Overview

This trial is active, not recruiting.

Conditions body weight, obesity, overweight, adiposity, obesity, abdominal
Treatment fructose-containing sugars
Sponsor John Sievenpiper
Collaborator American Society for Nutrition
Start date March 2015
End date March 2017
Trial size 1 participant
Trial identifier NCT02558920, ASN-Sugars 2015

Summary

Sugars have been implicated in the epidemics of overweight and obesity. This view is supported by lower quality evidence from ecological observations, animal models, and select human trials. Higher level evidence from controlled trials and prospective cohort studies has been inconclusive. Whether sugars contribute to weight gain or increases in adiposity independent of their calories and whether important food sources other than SSBs are associated with a higher risk of overweight and obesity remain unclear. To address the uncertainties, the investigators propose to conduct a series of systematic reviews and meta-analyses of the totality of the evidence from controlled trials and prospective cohort studies to distinguish the contribution of fructose-containing sugars and important food sources of added sugars (SSBs, pure fruit juice, cakes/sweets, yogurt, cereals, etc) from that of energy in the development of overweight and obesity. The findings generated by this proposed knowledge synthesis will help improve the health of consumers through informing evidence-based guidelines and improving health outcomes by educating healthcare providers and patients, stimulating industry innovation, and guiding future research design

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective

Primary Outcomes

Measure
Incident overweight or obesity
time frame: Up to 20 years

Secondary Outcomes

Measure
Global measures of adiposity with established clinical relevance - body weight
time frame: Up to 20 years
Global measures of adiposity with established clinical relevance - BMI
time frame: Up to 20 years
Global measures of adiposity with established clinical relevance - percentage body fat
time frame: Up to 20 years
Regional measures of adiposity with established clinical relevance - waist circumference
time frame: Up to 20 years
Regional measures of adiposity with established clinical relevance - waist-to-hip ratio
time frame: Up to 20 years

Eligibility Criteria

Male or female participants of any age.

Inclusion Criteria for controlled trials: - Trials in humans - Oral fructose-containing sugars intervention - Presence of an adequate comparator (substitution, addition, subtraction, or ad libitum control) - Diet duration >=2 weeks - viable outcome data Inclusion Criteria for prospective cohort studies: - Prospective cohort studies or case-cohort studies - Duration >= 1 year - Assessment of the exposure of fructose-containing sugars or important food sources - Ascertainment of viable data by level of exposure Exclusion Criteria for controlled trials: - non-human trials - observational studies - IV or parenteral fructose-containing sugars - lack of suitable comparator diet (i.e. a comparator arm that contains substantial fructose-containing sugars) - Diet duration <2-weeks - no viable outcome data Exclusion Criteria for prospective cohort studies: - Ecological, cross-sectional, and retrospective observational studies, clinical trials, and non-human studies - Duration < 1 year - No assessment of exposures of fructose-containing sugars or important food sources - No ascertainment viable clinical outcome data by level of exposure

Additional Information

Official title Relation of Fructose-Containing Sugars and Important Food Sources of These Sugars With Markers of Adiposity and Risk of Obesity: A Series of Systematic Reviews and Meta-Analyses of Controlled Trials and Prospective Cohort Studies
Principal investigator John Sievenpiper, MD,PhD,FRCPC
Description Background: Sugars have emerged as one of the most important public health concerns. Attention has focused squarely on fructose-containing sugars (fructose, sucrose, high fructose corn syrup, honey, etc). Collectively, these sugars have been indicted as drivers of the obesity epidemic and its and its downstream cardiometabolic complications. This special view rests on the unique metabolic and endocrine responses to fructose. Unlike glucose, fructose is thought to bypasses negative feedback control acting as an unregulated substrate for de novo lipogenesis and impair satiety signaling resulting in weight gain. In support of these mechanisms, animal models, low-quality ecological studies, and select human trials of overfeeding at levels of exposure far beyond population intakes have reported adverse metabolic effects of sugars. Higher level evidence from systematic reviews and meta-analyses of controlled trials, however, suggests that any effects of sugars are mediated by excess calories rather than the sugars per se. There is also evidence that not all food sources of these sugars are associated equally with obesity. While sugars-sweetened beverages (SSBs) have shown an adverse association with body weight, markers of adiposity and obesity, other important food sources of sugars such as pure fruit juice, cereals, yogurts, and even cakes/sweets have shown either no association or a beneficial association. It remains unclear whether sugars contribute to weight gain or increases in adiposity independent of their calories and whether important food sources other than SSBs are associated with a higher risk of overweight and obesity. Need for proposed research: High quality systematic reviews and meta-analyses of controlled trials and prospective cohort studies represent the highest level of evidence to support dietary guidelines and public health policy development. As dietary guidelines and public health policy have shifted toward food and dietary-pattern based recommendations, there is an urgent need for systematic reviews and meta-analyses comparing the role of different food sources of sugars in the development of overweight and obesity. Objective: The investigators will conduct a series of American Society of Nutrition (ASN)-commissioned systematic reviews and meta-analyses to (1) distinguish the effect of fructose-containing sugars from that of energy on body weight and markers of adiposity in controlled trials and (2) compare different sugars (total sugars, sucrose, fructose) and food sources of added/free sugars (SSBs, pure fruit juice, yoghurt, cereals, cakes, pastries, sweets, etc) in their associations with incident overweight/obesity and changes in weight and markers of adiposity in prospective cohort studies. Design: Each systematic review and meta-analysis will be conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data sources: MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials (Clinical Trials; CENTRAL) will be searched using appropriate search terms supplemented by hand searches of references of included studies. Study selection: The investigators will include either controlled dietary trials or prospective cohort studies. Randomized and non-randomized controlled trials will be included if they are >= 2-weeks duration and assess the effect of fructose-containing sugars (fructose, sucrose, high fructose corn syrup, honey, etc) on incident overweight/obesity, body weight or markers of adiposity. To allow for the separation of the effect of sugars from that of energy, 4 trial designs will be considered: (1) 'substitution' trials, in which fructose-containing sugars added to foods and beverages are compared with other macronutrient sources (usually starch or other sugars) under energy matched conditions; (2) 'addition' trials, in which fructose-containing sugars supplement a diet with excess energy compared to the same diet alone without the excess energy; (3) 'subtraction' trials, in which energy from fructose-containing sugars (usually in the form of sugars-sweetened beverages) is reduced by displacing it with water and/or no-calorie or low-calorie sweeteners or by eliminating it altogether from the background diet; and (4) 'ad libitum' trials, in which energy from fructose-containing sugars are freely replaced with other sources of energy (usually complex carbohydrates or fat) without any strict control of either the study foods or the background diet. Prospective cohort studies will be included if they are >= 1-year duration and assess the relation of different sugars (total sugars, sucrose, fructose) or important food sources of added/free sugars (SSBs, pure fruit juice, cakes/sweets, cereals, yoghurt, etc.) with incident overweight/obesity or changes in body weight or markers of adiposity. Data extraction: Two or more investigators will independently extract relevant data and assess risk of bias using the Cochrane Risk of Bias Tool. All disagreements will be resolved by consensus. Standard computations and imputations will be used to derive missing variance data. Outcomes: Three sets of outcomes will be assessed: (1) incidence of overweight/obesity, (2) measures of global adiposity (body weight, body mass index (BMI), body fat), (3) measures of abdominal adiposity (waist circumference, waist-to-hip ratio). Data synthesis: Risk ratios will be pooled for incident overweight/obesity and mean differences for measures of global and abdominal adiposity using the generic inverse variance method. Random-effects models will be used even in the absence of statistically significant between-study heterogeneity, as they yield more conservative summary effect estimates in the presence of residual heterogeneity. Fixed-effects models will only be used where there is <5 included studies. Paired analyses will be applied for crossover trials. Heterogeneity will be assessed by the Cochran Q statistic and quantified by the I2 statistic. To explore sources of heterogeneity, the investigators will conduct sensitivity analyses, in which each study is systematically removed. If there are >=10 studies, then the investigators will also explore sources of heterogeneity by a priori subgroup analyses by age (children [=<18 years of age], adults), health status (metabolic syndrome/diabetes, overweight, normal weight), comparator, fructose form (solid, liquid, or mixed), dose (=<10% energy, >10%), baseline measurements, randomization, study design (parallel, crossover), energy balance (positive, neutral, negative), follow-up (=<8-weeks, >8-weeks), and risk of bias. Meta-regression analyses will assess the significance of categorical and continuous subgroups analyses. When >=10 studies are available, publication bias will be investigated by inspection of funnel plots and formal testing using the Egger and Begg tests. If publication bias is suspected, then the investigators will attempt to adjust for funnel plot asymmetry by imputing the missing study data using the Duval and Tweedie trim and fill method. Evidence Assessment: The strength of the evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Knowledge translation plan: The results will be disseminated through interactive presentations at local, national, and international scientific meetings and publication in high impact factor journals. Target audiences will include the public health and scientific communities with interest in nutrition, diabetes, obesity, and cardiovascular disease. Feedback will be incorporated and used to improve the public health message and key areas for future research will be defined. Applicant/Co-applicant Decision Makers will network among opinion leaders to increase awareness and participate directly as committee members in the development of future guidelines. Significance: The proposed project will aid in knowledge translation related to the role of dietary fructose-containing sugars and important food sources of these sugars in the development of overweight and obesity, strengthening the evidence-base for guidelines and improving health outcomes by educating healthcare providers and patients, stimulating industry innovation, and guiding future research design.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by University of Toronto.