The recent awareness of an epidemic of obesity coincides with, and may have contributed to a dramatic increase in the popularity of a variety of low carbohydrate diets. This rapid switch in dietary habits of a significant part of the population, and the virtual revolution in the food industry, is unusual in that it stands in direct opposition to long-standing recommendations of the majority of the nutritional and medical establishment (e.g. [1, 2]). Despite isolated examples, such as a recent editorial by Walter Willet pointing to the need to understand low carbohydrate diets [3], there is still little real acceptance by nutrition professionals or health organizations. One aspect of these diets that has been especially controversial is the so-called metabolic advantage – the idea that more weight may be lost calorie for calorie compared with diets of higher carbohydrate content.

We recently reviewed the literature on metabolic advantage [4]. We showed that there is a sufficient number of reports in the literature to establish the existence of metabolic advantage and we tabulated results from ten or so studies demonstrating that low carbohydrate diets can lead to greater weight loss than isocaloric low fat diets. The reports we cited have frequently been met with the criticism that the data could not be right because they would violate the laws of thermodynamics ([5, 6]). An example is the recent demonstration of metabolic advantage in a small, pilot study [7] which, despite its preliminary status, was extremely well controlled. Three groups were studied: A low carbohydrate group (LoCHO = 1800 kcal for men; 1500 kcal for women), a low fat group (LoFat, 1800 and 1500); a third group also consumed a low carbohydrate diet but an additional 300 kcalories were provided (LoCHO+300, 2100 and 1800). The order of average amount of weight lost was LoCHO = 23 lbs, LoCHO+300 = 20 lbs LoFat = 17 lbs. This work received a good deal of attention in the popular press. Media reports, however, included comments of experts that "It doesn't make sense, does it?" "It violates the laws of thermodynamics. No one has ever found any miraculous metabolic effects." ([5]). If this is an accurate quotation, it is odd indeed. Miraculous, or otherwise, a metabolic effect was found. In the absence of an identifiable methodological error, experimental data has to be accepted and numerous investigations, in fact, serve as precedents for Greene et al.'s findings (Reviews: [4, 8]).

In our previous review of metabolic advantage [4] we showed that there is, in fact, no theoretical violation of the laws of thermodynamics, and we provided a plausible mechanism. In general the pathways for gluconeogenesis that are required in order to supply obligate glucose (e.g. to brain and CNS), in combination with increased protein turnover, could account for the missing energy. Here, we simplify the thermodynamic argument and review some of the relevant principles. We show, moreover, that well-established data in the traditional nutritional literature predict metabolic advantage and no one should be surprised. The ironic conclusion is that the principle that weight gain on isocaloric diets must always be independent of macronutrient composition would violate the second law of thermodynamics.