Low- and no-calorie sweeteners and health: unravelling the evidence and controversy.

Low- and no-calorie sweeteners (LNCS) (also referred to as non-nutritive sweeteners) have been the subject of controversy, especially considering recent conditional recommendations by the World Health Organization (WHO) not to use LNCS as a means of controlling weight and disease risk reduction. We summarize the data presented and discussions held between a panel of international nutrition research experts at a high-level Canadian Nutrition Society Thematic conference on "Non-nutritive sweeteners and health: unravelling the evidence and controversy", which took place in Toronto, Canada on 27 January 2024. This paper summarizes the proceedings, including discussions on global sugar reduction policies, the toxicological safety and public perceptions of LNCS, divergence between public health and clinical practice guidance, and potential biological mechanisms underlying their effects. Randomized controlled trials show benefits of LNCS when substituting for sugars, while long-term cohort data have methodological limitations such as reverse causation and residual confounding. Mechanistic evidence does not support major adverse effects on energy intake regulation, glycemia, or gut microbiota. Together, these findings highlight the need for harmonized global policies, rigorous study designs that model real-world substitutions, and improved communication strategies to address misinformation.