For Patients & Caregivers
How It Works
In laboratory studies, resveratrol was found to reduce inflammation and to have antitumor properties, but human studies have not been conducted.
A naturally occurring compound in the skin of red grapes and other botanicals, resveratrol has been shown to reduce inflammation. It also has antioxidant properties and may help to protect against thickening of arterial walls and heart disease. Animal studies have shown that resveratrol has the ability to prevent certain cancer cells from dividing. Human studies on the anticancer effect of resveratrol supplements are lacking. Eating a diet rich in resveratrol does not lower the risk of dying from cancer or heart disease.
Purported Uses
- Thickening of arterial walls
Laboratory studies have shown that resveratrol helps in preventing atherosclerosis. - Coronary heart disease
There is limited scientific evidence to support this use. - Cancer prevention
Several laboratory studies have demonstrated the ability of resveratrol to prevent the growth of cancer cells. However, it is not clear if similar effects could occur in humans, and its hormone-like properties may stimulate some types of cancer cells. - Inflammation
This use is supported by data from laboratory studies. - Anti-aging
This effect has only been demonstrated in lab studies. - To treat metabolic disorders
In a study of obese healthy men, resveratrol did not affect blood pressure, fat content, or inflammatory and metabolic biomarkers.
Do Not Take If
- You have a hormone-sensitive cancer: Resveratrol has hormone-like properties that may stimulate some types of cancer cells.
- You are taking antiplatelet drugs: Resveratrol may increase the risk of bleeding.
- You are taking cytochrome P450 substrate drugs: Resveratrol may increase the risk of side effects of some drugs and make others less effective.
- You are taking carbamazepine: An herbal supplement rich in resveratrol was found to increase blood levels of this antiepileptic drug.
For Healthcare Professionals
Clinical Summary
Resveratrol is a polyphenolic compound found in many botanical products. Red wine is a natural source of resveratrol as it is rich in grape skin and seeds. However, resveratrol is usually consumed as a dietary supplement for its purported antioxidant and anti-inflammatory properties. It is also marketed as an anti-aging supplement based on findings that it prolongs the life span of yeast cells (1) (2). This effect has not yet been demonstrated in humans.
A long-term randomized double-blind trial indicates that resveratrol and its major metabolites penetrate the blood-brain barrier to have effects on some biomarkers associated with Alzheimer’s disease (45), but a meta analysis did not find any significant effect on memory or cognitive performance (47). Resveratrol is also thought to have cardioprotective effects. Earlier studies found that it reduces the oxidation of low density lipoproteins (LDL), inhibits platelet aggregation, and may protect against atherogenesis (3) (4). Consumption of wine or a resveratrol-rich grape supplement is associated with reduction in risk of cardiovascular disease (5) (6) and may help promote circulatory system health (7) (8) (9). However, it does not decrease the risk of all-cause mortality in older adults (42). Data on effectiveness of resveratrol against non-alcoholic fatty liver disease are conflicting (44) (48).
Resveratrol has also been shown to increase insulin sensitivity in diabetic patients (10) (11) (43), but supplementation did not improve their metabolic patterns nor reduce C-reactive protein concentrations (46). Interestingly, conclusions of a meta analysis suggest that high doses of resveratrol are effective in promoting cardiovascular health (49); and supplementation improved arterial stiffness and reduced oxidative stress (50). But data on the effects of resveratrol in controlling metabolic syndromes in obese subjects are inconclusive (12) (13)
In vitro and animal studies show that resveratrol inhibits proliferation of cancer cells via different mechanisms (14) (15) (16) (17) (18) (19). It may also protect against chemotherapy-induced cardiotoxicity (19) (20). Further clinical studies are needed to confirm these effects in humans.
External application of a resveratrol-containing gel reduced acne symptoms (21). Whereas resveratrol is generally safe, high doses can cause gastrointestinal side effects, such as diarrhea. Resveratrol inhibits cytochrome P450 enzymes (22) (23) and may increase the risk of adverse effects of certain drugs. It also exhibits estrogen-like properties and activates transcription by both estrogen and androgen receptors that can lead to the stimulation of cancer cell proliferation (18).
Purported Uses
Mechanism of Action
Resveratrol acts as an antioxidant and inhibits oxidation of low density lipoproteins (LDL) (21), platelet aggregation, and eicosanoid synthesis (4); induces nitric oxide (NO) production (24) (25) and increases arterial blood flow (8). These actions may contribute to its purported cardiovascular health benefits. Resveratrol also acts as an anti-inflammatory agent by inhibiting cyclooxygenase (COX) activity (26). It has been shown to decrease C-reactive protein and tumor necrosis factor, and to increase anti-inflammatory interleukin-10 and intercellular adhesion molecule-1 in humans (5). Other effects include decreasing oxidative stress and improving insulin sensitivity by increasing protein kinase activities (10). Resveratrol was also shown to decrease circulating insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels (27) which may account for its anti-diabetic effects in humans. Preliminary data suggest that it increases the life span of yeast cells by activating sirtuins (1) (2), inhibiting human Sirt3 along with stimulating Sirt5 and Sirt1 (28). The neuroprotective effects of resveratrol were shown to be via regulating autophagy and apoptosis mediated by the Akt/mTOR pathway (51).
Resveratrol has also been investigated for its anticancer potential. It was found to inhibit proliferation of cancer cells via apoptosis and by exerting anti-estrogenic effects (14) (15) (16) (17). Trans-resveratrol appears to decrease methylation of the tumor suppressor gene RASSF-1alpha in women at increased breast cancer risk (29). In addition, reductions in breast cancer cell migration and invasion were observed after supplementation (30) (31). Resveratrol growth factor heregulin-beta1 (HRG-beta1) mediated matrix metallopeptidase 9 (MMP-9) expressions in human breast cancer cells (30). But contradictory data show that resveratrol mimics phytoestrogens and could activate genes that are normally regulated by estrogens (18) or androgens (19). In other studies resveratrol helped reduce prostate tumorigenesis through a reduction in prostatic levels of mTOR complex 1 (mTORC1) activity and increased expression of SIRT1 (32); and modulated steroid hormone-dependent pathways to inhibit prostate cancer cell growth. However, it also increases angiogenesis and inhibits apoptosis in vivo (19). Further research is needed.
Additional findings show that resveratrol downregulates p21 and upregulates cyclin E leading to S-phase accumulation and apoptosis in neuroblastoma cells (14). It also inhibits CYP1A1, CYP1A2, and CYP1B1 enzymes in tumor cells, perhaps exerting antitumor effects as some of these enzymes are known to be involved in the activation of procarcinogens and toxins (22) (23). Protective effects of resveratrol against doxorubicin-induced cardiotoxicity are due to upregulation of SIRT1-mediated p53 deacetylation. (20). Also, it protects against cisplatin-induced cardiotoxicity by suppressing oxidative stress (19).
Contraindications
Patients with hormone-sensitive cancers should use caution, as resveratrol exhibits estrogen-like properties and activates transcription by both estrogen and androgen receptors that lead to the stimulation of cancer cell proliferation (18).
Adverse Reactions
Herb-Drug Interactions
- Antiplatelet drugs: Because resveratrol inhibits platelet aggregation, concurrent use of other antiplatelet drugs may increase bleeding risk.
- Cytochrome P450 substrates: Resveratrol inhibits CYP3A4, CYP2D6, CYP2C9, and induces CYP1A2, thereby affecting the levels of drugs that are metabolized by these enzymes (39).
- Carbamazepine: Polygonum cuspidatum, an herbal supplement rich in resveratrol, can increase carbamazepine blood levels due to CYP3A inhibition and multidrug resistance-associated protein 2 (MRP 2) (40).