There are a lot of things we do know. For example, the reason most “diets” don’t work is that the body responds to the caloric intake given to it by reducing outgo to match intake. What the body does with food is determined by the hormonal milieu. In fat-storing mode, we are hungry most of the time, because insulin is blocking the leptin receptors in the hypothalamus that are supposed to shut off ghrelin production. Also, because so much of the food energy is being directed into storage, it is not available for powering cells, so the body is in a perpetual state of needing energy that is not available.
In a low-carbohydrate milieu, things are different. The body is not in storage mode, it is in energy-use mode. Energy flows into fat cells, but is free to leave, so cells throughout the body have all the energy they need. With insulin low, the hypothalamus can register leptin again, so we are not hungry for long periods of time. Given an abundant caloric intake, the body is free to ramp up the metabolism, and to activate processes that may have been put on hold—again adjusting outgo to match intake, but this time in the opposite direction.
The foregoing is all known science. And it explains why caloric intake is not particularly important on a low-carbohydrate/ketogenic diet. The mechanism of satiety generally prevents overeating, so calorie-counting becomes unnecessary. The problem I have with people who insist that calories are relevant is that the human race has known of the caloric content of food for 0.005% of its time on earth, so if calorie-counting is so necessary, how did the race manage to survive for the other 99.995% of its existence?
I also like Gary Taubes’s point that the First Law of Thermodynamics says nothing about the direction of causality. Why are people so insistent that we grow bigger because we ate too much? Why can’t we have eaten so much because we were growing bigger? No one sane claims that the pubertal growth spurt is the result of children’s eating too much—we all know that the growth spurt is caused by hormones and that food intake must increase to supply the energy and materials for that growth. Why can’t hormones still be the cause of growth in adulthood?
I can testify that I grew to weigh 300 lb./90.9 kg by eating in a manner that put my body in fat storage mode. Like many obese people, I had the experience that I seemed to grow fatter no matter how little I ate—cutting back only made me hungrier. When I switched to a ketogenic diet, I paid no attention to the quantity of food I was eating, nor did I track its caloric content. I paid attention only to whether I was hungry or not, stopping eating when I stopped being hungry, and somehow, with no effort on my part, I shed over 80 pounds of fat. In light of that experience, to insist that our primary concern must be establishing and maintaining a caloric imbalance seems rather naive.