ISA scientific response to the World Health Organization (WHO) guideline on use of non-sugar sweeteners

The WHO guideline on use of non-sugar sweeteners risks hindering global efforts to stem the rise of non-communicable diseases (NCDs)

 

Highlights

  • Scientifically rigorous studies have repeatedly demonstrated the benefits of low/no calorie sweeteners in calorie reduction and weight control, dental health and diabetes management
  • The WHO guideline lacks scientific rigour as it is not based on a robust evidence base or supported by the evidence presented in a systematic review commissioned by WHO itself
  • There is an important misalignment between the WHO guideline and the objectives and approach of the global NCD agenda, which stresses the importance of reformulation
  • The conditional WHO recommendation on non-sugar sweeteners’ use risks hampering public health efforts to reduce excess sugars intake
  • ISA shares concerns with UK and Australian government agencies on WHO’s methodology in this review to support its recommendation

 

In May 2023, the World Health Organization (WHO) published a guideline on the use of non-sugar sweeteners, also known as low/no calorie sweeteners, with a conditional recommendation suggesting that non-sugar sweeteners not be used as a means of achieving weight control or reducing the risk of non-communicable diseases [NCDs]”.1

The WHO recommendation is not scientifically rigorous. It is not based on a strong evidence base or supported by the evidence presented in the WHO systematic review2 that was commissioned with the aim to inform the guideline. It is only a conditional, or else weak, recommendation for which WHO is uncertain about the desirable or undesirable effects of its implementation, for example if the guideline risks leading to increased sugars intake and associated health outcomes.

The ISA’s concerns over the limitations of WHO’s approach to the guideline are shared by government agencies who have responded to the public consultation on the draft guideline3, including the UK Office for Health Improvement and Disparities and the Australian Government Department of Health and Aged Care.

Importantly, the WHO recommendation is inconsistent with the commitment of United Nations (UN) Member States to a coherent, inclusive, multi-stakeholder global effort to stem the rise of NCDs, of which sugar reduction reformulation of foods and drinks is an integral part.4,5,6

The conditional WHO recommendation lacks scientific rigour

The WHO guideline on use of non-sugar sweeteners is exclusively based on a WHO-commissioned systematic review of randomised controlled trials (RCTs) and observational studies that assessed the health effects of sweetener use in adults, children, and pregnant women.2 The benefits of low/no calorie sweeteners in reducing sugars and calorie intake and assisting with short-term weight loss are clearly demonstrated in the results of RCTs analysed in the WHO review, while observational studies report conflicting outcomes. Other systematic reviews and meta-analyses of both acute (which were not considered in the WHO guideline) and long-term RCTs also confirm a beneficial role of low/no calorie sweeteners in energy intake reduction and weight management 7,8,9, glucose control 10,11,12 and dental health.13

Nevertheless, the conditional WHO recommendation was largely and disproportionally based on very low to low certainty evidence from observational studies. Due to their nature, observational studies do not provide evidence of causal relationships and are at high risk of reverse causality.14 In contrast, higher-quality research of randomised controlled design, considered the gold standard in clinical and nutrition research, was not given the weight it deserves in the WHO guideline.

In comments submitted to the online public consultation in response to the draft guideline, governmental agencies, non-governmental organisations, industry associations, as well as academics and researchers criticised the WHO decision to base a recommendation for non-sugar sweeteners on such a poor, low-quality evidence base.3 For example, the UK’s Office for Health Improvement and Disparities commented that “the recommendation may be too strong given the limitations of the evidence base including possible concerns regarding study design and reverse causality”. In the interest of public health, recommendations should be based on the comprehensive set of available evidence and interpreted considering the hierarchy and weight of scientific evidence.

Concerns about probable undesirable effects of the WHO guideline were also raised by government agencies in the context of the public consultation.3 The Australian government’s Department of Health and Aged Care cautioned that the recommendation may result in undesirable health outcomes for some individuals resulting in increased sugars intake and associated adverse health outcomes. Indeed, a conditional (weak) recommendation that is based on overall low certainty in the evidence, for which the WHO “is uncertain that the desirable consequences of implementing the recommendation outweigh the undesirable consequencesrisks hindering public health efforts to reduce excess free sugars intake, a strong recommendation by WHO15, and hence, actions to address oral health diseases and the epidemic of obesity and associated NCDs.

In addition, a disproportionate effect may be seen in people living with diabetes for whom low/no calorie sweeteners are an important dietary tool. While it is stated that the conditional recommendation may not be relevant to people with diabetes, a potential negative impact on this population group cannot be ruled out. By potentially discouraging reformulation, the WHO guideline may negatively impact the availability of food and drink choices that can be safely used by people living with diabetes, inadvertently hindering individual efforts to limit the intake of sugars and negatively impacting quality of life.

The safety of low/no calorie sweeteners is confirmed by food safety bodies worldwide

The WHO guideline on use of non-sugar sweeteners did not, and was not aimed to, assess the safety of these food ingredients. The safety assessment of low/no calorie sweeteners is the responsibility of food safety bodies such as the European Food Safety Authority (EFSA), the US Food and Drug Administration (FDA) or the Joint Expert Committee on Food Additives (JECFA) of the Food and Agriculture Organization (FAO) and the World Health Organization (WHO). Global and regional food safety regulatory bodies worldwide consistently support that approved low/no calorie sweeteners are safe for consumption.16

While it is acknowledged by WHO that the safety assessment of sweeteners is the responsibility of food safety agencies like JECFA, and involves the thorough examination of a much larger data set of the available scientific literature, the WHO guideline on use of non-sugar sweeteners may still raise groundless doubts over sweeteners’ safety by stating that there is no clear consensus on “whether NSS are linked to other long-term health effects at habitual intakes within the ADI”. This is not only inconsistent with the safety assessment of all approved low/no calorie sweeteners by the responsible regulatory bodies at global and national level, but also outside of the scope of this guideline. Importantly, there is no mechanistic or clinical evidence to support “possible long-term adverse effects” in the form of increased risk of NCDs.17,9 The WHO systematic review that informed this guideline also confirms that RCTs show no impact of low/no calorie sweeteners’ use on intermediate markers of NCDs, including blood glucose and insulin levels, blood pressure or blood lipids, and body weight.2

This lack of alignment between different WHO bodies and their respective responsibilities has been pointed out as concerning in comments submitted to the public consultation on the draft WHO guideline, including by governmental agencies.3 Such inconsistency has the potential to lead to considerable confusion among public health professionals and policy-makers, and groundless concerns among the users of low/no calorie sweeteners.

The conditional WHO recommendation is inconsistent with the global approach to addressing NCDs

Rising rates of NCDs is a shared global challenge, affecting lives and economies worldwide. At the United Nations General Assembly meeting in 20114, UN Member States committed to responding to this challenge with a political declaration which recognised that effective NCDs prevention and control requires a whole-of-society effort, working with all sectors, including industry. This multi-stakeholder engagement was re-confirmed at subsequent UN High-level Meetings on NCDs in 20145 and 2018.6

Industry was called upon to contribute to reducing NCDs risk factors and creating health-promoting environments by reformulating products to provide healthier options. Following WHO’s strong recommendation to limit free sugars intake15, various actions are being taken to reduce consumption of free sugars. For example, the use of low/no calorie sweeteners has enabled manufacturers to develop foods and drinks with less sugar and less calories, while keeping the taste consumers know and expect. To advance the efforts to tackle the complex challenge of NCDs by sustaining and scaling up reformulation, industry relies on consumer confidence in low/no calorie sweeteners as approved food ingredients which provide the consumer with wider choice.

Taken together, the conditional WHO recommendation that “NSS not be used as a means of achieving weight control or reducing the risk of noncommunicable diseases” lacks scientific rigour and is inconsistent with the global integrated approach to addressing NCDs to which UN Member States have committed, and of which sugar reduction reformulation of foods and drinks is an integral part. Such misalignment may be detrimental to global efforts to address the complex challenge of NCDs.

  1. World Health Organization (WHO). Use of non-sugar sweeteners: WHO guideline. Geneva: World Health Organization; 2023. Licence: CC BY-NC-SA 3.0 IGO. Available at: https://www.who.int/publications/i/item/9789240073616
  2. Rios-Leyvraz Mand Montez J (World Health Organization)‎. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. World Health Organization (WHO) 2022. https://apps.who.int/iris/handle/10665/353064. License: CC BY-NC-SA 3.0 IGO
  3. Comments and responses on WHO draft guideline. Available at: https://www.who.int/news-room/articles-detail/online-public-consultation-draft-guideline-on-use-of-non-sugar-sweeteners [Comments were received from 3 Government agencies (Australian Government Department of Health and Aged Care; Office for Health Improvement and Disparities, UK; Standards Organization of Nigeria), 12 nongovernmental and consumer organizations/ associations, 22 industry organisations/ associations, and 7 academic/ research individuals]
  4. UN High-level Meeting on NCDs, September 2011. https://digitallibrary.un.org/record/710899?ln=en
  5. UN High-level Meeting on the comprehensive review and assessment of the progress achieved in the prevention and control of NCDs, July 2014 https://digitallibrary.un.org/record/774662
  6. UN High-level Meeting on NCDs, September 2018 https://www.un.org/pga/73/event/prevention-of-non-communicable-diseases/
  7. Laviada-Molina H, Molina-Segui F, Pérez-Gaxiola G, Cuello-García C, Arjona-Villicaña R, Espinosa-Marrón A, Martinez-Portilla RJ. Effects of nonnutritive sweeteners on body weight and BMI in diverse clinical contexts: Systematic review and meta-analysis. Obes Rev. 2020;21(7):e13020.
  8. 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;45(3):464-478
  9. McGlynn ND, Khan TA, Wang L, Zhang R, Chiavaroli L, Au-Yeung F, Lee JJ, Noronha JC, Comelli EM, Blanco Mejia S, Ahmed A, Malik VS, Hill JO, Leiter LA, Agarwal A, Jeppesen PB, Rahelic D, Kahleová H, Salas-Salvadó J, Kendall CWC, 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 Network Open. 2022;5(3):e222092
  10. Nichol AD, Holle MJ, An R. Glycemic impact of non-nutritive sweeteners: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2018 Jun;72(6):796-804
  11. Greyling A, Appleton KM, Raben A, Mela DJ. Acute glycemic and insulinemic effects of low-energy sweeteners: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2020;112(4):1002-1014
  12. Zhang R, Noronha JC, Khan TA, McGlynn N, Back S, Grant SM, Kendall CWC, Sievenpiper JL. The Effect of Non-Nutritive Sweetened Beverages on Postprandial Glycemic and Endocrine Responses: A Systematic Review and Network Meta-Analysis. Nutrients. 2023;15(4):1050.
  13. EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to intense sweeteners and contribution to the maintenance or achievement of a normal body weight (ID 1136, 1444, 4299), reduction of post-prandial glycaemic responses (ID 4298), maintenance of normal blood glucose concentrations (ID 1221, 4298), and maintenance of tooth mineralisation by decreasing tooth demineralisation (ID 1134, 1167, 1283) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal 2011;9(6):2229. [26 pp.]. Available online: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2011.2229/epdf
  14. Lee JJ, Khan TA, McGlynn N, Malik VS, Hill JO, Leiter LA, Jeppesen PB, Rahelić D, Kahleová H, Salas-Salvadó J, Kendall CWC, 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
  15. World Health Organization (WHO). Guideline: Sugars intake for adults and children. Geneva: World Health Organization; 2015. https://www.who.int/publications/i/item/9789241549028
  16. Ashwell M, Gibson S, Bellisle F, Buttriss J, Drewnowski A, Fantino M, Gallagher AM, de Graaf K, Goscinny S, Hardman CA, Laviada-Molina H, López-García R, Magnuson B, Mellor D, Rogers P, Rowland I, Russell W, Sievenpiper J, la Vecchia C. Expert consensus on low calorie sweeteners: facts, research gaps and suggested actions. Nutr Res Rev. 2020 Jun;33(1):145-154
  17. Magnuson BA, Carakostas MC, Moore NH, Poulos SP, Renwick AG. Biological fate of low-calorie sweeteners. Nutr Rev. 2016 Nov;74(11):670-689