Substitution analysis in nutritional epidemiology: proceed with caution
Substitution analysis has been increasingly used in nutritional epidemiologic research. It was originally used to compare the health effects of different macronutrients in an isocaloric setting [1]. This application is easy to understand, since calories are considered relatively constrained for an individual. In essence, substitution analysis provides a statistical technique to mimic feeding studies that aim to identify the optimal diet by altering macronutrient composition while holding total caloric intake constant [2]. Using this approach, for instance, it has been established that replacing saturated fats and trans fats with monounsaturated and polyunsaturated fats is more effective in preventing coronary heart disease than reducing overall fat intake by replacing it with the commonly consumed carbohydrate sources [3].
Beyond the health effects of macronutrient composition, an increasing number of studies have started using substitution analysis to compare the relative health...
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