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).
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. , 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.