An overview of reviews on the association of low calorie sweetener consumption with body weight and adiposity

Authors: HIGGINS, KELLY - Exponent; RAWAL, RITA - University Of Maryland; KRAMER, MATTHEW - Retired ARS Employee; Baer, David; YERKE, AARON - Orise Fellow; KLURFELD, DAVID - Retired ARS Employee

Submitted to: Advances in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2024
Publication Date: 12/1/2024
Citation: Higgins, K.A., Rawal, R., Kramer, M., Baer, D.J., Yerke, A., Klurfeld, D.M. 2024. An overview of reviews on the association of low calorie sweetener consumption with body weight and adiposity. Advances in Nutrition. 15(12). Article 100239. https://doi.org/10.1016/j.advnut.2024.100239.
DOI: https://doi.org/10.1016/j.advnut.2024.100239

Interpretive Summary: Numerous systematic reviews (SR) and meta-analyses on low calorie sweeteners (LCS) have been published in recent years, concluding that LCS have beneficial, detrimental, or no effects on body weight (BW) and measures of adiposity, depending on the review. If SR and MA are designed to be systematic evaluations of the published literature, why do SR and MA that seemingly ask the same research question come to conflicting conclusions? The objective of this overview of reviews was to determine if the different inclusion criteria and methodologies of SR investigating the association between LCS consumption and BW and adiposity influence their findings, and whether meta-analyses overcome these problems and produce a consistent estimated effect. Systematic searches of PubMed, Cochrane Library, and Scopus were conducted to identify SR of randomized controlled trials and/or non-randomized studies investigating the association between LCS consumption and BW-related outcomes. The inclusion/exclusion criteria, literature search methods, evidence synthesis methods, meta-analysis results, and conclusions were extracted from each eligible SR. Of the 985 results recovered in the search, a total of 20 SR evaluated the association between LCS and BW-related outcomes, concluding the effect of LCS on BW was beneficial, adverse, or the evidence was insufficient to draw conclusions. There was considerable lack of overlap of studies included within each SR attributed, in part, to differences in inclusion criteria and literature search strategy. Methods of evidence synthesis were heterogeneous and often opaque, making it difficult to determine why disparate results were observed between SR. In general, there was a mismatch between the objective and the conclusions that could be drawn from the excessively heterogeneous studies utilized by each SR. Further, SR investigating the effect of LCS on BW implement different approaches, criteria, and methodologies. These factors were largely responsible for the conflicting results and conclusions. While previous meta-analyses highlight the large effect of study design and population characteristics on the observed effect, they do not provide consistent estimates of the effect of LCS on BW due to the factors mentioned above. Instead of trying to mathematically combine studies to explain the complex relationship between LCS intake and BW, using methods that continually yield mixed results, future high quality primary research should be designed to delineate under which conditions LCS intake decreases, increases, or has no effect on BW.

Technical Abstract: Numerous systematic reviews (SR) and meta-analyses (MA) on low calorie sweeteners (LCS) have been published in recent years, concluding that LCS have beneficial, neutral, or detrimental effects on various health outcomes, depending on the review. The objective of this overview of reviews was to determine how the methodologies of SR investigating the association between LCS consumption and body weight (BW) influence their findings and whether MA results can provide a consistent estimated effect. Systematic searches of PubMed, Scopus, and Cochrane Library were conducted in November 2022 to identify SR of randomized controlled trials (RCT) or non-randomized studies (NRS) investigating the association between LCS consumption and BW. The methods, MA results, and conclusions were extracted from each eligible SR. Of the 985 search results, 20 SR evaluated the association between LCS and BW, drawing from publications of 75 RCT, 42 prospective cohort studies, and 10 cross-sectional studies. There was a considerable lack of overlap of studies included within each SR attributed, in part, to the inclusion of studies based on design; thus, each SR synthesized results from distinctly different studies. Evidence synthesis methods were heterogeneous and often opaque, making it difficult to determine why results from certain studies were excluded or why disparate results were observed between SR. SR investigating the effect of LCS on BW implement different methodologies to answer allegedly the same question, drawing from a different set of heterogeneous studies, ignoring the basic assumptions required for MA, resulting in disparate results and conclusions. Previous MA show the large effects of study design, which results in inconsistent estimates of the effect of LCS on BW between MA of RCT and NRS. Given the availability of long-term RCT, these studies should be the basis of determining causal relationships (or lack thereof) between LCS and BW.