ISA statement in response to Azad et al study

The conclusions of a new systematic review by Azad et al.¹ that low calorie sweeteners might be linked to risk of weight gain and heart disease on the basis of findings from observational cohort studies are not supported by the collective evidence from well-designed human intervention studies and previous thorough systematic reviews and meta-analysis^2,3. Importantly, these claims are not confirmed by the findings of the meta-analysis of randomised controlled trials (RCTs) conducted by the authors of this paper.

Indeed, a strong body of human trials have consistently shown that low calorie sweeteners can be helpful in weight control, when used in place of sugar and as part of a healthy diet and lifestyle. Contrary to assertions in the study by Azad et al., observational cohort studies, by design, do not and cannot provide evidence that low calorie sweeteners are linked to weight gain or heart disease, as they are subject to indication bias and reverse causation cannot be ruled out. Importantly, there is not a single published randomised controlled trial, the gold standard in nutrition research, that has shown that low calorie sweeteners use can lead to weight gain or any negative health effect.

To put the findings of Azad et al. publication into context, some observational studies do find that people who are overweight or obese, individuals with diabetes or other cardiometabolic health issues that are usually accompanying obesity, tend to use more frequently low calorie sweeteners. However, this might be happening in their attempt to and as a strategy to reduce their calorie and sugar intake, which is a common dietary recommendation in such health conditions. Furthermore, in most observational studies, adjustment for variables related to adiposity attenuates or diminishes the observed relations, leading to no significant associations anymore.⁴

In order to attribute the observation of higher obesity rates in frequent low calorie sweeteners’ consumers to the use of low calorie sweeteners per se, rather than to some other unmeasured confounding factors, meaning to prove causation, a trial of randomised controlled design is required. This is the only study design in human studies that does rise to the level of demonstrating cause and effect, and in the case of low calorie sweeteners’ effect on body weight, evidence from RCTs is clear and consistent pointing to a modest benefit of low calorie sweeteners’ use in weight loss and maintenance.^2,3 Importantly, trials of longer duration have shown higher weight loss and maintenance with low calorie sweeteners’ use.^5,6

Surprisingly, the authors also support that ‘evidence from RCTs does not clearly support the intended benefits for non-nutritive sweeteners for weight management’, however, the selection criteria used for the meta-analysis of RCTs in this study led to the exclusion of several well-designed clinical trials that were included in a previous, more thorough, systematic review and meta-analysis by Rogers et al.³

At a time when obesity and related health conditions are increasing, low calorie sweeteners can be a helpful dietary tool as part of balanced diet and healthy lifestyle, based on the balance of strong evidence concluding that, overall, their use in place of sugar leads to reduced energy intake and modest weight loss. 

To read to detailed commentary on the study by Azad et al., please click here.