Resveratrol

Resveratrol is a stilbene polyphenol produced by plants as a defense mechanism against environmental stressors like UV radiation, infection, and injury. It is found in the skin of red grapes, red wine, blueberries, raspberries, mulberries, and peanuts — with Japanese knotweed (Polygonum cuspidatum) being the most concentrated natural source used in supplements.

Resveratrol gained enormous scientific attention in the early 2000s following landmark research suggesting it could activate sirtuins — proteins linked to longevity — and potentially mimic the life-extending effects of caloric restriction.

Resveratrol exerts its effects through several distinct mechanisms:

- Sirtuin activation — activates SIRT1, a protein deacetylase involved in cellular repair, mitochondrial function, and longevity signaling

- AMPK activation — activates AMP-activated protein kinase, a cellular energy sensor that improves metabolic function and mimics some effects of exercise

- Antioxidant — neutralizes free radicals and upregulates the body's own antioxidant enzyme systems (superoxide dismutase, catalase)

- Anti-inflammatory — inhibits NF-κB and COX enzymes, key drivers of chronic inflammation

- Cardiovascular — reduces LDL oxidation, improves endothelial function, and mildly thins blood

- Neuroprotective — crosses the blood-brain barrier and reduces amyloid plaque formation and neuroinflammation

Resveratrol is generally well tolerated though a few considerations apply:

- Digestive effects (nausea, diarrhea) may occur at very high doses (1,000mg+)
- May have mild blood thinning effects — use caution with anticoagulants
- May interact with some medications metabolized by cytochrome P450 enzymes
- Estrogenic activity at high doses — those with hormone-sensitive conditions should consult a doctor
- Bioavailability is limited — absorption enhanced by taking with fat or combining with piperine (black pepper extract)
- Consult healthcare provider if pregnant, nursing, or on medications

- Baur et al. (2006) — Landmark study in Nature found resveratrol activated SIRT1 and extended lifespan in obese mice fed a high-fat diet — the study that launched modern resveratrol research.

- Bhatt et al. (2012) — Published in Cell Metabolism, demonstrated resveratrol improved mitochondrial function and metabolic markers in obese humans.

- Turner et al. (2011) — Study in Journal of Physiology found resveratrol enhanced exercise training adaptations and improved cardiovascular fitness in mice.

- Witte et al. (2014) — Published in Journal of Neuroscience, showed resveratrol supplementation improved memory performance and hippocampal connectivity in older adults.