Rationale, Design and Participants Baseline Characteristics of a Crossover Randomized Controlled Trial of the Effect of Replacing SSBs with NSBs versus Water on Glucose Tolerance, Gut Microbiome and Cardiometabolic Risk in Overweight or Obese Adult SSB Consumer: Strategies to Oppose SUGARS with Non-Nutritive Sweeteners or Water (STOP Sugars NOW) Trial and Ectopic Fat Sub-Study

Abstract

Background: Health authorities are near universal in their recommendation to replace sugar-sweetened beverages (SSBs) with water. Non-nutritive sweetened beverages (NSBs) are not as widely recommended as a replacement strategy due to a lack of established benefits and concerns they may induce glucose intolerance through changes in the gut microbiome. The STOP Sugars NOW trial aims to assess the effect of the substitution of NSBs (the “intended substitution”) versus water (the “standard of care substitution”) for SSBs on glucose tolerance and microbiota diversity. Design and Methods: The STOP Sugars NOW trial (NCT03543644) is a pragmatic, “head-to-head”, open-label, crossover, randomized controlled trial conducted in an outpatient setting. Participants were overweight or obese adults with a high waist circumference who regularly consumed ≥1 SSBs daily. Each participant completed three 4-week treatment phases (usual SSBs, matched NSBs, or water) in random order, which were separated by ≥4-week washout. Blocked randomization was performed centrally by computer with allocation concealment. Outcome assessment was blinded; however, blinding of participants and trial personnel was not possible. The two primary outcomes are oral glucose tolerance (incremental area under the curve) and gut microbiota beta-diversity (weighted UniFrac distance). Secondary outcomes include related markers of adiposity and glucose and insulin regulation. Adherence was assessed by objective biomarkers of added sugars and non-nutritive sweeteners and self-report intake. A subset of participants was included in an Ectopic Fat sub-study in which the primary outcome is intrahepatocellular lipid (IHCL) by 1H-MRS. Analyses will be according to the intention to treat principle. Baseline results: Recruitment began on 1 June 2018, and the last participant completed the trial on 15 October 2020. We screened 1086 participants, of whom 80 were enrolled and randomized in the main trial and 32 of these were enrolled and randomized in the Ectopic Fat sub-study. The participants were predominantly middle-aged (mean age 41.8 ± SD 13.0 y) and had obesity (BMI of 33.7 ± 6.8 kg/m2) with a near equal ratio of female: male (51%:49%). The average baseline SSB intake was 1.9 servings/day. SSBs were replaced with matched NSB brands, sweetened with either a blend of aspartame and acesulfame-potassium (95%) or sucralose (5%). Conclusions: Baseline characteristics for both the main and Ectopic Fat sub-study meet our inclusion criteria and represent a group with overweight or obesity, with characteristics putting them at risk for type 2 diabetes. Findings will be published in peer-reviewed open-access medical journals and provide high-level evidence to inform clinical practice guidelines and public health policy for the use NSBs in sugars reduction strategies. Trial registration: ClinicalTrials.gov identifier, NCT03543644

Empfehlungen zur Ernährungsprävention des Typ-2-Diabetes mellitus

“…Eine kürzlich durchgeführte Meta-Analyse zeigte, dass eine Zunahme des Konsums von Getränken mit nicht-nutritiven Süßungsmitteln um eine Portion/Tag mit einem 13 %igen Anstieg des T2Dm-Risikos verbunden war [96]. Zudem zeigen jüngste Daten, dass Getränke mit nicht-nutritiven Süßungsmitteln als Ersatzstrategie empfohlen werden, obwohl ihre Vorteile noch umstritten sind und zu befürchten ist, dass sie durch Veränderungen des Darmmikrobioms eine Glukoseintoleranz hervorrufen könnten [97]. Süßungsmittel werden wegen ihrer verschiedenen chemischen Eigenschaften unterschiedlich verstoffwechselt, mit diversen Auswirkungen auf die Glukosehomöostase und die zugrundeliegenden Mechanismen, was die Ursache für die Unterschiede im Stoffwechselverhalten von Süßungsmitteln und die widersprüchlichen Ergebnisse sein kann [98].…”

Nutritional Recommendations for the Prevention of Type 2 Diabetes Mellitus

“…A recent meta-analysis showed that a one-serving/day increase in the consumption of beverages containing artificial sweeteners was associated with a 13 % increase in T2DM risk [96]. In addition, recent data show that beverages with artificial sweeteners are recommended as a substitute strategy, although their benefits are still controversial and it is feared that they could induce glucose intolerance through changes in the gut microbiome [97]. Artificial sweeteners are metabolized differently because of their different chemical properties, with various effects on glucose homeostasis and underlying mechanisms, which may be the cause of the differences in the metabolic behaviour of artificial sweeteners as well as the conflicting results [98].…”

Association between added sugars and frailty in U.S. adults: a cross-sectional study from the National Health and Nutrition Examination Survey 2007–2018

“…The National Health and Nutrition Examination Survey (NHANES) investigates a spectrum of added sugar sources, including brown sugar, sugarcane syrup, corn syrup, honey, molasses, and white sugar ( 7 , 8 ). Previous studies have demonstrated the association of added sugars with elevated risks of obesity ( 9 , 10 ), diabetes mellitus (DM), and cardiovascular disease (CVD) ( 11 ), which are intrinsically correlated with frailty. Despite previous studies focusing on factors precipitating frailty in the older adults, there is limited evidence revealing the association between added sugars and frailty in the general population.…”