Adverse associations of low- and no-calorie sweetened beverages (LNCSB) with cardiometabolic outcomes in observational studies may be explained by reverse causality and residual confounding.
To address these limitations we used change analyses of repeated measures of intake and substitution analyses to synthesize the association of LNCSB with cardiometabolic outcomes.
MEDLINE, Embase, and the Cochrane Library were searched up to 10 June 2021 for prospective cohort studies with ≥1 year of follow-up duration in adults.
Outcomes included changes in clinical measures of adiposity, risk of overweight/obesity, metabolic syndrome, type 2 diabetes (T2D), cardiovascular disease, and total mortality.
Two independent reviewers extracted data, assessed study quality, and assessed certainty of evidence using GRADE. Data were pooled with a random-effects model and expressed as mean difference (MD) or risk ratio (RR) and 95% CI.
A total of 14 cohorts (416,830 participants) met the eligibility criteria. Increase in LNCSB intake was associated with lower weight (5 cohorts, 130,020 participants; MD −0.008 kg/year [95% CI −0.014, −0.002]). Substitution of LNCSB for sugar-sweetened beverages (SSB) was associated with lower weight (three cohorts, 165,579 participants; MD, −0.12 [−0.14, −0.10,] kg/y) and lower incidence of obesity (OB) (one cohort, 15,765 participants; RR 0.88 [95% CI 0.88, 0.89]), coronary heart disease (six cohorts, 233,676 participants; 0.89 [0.81, 0.98]), cardiovascular disease mortality (one cohort, 118,363 participants; 0.95 [0.90, 0.99]), and total mortality (one cohort, 118,363 participants; 0.96 [0.94, 0.98]) with no adverse associations across other outcomes. Substitution of water for SSB showed lower weight (three cohorts, 165,579 participants; MD −0.10 kg/year [−0.13, −0.06]), lower waist circumference (one cohort, 173 participants; −2.71 cm/year [−4.27, −1.15]) and percent body fat (one cohort, 173 participants; −1.51% per year [−2.61, −0.42]), and lower incidence of OB (one cohort, 15,765 participants; RR 0.85 [0.75, 0.97]) and T2D (three cohorts, 281,855 participants; 0.96 [0.94, 0.98]). Substitution of LNCSB for water showed no adverse associations.
The evidence was low to very low certainty owing to downgrades for imprecision, indirectness, and/or inconsistency.
LNCSB were not associated with cardiometabolic harm in analyses that model the exposure as change or substitutions. The available evidence provides some indication that LNCSB in their intended substitution for SSB may be associated with cardiometabolic benefit, comparable with the standard of care, water.
The aim of the present systematic review and meta-analysis of prospective cohort studies, conducted by the Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD), was to assess the relation of low/no calorie sweetened beverages to cardiometabolic outcomes in order to update the EASD clinical practice guidelines for nutrition therapy. The results supported the assertion that the substitution of sugar-sweetened beverages with low/no calorie sweetened beverages may be associated with cardiometabolic benefit, comparable with the standard of care, water. Importantly, low/no calorie sweetened beverages were not associated with cardiometabolic harm in analyses that model sweetened beverage intake as change or substitutions.
Overall, 14 prospective cohort studies in 416,830 adults were included in the review. The intended substitution of sugar-sweetened beverages with low/no calorie sweetened beverages was associated with lower weight and lower risk of obesity, coronary heart disease, total cardiovascular disease mortality, and total mortality, without an adverse association with any other cardiometabolic outcomes. Substitution of water for sugar-sweetened beverages was associated with lower risk of obesity and type 2 diabetes. Substitution of low/no calorie sweetened beverages for water was not associated with changes in any outcomes. In addition, a 1 serving/day increase of low/no calorie sweetened beverages was associated with lower weight and lower waist circumference, with no association with risk of type 2 diabetes. Overall, the evidence was rated as low or very low across the outcomes owing to downgrades for imprecision, indirectness, and/or inconsistency.
An important strength of this study is the inclusion of cohort comparisons with adjustment for initial adiposity and modelling of the exposure as change in intake or substitutions, to mitigate the influence of reverse causality and residual confounding and to provide more consistent, robust, and biologically plausible associations. The study results are in line with evidence from systematic reviews and meta-analyses of randomised controlled trials of intermediate cardiometabolic risk factors, and do not support findings of other systematic reviews and meta-analyses of prospective cohort studies that have relied largely on baseline or prevalent intakes of low/no calorie sweeteners.