Reconciling Conflicting Evidence on Low- and No-Calorie Sweeteners and Cardiometabolic Outcomes: An Umbrella Review Using Naïve and Bias-adjusted Methods

Umbrella Review Supports Low- and No-Calorie Sweeteners for Sugar Reduction and Cardiometabolic Health

An umbrella review of systematic reviews and meta-analyses found that low- and no-calorie sweeteners may help reduce energy intake, body weight, and adiposity when used in place of sugar. Researchers concluded that bias-adjusted evidence consistently supports low- and no-calorie sweeteners as a safe and effective sugar-reduction strategy that may support cardiometabolic health.

Abstract 

Inconsistency among evidence syntheses has led to opposing guidelines and public confusion regarding low- and no-calorie sweeteners (LNCS) in noncommunicable diseases. To understand the role of different analytical approaches in assessing LNCS and cardiometabolic outcomes, an umbrella review of systematic reviews and meta-analyses was conducted. Included were six trial- and five cohort-based analyses. In trials, LNCS reduced energy, body weight, and body fat in both analyses and body mass index and systolic blood pressure in bias-adjusted only, while glycosylated hemoglobin showed smaller reductions than water in bias-adjusted only.

In analyses of cohorts, LNCS was associated with higher obesity, diabetes, stroke, and cardiovascular and all-cause mortality in naïve analyses but lower body weight, waist circumference, obesity, coronary heart disease, and cardiovascular and all-cause mortality in bias-adjusted analyses. The certainty of evidence was generally moderate for trials and very low for cohorts. LNCS show benefits across analytical approaches in both analyses of trials. These results agree with bias-adjusted analyses of cohorts, in which LNCS are associated benefits across cardiometabolic outcomes, but not naïve analyses of cohorts. Systematic reviews and meta-analyses using bias-reduction methods support the use of LNCS as a sugar-reduction strategy. 

Key Findings

  • Evidence from trial-based SRMAs consistently supports LNCS use, especially in substitution for sugars, to reduce energy intake and improve adiposity outcomes, without harm to other intermediate cardiometabolic outcomes.
  • Cohort-based SRMA evidence appears inconsistent when considering only naïve prevalent associations, as is often the case. However, bias-adjusted intended substitution and change analyses reconcile trial-cohort discrepancies. Intended substitution modeling, utilizing bias-reducing methods, demonstrates LNCS’s potential to lower adiposity, obesity incidence, cardiovascular, and all-cause mortality, with no harm observed in reference substitution modeling.
  • LNCS are a useful strategy to reduce calories from sugars and should be promoted to reduce adiposity and disease risk, when used as substitutes for caloric sweeteners.

Key Takeaways

The evidence on low- and no-calorie sweeteners has often been cited to be discordant between trials and cohorts. The review shows that when cohorts employ bias-adjusted methodologies, the evidence consistently supports the use of sweeteners for sugar-reduction.

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