In general, alcohol-containing beverages that are darker in color (e.g., bourbon, red wine) typically have higher congener levels than those lighter in color (e.g., vodka, white wine) and are linked to triggering more pronounced hangover symptoms with more severe headaches (43, 44). Although the mechanism linking congeners with headaches has been elusive, a recent in vitro study that focused on the congener quercetin offers some insight. In its metabolism, alcohol is first oxidized by ADH to acetaldehyde, a toxic byproduct (6), and then to acetate by aldehyde dehydrogenase (ALDH). Recent evidence suggests that quercetin, a flavonoid abundant in red grapes, is metabolized in the liver into quercetin-3-glucuronide, which strongly inhibits an isoform of ALDH (44). Reduced ALDH enzymatic activity causes acetaldehyde to accumulate in the bloodstream after alcohol consumption, triggering symptoms such as nausea, tachycardia, facial flushing, and headache (45). These findings suggest that it is the combined metabolism of quercetin and ethanol in red wine that leads to acetaldehyde buildup and may be a mechanism underlying the headaches associated with drinking 1 or 2 glasses of red wine. However, clinical studies that confirm these in vitro observations are warranted.
