Resveratrol

What is resveratrol?

Resveratrol is a polyphenol produced by plants under stress, particularly in the skins of red grapes, blueberries, cranberries, mulberries, and peanuts. It gained public attention through the "French Paradox" in the 1990s, when researchers noticed that French populations drinking moderate amounts of red wine had lower rates of cardiovascular disease despite a diet high in saturated fat ^[1]. The compound responsible turned out to be resveratrol, specifically the trans-resveratrol isomer, which is the biologically active form.

At the cellular level, resveratrol activates SIRT1, one of seven sirtuin enzymes that depend on NAD+ to function. SIRT1 deacetylates proteins involved in mitochondrial biogenesis (PGC-1alpha), stress resistance (FOXO3), and inflammation control (NF-kB). Resveratrol also activates AMPK, the cell's energy sensor, and inhibits mTOR signaling. These are the same pathways activated by caloric restriction and exercise, which is why resveratrol has attracted so much interest in aging research ^[2].

What does the research actually show?

The evidence for resveratrol is a mixed bag. Animal data is strong: mice on high-fat diets given resveratrol showed improved glucose tolerance, better mitochondrial function, and protection against metabolic disease ^[3]. But lifespan extension in normal-weight, healthy mice has not been confirmed. Resveratrol extends lifespan in metabolically stressed animals, not healthy ones.

Human clinical trials tell a more modest story. A 2024 systematic review analyzing over 240 clinical trials found that resveratrol consistently reduces inflammatory markers like CRP and TNF-alpha, improves insulin sensitivity, and lowers blood pressure ^[4]. A meta-analysis of randomized controlled trials showed significant reductions in both systolic and diastolic blood pressure ^[5]. For type 2 diabetes specifically, resveratrol supplementation decreased body weight, BMI, and waist circumference according to a 2025 meta-analysis ^[6]. However, effects on healthy populations are much less clear. There is currently no consensus treatment protocol for any specific condition.

One important finding from 2024: a meta-analysis examining resveratrol's effect on human SIRT1 levels found that supplementation did not significantly raise circulating SIRT1 in pooled analyses ^[7]. This suggests the dramatic sirtuin-mediated lifespan effects seen in animal models may not translate directly to humans at typical supplement doses.

The bioavailability problem

Resveratrol's biggest limitation is poor bioavailability. Although roughly 75% is absorbed in the gut, the compound is rapidly metabolized by the liver and intestinal enzymes into sulfate and glucuronide conjugates. The result: only about 1-5% of oral resveratrol reaches the bloodstream in its active free form, and it has a plasma half-life of just 8-14 minutes ^[8]. This means the doses that produce effects in cell culture (micromolar concentrations) are hard to achieve in vivo.

Pterostilbene, a methylated analog of resveratrol found in blueberries and grapes, has roughly 4x higher bioavailability (about 80% vs 20%) and a half-life of 105 minutes due to two methoxy groups that resist metabolic conjugation ^[9]. Some researchers and supplement companies now favor pterostilbene for this reason, though head-to-head human trials comparing the two compounds remain scarce.

Taking resveratrol with fat improves absorption. David Sinclair, the Harvard geneticist who popularized resveratrol research, takes 1 gram daily mixed into yogurt for this reason. Quercetin, another polyphenol found in onions and apples, may also slow resveratrol metabolism when taken together.

Food sources and supplement dosing

Red wine contains about 0.2-5.8 mg of resveratrol per glass depending on grape variety, with Pinot Noir typically having the highest concentrations. Muscadine grapes contain even more, as resveratrol concentrates in the skin and seeds. Other food sources include peanuts (0.01-0.26 mg per cup), blueberries, cranberries, dark chocolate, and Japanese knotweed (Polygonum cuspidatum), which is actually the most common commercial supplement source ^[1].

Clinical trials have used doses ranging from 75 mg to 5 grams per day. The European Food Safety Authority (EFSA) considers up to 150 mg/day of trans-resveratrol safe for long-term use. Doses above 2.5 grams per day commonly cause gastrointestinal side effects including nausea, cramping, and diarrhea. Most supplement products contain 150-500 mg of trans-resveratrol per capsule.

Safety and drug interactions

Resveratrol is generally well tolerated at doses up to 1 gram per day ^[10]. At higher doses, it can inhibit cytochrome P450 enzymes (CYP1A2, CYP3A4, CYP2D6), which affects the metabolism of many prescription drugs. People taking blood thinners like warfarin should be cautious, as resveratrol has mild antiplatelet activity. It may also interact with statins and immunosuppressants. Anyone on prescription medication should consult their doctor before starting resveratrol supplements.

Because resveratrol has weak estrogenic activity through estrogen receptor beta, women with hormone-sensitive cancers should discuss supplementation with their oncologist. Paradoxically, resveratrol also shows anti-estrogenic effects at high doses, making the picture complex. During pregnancy and breastfeeding, supplementation is not recommended due to insufficient safety data.