What are the anti-cancer effects of Resveratrol?

Resveratrol: General and Anti-Cancer Effects

Resveratrol cannot be recommended for cancer prevention or treatment based on current evidence, and should be held 2 weeks before surgery due to antiplatelet effects. 1

General Properties and Mechanisms

Resveratrol (trans-3,5,4'-trihydroxystilbene) is a polyphenol compound found in grapes, berries, peanuts, red wine, and other plant sources. 2 While it demonstrates multiple biological activities in laboratory settings, its clinical utility remains unproven.

Proposed Mechanisms of Action

Resveratrol exhibits several theoretical anti-cancer mechanisms in preclinical studies:

• Cell cycle modulation: Upregulates p21Cip1/WAF1, p53, and Bax while downregulating survivin, cyclin D1, cyclin E, Bcl-2, and Bcl-xL 2
• Transcription factor suppression: Inhibits NF-κB, AP-1, and Egr-1 activation 2
• Enzyme inhibition: Blocks COX-2,5-LOX, and multiple protein kinases including IκBα kinase, JNK, MAPK, Akt, and PKC 2
• Anti-angiogenic effects: Downregulates VEGF, IL-1, IL-6, and IL-8 2
• Carcinogen metabolism: Inhibits aryl hydrocarbon-induced CYP1A1 expression 2

Clinical Evidence: The Reality Check

Cardiovascular Context (Not Cancer-Specific)

The American Heart Association concluded that wine consumption as cardiovascular protection due to antioxidant content is an unproven strategy. 1 Studies of resveratrol effects on atherosclerosis in animals show conflicting results. 1 Fresh fruits and vegetables should provide similar antioxidant effects without alcohol-related risks. 1

Liver Disease Studies: Mixed and Concerning Results

The ESPEN guidelines (2019-2020) provide the most relevant clinical data with strong consensus (100% agreement) that resveratrol cannot be recommended for treating NAFL/NASH. 1

Critical findings from human trials:

• High-dose resveratrol (3000 mg for 8 weeks) in overweight/obese men with NAFLD showed NO benefit for insulin resistance, steatosis, abdominal fat distribution, plasma lipids, or antioxidant activity. Importantly, ALT and AST levels increased significantly, suggesting potential hepatotoxicity. 1

• Lower doses (150 mg twice daily for 3 months) showed improvements in AST, ALT, LDL cholesterol, and HOMA-IR in normal-weight men with NAFLD. 1

• 500 mg daily with lifestyle intervention was more effective than lifestyle alone for ALT, inflammatory cytokines, and hepatic steatosis in overweight patients. 1

Cancer-Specific Evidence: Preclinical Promise, Clinical Uncertainty

In vitro studies demonstrate resveratrol suppresses proliferation of multiple cancer types including lymphoid/myeloid cancers, multiple myeloma, breast, prostate, stomach, colon, pancreatic, thyroid, melanoma, head and neck, ovarian, and cervical cancers. 2

Animal studies show highly variable results depending on route of administration, dose, tumor model, species, strain, age, sex, timing of supplementation, and other factors. 3 Outcomes range from positive to neutral to negative effects. 3

Human cancer trials: The evidence remains insufficient, with ongoing interventional clinical trials but no definitive therapeutic benefit established. 4, 5

Perioperative Safety Concerns

The Society for Perioperative Assessment and Quality Improvement (SPAQI) recommends holding resveratrol 2 weeks before surgery due to:

• Antiplatelet effects via COX pathway inhibition or cellular calcium channel blockade 1
• Potential bleeding complications 1

Bioavailability and Pharmacokinetics

A major limitation is poor oral bioavailability. 3 After absorption, resveratrol concentrates primarily in liver and kidney, where it converts to sulfated and glucuronide conjugate forms. 2 This metabolic conversion may explain the discrepancy between promising in vitro effects and disappointing clinical outcomes.

Potential Toxicity

While limited human data suggest resveratrol is "pharmacologically quite safe" at standard doses 2, the dose-dependent hepatotoxicity observed in NAFLD patients (elevated transaminases at 3000 mg daily) raises significant concerns. 1

Animal studies targeting maternal obesity showed beneficial effects on offspring metabolic programming but also demonstrated toxic effects at high doses and adverse effects on pancreatic development. 1 Corresponding human pregnancy safety data are lacking. 1

Common Pitfalls to Avoid

• Do not extrapolate in vitro cancer cell studies to clinical efficacy: The gap between laboratory and bedside remains substantial 3, 5
• Do not assume "natural" equals safe: Dose-dependent hepatotoxicity has been documented 1
• Do not continue perioperatively: Bleeding risk necessitates 2-week discontinuation 1
• Do not recommend as cancer therapy: No established clinical benefit for cancer prevention or treatment 2, 3, 4, 5

Practical Clinical Approach

For cancer prevention/treatment: Advise patients that despite promising laboratory research, resveratrol lacks proven clinical efficacy for cancer outcomes. 2, 3, 4, 5 Direct patients toward evidence-based cancer prevention strategies including dietary patterns rich in fruits and vegetables rather than isolated supplements. 1

For surgical patients: Discontinue resveratrol 2 weeks before any surgical procedure. 1

For liver disease: Do not recommend resveratrol for NAFL/NASH treatment given inconsistent results and potential for hepatotoxicity at higher doses. 1