High-quality research resolves inconsistencies between study types reporting on health effects of sweeteners

Science news from the 41st International Symposium on Diabetes and Nutrition, the 31st European Congress on Obesity, and the ISA-FINUT webinar



  • Data analysis of observational studies using advanced methodologies to reduce bias rejects the notion that sweeteners’ intake is associated with weight gain
  • Prospective cohort studies with substitution analysis report a reduced obesity and cardiometabolic disease risk when low/no calorie sweetened beverages are used to substitute sugar sweetened drinks in the diet
  • New findings from observational studies with advanced methodologies are consistent with evidence from clinical trials which confirm no harm, and a modest benefit of low/no calorie sweeteners’ use in weight loss management in people living with overweight and obesity, at risk of type 2 diabetes


The benefits of using low/no calorie sweeteners (LNCS) to replace sugars in the diet are often questioned in the literature due to conflicting results reported in different study types. Clinical trials consistently show a modest but significant benefit of LNCS use in glucose and weight control and no evidence of harm, while observational studies sometimes report a positive association between sweeteners’ intake and increased risk of obesity or cardiometabolic diseases. In 2023, the World Health Organization (WHO) called for better research to resolve this issue and scientists are responding with new high-quality studies that provide new evidence to help resolve inconsistencies.

This article discusses new findings presented at recent scientific events including the 41st International Symposium on Diabetes and Nutrition, the 31st European Congress on Obesity, and the ISA-FINUT webinar.

Prospective cohort studies using more robust intake assessment methods show protective associations, in line with results from clinical trials

Observational studies are prone to bias due to residual confounding, reverse causality, and self-reported dietary intakes.1 However, advances in analytical methodologies may reduce bias, mitigate some of the limitations of the observational study design, and provide more robust associations.2

Most observational studies exploring LNCS health effects use traditional self-reported dietary data, assessed usually at a single point of time only at baseline, which may inaccurately estimate LCNS consumption and does not capture changes in intake over time. New methods including the use of LNCS biomarkers to allow more accurate exposure estimates, as well as repeated assessments to measure change in dietary intakes, and substitution analysis modelling LNCS as a replacement for caloric sugars, may reduce bias in observational research.1,2

A study that was part of the EU-funded project SWEET compared two traditional, self-reported dietary intake assessment methods with intakes estimated with a newly developed urinary biomarker approach and showed that self-reports of LNCS intakes introduce bias. The results highlighted an important underestimation of the number of LNCS consumers using self-reports compared to the more accurate biomarker approach.3 As a more objective method of intake, LNCS biomarkers may help to further clarify the association between LNCS and health in future observational research. Preliminary results presented at two congresses showed no association between LNCS intake, as assessed by biomarkers in the SWEET project, with changes in body weight over 2 years.

Similarly, no adverse association between LNCS intake and obesity or cardiometabolic diseases is reported in prospective cohort studies with change analysis of sequential assessments and substitution analysis modelling LNCS as a replacement for sugar-sweetened beverages, adjusted for baseline adiposity.4 A systematic review of 14 prospective cohorts using these advanced methodologies showed that an increase in LNCS intake was associated with lower weight and waist circumference.4 In addition, the substitution of LNCS beverages for sugar-sweetened beverages was associated with lower weight and lower risk of obesity, coronary heart disease and cardiovascular mortality, without any adverse effect on any other cardiometabolic outcomes, including type 2 diabetes.2 In line with this finding, a substitution analysis of US data from three large prospective cohort studies that was presented at the ISA-FINUT webinar showed that replacing sugar-sweetened beverages with LNCS beverages was associated with lower odds of weight gain.

Findings from observational studies with advanced methodologies are consistent with trial evidence

The importance of these new findings from observational studies using advanced methodologies is that they help clarify inconsistencies in the literature regarding the LNCS health effects. These observational results agree with evidence from randomised controlled trials (RCT), a study design that allows causal inference.2 As assessed in systematic reviews, clinical trials consistently show that LNCS can assist in weight control when used in place of sugars.5,6 New studies presented at the recent congresses also show a modest additional benefit in longer-term weight loss management, which may be linked to greater diet satisfaction as low/no calorie sweeteners provide the enjoyment of sweet taste without the calories of sugar.7

Clinical practice guidelines based on the best available evidence

The importance of developing evidence-based dietary guidelines was highlighted at the 41st International Symposium on Diabetes and Nutrition which marked one year after the publication of the updated European recommendations for the dietary management of diabetes by the Diabetes and Nutrition Study Group of the European Association for Study of Diabetes.8 Upon conducting a series of systematic reviews of the available literature, the group concluded to a set of evidence-based nutrition recommendations including about the intake of sugars and sweeteners. Based on the best available evidence from RCTs and observational studies with advanced methodologies to reduce bias, the use of LNCS to replace sugars in beverages and foods was recommended as a risk reduction strategy.8

  1. Ashwell M, Gibson S, Bellisle F, et al. Expert consensus on low-calorie sweeteners: facts, research gaps and suggested actions. Nutr Res Rev. 2020 Jun;33(1):145-154
  2. Khan TA, Lee JJ, Ayoub-Charette S, et al. WHO guideline on the use of non-sugar sweeteners: a need for reconsideration. Eur J Clin Nutr. 2023 Nov;77(11):1009-1013
  3. Buso ME, Boshuizen HC, Naomi ND, et al. Relative validity of habitual sugar and low/no-calorie sweetener consumption assessed by food frequency questionnaire, multiple 24-h dietary recalls and urinary biomarkers: an observational study within the SWEET project. Am J Clin Nutr. 2024 Feb;119(2):546-559
  4. Lee JJ, Khan TA, McGlynn N, et al. Relation of Change or Substitution of Low- and No-Calorie Sweetened Beverages With Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies. Diabetes Care. 2022 Aug 1;45(8):1917-1930
  5. Laviada-Molina H, Molina-Segui F, Pérez-Gaxiola G, et al. Effects of nonnutritive sweeteners on body weight and BMI in diverse clinical contexts: Systematic review and meta-analysis. Obes Rev. 2020 Jul;21(7):e13020
  6. Rogers PJ, Appleton KM. The effects of low-calorie sweeteners on energy intake and body weight: a systematic review and meta-analyses of sustained intervention studies. Int J Obes (Lond). 2021 Mar;45(3):464-478
  7. Harrold JA, Hill S, Radu C, et al. Non-nutritive sweetened beverages versus water after a 52-week weight management programme: a randomised controlled trial. Int J Obes (Lond). 2024 Jan;48(1):83-93
  8. Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD). Evidence-based European recommendations for the dietary management of diabetes. Diabetologia. 2023 Jun;66(6):965-985