At that point I would imagine it's the same concept as net carbs. Obviously not all food/matter is digestible. I do think it's still safe to say calories in/calories out however since most of us aren't entering shredded paper, charcoal and wood into MFP logs.

While you can control the input, the output gets harder - one cannot just simply double/triple their defecation rate, and exercise tends to work out an appetite.

http://well.blogs.nytimes.com/2014/11/12/exercising-but-gain...

Output is governed by hormones, and the only reliable hack for now seems to be significantly lowering insulin by switching to ketogenic diet (or a variation thereof, /r/zerocarb, /r/keto, Atkins, Dukan). I'd recommend this book https://en.wikipedia.org/wiki/Good_Calories,_Bad_Calories with understanding that a lot of nutrition and diet science is in very premature stage because of World War 2 and lack of funding thereafter.

I once read that different kinds of food deliver calories in forms with different degrees of absorb-ability.

Source: http://www.iflscience.com/health-and-medicine/why-most-food-...