Deciphering the Effect of Moderate Wine Consumption on Healthy Aging Through Postprandial Extracellular Vesicles.

Deciphering the Effect of Moderate Wine Consumption on Healthy Aging Through Postprandial Extracellular Vesicles

This study aims to investigate how moderate wine consumption influences circulating extracellular vesicles (EVs) in healthy adults. EVs are small particles released by cells that carry proteins, lipids, and genetic material, and play important roles in communication between cells. Participants will consume a single serving of red or white wine, and blood samples will be collected before and after consumption to study changes in the composition and function of EVs. The study will also assess how these EVs affect vascular, immune, and brain-related cells. The results are expected to improve our understanding of how moderate wine intake contributes to cardiovascular and brain health.

Dietary interventions have been consistently proposed as a part of a comprehensive strategy to lower the incidence and severity of atherosclerosis and coronary vascular disease. According to the Dietary Guidelines for Americans 2015-2020, moderate red wine consumption-defined as up to two units of alcohol per day for men and up to one unit of alcohol per day for women-significantly reduces the risk of cardiovascular disease (CVD). Wine is a complex matrix consisting primarily of water (86%) and ethyl alcohol (12%), as well as other different molecules, such as polyphenols, organic acids, tannins, compound minerals, vitamins and biologically active compounds. While most of the nutritional studies have focused on elucidating the mechanisms by which biologically active compounds directly affect cardiovascular-related events, little or nothing is known about the regulatory effect of wine consumption on extracellular vesicles (EVs). EVs are small phospholipid particles that convey molecular bioactive cargoes and play essential roles in intercellular communication and, hence, a multifaceted role in health and disease. Recent advances in research on EVs have significantly enhanced their potential as therapeutic agents for neurological diseases. Owing to their therapeutic properties and ability to cross the blood-brain barrier (BBB), extracellular vesicles are recognized as promising drug delivery vehicles (e.g. polyphenols) for various neurological conditions. For the first time, the purpose of this project is to establish whether the moderate wine consumption may alter the structure, cargo, and functionality of postprandial EVs. In the precision nutrition era, we expect to offer a new insight on EVs and their relationship with wine through the following objectives: 1) To map changes in the lipidome, proteome, polyphenolic cargo, and functional properties of circulating EVs in healthy subjects both at fasting and at postprandial state upon a challenge of a one unit of red or white wine; 2) To analyse the effect of postprandial EVs on atherosclerotic-related events in endothelial and immune cells. 3) To analyse the effect of postprandial EVs on healthy ageing in blood-brain barrier and microglial cells. Collectively, this project will provide fundamental insight into EV biology and remarks the clinical and functional relevance and consequences of moderate wine consumption in health and disease.

Inclusion Criteria

• Healthy adult men and women aged 35 to 65 years.
• Body Mass Index (BMI) between 18.5 and 29.9 kg/m².
• Non-smokers or ex-smokers for at least 12 months.
• Moderate alcohol consumers, defined as ≤2 units/day for men and ≤1 unit/day for women.
• Normal fasting glucose and lipid profile at screening.
• Willing and able to refrain from alcohol, polyphenol-rich foods, and intense exercise for 48 hours before each study visit.
• Able to understand the study procedures and provide written informed consent.

Exclusion Criteria

• History or clinical evidence of cardiovascular, hepatic, renal, thyroid, gastrointestinal, or metabolic diseases (including diabetes, dyslipidemia, or hypertension).
• Use of medications or supplements known to affect glucose, lipid, or inflammatory metabolism (e.g., statins, corticosteroids, anti-inflammatory drugs).
• Pregnancy or breastfeeding.
• Recent blood donation (within the last 3 months) or planned blood donation during the study period.
• Major weight change (>5% of body weight) within the last 3 months.
• Participation in another clinical or biomedical study within the previous 3 months.
• Known allergy or intolerance to wine, alcohol, or its components (e.g., sulfites).
• History of alcohol abuse or inability to abstain from alcohol outside the study context.
• Reluctance to receive information about incidental health findings arising from the study.
• Any condition judged by the investigators to limit compliance or increase study risk (e.g., psychiatric disorders, inability to adhere to fasting requirements).