Network Analysis Reinforces Benefits of Low- And No- Calorie Sweetened Beverages

March 14, 2022


McGlynn ND, Khan TA, Wang L, et al.

JAMA Network Open. 2022;5(3):e222092. doi:10.1001/jamanetworkopen.2022.2092

A recent review published in JAMA Network Open examined the association of low- and no-calorie sweetened beverages (LNCSBs) with body weight and cardiometabolic risk factors in adults with and without diabetes. Recent trials and reviews have reported inconsistent findings regarding these outcomes, and methodological considerations limit the conclusions that can be drawn from their reported results. For example, the authors note that the syntheses of randomized controlled trials (RCTs) do not fully account for the calories available to be displaced by LNCSBs, leading to an underestimation of the outcome of LNCSBs. In an effort to update the recommendations of the European Association for the Study of Diabetes, the Diabetes and Nutrition Study Group commissioned this new systematic review and meta-analysis to summarize evidence regarding the association of LNCSBs with intermediate cardiometabolic outcomes, including:

  • Adiposity
  • Glycemic Control
  • Blood Lipids
  • Blood Pressure
  • Measures of Non-Alcoholic Fatty Liver Disease
  • Uric Acid

Medline, Embase and the Cochrane Central Register of Controlled Trials were utilized to search RCTs with at least 2 weeks of interventions comparing LNCSBs, sugar-sweetened beverages (SSBs), and/or water (the standard of care substitution) from inception through December 2021. In contrast with the standard pairwise approach, researchers conducted a network meta-analysis, which allowed for the simultaneous assessment of three pre-specified substitutions (i.e., LNCSBs for SSBs, water for SSBs, and LNCSBs for water). This approach leverages direct and indirect comparisons with a common comparator to increase the information size, allowing for more precise estimates and the comparison of interventions that have not been previously compared.

Seventeen RCTs with twenty-four trial comparisons were included in the network meta-analysis. In total, the sample included 1733 adults with an average age of 33 years. The majority of included individuals (77.4%) were women who were overweight or obese and at-risk for or diagnosed with diabetes. In 12 of the RCTs included, LNCSBs were a substitute for SSBs, while 3 RCTs used water was a substitute for SSBs. LNCSBs were a substitute for water in 9 RCTs.

Network analyses of the prespecified substitutions yielded the following results:

  • Substitution of LNCSBs for SSBs (intended substitution with caloric displacement) was associated with reduced body weight body mass index, percentage of body fat, and intrahepatocellular lipid.
  • Substitution of water for SSBs (standard-of-care substitution with caloric displacement) was not associated with any outcome, although the direction of association favored water for most of the outcomes.
  • Substitution of LNCSBs for water (reference substitution without caloric displacement) was associated with lower-level glycated hemoglobin A1C seen with water and decreased body weight and systolic blood pressure with LNCSBs.

Certainty of the evidence assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Network estimates of RCTs and the direct and indirect estimates that composed these network estimates started at a high certainty of evidence but were downgraded by established criteria for risk of bias, inconsistency (incoherence), indirectness, imprecision, and publication bias. As a result, for the body weight outcome, the certainty of the evidence was rated as “moderate” for the substitution of LNCSBs for SSBs, and “low” for substitutions of water for SSBs and LNCSBs for water. The certainty of evidence was generally moderate for all other outcomes across all substitutions.

The findings in this study are in agreement with those reported in other systematic reviews and meta-analyses, which have allowed for the interpretation of results by comparator. Previous analyses have also reported reduced body weight, BMI, and body fat associated with the use LNCSBs as a substitute for SSBs with caloric displacement, which is consistent with the utility of LNCSBs in reducing net energy intake. Neutral outcomes associated with the use of LNCSBs as a substitute for water without caloric displacement were reported in previous analyses. The authors note, “Although water is considered to be the standard-of-care substitution for SSBs by authoritative bodies, with many health organizations recommending against the use of LNCSBs, the existing evidence confirms the intended benefits of LNCSBs as a substitute for SSBs over the moderate term.”

In conclusion, the authors state, “There is a need for high-quality RCTs that focus on quantifying the outcome of LNCSBs using different LNCS blends as substitutes for SSBs compared with the outcome of water (the standard-of care substitution).” They note that their findings provide a good indication of the benefits of LNCSBs 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. Future research using a range of designs is warranted to confirm whether the intended benefits of using LNCSBs as a substitute for SSBs are durable and extend to hard clinical outcomes.

faq2Do you have questions about low-calorie sweeteners? Want to learn more about maintaining a healthy lifestyle? You asked and we listened. Our resident Registered Dietitians answered the most popular questions about low-calorie sweeteners.

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