A Randomized Controlled Trial of the Effect of Replacing Sugar-sweetened Beverages With Non-nutritive Sweetened Beverages or Water on Gut Microbiome and Metabolic Outcomes: STOP Sugars NOW Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Toronto
- Enrollment
- 81
- Locations
- 2
- Primary Endpoint
- Gut microbiome composition measured by 16S rRNA gene sequencing
Study Overview
Brief Summary
Health authorities recommend a reduction in added sugars from sugar-sweetened beverages (SSBs) due to risk of obesity and diabetes. As a sugar-reduction strategy, finding the ideal SSB replacement is of the utmost importance. Those who are already consuming SSBs might not easily replace it with water and therefore non-nutritive sweetened beverages (NSBs) present a sweetened alternative, though guidelines recommend water instead of NSBs as a replacement for SSBs. Recent evidence suggests that saccharine, a non-nutritive sweetener, which is not found in NSBs, might induce glucose intolerance by altering gut microbiota in humans. It is currently not known if replacing SSBs with NSBs (which contain low-calorie sweeteners other than saccharine) or water will have any effect on the human gut microbiota and any downstream diabetic risk. The investigators plan to undertake a randomized controlled cross-over trial in 75 healthy adults to assess the effect of replacing SSBs with equal amounts of NSBs or water for 4 weeks on the composition and diversity of human gut microbiota, changes in glucose tolerance and total body fat in those who regularly drink SSBs. Each participant will act as their own control receiving each of the three interventions of SSB, NSB and water for four weeks in random order, each period separated by a four-week wash-out period. All study visits will occur at the Clinical Nutrition and Risk Factor Modification Centre at St. Michael's Hospital. This study will contribute to knowledge that will inform dietary guidelines and public policy with regards to the best possible replacement for SSBs. It will also shed light on the potential mechanism of the adverse effects of NSBs and if the replacement of SSBs by NSBs or water are in fact similar with respect to their effect on gut bacteria and any downstream diabetic risk.
Detailed Description
BACKGROUND AND SIGNIFICANCE:
International health agencies and chronic disease associations have called for reductions in free/added sugars to ≤5-10% of energy to address the growing epidemics of obesity and diabetes. Attention has focused especially on the reduction of major source of free sugars, sugar sweetened beverages (SSBs), of which the excess consumption has been associated with weight gain, diabetes, and their downstream complications including hypertension and coronary heart disease (CHD). Ontario's Healthy Kids Panel, Health Canada, the Standing Senate Committee, the Heart and Stroke Foundation and Diabetes Canada have recommended policies to reduce SSBs including replacement strategies, taxation, and/or bans on advertising to children. A role for non-nutritive sweeteners (NNSs) in these policy options has been conspicuously absent.
There is an emerging concern that NNSs may contribute to an increase in the diseases that they are trying to prevent. Systematic reviews and meta-analyses of prospective cohort studies have shown that NNSs are associated with increased risk of weight gain, diabetes, and CHD. Although this evidence is recognized to be at high risk of reverse causality and disagrees with the higher quality evidence from randomized controlled trials, several biological mechanisms have been proposed, among them changes in gut microbiome. One highly-influential study concluded that NNSs induce glucose intolerance through a loss of diversity in microbiome. This study, however, disagreed with a subsequent study and had several methodological weaknesses including the lack of a control group. Despite the uncertainties, these data have contributed to a negative view of NNSs in the media.
There is an urgent need to address the ongoing concerns related to NNSs. Health Canada, in particular, has indicated that studies of sugar reduction strategies that use NNSs and target microbiome are an important research priority. The investigators propose to conduct a CIHR-funded randomized controlled trial that assesses the effect of a 'real world' strategy to reduce SSBs using non-nutritive sweetened beverages (NSBs) or water on gut microbiome, glucose tolerance, and cardiometabolic risk factors in overweight or obese participants.
OBJECTIVES
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy, adult (age, 18-75 years) men and non-pregnant women;
- •Overweight or obese (BMI > 23 kg/m2 for Asian individuals and > 25 kg/m2 other individuals);
- •High waist circumference (> 94 cm in men, > 80 cm in women in Europid, Sub-Saharan African, Eastern Mediterranean, and Middle Eastern individuals; > 90 cm in men and > 80 cm in women for South Asian, Chinese, Japanese, and South and Central American individuals);
- •Currently report drinking SSBs regularly (≥ 1 serving daily);
- •Have a primary care physician;
- •Nonsmoker;
- •Free of any diseases or illnesses;
- •Not regularly taking any medications that have a clinically relevant effect on the primary outcomes, as deemed inappropriate by investigators
Exclusion Criteria
- •Age < 18 or > 75 years;
- •BMI < 23 kg/m2 for Asian individuals and < 25 kg/m2 other individuals;
- •Waist circumference < 94cm in men, < 80cm in women in Europid, Sub-Saharan African, Eastern Mediterranean, and Middle Eastern individuals; < 90cm in men and < 80 cm in women for South Asian, Chinese, Japanese, and South and Central American individuals;
- •Not regularly drinking SSBs (≥1 serving per day);
- •Pregnant or breast feeding females, or women planning on becoming pregnant throughout study duration;
- •Regular medication use that have a clinically relevant effect on the primary outcomes, as deemed inappropriate by investigators
- •Antibiotic use in the last 3 months;
- •Complementary or alternative medicine (CAM) use as deemed inappropriate by investigators;
- •Self-reported diabetes;
- •Self-reported uncontrolled hypertension (or systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg [26]);
- •Self-reported polycystic ovarian syndrome;
- •Self-reported cardiovascular disease;
- •Self-reported gastrointestinal disease;
- •Previous bariatric surgery;
- •Self-reported liver disease;
- •Self-reported uncontrolled hyperthyroidism or hypothyroidism;
- •Self-reported kidney disease;
- •Self-reported chronic infection;
- •Self-reported lung disease;
- •Self-reported cancer/malignancy;
- •Self-reported schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, and dissociative disorders;
- •Major surgery in the last 6 months;
- •Other major illness or health-related incidence within the last 6 months;
- •Regular recreational drug users;
- •Heavy alcohol use (> 3 drinks/day);
- •Do not have a primary care physician;
- •Participation in any trials within the last 6 months or for the duration of this study;
- •Individuals planning on making dietary or physical activity changes throughout study duration;
- •If participating in MRI portion of study: any condition or circumstance which would prevent the participant from having an MRI (e.g. having prostheses or metal implants, tattoos, or claustrophobia)
Outcomes
Primary Outcomes
Gut microbiome composition measured by 16S rRNA gene sequencing
Time Frame: Week 0 and week 4 of each intervention
75g OGTT derived plasma glucose iAUC
Time Frame: Week 0 and week 4 of each intervention
Secondary Outcomes
- Change in waist circumference(Week 0 and week 4 of each intervention)
- Change in body weight(Week 0 and week 4 of each intervention)
- 75g OGTT derived Matsuda whole body insulin sensitivity index [Matsuda ISI OGTT](Week 0 and week 4 of each intervention)
- 75g OGTT derived 2-hour plasma glucose [2h-PG](Week 0 and week 4 of each intervention)
- Change in fasting plasma glucose(Week 0 and week 4 of each intervention)
Investigators
John Sievenpiper
Principal Investigator, Associate Professor, Staff Physician, Scientist
University of Toronto