"A calorie is a calorie": does it truly contradict thermodynamics? Giuseppe Marineo, Delta Research & Development, Bioengineer Research Center, affiliated to “Tor Vergata” University 6 October 2004 Dear Sirs, In regard to the article “A calorie is a calorie violates the second law of thermodynamics” by Feinman RD et al (Nutr J 2004; Jul 28;3:9 ), I believe it is a useful brief thought on the proper application and interpretation of thermodynamics in nutrition. We agree with several aspects of the article and with its overall meaning. However, we believe there are still some potential conflicts regarding the analytical methods to be used when a complex system such as the biological one is considered. This occurs because we are forced to use a number of general laws and conceptually adjust them to biology with its complexity and dynamics. To examine energy transformations from a thermodynamic point of view, we adopt the definition from physics of a calorie as the thermic energy needed to increase the temperature from 14.5°C to 15.5°C of 1g of distilled water at 1 atm pressure, even though the concepts are not wholly applicable to biology. In such a context, the concept of a calorie used by nutritionists implies a somewhat arbitrary and "static" equivalence which isn't suitable to thermodynamics. Briefly, since the thermic energy cannot be directly utilized, the free energy of glucose (or other nutrients) does not have a clear functional definition since it is practically impossible to foresee whether and how such substrates will be transformed in work and heat, nor the efficiency of their conversion which is understandably variable in a complex and dynamic system such as the biological one (mainly due to the ever increasing entropy of the total system). As an example, I believe that we might agree that the thermogenesis of an individual exposed to low temperature (below the physiological one) has to be regarded as useful work. Thus, heat production corresponds to an effective utilization of available energy by contributing to homeostasis. However, the same thermogenesis occurring in an individual exposed to a temperature higher than normal, forces the body to use the available energy to produce work and recruits other physiological responses such as sweating etc.). Since vital chemical reactions cannot be shut down. I believe that even in considering apparently simple phenomena such as thermogenesis / thermoregulation, we cannot ignore the complexity and properties of what is a dynamic system. Such properties may change over a very short time, changing the related thermodynamics. Since the complexity of biological systems is a primary factor and not secondary to thermodynamic processes, we believe it isn’t possible to use a specific conceptual analysis to clarify the relationship between calorie and body weight, beyond “conceptually-guided” probability calculations [1, 2]. G. Marineo, F. Marotta Delta Research & Development, Bioengineer Research Center, affiliated to “Tor Vergata” University, Rome. Via di Mezzocammino 85 00127, Rome, Italy email@example.comReferences:1. Marineo G, Marotta F, Sisti G (2004). Cirrhosis progression as a model of accelerated senescence: affecting the biological aging clock by a breakthrough biophysical methodology. Ann. NY Acad. Sci. 1019: 572-576. 2. Marineo, G. Marotta, F.. Biophysics of aging and therapeutic interventions by entropy-variation systems. BioGerontology 2004 (in press) Competing interests Giuseppe MarineoQualifications and Titles:Researcher, Bioengineer (MD, PhD)National affiliations:Convention with "Tor Vergata" University of RomeProfessional experience:-Basic research on developing theoretical biophysical models for medical use. -Research and Development phase aimed at the treatment of chronic degenerative diseases (Delta-S Entropy Variation System) and of untreatable neuropathic and oncological pain (Scrambler Therapy).- Founder and manager of Delta Research & Development, Medical Bioengineering Research Centre with special convention with 'Tor Vergata' University of Rome.