Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar Sweetened Beverages With Body Weight and Cardiometabolic Risk. A Systematic Review and Meta-analysis

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Auteur(s): McGlynn ND, Khan TA, Wang L, Zhang R, Chiavaroli L, Au-Yeung F, Lee J, Norohna JC, Comelli, EM, Mejia SB, Ahmed A, Malik VS, Hill JO, Leiter LA, Agarwal A, Jeppesen PB, Rahelić D, Kahleová H, Salas-Salvadó J, Kendall CC, Sievenpiper JL.
Nom de la publication : JAMA Network Open 2022;5(3):e222092. doi:10.1001/jamanetworkopen.2022.2092
Année de publication : 2022


There are concerns that low- and no-calorie sweetened beverages (LNCSBs) do not have established benefits, with major dietary guidelines recommending the use of water and not LNCSBs to replace sugar-sweetened beverages (SSBs). Whether LNCSB as a substitute can yield similar improvements in cardiometabolic risk factors vs water in their intended substitution for SSBs is unclear.

To assess the association of LNCSBs (using 3 prespecified substitutions of LNCSBs for SSBs, water for SSBs, and LNCSBs for water) with body weight and cardiometabolic risk factors in adults with and without diabetes.

Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through December 26, 2021.

Randomized clinical trials (RCTs) with at least 2 weeks of interventions comparing LNCSBs, SSBs, and/or water were included.

Data were extracted and risk of bias was assessed by 2 independent reviewers. A network meta-analysis was performed with data expressed as mean difference (MD) or standardized mean difference (SMD) with 95%CIs. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to assess the certainty of the evidence.

The primary outcome was body weight. Secondary outcomes were other measures of adiposity, glycemic control, blood lipids, blood pressure, measures of non-alcoholic fatty liver disease, and uric acid.

A total of 17 RCTs with 24 trial comparisons were included, involving 1733 adults (mean [SD] age, 33.1 [6.6] years; 1341 women [77.4%]) with overweight or obesity who were at risk for or had diabetes. Overall, LNCSBs were a substitute for SSBs in 12 RCTs (n = 601 participants), water was a substitute for SSBs in 3 RCTs (n = 429), and LNCSBs were a substitute for water in 9 RCTs (n = 974). Substitution of LNCSBs for SSBs was associated with reduced body weight (MD, −1.06 kg; 95%CI, −1.71 to –0.41 kg), body mass index (MD, −0.32; 95%CI, −0.58 to –0.07), percentage of body fat (MD, −0.60%; 95%CI, −1.03%to –0.18%), and intrahepatocellular lipid (SMD, −0.42; 95%CI, −0.70 to –0.14). Substituting water for SSBs was not associated with any outcome. There was also no association found between substituting LNCSBs for water with any outcome except glycated hemoglobin A1c (MD, 0.21%; 95%CI, 0.02%to 0.40%) and systolic blood pressure (MD, −2.63mm Hg; 95%CI, −4.71 to −0.55 mm Hg). The certainty of the evidence was moderate (substitution of LNCSBs for SSBs) and low (substitutions of water for SSBs and LNCSBs for water) for body weight and was generally moderate for all other outcomes across all substitutions.

This systematic review and meta-analysis found that using LNCSBs as an intended substitute for SSBs was associated with small improvements in body weight and cardiometabolic risk factors without evidence of harm and had a similar direction of benefit as water substitution. The evidence supports the use of LNCSBs as an alternative replacement strategy for SSBs over the moderate term in adults with overweight or obesity who are at risk for or have diabetes. 


The aim of the present systematic review and meta-analysis was to update the recommendations of the European Association for the Study of Diabetes (EASD) by EASD’s Diabetes and Nutrition Study Group (DNSG). The results supported the assertion that substituting sugar-sweetened beverages (SSBs) with low/no calorie sweetened beverages was associated with reductions in body weight and cardiometabolic risk factors, with no evidence of harm. These improvements were similar in direction to those associated with water substitution, the standard of care.

The meta-analysis included 17 randomised controlled trials (RCTs) with 24 trial comparisons and with a median duration of 12 weeks, involving 1733 adult participants with overweight or obesity who were at risk for or had diabetes. The trials examined the association of beverages with cardiometabolic risk factors (adiposity, glycemia, blood lipids, blood pressure, non-alcoholic fatty liver disease [NAFLD], and uric acid). A network meta-analyses rather than traditional pairwise meta-analyses was conducted, using three prespecified substitutions: SSBs with low/no calorie sweetened beverages (intended substitution with caloric displacement), SSBs with water (standard-of-care substitution with caloric displacement), and low/no calorie sweetened beverages with water (reference substitution without caloric displacement). The network meta-analysis methodology provided more precise estimates than single direct or indirect estimates.

Results showed that the intended substitution of SSBs with low/no calorie sweetened beverages was associated with small reductions in body weight and lower BMI, percentage of body fat and intrahepatocellular lipid. Importantly, there was no evidence of harm or adverse events with this substitution. Also, a small reduction in body weight was associated with low/no calorie sweeteners compared with water; among secondary outcomes, water was associated with lower level of HbA1c, while low/no calorie sweetened beverages were associated with a greater decrease in systolic blood pressure compared with water. Finally, for the comparison between SSBs with water, neither the primary outcome of body weight nor any of the secondary outcomes showed significant differences, although the direction of association favoured water for most of the outcomes. Balancing the strengths and limitations of the current study, the authors concluded that the certainty of the evidence is generally low to moderate for most outcomes.

The findings of this study are consistent with the results of other systematic reviews and meta-analyses of RCTs (Laviada-Molina et al, 2020; Rogers and Appleton, 2021). The authors conclude that the current evidence provides a good indication of the benefits of low/no calorie sweetened beverages as an alternative replacement strategy over the moderate term for SSBs in adults with overweight or obesity who are at risk for or have diabetes. These findings can inform guidance on the role of beverages sweetened with low/no calorie sweeteners in sugar-reduction strategies.

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