How many times have you seen both of these phrases, at one time or another?:
1. "A Calorie is a Calorie." (Thus insinuating that the composition of our food doesn't matter.)
2. "A Calorie is not a Calorie." (Thus implying that the quality and composition of the food we eat is the only thing that matters.)
In order to satisfactorily answer the question whether a Calorie is a Calorie, we must first define our terms.
A calorie is a unit of thermochemical energy, equal to approximately 4.184 joules. Roughly speaking, it is the amount of heat released from a substance when that substance is oxidized, or burned. Classically: a calorie is the "amount of energy needed to raise the temperature of 1 g of water by 1 degree Celsius, at a pressure of 1 atm."
Important to note here is that a calorie and a Calorie are not mathematically equivalent. Calorie, with a capital C, is actually 1,000 gram calories, or 1 kilocalorie (kilogram calories; 4,184 J). It's confusing at first, I know, but you'll get it.
The thing that bothers me is this: by saying "a Calorie is not a Calorie," what you are effectively suggesting is that 4.184 J does not equal 4.184 J. Uh... Yes it is and yes it does. It's math, and the thing about mathematical proofs is: they can be proven. But let's ignore the philosophy and science of mathematics, for the time being. I understand what you are really trying to say. You're trying to say that "Counting calories is ineffective." So, why why not just say that? Let us all choose to be more precise in our thinking, and in the way we convey those thoughts to the world.
Make no mistake about it. A Calorie is a Calorie is a Calorie, because, 4.184 J is 4.184 J is 4.184 J.
That said, just because 1 Calorie = 1 Calorie, chemically and mathematically, that does not necessarily mean that oxaloacetate is phosphoenolpyruvate is acetyl-CoA is alpha-ketogluterate, or that protein is carbohydrate is fat. Or, for that matter, that glucose is fructose is cellulose is ribose. Or, really, any other combination of similar nutrition-related sets you can conceive of. Do you see where this is going? That's because these compounds are actually different "things" with different biochemical and physiological actions. Different molecules, different substrates, different structures, composed of different things, or even just different amounts of different "stuff." Point being, just as 8 of something is always the same as any other 8 of the same something, a Calorie is and will always be a calorie.
But by conceding the truth of that cliched statement, I've told you nothing useful about metabolic processes. At least not with regard to their various causes and effects. Appealing to an energy flux, with respect to physiology and metabolism, speaks only to the large-scale (macro-level) results of thousands of chemical interactions happening within the system, yet it says nothing about those (micro-level) biochemical interactions.
What frustrates me about the opposing idea, that "a Calorie is a Calorie," at least as it is currently argued in the nutrition sphere, is that this notion implies that the 1st law of thermodynamics (the conservation of mass and energy) and "Calories in, Calories out" are exactly equivalent scientific hypotheses. In fact, they are not -- at least not from a pragmatic perspective, and I'll tell you why.
Calories in, calories out (CICO) could only be identical to Energy Conservation if all of the incoming energy and all of the outgoing energy (and every biochemical or biophysical transformation in the middle) could be measured and accounted for. As far as I am aware, this is currently impossible. Calories in, as measured by the average person, is often hundreds of Calories off the mark; and even our best methods of measurement in this area are not precise enough to account for all the physiological activity that takes place after said energy has been consumed. (After all, we don't just care about what's incoming, we care about what our cells are doing with this energy, and this is incredibly complex. To my knowledge, this is not something we are able to measure with any amount of precision.) On the other end of the spectrum, Calories out is equally, if not much more, challenging to measure.
You know that little monitor on your elliptical which tells you how many calories you're supposedly burning, during your workout? It's wrong; and not just some of the time, it's always wrong. So wrong, you'd be astonished. You might as well put a piece of black electrical tape over it and forget it's even there, that's how useless it is.
In most cases, energy expenditure is so multivariate, complicated, dynamic and difficult to measure with sufficient accuracy and precision, that it's a wonder anyone can conflate CICO with energy conservation - even if the underlying conception isn't entirely incorrect.
You shouldn't come away from this post going: this author thinks all Calories are equivalent, so eat whatever you'd like. Don't misinterpret. I'm saying all calories of the same amount are equivalent amounts of energy -- however, the substrates from which they came may not be. The latter is not only more important, but far more interesting, in my opinion, as this is where the intricate biology takes place, and is one of the things that separates us from physical machines.
Human beings are not bomb calorimeters.
(As an aside: we do not "burn calories" -- our cells burn chemical substrates and release the thermochemical energy in their chemical bonds as heat. Which substrates are oxidized, at what rates, in which pathways, etc., all of this matters far more in describing the "whys" of metabolic interactions than any appeal to an energy flux ever could.)**
**To the many internet nutrition gurus who have come to believe that the human body - or, indeed Life (i.e. cells), in general - does not obey and cannot be described by the laws of thermodynamics, I suggest you do some reading in statistical mechanics and non-equilibrium thermodynamics, because the statement: "We are open systems, therefore, thermodynamics doesn't apply" is misleading and incorrect.