The current systematic review and meta-analysis by the World Health Organization (WHO) suggests that the use of low/no calorie sweeteners leads to modest yet significant reductions in body weight in adults without any significant impact on cardiometabolic risk, as assessed in randomised controlled trials (RCTs); in contrast, observational studies report a positive association between low/no calorie sweeteners and obesity or cardiometabolic diseases, which however is at risk of reverse causation.
The current review is an update and expansion of the WHO-supported systematic review by Toews et al (2019). A total of 283 studies were included in the review. Meta-analyses focused on RCTs, prospective cohort studies and case–control studies assessing cancer, and certainty in results was assessed via GRADE (Grading of Recommendations Assessment, Development and Evaluation).
Meta-analyses of RCTs showed that low/no calorie sweeteners may be effective at assisting with short-term weight loss in adults, particularly when compared with sugars and their use leads to a reduction in total energy intake (low certainty evidence). Importantly, there was no evidence of harm on measures of cardiometabolic health including fasting glucose, insulin, blood lipids and blood pressure, as assessed in RCTs (low to high certainty evidence). No significant effects were reported for children, however, one large, well-conducted RCT reported significant reductions in body weight, BMI z-score, waist circumference and body fat mass when sugar-sweetened beverages were replaced with low/no calorie sweetened beverages (moderate certainty evidence).
Results from prospective cohort studies suggest that higher low/no calorie sweetener intake may be associated with increased risk of obesity, type 2 diabetes, and cardiovascular diseases (very low to low certainty evidence). No significant association was observed between higher intakes of low/no calorie sweeteners and several types of cancer (brain, breast, colorectum, endometrium, kidney, larynx, lung, oesophagus, oral cavity and pharynx, ovary, pancreas, prostate, stomach, leukaemia, multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma), except for a subgroup analysis which suggested a link between saccharin and bladder cancer based on case–control studies, which were decades old, with important limitations and serious risk of bias (very low certainty evidence). Further research is needed in pregnant women, for which limited prospective cohort studies suggest a possible association of higher LNCS consumption with risk of preterm birth (low certainty evidence). However, the authors recognise limitations of the observational study design, concluding that further research is needed to determine whether the observed associations are genuine or a result of reverse causation and/or residual confounding.
A critical appraisal of the systematic review by Rios-Leyvraz and Montez discussing the findings of this study is available on the ISA website here.