There are thousands of nutrients at thousands of locations throughout the body.
It is mathematically impossible for all of these millions (thousands of nutrients times thousands of locales) of values to be optimal or even within the optimal range.
Of necessity, some will be excesses and some will be deficiencies.
Optimal nutrition that seeks to make every calorie count will do a better job of shoring up deficiencies than a diet with lots of empty calories.
However, a diet in which every calorie is adding nutrition, implying that there are no empty calories, may result in greater imbalances wherever some nutrient is already in excess, unless that good diet is supplying more of nutrients – and these nutrients cannot themselves be in excess, unless some metabolic or excretory process is not working properly – that metabolize and/or excrete the nutrients that are currently in excess.
Thus there may be a problem with over-nutrition, especially in the isolated, indigenous peoples, who unlike us, had no pantries, refrigerators, or freezers filled with foods with empty calories, peoples described so eloquently by Weston Price.
Supplementation may make some of these local excesses even worse.
So, contrary to common sense, we may need some empty calories to counterbalance some of our nutrient excesses.