Bray, et al. Shows that a Calorie is Not a Calorie and that Dietary Carbohydrate Controls Fat Storage.

Posted: March 19, 2012 in Crisis in Nutrition, energy metabolism, low-carbohydrate diet, Protein, Volek-Westman principle
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I did not indicate, in my previous post about the article by Bray, et al, “Effect of dietary protein content on weight gain….,” the most important outcome of the paper, undoubtedly unintended: their data actually support the Volek-Westman principle — the primacy of the glucose-insulin axis in fat storage. I had not explained this because the analysis had been sent as a Letter to the Editor to JAMA and they do not want the content of Letters to be published elsewhere and I wasn’t sure about their editorial policy on blogs.  The editors have since rejected the Letter and I have reproduced it below.

In the way of background, the study was one of several recent attempts to show that only calories count in diet experiments. I criticized the obvious bias in the paper suggesting that they were setting up the straw-man of protein as the key component of the diet.  By keeping carbohydrate, the dietary component most likely to have a strong effect, at a constant percentage of energy, Bray, et al showed that, contrary to the group’s previous position, macronutrient composition did have an effect on weight gain but that the effect was on lean body mass rather than fat which, they claimed, depended only on calories (although other groups had shown the opposite).

The experiment:

Three diets of the same energy intake were compared.  All were designed to provide an increase of 40 % above the energy requirements of the subjects. The energy requirement was determined in a “run-in” period over 2-3 weeks prior to the experiment.  The composition of the diet was set to a constant percentage of carbohydrate of 41% of calories. The protein levels were then specified at 5 %, 15 % or 25 %.  (It is worth noting that the fat composition ranged from 64 % to 34 %). The study was a random controlled study and was carried out in a metabolic ward so the results are probably more accurate than the usual diet study that relies on dietary records.  The complicated part of the study, though, is that although the calories are a constant level above each individual’s initial energy expenditure, they are not absolutely the same for each participant in the study.  In essence, this is a study of the effect of varying calories while keeping individual energy requirements constant. The figure below, re-drawn from Figure 6 of the paper compares the effect of intake of absolute energy and the effect of protein intake.

In my original post, I pointed out how the correlation might depend on a single high value for one subject but let’s take the authors’ interpretation at face value.  They draw the conclusion that, since there is a correlation between calories and fat storage but not between protein and fat storage, that “…excess calorie consumption alone and not the amount of protein in an individual’s diet contributes to the accumulation of unwanted fat….”  (Again, fat storage was also independent of dietary fat).  The conclusion is certainly consistent with the data but one can look further.

Remember that, as the experiment was  set up, the carbohydrate level was maintained at a constant 41 % of energy. In other words, the carbohydrate for each subject is directly proportional to the number of calories, or: carbohydrate = 0.41 x K x energy, with K the conversion from calories, or in this case, Joules, to grams of carbohydrate. (A Joule is equal to 4.19 calories).  The calorimeter value for carbohydrate in Joules = 16.75 J/g, so dividing the energy in the paper’s Figure 6 by 16.75 g and multiplying by 0.41 will give us the increase in g carbohydrate.

 Now we do not have to change the figure at all but we merely relabel the x axis as “Carbohydrate Intake”.  We have the same correlation as before except that now the independent variable is grams of carbohydrate.  So the data can be interpreted as showing a direct dependence of increased body fat on calories or, alternatively, a direct dependence on carbohydrate.  Which is the preferred interpretation?  Well, which is most consistent with biology? We know that there are numerous receptors for carbohydrate and that the effect of carbohydrate is to stimulate release of insulin and other hormones that have a lipogenic effect.  We have never identified a calorie receptor and it is unlikely that there is such a thing; an effect of calories has sometimes been shown to be due specifically to the contribution of the carbohydrate calories.  So, here is my Letter to the Editor at JAMA:

Calories or Carbohydrates?

To the Editor,

The recent study by Bray, et al. [1], in which patients were overfed diets of varying protein content, provided evidence that “calories alone account for the increase in fat; protein affected energy expenditure and storage of lean body mass.….”   The data, however, are equally consistent with the idea that it is dietary carbohydrate that is the controlling variable.  In Bray’s experiment, carbohydrate was a fixed percentage of energy and therefore the level of this macronutrient is directly proportional to the number of calories. Thus, while the results are consistent with the primacy of calories, they can just as accurately be interpreted as control by carbohydrates. This perspective has a stronger basis in underlying biochemistry deriving from the anabolic effects of insulin and glucose itself; if nothing else, there is no known receptor for calories.  The results are thus in concert with the many studies showing the control of fat mass by dietary carbohydrate. [2-4 ] Figure 6 of the paper could now simply be relabeled with carbohydrate in place of calories as the independent variable.  A more reasonable conclusion from a fundamental biochemical perspective would then be: “the amount of dietary carbohydrate accounted for the increase in fat; protein affected energy expenditure….”

Bray’s study used a metabolic ward and doubly labeled water techniques providing more accurate data than dietary recall on which much of the literature relies. Given the dramatic improvement in weight and body composition reported for low-carbohydrate diets [2-4],  it might have been better for the authors to employ these methods to test whether carbohydrate restriction is as effective as it appears.

As shown in the revised figure, it cannot be excluded that a fitting conclusion from Bray’s work would be: accumulation of fat mass in over-feeding correlates with increased carbohydrate, a limited effect of protein and significant decrease in fat consumption, somewhat like the obesity epidemic itself.


  1. benfury22 says:

    Could we have those [2-4] references please?


    • rdfeinman says:


      Bray GA, Smith SR, de Jonge L, Xie H, Rood J, Martin CK, Most M, Brock C, Mancuso S, Redman LM: Effect of dietary protein content on weight gain, energy expenditure, and body composition during overeating: a randomized controlled trial. JAMA 2012, 307(1):47-55.

      Volek, J.S., et al., Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog Lipid Res, 2008.

      Krieger, J.W., et al., Effects of variation in protein and carbohydrate intake on body mass and composition during energy restriction: a meta-regression. Am J Clin Nutr, 2006. 83(2): p. 260-274.

      Volek JS, Sharman MJ, Gomez AL, Judelson DA, Rubin MR, Watson G, Sokmen B, Silvestre R, French DN, Kraemer WJ: Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutr Metab (Lond) 2004, 1(1):1

  2. LeonRover says:


    I recall recall reading this study in detail when it it was first published, and I have since read it again.

    I understood that each participant was first fed to a weight stable diet of C:P:F = 60:15:25.

    The over-feeding consisted of increasing each participant’s intake by 40% while keeping CHO constant, and I quote:

    carbohydrate intake was kept
    constant throughout the study. The experimental
    diets varied by chemical
    analysis in the ratio of protein to fat.”

    I am at a loss to understand how you explain ascribing Delta KJ above baseline to a Delta gms CHO above baseline when no such change happened in the experimental protocol.

    It seems to me that this study showed that the human body experiences one of the body composition consequences of fasting, even in overfeeding – to wit, lean body loss – when protein is reduced to .67 gm/kg of initial body mass.

    One of my conclusions is that the protocols used by Kirsch et al in their studies were seriously deficient as participants experienced excessive lean body loss in the weight reduction part of those experiments. It throws even more doubt on their “experimental verification” of the existence of an adipostat, to any degree of statistical relevance.


    • rdfeinman says:

      No, I think that is not right. I went back to the paper which says “The low protein diet had 6% of energy from protein, 52% from fat, and 42% from carbohydrates. The normal protein diet had 15% of energy from protein, 44%
      from fat, and 41% from carbohydrates. The high protein diet had 26% of energy from protein, 33% from fat,
      and 41% from carbohydrates.”

      I think if you take percentages of the quantity based on resting energy, the carbohydrate level will change.

      The study was designed to prove an unprovable idea that the authors are clearly obsessed with. I confess to an equally un-admirable exercise to show that, if anything, their data demonstrate the opposite but the truth is that this study does not show much of anything. The changes are small compared to the individual variations among participants which is what happens if you set up the experiment trying to keep constant the thing that will give you the biggest changes. This experiment involved a good deal of careful work and government money. It is the sad twilight of the lipophobes.

      • Colleen says:

        “The changes are small compared to the individual variations among participants which is what happens if you set up the experiment trying to keep constant the thing that will give you the biggest changes.”

        Thereby proving that the one thing that was kept constant (carbs) is the one thing that will have the most effect, right? That was my first thought on reading your original blog post on the study, but I don’t recall anybody coming right out and saying so.

      • rdfeinman says:

        I think other bloggers have said this. I pointed out, however, that I told Bray how to do it right. In addition, in the ORI post, I added two other things that we can get the government to do. If you bring these suggestions to your elected officials, they may notice. If your friends bring up the same issues, they will definitely notice. If a thousand people write, or go see them (they, or their aides, have to meet with you. It is their job), they will do something. If you’re active, you can do something. By you, of course, I mean me. I know how hard it is.

  3. George Henderson says:

    “if nothing else, there is no known receptor for calories”
    That’s a statement that cuts the Gordian knot.

    • Brian says:

      There is some evidence that there are ‘receptors’ in the oral cavity that ‘taste’ calories. Look into the work of Rollo regarding oral sensors for motor output in endurance running.

      Basically simply rinsing the mouth with carbohydrate and expectorating the fluid leads to a lowered rating of perceived exertion (and increased performance) when completed in the fasted state (typically after a 10+ hour fast). The most common sugar used was maltodextrin. I can’t recall the paper right now, but I believe using fMRI it was shown that the non-sweet mouth rinse activated a center in the brain separate from the taste receptors.

      • rdfeinman says:

        That is different from a calorie receptor. The intestine responds to all kinds of food and releases incretins, glucagon-like-peptide (GLP) — but the controlling variable is not the number of calories and may be a pressure receptor. That’s also one reason that the conclusion in Bray, “calories alone account for the increase in fat; protein affected energy expenditure and storage of lean body mass, but not body fat storage” shows a lack of precise language, since protein is part of the calories.

  4. greensleeves says:

    With deepest respect, Dr., this ship has sailed for another generation. Marion Nestle, the adviser to governments, has issued her new book “proving” CI/CO, and this Bray study was just the final trimming. Despite your courageous efforts, this is one we have just lost. Like global warming, CIH may be true, but no one believes it now except for a few “crazy people” like ourselves. Pity.

    • rdfeinman says:

      Not at all. Bray, et al. is the leitmotif of the twilight of the lipophobes. Marian Nestle is a dietitian and the battle will be won with the science and the voice of the people. Whether global warming is true or not will be decided ultimately by the scientists but the playing out of the story will be generally beneficial as it already has been in some way (although mostly benefitting efficiency in industry). Or battle is greater but will be won by the science and the people who have experience. Of course, as in my post, it will actually turn around overnight because of the lawyers which, while not the best possible approach, this is America.

    • rdfeinman says:

      Here’s an interesting link on Marian Nestle:

      • benfury22 says:

        Well… I’d be careful about citing The Center for Consumer Freedom’s (CCF) comments about anything… even if they’re right about Nestle. CCF is a notorious industry front group:

        Be well,

      • rdfeinman says:

        Yes. As in my comment above, they can help keep the nutrition establishment for blaming the food industry which, in the end, follows what people want. That, it turn, is determined by the NIH-USDA-ADA conglomerate.

      • Colleen says:

        I poked around on that site ( a bit. The food articles, at least, seem to be militantly Calories-In/Calories-Out.

        The Nestle link you provided is useful for its further links to her activities.

      • rdfeinman says:

        Yes. They would be strange bedfellows for us but any enemy of the sugar tax is a friend of mine. They are not nutrition people at all but, as benfury22 says, a food industry organization. Part of the fight is that the nutrition establishment has a sequence of scapegoats, sugar, salt, fast food, saturated fat that they use to hide the failures of their recommendations and, of course, little as they know about nutrition, they know less about behavior and policy so they immediately resort to taxation and punishment of some kind. If they can go after the Bloomberg-Nestle-Lustig group, we can focus on the science.

      • Colleen says:

        At least I didn’t see Koch Industries in their lost of donors.

        Soda tax is silly. It would never be stiff enough to make a difference, for one thing. Better to convince people to lay off the sugar. Of course, people are weary of being told that various foods are bad for them. I think grass-roots is a good vector, especially once we get enough irrefutable evidence to back us up.

        I have a friend who edits medical textbooks–another vector. She’s on board with much of this stuff, and despite encountering a lot of resistance in her fellow editors about things like inflammation and heart disease, is seeing slow but steady acceptance. Get the textbooks right, and the doctors and people will follow.

      • rdfeinman says:

        I completely agree with everything you have to say except it seems Koch Industries creates value by using resources more efficiently; protecting the environment and the safety and health of our workers and others; consistently applying good science. I know, because their website says so.

      • Colleen says:

        Color me chastened.

        Seriously, has anyone systematically tried to influence textbook authors and editors? Showing them evidence of the lousy science involved? In my one little window into the textbook industry via my friend, I can see that such a thing might be possible. They redo their big textbook every year or two; little incremental steps toward The Light certainly wouldn’t hurt.

        Uffe Ravnskov’s Fat And Cholesterol Are Good For You is all about debunking bad studies…what do you think of it? (Aside from the fact that it costs $25 as a paperback!)

      • rdfeinman says:

        I don’t know about textbooks in nutrition but in biochemistry there is a whole story that will be a blogpost and article for biochemical education journal.

        I think Uffe’s first book was better. As I told him, when I read the book, I thought “it could’t be this bad,” and I had to go back to the original studies and I was shocked to discover that it was that bad. Along these lines, here’s a question that I ask my medical students in lecture (I think it is not hard to guess the answer):

        00. Several large clinical or population studies have been carried out to
        determine if their is an association between dietary saturated fat (SF)
        and cardiovascular disease (CVD). The trial(s) that have successfully
        shown such an association:

        A. The Framingham Study.
        B. The Multiple Risk Factor Investigation Trial (MR FIT).
        C. The Women’s Health Initiative.
        D. All have demonstrated a relation between SF and CVD
        E. A and B
        F. Only A
        G. None have demonstrated a relation.

      • Martin Levac says:

        @Colleen, we used to pay taxes on refined carbs, “soda”. But we now call this old tax “natural selection”. Basically, refined carbs, or any carbs for that matter, used to be so rare that this very fact restricted our total intake. In order to increase this intake, we had to do all kinds of things like agriculture and preservation for future use. Today we call this tax “subsidies”. We pay it, but it’s invisible because we pay it indirectly. Remove those subsidies, and the tax is now made visible. Add direct tax on top and it becomes prohibitive.

        Taxation and subsidy is a form of natural selection. But it’s artificial selection. The effect is the same though. And so it has the same effect on total intake. I agree with you though, it must be stiff enough to make a difference.

        I am reminded of the diseases of the rich. Obesity, gout, etc. Subsidies, therefore taxes, have made those diseases available to the poor. Remove those subsidies, add tax on top, and those same diseases will return to where they belong. Taxes. I’m for ‘em!

      • rdfeinman says:

        Reminds me of the old “Beyond the Fringe” review (some of which is available on YouTube). One of the characters is opposed to the heavy tax on cigarettes because it takes lung cancer out of the reach of the middle class.

  5. “The editors have since rejected the Letter…”

    What a surprise!

    • George Henderson says:

      Arthur C Clark summarises the first two laws of Thermodynamics: “There are no concessions and no cheap rates. You may have to pay more, but you can never pay less.”

      If you fridge runs inefficiently, you may know because food perishes, or it makes a funny noise.
      But maybe you’ll only notice when you get the unusually high power bill.

      Given that fats and carbohydrates enter the body through completely different routes and arrive at cells via different receptors, it seems unlikely that our perception of caloric sufficiency is exactly the same for a given amount of energy from either source.

  6. George Henderson says:

    Experimental refutations of calories-in calories out come from high-fat rodent studies.

    Control rats fed beef fat + MTCs gain less weight than control rats fed equal calories from corn oil:

    Mice given time-restricted feeding gain 28% less weight than ad lib feeders on equal calories:
    (Usually high-fat diet is bad for rodents; these “outperformed” healthy-eating rats).

    In neither of these cases did equal caloric intake result in equal weight gain, despite the high-fat rodent bias towads adiposity.
    And this is just comparing fats with fats…

    • rdfeinman says:

      Thanks for these links. At least in some strains of mice, there is what might be called a metabolic disadvantage. We are presenting our study of C57Bl6 mice who gain more weight per calorie on high fat diets, even if carbohydrate is low (or absent). Abstract points out that “rodent models of obesity may be most valuable in the understanding of how metabolic mechanisms work in ways opposite to their effect in humans.”

      • George Henderson says:

        High-fat diets are used in rats because they produce obesity and it is obesity they want to study, not high fat diets.
        However, there is a bush rat I see from my window who raids bird nests for eggs and chicks. I imagine his diet is pretty high-fat at the moment. He is sleek and muscular, with not a trace of excess adiposity.

      • rdfeinman says:

        “High-fat diets are used in rats because they produce obesity and it is obesity they want to study, not high fat diets” but the published papers almost always say “high-fat diets,” or at least “diet-induced obesity.” Right?

      • George Henderson says:

        Yes, in the “conclusions” they usually jump to conclusions.
        Which are reflected in the abstracts.
        Which is why your abstract is so valuable.

  7. George Henderson says:


    Nice touch in the abstract. Hope it catches on.

  8. Laura says:

    Dear Prof Feinman

    Long time not seen
    I am following the thread with interest. As a geneticist I feel the calories in/calories out argument does not explain all observations (in humans and animals) and does not explain obesity, cravings, resistance to weight loss and rebound weight and all the rest. As you know I msyelf have embraced the LCHF with amazing results. In my modest opinion CI/CO is almost as bad at explainig the obesity problem as Lamarckian theory explains the transmutation of species.

    Anyway, I would much value your opinion on this other more sublte aspect of macronutrient effect on body weight. I bring to your attention this oldish paper bay Dulloo et al in Metabolism 1995; 44: 273-279. In a nutshell as well as there being differences between MACROnutrients P-C-F in they way body composition is influenced there is also ‘within’ macronutrient categories effect. We know, for example, that liquid sugar is particularly good at elevating blood insulin. Within fats I had from personal experience noticed that vegetable fats even in the more natural form as nuts for example (rather than processed oils) are more fattening within a lchf context than lard or other animal fat.

    Well in the paper cited above they put rats on a diet and then split them into groups receiving different amounts of fats from animal to vegeteble and they measure how well the rats recovered body weight. At least in rats vegetable oils were indeed more fattening.

    I am fascinated by this because I can gorge on nuts to the point of making myself sick but I could not possibly gorge on animal fat. However I do not think this is simply a matter of quantity. Even keeping amounts equal long chain fats seem to encourage fat deposition.

    I would much appreciate your expert opinion on this matter.
    Thank you

    • rdfeinman says:

      … As you know I msyelf have embraced the LCHF with amazing results. In my modest opinion caloriesin/calories out is almsot as bad at explaining the obesity problem as Lamarckian theory explains the transmutation of species.

      Of course, epigenetics gives us a different view on Lamarckianism which was only rejected as being a major contributor.

Well in the paper cited above they put rats on a diet and then split them into groups receiving different amounts of fats from animal to vegeteble and they measure how well the rats recovered body weight. At least in rats vegetable oils were indeed more fattening.
..Even keeping amounts equal long chain fats seem to encourage fat deposition.

      I think that it is certainly possible, even likely, although in rodents fat itself has a relatively greater effect than carbohydrate compared to the effect in humans. Forsythe, et al., for example, showed different effects of saturated fat vs. Unsaturated fat although under conditions of carbohydrate restriction althought the effects were smaller than the effect of reducing the carbohydrate.

      • George Henderson says:

        Sexual selection is also a kind of Lamarkian evolution; the giraffe’s neck gets longer because female giraffes fancy a longer-necked male; by small increments the neck of part of the species becomes long enough to eventually confer a survival advantage on that part, confirmed by natural selection during hard times.
        Evolution by force of whim.

        Here’s another calorie-not-a-calorie paper

        FASEB J. 2012 May 25. [Epub ahead of print]
        Timed high-fat diet resets circadian metabolism and prevents obesity.
        Sherman H, Genzer Y, Cohen R, Chapnik N, Madar Z, Froy O.

        Although timed HF-diet-fed mice consumed the same amount of calories as ad libitum low-fat diet-fed mice, they showed 12% reduced body weight, 21% reduced cholesterol levels, and 1.4-fold increased insulin sensitivity. Compared with the HF diet ad libitum, the timed HF diet led to 18% lower body weight, 30% decreased cholesterol levels, 10% reduced TNF-α levels, and 3.7-fold improved insulin sensitivity. Timed HF-diet-fed mice exhibited a better satiated and less stressed phenotype of 25% lower ghrelin and 53% lower corticosterone levels compared with mice fed the timed low-fat diet.

        I read this as, a 12% difference when feeding is isocaloric, an 18% difference when it is ad lib.
        In which case, 2/3 of the difference is NOT appetite-related.

      • Laura says:

        Thanks for your comment. I have worked on Epigenetics in various model organisms including fruit flies and birds at a time when many researchers were inclined to think this type of processes were not so important in humans and it was probably limited to one generation effects (think idiomorphic moles, pathenogenesis and prader-Willi syndrome). In flies epigenetic effects of heat shock for example can be seen for generations as measured by certain genetic events such as hybrid dysgenesis. I always thought that this had to be important in humans as well but we just had not measured it yet then one day attending a seminar by a certain Professor Pembrey I almost lept off my seat!!
        His work was on transgenerational effects of famine in humans….I am sure you have heard about it. Although yes one could invoke a certain Lamarckianism in this I think Epigenetics is more like a molecular programming system/molecular memory than a use/disuse mechanism…

      • rdfeinman says:

        Yes. Epigenetics is more sophisticated than Lamarckianism but even there it was its generality that was questioned. I assume you meant “idiomorphic.” Did you mean “moles?” I am not familiar with the phenomenon.

  9. George Henderson says:

    Here’s a review
    A time to fast, a time to feast: The crosstalk between metabolism and the circadian clock

    Of note: the liver’s release of glucose from hepatic glycogen is timed to be antiphasic to feeding behaviour and glucose intake. Ergo, shift-workers have increased risk of type 2 diabetes.

  10. Laura says:

    Fats and recovery of body weight…sorry for going on about this but my point is not jsut that vegetable long chain fatty acids are fattening in rats but that these nutrients are MORE fattening than other types of fat such as animal fats. My point is that different fats appear to be DIFFERENTIALLY fattening….I think this may be important I also see it on myself that olive oil is more fattening to me than lard…I wondered if you have any comments or more info on this. Thank you in advance

  11. [...] Bray, et al. Shows that a Calorie is Not a Calorie and that Dietary Carbohydrate Controls Fat Storag…. [...]

  12. [...] a look at this graphic, created by and graciously lent to me by Dr. Richard Feinman, professor of cellular biology at SUNY Downstate Medical School. He uses this slide to teach medical [...]

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