Resveratrol

Proposed mechanisms: direct SIRT1 activation (controversial — some studies suggest the in vitro effect is an artefact of the fluorescent assay), AMPK activation, PDE4 (phosphodiesterase 4) inhibition that raises cAMP and activates favourable cascades, direct antioxidant activity, NF-κB modulation (anti-inflammatory effect).

Human results: modest effects at usual supplementary doses (250-500 mg/day). Consistent improvements in insulin sensitivity, lipid profile, systolic blood pressure, and endothelial function. Small positive results in cognition in older adults. The 'magical' lifespan extension effects have not been replicated in mammals on normal diet (yes in obese mice on high-fat diet, Baur 2006 study).

Critical clinical problem: free resveratrol oral bioavailability is very low (<5%), with rapid metabolism to glucuronides and sulphates without known biological activity. Modern formulations (micronised resveratrol, liposome-encapsulated, cyclodextrin-complexed) significantly improve bioavailability.

Dosing: 250-500 mg/day with fat (better absorption). Red wine consumption provides insufficient amounts for clinical effect (one glass contains <1 mg resveratrol — to reach 250 mg one would need to drink 250 glasses).

The resveratrol narrative summarises an important lesson in longevity: animal model effects do not necessarily translate to humans, and 'magical' compounds rarely survive rigorous clinical trial confrontation. It remains a reasonable supplement as part of a polyphenol cocktail, not as a magic bullet.