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

Azad, Meghan B.; Abou‐Setta, Ahmed M; Chauhan, Bhupendrasinh F; Rabbani, Rasheda; Lys, Justin; Copstein, Leslie; Mann, Amrinder Singh; Jeyaraman, Maya M.; Reid, Ashleigh; Fiander, Michelle; MacKay, Dylan; McGavock, Jon; Wicklow, Brandy; Zarychanski, Ryan

doi:10.1503/cmaj.161390

Cited by 271 publications

(211 citation statements)

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“…In a recent systematic review and meta-analysis on the topic of artificial sweeteners and cardiometabolic health, the authors concluded that routine consumption of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. 10 Similarly, previous publications have reported an association between high diet soft drink consumption and worse cardiovascular profile in patients with diabetes. 8,9 For instance, in a large, cross-sectional study of youths with type 1 diabetes mellitus in the United Diet soft drink and diabetic retinopathy 5…”

Section: Discussionmentioning

confidence: 79%

“…8,9 To address the health consequences associated with regular soft drink consumption, artificially sweetened 'diet' soft drinks have been marketed as a healthier alternative due to their lack of sugar. However, several studies including a recent systematic review and meta-analysis, 10 have linked diet soft drinks with poor cardiovascular outcomes. 3,[11][12][13][14][15][16] The population-based Multi-Ethnic Study of Atherosclerosis (MESA), for example, found that a daily consumption of diet soda was associated with 36% and 67% greater relative risks of incident metabolic syndrome and type 2 diabetes mellitus, respectively, compared with non-consumption.…”

Section: Introductionmentioning

confidence: 99%

“…12 Therefore, welldesigned, longitudinal studies to determine whether diet soft drinks are healthy substitutes for regular soft drinks are required. 10,16 Finally, previous prospective analyses of the association between diet soft drink consumption and metabolic syndrome suggest that the association between diet soft drinks and vascular events may be largely mediated by adiposity and fasting glucose. 12 Although we controlled for BMI, blood sugar, BP and lipids, as well as intake of total calories, these variables may still be on the pathway linking diet soft drink consumption with vascular disease risk.…”

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confidence: 96%

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Diet soft drink is associated with increased odds of proliferative diabetic retinopathy

Fenwick

Gan

Sabanayagam

et al. 2018

Clinical Exper Ophthalmology

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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 96%

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Diet soft drink is associated with increased odds of proliferative diabetic retinopathy

Fenwick

Gan

Sabanayagam

et al. 2018

Clinical Exper Ophthalmology

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“…Subgroup analyses were planned a priori to explore heterogeneity and determine summary effect estimates in several prespecified strata including gender, age, and body composition at baseline; type of NNS; type of comparator; study quality; NNS dose and duration of exposure; and follow-up. 27 …”

Section: Resultsmentioning

confidence: 99%

“…27 Our primary research question was "Does exposure to NNSs during gestation, infancy, or childhood have adverse long-term metabolic effects? "…”

Section: Methodsmentioning

confidence: 99%

Early Exposure to Nonnutritive Sweeteners and Long-term Metabolic Health: A Systematic Review

Reid¹,

Chauhan

Rabbani

et al. 2016

Pediatrics

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CONTEXT: Nonnutritive sweetener (NNS) consumption is increasing among children, yet its long-term health impact is unclear, particularly when exposure occurs during early life.OBJECTIVE: To synthesize evidence from prospective studies evaluating the association of early-life NNS exposure and long-term metabolic health.DATA SOURCES: Medline, Embase, and Cochrane Library (inception to July 2015). STUDY SELECTION:We aimed to include randomized controlled trials (RCTs) evaluating NNSbased interventions and prospective cohort studies reporting NNS exposure among pregnant women, infants, or children (<12 years of age), with a minimum study duration of 6 months. DATA EXTRACTION:The primary outcome was BMI; secondary outcomes included growth velocity, overweight/obesity, adiposity, and adverse metabolic effects. Study quality and risk of bias were evaluated using validated assessment tools. RESULTS:We identified 6 eligible cohort studies and 2 RCTs (n = 15 641 children). Half of the cohorts reported increasing weight gain or fat mass accumulation with increasing NNS intake, and pooled data from 2 cohorts showed a significant correlation with BMI gain (weighted mean correlation 0.023, 95% confidence interval 0.006 to 0.041). RCTs reported contradictory effects on weight change in children receiving NNSs. No eligible studies evaluated prenatal or infant NNS exposure.LIMITATIONS: Meta-analysis was limited because of the small number of eligible studies and heterogeneity of populations and outcomes. CONCLUSIONS:There is limited and inconsistent evidence of the long-term metabolic effects of NNS exposure during gestation, infancy, and childhood. Further research is needed to inform recommendations for the use of NNSs in this sensitive population.

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Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort

et al. 2020

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IMPORTANCE Ultraprocessed foods (UPF) are widespread in Western diets. Their consumption has been associated in recent prospective studies with increased risks of all-cause mortality and chronic diseases such as cancer, cardiovascular diseases, hypertension, and dyslipidemia; however, data regarding diabetes are lacking.OBJECTIVE To assess the associations between consumption of UPF and risk of type 2 diabetes (T2D). DESIGN, SETTING, AND PARTICIPANTSIn this population-based prospective cohort study, 104 707 participants aged 18 years or older from the French NutriNet-Santé cohort (2009-2019) were included. Dietary intake data were collected using repeated 24-hour dietary records (5.7 per participant on average), designed to register participants' usual consumption for more than 3500 different food items. These were categorized according to their degree of processing by the NOVA classification system. MAIN OUTCOMES AND MEASURESAssociations between UPF consumption and risk of T2D were assessed using cause-specific multivariable Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors).RESULTS A total of 104 707 participants (21 800 [20.8%] men and 82 907 [79.2%] women) were included. Mean (SD) baseline age of participants was 42.7 (14.5) years. Absolute T2D rates in the lowest and highest UPF consumers were 113 and 166 per 100 000 person-years, respectively. Consumption of UPF was associated with a higher risk of T2D (multi-adjusted hazard ratio [HR] for an absolute increment of 10 in the percentage of UPF in the diet, 1.15; 95% CI, 1.06-1.25; median follow-up, 6.0 years; 582 252 person-years; 821 incident cases). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet, for other metabolic comorbidities (HR, 1.13; 95% CI, 1.03-1.23), and for weight change (HR, 1.13; 95% CI, 1.01-1.27). The absolute amount of UPF consumption (grams per day) was consistently associated with T2D risk, even when adjusting for unprocessed or minimally processed food intake (HR for a 100 g/d increase, 1.05; 95% CI, 1.02-1.08). CONCLUSIONS AND RELEVANCEIn this large observational prospective study, a higher proportion of UPF in the diet was associated with a higher risk of T2D. Even though these results need to be confirmed in other populations and settings, they provide evidence to support efforts by public health authorities to recommend limiting UPF consumption.TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03335644

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

Cited by 271 publications

References 73 publications

Diet soft drink is associated with increased odds of proliferative diabetic retinopathy

Diet soft drink is associated with increased odds of proliferative diabetic retinopathy

Early Exposure to Nonnutritive Sweeteners and Long-term Metabolic Health: A Systematic Review

Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort

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