Assessments should be carried out to determine if NSSs are safe for obese children to use.

evidence profiles. Assessments of the certainty of evidence for all outcomes were reviewed with the WHO Nutrition Guidance Expert Advisory Group Subgroup on Diet and Health as part of the WHO guideline development process.

Presentation of the results in this systematic review is primarily structured according to age group – adults or children – and outcome. Within each outcome, the review presents the results for each PICO question separately – that is, population, intervention, comparator, and outcome – describing results of randomised controlled trials first, followed by those of non-randomised and observational studies. No patients were involved in setting the research question or the outcome measures, nor were they involved in developing plans for design or implementation of this systematic review. No patients were asked to advise on interpretation or writing up of results. It was not evaluated whether the studies included in the review had any patient involvement.

Implications for clinicians and policy makers

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The risk ratios were calculated at high respective confidence intervals for randomised controlled trials, controlled clinical trials, and cohort studies.

This review was prepared to inform a WHO guideline on NSS use and the guideline will provide information on implications for actions by health experts and policymakers. So far, several studies on the effects of NSSs on different health outcomes have been conducted. However, their methodological or reporting quality is mostly limited and often not sufficiently detailed to include their results in meta-analyses. Moreover, included studies differed substantially in their design –that is, choice of population, intervention, comparator, and outcome measures.

Given these relevant differences between studies, a reliable review of the effects by type of sweetener or of the caloric effects versus non-caloric effects is challenging. The type of intervention and comparator might affect health outcomes differently and should be considered in future research. Study planning should

consider the duration necessary for plausible, relevant effects to occur in the different outcomes of interest. Longer-term studies are needed to assess effects on overweight and obesity, risk for diabetes, cardiovascular disease, and kidney disease. Type and dose of sweetener use should be reported precisely and transparently in all studies. Precise reporting of sweetener content – that is, type and number of sweeteners – in ready-to-consume foods and beverages is highly desirable and could be helped by more detailed information on ingredients as provided by manufacturers. Consistent use of core outcome measures and consensus on timing and mode of assessment would further help researchers pool data across studies. In addition to studying the effects on NSS use in a general healthy population of adults and children, research should focus on diseased populations and other subgroups, including pregnant women and their offspring and people who use NSSs in amounts higher than average – such as those with diabetes.

Most of the studies identified for this review used single sweeteners and the use patterns of sweeteners in the studies might differ from that in real life practice. Therefore, the certainty in the evidence presented in this review might further be affected by indirectness. For example, NSSs can be consumed in different ways, including as a table-top sweetener – that is, added to tea or coffee as a replacement for sugar – where the dose is freely determined by users themselves and might be higher than that recorded in the studies. Moreover, by contrast to many of our included studies that used a single NSS only, many food items have different types of NSSs that are combined to cover different bitter or metallic aftertastes of individual sweeteners.

Future research might consider exploring the effects of different combinations of sweeteners in doses similar to real life use patterns and compare the effects of higher versus lower NSS doses. Development and research on NSSs is ongoing, and new alternatives to sugar are presented on a regular basis. Therefore, data is also needed on the safety and benefits and harms of other sweeteners not assessed in this review for a comprehensive overview of the health effects of NSSs. Results of observational studies on the health effects of NSSs should be interpreted with caution, and attention should focus on plausible residual confounding as well as reverse causality (such as a higher consumption of NSSs by overweight or obese populations aiming at weight management). Appropriate long-term studies that consider baseline consumption of sugar and NSSs, and have an appropriate comparator 106, should investigate whether NSSs are a safe and effective alternative to sugar, and results should be interpreted in light of these study design characteristics. ●

Ingredients Insight /


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