Figure 1.

Diet design hierarchy. (a) Dietary pattern design. Chow vs. purified design. All nutrients between standard chow (SC) and HFD are mismatched. An undetermined component or components within the overall dietary pattern are responsible for the study outcome. No further causal inference is possible on the basis of the experimental diets alone. Addition design. All nutrients between SC and SC + puree (SC + P) are mismatched. An undetermined component or components within the overall dietary pattern are responsible for the study outcome. No further causal inference is possible on the basis of the experimental diets alone. (b) Substitution design. Ad libitum design. Matched protein, micronutrients, and fiber content. Mismatched energy density may cause excess calorie intake in the HFD group compared to low-fat diet (LFD) group. Pair-fed. Matched protein, micronutrients, and fiber content. Mismatched energy density may cause excess calorie intake in the HFD group compared to LFD group; pair feeding can equalize for differences in energy intake. However, pair feeding may introduce differences in feeding times, lengths of feeding windows, or volumetric differences with physiological import. Energy density matched. Matched protein, micronutrients, and energy density. However, mismatches in fiber content may have independent physiological import. (c) Multiple substitution design. An extension of the substitution design, a multiple substitution design creates relative rankings of all nutrients of interest with respect to an outcome or outcomes of interest.