ABSTRACT
The aim of this review was to evaluate data regarding potential thermodynamic mechanisms for increased rates of weight loss in subjects consuming diets high in protein and/or low in carbohydrate. Studies that compared weight loss and energy expenditure in adults consuming diets high in protein and/or low in carbohydrate with those in adults consuming diets low in fat were reviewed. In addition, studies that measured the metabolizable energy of proteins, fats, and carbohydrates were reviewed. Diets high in protein and/or low in carbohydrate produced an ≈2.5-kg greater weight loss after 12 wk of treatment. Neither macronutrient-specific differences in the availability of dietary energy nor changes in energy expenditure could explain these differences in weight loss. Thermodynamics dictate that a calorie is a calorie regardless of the macronutrient composition of the diet. Further research on differences in the composition of weight loss and on the influence of satiety on compliance with energy-restricted diets is needed to explain the observed increase in weight loss with diets high in protein and/or low in carbohydrate.
A Calorie is Not A Calorie - A Discussion of Thermodynamics
Abstract
…In summary, we propose that, in isocaloric diets of different macronutrient composition, there is variable flux of stored TAG controlled by the kinetic effects of insulin and other hormones. Because the fatty acid-TAG cycle never comes to equilibrium, net gain or loss is possible. The greater weight loss on carbohydrate restricted diets, popularly referred to as metabolic advantage can thus be understood in terms of the principles of nonequilibrium thermodynamics and is a consequence of the dynamic nature of bioenergetics where it is important to consider kinetic as well as thermodynamic variables.
Note, TAG: triacylglycerol (triglycerides)
The perception that “a calorie is a calorie” was refuted by Young et al in 1971 (5). They compared 3 diets that contained the same amount of calories (1800 kcal/d) and protein (115 g/d) but that differed in carbohydrate content (3). After 9 wk on the 30-g, 60-g, and 104-g carbohydrate diets, weight loss was 16.2, 12.8, and 11.9 kg and fat accounted for 95%, 84%, and 75% of the weight loss, respectively. Thus, the authors concluded, “Weight loss, fat loss, and percent of weight loss as fat appeared to be inversely related to the level of carbohydrate in the isocaloric, isoprotein diets.”
5. YoungCM,ScanlanSS,ImHS,LutwakL.Effect of body composition and other parameters in obese young men of carbohydrate level of re- duction diet. Am J Clin Nutr 1971;24:290 – 6.
The point of Prof. Feinman’s article is, I believe, that any metabolic theory that claims that all food energy is fungible fails to account for the entropic loss associated with every chemical reaction, hence the invocation of the Second Law. Prof. Arencibia’s article makes the point that it is the mass of food consumed, not its energy, that leads to weight gain. It’s an interesting point, but I may quarrel with his conculsion after finishing the article.
I would simply add that the caloric energy from burning the food item in a bomb calorimeter is not the same as the metabolic energy derived from metabolising the food. For one thing, since protein is not metabolised under normal circumstances, but is rather broken down into its constituent amino acids and rebuilt into other proteins, its caloric value probably should not be counted in the energy intake/output analysis. (Granted, on a low-carb diet, a small quantity of protein is transformed into glucose each day, which is then metabolised, but that amount is very small.)
It should probably be re-stated in this connexion that a food calorie, which a physicist would call a kilocalorie, is the amount of heat required to raise the temperature of a kilogram of water one degree Celsius—whereas the metabolic currency of the human body is in molecules of adenosine triphosphate (ATP) produced. I have no idea how the energy liberated from reducing ATP to adenosine diphospate (ADP) compares with the energy liberated from combustion in a calorimeter, or how to account for the energy required to metabolise fat or glucose into ATP in the first place. It would be nice if someone were to consider these points.
And just to make the standard energy accounting more complicated, the values of 4, 4, and 9 kcals/g for protein, carbohydrate, and fat are rounded from the actual values. Protein and carbohydrate both, if I remember correctly, contain 3-point-9-something kilocalories of heat energy per gram when burned, and the value for fats depends entirely on which fat, and ranges from something like 6-point-something to a little under 10-something. Add to that the difficulties of obtaining a truly accurate figure for energy expended by the body, and we reach the point of absurdity.
Sigh… Wrong. It does not address CICO. This is the same strawman argument that many have commented about - it’s a logical fallacy. This is misrepresenting what the argument is, pretending about what the science is, to try and make it easier to attack. Very much the textbook definition of a strawman argument.
Same question others have asked - who do you see saying that “a calorie is a calorie”? To be clear, this means “per se” or “as simple as that,” as people have mentioned on various threads of this forum.
Exactly.
The “pretend equivalence” is this, in spades. “Calories in, calories out” - how, logically, do we get from there to pretending that calories cannot differ in their effect? Or that CICO is a statement of “equality”? It’s obvious that it’s not. Nobody with any sense is saying they have to be equal.
You found something from 16 years ago that doesn’t talk about CICO. Meanwhile, just last week on the “Spoon-Fed” thread you were saying
This is not true. This is a strawman argument.
@ElmosUzi Addresses CICO right up front in the very first sentence:
The principle of “a calorie is a calorie,” that weight change in hypocaloric diets is independent of macronutrient composition, is widely held in the popular and technical literature, and is frequently justified by appeal to the laws of thermodynamics.
Just expand the parsimony (a scientific principle) of that sentence to its fulness.
The principle of “a calorie is a calorie” [that would be CICO, ie calorie in calorie out], that weight change in hypocaloric diets [that would be calorie restricted diets, ie CICO] is independent of macronutrient composition [that would be a calorie is a calorie no matter what its source nutrient, ie CICO] is widely held in popular and technical literature [that would be diet plans and nutritional advice to ‘eat less and move more’, ie CICO], and is frequently justified by appeal to the laws of thermodynamics [that would be if energy in is less, the eat less part, than energy out, the move more part, then weight loss occurs because of the first law of thermodynamics, ie CICO].
BTW, CICO is actually 3 equations:
CI = CO means no change in weight
CI > CO means gain in weight
CI < CO means loss in weight
In the real world we can’t totally separate mass and energy in food, On @OldDog’s study (above) about energy balance versus mass change, they’re not mutually exclusive. Sure, ‘mass change’ is the bottom line, but the energy balance is a driver of this, as with the body needing to take energy from fat stores. Mass and energy can’t be entirely separated, i.e. if you don’t take in energy you’ll eventually die. I did have to laugh about the “weight fluctuations are ultimately dependent on the difference between daily food mass intake and daily mass loss.” I’ve seen people complain that CICO “is a tautology,” but here we have to realize that for practical purposes with our weight, it’s the same thing as mass 
(even going all the way from sea level to the top of Mt. Everest results in less than a 0.3% change in weight). Food energy has to be somewhat fungible. If it’s not totally so, is that a practical concern for us?
Been there… We do know about energy consumption and density at the basic levels where they operate in the human body. The ATP to ADP conversion is where essentially ALL our energy comes from. A mole of ATP thus used under physiological conditions gives us ~7.3 calories. At the level of a cell, we know the energy involved in the oxidation of carbon and hydrogen atoms - for decades we’ve known, to a level of accuracy that would not even swing a day’s energy usage for a person by one calorie. That “mole of ATP” is 240.974 grams, so we’re getting only 3% of a calorie per gram.
Does it really matter if we consider calories at the level of ATP conversion or if we just go with the 3500 cals/lb deal? In the end, energy expenditure and weight/mass change (if any) cover such a huge portion of the total picture. Trying to think of food in terms of eventual ATP conversion is enormously cumbersome, by comparison.
This may involve that inseparability or crossover between energy and mass in food. Even if we are not directly using it for energy, it certainly represents mass.
There is a reluctance in the body to metabolize protein for energy. @ctviggen’s study here Check out my comment I made at KetoCon2019 demonstrates this.
There were 3 different groups of people, fed diets with varying percentages of protein: 6%, 16%, and 27%. All diets were definitely hypercaloric. Considering things from the 3500 cals/lb standpoint, those groups gained 69%, 75%, and 80% of the weight predicted from assuming that all excess calories would go to weight gain.
Nothing earth-shaking, so far, but the figures are decently consistent, especially across diets with varied protein content. The higher the percentage of protein, the higher percentage of energy converted to weight there was - makes sense if we view the body as not wanting to ‘burn’ protein.
What’s remarkable is how completely the weight gain and the increased energy expenditure covered the increased calories. I don’t think such accuracy/completeness would have been expected.
Again, is it really practical to worry about the slight possible variances? Going through the calculations and measurements involved with the rule-of-thumb ‘3500 calories’ thing, for example, it works out exceedingly well for human adipose tissue - the triglyceride mix we store as fat, that our fat tissue averages 87% fat, etc.
Energy expenditure is not actually hard to measure. For the best, most complete results, put people in a direct calorimeter. But even indirects ones have displayed very small error, like ~0.25%, and it’s easy to get only 1% or 2% error.
No, no, no… 
First of all, it’s “calories in, calories out.” Furthermore, consider something where we will have no disagreements about the terminology (I hope, anyway… ) - let’s try “Dollars in, Dollars out.” There is no necessary equivalence here. If we’re talking about a budget or balance, then one side can be bigger than the other.
Nope, that’s not CICO (you’re only looking at the 'in"). But to continue being logical about it, don’t you agree that if one maintains the hypocaloric diet for long enough, one will necessarily lose weight?
No, no, good gravy, no. “Calories in, calories out” does not pronounce that macronutrients do not matter. It’s just saying, “Here’s where you are as far as calories.” The type of calories is a separate matter. From ‘CICO,’ while we can infer certain other important factors that relate to metabolism and weight, there is not enough information given to address macronutrient type.
Same as above. No, that’s not “calories in, calories out.” You have changed to the assumption that the “in” will be less than the “out.” This is right after you were pretending there was an ‘equals’ sign in there. Honestly… 
You are conflating humanity’s difficulty with maintaining a prescription for weight loss with the prescription itself.
That’s hopelessly confused. We begin with the law of conservation of energy. CICO fits right in. Beyond that, we can go on to other considerations, and you reflect that, below. Knowing only ‘CICO’ and relating it to time, we can infer to a high degree of confidence that weight change is occurring. This is demonstrated by endless studies, as @ctviggen’s, above. It also should be intuitive and self-evident, i.e. how could it logically be otherwise? This is not saying that caloric change will directly relate to weight in a linear manner (this too, as above). But weight change (if any) and energy expenditure will explain almost almost all the goings-on in the human thermodynamic realm. Here I mean that there is not much left, at all - a comparatively very, very little amount of energy in waste, normally. Liquid waste normally has essentially zero energy (or fat, protein, carbs if you wish) in it. Human stool normally has a very limited amount of fat, around 10-25 grams per day, almost no protein at all, and 1 or 2 grams of digestible carbs. So, in considering exogenous food, “calories in” either goes to metabolism or fat storage. Those are the 2 elephants in the room, there. On the “out side” is metabolism, standing alone, pretty much. If we’re getting energy from our fat stores, then that becomes part of the “in” side while that is true. The whole package is “in,” then either metabolism, storage or excretion (waste).
Sure - we’ve seen this before, and this is better than pretending that some permanent imaginary equals sign is actually there. Now we are going on to other considerations, and don’t those relationships make sense? We could as well go farther, to the movement of calories by macronutrient type.
For those 3 equations, aren’t they self-evident, if one looks at a long enough time?
Or, how long could a human satisfy the equations without having the stated conclusions be true?
Please read the article and direct your comments to refuting the authors’ terminology, claims and conclusions.
Until and unless you can cite some evidence, I think you are just making up your own definitions of various common ideas used by the proponents of CICO to define and explain their theory and methods of weight management.
Specifically, refute the following:
Conclusions
A review of simple thermodynamic principles shows that weight change on isocaloric diets is not expected to be independent of path (metabolism of macronutrients) and indeed such a general principle would be a violation of the second law. Homeostatic mechanisms are able to insure that, a good deal of the time, weight does not fluctuate much with changes in diet – this might be said to be the true “miraculous metabolic effect” – but it is subject to many exceptions. The idea that this is theoretically required in all cases is mistakenly based on equilibrium, reversible conditions that do not hold for living organisms and an insufficient appreciation of the second law. The second law of thermodynamics says that variation of efficiency for different metabolic pathways is to be expected . Thus, ironically the dictum that a “calorie is a calorie” violates the second law of thermodynamics , as a matter of principle.
… Metabolic advantage with low carbohydrate diets is well established in the literature. It does not always occur but the important point is that it can occur. To ignore its possibilities and to not investigate the precise conditions under which it appears would be cutting ourselves off from potential benefit. The extent to which metabolic advantage will have significant impact in treating obesity is unknown and it is widely said in studies of low carbohydrate diets that “more work needs to be done.” However, if the misconception is perpetuated that there is a violation of physical laws, that work will not be done, and if done, will go unpublished due to editorial resistance. Attacking the obesity epidemic will involve giving up many old ideas that have not been productive. “A calorie is a calorie” might be a good place to start.
No thats exactly what doesn’t happen over time due to metabolic slowdown… it might work in the short term but eventually (for some sooner rather than later) then the metabolism will slow thus you’ll stop losing. Then if you can’t speed it up again you’ll start to re-gain even on the reduce calorific intake and that’s when you are truly screwed.
What I’m gathering from this awesome debate is:
How can something be thermodynamic that is not thermodynamic unless you are dealing with brown adipose tissue?
You put food into steel chamber turn up the heat and the protein, fat or carbohydrate explodes and you get numbers for units of energy?
We are not steel chambers and cannot get hot or have the thermal capacity like a steel chamber calorimeter to measure the heat involved in chemical reactions?
If you could heat up a plastic bottle of water with your bare hands then your talking thermodynamics?
White adipose tissue is strictly or mostly chemical reactions, not thermal?
Brown adipose tissue requires cold conditions that create a chemical reaction that generate heat in the brown adipose fat UCP-1 (phosphorylation) which drains glycogen storage in muscle then uses fat to burn and brown neighboring fat by filling it with iron rich mitochondria? All electrical and thermodynamic?
Do we really think that counting calories 9, 4 and 4 and burning/oxidizing them with heat adequately is going to happen in the human body especially under white adipose tissue conditions? Hell no!
”…According to a 2010 study in the journal Applied Physiology, Nutrition, and Metabolism, “exercise in the heat—40 degrees Celsius [or 104 degrees Fahrenheit]—increases muscle glycogen oxidation and reduces whole-body fat oxidation in comparison to the same exercise intensity performed at 20 degrees Celsius [or 68 degrees Fahrenheit] …” …More
Counting Calories vs. Mass ?
Mass vs. Thermal?
Chemical vs. Mass?
That’s not answering the question. You’re talking about where it’s not maintained. The question was about if it was maintained.
You’ve switched from
to
Two different things.
@Festus I think @MarkGossage answered the question concisely by stating an unfortunate, although predictable fact. Most folks who stick with CI < CO long enough lose weight and there are hundreds of folks on this forum who did so on various renditions of CICO diets. BUT in the process they also slowed their metabolisms to the point of not being able to sustain themselves at that lowered energy level. You can’t eat CI < CO forever. At some point you have to stop or die. Once these folks ceased and started eating a bit more - even still much much less than originally - they quickly gained all the weight back and then some more. Many folks did this multiple times during their lives causing themselves all manner of harm.
Here’s what the National Health Service of UK recommends as a healthy diet:
Here’s the way they deal with the obese consequences of their healthy diet:
The plan is designed to help you lose weight at a safe rate of 0.5kg to 1kg (1lb to 2lb) each week by sticking to a daily calorie allowance.
For most men, this means sticking to a calorie limit of no more than 1,900kcal a day, and 1,400kcal for most women.
…
learn how to count calories on the plan
Looks a lot like CICO. No mention of differential metabolic processing paths for carbs, proteins and fats. No mention of the role of insulin in controlling glucose and storing/freeing fats…
He answered a different question. Sure, we’ve all heard about metabolic slowdowns, etc., the ‘Biggest Loser’ people and whatnot. Mark changed the question to “If one maintains a hypercaloric diet for long enough, one will necessarily gain weight?” The answer to this one is a bit different. For most people, yes - (as with a slowed metabolism (eventually) meaning weight gain; what’s being described is a hypercaloric situation). Same case for just increasing calories, no diet beforehand required. An exception would be if the metabolism increased enough to cover the increased calories, and stayed there forever.
The answer to the original question is obviously just “yes.”
A Calorie Is Still A Calorie
Why Keto Does Not Work
Abstract
…The rationale and features of the carbohydrate-insulin hypothesis postulate that carbohydrate restriction confers a metabolic advantage. According to this model, a large amount of fat intake is enabled without weight gain. Evidence concerning this possibility is detailed…Results from a number of sources refute both the theory and effectiveness of the carbohydrate-insulin hypothesis. Instead, risk for obesity is primarily determined by total calorie intake.
There’s a big difference between having a general awareness of the science, with the admitted limitations therein, and having an opinion and then groping toward something that sounds sciency and at least superficially, at first, appears to support one’s opinion. Logical fallacies do seem to come to the CICO debate, like moths to a flame.
I was thinking about the mass vs. energy thing - just enumerating calories certainly is not a complete view, given what can happen downstream, but the mass of macronutrients consumed is an even more complex thing. Would this really catch on? Some people really break things down already, bodybuilders, those who just love all the data…
I’m going to read it too, Paul. Entropy is unavoidable, right? 
If we’re talking about “entropic loss” in reactions, would that not just always be going to “calories out” or “energy loss” or “waste” - things we already consider to be there?
If you think about it, it makes sense if you look at the amount of food a bariatric patient can eat?
Bariatric diet demonstrates to me logically that we eat way more food than we actually need?
It is hard to believe if you were a prisoner of war starving in a concentration camp that there would be obese people walking around who do not lose body fat?
Then you have centenarians in Okinawa who do not eat until full and they eat very little meat and when they do it is usually pork and fish and mostly carbs like an endless variety of veggies, sea weed (high iodine) and bitter melon which is a brown fat activator?
Look at how long they live with no health problems? And past 100, one of them lived to 115 and one that lived to 125 which is not so well known?
Hara hachi bun me: According to the Japanese saying ‘Hara Hachi Bu’, eat until you are 80% full. Experts say that this is the key to a long, healthy life. The residents of Okinawa Island in Japan have the longest life expectancy in the world. They live up to 100 years. …More
How Okinawan People Live SO Much Longer Than Everyone Else | Longevity Film