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Actually, respiration is burning the food, it's literally the same energy release, and the methods of calculation take into account the portion of the food that's burnable but non-digestable. If you're saying that the corrections for indigestible food are the subject of scrutiny, that's true, but that has nothing to do with the fact that "burning" is a problem for calculating caloric content. I used to work in aquaculture, where we measured the amount of food going into a fish (via the bomb calorimetry that we're talking about, directly), the amount of energy spent by the fish in respiration (by measuring carefully increases in water temperature in their tank), and then we measured how much energy the fish had at the end (by burning the fish). And quite simply, calories in was equal to calories out. It was a good relationship within very acceptable experimental error. Now of course, the fish were growing very rapidly and we could control their food exactly. Humans, growing over a longer period, can be subject to different metabolic pathways, and we can't measure their respiration directly of these pathways [Edit: this is where the gene expression you mention comes in] - this is a far, far bigger source of error than the calorimetry, so calories alone can be less predictive of outcome. But this doesn't take away from the basic definitions of thermodynamics. |
2) All other things being equal, changing "calories in" will make you lose/gain weight. The trouble is, all other things are not equal - simply changing how much you eat will significantly change those other things, it has an effect on your metabolism and eagerness for physical activity, thus directly affecting also "calories out" if you don't carefully monitor that and work to keep that stable.
3) All other things being equal, changing "calories out" will make you lose/gain weight. The trouble is, all other things are not equal - simply starting/stopping working out will significantly change your natural appetite, how hungry you are and how often you're hungry, and which types of food you have cravings for, thus directly affecting "calories in" unless you carefully track what and how much you eat everything and actually do keep that schedule exactly the same.