever, something you would think had nothing to do with the gut.
      The “caveman” diet was supposedly very high in iron- over 30mg daily – however, compared to modern diets, it was also very high in polyphenols which tend to chelate iron, both in the gut and in the blood. See the Douglas Kell link in my comment below.

  21. In the last year, or so, I have experienced a re-education on thermodynamics. In the last 20 years or so, there has been a mojor change in the way the subject has been taught.

    For over a century, the field was taught with primary emphasis on the heat engine, and a rigorous and nearly total exclusion of modern physics concepts – in particular quantum mechanics.

    By introducing quantum concepts of “states” of a system, and the ability of people to “count” or enumerate the possible states of a system, the whole field can be made easier to understand.

    Under the old system, it was often easiest to rely on memorization and pushing equations around to survive and answer test questions — but still to not UNDERSTAND what is going on.

    The new system is much more rational. Less memorization is called for.


    If you drop a book onto a table, all of the potential energy of the book is converted into heat in the table (and to pressure waves of the sound which ultimately end up as heat). The conversion of potential energy to heat is essentially perfect.

    Yet, the heat in the table and the sound waves in the air never come back focused in time and space to recreate the conditions that existed on the falling book impact and then propel the book back into the air.

    However, it is possible to convert electricity into potential energy at nearly perfect efficiency with a friction free electric motor(with superconducting wires) and a pulley and weight. It is possible to take the same weight and pulley and an electric generator (frictionless and superconductive wires) and nearly perfectly convert potential energy into electrical energy.

    Heat – is impossible to convert perfectly into any other form of energy.

    Heat = Thermal

    Thermodynamics = dynamics of heat. conversions…. as the origin of the word.

    The study of the strange way heat stubbornly resists efficient conversions to work or other forms of energy.

    When I first ventured into Bioengineering, I had a heck of a time beginning learning the many fundamentals involved in the new field, and managed to get by on not knowing them well, but just enough and often “just in time”.

    There are some wonderful web pages on “The Second Law of Thermodynamics” that helped re-educate me, and then buying some of the more modern texts on thermodynamics taught the new way.

    The old books are truly terrible. You learn to do things, but understanding of the “dynamics of heat” is completely missed.

    I wish you good fortune in thermodynamic re-education, and suggest that you find another mind as good as yours – but fully tuned into modern thermo. Y

    You could even honestly enjoy it, with the right materials.

    • Maybe I should go back and give it another look. I still get hives when I think about the steam table problems I had to do in my thermodynamics course in engineering school.

    • Jim B,
      What are the sites on the internet you had in mind? I did not find my thermodynamics courses so bad as difficult to understand (although I may still not know enough to distinguish). The reason that the subject is so elusive is that it is not a molecular science which is what we are good at. Rather it is physics of aggregates, that is, ensemble properties which we don’t have good intuitions about. Arnold Sommerfeld put it well.

      He was one of the great physicists in the development of quantum mechanics but was considered an expert on most areas of physics. His take on thermodynamics along the lines of your description:

      The first time I studied it, I thought I understood it except for a few minor details.
      The second time I studied it, I thought I didn’t understood it except for a few minor details.
      The third time I studied it, I knew I didn’t understood it but it didn’t matter because I already knew how to use it.

      • The first law is “just the conservation of energy” but it is applied carefully to systems. Closed and open systems. “A calorie is a calorie” isn’t close to a careful application to a system – closed or open.

        The second law is the source of the greatest confusion and misunderstanding and misapplication. The recent version of the Second Law website The original version. Both on the second law of thermodynamics. About the third law. This is the educator’s version of the website Here are some books that meet the criterion of referring to entropy as a mesaure of “energy dispersal” rather than “disorder”. The listing of these 21 book is described as—–

        “There have been some noteworthy improvements in texts’ treatment of entropy in terms of energy dispersal. A few will be mentioned here. In May will be listed the 21 chemistry texts that no longer define entropy as “disorder” but rather emphasize molecular energy dispersal, concretely in space or abstractly on more energy levels in each microstate, as a useful approach to understanding standard entropy and entropy change.” The May listing of these books is on the page above this quotation as the page is chronological from the most recent to the oldest .

        The two books I used are:
        “Entropy Analysis: An Introduction to Chemical Thermodynamics (Paperback)”
        ~ Norman C. Craig (out of print and hard to find – interlibrary loan) Actually focuses on the subject and refuses to use calculus for anything. The goal is to make it more understandable, not more full of computation. It is kind of tedious at times because of the rejection of calculus from the discussion.

        “Elements of Thermal Physics: Physics 213″ by James P Wolfe was found at a library sale and was evidently a nearly private printing at the University of Illinois. Perhaps a few rare book dealers might have it. A lot of “used to be” advanced subjects can be simply introduced at the Sophomore/Junior college level with the right approach.

        Until now, I didn’t realize how poorly available were the two books I used to re-educate myself on thermodynamics.

        Dr. Mike, There isn’t a steam table in sight or even a hint of one in both of these books. UCSB has a bunch of fine physical scientists and surely a campus visit would bring you some excellent selections of books and stories to keep you motivated.

    • Jim B: Thanks for those comments. One thing that upset me in college was when a professor “proved” something by covering the board with equations. I could reproduce the equations on exams, but I still didn’t really understand the concept. When I went to a teaching fellow for help, he (I didn’t have any shes) would reproduce the equations so of course I still didn’t understand it. Luckily, I never found that the Carnot Cycle was discussed a lot at potluck supper.

      I thought I was stupid. It took me years to realize the teaching fellow probably didn’t really understand it either. If you really understand something, you can explain it to a novice without using equations and technical words.

      I think one thing Dr Eades is trying to do is to explain diet concepts to nonspecialists in terms everyone can understand.

  22. People like to make a lot of the “individual differences” in people and how some can tolerate more this or that than others can. Yes, we’re all Individuals, but the underlying mechanisms of food, energy, weight gain or loss must be the same. I do believe that some genetic differences exist between populations exposed to higher carb diets over millennia, which probably protect those populations a little bit from the depredations of the high carb diet. Beyond that, though, it seems to me that individuals have variable food histories, activity levels, pre-natal environments, etc. and that these differences, not true genetic ones, will allow one person to seem healthy on a diet that is literally killing another person.

    My only point being I do get tired of hearing that I must be anomalous if I have to keep my carbs so low to avoid weight gain.

  23. Prof er not really as both your side and the Colpo side are adamantly assuredly convinced they are right i.e both convinced you’ve got the insight !
    Did you ever read the uber super Intuition its Powers and Perils by Dave Myers ?
    You’d like it i reckon not least as he marshalls(the science) in one chapter why few ever seldom change their perspective even when presented with clear evidence they understand.
    i.e. put yr labours and yr nodoubt large body of knowledge to more useful endeavours instead of reciprocal chest-beating with some twot with a def. chip on both shoulders..the definition of a well balanced Australian..i heard that in Down Under BTW !

  24. But do we know for sure that very low carb over long periods of time does not adversely effect metabolism? I can’t help but wonder given my own experiences, my health is much worse and now vlc gives me the most unbearable itchy rash as well virtually straight away.
    I love low carb, before the rash when I first started (2002) I found it so easy to do, ketosis was very easy for me, I never seemed to adapt in that I always had dark purple sticks months and months down the track and I never experienced any “induction flu”. My only problem was that my progesterone only pill stopped working on LC and caused lots of hormonal problems, I have seen may others have this same issue and it does not clear up within a few months. I am not a big bread or cereal eater and I find dairy very satiating so it was easy to stick to and perfect for me to maintain so I am not trying to bash it. But I don’t feel comfortable telling people to stay at 20g or less for long periods of time anymore because I always wonder in the back of my mind so now I always encourage them to go up the ladder.

    On the insulin comment, I did weights when I started LC and later tried refeeds for a little while when my hormones went wonky but in my experience then I found the longer I did the diet and weights (I can’t say if one or both were behind it) I found I handled carbohydrates much better, not worse.

    • Sherrie, this sounds like allergic reactions to certain proteins. One of the factors that some people will have to deal with on LC diets is that the most common food allergens are complex proteins, often from high-protein foods; casien from milk, gluten, zein from maize, and egg, soy, and beef protein are very common allergens in the US.
      We are not talking about the anaphylactic peanut-type allergy here, but the leaky gut/ low digestive enzyme exposure to undigested antigenic proteins, immune reaction to which can cause symptoms as diverse as mental disorders, sinus, and skin problems (casien and gluten) or rheumatic joint and muscle conditions (maize).
      One way to rule these foods out while on LC would be to use a purified protein such as whey or rice protein to replace the suspect food in the diet.
      In general the LC diet, by reducing inflammation, should reduce the response to these antigenic proteins, but the underlying digestive issues need treating (probiotics and aloe being a good place to start).
      It’s my hunch that these problems are spreading not because the foods are intrinsically bad but because maize, soy, milk, gluten are ADDED TO EVERYTHING these days, often in a single GM form, and the immune system objects to this blanket, cradle-to-grave exposure.

  25. If humans were merely furnaces then the data from the thermo lab bomb calorimeter measurements would SEEM to confirm that eating fat would make us fatter than eating carbs– 9 cals/g v 4 cals/g. But, the fat and cholesterol we eat isn’t primarily for fuel and heating us. It’s mostly for ‘house-keeping’ and BUILDING AND MAINTAINING OUR ENORMOUS FATTY BRAINS. The following example of throwing around the term ‘thermodynamics’ sticks in my craw. I was listening to a radio segment some years ago about the creationism-evolution debate. There is a topic that has some legs in the anti-evolutionists argument and that’s thermodynamics, and that evolution violates one or more of the laws of thermo. It is not a valid argument. A woman called in and said something like “have you seen those equations” and how they don’t support evolutionary theory? The host agreed with her. Well, here’s the thing. I’m not being snooty, but I’m pretty sure the caller and the radio host had never taken a course in thermodynamics or physical chemistry and had never seen ‘those equations’. I have. I teach a section on biochemical thermo and I’ve taken up through calc 3, multivariable calculus. I’ve even worked with a bomb calorimeter in a thermo lab. Yes, I have seen ‘those equations’ and nothing in evolutionary theory and energy balance or transfer violates a thing. Caller knew nothing, nada, zip, zero about what she was commenting on, and sadly her statements went unchallenged. And she was incorrect to assume that evolution violates any of the thermodynamic laws or equations. She was just repeating and parroting incorrect info- ARGHH! This is so completely analogous to the ‘eat low-fat, eat low-cholesterol, and drug down your cholesterol ever lower MANTRA. It’s repeatedly justified because of ‘all the research backing it up’. There is no research that backs up much of any of it. And much research that better confirms the opposite.  I was raised a religious liberal. I’m a dyed in the wool scientist (biochemist) and I have absolutely no issue with the theory of evolution, but not because I’m a Unitarianl. I think Darwin helped us with HOW we got here. I can separate that from the more philosophical (more religious, really) question of WHY we are even here!
    Sorry I’m rambling and discussing two different topics, but I can tell you that NOT getting fat by consuming dietary fat catagorically does not violate any of the laws of thermodynamics.

    • Believe me, I feel your pain. I hate hearing people rabbit on about stuff they know absolutely nothing about. The one that makes me want to blow my brains out is one that I hear all the time. If I’m at some kind of get together, and I end up chatting with someone and reach the point when the conversation turns, as they all do, to ‘So, what do you do?’ I cringe because I know it’s coming. When I explain what I do, the person I’m talking to – who, just by the law of averages is overweight – almost always says, Well, I’ve always just believed in everything in moderation. AAARRRGGGHHHHH!!!!!

      • Were you aware that apparently, the term “Balanced diet” came into being in the 1920’s and early 1930’s? This was the decade of the explosion of vitamin identification. Almost everywhere you looked, there was another one of the darned things being doscovered. Some of them had brothers and relatives like all of the many B vitamins.

        It was scary. Who the heck knows what to eat when all of these vitamins are cropping up in different foods.

        NO WORRY — Eat a lot of different things . EAT A BALANCED DIET.

        So, the “balanced diet” was an answer to basic feelings of ignorance about what we might discover next.

        I forgot where I first heard the story.

        You can get a sense of this by Googling for “balanced diet history vitamin deficiency” and you may eventually find this page….. a timeline of the thing. It indicates the period as the origin of the term “balanced diet” and it is smack in the explosion of vitamins ….. “how to NOT get a vitamin deficiency”,tll:1931,tlh:1931&ei=1GSBS9yeB4XcNf6c_cQJ&oi=toolbelt_timeline_result&resnum=3&ct=timeline-date&ved=0CEMQzQEwAg&fp=212ef43bde1bb7cd

      • “Well, I’ve always just believed in everything in moderation”

        Well, that brings up a question I have, Dr. Eades (or do you prefer Dr Mike :-) ):

        Everyone says the above, and also another one of my favorites: “eat a balanced diet.”

        PLEASE correct me if I’m wrong, but everything I’ve been researching and reading in my layman’s brain has led me to conclude that, if you can get all of your nutrients and energy in a lowcarb diet, and starchy carbohydrates for the most part have little to no nutrition in them, then balance is exactly what you DONT need. In fact, based on the science I have read from Atkins, yourself, Gary Taubes, and countless others, then a lowcarb diet — and by popular definition, “unbalanced” is in fact optimal.

        I know that this is very simplistic, but would you argree?

  26. My temp is about 97 degrees. So is it possible my struggling to lose weight is in part an uncoupling problem because of low body temperature?

  27. Squire i have the perfect antidote for the ‘moderation in all things’ shite. OOOO when folks say that i have often said ‘Do you really reflect on what that actually means ?”
    I blithely trot out that i work with folks whom have HIV and are addicted to mainly crack due to them no doubt starting of pre-moderation and by the time crack addiction becomes moderate( all things relative of course) well..

    I now a rather well known addictions shirnk on the UK and for most of his kids lives as parental functions he would say he was an engineer simply cos of all the hassle he’d get when he told people he was a shrink.
    When initially qualified and then telling what he did, folks would invariably say ‘whats the difference between a psychiatrist and a psychologist’ and he’d give the oldie ‘about 30000 a year !”

    • Inability to be moderate – binge mentality – may be down to an inter-related combination of a lack of antioxidants and poor glutamate metabolism.
      N-acetylcysteine, which elevates glutathione and lowers glutamate, seems to break addiction cycles,especially when combined with niacinamide, which increases sensitivity to GABA (countering the effect of glutamate), and all the other nutrients that support the antioxidant systems.
      Certainly, this was my experience in relation to addiction to amphetamines, benzos and opiates. After months of supplementing these things for completely other reasons, decades of drug addiction started to wear off.
      I’ve read about this approach working for self-harm behaviours (and drug addiction can become a kind of self-harm obsessive compulsive behaviour) and gambling addictions; it must be worth trying for food addictions.

  28. Hi Dr. Mike—I respectfully express confusion:

    Futile cycling vs. “acylation stimulating protein”.

    I first read about ASP at Peter’s (Hyperlipid) blog. The pertinent link to his post is here:

    Does one or the other control under certain conditions, or is more/less active? From this link ( I think I get that ASP and insulin work together, both act on glucose, ASP is high in obese people but goes down when they’ve fasted for 4 weeks. All this, along with insulin increasing ASP 3-fold, makes me think of the carbs-insulin-obesity thing.

    But then there’s this (also from that 2nd link, under “Regulators of ASP”): “postprandial rise in chylomicrons results in the strongest stimulus for ASP production (150 fold rise) in a dose dependent manner.”

    And what about this: “Exercise increases ASP acutely by up to 67% in athletes with relatively rapid return to normal levels afterwards.” Now I feel like the world just turned upside-down. Exercise increases ASP which stores body fat so…does exercise cause us to store body fat?

    (If you can’t tell, all of my questions are from the I’m-trying-to-lose-weight-but-can’t-so-I-worry-about-why-centric viewpoint.)

    Also, thank you for this post, and for posting Dr. Feinman’s comments—they were very informative.

    • The research group that found ASP is uncertain as to exactly what it does – if anything – in humans. The other group doing work on ASP has conflicting ideas as compared to the first group. Until it is all sorted out – if it ever is – I don’t put a lot of stock in ASP.

  29. I believe in LC. I have metabolic syndrome. I am a hobby runner. While training for a marathon I gained 25lbs (all while doing upwards of 30-50 miles a week) Now that I am “in the know” I successfully enjoy runs up to 10 miles (so far) with my running group all while being LC (Something I would have never thought possible) Since going LC, I have lost 25lbs but I seem to be stuck. I don’t really count carbs, but when I think back to what I have eaten, my calories add up to slightly less than 2000 calories. I am 42, 5’10” and 225lbs. I know that the amount may be on the low side, but I am not restricting, I just eat when I am hungry. Anyway- Is the mileage I am running now (no more than 20 miles/ week) counter productive to my weight loss?

    • I wouldn’t think so. All you would have to do to test it is to quit running for a couple of weeks while maintaining the same eating pattern to see what happens.

  30. To Dr. Kurt Harris,
    Some people like Biological Thermodynamics by Don Haynie, Cambridge Press. I’ve not read it myself but I’ve heard good things about it. I went to grad school with the author.

      • Dear Dr Eades,

        I wrote the original message about the miscalculation. Takes only a minute to check it. Not a big deal, just a note to let you know. Feinman’s response was more general and didn’t really address this point. Don’t get me wrong, I’m fine with the theory. I even consider eating Manninen Nutraceuticals products (a buddy of Feinman) some day.
        I especially liked the signature in the video: R. Feynman, the second. After the famous Nobel laureate. My hero.
        BTW, funnily, my thermodynamics education comes from Atkins’ books. Not the one you think right now, but another hero namely Peter W Atkins, Oxford. Search for Atkins’ Physical Chemistry and you have it.

        • I am re-checking the calculation (translation: I am having somebody else re-check my calculation). It must be wrong. If you assume ballpark 25 % TEF for protein there must be a much bigger effect than we wrote.
          Toni, please give us your figure. I think the predicted value would be easily measurable but that was, in any case, not the point. I was making the point that reasonable assumptions show that metabolic advantage is possible. If you dismiss it, you will miss any potential payoff.

  31. If I may add something about ASP, I believe the effects of ASP are very short-lived (unlike the effects of insulin). That helps me understand why they’re probably not very significant.
    Sorry if that makes a tangent to the thermodynamics thread.
    Really interesting stuff here.

  32. I’ve always maintained that the least understood facet of chemistry and biochemistry is thermodynamics.

    I did an undergrad in chemistry and now a PhD in biochem, I never really started to understand these concepts well until I took stats thermo as a senior. I also had to realize though that the human body isn’t a calorimeter, and thats a tough thing to get. We’re in a point where you can’t just be an expert in one area (thermo, etc) and comment on human health. There are so many more concepts to understand that so often these experts bring an incomplete view.

    The price of elite science tends to be over specialization. I think this is reflected strongly in the scientific literature lately, specifically when it comes to a diverse and complicated subject like human health.

  33. BTW, this is by far your best blog post illustration. Please keep this photo in mind when making cover suggestions to the publisher for your next book.

    • I’ve loved this photo since the first time I saw it. I’ve just been waiting for the perfect place to use it.

      Sadly, others weren’t as enamored with it as you.

  34. Suggestions on thermo books:
    All of the major biochemistry texts, Devlin, Stryer, Voet & Voet have a good section on thermo, the last is personal recommendation. They are encyclopedic and most are in n editions, n large so that the (n-1)th edition is sufficiently up to date and probably available for not too much. Amazingly, none of the nutritional experts appear to have read these and appear to think that bioenergetics is a revealed subject.

    On popular books, best is probably von Baeyer HC: Warmth Disperses and Time Passes. The History of Heat. New York: Random House; 1998. Down to earth and even includes game you can play with your kids on probability which is essentially equivalent to entropy. Buy used from Amazon for very little. Also, Prigogine and Stengers: Order out of Chaos is great but parts are more technical.

    The truly great comprehensive philosophical works are Harold J. Morowitz: Foundations of Bioenergetics and Mae-Wan Ho: Rainbow and the Worm. These are comprehensive. Definitely not page-turners but very good to dip into from time to time.

    Of the serious texts, I like Modern Thermodynamics: Kondepudi and Prigogine. People refer to Kenneth Denbigh: The Principles of Chemical Equilibrium but I find it very dry and and dense. (Disclaimer is that it is one of the texts I used in graduate school and I find the typography off-putting which counts in a book where it can take you a long time to read one page).

  35. I’m still curious — I opened Excel and entered the data and came up with 1825.5 as well — the response you posted by the study author didn’t mention that. Was that in fact a typo? thx

  36. If you read Gary Taubes’ book, he points out that alpha glycerol phosphate is required to store fat in a fat cell, and that alpha glycerol phosphate can only be obtained in any significant quantity as a result of carbohydrate metabolism. So in the absence of any carbs in the diet (or, on a diet almost entirely mad up as fat), there is almost no alpha glycerol phosphate in the diet to help store the fat in the fat cell, which may be an explanation for why people on high calorie, high fat (low carbohydrate) diets don’t seem to gain any weight.

    • This is the basic idea of carbohydrate restriction for fat loss but it is important to know that It is only part of the picture. The adipocyte has several mechanisms for homeostasis. Glycerol-3-phosphate can also be synthesized by the process of glyceroneogenesis. This is a truncated form of gluconeogenesis. So whereas GNG overcomes the irreversible steps in pyruvate generation and essentially reverses glycolysis up to the hexose-phosphate, glyceroneogenesis reversis glycolysis up to the triose-phosphate and a dehydrogenase catalyzes conversion of dihydroxyacetone-phosphate to glycerol-3-phosphate. Also, hormone-sensitive lipase-knockouts are actually protected against obesity, a counter-intuitive effect that I think has never been explained.

  37. Apologies for the delay in answering the original criticism of our paper in Nutrition J. In fact, the comment was correct and we made some kind of arithmetic error and the actual degree of inefficiency is less than we calculated. The loss in calories due to thermic effect of feeding when CHO is reduced to 20 % is only 56 kcal. This is embarrassing but doesn’t change the conclusion which, as we pointed out is over-kill since the idea of the thermic effect of feeding is an indication of metabolic advantage. The point of our paper was that once metabolic advantage is established as possible which, in some way, it always was, it is worthwhile to find out how to maximize it.

    To put the problem in perspective it might help to look at the historical context. Thermodynamics is about the second law (it was actually formulated before the first law), that all real processes are inherently inefficient. As described by Prigogine (Order out of Chaos), thermodynamics was the first non-classical science and “part of a more global intellectual move” because it recognized irreversible processes. These were not part of classical, Newtonian dynamics which was repetitive and and reversible. Conservation of energy is essentially equivalent to conservation of matter which was understood in the eighteenth century. Thermodynamics is about dissipation not conservation.

    In the matter at hand, all Gene and I wanted to do was ask: if metabolic advantage does take place, how could it come about and even if you think it has never been seen, does it violate any physical law (in which case we could stop discussing it). The answer to the second is no and, in fact, thermodynamics more or less demands metabolic inequalities. The cases where energy balance are found is due to the special properties of biology, not physics.

  38. How about just dropping all the high-polluting stuff and saying that the calories you don’t burn from a low-carb diet are flushed down the toilet in the form of ketones when you urinate? That is why you don’t gain weight even though you may be eating a lot of fat, yes?

  39. On ketosis, possibly of interest: in the metabolism course at Downstate, students were asked to study an MCAD (medium chain acyl-CoA dehydrogenase) deficiency. This is the enzyme that begins the process of breaking down medium chain fatty acids which, in turn, are the product of long chain fatty acid metabolism. The kid in the case was in life threatening situation due to not eating in her usual schedule because she had a flu and didn’t feel like eating. The problem is that whereas normal schedule of eating allowed her to have enough energy from conversion of long chain to medium chain fatty acids (and carbohydrate), she did not have enough fat metabolism to provide ketone bodies for period where she was in effective starvation: a life threatening absence of ketone bodies. (I gather more common in children who have less stored glycogen, fat, etc.). Apparently such patients have to avoid skipping meals and low fat diet per se is without effect.

  40. This is answer to post by Felix which was sent to my email but I don’t see:

    You mean fewer microstates (fewer possible ways to do ketone body metabolism than oxidation), therefore lower entropy to go through ketosis and therefore a requirement for more energy. The important point is that ketonuria is a small amount of energy and a reflection of ketone body metabolism where a different process for oxidation of fatty acids. The important point is that calories in chemical thermodynamics are for processes not substances. So, the process

    FA –> ketone bodies –> transport –> CO2 is more inefficient (uses more energy) than the process
    FA –> CO2

    and is probably one source of metabolic advantage.


  41. “Metabolic advantage has to be consistent with thermodynamics . “”Thermodynamics is about the second law (it was actually formulated before the first law), that all real processes are inherently inefficient.” I was searching for this information over time and to no avail and now i have it.Thanks. I got a good read!

  42. if you’re interested in learning more about thermodynamics from a non-book junkie perspective, i suggest reading into walter russell’s book the universal one and also viktor schauberger. They’ll define energy from a radiation and gravitational perspective, opposite spins, so that you can have yet another perspective on why current orthodox’s understanding of thermodynamics is only half truth.