Sweeteners and Sweetness Enhancers: Prolonged Effects on Health, Obesity and Safety

NCT04226911 | Completed DMC

• 1 other identifier: SWEET WP3
• Study Type: interventional
• Target: 379
• Locations: 4 countries
• Sites: 4

Brief Summary

The aim of this randomised controlled trial (RCT) is to investigate if prolonged consumption of sweetener and sweetness enhancers (S\&SEs) within a healthy diet approach will improve weight loss maintenance and obesity related risk factors, and affect safety markers, compared to sugar. We hypothesize, that:

• Prolonged use of S\&SEs in beverages and food matrices will result in improved body weight control because S\&SEs will increase palatability of the diet and thereby increase compliance to the recommendations for a healthy diet.
• There will be no safety concerns using S\&SEs in the long term. Overweight/obese adults and families where at least one adult (both gender) and one child (both gender) are overweight/obese will be recruited. The majority of measurements will only be conducted in the adult population and some measurement will only be done in sub-groups. The intervention will be performed in four countries: Denmark, Greece, Spain and the Netherlands. The goal is approximately 370 participants - 330 adults (18-65 years of age) and 40 children (6-12 years of age) - will be recruited for the study. All adult participants are first treated by a low energy diet (LED) for 2 months with the aim to reduce body weight (minimum 5% weight loss (WL)), whereas children are treated separately with a conventional weight maintenance (WM) diet, without a specific aim for absolute WL. The participants - both adults and families - are randomized into two different diet interventions for 10 months with or without inclusion of S\&SEs products (foods and drinks). For adults, this period aims at preventing weight re-gain and for children maintaining body mass index (BMI)-for-age. The participants will receive food exchange lists and will be guided by dieticians. The randomization will be stratified by age, sex and BMI. Adults (not participating with children) belonging to the same household and all members of a family will be assigned the same intervention - the randomization will here solely be based on the oldest adult in the family/household. The adult participants are weighed at months 0, 0.5 and 1, and if needed at month 1.5. They are supervised during the WL period at months 0 and 1, and if needed at months 0.5 and 1.5, and throughout the WM period at months 2, 4, 6, 9 and 12. Children will follow a similar, but less strict time schedule (their participation is preferred but not required for all dietician meetings). The main assessment points are the clinical investigation days (CIDs) at month 0 (baseline, start of the WL period), 2 (end of the WL period/start of randomized intervention), 6 (6 months from baseline) and 12 (1 year from baseline).

Conditions

Obesity

Outcome Measures

Primary Outcomes (2)

• Change in body weight (adults)

  Efficacy: Change in body weight will be measured by a calibrated digital scale.

  Up to 1 year.

• Changes in gut microbiota composition (adults)

  Safety: Change in gut microbiota associated with impaired health (e.g. change in microbial beta-diversity and composition) will be measured by fecal samples.

  Up to 1 year.

Secondary Outcomes (34)

• Change in BMI-for-age z-score (children)

  Up to 1 year.

• Changes in waist and hip circumferences (adults and children)

  Up to 1 year.

• Change in body composition (adults and children)

  Up to 1 year.

• Change in blood pressure and heart rate (adults and children)

  Up to 1 year.

• Change in glucose (adults and children)

  Up to 1 year.

Other Outcomes (11)

• Food preferences (adults and children)

  Up to 1 year.

• Perception of S&SEs (adults)

  Up to 1 year.

• Cravings (adults)

  Up to 1 year.

Study Arms (2)

Sweeteners and sweetness enhancers (S&SEs)

EXPERIMENTAL

Healthy diet \< 10 energy % (E%) sugar, foods and drinks with S\&SEs allowed.

Behavioral: S&SEs

Sugar group

ACTIVE COMPARATOR

Healthy diet, \< 10 E% sugar, foods and drinks with S\&SEs not allowed.

Behavioral: Sugar

Interventions

S&SEs BEHAVIORAL

S\&SEs: As many sugar-containing products in the diet as possible should be replaced with S\&SE-containing products. To ensure that a certain amount of S\&SE products is consumed every day, a fixed minimum amount of units for each individual is planned.

Sweeteners and sweetness enhancers (S&SEs)

Sugar BEHAVIORAL

Sugar group: In the sugar group it is allowed to consume up to a certain number of units of sugar-containing products each day, corresponding to \< 10 E% added sugar. The sugar group is not allowed to consume any S\&SE products.

Sugar group

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-65 years.
• BMI: ≥25.0 kg/m2 (no upper limit). For women: Use of contraceptive methods and not wishing/planning to become pregnant in the 1 year of the intervention study.
• Regular consumption of sugar-containing/sugar-sweetened products.
• Able to participate in CIDs and dietician meetings during normal working hours.
• Motivation and willingness to be randomized to any of the two groups and to do the best to follow the given protocol.
• Age: 6-12 years.
• BMI-for-age: \>85th percentile (no upper limit).
• Able to participate in CIDs during normal working hours.
• Motivation and willingness to be randomized to any of the two groups and to do the best to follow the given protocol.

You may not qualify if:

• Weight change (increase or decrease) \>5% during the past 2 months prior to the study.
• Surgical treatment of obesity.
• Blood donation \< 3 month prior to study.
• Change in smoking habits during the last month. Smoking is allowed provided subjects have not recently changed habits. However, smoking status is monitored throughout the study and used as a confounding variable.
• Regularly drinking \>21 alcoholic units per week (men), or \>14 alcoholic units/week (women).
• Intensive physical training (\>10 hours of per week).
• Self-reported eating disorders.
• Intolerance and allergies expected to interfere with the study.
• Self-reported drug abuse within the previous 12 months.
• Night- or shift work that ends later than 11 PM.
• For women: Pregnancy, lactation.
• Persons who do not have access to either (mobile) phone or internet (this is necessary when being contacted by the study personnel during the study).
• Insufficient communication with national language.
• Inability, physically or mentally, to comply with the procedures required by the study protocol as evaluated by the daily study manager, site-PI, PI or clinical responsible
• Participant's general condition contraindicates continuing the study as evaluated by the daily study manager, site-PI, PI or clinical responsible.

Sponsors & Collaborators

• Anne Birgitte Raben: lead
• Harokopio University: collaborator
• University of Navarra: collaborator
• University of Liverpool: collaborator
• Maastricht University: collaborator
• University of Leeds: collaborator
• Wageningen University: collaborator
• European Clinical Research Infrastructure Network: collaborator
• University of Surrey: collaborator
• Bioiatriki Idiotiko Polyiatreio Iatpikh Anonymos Etairia: collaborator
• NetUnion SARL: collaborator
• Pectolite GMBH: collaborator

Study Sites (4)

Department of Nutrition, Exercise and Sports

Frederiksberg, 1958, Denmark

Location

Harokopio University

Kallithea-Athens, Greece

Location

University of Maastricht

Maastricht, 6200, Netherlands

Location

University of Navarra

Pamplona, 31008, Spain

Location

Related Publications (3)

• Pang MD, Kjolbaek L, Bastings JJAJ, Andersen SSH, Umanets A, Sost MM, Navas-Carretero S, Reppas K, Finlayson G, Hodgkins CE, Del Alamo M, Lam T, Moshoyiannis H, Feskens EJM, Adam TCM, Goossens GH, Halford JCG, Harrold JA, Manios Y, Martinez JA, Blaak EE, Raben A. Effect of sweeteners and sweetness enhancers on weight management and gut microbiota composition in individuals with overweight or obesity: the SWEET study. Nat Metab. 2025 Oct;7(10):2083-2098. doi: 10.1038/s42255-025-01381-z. Epub 2025 Oct 7.

  PMID: 41057614 DERIVED

• Pang MD, Bastings JJAJ, Op den Kamp-Bruls YMH, Harrold JA, Kjolbaek L, Halford JCG, Adam TCM, Raben A, Schrauwen-Hinderling VB, Goossens GH, Blaak EE. The effect of weight loss on whole-body and tissue-specific insulin sensitivity and hepatic lipid content and composition: SWEET substudy. Obesity (Silver Spring). 2023 Jul;31(7):1745-1754. doi: 10.1002/oby.23773.

  PMID: 37368517 DERIVED

• Kjolbaek L, Manios Y, Blaak EE, Martinez JA, Feskens EJM, Finlayson G, Andersen SSH, Reppas K, Navas-Carretero S, Adam TC, Hodgkins CE, Del Alamo M, Lam T, Moshoyiannis H, Halford JCG, Harrold JA, Raben A. Protocol for a multicentre, parallel, randomised, controlled trial on the effect of sweeteners and sweetness enhancers on health, obesity and safety in overweight adults and children: the SWEET project. BMJ Open. 2022 Oct 12;12(10):e061075. doi: 10.1136/bmjopen-2022-061075.

  PMID: 36223962 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Sugars

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 18, 2019
• First Posted: January 13, 2020
• Study Start: January 30, 2020
• Primary Completion: October 6, 2022
• Study Completion: October 6, 2022
• Last Updated: November 1, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: See above in the plan description.
• Access Criteria: See above in the plan description.

Locations

GR (1); DK (1); ES (1); NL (1)