A critical appraisal of the draft WHO guideline on use of non-sugar sweeteners
- Evidence from higher quality research reviewed recently by WHO supports the useful role of low/no calorie sweeteners in sugar and energy reduction and, in turn, in weight loss, despite a draft recommendation today suggesting against their use in weight control
- A large battery of controlled clinical trials confirming beneficial effects of low/no calorie sweeteners’ use in place of sugars on post-prandial glycaemia and dental health have not been considered in this draft guideline
- Today’s draft WHO recommendation may be confusing for people with diabetes for whom low/no calorie sweeteners are a useful dietary aid to manage their carbohydrate and sugar intake
On 15th July 2022, the World Health Organization (WHO) published its draft guideline on the use of non-sugar sweeteners1 aiming to provide guidance on their intake for the general population, especially regarding their impact on weight control and non-communicable diseases. As highlighted by WHO, the assessment of the safety of low/no calorie sweeteners, which has been repeatedly confirmed by food safety authorities around the world, including the Joint FAO/WHO Expert Committee on Food Additives (JECFA)2, was not within the scope of the WHO guideline. All approved low/no calorie sweeteners are safe within the established Acceptable Daily Intake (ADI) levels.
To develop this draft guideline, WHO considered evidence on the health effects of low/no calorie sweeteners that were reviewed in 2022 in a systematic way and meta-analysed by Rios-Leyvraz and Montez.3 However, the results of the WHO meta-analyses of randomised controlled trials (RCTs) do not support the draft recommendation suggesting that “non-sugar sweeteners not be used as a means of achieving weight control or reducing risk of non-communicable diseases (conditional recommendation)”. Also, important data from a large battery of clinical trials confirming beneficial short-term effects of low/no calorie sweeteners use in place of sugars on post-prandial glycaemia and dental health4 were not considered in formulating the recommendation.
Evidence supports the useful role of low/no calorie sweeteners in weight control
The helpful role of low/no calorie sweeteners in reducing energy (calorie) intake and in assisting with modest weight loss when used to replace sugars has been confirmed in numerous studies and systematic reviews,5-10 including the WHO study that informed the draft WHO guideline.3 In fact, in the WHO meta-analysis of RCTs, the gold standard in nutrition and clinical research, Rios-Leyvraz & Montez showed that low/no calorie sweeteners’ use results in reductions in sugars and calorie intakes and in modest but significant weight loss in adults.3 It is therefore surprising that the benefit of using low/no calorie sweeteners as a way to reduce excess sugars and calories intake, and in turn, to assist in weight management, is not acknowledged in the WHO recommendation suggesting against using non-sugar sweeteners for weight control.
Longer-term RCTs with a duration up to 2 years studying the impact of low/no calorie sweeteners on weight control are also supportive of their useful role in weight management.11,12,13 Importantly, observational data provide inconsistent and unreliable evidence about the association between low/no calorie sweeteners and obesity, as observational research in this field is prone to reverse causality, meaning that “a positive association between NNS [non-nutritive sweeteners] consumption and weight gain in observational studies may be the consequence of and not the reason for overweight and obesity.”, as also recognised in WHO-supported studies.14
Experts have expressed concern about the weight that should be placed on observational data exploring the association between low/no calorie sweeteners and obesity when data from sustained RCTs are available.15 By design, observational studies cannot establish a cause-and-effect relationship and provide evidence of low quality, as recognised in the WHO handbook for guideline development.16 It is well documented that prospective cohort studies are also at a high risk of residual confounding and reverse causality, as higher consumers of low/no calorie sweeteners may choose these products because they are at greater risk for adverse cardiometabolic outcomes and not the other way around.17 This is also recognised in the reviews supported by the WHO: results of observational studies on the health effects of low/no calorie sweeteners should be interpreted with caution, and attention should focus on plausible residual confounding as well as reverse causality.14,18
In contrast, a body of evidence based on RCTs is rated as being of higher quality and thus RCTs are the preferred source of evidence for measuring the effects of interventions related to measurable health outcomes such as body weight. Comprehensive systematic reviews and meta-analyses of RCTs are supportive of the beneficial role of low/no calorie sweeteners, as sugars substitutes in calorie and sugar reduction, and in turn, in weight loss.5-10 In fact, some studies have also found that this beneficial effect is greater in people with overweight or obesity, who need to manage their body weight.7,18 The benefit of replacing added sugars with low/no calorie sweeteners in reducing calorie intake in the short-term and aiding in weight management is also supported by a systematic review by the US Dietary Guideline Advisory Committee of the Dietary Guidelines for Americans, 2020-2025.19
Weight control and especially long-term weight loss maintenance has been proven to be very challenging to individuals living with overweight and obesity. While low/no calorie sweeteners are not a magic bullet in weight loss, they can be a useful dietary tool in providing wider options for sweet-tasting foods and beverages with fewer calories and sugars and help people living with obesity to adhere to an overall higher quality diet while trying to manage their body weight.
The WHO recommendation may be confusing for people living with diabetes
The draft guideline states that assessing the health effects of non-sugar sweeteners on individuals with pre-existing diabetes was beyond the scope of this guideline, and therefore this recommendation possibly is not relevant for individuals with diabetes.1 However, low/no calorie sweeteners are a useful dietary aid for people with diabetes who need to manage their carbohydrate and sugars intake and missing to consider the needs of patients living with diabetes, consisting approximately 10% of the global population, is an important shortcoming of this draft guideline. In fact, the WHO recommendation suggesting not to use non-sugar sweeteners as a means for weight control might even be confusing to people living with diabetes, especially when diabetes and nutrition-related organisations support the use of low/no calorie sweeteners for diabetes management.
Based on the scientific opinion of the European Food Safety Authority,4 in an authorised health claim in the EU Register of nutrition and health claims, it is recognised that ‘the consumption of foods containing intense sweeteners instead of sugar induces a lower blood glucose rise after their consumption compared to sugar-containing foods’ (Commission Regulation (EU) No 432/2012).20 Also, several reviews have confirmed that low/no calorie sweeteners, by themselves, do not affect glycaemia and insulin levels post-prandially.21,22 The absence of glycaemic effect of low/no calorie sweeteners, and the lower spike in postprandial blood glucose they cause when used instead of sugars, makes them a useful dietary aid for people with diabetes who need to manage their carbohydrate and sugars intake. Health organisations globally recognise that low/no calorie sweeteners can be safely used to replace sugar in the nutritional management of diabetes.23-25 For example, both the American Diabetes Association (ADA)24 and the US Academy of Nutrition and Dietetics (AND)25, in their nutrition recommendations for type 1 and type 2 diabetes, conclude that the use of low/no calorie sweeteners has the potential to reduce overall calorie and carbohydrate intake if substituted for caloric sweeteners and without compensation by intake of additional calories from other food sources. Also, the latest Diabetes UK Position Statement on low/ no calorie sweeteners (LNCS) concludes that: “LNCS are shown to be safe and they can be used as part of a strategy for adults and children in the management of weight and diabetes”.23
The role of low/no calorie sweeteners in dental health is important and well-established
The excess intake of dietary sugars is a recognised hazard in relation to dental caries in humans.26,27 In contrast, by being non-fermentable by oral bacteria, low/no calorie sweeteners can contribute to good dental health, when used in place of sugar.28 EFSA supports in the respective scientific opinions that “there is sufficient scientific information to support the claims that intense sweeteners, as all sugar replacers, maintain tooth mineralisation by decreasing tooth demineralisation if consumed instead of sugars”.4 The draft WHO guideline missed to consider the totality of evidence confirming this well-established benefit of low/no calorie sweeteners use in dental health, which was in fact also supported by evidence reviewed in WHO’s own study. This is concerning because dental caries is amongst the most widespread non-communicable disease.
Low/no calorie sweeteners are safe and do not affect cardiometabolic health
Food safety authorities around the world have repeatedly and consistently confirmed the safety of low/no calorie sweeteners, including during pregnancy. In fact, for a low/no calorie sweetener to be approved for use on the market, it must first undergo a thorough safety assessment by the competent food safety authority assessing all the available literature, including but not limited to the data reviewed by WHO as evidence from short-term RCTs in humans, animal and in-vitro data are also assessed. Such scientific regulatory bodies include the Joint Expert Scientific Committee on Food Additives (JECFA) of the United Nations Food & Agriculture Organization (FAO) and of the World Health Organization (WHO)2, the European Food Safety Authority (EFSA)29 and the US Food and Drug Administration (FDA).30
Based on very low quality evidence, the draft WHO guideline points to “potential undesirable effects from long-term use in the form of increased risk of type 2 diabetes, cardiovascular diseases, and mortality in adults. Limited evidence suggests potential undesirable effects in the form of increased risk of preterm birth with NSS use during pregnancy.”1 However, this statement is based solely on very low to low evidence from observational studies, which are at risk of residual confounding and reverse causality, as acknowledged in this guideline. Importantly, and contrary to observational findings, results from meta-analyses of RCTs, including in the recent WHO study, confirm that low/no calorie sweeteners have no adverse impact on cardiometabolic risk factors, including glucose and insulin levels, blood lipids and blood pressure.3,10,31 In fact, a recent systematic review of RCTs found potential cardiometabolic health benefits when low/no calorie sweetened beverages are used to replace sugars.10
What does it mean that the recommendation is conditional?
The draft recommendation on use of non-sugar sweeteners is a conditional (weak) recommendation. Conditional recommendations are those recommendations for which the WHO guideline development group is uncertain that the desirable consequences of implementing the recommendation outweigh the undesirable consequences or when the anticipated net benefits are small. This decision was based on the assessment of the available evidence as overall low certainty in the recent WHO systematic review that supported today’s draft guideline.3 However, this study examined only a fraction of the available literature and missed to assess strong evidence from RCTs examining the impact of low/no calorie sweeteners on postprandial glycaemia and in tooth mineralisation.
The benefits of low/no calorie sweeteners when used in place of sugars are supported by a wealth of well conducted, acute, short- and longer-term randomised controlled trials in humans, which provide high quality evidence.32 Failing to consider the collective evidence on the health effects of non-sugar sweeteners and to accurately translate the totality of available evidence into a recommendation in view of the hierarchy of scientific evidence, may hinder public health efforts to reduce excess sugars intake and to tackle obesity.
This article is also available in Arabic here.