SucroMet Nutritional Intervention Trial

Official title

SucroMet' Nutritional Intervention: Study of the Metabolic Impact of Sucrose (Natural Sugar) and Sucralose (Artificial Sweetener) Intake at Different Doses and Modes of Consumption in Adults With Normal Weight, Overweight, and Obesity

Overview

SucroMet is designed to evaluate how adding two commonly used sweeteners-sucrose (table sugar) and sucralose (a low-calorie sweetener)-at low and high doses may influence glucose regulation, including insulin resistance and fasting plasma glucose, in adults aged 18 to 65 years with normal weight, overweight, or obesity. The low-dose intervention consists of 5% of the Estimated Energy Requirement (EER) from sucrose or 5 sucralose tablets per day (approximately 33.35 mg/day of sucralose). The high-dose intervention consists of 10% of EER from sucrose or 10 sucralose tablets per day (approximately 66.7 mg/day of sucralose). These doses maintain the planned 1:2 exposure ratio between the low- and high-dose intervention groups. Before the intervention begins, participants' habitual dietary intake is assessed and, when necessary, minor dietary adjustments are made to support a stable overall eating pattern while maintaining energy intake. Participants then complete a four-week run-in period during which these recommendations are followed, and dietary records are used to verify dietary stability before the intervention starts. Participants will consume the assigned sweetener incorporated into foods or beverages that they already consume as part of their habitual diet, without substantial changes to their usual eating patterns. The intervention includes two consecutive 12-week phases, one involving solid food intake and the other involving liquid intake, separated by a two-week washout period. This design allows evaluation of the effects of sweetener type, dose, and mode of consumption. The primary outcomes are changes in glucose regulation, including fasting plasma glucose and insulin resistance assessed by HOMA-IR. Secondary outcomes include changes in body composition, anthropometric measurements, blood pressure, routine biochemical parameters, gut microbiota composition, DNA methylation patterns in peripheral blood cells, and biomarkers related to inflammation, oxidative stress, and metabolomic profiles measured in blood and urine. Participants will attend scheduled study visits for anthropometric assessments, dietary evaluations, and biological sample collection. Blood, urine, and stool samples will be obtained at baseline and after each intervention phase. The study aims to address the following questions: 1. Do metabolic responses to sucrose and sucralose, including changes in insulin resistance (HOMA-IR) and fasting plasma glucose, differ according to participants' body mass index (BMI)? 2. Do low and high doses of sucrose and sucralose differentially affect glucose regulation, body composition, and metabolic health? 3. Does the mode of intake (solid versus liquid) influence changes in gut microbiota composition? 4. Are changes in DNA methylation patterns in peripheral blood cells associated with the consumption of sucrose and sucralose at different doses and in different forms? 5. Do different doses of sucrose and sucralose influence biomarkers related to inflammation, oxidative stress, and metabolomic profiles?

Detailed description

SucroMet is a randomized controlled nutritional intervention designed to investigate the metabolic effects of sucrose and sucralose consumption under conditions that closely reflect habitual dietary practices. The study aims to determine whether sweetener type, dose, and mode of consumption influence glucose regulation and related biological pathways in adults with normal weight, overweight, or obesity. The study evaluates the independent and combined effects of sweetener type, dose, and mode of consumption. By maintaining overall dietary habits and energy intake as stable as possible throughout the intervention, the design aims to isolate the specific contribution of sweetener exposure to observed metabolic changes.

A distinctive feature of the study is the comparison of sweeteners administered in both solid and liquid forms, allowing assessment of whether the food matrix modifies physiological responses. The study also examines whether responses differ according to adiposity status, enabling exploration of potential interactions between sweetener exposure and body mass index.

Beyond glucose regulation, the study investigates several biological pathways that may contribute to individual variability in response to sweetener intake, including gut microbiota composition, epigenetic regulation, inflammation, oxidative stress, and systemic metabolic profiles. The integration of clinical, biochemical, molecular, and metabolomic data is intended to provide a comprehensive characterization of the biological effects associated with long-term sweetener consumption.

The results are expected to improve understanding of the metabolic consequences of sucrose and sucralose intake and to contribute evidence relevant to future nutritional recommendations and public health strategies.

Interventions

• Behavioral Sucrose- Low dose
  Sucrose administered at a dose equivalent to 5% of the participant's estimated daily energy requirement. The required amount is individually calculated and provided in pre-weighed sachets for daily consumption. Participants consume the assigned dose in foods or beverages during both intervention periods according to the crossover schedule.
• Behavioral Sucrose - High Dose
  Sucrose administered at a dose equivalent to 10% of the participant's estimated daily energy requirement. The required amount is individually calculated and provided in pre-weighed sachets for daily consumption. Participants consume the assigned dose in foods or beverages during both intervention periods according to the crossover schedule.
• Behavioral Sucralose - Low Dose
  Sucralose tablets administered at a total dose of approximately 33.35 mg/day (5 tablets/day). Tablets are consumed daily and distributed across meals. Participants receive the assigned dose throughout both intervention periods and consume the sweetener in both solid and liquid forms according to the study crossover schedule.
• Behavioral Sucralose - High Dose
  Sucralose tablets administered at a total dose of approximately 66.7 mg/day (10 tablets/day). Tablets are consumed daily and distributed across meals. Participants receive the assigned dose throughout both intervention periods and consume the sweetener in both solid and liquid forms according to the study crossover schedule.

Primary outcome measures

• Change in HOMA-IR Index [Time frame: Baseline (before intervention) and End of each 12-week intervention phase]

Secondary outcome measures (7)

• Glycemic biomarker [Time frame: Baseline and End of each 12-week intervention phase]
• Change in Fat Mass [Time frame: Baseline and End of each 12-week intervention phase]
• Change in Systolic Blood Pressure [Time frame: Baseline and End of each 12-week intervention phase]
• Change in Triglycerides [Time frame: Baseline and End of each 12-week intervention phase]
• Change in Relative Abundance of Gut Microbiota [Time frame: Baseline and End of each 12-week intervention phase]
• Change in DNA Methylation in Peripheral Blood Mononuclear Cells [Time frame: Baseline and End of each 12-week intervention phase]
• Change in Urinary Oxylipin Levels [Time frame: Baseline and End of each 12-week intervention phase]

Eligibility criteria

Inclusion criteria

• Adults aged 18 to 65 years at the time of enrollment.
• Body Mass Index (BMI) between 18.5 and 39.9 kg/m².
• Men and women who report a preference for sweet taste and habitual consumption of sugar and/or sweeteners.
• Individuals in good general health, as determined by:

• Medical history and clinical evaluation;
• Absence of uncontrolled chronic diseases, such as diabetes, metabolic syndrome, severe hypertension, or advanced liver or renal disease; and
• Baseline biochemical parameters within normal reference ranges, including fasting plasma glucose <100 mg/dL, HbA1c <5.7%, normal liver and renal function (ALT/AST and creatinine within reference ranges), and blood pressure <140/90 mmHg without pharmacological treatment.
• Less than 4 hours per week of moderate-to-vigorous physical activity.
• Not following special or restrictive diets (e.g., ketogenic, strict vegetarian, or vegan diets).
• Not taking medications known to affect metabolism, including, for example, antidiabetic drugs, systemic corticosteroids, weight-loss medications, or high-dose antioxidant supplements, except for stable use of hormonal contraceptives.
• Willingness to maintain habitual diet and physical activity throughout the study, with the only modification being the assigned sweetener intervention.
• Ability and willingness to comply with all study procedures and scheduled visits.
• Provision of written informed consent before participation.

Exclusion criteria

• Gastrointestinal disorders influencing digestion or nutrient absorption (e.g., inflammatory bowel disease, celiac disease, malabsorption syndromes).
• History of cancer not in remission.
• Uncontrolled thyroid disorders.
• History of bariatric surgery or extreme weight loss within the past 12 months.
• Pregnancy, breastfeeding, or planning pregnancy during the study period.
• Acute illness, major infection, hospitalization, or major surgery within the previous 6 months.
• Any condition that, in the investigators' judgment, could compromise participant safety, protocol adherence, or interpretation of the study results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Basic science

Study locations

Spain · 1 center

• Hospital Universitario Virgen de la Victoria — Málaga

Identifiers

NCT: NCT07656298 · SucroMet

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗