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Year in review: Low/no calorie sweeteners’ science in 2024

Looking back at new research on low/no calorie sweeteners and scientific milestones of 2024

 

Highlights:

  • The beneficial role of low/no calorie sweetened beverages in weight control of children and adults has been clarified in new research
  • A comprehensive review of the literature rejected the widespread assumption that exposure to sweet taste drives a “sweet tooth”
  • The European Food Safety Authority (EFSA) re-confirmed that saccharin is safe and increased its Acceptable Daily Intake (ADI) from 5 to 9 mg/kg body weight/day

New research published in 2024 explored the benefits and health effects of low/no calorie sweeteners to help provide higher quality evidence on their impact on weight control and the risk of non-communicable diseases (NCDs). The present article provides a summary of selected key scientific studies published this year and news from scientific events.

Relying on clinical trials for determining causal relationships between low/no calorie sweeteners and health outcomes

There is a well described discrepancy in the scientific literature when it comes to low/no calorie sweeteners’ effects on body weight and risk of NCDs, resulting from different study designs and methodologies. An umbrella review by Higgins and colleagues described a consistent pattern where systematic reviews and meta-analyses of randomised controlled trials (RCTs) show a benefit in weight control, especially when sweeteners are used to replace sugars, while weight effect estimates of meta-analyses of observational studies lead to a range of results, from significantly beneficial to significantly adverse1. New reviews published in 2024 are in line with these remarks.

A meta-analysis of both RCTs and prospective cohorts evaluated the impact of low/no calorie sweeteners on BMI changes in children and adolescents2. Results from RCTs showed less BMI gain in children and especially among adolescents who replaced sugar-sweetened with low/no calorie sweetened beverages. The effect was even greater for adolescents living with obesity and in longer-term studies. On the other hand, the meta-analysis of prospective cohorts found no association between low/no calorie sweeteners consumption and BMI changes.

Another systematic review and network meta-analysis of 78 RCTs including 4168 adult participants evaluated the comparative effects on body weight measures of different beverages (milk, fruit juices, sweetened beverages, and calorie-free beverages) and also compared these drinks with water3. Low/no calorie sweetened beverage consumption was the most effective beverage option for weight loss in adults when compared with sugary drinks, fruit juice as well as water.

Higgins and colleagues supported that more systematic reviews are not going to resolve the issue of conflicting results between RCTs and observational studies1. Instead of trying to statistically combine data to explain the complex relationship between sweeteners and body weight, the authors recommend to rely on the high-quality RCT study design to establish causal relationships that could help explain under which conditions sweeteners’ intake can assist with weight control.

Data presented at scientific congresses in 2024 confirm benefits of low/no calorie sweeteners in weight loss and maintenance in long-term trials

New evidence from the long-term Switch trial and the European Commission Horizon 2020 funded project SWEET, which examined the long term benefits and effects of sweeteners, was presented at the 31st European Congress on Obesity and the 41st International Symposium on Diabetes and Nutrition. The results indicate modest benefits of low/no calorie sweeteners in weight loss maintenance in trials lasting up to one year, with no impact on glucose control and cardiometabolic risk markers4,5.Observational data analysed within the SWEET project report mixed results on the association between sweeteners and risk of obesity and NCDs, with high risk of bias due to residual confounding and reverse causation. However, the SWEET study also identified a mismatch between the assessment of sweeteners intake with traditional, self-reported assessment methods such as food frequency questionnaires and exposure assessments with newly developed urinary biomarkers. This highlights an important underestimation of sweeteners’ exposure using self-reports in observational studies6. Causal relationships cannot be established by observational findings due to the limitations of this study design.

Low/no calorie sweeteners, sweet taste exposure and appetite control

It is logical to expect that nutrition recommendations are based on strong scientific evidence. However, this is not the case with the recommendation to reduce the exposure to sweet taste in our diet, irrespective of where it comes from (sugars or sweeteners). Researchers of a comprehensive literature review that was published in early 2024 note that there is no supporting evidence for the common hypothesis that exposure to sweetness from any dietary source drives a ‘sweet tooth’7. These conclusions are similar for research in adults and children, for low/no calorie sweeteners and sugars, and from both intervention and cohort studies.

Controversy also exists about the effects of low/no calorie sweeteners on appetite control and food intake. A systematic review with meta-analysis of RCTs exploring the impact of low/no calorie sweeteners on long-term total energy (calorie) and macronutrient intake showed reductions in total energy, carbohydrates and sugar intake when sweeteners were compared with sugars, and no effect whatsoever when compared with water8. These findings do not support an increase in food intake with sweeteners. Similarly, research does not support an adverse effect of low/no calorie sweeteners on appetite control.

SWEET project findings presented at the French Nutrition Days 2024 confirm no effect of low/no calorie sweetened foods on appetite control

New evidence from acute and medium-term clinical trials of the European Commission Horizon 2020 funded project SWEET was presented at the French Nutrition Days (JFN 2024). These studies explored the effects of acute and repeated exposure to sweetener blends in beverages, semi-solid and solid foods on appetite and endocrine responses9. Generally, beverages and foods with different blends of low/no calorie sweeteners had no adverse impact on appetite measures while on some occasions there were favourable effects on postprandial insulin and glucose reponse when compared with sugar-sweetened products10. It is likely though that the food matrix may play a role in the overall impact.

Re-evaluation of saccharin by EFSA: Safety re-confirmed with ADI increase

In its re-evaluation of saccharin and its salts, the European Food Safety Authority (EFSA) concluded that saccharin and its sodium, potassium and calcium salts are safe for human consumption and increased the acceptable daily intake (ADI) from 5mg/kg of body weight per day (expressed as sodium saccharin corresponding to 3.8 mg /kg bw per day saccharin as free imide) to 9 mg/kg bw/day expressed as saccharin free imide11. It was also confirmed that chronic exposure to saccharin was below the ADI, even for high consumers, as estimated by conservative exposure assessment scenarios.

The EFSA Panel on Food Additives and Flavourings evaluated data published from January 1994 to February 2024, meaning all the available studies published after the previous evaluation of saccharin in Europe in 1995, as well as data gathered in response to an EFSA call for information. EFSA experts followed structured protocols previously established by EFSA to assess the available dataset of animal and human studies investigating a range of endpoints beyond toxicological effects, including effects on body weight, glucose/ insulin homeostasis, cancer risk and cardiovascular risk factors.

The re-evaluation of saccharin was part of the food additives re-evaluation programme in the European Union (EU). At the request of the European Commission, EFSA has been re-evaluating the safety of all food additives, including sweeteners, which were already approved on the EU market before 20th January 2009. Aspartame was the first sweetener to have undergone this thorough re-evaluation process by EFSA reconfirming its safety12 (the global JECFA also reconfirmed aspartame’s safety in 2023). The safety assessment has also been completed, and safety reaffirmed, for thaumatin13, neohesperidine DC14 and erythritol15.

Intake of low/no calorie sweeteners is below the permitted levels worldwide

Toxicology and food science experts talked about the regulation and safety assessment procedures by global and European food safety authorities in scientific symposia organised by the ISA in the context of the Ibero-American Nutrition Foundation congress (FINUT 2024) and the French Nutrition Days (JFN 2024).

During the safety evaluation process, the authorities assess data on the absorption, distribution, metabolism and excretion (ADME) of a sweetener, short- and long-term toxicological studies, data on mutagenicity, carcinogenicity, reproduction, and all type of human clinical and epidemiological studies, and establish an Acceptable Daily Intake (ADI) that covers all population groups. Assessing the actual dietary exposure levels is also part of the evaluation. Data from around the world confirm that the consumption levels of low/no calorie sweeteners are well below the ADI even for high consumers. In Latin American countries such as Chile where food reformulation has been high in recent years following the implementation of Front-of-Pack labelling laws, data show a safe consumption, always below the ADI for all approved LNCS.

Nutritional recommendations should be based on the highest quality evidence available

The reliance on a WHO guideline for non-sugar sweeteners’ use16 on observational studies has been criticised this year in scientific publications and discussed in scientific events. Higgins et al supported that dietary guidance should be based on established causal relationships determined through the conduct of high-quality RCTs1.

In a webinar co-organised by the Ibero-American Nutrition Foundation (FINUT) and the ISA, it was highlighted that there is consistency between RCT evidence and findings of prospective cohort studies with advanced change and substitution analysis, supporting a useful role for low/no calorie sweeteners in weight management and a neutral or slightly beneficial effect on cardiometabolic risk factors when sweeteners are used in place of sugars17. You may watch on demand the ISA-FINUT webinar “Science update on low/no calorie sweeteners: from safety assessment to evidence-based recommendations and emerging research”, by clicking here.

We hope you enjoyed reading the year-in-review article for 2024. Next year, the ISA will continue to bring the latest scientific news on low/no calorie sweeteners to healthcare professionals, researchers, regulatory bodies, policymakers, the media and consumers.

We wish you a happy and healthy New Year!

  1. Higgins KA, Rawal R, Kramer M, Baer DJ, Yerke A, Klurfeld DM. An Overview of Reviews on the Association of Low Calorie Sweetener Consumption With Body Weight and Adiposity. Adv Nutr. Published online August 8, 2024. doi:10.1016/j.advnut.2024.100239.
  2. Espinosa A, Mendoza K, Laviada-Molina H, et al. Effects of Nonnutritive Sweeteners on the BMI of Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies. Adv Nutr. Published online September 13, 2024. doi:10.1016/j.advnut.2024.100292.
  3. Shahinfar H, Payandeh N, Zeraattalab-Motlagh S, et al. Comparative effects of different beverages on weight loss in adults: a systematic review and network meta-analysis of randomized trials. Int J Obes (Lond). Published online November 14, 2024. doi:10.1038/s41366-024-01673-6.
  4. 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;48(1):83-93. doi:10.1038/s41366-023-01393-3.
  5. Raben A, Kjølbaek L, Andersen SS, et al. Effect of sweeteners and sweetness enhancers on weight loss maintenance in adults and children with overweight or obesity – results from the SWEET multicentre, randomised, controlled, trial. in: Abstract book of the 31st European Congress on Obesity (ECO 2024). Obes Facts. 2024;17(Suppl. 1):7–515 (pp. 464). https://doi.org/10.1159/000538577.
  6. 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;119(2):546-559. doi:10.1016/j.ajcnut.2023.11.019.
  7. Mela DJ, Risso D. Does sweetness exposure drive ‘sweet tooth’?. Br J Nutr. 2024;131(11):1934-1944. doi:10.1017/S0007114524000485.
  8. Rostampour K, Moghtaderi F, Najafi A, Seyedjafari B, Salehi-Abargouei A. The effects of non-nutritive sweeteners on energy and macronutrients intake in adults: a grade-assessed systematic review and meta-analyses of randomized controlled trials. Front Nutr. 2024;11:1475962. Published 2024 Nov 13. doi:10.3389/fnut.2024.1475962.
  9. Gibbons C, O’Hara B, O’Connor D, et al. Acute and repeated impact of sweeteners and sweetness enhancers in solid and semi-solid foods on appetite: protocol for a multicentre, cross-over, RCT in people with overweight/obesity – the SWEET Project. BMJ Open. 2022;12(12):e063903. Published 2022 Dec 23. doi:10.1136/bmjopen-2022-063903.
  10. Gibbons C, Beaulieu K, Almiron-Roig E, et al. Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity-a randomised crossover trial from the SWEET consortium. EBioMedicine. 2024;102:105005. doi:10.1016/j.ebiom.2024.105005.
  11. EFSA Panel on Food Additives and Flavourings (FAF), Castle L, Andreassen M, et al. Re-evaluation of saccharin and its sodium, potassium and calcium salts (E 954) as food additives. EFSA J. 2024;22(11):e9044. Published 2024 Nov 15. doi:10.2903/j.efsa.2024.9044.
  12. EFSA. Scientific Opinion on the re-evaluation of aspartame (E 951) as a food additive. EFSA J. 2013;11:3496. https://doi.org/10.2903/j.efsa.2013.3496.
  13. EFSA Panel on Food Additives and Flavourings (FAF), Younes M, Aquilina G, et al. Re-evaluation of thaumatin (E 957) as food additive. EFSA J. 2021;19(11):e06884. Published 2021 Nov 30. doi:10.2903/j.efsa.2021.6884.
  14. EFSA Panel on Food Additives and Flavourings (FAF), Younes M, Aquilina G, et al. Re-evaluation of neohesperidine dihydrochalcone (E 959) as a food additive. EFSA J. 2022;20(11):e07595. Published 2022 Nov 17. doi:10.2903/j.efsa.2022.7595.
  15. EFSA Panel on Food Additives and Flavourings (FAF), Younes M, Aquilina G, et al. Re-evaluation of erythritol (E 968) as a food additive. EFSA J. 2023;21(12):e8430. Published 2023 Dec 20. doi:10.2903/j.efsa.2023.8430.
  16. World Health Organization (WHO). Use of non-sugar sweeteners: WHO guideline. Geneva: World Health Organization; 2023. Licence: CC BY-NC SA 3.0 IGO. https://www.who.int/publications/i/item/9789240073616.
  17. 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;77(11):1009-1013. doi:10.1038/s41430-023-01314-7.