Please select the eligibility criteria that correspond to the clinical trial below.
Title: 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
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.


Options:
A: Inclusion Criteria:

* Body Mass Index (BMI) 21.0 -33.0

Exclusion Criteria:

* More than a 3% change in weight within the 3 months prior to enrollment in the study.
* Currently smoking cigarettes
* Currently taking any prescription medication for less than 3 months.
* Currently taking a prescription medication for weight loss (4 week wash out period required).
* Currently taking any over-the-counter weight loss supplement/s (2 week wash out period required).
* History of thyroid disease, but not taking medication or medication dosage changed one or more times over last 6 months.
* Diagnosed with Type I or Type II diabetes or prediabetes.
* Major surgery within three months of enrollment.
* History of heart problems (e.g. angina, bypass surgery, MI, etc.) within three months prior to enrollment.
* Presence of implanted cardiac defibrillator or pacemaker.
* Uncontrolled hypertension/high blood pressure.
* History of a surgical procedure for weight loss at any time.
* Gastrointestinal disorders including chronic malabsorptive conditions, peptic ulcer disease, Crohn's disease, chronic diarrhea or active gallbladder disease.
* History of inflammatory bowel disease
* History of fatty liver
* History or presence of cancer (except for successfully resected basal cell carcinoma of the skin more than 6 months prior to enrollment).
* History of clinically diagnosed eating disorders including anorexia nervosa, bulimia nervosa or binge eating disorder.
* Women who are pregnant, lactating or trying to become pregnant.
* History of alcohol dependency
* Currently consuming \>14 alcoholic drinks (1 drink = 12 fl oz beer, 4 fl oz wine or 1.5 fl oz liquor) per week and/or unwilling to limit intake to less than 3 drinks per week during study participation.
* Lactose intolerance
* Known allergy to HFCS, sucrose, fructose or glucose.
* Any clinically significant food allergy
* Participation in another clinical trial within 30 days prior to enrollment.
B: Inclusion Criteria:

* BMI 22-28 kg/m2
* Self-reported stable body weight during the prior six months

Exclusion criteria:

* Fasting glucose \>105 mg/dl
* Evidence of liver disorder \[AST (Aspartate Aminotransferase) or ALT (Alanine Aminotransferase)\] \>200% upper limit of normal range)
* Evidence of kidney disorder (\>2.0mg/dl creatinine)
* Evidence of thyroid disorder (out of normal range)
* Systolic blood pressure consistently over 140mm Hg (mercury) or diastolic blood pressure over 90mmHg
* Triglycerides \> 200mg/dl
* LDL-C \> 130mg/dl in combination with Chol:HDL \> 4
* Hemoglobin \< 8.5 g/dL
* Pregnant or lactating women
* Any other condition that, in the opinion of the investigators, would put the subject at risk
* Current, prior (within 12 months), or anticipated use of any hypolipidemic or anti-diabetic agents.
* Use of thyroid, anti-hypertensive, anti-depressant, weight loss medications or any other medication which, in the opinion of the investigator, may confound study results
* Use of tobacco
* Strenuous exerciser (\>3.5 hours/week at a level more vigorous than walking)
* Surgery for weight loss
* Diet exclusions: Food allergies, special dietary restrictions, food allergies, routine consumption of less than 3 meals/day, routine ingestion of more than 2 sugar-sweetened beverages or 1 alcoholic beverage/day, unwillingness to consume any food on study menu
* Hydrogen concentration in breath sample following consumption of HFCS-beverage during screening \>50ppm
* Veins that are assessed by the CCRC (Clinical Research Center) R.N.s as being unsuitable for long-term infusions and multiple blood draws from a catheter.
* Pre-existing claustrophobia or metal implants that preclude MRI
C: Inclusion Criteria:

* Body mass index 18.5-29.9 kg∙m-2
* Age 18-65 years
* Able and willing to provide informed consent and safely comply with study procedures
* Females to maintain record of regular menstrual cycle phase/contraceptive use
* No anticipated changes in physical activity during the first 4 weeks of the study (e.g. holidays or training programmes)

Exclusion Criteria:

* Any reported condition or behaviour deemed either to pose undue personal risk to the participant or introduce bias
* Any diagnosed metabolic disease (e.g. type 1 or type 2 diabetes)
* Any reported use of substances which may pose undue personal risk to the participants or introduce bias into the experiment
* Lifestyle not conforming to standard sleep-wake cycle (e.g. shift worker)
* Any reported recent (\<6 months) change in body mass (± 3%)
* Use of antibiotic medication in the last 3 months
* Use of prebiotic or probiotic products in the last month
D: 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;
* Smoker;
* 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)

Answer: D