Long-term food consumption and body weight changes in neotame safety studies are consistent with the allometric relationship observed for other sweeteners and during dietary restrictions

In long-term safety studies with neotame, a new high-intensity sweetener 7000–13,000 times sweeter than sucrose, the percent changes (%Δ) in body weight gain (BWG) in Sprague–Dawley rats were several-fold greater than the %Δ in overall food consumption (FC). This study investigates the question of whether the changes in BWG were adverse or secondary to small, long-term decrements in FC. The hypothesis tested in Sprague–Dawley rats was that the relationship between long-term %Δ in FC and %Δ in BWG is linear and in a ratio of 1:1. The %Δ in FC were compared to %Δ in BWG after 52 weeks on study in one saccharin (825 rats), two sucralose (480 rats), two neotame (630 rats), and five dietary restriction (>1000 rats) studies. Non-transformed plotting of data points demonstrated an absence of linearity between %Δ in FC and %Δ in BWG; however, log–log evaluation demonstrated a robust (R2=0.97) linear relationship between %Δ in FC and %Δ in BWG. This relationship followed the well-known allometric equation, y=bxa where x is %ΔFC, y is %ΔBWG, b is %ΔBWG when ΔFC=1, and a is the log–log slope. Thus, in Sprague–Dawley rats at week 52, the long-term relationship between %Δ in FC and %Δ in BWG was determined to be: %ΔBWG=3.45(%ΔFC0.74) for males and %ΔBWG=5.28(%ΔFC0.68) for females. Sexes were statistically different but study types, i.e., the high-intensity sweeteners saccharin and sucralose versus dietary restriction, were not. The %Δ in BWG are allometrically consistent with the observed %Δ in FC for these high-intensity sweeteners, including neotame. BW parameters are not appropriate endpoints for setting no-observed-effect levels (NOELs) when materials with intense taste are admixed into food. An approach using objective criteria is proposed to delineate BW changes due to toxicity from those secondary to reduced FC.