Abstract

Macronutrient substitutes, reduced-calorie substances used to replace organoleptic and/or functional properties of fats and sugars in the diet, may become a significant part of the diet as the trend toward lower fat and lower calorie diets continues. Procedures currently used to evaluate the safety of traditional food additives (microadditives) may be inadequate to properly assess the safety of macronutrient substitutes (macroadditives) because of the unique nature of these substances and the potentially large intakes. An evaluation procedure is proposed that recognizes the benefits to be derived from the test material, uses a structured approach to obtain animal and human nutritional and toxicological (including kinetic and dispositional) data that are critically evaluated and that provide a basis for further testing, encourages consultation with the regulatory agency (FDA), and recommends postmarketing surveillance of the macronutrient substitute. The proposed scheme differs from the traditional approach in many respects, such as using dispositional and kinetic data, assessing nutritional status, using human data collected under carefully controlled conditions early in the process, and consulting with the FDA. A case-by-case approach is recommended for safety evaluation of these macroadditives.