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Resveratrol

Scientific Name(s): 3,4′,5-trans-trihydroxystilbene, 3,5,4′-cis-trihydroxystilbene, 3,5,4′-trihydroxy-trans-stilbene
Common Name(s): Darakchasava, Phytoalexin, Piceatannol (analogue), Resveratrol

Medically reviewed by Drugs.com. Last updated on Jan 12, 2023.

Clinical Overview

Use

Researchers have suggested that consumption of resveratrol may potentially benefit numerous clinical conditions, including cancer, cardiovascular disease, obesity and related conditions including diabetes and non-alcoholic fatty liver disease, and neurological diseases. However, current evidence is insufficient to support a definitive place in therapy for resveratrol in these conditions. Resveratrol improved lumbar bone mineral density and bone resorption in post-menopausal women; however, the whole-body risk of major factures was unaffected. The adverse effects associated with higher dosages limit its applications.

Dosing

Lumbar bone mineral density: 75 mg (more than 98% trans-resveratrol) twice daily was used for 12 months. Evidence from other clinical studies is insufficient to provide dosing guidelines.

Contraindications

Depending on the formulation, some products are contraindicated in growing children, menstruating females, and in the presence of anemia due to binding of resveratrol to copper and iron.

Pregnancy/Lactation

Avoid due to lack of clinical data.

Interactions

Resveratrol may interact with carbamazepine and other substrates of CYP3A4.

Adverse Reactions

Adverse events for lower doses and shorter courses of treatment have been rare. Higher dosages (more than 1 g/day) may result in GI symptoms; a case of serious leukopenia and thrombocytopenia has also been reported. Resveratrol may negate exercise-induced cardiovascular benefit.

Toxicology

Limited animal studies suggest that resveratrol is noncarcinogenic and nontoxic at lower dosages, although renal toxicity has been observed at higher doses. No toxicity data for long-term administration in humans is available.

Source

Resveratrol is a naturally occurring phytoalexin produced by plants in response to stress such as injury, ultraviolet radiation, ozone exposure, and fungal attack. Commercial preparation of resveratrol is possible, although low yield and purity result. Extraction from plant sources is an intensive process. Microorganisms are used to produce resveratrol via genetic manipulation. Plant and dietary sources include purple grapes, the dried roots of Japanese knotweed, blueberries, cranberries, mulberries, rhubarb, pistachio, groundnuts, and cocoa.1, 2, 3

History

The traditional Ayurvedic medicine darakchasava contains resveratrol in its formulation. Resveratrol was initially identified in the roots of Veratrum grandiflorum (false hellebore) in 1940, and then later in Japanese knotweed in 1963, when interest was focused primarily on its potential in cardiovascular disease. Resveratrol's possible activity against carcinogens was identified in 1997, and research now also includes interest in its activity in inflammation, aging, diabetes, and neurological diseases.1, 2

Although World Health Organization data associate fat consumption with coronary heart disease, among certain populations where high-fat intake is observed with daily consumption of wine (eg, Italy, Switzerland, France), low coronary heart disease mortality rates exist. Termed the "French paradox," it is attributed in part to the presence of resveratrol in wine.1, 2, 4

Chemistry

Resveratrol is found in nature as cis-resveratrol and trans-resveratrol. Of the 2 isomers, research has been focused on the trans-resveratrol isomer because it is thought to be more abundant and more biologically active than the cis-resveratrol form. However, trans-resveratrol is highly photosensitive and easily converts to cis-resveratrol.1

Several analogues and encapsulated formulations exist that may have a greater bioavailability than resveratrol, including piceatannol, M8, pterostilbene, viniferin, and piceid.1, 5

Uses and Pharmacology

Data from animal studies should be extrapolated cautiously to humans because bioavailability of orally administered resveratrol is poor, and the matrix in which resveratrol is delivered may exert an influence on bioavailability.(3) Efficacy has largely been attributed to antioxidant activity; however, antioxidant activity has not been demonstrated in all in vivo studies.(3, 5) Activity of resveratrol in the sirtuin system has been described.(6, 7, 8)

Antiaging

Animal data

Numerous studies have explored the molecular biology and antiaging activity of resveratrol.(9, 10) Resveratrol was reported to slow aging and increase life span in simple organisms such as yeast, fish, and mice.(11, 12, 13) Trans-resveratrol concentrations in plasma and tissues after oral administration of red wine to rats or humans are similar to concentrations that have been active in vitro, usually in the range of 1 to 30 mcmol.(9)

Clinical data

Research reveals no clinical data regarding resveratrol's use in antiaging. The reported antiaging activity of resveratrol has been promoted in the marketing of skin care formulations, although unproven.(14)

A 9-year prospective cohort study (InCHIANTI) of 783 Italian community-dwelling adults 65 years or older utilized a food questionnaire and found no association between total urinary resveratrol metabolite concentrations and all-cause mortality; however, a higher proportion of participants who lacked urinary resveratrol died compared with those with urinary measurements. Urinary resveratrol was strongly associated with alcohol intake.(71)

Anti-inflammatory

Resveratrol inhibits the synthesis and release of proinflammatory mediators, modifies eicosanoid synthesis, inhibits activated immune cells, and inhibits cyclooxygenase (COX)-1 and COX-2 in vitro.(15, 16, 17)

Animal data

In rat models of chronic colitis, resveratrol reduced neutrophil infiltration and proinflammatory cytokines, and NF-kappaB protein expression was reduced.(18, 19) Resveratrol suppressed inflammation and inhibited lipid peroxidation in glycerol-induced renal injury in rats.(20)

Clinical data

In a meta-analysis, data pooled from 6 randomized controlled trials (N=415) that enrolled patients with cardiovascular disease revealed that administration of resveratrol significantly reduced levels of tumor necrosis factor (TNF)-alpha (mean difference [MD] −0.55; 95% confidence interval [CI], −1.04 to −0.063; P=0.027) and C-reactive protein (CRP) (MD, −0.63; 95% CI, −1.133 to −0.128; P=0.014) but not those of interleukin (IL)-6. Heterogeneity was not significant for any of the outcomes. Subgroup analyses revealed that doses more than 15 mg/day, but not less than that, produced significant reductions in both TNF-alpha (P<0.01) and CRP (P=0.01). However, only TNF-alpha reductions remained significant when the duration of supplementation was 9 weeks or less (P=0.04) but for CRP it was only significant at more than 9 weeks (P=0.01). Resveratrol was dosed at 20 mg/day or less (range, 8.1 to 20 mg/day) in all but 2 studies, which used 100 and 500 mg/day, and was given for durations that ranged from 4 to 52 weeks. The studies were published between 2012 and 2019, categorized as good (n=4) or fair (n=2) quality with sample sizes that ranged from 9 to 30 subjects in each study.(118)

Resveratrol inhibited basal release of the inflammatory cytokine IL-8 from alveolar macrophages in patients who smoke and in those with chronic obstructive pulmonary disease.(21)

An author-funded study reported reduction in facial redness in subjects (n=16) treated topically twice daily for 8 to 12 weeks with a combination product containing resveratrol, green tea polyphenols, and caffeine. Subjective evaluation by trained observers and clinicians documented improvement in 100% and 81% of subjects’ clinical photographs and spectrally-enhanced red images, respectively. The preliminary split-face study (with and without resveratrol) demonstrated decreased redness only when resveratrol was added to the treatment.(65)

A 9-year prospective cohort study (InCHIANTI) of 783 Italian community-dwelling adults 65 years and older utilized a food questionnaire and found no association between total urinary resveratrol metabolite concentrations and inflammatory markers (ie, serum c-reactive protein, IL-6, IL-1-beta, TNF); however, participants with no urinary resveratrol metabolites were more likely to have higher levels of IL-1-beta and TNF. Urinary resveratrol was strongly associated with alcohol intake.(71)

Cancer

Resveratrol has been reported to be effective in blocking all 3 stages of carcinogenesis (ie, initiation, promotion, progression).(22) Numerous molecular mechanisms of anticancer activity are associated with resveratrol, including blocking carcinogen activation by inhibiting phase I enzymes, enhancing antioxidant capacity and inducing phase II carcinogen detoxifying enzymes, arresting cell proliferation by modulating cell cycle regulatory machinery, inducing apoptosis of damaged or transformed cells, turning off the angiogenic switches and blocking neovascularization in tumor tissues, suppressing invasion and metastasis, and sensitizing tumor cells for chemotherapy-induced apoptosis.(23, 24, 25)

Animal data

Resveratrol induces differentiation and apoptosis in cancer cell lines, including leukemia, colon, breast, and prostate cancers, and esophageal cells and radiation-induced chromosome aberration. Several review articles report on resveratrol's anticancer activity,(22, 23, 24, 25, 26, 27) and the publication of experimental studies is exponential. Studies evaluating the effects of combinations of resveratrol and chemotherapeutic agents and other polyphenols have been published.(27)

Clinical data

Limited clinical trial data is available beyond dose-escalation tolerability and safety studies in healthy volunteers.(2, 5, 27) Several trials are currently listed in the ClinicalTrials.gov database of publicly and privately supported clinical studies of human participants conducted around the world, but results are not yet available.(28) The effect of resveratrol on cell proliferation in colorectal epithelial cells was positively reported in a small study (N=6).(27) In a study of 24 patients with refractory multiple myeloma, investigators noted minimal efficacy together with unacceptable adverse events following the administration of resveratrol SRT501 5 g daily.(29) Another small clinical study (N=39) evaluated the effect of resveratrol 100 mg daily for 12 weeks on markers of breast cancer.(30) While another, conducted in 34 overweight postmenopausal women, documented some favorable effects of resveratrol 1 g/day for 12 weeks on hormone-related breast cancer risk factors including estrogen metabolism, sex steroid hormone-binding globulin, and urinary 2-hydroxyestrone levels.(73)

A 9-year prospective cohort study (InCHIANTI) of 783 Italian community-dwelling adults 65 years and older utilized a food questionnaire and found no association between total urinary resveratrol metabolite concentrations and prevalence of cancer; urinary resveratrol was strongly associated with alcohol intake.(71)

Cardiovascular disease

Animal data

Numerous mechanisms have been suggested for the observed beneficial cardiovascular effects of resveratrol based on in vitro and animal studies.(31, 32) Resveratrol 5 to 25 mmol/L may have antifibrotic activity; it inhibits growth paths stimulated by angiotensin II, epidermal growth factor, or transforming growth factor beta, all of which are essential in fibroblast proliferation and differentiation.(32) Resveratrol reduced infarct size and improved left systolic and diastolic function following myocardial ischemia in rats, possibly by reducing atrial natriuretic peptide and transforming growth factor beta1, both of which protect the heart from detrimental remodeling.(33) Prevention of ischemic reperfusion injury has also been documented in other studies.(34)

Clinical data

Despite evidence to support a reduction in hypertension, heart failure, and ischemic heart disease in rodents, clinical trial data for the use of resveratrol in human pathology are limited.(26) Small trials have reported increased flow-mediated vasodilation following administration of resveratrol doses up to 270 mg and increased cerebral blood flow following doses of resveratrol 500 mg.(2) Flow-mediated vasodilation (FMD) was also significantly improved in a small double-blind crossover trial in 28 obese, otherwise healthy, patients who took trans-resveratrol 75 mg/day for 6 weeks; extent of benefit was negatively correlated with baseline FMD. No benefit was noted in cognitive performance.(68)

One clinical trial demonstrated improvement in ventricular function marker (brain natriuretic peptide) following administration of resveratrol 20 mg/day over 60 days,(35) and another found improved biomarkers among patients with stable coronary artery disease who took resveratrol 10 mg daily for 3 months.(36) Similar effects with resveratrol 350 mg daily over 6 months have been reported in studies conducted in Spain.(37, 38, 39)

High-dose resveratrol (1,000 mg daily × 1 week then 2,000 mg daily × 1 week) reduced intestinal and hepatic lipoprotein particle production in overweight or obese men with mild hypertriglyceridemia in a double-blind, cross-over randomized clinical trial (n=8). ApoB-48 and apoB-100 production were significantly reduced by 22% and 27%, respectively; however, insulin sensitivity, fasting, and fed plasma triglyceride levels were not significantly affected. No adverse effects were reported.(64) A systematic review and meta-analysis evaluated 7 trials (N=282) and determined that, overall, resveratrol supplementation had no significant effect on any lipid concentrations. Subgroup analyses based on coronary heart disease risk and duration of therapy yielded results consistent with the overall analysis.(67)

Cardiovascular benefit in 27 men 60 to 72 years of age induced by intensive exercise training was negated by the administration of trans-resveratrol 250 mg/day over 8 weeks. Mean arterial blood pressure, certain cholesterol parameters (ie, total cholesterol:high-density lipoprotein ratios, low-density lipoprotein, and triglycerides), and maximal oxygen uptake were significantly higher in men randomized to exercise plus placebo. Additionally, the vasodilator prostacyclin was significantly higher in the exercise plus placebo group, indicating a vasoconstrictive state in the resveratrol group.(69) A 2015 meta-analysis of data from 6 randomized clinical trials (N=247) investigating the effect of at least 2 weeks of resveratrol supplementation on blood pressure identified a significant benefit by subgroup analysis only on systolic blood pressure [SBP] (−11.9 mm Hg, P=0.01) and only at "higher" doses (at least 150 mg/day). Of the 6 included studies, 1 trial enrolled healthy volunteers, while the others included patients with type 2 diabetes mellitus, cardiovascular disease, metabolic syndrome, and obesity. Overall, significant publication bias was documented and no significant dose effects of resveratrol on SBP or diastolic blood pressure (DBP) were found.(77)

A 9-year prospective cohort study (InCHIANTI) of 783 Italian community-dwelling adults 65 years and older utilized a food questionnaire and found no association between total urinary resveratrol metabolite concentrations and prevalence of cardiovascular disease; however, a significantly higher proportion of participants who lacked urinary resveratrol had strokes compared with those with urinary resveratrol measurements. Urinary resveratrol was strongly associated with alcohol intake.(71)

CNS

Clinical data

The effect of adjunctive resveratrol on irritability in 62 children with autism spectrum disorder concurrently treated with risperidone was explored in a double-blind, randomized, placebo-controlled trial. After 10 weeks, both resveratrol (250 mg twice daily) and placebo resulted in significant improvements from baseline in 4 of the 5 total measures: irritability, lethargy, stereotypic behavior, and inappropriate speech (P<0.001 for all) with no significant difference between groups. In contrast, the hyperactivity/noncompliance score was significantly improved with resveratrol compared to placebo (mean difference, 4.51; 95% confidence interval, 0.1 to 8.92; P=0.04).(114)

Diabetes

Animal data

Studies in animals (largely in rodents) support a role for resveratrol in the treatment of obesity and diabetes, with improved glucose metabolism and lipid profiles observed. In addition, weight loss has been reported in some studies, with possible increases in metabolic rate.(2, 5, 26)

Clinical data

Although improved insulin sensitivity has been reported following higher doses of resveratrol, some studies have produced equivocal results.(2, 5) Clinical studies have primarily been conducted in nondiabetic obese volunteers or have been pilot or open-label studies.(40, 41, 42, 43, 44)

A meta-analysis of 11 randomized clinical trials (N=388) published through March 2014 and evaluating the effects of resveratrol on glucose control and insulin sensitivity revealed a significant effect in diabetic, but not nondiabetic, participants. Resveratrol dosing ranged from 8 to 1,500 mg/day for a duration of 2 weeks to 6 months. Trials were conducted in participants with type 2 diabetes (n=3), cardiovascular disease (n=3), obesity (n=3), metabolic syndrome (n=1), and healthy volunteers (n=1); 8 of the studies included overweight or obese patients with a body mass index of 25 or more (in kg/mg2). Diabetic patients experienced significant reductions in fasting glucose (−35.22 mg/dL; P<0.01), fasting insulin concentrations (−4.55 microunits/mL; P<0.01), HbA1c (−0.79%; P=0.02), and insulin resistance (homeostatic model assessment - insulin resistance [HOMA-IR]; −2.25; P<0.01). Significant between-study heterogeneity was observed for blood glycemic measures of diabetics.(74)

Similar results were found in a small randomized, double-blind, placebo-controlled trial (n=24) in adults with metabolic syndrome and a body mass index (BMI) between 30 and 39 such that patients who received resveratrol 1,500 mg/day for 90 days experienced significant reductions in total weight (P=0.007), BMI (P=0.006), fat mass (P=0.001), waist circumference (P=0.004), and insulin secretion (P=0.004). No differences were observed in the placebo group. Treatment was well tolerated and no serious adverse events were noted.(75) In men with metabolic syndrome, 2 doses of resveratrol were investigated for effects on cellular inflammation and glucose metabolism in a randomized, double-blind, placebo-controlled trial (n=74). Participants randomly received resveratrol 75 mg or 500 mg twice daily or placebo for 16 weeks. No significant improvements in inflammatory biomarkers, insulin sensitivity, lipids, or subcutaneous fat accumulation were observed. Instead, a significant worsening of glucose and lipid metabolism were observed in the high-dose resveratrol group compared to placebo as reflected by increases in fructosamine (+11.8 micromol/L; P<0.0113), LDL cholesterol (+0.61 mmol/L; P<0.006), and total cholesterol (+0.69 mmol/L; P<0.002).(86) Similarly, a slight increase in total cholesterol and triglycerides was observed with 6-month administration of 500 mg/day, but not 40 mg/day, of resveratrol in adults with type 2 diabetes managed with oral medications. This double-blind, randomized, placebo-controlled trial (n=192) found no significant effect of resveratrol on C-reactive protein, BMI, waist circumference, BP, IL-6, fasting glucose, HbA1c, HOMA-IR, C-peptide, AST, ALT, GGT, uric acid, adiponectin, free fatty acids, or lipid parameters. Compared to placebo, subgroup analysis revealed a significantly higher reduction in C-reactive protein in patients taking the higher dose (500 mg/day) who had a shorter duration of diabetes (less than 8 years), were of a younger age (65 years), used aspirin, and smoked. Additionally in the 40 mg/day group, a significant interaction effect was found with duration of diabetes and C-reactive protein values, such that values decreased with a duration of disease of less than 8 years and increased with a longer history of disease. Both doses were well tolerated with no major adverse effects reported.(87)

As an adjunct to pharmacological treatment in patients with type 2 diabetes mellitus, resveratrol supplementation ranging from 10 to 5,000 mg/day for 4 weeks to 12 months duration was found to be significantly more effective than placebo or control for improving SBP, hemoglobin A1c, and creatinine (P<0.05 for each) in a systematic review and meta-analysis that included data from 6 clinical trial registries (N=196). No significant effects were found for fasting glucose, DBP, insulin, trigylcerides, low-density lipoprotein (LDL), high-density lipoprotein, or homeostatic model assessment of insulin resistance.(78) In a meta-analysis of 31 randomized controlled trials (N=1,722), the effects of resveratrol on lipid and liver enzymes in patients with metabolic syndrome and related disorders was investigated. Dosages ranged from 20 to 3,000 mg/day given for 4 to 48 weeks. A significant benefit for resveratrol was reported only for total cholesterol (weighted mean difference [WMD]= −7.65 mg/dL; 95% CI, −12.93 to −2.37; P<0.01) and GGT (WMD= +1.76 units/L; 95% CI, 0.58 to 2.94; P<0.01) but not for triglycerides, LDL, HDL, ALT, or AST. Subgroup analysis revealed no significant differences based on dose, duration of therapy, or type of disease (ie, overweight/obese, type 2 diabetes, other).(116)

In a double-blind, randomized, placebo-controlled study (n=110) conducted in type 2 adult diabetics on oral hypoglycemic agents for at least a year, administration of resveratrol 200 mg/day for 24 weeks significantly improved fasting blood glucose (by 7.56%), HgA1c (by 6.31%), fasting insulin (9.96%), insulin resistance (HOMA-IR by 17.96%; P<0.05 each). In addition to improvement seen in glycemic parameters with resveratrol, anti-inflammatory and redox markers also improved and included TNF-alpha, IL-6, malondialdehyde, and microalbuminuria by 13.67%, 13.27%, 8.46%, and 13.48%, respectively (P<0.05). Non-significant changes in lipids were observed between groups.(119)

The safety and efficacy of adjunctive resveratrol have also been investigated in patients with type 1 diabetes. Resveratrol 500 mg twice daily was supplemented for 2 months in patients 12 to 45 years of age who were currently on oral antidiabetic therapy and insulin injection in an exploratory uncontrolled trial. Compared to baseline, HbA1c and fasting blood glucose were statistically significantly reduced by −0.52% (P=0.033) and by −79.31 mg/dL (P<0.001), respectively. The antioxidant measure of malondialdehyde and total antioxidant capacity were also significantly improved (P<0.002 and P<0.001, respectively). No other parameters (ie, anthropomorphic, insulin resistance, C-reactive protein, liver function tests) were significantly affected.(117)

Exercise capacity

Clinical data

In a phase 2 randomized, double-blind, placebo-controlled, crossover pilot study in 13 healthy sedentary adults, the effect of resveratrol on exercise capacity was assessed via exercise duration on constant load at 75% max and peak oxygen uptake on incremental exercise testing. Oral resveratrol was initiated at 500 mg twice daily for 1 week then increased to 1,000 mg twice daily for 3 more weeks, if tolerated, with a 2-week washout. No significant effect was found on exercise capacity. All but 1 participant was able to tolerate the 2 g/day dose; however, GI complaints were significantly more common (77%) with resveratrol than placebo (15%) and included diarrhea, nausea, and cramping.(83)

Macular degeneration

Clinical data

Three case studies in octogenarians with age-related macular degeneration demonstrated dramatic anatomic retinal restoration and visual improvement, in addition to unexpected systemic benefits, subsequent to daily administration of a resveratrol-based nutritional supplement. The product contained 100 mg micronized/microencapsulated trans-resveratrol combined with quercetin, ferulic acid, vitamin D3, and a copper-iron-calcium binding molecule (inositol hexaphosphate). Objective retinal imaging suggested improvements in both anterior and posterior retinal photoreceptor structural health that was accompanied by superior acuity and greater comprehensive visual function (ie, contrast sensitivity, scotoma resolution). Improvements occurred bilaterally, less in the more severely diseased eye, and were noticeable within 4 days of supplementation and continued for more than 1 year with daily use. Medically documented improvements in comorbidities as well as physical stamina were also reported during supplement administration. Lab development funding was provided by the product sponsor.(66)

Memory performance

Clinical data

A double-blind, placebo-controlled interventional study (n=46) evaluated the effects of resveratrol supplementation on memory performance in healthy overweight adults. Resveratrol 200 mg/day for 26 weeks significantly improved specific memory function (ie, word retention over a 30-minute delay; P=0.038), increased hippocampal functional capacity (P<0.05), reduced HbA1c (P=0.014), and increased leptin (P<0.001) compared with placebo. Compared with baseline, the resveratrol group also experienced significant benefit on the delayed recall and recognition score (P<0.05); however, the difference between groups was not significant. Improved cognitive function was positively correlated to improvements in leptin and HbA1c; the latter suggesting improved glucose metabolism (even within normal limits) as a potential underlying mechanism.(70)

Neurodegenerative conditions

Animal data

Most evidence supports resveratrol's role in activating the SIRT1/PGC-1 pathway, which improves mitochondrial function.(45) A role for resveratrol in Alzheimer, Huntington, and Parkinson diseases, as well as in neurological injury, has been suggested on the basis of studies in rodents.(26, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)

Clinical data

A randomized, double-blind, placebo-controlled, within-subjects crossover trial (n=23) found that the combination of piperine 20 mg with trans-resveratrol 250 mg, but not resveratrol alone, significantly improved central blood flow but not cognitive performance in healthy young adults.(72) In a 9-year prospective cohort study (InCHIANTI) of 783 Italian community-dwelling adults 65 years and older, a food questionnaire was utilized to examine the relationship between urinary resveratrol levels and all-cause mortality. Although no association was found for the primary end point, a significantly higher proportion of participants had cognitive impairment (Mini-Mental State Examination score, <24) who had no urinary resveratrol metabolites compared with those who did have urinary resveratrol measurements. Urinary resveratrol was strongly associated with alcohol intake.(71) Statistically significant improvements in performance of a single cognitive task on day 1 and subjective ratings of fatigue throughout the 28 day study were observed in healthy, young adults who received trans-resveratrol 500 mg/piperine10 mg for 28 days in a double-blind, randomized, placebo-controlled, parallel-group study. Additionally, a significant increase in diastolic blood pressure was observed in the resveratrol group. No effect was found on mood, sleep quality, general health, or other cognitive tasks.(81) A double-blind, randomized, placebo-controlled multicenter phase 2 trial examined the primary outcomes of safety, tolerability, and effects on biomarkers and volumetric magnetic resonance image of resveratrol over a 52-week period in 119 adults with mild to moderate Alzheimer disease (mini-mental state examination 14 to 26 at screening). Resveratrol was initiated at 500 mg once daily and escalated every 13 weeks to a final dose of 1,000 mg twice daily. The placebo group was noted as having a longer duration of disease from symptom onset but not in years from diagnosis. The group treated with resveratrol lost a statistically significant amount of weight resulting also in a significantly lower BMI over the study period compared to the placebo group. The cerebrospinal fluid and plasma level of biomarker Aβ40 declined significantly with resveratrol treatment as did brain volume. No serious adverse events were related to the use of resveratrol.(82)

Nonalcoholic fatty liver disease

Clinical data

A randomized, double-blind, placebo-controlled trial evaluating the effects of resveratrol supplementation on liver enzymes, inflammatory biomarkers, hepatic elasticity, and echogenecity was conducted in patients with nonalcoholic fatty liver disease (NAFLD) (n=50). Patients were randomized to either 500 mg trans-resveratrol or placebo (medium chain triglycerides) for 90 days in conjunction with lifestyle interventions that included an energy-balanced diet and physical activity. Anthropomorphic measurements, liver enzymes, and steatosis grade improved significantly in both groups (P<0.005); however, resveratrol supplementation was associated with significantly greater improvements in ALT, inflammatory cytokines, nuclear factor kappaB activity, serum cytokeratin-18 (a biomarker of hepatic apoptosis), and hepatic steatosis grade (P<0.05).(76) Similarly, resveratrol 600 mg/day for 3 months significantly decreased liver enzymes (ALT, AST), glucose, insulin resistance, LDL-cholesterol, and total cholesterol, as well as serum cytokines including TNF-alpha (an inflammatory cytokine that independently predicts histological fibrosis in NAFLD), cytokeratin 18 fragment (a biomarker of hepatic apoptosis), fibroblast growth factor 21, and elevated adiponectin levels in adults with NAFLD enrolled in a double-blind, randomized, placebo-controlled trial in China. No adverse events were reported by participants.(80) In contrast, administration of resveratrol 500 mg 3 times daily for 6 months to patients with transaminasemia, suspected NAFLD, BMI of at least 25 kg/cm2, and at least 1 additional element of metabolic syndrome, but not diabetes, failed to produce significant benefit in a prospective, double-blind, randomized controlled trial (n=28). Although ALT levels and intrahepatic lipid content significantly decreased with resveratrol compared to baseline, the difference was not significant compared to placebo. The major limiting factor of the study was the small sample size. The study was underpowered; a change in plasma ALT of 25 units/L could be detected with a 2-sided 0.05 significance at 0.60. Adverse events in the resveratrol group that led to study discontinuation included 1 case with GI problems and 1 case of serious febrile leukopenia and thrombocytopenia (after 10 days of treatment that recurred upon repeated exposure).(84)

A meta-analysis of randomized controlled trials sought to determine if resveratrol supplementation was beneficial for patients with NAFLD. The 4 eligible studies were published between 2014 and 2016 and included 156 participants. Besides significant increases in total cholesterol and LDL cholesterol (P<0.05 each) observed with resveratrol supplementation in patients with NAFLD compared to controls, no other significant changes were detected for weight, body mass, blood pressure, HDL cholesterol, insulin, insulin resistance, liver enzymes, bilirubin, or tumor necrosis factor-alpha. Publication bias was not statistically significant.(85)

Osteoporosis and bone metabolism

Clinical data

Although lumbar bone mineral density (BMD) and bone resorption were significantly improved with resveratrol supplementation, the overall risk of major fractures was not in the Resveratrol for Healthy Ageing in Women (RESHAW) 24-month crossover trial conducted in 125 postmenopausal women. Supplementation with 150 mg/day of resveratrol significantly improved BMD of the lumbar spine (P<0.001) but not femur neck (P=0.058) or total hip (P=0.054) compared to placebo treatment after adjusting for false discovery rate; absolute values were significant for all 3 outcomes (P<0.001, P=0.035, and P=0.029, respectively). Bone resorption markers were also significantly lower during the resveratrol phase compared to the placebo phase (P=0.015, adjusted). Subgroup analysis showed an enhanced effect of resveratrol for women who regularly used vitamin D plus calcium supplements in lumbar BMD compared to calcium only, and in total hip BMD compared to those who consumed neither vitamin D nor calcium supplements.(115)

Sleep

Clinical data

In an observational study (n=60) of patients with hepatitis C treated with peg-IFN-alpha and ribavirin, the addition of resveratrol (19.8 mg 3 times daily × 12 months) significantly improved sleepiness scores in responders (P<0.05) compared with placebo. Scores among patients overall for general health, mood, sleep quality (P<0.001 each), and sleepiness (P<0.05) were better with resveratrol than placebo. No serious adverse events were noted; the incidence of psychological adverse events was found to be lower in the resveratrol group.(88)

Dosing

Although resveratrol is extensively absorbed orally (approximately 70%), due to rapid metabolism, bioavailability is poor. Significant person-person variability has been reported, and the presence of food in the stomach is likely to decrease absorption. Metabolism is dependent on intestinal microflora and hepatic function for sulfation.1, 2, 5, 58 The plasma pharmacokinetics of resveratrol and its metabolites in healthy volunteers have been described.59, 60

Lumbar bone mineral density

Resveratrol (more than 98% trans-resveratrol) 75 mg twice daily was used for 12 months.115

Evidence from other clinical studies is insufficient to provide dosing guidelines.

acetylcysteine, ascorbic acid, biotin, multivitamin, Dextrose

Pregnancy / Lactation

Avoid due to lack of clinical data. Resveratrol is structurally similar to the synthetic estrogen diethylstilbestrol and may have estrogenic activity.61

Interactions

A pharmacokinetic study in 12 healthy males was conducted to determine the effect of resveratrol pretreatment on the pharmacokinetics of carbamazepine and on the CYP3A4 enzyme activity. Compared to control, a single 500 mg dose of resveratrol administered once daily for 10 days prior to a single dose of carbamazepine 200 mg significantly increased maximal drug concentration (by 46.2%), area under the curve (by 37.1%), and half-life (by 22.8%) of carbamazepine and significantly decreased apparent oral clearance (by 33.1%) and apparent volume of distribution (by 19.3%). However, time to reach maximum drug concentration and elimination rate constant were not significantly changed. Additionally, carbamazepine metabolite:parent ratios of Cmax and AUC were also significantly decreased.79

Aripiprazole: CYP3A4 inhibitors (weak) may increase the serum concentration of aripiprazole. Further dose reductions may be recommended with concomitant use of a CYP2D6 inhibitor. Aripiprazole dose reductions may be recommended in CYP2D6 "poor metabolizers." Aripiprazole dose reduction is not recommended when used as adjunctive therapy for major depressive disorder.95, 96, 97, 98, 99

Buspirone: Resveratrol may increase the serum concentration of buspirone. Monitor therapy.100, 101, 102, 103

Carbamazepine: Resveratrol may increase the serum concentration of carbamazepine. Monitor therapy.101, 102, 103, 104

Diclofenac (systemic): Resveratrol may increase the serum concentration of diclofenac (systemic). Monitor therapy.100, 105, 106

Dofetilide: CYP3A4 inhibitors (weak) may increase the serum concentration of dofetilide. Monitor therapy.107, 108, 109

Flibanserin: CYP3A4 inhibitors (weak) may increase the serum concentration of flibanserin. Monitor therapy.110

Lomitapide: CYP3A4 inhibitors (weak) may increase the serum concentration of lomitapide. Consider therapy modification.93, 94

Losartan: Resveratrol may decrease serum concentrations of the active metabolite(s) of losartan. Resveratrol may increase the serum concentration of losartan. Monitor therapy.100, 111, 112

Nimodipine: CYP3A4 inhibitors (weak) may increase the serum concentration of nimodipine. Monitor therapy.113

Pimozide: CYP3A4 inhibitors (weak) may increase the serum concentration of pimozide. Avoid combination.89, 90, 91, 92

Adverse Reactions

Clinical studies of single doses of trans-resveratrol 5 g resulted in no observed adverse events, and adverse events for low doses (less than 1 g) or short courses of treatment (1 month) have been rare.5 However, at higher dosages, abdominal disorders (diarrhea, pain, nausea, and flatulence) have been reported, as well as elevated bilirubin levels.5, 26, 27 A case of serious fever, leukopenia and thrombyocytopenia (that recurred with rechallenge) was reported in a patient with NAFLD receiving 500 mg 3 times daily for 6 months in a randomized, controlled trial.84 (84) Doses of resveratrol SRT5021 5 g daily resulted in severe adverse events, including renal failure, in a small clinical trial.2, 29 Resveratrol is structurally similar to the synthetic estrogen diethylstilbestrol and may have estrogenic activity.61

Toxicology

Limited toxicity studies using resveratrol in large doses (2 to 4 g/kg in rodents) have suggested renal toxicity; however, lower doses (20 mg/kg) were not toxic. Toxicity studies in rats (100 mg/kg for 28 days) and dogs (up to 1,200 mg/kg/day) showed no adverse effects on histopathological analysis and no hematological effects.27, 62 No hepatic toxicity was observed in rodents following oral administration despite evidence of accumulation in the liver.1, 5

A daily dose of resveratrol 100 mg/kg did not induce chromosome aberrations after 30 days of ingestion, and no carcinogenicity was observed.1, 5, 63 No toxicity data for long-term administration in humans are available.26

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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1. Neves AR, Lucio M, Lima JL, Reis S. Resveratrol in medicinal chemistry: a critical review of its pharmacokinetics, drug-delivery, and membrane interactions. Curr Med Chem. 2012;19(11):1663-1681.22257059
2. Smoliga JM, Baur JA, Hausenblas HA. Resveratrol and health—a comprehensive review of human clinical trials. Mol Nutr Food Res. 2011;55(8):1129-1141.21688389
3. Piotrowska H, Kucinska M, Murias M. Biological activity of piceatannol: leaving the shadow of resveratrol. Mutat Res. 2012;750(1):60-82.22108298
4. Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet. 1992;339(8808):1523-1526.1351198
5. Cottart CH, Nivet-Antoine V, Beaudeux JL. Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans [published online ahead of print June 6, 2013]. Mol Nutr Food Res.2374085510.1002/mnfr.201200589
6. Kelly G. A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 1. Altern Med Rev. 2010;15(3):245-263.21155626
7. Engel N, Mahlknecht U. Aging and anti-aging: unexpected side effects of everyday medication through sirtuin1 modulation. Int J Mol Med. 2008;21(2):223-232.18204789
8. Kaeberlein M, McDonagh T, Heltweg B, et al. Substrate-specific activation of sirtuins by resveratrol. J Biol Chem. 2005;280(17):17038-17045.15684413
9. Orallo F. Trans-resveratrol: a magical elixir of eternal youth? Curr Med Chem. 2008;15(19):1887-1898.18691046
10. Holme AL, Pervaiz S. Resveratrol in cell fate decisions. J Bioenerg Biomembr. 2007;39(1):59-63.17308975
11. Howitz KT, Bitterman KJ, Cohen HY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425(6954):191-196.12939617
12. Valenzano DR, Cellerino A. Resveratrol and the pharmacology of aging: a new vertebrate model to validate an old molecule. Cell Cycle. 2006;5(10):1027-1032.16687936
13. Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444(7117):337-342.17086191
14. Baxter RA. Anti-aging properties of resveratrol: review and report of a potent new antioxidant skin care formulation. J Cosmet Dermatol. 2008;7(1):2-7.18254804
15. Das S, Das DK. Anti-inflammatory responses of resveratrol. Inflamm Allergy Drug Targets. 2007;6(3):168-173.17897053
16. Murias M, Handler N, Erker T, et al. Resveratrol analogues as selective cyclooxygenase-2 inhibitors: synthesis and structure-activity relationship. Bioorg Med Chem. 2004;12(21):5571-5578.15465334
17. Zykova TA, Zhu F, Zhai X, et al. Resveratrol directly targets COX-2 to inhibit carcinogenesis. Mol Carcinog. 2008;47(10):797-805.18381589
18. Martín AR, Villegas I, La Casa C, de la Lastra CA. Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats. Biochem Pharmacol. 2004;67(7):1399-1410.15013856
19. Martín AR, Villegas I, Sánchez-Hidalgo M, de la Lastra CA. The effects of resveratrol, a phytoalexin derived from red wines, on chronic inflammation induced in an experimentally induced colitis model. Br J Pharmacol. 2006;147(8):873-885.16474422
20. de Jesus Soares T, Volpini RA, Francescato HD, Costa RS, da Silva CG, Coimbra TM. Effects of resveratrol on glycerol-induced renal injury. Life Sci. 2007;81(8):647-656.17698148
21. Culpitt SV, Rogers DF, Fenwick PS, et al. Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD. Thorax. 2003;58(11):942-946.14586044
22. Singh CK, George J, Ahmad N. Resveratrol-based combinatorial strategies for cancer management. Ann N Y Acad Sci. 2013;1290:113-121.23855473
23. Saiko P, Szakmary A, Jaeger W, Szekeres T. Resveratrol and its analogs: defense against cancer, coronary disease and neurodegenerative maladies or just a fad? Mutat Res. 2008;658(1-2):68-94.17890139
24. Delmas D, Lançon A, Colin D, Jannin B, Latruffe N. Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer. Curr Drug Targets. 2006;7(4):423-442.16611030
25. Kundu JK, Surh YJ. Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. Cancer Lett. 2008;269(2):243-261.18550275
26. Vang O, Ahmad N, Baile CA, et al. What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PLoS One. 2011;6(6):e19881.21698226
27. Gescher A, Steward WP, Brown K. Resveratrol in the management of human cancer: how strong is the clinical evidence? Ann N Y Acad Sci. 2013;1290:12-20.23855461
28. ClinicalTrials.gov website. http://www.ClinicalTrials.gov. Accessed Aug 16, 2013.
29. Popat R, Plesner T, Davies F, et al. A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. Br J Haematol. 2013;160(5):714-717.23205612
30. Zhu W, Qin W, Zhang K, et al. Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer. Nutr Cancer. 2012;64(3):393-400.22332908
31. Wu JM, Hsieh TC, Wang Z. Cardioprotection by resveratrol: a review of effects/targets in cultured cells and animal tissues. Am J Cardiovasc Dis. 2011;1(1):38-47.22254184
32. Opie LH, Lecour S. The red wine hypothesis: from concepts to protective signalling molecules. Eur Heart J. 2007;28(14):1683-1693.17561496
33. Lin JF, Lin SM, Chih CL, et al. Resveratrol reduces infarct size and improves ventricular function after myocardial ischemia in rats. Life Sci. 2008;83(9-10):313-317.18639559
34. Dudley J, Das S, Mukherjee S, Das DK. Resveratrol, a unique phytoalexin present in red wine, delivers either survival signal or death signal to the ischemic myocardium depending on dose. J Nutr Biochem. 2009;20(6):443-452.18789672
35. Militaru C, Donoiu I, Craciun A, Scorei ID, Bulearca AM, Scorei RI. Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life. Nutrition. 2013;29(1):178-183.23153742
36. Magyar K, Halmosi R, Palfi A, et al. Cardioprotection by resveratrol: a human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc. 2012;50(3):179-187.22240353
37. Tomé-Carneiro J, Gonzálvez M, Larrosa M, et al. Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial. Mol Nutr Food Res. 2012;56(5):810-821.22648627
38. Tomé-Carneiro J, Gonzálvez M, Larrosa M, et al. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Am J Cardiol. 2012;110(3):356-363.22520621
39. Zamora-Ros R, Urpi-Sarda M, Lamuela-Raventós RM, et al; PREDIMED Study Investigators. High urinary levels of resveratrol metabolites are associated with a reduction in the prevalence of cardiovascular risk factors in high-risk patients. Pharmacol Res. 2012;65(6):615-620.22465220
40. Yoshino J, Conte C, Fontana L, et al. Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab. 2012;16(5):658-664.23102619
41. Poulsen MM, Vestergaard PF, Clasen BF, et al. High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes. 2013;62(4):1186-1195.23193181
42. De Groote D, Van Belleghem K, Devière J, Van Brussel W, Mukaneza A, Amininejad L. Effect of the intake of resveratrol, resveratrol phosphate, and catechin-rich grape seed extract on markers of oxidative stress and gene expression in adult obese subjects. Ann Nutr Metab. 2012;61(1):15-24.22776850
43. Crandall JP, Oram V, Trandafirescu G, et al. Pilot study of resveratrol in older adults with impaired glucose tolerance. J Gerontol A Biol Sci Med Sci. 2012;67(12):1307-1312.22219517
44. Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res. 2012;32(7):537-541.22901562
45. Kelly GS. A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 2. Altern Med Rev. 2010;15(4):313-328.21194247
46. Karaoglan A, Akdemir O, Barut S, et al. The effects of resveratrol on vasospasm after experimental subarachnoidal hemorrhage in rats. Surg Neurol. 2008;70(4):337-343.18207513
47. Ritz MF, Curin Y, Mendelowitsch A, Andriantsitohaina R. Acute treatment with red wine polyphenols protects from ischemia-induced excitotoxicity, energy failure and oxidative stress in rats. Brain Res. 2008;1239:226-234.18801346
48. Quincozes-Santos A, Andreazza AC, Nardin P, Funchal C, Gonçalves CA, Gottfried C. Resveratrol attenuates oxidative-induced DNA damage in C6 Glioma cells. Neurotoxicology. 2007;28(4):886-891.17498806
49. Monteiro R, Faria A, Mateus N, Calhau C, Azevedo I. Red wine interferes with oestrogen signalling in rat hippocampus. J Steroid Biochem Mol Biol. 2008;111(1-2):74-79.18534843
50. Tang BL, Chua CE. SIRT1 and neuronal diseases. Mol Aspects Med. 2008;29(3):187-200.17397914
51. Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides. J Biol Chem. 2005;280(45):37377-37382.16162502
52. Kim D, Nguyen MD, Dobbin MM, et al. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J. 2007;26(13):3169-3179.17581637
53. Kumar P, Padi SS, Naidu PS, Kumar A. Effect of resveratrol on 3-nitropropionic acid-induced biochemical and behavioural changes: possible neuroprotective mechanisms. Behav Pharmacol. 2006;17(5-6):485-492.16940769
54. Solans A, Zambrano A, Rodríguez M, Barrientos A. Cytotoxicity of a mutant huntingtin fragment in yeast involves early alterations in mitochondrial OXPHOS complexes II and III. Hum Mol Genet. 2006;15(20):3063-3081.16968735
55. Lu KT, Ko MC, Chen BY, et al. Neuroprotective effects of resveratrol on MPTP-induced neuron loss mediated by free radical scavenging. J Agric Food Chem. 2008;56(16):6910-6913.18616261
56. Blanchet J, Longpré F, Bureau G, et al. Resveratrol, a red wine polyphenol, protects dopaminergic neurons in MPTP-treated mice. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1243-1250.18471948
57. Lee MK, Kang SJ, Poncz M, Song KJ, Park KS. Resveratrol protects SH-SY5Y neuroblastoma cells from apoptosis induced by dopamine. Exp Mol Med. 2007;39(3):376-384.17603292
58. Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004;32(12):1377-1382.15333514
59. Boocock DJ, Faust GE, Patel KR, et al. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1246-1252.17548692
60. Rotches-Ribalta M, Andres-Lacueva C, Estruch R, Escribano E, Urpi-Sarda M. Pharmacokinetics of resveratrol metabolic profile in healthy humans after moderate consumption of red wine and grape extract tablets. Pharmacol Res. 2012;66(5):375-382.22906730
61. Basly JP, Marre-Fournier F, Le Bail JC, Habrioux G, Chulia AJ. Estrogenic/antiestrogenic and scavenging properties of (E)- and (Z)-resveratrol. Life Sci. 2000;66(9):769-777.10698352
62. Sangeetha MK, Vallabi DE, Sali VK, Thanka J, Vasanthi HR. Sub-acute toxicity profile of a modified resveratrol supplement. Food Chem Toxicol. 2013;59:492-500.23819915
63. Carsten RE, Bachand AM, Bailey SM, Ullrich RL. Resveratrol reduces radiation-induced chromosome aberration frequencies in mouse bone marrow cells. Radiat Res. 2008;169(6):633-638.18494544
64. Dash S, Xiao C, Morgantini C, Szeto L, Lewis GF. High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler Thromb Vasc Biol. 2013;33(12):2895-2901.24072699
65. Ferzil G, Patel M, Phrsai N, Brody N. Reduction of facial redness with resveratrol added to topical product containing green tea polyphenols and caffeine. J Drugs Dermatol. 2013;12(7):770-774.23884488
66. Richer S, Stiles W, Ulanski L, Carroll D, Podella C. Observation of human retinal remodeling in octogenarians with a resveratrol based nutritional supplement. Nutrients. 2013;5(6):1989-2005.23736827
67. Sahebkar A. Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2013;71(12)822-835.24111838
68. Wong RH, Berry NM, Coates AM, et al. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults. J Hypertens. 2013;31:1819-1827.23743811
69. Gliemann L, Schmidt JF, Olesen J, et al. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol. 2013;591(pt 20):5047-5059.23878368
70. Witte AV, Kerti L, Margulies DS, Floel A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci. 2014;34(23):7862-7870.24899709
71. Semba RD, Ferrucci L, Bartali B, et al. Resveratrol levels and all-cause mortality in older community-dwelling adults. JAMA Intern Med. 2014;174(7):1077-1084.24819981
72. Wightman EL, Reay JL, Haskell CF, Willimason G, Dew TP, Kennedy DO. Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation. Br J Nutr. 2014;112:203-213.24804871
73. Chow HH, Garland LL, Heckman-Stoddard BM, et al. A pilot clinical study of resveratrol in postmenopausal women with high body mass index: effects on systemic sex steroid hormones. J Transl Med. 2014;12:223.25115686
74. Liu K, Zhou R, Wang B, Mi MT. Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr. 2014;99(6):1510-1519.24695890
75. Mendez-del Villar M, Gonzalez-Ortiz M, Martinez-Abundis E, Perez-Rubio KG, lizarraga-Valdez R. Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord. 2014;12(10):497-502.25137036
76. Faghihzadeh F, Adibi P, Rafiei R, Hekmatdoost A. Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. Nutr Res. 2014;34(10):837-843.25311610
77. Liu Y, Ma W, Zhang P, He S, Huang D. Effect of resveratrol on blood pressure: a meta-analysis of randomized controlled trials. Clin Nutr. 2015;34(1):27-34.24731650
78. Hausenblas HA, Schoulda JA, Smoliga JM. Resveratrol treatment as an adjunct to pharmacological management in type 2 diabetes mellitus – systematic review and meta-analysis. Mol Nutr Food Res. 2015;59(1):147-159.25138371
79. Bedada SK, Nearati P. Effect of resveratrol on the pharmacokinetics of carbamazepine in healthy human volunteers. Phytother Res. 2015;29(5):701-706.25624269
80. Chen S, Zhao X, Ran L, et al. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Digestive Liver Dis. 2015;47(3):226-232.25577300
81. Wightman EL, Haskell-Ramsay CF, Reay JL, et al. The effects of chronic trans-resveratrol supplementation on aspects of cognitive function, mood, sleep, health and cerebral blood flow in healthy, young humans. Br J Nutr. 2015;114(9):1427-1437.26344014
82. Turner RS, Thomas RG, Craft S, et al. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015;85:1383-1391.26362286
83. Voduc N, Porte Cl, Tessier C, Mallick R, Cameron DW. Effect of resveratrol on exercise capacity: a randomized placebo-controlled crossover pilot study. Appl Physiol Nutr Metab. 2014;39:1183-1187.25051174
84. Heeboll S, Kreuzfeldt M, Hamilton-Dutoit S, Poulsen MK, Stodkilde-Jorgensen H, Moller HJ, Jessen N, Thorsen K, Hellberg YK, Pedersen SB, Gronbaek H. Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease. Scand J Gastroenterol. 2016;51(4):456-464.
85. Zhang C, Yuan W, Fang J, et al. Efficacy of resveratrol supplementation against non-alcoholic fatty liver disease: a meta-analysis of placebo-controlled clinical trials. PLoS ONE. 2016;11(8):e0161792.27560482
86. Kjaer TN, Ornstrup MJ, Poulsen MM, et al. No beneficial effect of resveratrol on the metabolic syndrome: a randomized placebo-controlled clinical trial. J Clin Endocrinol Metab. 2017;102(5):1642-1651.28182820
87. Bo S, Ponzo V, Ciccone G, et al. Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial. Pharmacol Res. 2016;111:896-905.27520400
88. Pennisi M, Bertino G, Gagliano C, et al. Resveratrol in hepatitis c patients treated with pegylated-interferon-α-2b and ribavirin reduces sleep disturbance. Nutrients. 2017;9(8):897.28820468
89. Desta Z, Kerbusch T, and Flockhart DA. Effect of clarithromycin on the pharmacokinetics and pharmacodynamics of pimozide in healthy, poor, and extensive metabolizers of cytochrome P450 2D6 (CYP2D6). Clin Pharmacol Ther. 1999;65(1):10-20.9951426
90. Orap (pimozide) [prescribing information].Sellersville, PA: Teva Pharmaceuticals USA; August 2011.
91. Flockhart DA, Richard E, Woosely RL, et al. A metabolic interaction between clarithromycin and pimozide may result in cardiac toxicity. Clin Pharmacol Ther. 1996;59:189.
92. Desta Z, Kerbusch T, Soukhova N, et al. Identification and characterization of human cytochrome P450 isoforms interacting with pimozide. J Pharmacol Exp Ther. 1998;285(2):428-437.9580580
93. Patel G, King A, Dutta S, et al. Evaluation of the effects of the weak CYP3A inhibitors atorvastatin and ethinyl estradiol/norgestimate on lomitapide pharmacokinetics in healthy subjects. J Clin Pharmacol. 2016;56(1):47-55.26120010
94. Juxtapid (lomitapide) [prescribing information]. Cambridge, MA: Aegerion Pharmaceuticals Inc; March 2016.
95. Abilify (aripiprazole) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; February 2011.
96. Kubo M, Koue T, Inaba A, et al. Influence of itraconazole co-administration and CYP2D6 genotype on the pharmacokinetics of the new antipsychotic aripiprazole. Drug Metab Pharmacokinet. 2005;20(1):55-64.15770075
97. Azuma J, Hasunuma T, Kubo M, et al. The relationship between clinical pharmacokinetics of aripiprazole and CYP2D6 genetic polymorphism: Effects of CYP enzyme inhibition by coadministration of paroxetine or fluvoxamine. Eur J Clin Pharmacol. 2012;68(1):29-37.21739267
98. Aung GL, O'Brien JG, Tien PG, et al. Increased aripiprazole concentrations in an HIV-positive male concurrently taking duloxetine, darunavir, and ritonavir. Ann Pharmacother. 2010;44(11):1850-1854.20978219
99. Abilify Maintena (aripiprazole) [prescribing information]. Rockville, MD: Otsuka America Pharmaceutical Inc; February 2013.
100. Chow HH, Garland LL, Hsu CH, et al. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev Res (Phila). 2010;3(9):1168-1175.20716633
101. Piver B, Berthou F, Dreano Y, Lucas D. Differential inhibition of human cytochrome P450 enzymes by epsilon-viniferin, the dimer of resveratrol: comparison with resveratrol and polyphenols from alcoholized beverages. Life Sci. 2003;73(9):1199-1213.12818727
102. Yu C, Shin YG, Kosmeder JW, Pezzuto JM, van Breemen RB. Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Commun Mass Spectrom. 2003;17(4):307-313.12569440
103. Piver B, Berthou F, Dreano Y, Lucas D. Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett. 2001;125(1-3):83-91.11701226
104. Bedada SK, Nearati P. Effect of resveratrol on the pharmacokinetics of carbamazepine in healthy volunteers. Phytother Res. 2015;29(5):701-706.25624269
105. Bedada SK, Yellu NR, Neerati P. Effect of resveratrol treatment on the pharmacokinetics of diclofenac in healthy human volunteers. Phytother Res. 2016;30(3):397-401.26633237
106. Arthrotec (diclofenac) [prescribing information]. New York, NY: Pfizer Inc; March 2015.
107. Tikosyn (dofetilide) [prescribing information]. New York, NY: Pfizer Inc; February 2011.
108. Walker DK, Alabaster CT, Congrave GS, et al. Significance of metabolism in the disposition and action of the antidysrhythmic drug, dofetilide. In vitro studies and correlation with in vivo data. Drug Metab Dispos. 1996;24(4):447-455.8801060
109. Johnson BF, Cheng SL, Venitz J. Transient kinetic and dynamic interactions between verapamil and dofetilide, a class III antiarrhythmic. J Clin Pharmacol. 2001;41(11):1248-1256.11697758
110. Addyi (flibanserin) [prescribing information]. Raleigh, NC: Sprout Pharmaceuticals Inc; August 2015.
111. Cozaar (losartan) [prescribing information]. Whitehouse Station, NJ: Merck & Co Inc; December 2015.
112. Munafo A, Christen Y, Nussberger J, et al. Drug concentration relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist. Clin Pharmacol Ther. 1992;51(5):513-521.1587065
113. Nimodipine [prescribing information]. Montvale, NJ: Ascend Laboratories LLC; April 2015.
114. Hendouei F, Sanjari Moghaddam H, Mohammadi MR, Taslimi N, Rezaei F, Akhondzadeh S. Resveratrol as adjunctive therapy in treatment of irritability in children with autism: a double-blind and placebo-controlled randomized trial. J Clin Pharm Ther. 2020;45(2):324-334.31714621
115. Wong RH, Zaw JJ, Xian CJ, Howe PR. Regular supplementation with resveratrol improves bone mineral density in postmenopausal women: a randomised, placebo-controlled trial. J Bone Mineral Res. 2020; doi.org/10.1002/jbmr.4115. [epub ahead of print]32564438
116. Akbari M, Tamtaji OR, Lankarani KB, et al. The effects of resveratrol on lipid profiles and liver enzymes in patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. Lipids Health Dis. 2020;19(1):25.32066446
117. Movahed A, Raj P, Nabipour I, et al. Efficacy and safety of fesveratrol in type 1 diabetes patients: A two-month preliminary exploratory trial. Nutrients. 2020;12(1):161.31935938
118. Teimouri M, Homayouni-Tabrizi M, Rajabian A, Amiri H, Hosseini H. Anti-inflammatory effects of resveratrol in patients with cardiovascular disease: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med. 2022;70:102863. doi:10.1016/j.ctim.2022.10286335905799
119. Mahjabeen W, Khan DA, Mirza SA. 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. Complement Ther Med. 2022;66:102819. doi:10.1016/j.ctim.2022.10281935240291

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