1. Introduction
obesity, glucose intolerance, SSBs, overweight, adiposity, sugar reduction
OBESITY, GLUCOSE INTOLERANCE, OBESE, RECRUITMENT, INSULIN RESISTANCE, ADIPOSITY
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/mSugar-sweetened beverages (SSBs) are the single largest contributor of added sugars in the diet [Recent comprehensive syntheses of the evidence of randomized controlled trials and prospective cohort studies have contributed to the uncertainty regarding NNS. A WHO-commissioned systematic review and meta-analysis of NNS concluded that most health outcomes showed no difference, meaning they failed to show the expected re-ductions in body mass index (BMI), body weight, plasma insulin levels, insulin resistance and β-cell function in randomized controlled trials (RCTs) or associations with lower risk of NCDs [Various biological mechanisms have been invoked to support the signals for concern regarding NNS consumption (e.g., through the brain’s reward center [There is an urgent need to address the remaining uncertainties related to NSBs. Health Canada, in particular, has indicated that studies of sugar reduction strategies that use NNSs with microbiome outcomes are an important research priority [