TABLE 1.

 Recommendations for research and reporting on LES¹

• Research hypotheses should be explicit a priori, and the underlying research question(s) reflected in the choice of exposures, comparators and analyses.

• The justification and interpretation of primary research studies and their representation in reviews should reflect the stated hypotheses, with particular regard to caloric vs. noncaloric comparators, and potential for extrapolation to LES in general vs. specific LES.

• Where outcomes are not attributable to energy reduction or perceived sweetness, interpretation relies on the chemical and ADME properties of specific LES.

• The selection and citation of existing research should fairly represent the balance and weight of different types of evidence, particularly where there are data from RCTs with relevant exposures and populations.

• Animal research and other studies generating evidence related to safety and toxicology should specifically refer to that literature.

• Reporting of evidence on health associations with LES from observational studies, including prospective cohort studies, should be clear that these are subject to residual confounding, including reverse causality, and may have been designed to answer a different research question.

• Hypotheses generated by observational and animal data must be interpreted in relation to the specific exposures, plausible causal pathways, and results of any related human intervention trials.

¹ADME, absorption, distribution, metabolism, and excretion; LES, low-energy sweetener(s); RCT, randomized controlled (intervention) trial.