Relation of Change or Substitution of Low Calorie Sweetened Beverages with Cardiometabolic Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Objectives Low calorie sweetened beverages (LCSBs) are associated with increased cardiometabolic diseases using prevalent exposure of LCSBs. Although this association is at high risk of reverse causality, it has led to concerns that LCSBs may not have the intended benefits, with recommendations to replace sugar-sweetened beverage (SSBs) with water and not LCSBs. To address this issue of reverse causality as part of the update of the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of prospective cohort studies of the relation of LCSBs with cardiometabolic outcomes using change and substitution analyses. Methods MEDLINE, EMBASE, and the Cochrane Library were searched through June 2019. We included prospective cohort studies of ≥1 year assessing change in LCSBs or substitution of LCSBs for SSBs in relation to cardiometabolic outcomes. Independent reviewers extracted data and assessed risk of bias. Data were pooled using random effects models and expressed as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CI). GRADE assessed the certainty of evidence. Results Nine studies (n = 218,880) inclusive of people at risk for or with diabetes were included. An Increase of 1 serving/day of LCSBs was associated with reduced body weight (MD, −0.07 kg [95% CI, −0.10 to −0.04]) and waist circumference (−1.35 cm [−2.60 to −0.05]) in change analyses. Substitution of LCSBs for SSBs was associated with a reduction in body weight (−0.47 kg [−0.55 to - 0.39]) and risk of diabetes (RR, 0.94 [0.90 to 0.98]), cardiovascular mortality (0.95 [0.90 to 0.99]) and total mortality (0.96 [0.94 to 0.98]), while substitution of LCSBs for water was not associated with any changes. The certainty of evidence was very low for all outcomes. Conclusions Substitution of LCSBs for SSBs is associated with reductions in major cardiometabolic outcomes with similar benefits to water as a replacement strategy for SSBs. The certainty of the available evidence is very low with a high likelihood that more studies will alter our estimates in people at risk for or with diabetes.(ClinicalTrials.gov identifier, NCT04245826) Funding Sources Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, Canadian Institutes of Health Research, Diabetes Canada.