Results from observational studies on the health outcomes of non-sugar sweetener use must be interpreted with caution due to plausible residual confounding and reverse causality, according to a systematic review published in BMJ.

For this systematic review, researchers analyzed data from Clinicaltrials.gov, Cochrane CENTRAL, EMBASE, MEDLINE (Ovid), WHO International Clinical Trials Registry Platform, and reference lists of relevant publications using standard Cochrane review methodology to identify associations between non-sugar sweetener intake and health outcomes in generally healthy children and adults with or without obesity.

Eligible studies had to clearly name the non-sugar sweeteners studied, doses needed to be within the acceptable daily intake, and the study duration needed to be at least 7 days. Main outcome measures were mood and behavior, body mass index or body weight, cancer, cardiovascular disease, glycemic control, kidney disease, neurocognition, and oral health.

A limited number of small studies showed very low and low certainty evidence that associated non-sugar sweeteners with a small beneficial effect on fasting blood glucose (mean difference -0.16 mmol/L; 95% CI, -0.26 to -0.06; 2 studies, n=52) and body mass index (-0.6; 95% CI, -1.19 to -0.01; 2 studies, n=174). One study showed very low certainty evidence associating lower doses of non-sugar sweeteners with lower weight gain (-0.09 kg; 95% CI, -0.13 to -0.05; n=17,934) compared with higher doses of non-sugar sweeteners.

No differences were observed between the use and non-use of non-sugar sweeteners or different doses of non-sugar sweeteners for all other outcomes, and no evidence of any effect was seen on children or adults actively trying to lose weight (very low to moderate certainty). Although a smaller increase in body mass index z score was indicated for non-sugar sweetener intake compared with sugar intake (-0.15, 95% CI, -0.17 to -0.12; 2 studies, n=528, moderate certainty of evidence), no significant differences were indicated in body weight (-0.60 kg, 95% CI, -1.33 to 0.14; 2 studies, n=467, low certainty of evidence), or between different doses of non-sugar sweeteners (very low to moderate certainty).

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Study investigators concluded that these kinds of studies “should be interpreted with caution, and attention should focus on plausible residual confounding as well as reverse causality (such as a higher consumption of [non-sugar sweeteners] by overweight or obese populations aiming at weight management). Appropriate long term studies that consider baseline consumption of sugar and [non-sugar sweeteners] and have an appropriate comparator should investigate whether [non-sugar sweeteners] are a safe and effective alternative to sugar, and results should be interpreted in light of these study design characteristics.”

Reference

Toews I, Lohner S, Küllenberg de Gaudry D, Sommer H, Meerpohl JJ. Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studiesBMJ. 2019;364:k4718.