Science news on low/no calorie sweeteners: 2022 year in review


  • Benefits of low/no calorie sweeteners in reducing sugars and calorie intakes and assisting with weight loss are confirmed in 2022 systematic reviews and meta-analyses of randomised controlled trials (RCTs)
  • Low/no calorie sweetened beverages may be associated with cardiometabolic benefit when used to replace sugar-sweetened beverages
  • New studies confirm that low/no calorie sweeteners’ intake is safe and well below their respective Acceptable Daily Intakes (ADIs)


From a low/no calorie sweeteners’ science perspective, 2022 has been marked by the publication of important systematic reviews of the current literature. The present year-in-review article provides a summary of key studies published in 2022, as well as science news from ISA-supported scientific events.

WHO-supported review on health effects of low/no calorie sweeteners: RCTs confirm benefits despite observational studies indicating potential adverse associations

A systematic review and meta-analysis of RCTs and observational studies was published in April 2022 by the World Health Organization (WHO).1 Evidence of low to moderate certainty as assessed from RCTs confirmed that low/no calorie sweeteners may assist with modest weight loss by reducing energy (calories) and sugar intakes, with no adverse effect on cardiometabolic health. Contrary to these results, meta-analyses of observational studies yielding very low to low certainty evidence reported positive associations between low/no calorie sweeteners and increased risk of obesity, diabetes or cardiovascular disease. However, by nature, observational studies cannot prove a causal relationship and provide evidence of lower quality. Inaccuracies resulting from the self-reported intake assessment methods and issues with residual confounding and, importantly, reverse causality raise concerns regarding the reliability and interpretation of associations from observational studies, especially when higher quality clinical controlled trials report opposite findings.

Mitigating the influence of reverse causality in observational research to establish reliable associations between low/no calorie sweeteners and cardiometabolic risk

In 2022, the Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD) published two systematic reviews and meta-analyses of RCTs2 and prospective cohort studies3, respectively. This work aims to inform the EASD clinical practice guidelines for nutrition therapy in diabetes, which is currently under review.

With the aim to mitigate the influence of reverse causation and to provide more robust associations, the DNSG systematic review and meta-analysis of prospective cohort studies restricted the analyses to cohort comparisons that model sweetener intake as change over time or substitutions of sugar-sweetened beverages (SSB) with low/no calorie sweetened beverages.3 Compared with the WHO review1 that did not adequetly address the issue of reverse causation in observational studies, the current review reported different results: the intended substitution of SSB with low/no calorie sweetened beverages was associated with lower weight and reduced risk of obesity, coronary heart disease, total cardiovascular disease (CVD) mortality, and total mortality, without an adverse association with any other cardiometabolic outcome.3

The results of the DNSG systematic review of observational prospective cohort studies with change and substitution analyses are in line with RCT evidence, including from a systematic review and meta-analysis of RCTs published earlier this year by the DNSG experts.2 Low/no calorie sweetened beverages were associated with reduced body weight, body mass index, percentage of body fat, and intrahepatocellular lipid in adults with overweight or obesity who are at risk for or have diabetes, when compared with sugar-sweetened beverages. Their benefits were similar to those of water, the standard-of-care substitution, making low/no calorie sweetened beverages a helpful alternative replacement strategy for sugary drinks.2

New nationally representative US study finds no association between low/no calorie sweeteners and risk of cancer

A new study that analysed data for the years 1988-2018 from the nationally representative US National Health and Nutrition Examination Survey (NHANES) found no association between higher low/no calorie sweeteners’ intake and overall risk of cancer.4 In addition, consumers of low/no calorie sweeteners had higher-quality diets including lower intakes of sugars and calories, and were less likely to be smoking, indicating an overall healthier lifestyle compared to non-consumers. The researchers stress that the present results stand in contrast to a recent report by Debras et al5 based on the French Nutrinet Santé volunteer cohort, a large but non-representative and predominantly female sample of convenience.

ISA webinar hosted by INAN: Intake of low/no calorie sweeteners is well below the Acceptable Daily Intakes

At a webinar about the “Safety of low/no calorie sweeteners and their role in weight control and diabetes”, organised by the ISA and hosted the National Food and Nutrition Institute (INAN) of Paraguay, invited experts talked about the safety and intake levels of low/no calorie sweeteners.

Independent food safety agencies worldwide examine and assess the best available scientific evidence and, on that basis, confirm the safety of low/no calorie sweeteners. During the safety assessment and approval process by the food safety agencies and regulatory authorities, an Acceptable Daily Intake (ADI) is set for each individual sweetener. The ADI is the amount of a food additive (e.g. a sweetener) that can be safely consumed on a daily basis during a person’s entire lifetime without any appreciable health risk and takes into account all population groups, including more vulnerable ones, such as children and pregnant women. Several recent studies in Latin America have confirmed that the intake of low/no calorie sweeteners is well below their respective ADIs. At the current webinar, the results of a recent study that was conducted by the Chilean Food Safety and Quality Agency (ACHIPIA) was presented, confirming that none of the low/no calorie sweeteners exceeded its respective ADI in any of the age groups (including children).6

You may watch on demand the ISA webinar on “Safety of low/no calorie sweeteners and their role in weight control and diabetes”, by clicking here.

ISA-supported webinars in the context of World Diabetes Day: Low/no calorie sweeteners in diabetes management

In November, in the context of World Diabetes Day 2022 themed “Education to protect tomorrow”, the International Sweeteners Association (ISA) supported two educational online events for healthcare professionals in Europe and Latin America.

A workshop organised by the Mexican Diabetes Federation (Federación Mexicana de Diabetes – FMD) and a webinar organised by the European Federation of Associations of Dietitians (EFAD) and its Specialist Network (European Specialist Dietetic Network – ESDN) on Obesity, featured latest evidence on low/no calorie sweeteners as well as dietary guidelines for obesity and diabetes management.

The speakers of the FMD workshop, Dr Rebeca López-García, consultant toxicologist, and Dr Hugo Laviada-Molina, MD, Universidad Marista de Mérida, Mexico, concluded that the rigorous safety assessment process by independent international food safety agencies reassures that all approved low/no calorie sweeteners are safe, and further pointed to higher-quality evidence from human clinical trials which indicate that they can be a helpful tool in reducing sugars intake for people living with obesity and/or diabetes.

With regard to clinical practice guidelines for the nutritional management of diabetes, these generally support the use of low/no calorie sweeteners as a way to help reduce sugars intake, as also presented at the EFAD webinar. For example, the American Diabetes Association (ADA)7, Diabetes Canada8, Diabetes UK9, and the Latin-American Association of Diabetes (Asociación Latinoamericana de Diabetes – ALAD)10 recognise that replacing added sugars with low/no calorie sweeteners could decrease daily intake of carbohydrates and calories, which in turn could beneficially affect glycaemic, weight, and cardiometabolic control.

You may watch on demand the EFAD webinar on “Latest dietary guidelines for obesity and diabetes management”, by clicking here.


We hope you enjoyed reading the 2022 year-in-review article. The International Sweeteners Association (ISA) is committed to bringing you the latest scientific news around low/no calorie sweeteners and will continue to do so in 2023.

We wish you a happy and healthy New Year!

  1. World Health Organization, Rios-Leyvraz Magali & Montez Jason‎. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. World Health Organization 2022. License: CC BY-NC-SA 3.0 IGO
  2. McGlynn ND, Khan TA, Wang L, …, Sievenpiper JL. Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022 Mar 1;5(3):e222092.
  3. Lee JJ, Khan TA, McGlynn N, …, Sievenpiper JL. 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.
  4. Fulgoni VL, Drewnowski No Association between Low-Calorie Sweetener (LCS) Use and Overall Cancer Risk in the Nationally Representative Database in the US: Analyses of NHANES 1988–2018 Data and 2019 Public-Use Linked Mortality Files. Nutrients 2022;14(23):4957
  5. Debras C, Chazelas E, Srour B, …, Touvier M. Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. PLoS Med. 2022 Mar 24;19(3):e1003950
  6. Agencia Chilena para la Inocuidad y Calidad Alimantaria – ACHIPIA (Chilean Food Safety and Quality Agency). Chronic dietary exposure assessment on sweeteners in food consumed by the Chilean population. ACHIPIA 2021. Available at:
  7. Evert AB, Dennison M, Gardner CD, Garvey WT, Lau KHK, MacLeod J, Mitri J, Pereira RF, Rawlings K, Robinson S, Saslow L, Uelmen A, Urbanski PB, Yancy Jr. WS. Nutrition Therapy for Adults with Diabetes or Prediabetes: A Consensus Report. Diabetes Care. 2019 May;42(5):731-754
  8. Sievenpiper JL, Chan C, Dworatzek PD, et al. Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Nutrition Therapy. Can J Diabetes. 2018;42(Suppl 1):S1-S325.
  9. Diabetes UK. The use of low or no calorie sweeteners. Position Statement (Updated December 2018). Available at:
  10. Laviada-Molina H, Escobar-Duque ID, Pereyra E, Romo-Romo A, Brito-Córdova G, Carrasco-Piña E, González-Suárez R, López-García R, Molina-Seguí F, Mesa-Pérez JA. Consenso de la Asociación Latinoamericana de Diabetes sobre uso de edulcorantes no calóricos en personas con diabetes [Consensus of the Latin-American Association of Diabetes on low calorie sweeteners in persons with diabetes]. Rev ALAD. 2018;8:152-74