Strategies To OPpose Sugars With Non-nutritive Sweeteners Or Water (STOP Sugars NOW) Trial

NCT03543644 | Completed

• 1 other identifier: CIHR-STOP Sugars NOW
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy; Overweight and Obesity; Metabolic Syndrome; PreDiabetes; Diabetes; Overweight; Obesity; Dysglycemia; Cardiovascular Diseases; Cardiovascular Risk Factor; Hypertension

Keywords

Microbiome; Sugar Sweetened Beverages; Diet Beverages; Non-Nutritive Sweetened Beverages; Glucose response

Outcome Measures

Primary Outcomes (2)

• Gut microbiome composition measured by 16S rRNA gene sequencing

  Week 0 and week 4 of each intervention

• 75g OGTT derived plasma glucose iAUC

  Week 0 and week 4 of each intervention

Secondary Outcomes (5)

• Change in waist circumference

  Week 0 and week 4 of each intervention

• Change in body weight

  Week 0 and week 4 of each intervention

• Change in fasting plasma glucose

  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

• 75g OGTT derived Matsuda whole body insulin sensitivity index [Matsuda ISI OGTT]

  Week 0 and week 4 of each intervention

Other Outcomes (35)

• Ectopic fat in liver (intra-hepatocellular lipid [IHCL]) by 1H-MRS (sub-study, n=30)

  Week 0 and week 4 of each intervention

• Ectopic fat in calf muscles (intra-myocellular lipid [IMCL]) by 1H-MRS (sub-study, n=30)

  Week 0 and week 4 of each intervention

• Fasting plasma insulin

  Week 0 and week 4 of each intervention

Study Arms (3)

Sugar-sweetened beverage (SSB)

ACTIVE COMPARATOR

The SSB intervention will consist the participants' consuming their usual serving of cans SSBs (each 355 ml, 42 grams sugar) per day. The calories of the SSB group will not be matched to allow for "real-world" substitutions using products available on the market.

Other: Sugar-sweetened beverage (SSB)

Non-nutritive sweetened beverage (NSB)

EXPERIMENTAL

The NSB intervention consists of substituting the participants' usual serving of cans SSBs with NSBs (each 355 ml, 0 grams sugar) per day. The calories of the NSB group will not be matched to allow for "real-world" substitutions using products available on the market.

Other: Non-nutritive sweetened beverages (NSB)

Water

EXPERIMENTAL

The water intervention consists of substituting the participants' usual serving of cans SSBs with bottles or cans of still or sparkling water (each 355 ml bottle or can, 0 grams sugar) per day. The calories of the water group will not be matched to allow for "real-world" substitutions using products available on the market.

Other: Water

Interventions

Sugar-sweetened beverage (SSB) OTHER

SSBs will be provided to each participant. Participants will be able to choose their SSB of choice from the list in the protocol. They will be instructed to drink their usual SSB intake, study drinks provided, while freely consume their usual background diets. They will revert to their usual SSB intake during wash-out phase during which they will not receive any beverage drinks from the study.

Sugar-sweetened beverage (SSB)

Non-nutritive sweetened beverages (NSB) OTHER

NSBs will be provided to each participant. Participants will be be given the NSB equivalent to the usual SSB chosen from the list in the protocol. They will be instructed to replace their usual SSBs with the NSBs while freely consume their usual background diets. They will revert to their usual SSB intake during wash-out phase during which they will not receive any beverage drinks from the study.

Non-nutritive sweetened beverage (NSB)

Water OTHER

Water will be provided to each participant. They will be instructed to replace their usual SSBs with the water while freely consume their usual background diets. They will revert to their usual SSB intake during wash-out phase during which they will not receive any beverage drinks from the study.

Water

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of Toronto: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5C2T2, Canada

Location

Related Publications (57)

• World Health Organization, WHO | Sugars intake for adult and children. 2015.

  BACKGROUND

• Dietary Guidelines Advisory Committee, 2015-2020 Dietary Guidelines for Americans - health.gov. 2015.

  BACKGROUND

• Heart and Stroke Foundation of Canada, Sugar, heart disease and stroke. 2014.

  BACKGROUND

• InterAct Consortium; Romaguera D, Norat T, Wark PA, Vergnaud AC, Schulze MB, van Woudenbergh GJ, Drogan D, Amiano P, Molina-Montes E, Sanchez MJ, Balkau B, Barricarte A, Beulens JW, Clavel-Chapelon F, Crispim SP, Fagherazzi G, Franks PW, Grote VA, Huybrechts I, Kaaks R, Key TJ, Khaw KT, Nilsson P, Overvad K, Palli D, Panico S, Quiros JR, Rolandsson O, Sacerdote C, Sieri S, Slimani N, Spijkerman AM, Tjonneland A, Tormo MJ, Tumino R, van den Berg SW, Wermeling PR, Zamara-Ros R, Feskens EJ, Langenberg C, Sharp SJ, Forouhi NG, Riboli E, Wareham NJ. Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct. Diabetologia. 2013 Jul;56(7):1520-30. doi: 10.1007/s00125-013-2899-8. Epub 2013 Apr 26.

  PMID: 23620057 BACKGROUND

• Greenwood DC, Threapleton DE, Evans CE, Cleghorn CL, Nykjaer C, Woodhead C, Burley VJ. Association between sugar-sweetened and artificially sweetened soft drinks and type 2 diabetes: systematic review and dose-response meta-analysis of prospective studies. Br J Nutr. 2014 Sep 14;112(5):725-34. doi: 10.1017/S0007114514001329. Epub 2014 Jun 16.

  PMID: 24932880 BACKGROUND

• McGuire S. Scientific Report of the 2015 Dietary Guidelines Advisory Committee. Washington, DC: US Departments of Agriculture and Health and Human Services, 2015. Adv Nutr. 2016 Jan 15;7(1):202-4. doi: 10.3945/an.115.011684. Print 2016 Jan. No abstract available.

  PMID: 26773024 BACKGROUND

• Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.

  PMID: 25231862 BACKGROUND

• Hartstra AV, Bouter KE, Backhed F, Nieuwdorp M. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care. 2015 Jan;38(1):159-65. doi: 10.2337/dc14-0769.

  PMID: 25538312 BACKGROUND

• David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11.

  PMID: 24336217 BACKGROUND

• Korem T, Zeevi D, Suez J, Weinberger A, Avnit-Sagi T, Pompan-Lotan M, Matot E, Jona G, Harmelin A, Cohen N, Sirota-Madi A, Thaiss CA, Pevsner-Fischer M, Sorek R, Xavier R, Elinav E, Segal E. Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples. Science. 2015 Sep 4;349(6252):1101-1106. doi: 10.1126/science.aac4812. Epub 2015 Jul 30.

  PMID: 26229116 BACKGROUND

• Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A, Ben-Yacov O, Lador D, Avnit-Sagi T, Lotan-Pompan M, Suez J, Mahdi JA, Matot E, Malka G, Kosower N, Rein M, Zilberman-Schapira G, Dohnalova L, Pevsner-Fischer M, Bikovsky R, Halpern Z, Elinav E, Segal E. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015 Nov 19;163(5):1079-1094. doi: 10.1016/j.cell.2015.11.001.

  PMID: 26590418 BACKGROUND

• Noble EE, Hsu TM, Jones RB, Fodor AA, Goran MI, Kanoski SE. Early-Life Sugar Consumption Affects the Rat Microbiome Independently of Obesity. J Nutr. 2017 Jan;147(1):20-28. doi: 10.3945/jn.116.238816. Epub 2016 Nov 30.

  PMID: 27903830 BACKGROUND

• Fedorak, R., et al., 546 High Sugar Diets Promote an Inflammatory Microbiota and Reduce Gene Expression Related to Intestinal Barrier Function. Gastroenterology, 2016. 150(4): p. S114-S115.

  BACKGROUND

• Kelly BJ, Gross R, Bittinger K, Sherrill-Mix S, Lewis JD, Collman RG, Bushman FD, Li H. Power and sample-size estimation for microbiome studies using pairwise distances and PERMANOVA. Bioinformatics. 2015 Aug 1;31(15):2461-8. doi: 10.1093/bioinformatics/btv183. Epub 2015 Mar 29.

  PMID: 25819674 BACKGROUND

• Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, McGilvray ID, Allard JP. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology. 2013 Jul;58(1):120-7. doi: 10.1002/hep.26319. Epub 2013 May 14.

  PMID: 23401313 BACKGROUND

• Aagaard K, Petrosino J, Keitel W, Watson M, Katancik J, Garcia N, Patel S, Cutting M, Madden T, Hamilton H, Harris E, Gevers D, Simone G, McInnes P, Versalovic J. The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters. FASEB J. 2013 Mar;27(3):1012-22. doi: 10.1096/fj.12-220806. Epub 2012 Nov 19.

  PMID: 23165986 BACKGROUND

• Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, Owens SM, Betley J, Fraser L, Bauer M, Gormley N, Gilbert JA, Smith G, Knight R. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012 Aug;6(8):1621-4. doi: 10.1038/ismej.2012.8. Epub 2012 Mar 8.

  PMID: 22402401 BACKGROUND

• Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, Huttley GA, Kelley ST, Knights D, Koenig JE, Ley RE, Lozupone CA, McDonald D, Muegge BD, Pirrung M, Reeder J, Sevinsky JR, Turnbaugh PJ, Walters WA, Widmann J, Yatsunenko T, Zaneveld J, Knight R. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010 May;7(5):335-6. doi: 10.1038/nmeth.f.303. Epub 2010 Apr 11. No abstract available.

  PMID: 20383131 BACKGROUND

• Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, Clemente JC, Burkepile DE, Vega Thurber RL, Knight R, Beiko RG, Huttenhower C. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol. 2013 Sep;31(9):814-21. doi: 10.1038/nbt.2676. Epub 2013 Aug 25.

  PMID: 23975157 BACKGROUND

• Kadish AH, Hall DA. A new method for the continuous monitoring of blood glucose by measurement of dissolved oxygen. Clin Chem. 1965 Sep;11(9):869-75. No abstract available.

  PMID: 5835655 BACKGROUND

• Livesey JH, Hodgkinson SC, Roud HR, Donald RA. Effect of time, temperature and freezing on the stability of immunoreactive LH, FSH, TSH, growth hormone, prolactin and insulin in plasma. Clin Biochem. 1980 Aug;13(4):151-5. doi: 10.1016/s0009-9120(80)91040-1.

  PMID: 6778631 BACKGROUND

• Canadian Diabetes, A. Waist Circumference. Available from: https://www.diabetes.ca/diabetes-and-you/healthy-living-resources/weight-management/waist-circumference.

  BACKGROUND

• Wolever TM, Jenkins DJ, Jenkins AL, Josse RG. The glycemic index: methodology and clinical implications. Am J Clin Nutr. 1991 Nov;54(5):846-54. doi: 10.1093/ajcn/54.5.846.

  PMID: 1951155 BACKGROUND

• Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999 Sep;22(9):1462-70. doi: 10.2337/diacare.22.9.1462.

  PMID: 10480510 BACKGROUND

• Phillips DI, Clark PM, Hales CN, Osmond C. Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med. 1994 Apr;11(3):286-92. doi: 10.1111/j.1464-5491.1994.tb00273.x.

  PMID: 8033528 BACKGROUND

• Brisbois TD, Marsden SL, Anderson GH, Sievenpiper JL. Estimated intakes and sources of total and added sugars in the Canadian diet. Nutrients. 2014 May 8;6(5):1899-912. doi: 10.3390/nu6051899.

  PMID: 24815507 BACKGROUND

• Singh GM, Micha R, Khatibzadeh S, Lim S, Ezzati M, Mozaffarian D; Global Burden of Diseases Nutrition and Chronic Diseases Expert Group (NutriCoDE). Estimated Global, Regional, and National Disease Burdens Related to Sugar-Sweetened Beverage Consumption in 2010. Circulation. 2015 Aug 25;132(8):639-66. doi: 10.1161/CIRCULATIONAHA.114.010636. Epub 2015 Jun 29.

  PMID: 26124185 BACKGROUND

• Bleich SN, Wang YC, Wang Y, Gortmaker SL. Increasing consumption of sugar-sweetened beverages among US adults: 1988-1994 to 1999-2004. Am J Clin Nutr. 2009 Jan;89(1):372-81. doi: 10.3945/ajcn.2008.26883. Epub 2008 Dec 3.

  PMID: 19056548 BACKGROUND

• Fernandes J, Su W, Rahat-Rozenbloom S, Wolever TM, Comelli EM. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr Diabetes. 2014 Jun 30;4(6):e121. doi: 10.1038/nutd.2014.23.

  PMID: 24979150 BACKGROUND

• Fernandes J, Wang A, Su W, Rozenbloom SR, Taibi A, Comelli EM, Wolever TM. Age, dietary fiber, breath methane, and fecal short chain fatty acids are interrelated in Archaea-positive humans. J Nutr. 2013 Aug;143(8):1269-75. doi: 10.3945/jn.112.170894. Epub 2013 Jun 5.

  PMID: 23739307 BACKGROUND

• Khan TA, Sievenpiper JL. Controversies about sugars: results from systematic reviews and meta-analyses on obesity, cardiometabolic disease and diabetes. Eur J Nutr. 2016 Nov;55(Suppl 2):25-43. doi: 10.1007/s00394-016-1345-3. Epub 2016 Nov 30.

  PMID: 27900447 BACKGROUND

• Wolf SM, Branum R, Koenig BA, Petersen GM, Berry SA, Beskow LM, Daly MB, Fernandez CV, Green RC, LeRoy BS, Lindor NM, O'Rourke PP, Breitkopf CR, Rothstein MA, Van Ness B, Wilfond BS. Returning a Research Participant's Genomic Results to Relatives: Analysis and Recommendations. J Law Med Ethics. 2015 Fall;43(3):440-63. doi: 10.1111/jlme.12288.

  PMID: 26479555 BACKGROUND

• Malik VS, Pan A, Willett WC, Hu FB. Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis. Am J Clin Nutr. 2013 Oct;98(4):1084-102. doi: 10.3945/ajcn.113.058362. Epub 2013 Aug 21.

  PMID: 23966427 BACKGROUND

• Jayalath VH, de Souza RJ, Ha V, Mirrahimi A, Blanco-Mejia S, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, Jenkins DJ, Sievenpiper JL. Sugar-sweetened beverage consumption and incident hypertension: a systematic review and meta-analysis of prospective cohorts. Am J Clin Nutr. 2015 Oct;102(4):914-21. doi: 10.3945/ajcn.115.107243. Epub 2015 Aug 12.

  PMID: 26269365 BACKGROUND

• Xi B, Huang Y, Reilly KH, Li S, Zheng R, Barrio-Lopez MT, Martinez-Gonzalez MA, Zhou D. Sugar-sweetened beverages and risk of hypertension and CVD: a dose-response meta-analysis. Br J Nutr. 2015 Mar 14;113(5):709-17. doi: 10.1017/S0007114514004383. Epub 2015 Mar 4.

  PMID: 25735740 BACKGROUND

• Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med. 2000 Jul 6;343(1):16-22. doi: 10.1056/NEJM200007063430103.

  PMID: 10882764 BACKGROUND

• Azad MB, Abou-Setta AM, Chauhan BF, Rabbani R, Lys J, Copstein L, Mann A, Jeyaraman MM, Reid AE, Fiander M, MacKay DS, McGavock J, Wicklow B, Zarychanski R. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ. 2017 Jul 17;189(28):E929-E939. doi: 10.1503/cmaj.161390.

  PMID: 28716847 BACKGROUND

• Sievenpiper JL, Khan TA, Ha V, Viguiliouk E, Auyeung R. The importance of study design in the assessment of nonnutritive sweeteners and cardiometabolic health. CMAJ. 2017 Nov 20;189(46):E1424-E1425. doi: 10.1503/cmaj.733381. No abstract available.

  PMID: 29158457 BACKGROUND

• Frankenfeld CL, Sikaroodi M, Lamb E, Shoemaker S, Gillevet PM. High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States. Ann Epidemiol. 2015 Oct;25(10):736-42.e4. doi: 10.1016/j.annepidem.2015.06.083. Epub 2015 Jul 17.

  PMID: 26272781 BACKGROUND

• Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Int J Surg. 2011;9(8):672-7. doi: 10.1016/j.ijsu.2011.09.004. Epub 2011 Oct 13. No abstract available.

  PMID: 22019563 BACKGROUND

• Leung AA, Daskalopoulou SS, Dasgupta K, McBrien K, Butalia S, Zarnke KB, Nerenberg K, Harris KC, Nakhla M, Cloutier L, Gelfer M, Lamarre-Cliche M, Milot A, Bolli P, Tremblay G, McLean D, Tran KC, Tobe SW, Ruzicka M, Burns KD, Vallee M, Prasad GVR, Gryn SE, Feldman RD, Selby P, Pipe A, Schiffrin EL, McFarlane PA, Oh P, Hegele RA, Khara M, Wilson TW, Penner SB, Burgess E, Sivapalan P, Herman RJ, Bacon SL, Rabkin SW, Gilbert RE, Campbell TS, Grover S, Honos G, Lindsay P, Hill MD, Coutts SB, Gubitz G, Campbell NRC, Moe GW, Howlett JG, Boulanger JM, Prebtani A, Kline G, Leiter LA, Jones C, Cote AM, Woo V, Kaczorowski J, Trudeau L, Tsuyuki RT, Hiremath S, Drouin D, Lavoie KL, Hamet P, Gregoire JC, Lewanczuk R, Dresser GK, Sharma M, Reid D, Lear SA, Moullec G, Gupta M, Magee LA, Logan AG, Dionne J, Fournier A, Benoit G, Feber J, Poirier L, Padwal RS, Rabi DM; Hypertension Canada. Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. Can J Cardiol. 2017 May;33(5):557-576. doi: 10.1016/j.cjca.2017.03.005. Epub 2017 Mar 10.

  PMID: 28449828 BACKGROUND

• Dalton M, Finlayson G, Hill A, Blundell J. Preliminary validation and principal components analysis of the Control of Eating Questionnaire (CoEQ) for the experience of food craving. Eur J Clin Nutr. 2015 Dec;69(12):1313-7. doi: 10.1038/ejcn.2015.57. Epub 2015 Apr 8.

  PMID: 25852028 BACKGROUND

• Blom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess L, Ceska R, Roth E, Koren MJ, Ballantyne CM, Monsalvo ML, Tsirtsonis K, Kim JB, Scott R, Wasserman SM, Stein EA; DESCARTES Investigators. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014 May 8;370(19):1809-19. doi: 10.1056/NEJMoa1316222. Epub 2014 Mar 29.

  PMID: 24678979 BACKGROUND

• Logue C, Dowey LRC, Strain JJ, Verhagen H, McClean S, Gallagher AM. Application of Liquid Chromatography-Tandem Mass Spectrometry To Determine Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel Biomarker Approach for Assessing Recent Intakes? J Agric Food Chem. 2017 Jun 7;65(22):4516-4525. doi: 10.1021/acs.jafc.7b00404. Epub 2017 May 24.

  PMID: 28506059 BACKGROUND

• Li S, Zhu Y, Chavarro JE, Bao W, Tobias DK, Ley SH, Forman JP, Liu A, Mills J, Bowers K, Strom M, Hansen S, Hu FB, Zhang C. Healthful Dietary Patterns and the Risk of Hypertension Among Women With a History of Gestational Diabetes Mellitus: A Prospective Cohort Study. Hypertension. 2016 Jun;67(6):1157-65. doi: 10.1161/HYPERTENSIONAHA.115.06747. Epub 2016 Apr 18.

  PMID: 27091899 BACKGROUND

• Nitsche MP, Carreno M. Is honey an effective treatment for acute cough in children? Medwave. 2016 May 30;16 Suppl 2:e6454. doi: 10.5867/medwave.2016.6454. English, Spanish.

  PMID: 27280298 BACKGROUND

• Dias AG, Rousseau D, Duizer L, Cockburn M, Chiu W, Nielsen D, El-Sohemy A. Genetic variation in putative salt taste receptors and salt taste perception in humans. Chem Senses. 2013 Feb;38(2):137-45. doi: 10.1093/chemse/bjs090. Epub 2012 Nov 1.

  PMID: 23118204 BACKGROUND

• Eny KM, Wolever TM, Fontaine-Bisson B, El-Sohemy A. Genetic variant in the glucose transporter type 2 is associated with higher intakes of sugars in two distinct populations. Physiol Genomics. 2008 May 13;33(3):355-60. doi: 10.1152/physiolgenomics.00148.2007. Epub 2008 Mar 18.

  PMID: 18349384 BACKGROUND

• Wolf SM, Lawrenz FP, Nelson CA, Kahn JP, Cho MK, Clayton EW, Fletcher JG, Georgieff MK, Hammerschmidt D, Hudson K, Illes J, Kapur V, Keane MA, Koenig BA, Leroy BS, McFarland EG, Paradise J, Parker LS, Terry SF, Van Ness B, Wilfond BS. Managing incidental findings in human subjects research: analysis and recommendations. J Law Med Ethics. 2008 Summer;36(2):219-48, 211. doi: 10.1111/j.1748-720X.2008.00266.x.

  PMID: 18547191 BACKGROUND

• Food and Drug Administration, Multiple Endpoints in Clinical Trials: Guidance for Industry [Draft Guidance]. 2017.

  BACKGROUND

• Benjamini, Y. and D. Yekutieli, The control of the false discovery rate in multiple testing under dependency. Annals of statistics, 2001: p. 1165-1188.

  BACKGROUND

• Benjamini, Y. and Y. Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the royal statistical society. Series B (Methodological), 1995: p. 289-300.

  BACKGROUND

• Noto, H., et al., Long-term Low-carbohydrate Diets and Type 2 Diabetes Risk: A Systematic Review and Meta-analysis of Observational Studies. Journal of General and Family Medicine, 2016. 17(1): p. 60-70.

  BACKGROUND

• Theytaz F, de Giorgi S, Hodson L, Stefanoni N, Rey V, Schneiter P, Giusti V, Tappy L. Metabolic fate of fructose ingested with and without glucose in a mixed meal. Nutrients. 2014 Jul 15;6(7):2632-49. doi: 10.3390/nu6072632.

  PMID: 25029210 BACKGROUND

• Health Canada, Draft Guidance Document on Food Health Claims Related to the Reduction in Post-Prandial Glycaemic Response F.D. Bureau of Nutritional Sciences, Health Products and Food Branch Editor. 2013. p. 12.

  BACKGROUND

• Ayoub-Charette S, McGlynn ND, Lee D, Khan TA, Blanco Mejia S, Chiavaroli L, Kavanagh ME, Seider M, Taibi A, Chen CT, Ahmed A, Asbury R, Erlich M, Chen YT, Malik VS, Bazinet RP, Ramdath DD, Logue C, Hanley AJ, Kendall CWC, Leiter LA, Comelli EM, Sievenpiper JL. 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. Nutrients. 2023 Feb 28;15(5):1238. doi: 10.3390/nu15051238.

  PMID: 36904237 DERIVED

• Bergwall S, Johansson A, Sonestedt E, Acosta S. High versus low-added sugar consumption for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2022 Jan 5;1(1):CD013320. doi: 10.1002/14651858.CD013320.pub2.

  PMID: 34986271 DERIVED

Related Links

• Diabetes Canada, Diabetes Canada's Position on sugars.
• Health Canada, Summary of Guiding Principles and Recommendations.
• Unhealthy Food and Beverage Marketing to Children Discussion paper for public consultation.
• Chang K, Artificial Sweeteners May Disrupt Body's Blood Sugar Controls. The New York Times, September 17, 2014.
• Kirkey S, Fake sugars linked to obesity, heart disease. National Post, July 17, 2017.
• Faherty S, Artificial Sweeteners May Have Despicable Impacts on Gut Microbes. Scientific American, Nov 26, 2014.
• Sifferlin A, Artificial Sweeteners Are Linked to Weight Gain-Not Weight Loss. Time, July 16 2017.
• Vergano D, Study: Artificial Sweeteners May Trigger Blood Sugar Risks. National Geographic, September 17, 2014.
• Leung W, Sugar substitutes associated with weight gain and health problems, study says. Globe and Mail, July 17, 2017.
• Brait E, More research needed into the effects sugar substitutes have on health. The Toronto Star, July 17, 2017.
• Thompson D, Do Artificial Sweeteners Raise Odds for Obesity? WebMD, July 17, 2017.
• FDA, Multiple Endpoints in Clinical Trials. Guidance for Industry (draft). January 2017. Food and Drug Administration Report.

MeSH Terms

Conditions

Overweight; Obesity; Metabolic Syndrome; Prediabetic State; Diabetes Mellitus; Cardiovascular Diseases; Hypertension

Interventions

Sugar-Sweetened Beverages; Water

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• John L Sievenpiper, MD,PhD,FRCPC

  University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Associate Professor, Staff Physician, Scientist

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: June 1, 2018
• Study Start: May 31, 2018
• Primary Completion: October 15, 2020
• Study Completion: October 15, 2020
• Last Updated: April 29, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)