In support of the J curve that describes the association between wine consumption and all-cause mortality, researchers and the lay press often advocate the health benefits of (poly)phenol consumption via red wine intake and cite the vast amount of in vitro literature that would corroborate the hypothesis. Other researchers dismiss such evidence and call for total abstention. In this review, we take a skeptical, Pythagorean stance and we critically try to move the debate forward by pointing the readers to the many pitfalls of red wine (poly)phenol research, which we arbitrarily treat as if they were pharmacological agents. We conclude that, after 30 years of dedicated research and despite the considerable expenditure, we still lack solid, "pharmacological", human evidence to confirm wine (poly)phenols' biological actions. Future research will eventually clarify their activities and will back the current recommendations of responsibly drinking moderate amounts of wine with meals.
Keywords: clinical trials; diet; flavonoids; metabolites; polyphenols; wine.