Unlike with most food additives, the safety evaluation of macronutrients poses a challenge to risk assessors because of their inherent nutritional value and relatively large dietary exposure. A safety assessment model of macronutrients based solely on traditional toxicological studies faces limitations, whereas nutritional studies of macronutrients are often designed to provide information to support dietary recommendations for optimal health.
Although both nutritional and toxicological research shares a common goal of improving public health, the manner in which the studies are used differ because of limitations in their design and conduct. Many nutritional studies enjoy the benefit of using human subjects that can reflect real-world exposure scenarios, but consequently these studies are beset with unknown confounding variables that make drawing causative conclusions difficult. Toxicological studies must be conducted with laboratory animals, but they are concomitantly more easily controlled, permitting better causation determinations. What is needed to improve the safety determination of macronutrients is a hybrid model that encompasses both types of studies integrated toward a shared problem definition.