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Unconjugated procyanidin B2 concentration in the systemic circulation reaches a peak at approximately 2 h after administration in humans. Likewise, some human studies have detected unconjugated procyanidin B1, B2, and B5 in plasma and serum within 30 min after consumption of the test material. These results should prompt the attention of the scientific community to the fact that the kinetics of these compounds is influenced by ethanol and body mass index. This effect was more pronounced in overweight and obese individuals. Moreover, this study indicated for the first time that ethanol enhances cyanidin-3- O-glucoside (C圓glc) metabolism potentiating its conversion into methylated and glucuronidated derivatives (Me-Cy-Glucr and 3′-Me-C圓glc). However, the majority of these compounds may originate in the liver and kidneys since the plasma concentration of total anthocyanin conjugates continued to increase after 60 min. On the basis of the rapid appearance of the conjugates (15 min after ingestion), it was suggested that anthocyanins could be metabolized in the upper gastrointestinal tract. In another work, several anthocyanin conjugates (methylated, glucuronidated and sulphated) were detected both in plasma and urine after ingestion of blackberry purees, with or without ethanol, by two groups of volunteers with different body mass indexes. Moreover, it is also necessary to better understand how biological interactions (with microbiota and cells, enzymes or general biological systems) could interfere with flavonoid bioavailability. More in vivo results as well as studies focused on flavonoid metabolites are still required. However, there is still a gap between the knowledge of wine flavonoids bioavailability and their health-promoting effects. Reports related to flavonoids and health highlight some relevant scientific information. This review summarizes some of these major issues which are directly related to the potential health-promoting effects of wine flavonoids. Hence, some reports have focused on flavonoids absorption, metabolism, microbiota effect and overall on flavonoids bioavailability. The way wine flavonoids may be absorbed and metabolized could interfere with their bioavailability and therefore in their health-promoting effect. The interaction between some wine flavonoids and some specific enzymes are one example. The different interactions that wine flavonoids may have with key biological targets are crucial for some of these health-promoting effects. Nevertheless, there are several reports on the health protective properties of wine phenolics for several diseases such as cardiovascular diseases, some cancers, obesity, neurodegenerative diseases, diabetes, allergies and osteoporosis. However, due to the insufficient epidemiological and in vivo evidences on this subject, the presence of a high number of variables such as human age, metabolism, the presence of alcohol, the complex wine chemistry, and the wide array of in vivo biological effects of these compounds suggest that only cautious conclusions may be drawn from studies focusing on the direct effect of wine and any specific health issue.

Flavonoids constitute a major group of polyphenolic compounds which are directly associated with the organoleptic and health-promoting properties of red wine. Chemically, wine is a hydroalcoholic solution (~78% water) that comprises a wide variety of chemical components, including aldehydes, esters, ketones, lipids, minerals, organic acids, phenolics, soluble proteins, sugars and vitamins. Wine, and particularly red wine, is a beverage with a great chemical complexity that is in continuous evolution.

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