The consumption of plant-based foods, particularly berries, has been associated with improved health due to their high content of bioactive compounds. Among these, polyphenols-especially proanthocyanidins (PACs)-may offer protective effects against chronic diseases related to overweight and obesity. Cranberries are naturally rich in PACs and may positively influence metabolic health by modulating the gut microbiota. However, their specific effects on intestinal integrity and broader metabolic outcomes remain underexplored.

The primary aim of this study is to assess the effects of cranberry supplementation on glucose metabolism, insulin sensitivity, blood lipid levels, and the composition and function of the gut microbiota in overweight and obese individuals.

This randomized, double-blind, placebo-controlled, crossover clinical trial will include two 12-week intervention periods-one with a cranberry beverage and one with a placebo-separated by a 4-week washout period and preceded by a 2-week lifestyle stabilization phase. Participants will undergo comprehensive metabolic assessments (glucose control, insulin sensitivity, lipid profile), body composition analysis, gut microbiota profiling, and liver fat imaging (MRI in a subsample of female participants). Additional evaluations will include markers of inflammation, appetite regulation, intestinal health, and lifestyle factors.

Inclusion Criteria:

• body mass index between 25 and 40 kg/m2
• at least one of the following criteria: fasting plasma insulin >60 pmol/L, fasting glycemia between 5.5 and 6.9 mmol/L, glycated hemoglobin (HbA1c) level of 5.7- 6.4% and/or fasting triglyceride >1.35 mmol/L.

Exclusion Criteria:

• to have aversion to cranberry products
• regularly drinking alcohol (>2 glasses/day)
• having a significant change in body weight in the past 3 months (±5% of their body weight) due to bariatric surgery or other conditions
• taking medication which may affect the study outcomes (i.e. antidiabetic and/or cholesterol or lipid-lowering medications and/or glucocorticosteroid in supraphysiological doses and/or anti-obesity medications)
• taking regular probiotics and prebiotics (including fruit/berry polyphenol supplements) in the past 3 months
• having eating disorders
• had undergone major surgery 3 months prior to the study or if they had one planned
• if they had intestinal malabsorption, cirrhosis or chronic kidney disease
• being pregnant, planning a pregnancy, or breastfeeding.