Whatever happened to the second law of thermodynamics ?

I just read with great interest the well-written paper by Buchholz and Schoeller that discusses thermodynamics and weight-loss diets (1). However, the authors ignored the fact that the energy utilization of different diets depends on the biochemical pathways taken (2). For example, a low-carbohydrate diet dramatically increases gluconeogenesis relative to a high-carbohydrate diet. Obviously, gluconeogenesis is an energy-consuming process: 6 mol ATP is consumed during the synthesis of 1 mol glucose from pyruvate or lactate (3). The transformation of gluconeogenic amino acids, such as alanine, into glucose requires even more energy because 4 mol ATP is needed to dispose of the nitrogen as urea (3). Furthermore, the energydependent processes of maintaining the turnover of body proteins— including synthesis, folding, targeting, regulatory processes, and protein breakdown—have an overall cost to body energy homeostasis that is significantly higher than previously appreciated (4). Thus, it is easy to understand why high-protein, low-carbohydrate weight-loss diets are so effective. However, the recent systematic review in the Journal of the American Medical Association concluded that “weight loss while using low-carbohydrate diets was principally associated with decreased caloric intake and increased diet duration, not with reduced carbohydrate content” (5). As pointed out by Kauffman in the Journal of American Physicians and Surgeons (6), this is a misleading conclusion. In the true lowcarbohydrate group, the mean weight loss in trials was 17 kg, whereas in the higher-carbohydrate group it was only 2 kg. Oddly, the authors did not consider this significant. Only by intermingling the results of trials of lowto mediumand high-carbohydrate diets could the authors have reached the misleading conclusion quoted above (6). Finally, there are valid concerns about possible adverse effects associated with high protein intakes. It should be noted, however, that there is no scientific evidence to support these contentions (7).