Resveratrol

Resveratrol/Drug Interactions:

  • AnalgesicsAnalgesics: In animal research, resveratrol reduced pain associated with application of nucleus pulposus (NP) tissue on the dorsal root ganglion for up to 14 days, by reducing inflammation (93).
  • AntiarthriticsAntiarthritics: In animal research, resveratrol reduced clinical parameters and bone erosion associated with collagen-induced arthritis (37).
  • AntibioticsAntibiotics: According to preliminary laboratory research, resveratrol may have additive effects when taken with actinomycin D (171; 172). According to animal research, there may be a protective effect of trans-resveratrol on gentamicin-induced kidney toxicity (86).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Laboratory research suggests that resveratrol inhibits platelet aggregation and thrombin activity (27; 28; 29; 30; 31; 32; 21; 129; 33; 15; 173; 94).
  • Antidepressants (MAOIs)Antidepressants (MAOIs): Resveratrol inhibited monoamine oxidase A activity in vitro in a dose-dependent manner (174). The antioxidant activity of resveratrol closely correlates with its monoamine oxidase-A inhibitory activity (175).
  • AntidiabeticsAntidiabetics: Based on a proposed mechanism of action, resveratrol may have the potential to aid in insulin resistance syndrome and type 2 diabetes (176). In animal and human research, resveratrol has been shown to increase insulin sensitivity (137; 138). In animal and human research, resveratrol reduced blood glucose (139; 135; 136; 138). In epidemiological research, high urinary levels of resveratrol metabolites, a marker of wine and resveratrol intake, were associated with beneficial changes in fasting blood glucose (141).
  • AntifungalsAntifungals: According to preliminary laboratory research, resveratrol may have additive effects when taken with nystatin (171; 172).
  • AntihypertensivesAntihypertensives: According to in vitro, animal, and human research, resveratrol may have antihypertensive effects, and in animal and human research, it has been shown to reduce blood pressure (130; 131; 132; 133; 134; 135; 136).
  • Anti-inflammatoriesAnti-inflammatories: According to in vitro and animal research, resveratrol may inhibit the synthesis of thromboxane and leukotrienes (177; 15) and may inhibit COX-1 and COX-2 activity (178; 179; 180; 181; 182; 183; 184).
  • AntilipemicsAntilipemics: In animal and human research, resveratrol, as well as LGP, which is rich in resveratrol, has been shown to reduce plasma triglycerides, LDL cholesterol, and apolipoprotein B and E concentrations, and to decrease cholesterol ester transfer protein activity (185; 82; 136; 135; 157). In epidemiological research, high urinary levels of resveratrol metabolites, a marker of wine and resveratrol intake, were associated with beneficial changes in blood lipids (HDL cholesterol, triglycerides) (141).
  • AntineoplasticsAntineoplastics: In in vitro and other laboratory research, resveratrol had anticancer effects (186; 187; 68; 188; 189; 190; 191; 192; 193; 36; 194).
  • Antiobesity agentsAntiobesity agents: According to a review, resveratrol had weight loss effects in laboratory research (195). In animal research, resveratrol reduced intra-abdominal fat deposition (168).
  • AntiviralsAntivirals: According to in vitro research, resveratrol may have antiviral effects (36). Resveratrol was also found to inhibit the replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) (34).
  • Cardiovascular agentsCardiovascular agents: In laboratory research, resveratrol had cardioprotective effects (196; 197; 198; 199; 200).
  • Cyclosporin ACyclosporin A: According to preliminary data, resveratrol may enhance the immune suppression caused by cyclosporin A (201).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Preliminary evidence suggests that resveratrol weakly inhibits multiple cytochrome P450 enzymes, including CYP1A1, CYP1B1, and CYP3A4 (202; 203; 204; 205; 206; 207; 208; 209; 210; 211; 56; 212; 183; 213; 214; 215; 216; 217). In vitro, resveratrol increased CYP4F2 mRNA expression (218).
  • Dermatologic agentsDermatologic agents: Topical application of a grape seed extract compound containing resveratrol has been shown to accelerate wound contraction and closure (108). Histologically, the wound was also improved, as defined by the hyperproliferative epithelial region, a higher cell density, and enhanced deposition of connective tissue. This is supported by in vitro data (101; 219).
  • EstrogensEstrogens: According to in vitro research, resveratrol has the potential to act as an estrogen agonist or antagonist, depending on such factors as cell type and estrogen receptor isoform (ER-alpha or ER-beta) (146; 144). The chemical structure of resveratrol has been found to be very similar to that of the synthetic estrogen agonist diethylstilbestrol (220). In estrogen receptor-positive breast cancer cells, resveratrol acted as an estrogen agonist in the absence of the endogenous estrogen 17-beta-estradiol, but as an estrogen antagonist in the presence of 17-beta-estradiol (145). However, according to laboratory research, resveratrol may act as an estrogen antagonist under some conditions (142; 143).
  • Fertility agentsFertility agents: In animal research, resveratrol improved erectile dysfunction in diabetic rats (221).
  • Gastrointestinal agentsGastrointestinal agents: In animal research, resveratrol reduced intestinal injury associated with a trauma hemorrhage (73). In animal research, resveratrol resulted in a decreased severity of esophagitis and a reduction in the carcinogenic progression to esophageal adenocarcinoma (222).
  • Heart rate regulating agentsHeart rate regulating agents: In human research, a polyphenol mixture, containing resveratrol, resulted in a significantly lower heart rate at 75W of exercise work (140). In epidemiological research, high urinary levels of resveratrol metabolites, a marker of wine and resveratrol intake, were associated with beneficial changes in heart rate (141).
  • Hepatoprotective agentsHepatoprotective agents: In animal research, resveratrol reduced hepatic injury associated with trauma hemorrhage (223) and improved levels of plasma aspartate aminotransferase (AST) and alanine amonotransferase (ALT) (224). However, according to secondary sources, drinking large quantities of red wine, which contains resveratrol, may have adverse effects on the liver.
  • ImmunostimulantsImmunostimulants: According to laboratory and in vitro research, immune function may be increased or inhibited by resveratrol, depending on its concentration (148; 149).
  • ImmunosuppressantsImmunosuppressants: According to laboratory and in vitro research, immune function may be increased or inhibited by resveratrol, depending on its concentration (148; 149).
  • Neurologic agentsNeurologic agents: In human research, resveratrol increased cerebral blood flow (156). According to reviews, resveratrol showed effects in in vitro and in vivo models of epilepsy, ischemia, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and nerve injury (8; 225; 226). It has been suggested that resveratrol has positive effects on neuronal cells (227; 228; 147).
  • Protease inhibitorsProtease inhibitors: In vitro, in myotubes, resveratrol protected against protease inhibitor-induced reactive oxygen species production, reticulum stress, and lipid raft perturbation (229).
  • Renal agentsRenal agents: Although details are limited, resveratrol and exercise improved kidney disease comorbidities in a uremia model (230).
  • Respiratory agentsRespiratory agents: In vitro, resveratrol inhibited TNF-alpha induced IL-8, granulocyte macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) release from human airway smooth muscle cells (231). Resveratrol improved mitochondrial and tissue damage in a pulmonary ischemia reperfusion injury model (232); further details are not available at this time. In animal research, resveratrol prevented pulmonary hypertension (96).
  • UDP-glucuronosyl transferase (UGT) 1A1-metabolized agentsUDP-glucuronosyl transferase (UGT) 1A1-metabolized agents: In individuals with low baseline enzyme levels or activity, resveratrol induced glutathione S-transferase (GST)-pi levels and UDP-glucuronosyl transferase 1A1 activity (233).
  • VasodilatorsVasodilators: In animal research, resveratrol induced vasorelaxation (105). Resveratrol was found to improve flow-mediated dilation in healthy exercising subjects (160). In vitro, resveratrol has been shown to significantly increase the expression of the gene-encoding eNOS, which synthesizes the vasodilator molecule NO, and to decrease expression of the potent vasoconstrictor endothelin-1 (ET-1) (234; 235).

    • Resveratrol/Herb/Supplement Interactions:

  • AnalgesicsAnalgesics: In animal research, resveratrol reduced pain associated with application of NP tissue on the dorsal root ganglion for up to 14 days, by reducing inflammation (93).
  • AntiarthriticsAntiarthritics: In animal research, resveratrol reduced clinical parameters and bone erosion associated with collagen-induced arthritis (37).
  • AntibacterialsAntibacterials: According to preliminary laboratory research, resveratrol may have additive effects when taken with antibacterials (171; 172).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Laboratory research suggests that resveratrol inhibits platelet aggregation and thrombin activity (27; 28; 29; 30; 31; 32; 21; 129; 33; 15; 173; 94). Use of resveratrol with garlic, saw palmetto, vitamin K, and other herbs and supplements with anticoagulant or antiplatelet effects may cause an increased risk of bleeding.
  • Antidepressants (MAOIs)Antidepressants (MAOIs): Resveratrol inhibited monoamine oxidase A activity in vitro, in a dose-dependent manner (174). The antioxidant activity of resveratrol closely correlated with its monoamine oxidase-A inhibitory activity (175).
  • AntifungalsAntifungals: According to preliminary laboratory research, resveratrol may have additive effects when taken with antifungals (171; 172).
  • Anti-inflammatoriesAnti-inflammatories: According to in vitro and animal research, resveratrol may inhibit the synthesis of thromboxane and leukotrienes (177; 15) and may inhibit COX-1 and COX-2 activity (178; 179; 180; 181; 182; 183; 184).
  • AntilipemicsAntilipemics: In animal and human research, resveratrol, as well as LGP, which is rich in resveratrol, has been shown to reduce plasma triglycerides, LDL cholesterol, and apolipoprotein B and E concentrations, and to decrease cholesterol ester transfer protein activity (185; 82; 136; 135; 157). In epidemiological research, high urinary levels of resveratrol metabolites, a marker of wine and resveratrol intake, were associated with beneficial changes in blood lipids (HDL cholesterol, triglycerides) (141).
  • AntineoplasticsAntineoplastics: In in vitro and other laboratory research, resveratrol had anticancer effects (186; 187; 68; 188; 189; 190; 191; 192; 193; 36; 194).
  • Antiobesity agentsAntiobesity agents: According to a review, resveratrol had weight loss effects in laboratory research (195). In animal research, resveratrol reduced intra-abdominal fat deposition (168).
  • AntioxidantsAntioxidants: In laboratory and human research, resveratrol had antioxidant effects (236; 162; 237; 80; 14; 238; 239; 48; 240; 43; 241). Resveratrol showed inhibition of various reactive oxygen species, including superoxide anion (O2-) generation in stimulated neutrophils, as well as decreased HOCl production and quenching of singlet oxygen and nitric oxide (NO) (43; 242; 243; 47; 244; 55; 245).
  • AntiviralsAntivirals: According to in vitro research, resveratrol may have antiviral effects (36). Resveratrol was also found to inhibit the replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) (34).
  • Cardiovascular agentsCardiovascular agents: In laboratory research, resveratrol had cardioprotective effects (196; 197; 198; 199; 200).
  • CurcuminCurcumin: In an animal lung carcinogenesis model, the combination of curcumin and resveratrol maintained adequate zinc levels and regulated inflammation (246).
  • Cytochrome P450-metabolized herbs and supplementsCytochrome P450-metabolized herbs and supplements: Preliminary evidence suggests that resveratrol weakly inhibits multiple cytochrome P450 enzymes, including CYP1A1, CYP1B1, and CYP3A4 (202; 203; 204; 205; 206; 207; 208; 209; 210; 211; 56; 212; 183; 213; 214; 215; 216; 217). In vitro, resveratrol increased CYP4F2 mRNA expression (218).
  • Dermatologic agentsDermatologic agents: Topical application of a grape seed extract compound containing resveratrol has been shown to accelerate wound contraction and closure (108). Histologically, the wound was also improved as defined by the hyperproliferative epithelial region, a higher cell density, and enhanced deposition of connective tissue. This is supported by in vitro data (101; 219).
  • Fertility agentsFertility agents: In animal research, resveratrol improved erectile dysfunction in diabetic rats (221).
  • Garlic oilGarlic oil: In vitro, a combination of garlic oil and resveratrol increased the expression of Bax and decreased the expression of bcl-2, playing a role in apoptosis of cancer cells (247).
  • Gastrointestinal agentsGastrointestinal agents: In animal research, resveratrol reduced intestinal injury associated with a trauma hemorrhage (73). In animal research, resveratrol resulted in a decreased severity of esophagitis and a reduction in the carcinogenic progression to esophageal adenocarcinoma (222).
  • Grape seed extractGrape seed extract: In vitro, resveratrol potentiated grape seed extract induced human colon cancer cell apoptosis (248).
  • Heart rate regulating agentsHeart rate regulating agents: In human research, a polyphenol mixture, containing resveratrol, resulted in a significantly lower heart rate at 75W of exercise work (140). In epidemiological research, high urinary levels of resveratrol metabolites, a marker of wine and resveratrol intake, were associated with beneficial changes in heart rate (141).
  • Hepatoprotective agentsHepatoprotective agents: In animal research, resveratrol reduced hepatic injury associated with trauma hemorrhage (223) and improved levels of plasma AST and ALT (224). However, according to secondary sources, drinking large quantities of red wine, which contains resveratrol, may have adverse effects on the liver.
  • HypoglycemicsHypoglycemics: Based on a proposed mechanism of action, resveratrol may have the potential to aid in insulin resistance syndrome and type 2 diabetes (176). In animal and human research, resveratrol has been shown to increase insulin sensitivity (137; 138). In animal and human research, resveratrol reduced blood glucose (139; 135; 136; 138). In epidemiological research, high urinary levels of resveratrol metabolites, a marker of wine and resveratrol intake, were associated with beneficial changes in fasting blood glucose (141).
  • HypotensivesHypotensives: According to in vitro, animal, and human research, resveratrol may have antihypertensive effects, and in animal and human research, it has been shown to reduce blood pressure (130; 131; 132; 133; 134; 135; 136).
  • ImmunomodulatorsImmunomodulators: According to laboratory and in vitro research, immune function may be increased or inhibited by resveratrol, depending on its concentration (148; 149).
  • MelatoninMelatonin: In animal research, a combination of resveratrol and melatonin resulted in a reduction of induced tumor incidence and decreased the quantity of invasive and in situ carcinomas (249).
  • Neurologic agentsNeurologic agents: In human research, resveratrol increased cerebral blood flow (156). Resveratrol showed effects in in vitro and in vivo models of epilepsy, ischemia, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and nerve injury (8; 225; 226). It has been suggested that resveratrol has positive effects on neuronal cells (227; 228; 147).
  • PhytoestrogensPhytoestrogens: According to in vitro research, resveratrol has the potential to act as an estrogen agonist or antagonist, depending on such factors as cell type and estrogen receptor isoform (ER-alpha or ER-beta) (146; 144). The chemical structure of resveratrol has been found to be very similar to that of the synthetic estrogen agonist diethylstilbestrol (220). In estrogen receptor-positive breast cancer cells, resveratrol acted as an estrogen agonist in the absence of the endogenous estrogen 17-beta-estradiol, but as an estrogen antagonist in the presence of 17-beta-estradiol (145). However, according to laboratory research, resveratrol may act as an estrogen antagonist under some conditions (142; 143).
  • QuercetinQuercetin: Resveratrol may increase inhibitory effects on carcinoma cells when combined with quercetin and rutin (250; 251).
  • Renal agentsRenal agents: Although details are limited, resveratrol and exercise improved kidney disease comorbidities in a uremia model (230).
  • Respiratory agentsRespiratory agents: In vitro, resveratrol inhibited TNF-alpha induced IL-8, GM-CSF, and VEGF release from human airway smooth muscle cells (231). Resveratrol improved mitochondrial and tissue damage in a pulmonary ischemia reperfusion injury model (232); further details are not available at this time. In animal research, resveratrol prevented pulmonary hypertension (96).
  • RutinRutin: Resveratrol may increase inhibitory effects on carcinoma cells when combined with quercetin and rutin (250; 251).
  • UDP-glucuronosyl transferase (UGT) 1A1-metabolized agentsUDP-glucuronosyl transferase (UGT) 1A1-metabolized agents: In individuals with low baseline enzyme levels or activity, resveratrol induced GST-pi levels and UDP-glucuronosyl transferase 1A1 activity (233).
  • VasodilatorsVasodilators: In animal research, resveratrol induced vasorelaxation (105). Resveratrol was found to improve flow-mediated dilation in healthy exercising subjects (160). In vitro, resveratrol has been shown to significantly increase the expression of the gene-encoding eNOS, which synthesizes the vasodilator molecule NO, and to decrease expression of the potent vasoconstrictor endothelin-1 (ET-1) (234; 235).
  • Vitamin DVitamin D: According to in vitro research, resveratrol may enhance the growth inhibitory effects of vitamin D (252).

    • Resveratrol/Food Interactions:

  • Dietary flavonoidsDietary flavonoids: Compounds in the diet, such as quercetin and other flavonoids, may inhibit the sulphation and glucuronidation of resveratrol, improving its bioavailability (253).
  • High fat dietHigh fat diet: In human research, the mean area under the plasma concentration-time curve from 0-12 hours and the Cmax of resveratrol were 3,558 ? 2,195ng per hour/mL and 1,274 ? 790ng/mL respectively, after a standard breakfast, and 45% and 46% less, respectively, after a high-fat breakfast (151).
  • Phytoestrogen-containing foodsPhytoestrogen-containing foods: According to in vitro research, resveratrol has the potential to act as an estrogen agonist or antagonist, depending on such factors as cell type and estrogen receptor isoform (ER-alpha or ER-beta) (146; 144). The chemical structure of resveratrol has been found to be very similar to that of the synthetic estrogen agonist diethylstilbestrol (220). In estrogen receptor-positive breast cancer cells, resveratrol acted as an estrogen agonist in the absence of the endogenous estrogen 17-beta-estradiol, but as an estrogen antagonist in the presence of 17-beta-estradiol (145). However, according to laboratory research, resveratrol may act as an estrogen antagonist under some conditions (142; 143).
  • Red wineRed wine: In human research, consumption of red wine increased resveratrol and its metabolites in plasma (254; 255; 256).

    • Resveratrol/Lab Interactions:

  • AdiponectinAdiponectin: In human research, an anti-inflammatory dietary mix (including resveratrol, green tea extract, alpha-tocopherol, vitamin C, omega-3 polyunsaturated fatty acids, and tomato extract) increased levels of plasma adiponectin (257).
  • Antibody titerAntibody titer: In human research, a supplement based on resveratrol was used, with evidence of benefit on antibody titer (162).
  • BilirubinBilirubin: In human research, resveratrol resulted in significant changes (direction unclear at this time) in total bilirubin (151).
  • Blood glucoseBlood glucose: Based on a proposed mechanism of action, resveratrol may have the potential to aid in insulin resistance syndrome and type 2 diabetes (176). In animal and human research, resveratrol has been shown to increase insulin sensitivity (137; 138). In animal and human research, resveratrol reduced blood glucose (139; 135; 136; 138). In epidemiological research, high urinary levels of resveratrol metabolites, a marker of wine and resveratrol intake, were associated with beneficial changes in fasting blood glucose (141).
  • Blood pressureBlood pressure: According to in vitro, animal, and human research, resveratrol may have antihypertensive effects, and in animal and human research, it has been shown to reduce blood pressure (130; 131; 132; 133; 134; 135; 136)
  • C-reactive protein (CRP)C-reactive protein (CRP): In human research, a resveratrol-enriched grape extract decreased levels of CRP vs. baseline, but a placebo or a grape extract lacking resveratrol enrichment did not (158).
  • Coagulation panelCoagulation panel: Laboratory research suggests that resveratrol inhibits platelet aggregation and thrombin activity (27; 28; 29; 30; 31; 32; 33; 15).
  • CytokinesCytokines: In an animal arthritis model, resveratrol decreased serum levels of proinflammatory cytokines (37). In early human research, resveratrol was shown to inhibit inflammatory cytokine release from isolated alveolar macrophages from bronchoalveolar lavage (BAL) fluid from patients with chronic obstructive pulmonary disease (COPD) (258). Inflammatory cytokines were reduced in other animal models (223), human studies (135; 158), or other studies with limited available details (259). In human research, a resveratrol-enriched grape extract increased levels of IL-10 (158).
  • Glycated hemoglobin (HbA1C)Glycated hemoglobin (HbA1C): In animal and human research, resveratrol decreased levels of HbA1C (136; 139).
  • Heart rateHeart rate: In human research, a polyphenol mixture, containing resveratrol, resulted in a significantly lower heart rate at 75W of exercise work (140). In epidemiological research, high urinary levels of resveratrol metabolites, a marker of wine and resveratrol intake, were associated with beneficial changes in heart rate (141).
  • Hormone panelHormone panel: The chemical structure of resveratrol has been found to be similar to that of the synthetic estrogen agonist diethylstilbestrol (220), suggesting that resveratrol may function as an estrogen agonist. However, according to laboratory research, resveratrol may act as either an estrogen antagonist under some conditions (142; 143) or an estrogen agonist (144) under other conditions. In estrogen receptor-positive breast cancer cells, resveratrol acted as an estrogen agonist in the absence of the endogenous estrogen 17-beta-estradiol, but as an estrogen antagonist in the presence of 17-beta-estradiol (145). According to in vitro research, resveratrol has the potential to act as an estrogen agonist or antagonist, depending on such factors as cell type and estrogen receptor isoform (ER-alpha or ER-beta) (146).
  • Immune panelImmune panel: According to laboratory and in vitro research, immune function may be increased or inhibited by resveratrol, depending on its concentration (148; 149).
  • InsulinInsulin: In human research, resveratrol decreased plasma insulin (135).
  • Insulin-like growth factor (IGF)-1Insulin-like growth factor (IGF)-1: In human research, resveratrol resulted in a decrease in circulating IGF-I and IGFBP-3 (152).
  • LeptinLeptin: In human research, resveratrol lowered leptin levels (135).
  • Lipid profileLipid profile: In animal and human research, resveratrol, as well as LGP, which is rich in resveratrol, has been shown to reduce plasma triglycerides, LDL cholesterol, and apolipoprotein B and E concentrations, and to decrease cholesterol ester transfer protein activity (185; 82; 136; 135; 157). In epidemiological research, high urinary levels of resveratrol metabolites, a marker of wine and resveratrol intake, were associated with beneficial changes in blood lipids (HDL cholesterol, triglycerides) (141).
  • Liver enzymesLiver enzymes: In animal and human research, resveratrol reduced plasma AST and ALT (224; 223; 135).
  • Plasminogen activator inhibitor (PAI)-1Plasminogen activator inhibitor (PAI)-1: In human research, a resveratrol-enriched grape extract decreased levels of PAI-1 vs. baseline (158).
  • PotassiumPotassium: In human research, resveratrol resulted in significant changes (direction unclear at this time) in serum potassium (151).
  • ProteinProtein: In human research, resveratrol decreased total protein (136).
  • Prothrombin time/INR (international normalized ratio)/plateletsProthrombin time/INR (international normalized ratio)/platelets: Laboratory research suggests that resveratrol has antiaggregating and antithrombin activity (27; 28; 29; 30; 31; 32; 33; 15).
  • ResveratrolResveratrol: In human research, resveratrol supplementation increased plasma levels of resveratrol (155).
  • Urea nitrogenUrea nitrogen: In human research, resveratrol decreased urea nitrogen (136).
  • Urinary F(2)-isoprostanesUrinary F(2)-isoprostanes: LGP, which is rich in resveratrol, has been shown to decrease whole-body oxidative stress, as measured by urinary F(2)-isoprostanes (185).
  • Urinary ortho-tyrosineUrinary ortho-tyrosine: In human research, resveratrol decreased urinary ortho-tyrosine excretion (161).
  • White blood cellsWhite blood cells: In human research, resveratrol decreased leukocyte counts (135).
  • X-irradiationX-irradiation: In preliminary research, simultaneous exposure to X-irradiation and resveratrol has been shown to have synergistic effects (260; 261).