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Meta-Analysis
. 2022 Mar 1;5(3):e222092.
doi: 10.1001/jamanetworkopen.2022.2092.

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

Néma D McGlynn  1   2 , Tauseef Ahmad Khan  1   2 , Lily Wang  1 , Roselyn Zhang  1   2   3 , Laura Chiavaroli  1   2 , Fei Au-Yeung  1   2 , Jennifer J Lee  1   2 , Jarvis C Noronha  1   2   4 , Elena M Comelli  1 , Sonia Blanco Mejia  1   2 , Amna Ahmed  1   2 , Vasanti S Malik  1   5 , James O Hill  6 , Lawrence A Leiter  1   2   7   8   9 , Arnav Agarwal  2   10 , Per B Jeppesen  11 , Dario Rahelic  12   13   14 , Hana Kahleová  15   16 , Jordi Salas-Salvadó  17   18 , Cyril W C Kendall  1   2   19 , John L Sievenpiper  1   2   7   8   9
Affiliations
Meta-Analysis

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

Néma D McGlynn et al. JAMA Netw Open. .

Abstract

Importance: 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.

Objective: 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.

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

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

Data extraction and synthesis: 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.

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

Results: 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, -2.63 mm 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.

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Ms McGlynn reported receiving a Canadian Institutes of Health Research (CIHR)-Masters Award during the conduct of the study and being a former employee of Loblaws Companies Limited outside the submitted work. Dr Khan reported receiving grants from CIHR, International Life Science Institute, and National Honey Board outside the submitted work. Dr Chiavaroli reported being a Mitacs Elevate postdoctoral fellow and receiving joint funding from the Government of Canada and the Canadian Sugar Institute. Mr Au-Yeung reported receiving personal fees from Inquis Clinical Research outside the submitted work. Ms Lee reported receiving graduate scholarship from CIHR and the Banting & Best Diabetes Centre at the University of Toronto outside the submitted work. Dr Comelli reported being the Lawson Family Chair in Microbiome Nutrition Research at the Joannah and Brian Lawson Centre for Child Nutrition, University of Toronto, during the conduct of the study and receiving nonfinancial support from Lallemand Health Solutions, donation to research program from Lallemand Health Solutions, personal fees from Danone, sponsored research and collaboration agreement from Ocean Spray, and nonfinancial support from Ocean Spray outside the submitted work. Ms Ahmed reported receiving scholarship from the Toronto Diet, Digestive tract, and Disease Centre (3D) outside the submitted work. Dr Malik reported receiving personal fees from the City and County of San Francisco, Kaplan Fox & Kilsheimer LLP, and World Health Organization outside the submitted work and support from the Canada Research Chairs Program. Dr Hill reported receiving personal fees from General Mills and McCormick Science Institute. Dr Rahelić reported receiving personal fees from the International Sweeteners Association, Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Merck, MSD, Salvus, and Sanofi outside the submitted work. Dr Salas-Salvadó reported receiving personal fees from Instituto Danone Spain, nonfinancial support from Danone Institute International, personal fees as director of the World Forum for Nutrition Research and Dissemination from the International Nut and Dried Fruit Council Foundation, financial support to the institution from Fundación Eroski, and financial support to the institution from Danone outside the submitted work. Dr Kendall reported receiving grants and/or in-kind support from Advanced Food Materials Network, Agriculture and Agri-Food Canada, CIHR, Almond Board of California, Barilla, Canola Council of Canada, International Nut and Dried Fruit Council, Peanut Institute, Pulse Canada, Tate and Lyle Nutritional Research Fund at the University of Toronto, and Unilever; receiving nonfinancial support from General Mills, Kellogg, Loblaw Brands Limited, Oldways Preservation Trust, Quaker Oats (Pepsi-Co), Sun-Maid, White Wave Foods/Danone, International Pasta Organization, California Walnut Commission, Primo, Unico, International Carbohydrate Quality Consortium (ICQC), and Toronto Diet, Digestive tract, and Disease Centre (3D) outside the submitted work; receiving personal fees from McCormick Science Institute and Lantmannen; and being a member of the Diabetes and Nutrition Study Group (DNSG) Executive Board and Dietary Guidelines, a member of the expert committee of the DNSG Clinical Practice Guidelines for Nutrition Therapy, a member of the scientific advisory board of the McCormick Science Institute, a scientific advisor for the International Pasta Organization and Oldways Preservation Trust, a member of the ICQC, an executive board member of the DNSG, and being the director of the Toronto Diet, Digestive tract, and Disease Centre (3D) Knowledge Synthesis and Clinical Trials Foundation. Dr Sievenpiper reported receiving nonfinancial support from DNSG of the European Association for the Study of Diabetes (EASD), grants from CIHR through the Canada-wide Human Nutrition Trialists' Network (NTN), PSI Graham Farquharson Knowledge Translation Fellowship, Diabetes Canada Clinician Scientist Award, CIHR Institute of Nutrition, Metabolism and Diabetes and the Canadian Nutrition Society (INMD/CNS) New Investigator Partnership Prize, and Banting & Best Diabetes Centre Sun Life Financial New Investigator Award during the conduct of the study; receiving grants from American Society for Nutrition, International Nut and Dried Fruit Council Foundation, National Honey Board (the US Department of Agriculture [USDA] honey checkoff program), Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America), Pulse Canada, Quaker Oats Center of Excellence, United Soybean Board (the USDA soy checkoff program), Tate and Lyle Nutritional Research Fund at the University of Toronto, Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), and Nutrition Trialists Fund at the University of Toronto (a fund established by an inaugural donation from the Calorie Control Council); receiving personal fees from Dairy Farmers of Canada, FoodMinds LLC, International Sweeteners Association, Nestlé, Abbott, General Mills, American Society for Nutrition, INC Nutrition Research and Education Foundation, European Food Safety Authority, Nutrition Communications, International Food Information Council, Calorie Control Council, Comité Européen des Fabricants de Sucre, International Glutamate Technical Committee, Perkins Coie LLP, Tate and Lyle Nutritional Research Fund at the University of Toronto, Danone, Inquis Clinical Research, Soy Nutrition Institute, and European Fruit Juice Association outside the submitted work; serving on the clinical practice guidelines expert committees of Diabetes Canada, EASD, Canadian Cardiovascular Society, and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons; being an unpaid scientific advisor for the Food, Nutrition, and Safety Program and the Technical Committee on Carbohydrates of IAFNS; being a member of the ICQC, executive board member of the DNSG of the EASD, and director of the Toronto Diet, Digestive tract, and Disease Centre (3D) Knowledge Synthesis and Clinical Trials Foundation; his spouse is an employee of AB InBev. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Literature Search for Randomized Clinical Trials of Low- and No-Calorie Sweetened Beverages
Figure 2.
Figure 2.. Substitution of Low- and No-Calorie Sweetened Beverages (LNCSBs) for Sugar-Sweetened Beverages (SSBs)
Data were pooled using network random-effects models and expressed as mean differences (MDs) and 95% CIs. To display the results for outcomes on the same plot, standardized mean differences (SMDs, represented by blue squares) and pseudo 95% CIs (represented by black horizontal lines and proportionally scaled to the 95% CIs of the MDs) were calculated. 2HPP indicates 2-hour postprandial glucose; ALT, alanine aminotransferase (to convert to μkat/L, multiply by 0.0167); AST, aspartate aminotransferase (to convert to μkat/L, multiply by 0.0167); BMI, body mass index; FPG; fasting plasma glucose; FPI, fasting plasma insulin; GRADE, Grading of Recommendations Assessment, Development and Evaluation; HbA1c; glycated hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model assessment of insulin resistance; IHCL, intrahepatocellular lipid; LDL-C, low-density lipoprotein cholesterol; and WC, waist circumference. aHDL-C result has been reversed for display purposes; that is, a negative MD would mean a positive improvement.
Figure 3.
Figure 3.. Substitution of Water for Sugar-Sweetened Beverages (SSBs)
Data were pooled using network random-effects models and expressed as mean differences (MDs) and 95% CIs. To display the results for outcomes on the same plot, standardized mean differences (SMDs, represented by blue squares) and pseudo 95% CIs (represented by black horizontal lines and proportionally scaled to the 95% CIs of the MDs) were calculated. 2HPP indicates 2-hour postprandial glucose; ALT, alanine aminotransferase (to convert to μkat/L, multiply by 0.0167); AST, aspartate aminotransferase (to convert to μkat/L, multiply by 0.0167); BMI, body mass index; FPG; fasting plasma glucose; FPI, fasting plasma insulin; GRADE, Grading of Recommendations Assessment, Development and Evaluation; HbA1c; glycated hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model assessment of insulin resistance; IHCL, intrahepatocellular lipid; LDL-C, low-density lipoprotein cholesterol; and WC, waist circumference. aHDL-C result has been reversed for display purposes; that is, a negative MD would mean a positive improvement.
Figure 4.
Figure 4.. Substitution of Low- and No-Calorie Sweetened Beverages (LNCSBs) for Water
Data were pooled using network random-effects models and expressed as mean differences (MDs) and 95% CIs. To display the results for outcomes on the same plot, standardized mean differences (SMDs, represented by blue squares) and pseudo 95% CIs (represented by black horizontal lines and proportionally scaled to the 95% CIs of the MDs) were calculated. 2HPP indicates 2-hour postprandial glucose; ALT, alanine aminotransferase (to convert to μkat/L, multiply by 0.0167); AST, aspartate aminotransferase (to convert to μkat/L, multiply by 0.0167); BMI, body mass index; FPG; fasting plasma glucose; FPI, fasting plasma insulin; GRADE, Grading of Recommendations Assessment, Development and Evaluation; HbA1c; glycated hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model assessment of insulin resistance; IHCL, intrahepatocellular lipid; LDL-C, low-density lipoprotein cholesterol; and WC, waist circumference. aHDL-C result has been reversed for display purposes; that is, a negative MD would mean a positive improvement.
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