SucroMet Nutritional Intervention Trial

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.

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.