Glucose Metabolism, Overweight , Obesity
Conditions
Keywords
Sucrose, Sucralose, Sweeteners, Body Composition, Glucose Metabolism, Gut Microbiota, DNA Methylation, Inflammation, Oxidative Stress Biomarkers, Nutritional Intervention
Brief summary
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
BEHAVIORALSucrose- 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.
BEHAVIORALSucrose - 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.
BEHAVIORALSucralose - 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.
BEHAVIORALSucralose - 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.
Sponsors
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Junta de Andalucia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
Although the study is conducted as an open-label nutritional intervention, all study data will be coded prior to analysis. Investigators performing the statistical analyses will work with anonymized datasets and will not have access to information identifying participants or intervention groups. Group allocation codes will be disclosed only after completion of the primary analyses.
Intervention model description
This is a randomized nutritional intervention with a crossover component designed to evaluate the effects of sweetener type, dose, and mode of consumption. Participants are randomized to one of four intervention groups: low-dose sucrose, high-dose sucrose, low-dose sucralose, or high-dose sucralose, and remain on the same sweetener and dose throughout the study. Participants are recruited across normal-weight, overweight, and obesity BMI categories.Following a 4-week run-in period, participants are randomized to begin with either solid or liquid intake. After completing the first 12-week intervention period, participants undergo a 2-week washout and then cross over to the alternate intake form for a second 12-week intervention period. The crossover applies only to the mode of consumption (solid versus liquid), while sweetener type and dose remain unchanged.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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: 1. Medical history and clinical evaluation; 2. Absence of uncontrolled chronic diseases, such as diabetes, metabolic syndrome, severe hypertension, or advanced liver or renal disease; and 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HOMA-IR Index | Baseline (before intervention) and End of each 12-week intervention phase | Insulin resistance will be assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Results will be reported as HOMA-IR values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic biomarker | Baseline and End of each 12-week intervention phase | Change in Hemoglobin A1c (%): Hemoglobin A1c measured as an indicator of long-term glycemic control. |
| Change in Fat Mass | Baseline and End of each 12-week intervention phase | Fat mass (kg) is assessed using bioelectrical impedance analysis (BIA). |
| Change in Systolic Blood Pressure | Baseline and End of each 12-week intervention phase | Systolic blood pressure is measured under standardized clinical conditions using validated devices. |
| Change in Triglycerides | Baseline and End of each 12-week intervention phase | Triglyceride levels (mg/dL) are measured using standard clinical laboratory methods. |
| Change in Relative Abundance of Gut Microbiota | Baseline and End of each 12-week intervention phase | Gut microbiota composition is assessed in stool samples using 16S rRNA gene sequencing by quantifying the relative abundance of bacterial taxa at different taxonomic levels. |
| Change in DNA Methylation in Peripheral Blood Mononuclear Cells | Baseline and End of each 12-week intervention phase | DNA methylation levels are assessed in peripheral blood mononuclear cells (PBMCs) by quantifying methylation at specific CpG sites using bisulfite-based epigenetic analysis techniques. |
| Change in Urinary Oxylipin Levels | Baseline and End of each 12-week intervention phase | Urinary oxylipin levels, including isoprostanes, prostaglandins, and thromboxanes, are quantified in first-morning urine samples using targeted mass spectrometry and normalized to urinary creatinine. |
Countries
Spain
Contacts
CONTACTLibia Alejandra Garcìa Flores, PhD.
CONTACTJosé Manuel García Almeida, MD, PhD.
PRINCIPAL_INVESTIGATORLibia Alejandra García Flores, PhD
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud (FIMABIS)
PRINCIPAL_INVESTIGATORJosé Manuel García Almeida, MD, PhD.
Andaluz Health Service
Outcome results
None listed