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TRANS-RESVERATROL

The biologically active trans isomer of resveratrol, a polyphenolic stilbene found in grapes and berries, known for activating sirtuins and AMPK to promote longevity-associated pathways, cardiovascular protection, and anti-inflammatory effects.

Trans-resveratrol is a polyphenolic compound found naturally in grapes, berries, and other plants that acts as a phytoestrogen and activates SIRT1 pathways. It has demonstrated antioxidant, anti-inflammatory, and potential anti-aging properties through multiple mechanisms including NAD+ metabolism support and mitochondrial function enhancement. Research suggests benefits for bone density, cardiovascular health, glucose metabolism, and longevity, though bioavailability is enhanced when consumed with dietary fats.

Research

Reported Effects

Bioavailability Concerns:: Users emphasize that resveratrol must be dissolved in fat (olive oil, coconut oil) for optimal absorption, with claims of 10-100x increased bioavailability when taken with dietary fats. Synergistic Effects:: Most effective when stacked with other compounds like NMN, TMG, quercetin, and curcumin rather than as standalone supplement. Dose-Response Variation:: Effectiveness appears highly individual, with some users noticing benefits at 500mg while others follow David Sinclair's 1g daily protocol. Mixed Evidence:: Skepticism exists about whether resveratrol optimizes flawed testing methods or provides genuine benefits, with some studies published after initial hype suggesting potential DNA replicative stress

  • Users emphasize that resveratrol must be dissolved in fat (olive oil, coconut oil) for optimal absorption, with claims of 10-100x increased bioavailability when taken with dietary fats
  • Most effective when stacked with other compounds like NMN, TMG, quercetin, and curcumin rather than as standalone supplement
  • Effectiveness appears highly individual, with some users noticing benefits at 500mg while others follow David Sinclair's 1g daily protocol
  • Skepticism exists about whether resveratrol optimizes flawed testing methods or provides genuine benefits, with some studies published after initial hype suggesting potential DNA replicative stress

Safety Profile

Safety Profile: Trans-Resveratrol

Common Side Effects

  • Generally well tolerated at doses of 150–500 mg/day in clinical studies
  • Gastrointestinal symptoms including nausea, diarrhea, abdominal pain, and flatulence, particularly at higher doses (>1000 mg/day)
  • Headache and dizziness
  • Mild skin rash in sensitive individuals
  • Loose stools at higher doses (>500 mg/day)

Serious Adverse Effects

  • Nephrotoxicity: A clinical trial using 2000–3000 mg/day reported kidney injury; high doses should be avoided
  • Estrogenic activity: Trans-resveratrol has weak phytoestrogenic properties; may stimulate estrogen receptor-positive tissues at high doses
  • Bleeding risk: Antiplatelet activity demonstrated in vitro and in some clinical studies; may increase bleeding risk at doses above 1000 mg/day
  • Potential for paradoxical pro-oxidant effects at very high concentrations
  • Rare cases of Achilles tendinopathy reported anecdotally (mechanism unclear)

Contraindications

  • Known hypersensitivity to resveratrol or related stilbene compounds
  • Hormone-sensitive conditions (breast cancer, endometrial cancer, ovarian cancer, endometriosis) without medical supervision due to phytoestrogenic activity
  • Active bleeding disorders or upcoming surgery (discontinue 2 weeks prior)
  • Severe renal impairment (given nephrotoxicity at high doses)
  • Pregnancy and lactation (estrogenic activity and insufficient safety data)

Drug Interactions

  • Anticoagulants/Antiplatelets (warfarin, aspirin, clopidogrel): Additive antiplatelet effects; monitor INR and bleeding signs
  • CYP3A4 and CYP1A2 substrates: Resveratrol inhibits these enzymes in vitro; may increase levels of drugs metabolized by these pathways
  • Estrogen and hormone therapies (HRT, oral contraceptives): Additive estrogenic effects or competition at estrogen receptors
  • Antidiabetic agents: May enhance hypoglycemic effects; monitor blood glucose
  • Immunosuppressants: Resveratrol has immunomodulatory properties; may interfere with immunosuppressive regimens

Population-Specific Considerations

  • Elderly: Generally well tolerated at moderate doses (150–500 mg/day); monitor renal function and drug interactions
  • Pediatric: No established safety data; not recommended for children
  • Diabetic patients: May improve insulin sensitivity; monitor blood glucose when combined with antidiabetic medications
  • Cancer patients: Conflicting evidence; may have both anti-cancer and pro-estrogenic effects; consult oncologist
  • Wine consumers: Dietary resveratrol from wine is far below supplemental doses; no additional safety concerns from food sources

Pharmacokinetic Profile

Quick Start

Typical Dose
Most common dosing is 500mg-1000mg daily of trans-resveratrol, typically taken in morning with fat source

Molecular Structure

2D Structure
TRANS-RESVERATROL molecular structure
Molecular Properties
Formula
C14H12O3
Weight
228.24 Da
PubChem CID
445154
Exact Mass
228.0786 Da
LogP
3.1
TPSA
60.7 Ų
H-Bond Donors
3
H-Bond Acceptors
3
Rotatable Bonds
2
Complexity
246
Identifiers (SMILES, InChI)
InChI
InChI=1S/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1+
InChIKeyLUKBXSAWLPMMSZ-OWOJBTEDSA-N

Safety Profile

Common Side Effects

  • Kidney Concerns:: Some users report warnings about long-term kidney damage with extended resveratrol use, leading to discontinuation
  • Exercise Blunting:: Reports that resveratrol may blunt the beneficial effects of exercise, similar to metformin, causing concern for fitness-focused users
  • Warfarin Interaction:: Research confirms resveratrol enhances anticoagulant effects of blood thinners, requiring medical monitoring for users on such medications
  • Individual Reactions:: Varied reports of side effects at higher doses (600-1200mg) that were 'not worth whatever benefit,' though specifics often undetailed

References (8)

  1. [1]
    Regular Supplementation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial

    → A 24-month randomized controlled trial found that resveratrol supplementation significantly improved bone mineral density in postmenopausal women, supporting its bone-protective role similar to effects seen in animal models of osteoporosis.

  2. [2]
    Role of resveratrol supplementation in regulation of glucose hemostasis, inflammation and oxidative stress in patients with diabetes mellitus type 2: A randomized, placebo-controlled trial

    → 200mg daily resveratrol supplementation for 24 weeks significantly improved glucose homeostasis, reduced inflammatory markers (TNF-α, IL-6, hs-CRP), and decreased oxidative stress in type 2 diabetic patients on oral hypoglycemic drugs.

  3. [3]
    Gut microbiota-derived 4-hydroxyphenylacetic acid from resveratrol supplementation prevents obesity through SIRT1 signaling activation

    → Resveratrol supplementation ameliorated high-fat-diet-induced obesity by enhancing beneficial gut bacteria (Akkermansia, Bacteroides, Blautia) and producing metabolites that activate SIRT1 signaling, as confirmed through antibiotic depletion and fecal microbiota transplantation studies.

  4. [4]
    Trans-resveratrol supplement lowers lipid peroxidation responses of exercise in male Wistar rats

    → Trans-resveratrol supplementation demonstrated antioxidant properties by reducing lipid peroxidation and protecting against exercise-induced oxidative damage in muscle fibers of male rats.

  5. [5]
    Effects of Mediterranean Diet, Curcumin, and Resveratrol on Mild-to-Moderate Active Ulcerative Colitis: A Multicenter Randomized Clinical Trial

    → An 8-week trial combining Mediterranean diet with resveratrol supplementation showed improvements in disease activity, inflammatory markers, and quality of life in patients with mild-to-moderate active ulcerative colitis.

  6. [6]
    Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis

    → Systematic review and meta-analysis found that dietary polyphenol supplementation including resveratrol showed efficacy in treating non-alcoholic fatty liver disease with favorable safety profiles.

  7. [7]
    Trans-Resveratrol Enhances the Anticoagulant Activity of Warfarin in a Mouse Model

    → Trans-resveratrol at 0.5% dietary concentration enhanced warfarin's anticoagulant effects in mice and slightly increased CYP1A1 activity, suggesting potential drug interactions requiring monitoring in patients taking anticoagulants.

  8. [8]
    Immunotoxicity studies of trans-resveratrol in male B(6)C(3)F(1)/N mice

    → A 28-day study in mice found no treatment-related immunotoxic effects from trans-resveratrol at doses up to 2500 mg/kg/day, with no impacts on humoral, cell-mediated, or innate immune function despite previous findings of decreased thymus weight.

Updated 2026-03-08Sources: peptidebay, pubchem

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Research
Reported Effects
Safety Profile
Pharmacokinetic Profile
Quick Start
Molecular Structure
Safety Profile
References
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