Is a calorie a calorie? Biologically speaking, no

Department of Physiology
Faculty of Medicine
University of Oulu
Finland
E-mail: anssi.manninen{at}oulu.fi

Dear Sir:

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 energy-dependent 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 low-carbohydrate 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 low- to medium- and 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).

REFERENCES

1. Buchholz AC, Schoeller DA. Is a calorie a calorie? Am J Clin Nutr 2004;79(suppl):899S-906S.
2. Feinman RD, Fine EJ. Thermodynamics and metabolic advantage of weight loss diets. Metab Syndr Relat Disord 2003;1:209-19.
3. Hue L. Regulation of gluconeogenesis in liver: In: Jefferson L, Cherrington A, eds. Handbook of physiology: the endocrine system. Vol 2. Oxford, United Kingdom: Oxford University Press, 2001:649-57.
4. Bier DM. The energy cost of protein metabolism: lean and mean on Uncle Sam's team. In: The role of protein and amino acids in sustaining and enhancing performance. Washington, DC: National Academies Press, 1999:109-19.
5. Bravata DM, Sanders L, Huang J. Efficacy and safety of low-carbohydrate diets: a systematic review. JAMA 2003;289:1837-50.
6. Kauffman JM. Bias in recent papers on diet and drugs in peer-reviewed medical journals. J Am Phys Surg 2004;9:11-4.
7. Manninen AH. High-protein weight loss diets and purported adverse effects: where is the evidence? Sports Nutr Rev J 2004;1:45-51. (Internet: www.sportsnutritionsociety.org.)