Meta-analysis of Low-calorie Sweetened Beverages and Cardiometabolic Outcomes

February 21, 2020 updated by: John Sievenpiper, University of Toronto

Changing or Substituting Low-calorie Sweetened Beverages for Sugar-Sweetened Beverages or Water and Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies

We propose to conduct a systematic literature review and meta-analysis to assess the association of low-calorie sweetened beverages (LCSBs) on cardiometabolic outcomes in prospective cohort studies. We will be using methodological approaches (change in LCSBs intake, and/or substitution analysis) that attempt to overcome the issue of reverse causality associated with studies of LCSBs and cardiometabolic disease. Ten cardiometabolic outcomes will be assessed:

  1. Global adiposity - body weight
  2. Global adiposity - BMI
  3. Global adiposity - body fat
  4. Abdominal adiposity - waist circumference
  5. Overweight/obesity incidence
  6. Metabolic syndrome incidence
  7. Type 2 diabetes incidence
  8. Cardiovascular disease incidence
  9. Cardiovascular disease mortality
  10. Total mortality

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Background:

Low-calorie sweetened beverages (LCSBs) may provide a potentially important means for displacing excess calories from free sugars in the diet. However, prospective cohort studies suggest that the use of LCSBs may contribute to an increased risk of obesity and diabetes. These findings are likely due to methodological limitations of study design and analysis that do not account for reverse causality, where higher risk of cardiometabolic outcomes may lead to people to switch to LCSBs. There is a need for a systematic review and meta-analysis (SRMA) of prospective cohort studies to overcome these methodological limitations.

Objective:

We will conduct a SRMA of prospective cohort studies in human subjects that have assessed cardiometabolic outcomes using two analytical strategies:

i) Assessment of change in intake of LCSBs with change in outcome (change analysis)

ii) Assessment of substitution of LCSBs for sugar-sweetened beverages (SSBs) or water.

Design:

We will conduct a SRMA according to the Cochrane Handbook for Systematic Reviews of Interventions and report the findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines.

Data sources:

MEDLINE, EMBASE, and the Cochrane Library databases will be searched using appropriate search terms, supplemented by hand searches of references of included studies. No restriction will be placed on language.

Study selection:

Prospective cohort studies reporting (a) change analysis (change in intake of LCSBs with the change in outcome), and/or (b) substitution analysis (substitution of SSBs with LCSBs or water) with more than 1-year of follow-up will be used. Cohort studies that have a follow-up duration <1 year, do not report assessment of exposure, or do not provide viable outcome data by level of exposure will be excluded.

Data extraction

Two or more investigators will independently extract relevant data and assess risk of bias using the Newcastle-Ottawa Scale (NOS) for prospective cohorts. All disagreements will be resolved by consensus. Risk ratios (RRs), odds ratios (ORs) and hazard ratios (HRs) for clinical outcomes in the prospective cohort studies will be extracted or derived from clinical event data across exposure categories.

Outcomes:

Ten cardiometabolic health outcomes will be assessed:

  1. Global adiposity - body weight
  2. Global adiposity - BMI
  3. Global adiposity - body fat
  4. Abdominal adiposity - waist circumference
  5. Overweight/obesity incidence
  6. Metabolic syndrome incidence
  7. Type 2 diabetes incidence
  8. Cardiovascular disease incidence
  9. Cardiovascular disease mortality
  10. Total mortality

Data synthesis:

Natural log-transformed RRs or HRs of clinical outcomes, comparing extreme quantiles (the highest exposure versus the lowest exposure or reference group), will be pooled separately using the generic inverse variance method with random effects models and expressed as RRs with 95% confidence intervals (CIs). Heterogeneity will be tested by Cochran's Q statistic and quantified by the I2 statistic. To explore sources of heterogeneity, we will conduct sensitivity analyses, in which each study is systematically removed. If ≥10 cohort comparisons are available, then we will perform an a-priori subgroup analyses by meta-regression for follow-up (<10 years vs. ≥10 years), sex (males vs. females, males vs. mixed, females vs. mixed), study quality (NOS <6 vs. ≥6) and funding source. Significant unexplained heterogeneity will be investigated by additional post hoc subgroup analyses and influence analysis. A study will be considered influential if it changes the direction or significance of the pooled estimates or the evidence of heterogeneity. Dose response estimates will be pooled using one-stage linear mixed model. 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, we 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 overall certainty of evidence for each outcome will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (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 to the role of the LCSBs role as a replacement strategy for SSBs, strengthening the evidence-base for guidelines and improving health outcomes by educating healthcare providers and patients, stimulating industry innovation, and guiding future research design.

Study Type

Observational

Enrollment (Anticipated)

1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5C 2T2
        • Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Varies

Description

Inclusion Criteria:

  • Prospective cohorts studies
  • Duration: more than 1 year follow-up
  • Exposure: LCSBs
  • Change analysis or substitution analysis of exposure

Exclusion Criteria:

  • Non-human studies
  • Less than 1 year follow-up
  • Analysis of baseline or prevalent intake of exposure only

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Low-calorie Sweetened Beverages (LCSBs)
Beverages exclusively using zero-energy (e.g., acesulfame-potassium, aspartame, cyclamate, saccharin, sucralose, advantame, neotame), and /or reduced-energy food additives (e.g., stevia, monk fruit).
Other: Change in LCSBs Intake
Effect of changing LCSBs intake
Other: Substitute LCSBs for SSBs or Water
Effect of substituting LCSBs for SSBs or Water

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Global measures of adiposity with established clinical relevance - body weight
Time Frame: More than 1 year
Change in body weight
More than 1 year
Global measures of adiposity with established clinical relevance - BMI
Time Frame: More than 1 year
Change in body mass index (BMI)
More than 1 year
Global measures of adiposity with established clinical relevance - body fat
Time Frame: More than 1 year
Change in body fat
More than 1 year
Abdominal measures of adiposity with established clinical relevance - waist circumference
Time Frame: More than 1 year
Change in waist circumference
More than 1 year
Overweight/obesity incidence
Time Frame: More than 1 year
Risk ratio of Overweight/obesity incidence
More than 1 year
Metabolic syndrome incidence
Time Frame: More than 1 year
Risk ratio of metabolic syndrome incidence
More than 1 year
Type 2 diabetes incidence
Time Frame: More than 1 year
Risk ratio of type 2 diabetes incidence
More than 1 year
Cardiovascular disease incidence
Time Frame: More than 1 year
Risk ratio of cardiovascular disease incidence
More than 1 year
Cardiovascular disease mortality
Time Frame: More than 1 year
Risk ratio of Cardiovascular disease mortality
More than 1 year
Total mortality
Time Frame: More than 1 year
Risk ratio of total mortality
More than 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 16, 2019

Primary Completion (Anticipated)

March 1, 2020

Study Completion (Anticipated)

May 1, 2020

Study Registration Dates

First Submitted

January 23, 2020

First Submitted That Met QC Criteria

January 28, 2020

First Posted (Actual)

January 29, 2020

Study Record Updates

Last Update Posted (Actual)

February 25, 2020

Last Update Submitted That Met QC Criteria

February 21, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DNSG-LCSBs (cohorts)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cardiovascular Diseases

Clinical Trials on Change in LCSBs Intake

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ghana

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe