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Research

Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies

Meghan B. Azad, Ahmed M. Abou-Setta, Bhupendrasinh F. Chauhan, Rasheda Rabbani, Justin Lys, Leslie Copstein, Amrinder Mann, Maya M. Jeyaraman, Ashleigh E. Reid, Michelle Fiander, Dylan S. MacKay, Jon McGavock, Brandy Wicklow and Ryan Zarychanski
CMAJ July 17, 2017 189 (28) E929-E939; DOI: https://doi.org/10.1503/cmaj.161390
Meghan B. Azad
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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  • For correspondence: meghan.azad@umanitoba.ca
Ahmed M. Abou-Setta
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Bhupendrasinh F. Chauhan
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Rasheda Rabbani
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Justin Lys
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Leslie Copstein
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Amrinder Mann
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Maya M. Jeyaraman
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Ashleigh E. Reid
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Michelle Fiander
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Dylan S. MacKay
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Jon McGavock
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Brandy Wicklow
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Ryan Zarychanski
George & Fay Yee Centre for Healthcare Innovation (Azad, Abou-Setta, Chauhan, Rabbani, Lys, Copstein, Mann, Jeyaraman, Fiander, Zarychanski); Children’s Hospital Research Institute of Manitoba (Azad, Chauhan, McGavock, Wicklow); Department of Pediatrics and Child Health (Azad, McGavock, Wicklow); Department of Community Health Sciences (Abou-Setta); College of Pharmacy (Chauhan); Max Rady College of Medicine (Reid); Department of Human Nutritional Sciences (Azad, MacKay); Department of Internal Medicine (Zarychanski), University of Manitoba; Department of Hematology and Medical Oncology, CancerCare Manitoba (Zarychan-ski), Winnipeg, Man.
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Abstract

BACKGROUND Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects.

METHODS We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points.

RESULTS From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference −0.37 kg/m2; 95% confidence interval [CI] −1.10 to 0.36; I2 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I2 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome.

INTERPRETATION Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749

  • Accepted March 10, 2017.
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Canadian Medical Association Journal: 189 (28)
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Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies
Meghan B. Azad, Ahmed M. Abou-Setta, Bhupendrasinh F. Chauhan, Rasheda Rabbani, Justin Lys, Leslie Copstein, Amrinder Mann, Maya M. Jeyaraman, Ashleigh E. Reid, Michelle Fiander, Dylan S. MacKay, Jon McGavock, Brandy Wicklow, Ryan Zarychanski
CMAJ Jul 2017, 189 (28) E929-E939; DOI: 10.1503/cmaj.161390

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Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies
Meghan B. Azad, Ahmed M. Abou-Setta, Bhupendrasinh F. Chauhan, Rasheda Rabbani, Justin Lys, Leslie Copstein, Amrinder Mann, Maya M. Jeyaraman, Ashleigh E. Reid, Michelle Fiander, Dylan S. MacKay, Jon McGavock, Brandy Wicklow, Ryan Zarychanski
CMAJ Jul 2017, 189 (28) E929-E939; DOI: 10.1503/cmaj.161390
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