Resveratrol is a plant compound derived from red grapes that has antioxidant-like properties. It is also present in products that are made from red grapes, such as wine and juice. Many people use resveratrol as a health-boosting supplement. Research has linked the compound to potential health benefits such as improved brain health and blood pressure. It may also come with some side effects. This article will explore the health benefits associated with resveratrol, side effects, when and how to consume it, and more.
It is present in more than 70 plant species, primarily in the skin and seeds of red grapes. Resveratrol is also a phytoalexin, which is a protective antibiotic that plants produce under stress. Phytoalexin is what helps plants recover from fungal attacks, ultraviolet radiation, and other threatening circumstances.
When people consume reservatrol, it helps the body detoxify harmful molecules, much like antioxidants. The human body metabolizes the compound quickly.
It is fat-soluble and possesses anticarcinogenic, antioxidant, and estrogenic activity. Resveratrol is one of the main ingredients behind the health benefits of drinking red wine. Learn more about the health benefits of red wine here. There are many benefits associated with resveratrol, though they are mostly correlated to the compound rather than directly linked to the consumable supplement.
A few of these health benefits include:. Research shows that resveratrol plays a role in protecting ovarian health, and in relieving poor pulmonary function. Resveratrol notably improves glucose homeostasis, providing insulin resistance by activating sirtuin, which regulates metabolism in insulin-target organs.
In addition, resveratrol may serve as a therapeutic agent for rheumatoid arthritis , as well as for male infertility and testicular malfunction. More research is needed, as most of the above studies were animal studies. These ailments include stomach aches, hepatitis, urinary tract infections, and fungal diseases. Because red wine is fermented with grape skins longer than white wine, red wine contains more resveratrol.
Simply eating grapes or drinking grape juice might be a way to get resveratrol without drinking alcohol. Red and purple grape juices may have some of the same heart-healthy benefits of red wine.
Peanuts, blueberries and cranberries also contain some resveratrol. It's not yet known how beneficial eating grapes or other foods might be compared with drinking red wine when it comes to promoting heart health. The amount of resveratrol in food and red wine can vary widely. Resveratrol supplements also are available. Researchers haven't found any harm in taking resveratrol supplements, but your body can't absorb most of the resveratrol in supplements. There's still no clear evidence that beer, white wine or liquor aren't any better than red wine for heart health.
Various studies have shown that moderate amounts of all types of alcohol benefit your heart, not just alcohol found in red wine. It's thought that alcohol:.
The potential heart-healthy benefits of red wine and other alcoholic drinks look promising. Those who drink moderate amounts of alcohol, including red wine, seem to have a lower risk of heart disease. However, it's important to understand that studies comparing moderate drinkers to nondrinkers might overestimate the benefits of moderate drinking because nondrinkers might already have health problems.
More research is needed before we know whether red wine is better for your heart than other forms of alcohol, such as beer or spirits. The American Heart Association and National Heart, Lung, and Blood Institute don't recommend that you start drinking alcohol just to prevent heart disease.
Alcohol can be addictive and can cause or worsen other health problems. If you have questions about the benefits and risks of alcohol, talk to your doctor about specific recommendations for you.
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This content does not have an English version. Endogenous estrogens are steroid hormones synthesized by humans and other mammals; these hormones bind to estrogen receptors within cells.
The estrogen-receptor complex interacts with unique sequences in DNA estrogen response elements; EREs to modulate the expression of estrogen-responsive genes The chemical structure of resveratrol is very similar to that of the synthetic estrogen agonist, diethylstilbestrol Figure 2 , suggesting that resveratrol might also function as an estrogen agonist, i.
Some compounds are not carcinogenic until they have been metabolized in the body by phase I biotransformation enzymes , especially cytochrome P enzymes 2.
By inhibiting the expression and activity of certain cytochrome P enzymes 25, 26 , resveratrol might help prevent cancer by limiting the activation of procarcinogens. In contrast, increasing the activity of phase II detoxification enzymes generally promotes the excretion of potentially toxic or carcinogenic chemicals.
Following DNA damage, the cell cycle can be transiently arrested to allow for DNA repair or activation of pathways leading to cell death apoptosis if the damage is irreparable Defective cell cycle regulation may result in the propagation of mutations that contribute to the development of cancer. Moreover, unlike normal cells, cancer cells proliferate rapidly and are unable to respond to cell death signals that initiate apoptosis.
Cancerous cells invade normal tissue aided by enzymes called matrix metalloproteinases. Resveratrol has been found to inhibit the activity of at least one type of matrix metalloproteinase 30, To fuel their rapid growth, invasive tumors must also develop new blood vessels by a process known as angiogenesis.
Resveratrol has been found to inhibit angiogenesis in vitro and in vivo Inflammation promotes cellular proliferation and angiogenesis and inhibits apoptosis Resveratrol has been found to inhibit the activity of several inflammatory enzymes in vitro , including cyclooxygenases and lipoxygenases 37, Atherosclerosis is an inflammatory process in which lipids deposit in plaques known as atheromas within arterial walls and increase the risk of myocardial infarction One of the earliest events in the development of atherosclerosis is the recruitment of inflammatory white blood cells from the blood to the arterial wall by vascular cell adhesion molecules Resveratrol has been found to inhibit the expression of adhesion molecules in cultured endothelial cells 43, The proliferation of vascular smooth muscle cells VSMCs plays an important role in the progression of hypertension , atherosclerosis , and restenosis when treated arteries become blocked again.
Resveratrol has been found to inhibit the proliferation of VSMCs in culture , as well as in vivo Endothelial nitric oxide synthase eNOS is an enzyme that catalyzes the formation of nitric oxide NO by vascular endothelial cells.
NO is needed to maintain arterial relaxation vasodilation , and impaired NO-dependent vasodilation is associated with an increased risk of cardiovascular disease Because physiological concentrations of resveratrol were found to stimulate eNOS activity in cultured endothelial cells , resveratrol might help maintain or improve endothelial function in vivo see Cardiovascular disease.
Platelet aggregation is one of the first steps in the formation of a blood clot that can occlude a coronary or cerebral artery, resulting in myocardial infarction or stroke , respectively. Resveratrol has been found to inhibit platelet activation and aggregation in vitro Age-related mood alterations and memory deficits result from a decrease in the function of the hippocampus in the elderly. Resveratrol was shown to stimulate neurogenesis and blood vessel formation in the hippocampus of healthy old rats.
These structural changes were associated with significant improvements in spatial learning, memory formation, and mood function Senile plaques are toxic to cells, resulting in progressive neuronal dysfunction and death. Resveratrol also reduced senile plaque counts in various brain regions of a transgenic AD mouse model A decreased occurrence of microglial activation and astrocyte hypertrophy was also reported in healthy aged rats treated with resveratrol Resistance against oxidative stress-related damage in primary neuronal cells treated with resveratrol has been associated with the induction of heme oxygenase-1 HO-1 , an enzyme that degrades pro-oxidant heme In an experimental model of stroke , resveratrol limited infarct size during ischemia -reperfusion in wild-type mice but not in mice lacking the HO-1 gene Also, resveratrol was able to correct experimentally induced oxidative stress and the associated cognitive dysfunction in rats Resveratrol has been found to inhibit the proliferation of a variety of human cancer cell lines, including those from breast, prostate , stomach, colon, pancreatic , and thyroid cancers 2.
The anti-cancer effects of resveratrol in rodent models involved the reduction of cell proliferation, the induction of apoptosis , and the inhibition of angiogenesis , tumor growth, and metastasis reviewed in Yet, a few animal studies have reported a lack of an effect of oral resveratrol in inhibiting the development of lung cancer induced by carcinogens in cigarette smoke 70, 71 , and the study of resveratrol administration on colon cancer has given mixed results The low bioavailability of resveratrol reported in human studies limits the clinical evaluation of possible systemic health effects of resveratrol in humans see Metabolism and Bioavailability.
Yet, in a pilot study , unmetabolized resveratrol and conjugates have been detected in colorectal tumor tissues from 20 cancer patients following daily oral supplementation with either 4 g or 8 g of resveratrol for 29 days.
Resveratrol appeared to be well tolerated and significantly, though modestly, reduced cell proliferation compared to baseline A micronized formulation of resveratrol named SRT , which was meant to increase resveratrol delivery to target tissues, was given for 14 days to 6 patients with colorectal cancer and liver metastasis in a small randomized , double-blind , placebo -controlled trial Unmetabolized resveratrol was measurable in the liver of five out of six patients who consumed 5 g of SRT, and SRT administration resulted in an increased detection of the apoptotic marker, cleaved caspase-3, in hepatic tumor tissues.
Yet, in an unrandomized and unblinded trial in patients with multiple myeloma, the administration of SRT was associated with a number of serious adverse effects, including kidney failure, such that the trial was halted Since kidney failure is a frequent complication in myeloma patients, it is unclear whether kidney failure cases should be solely attributed to the use of SRT Nevertheless, there is a need to find safe ways to increase resveratrol bioavailability in humans before exploring its putative benefits in clinical settings 6 , Significant reductions in cardiovascular disease risk have been associated with moderate consumption of alcoholic beverages Red wine contains variable and usually low concentrations of resveratrol see Sources and higher concentrations of flavonoids like procyanidins.
These polyphenolic compounds have displayed antioxidant , anti-inflammatory, and other potentially anti-atherogenic effects in the test tube and in some animal models of atherosclerosis The results of epidemiological studies addressing this question have been inconsistent.
While some large prospective cohort studies found that wine drinkers were at lower risk of cardiovascular disease than beer or liquor drinkers , others found no difference Socioeconomic and lifestyle differences between people who prefer wine and those who prefer beer or liquor may explain part of the additional benefit observed in some studies: people who prefer wine tend to have higher incomes, more education, smoke less, and eat more fruit and vegetables and less saturated fat than those who prefer other alcoholic beverages Although moderate alcohol consumption has been consistently associated with reductions in coronary heart disease risk, it is not yet clear whether red wine polyphenols confer any additional risk reduction.
Interestingly, studies that administered alcohol-free red wine to rodents noted improvements in various parameters related to cardiovascular disease 93, 94 , and a placebo -controlled human study found that heart disease patients administered red grape polyphenol extract experienced acute improvements in endothelial function Endothelial dysfunction is usually associated with the presence of cardiovascular risk factors e.
Endothelial dysfunction is characterized by abnormal vasoconstriction, leukocyte adherence to vascular endothelial cells , platelet activation and aggregation, smooth muscle cell proliferation, vascular inflammation , thrombosis clot formation , impaired coagulation , and atherosclerosis Experimental studies : Resveratrol has been found to exert a number of protective effects on the cardiovascular system in vitro , including inhibition of both platelet activation and aggregation 53 , 98, 99 , promotion of vasodilation by enhancing the production of nitric oxide NO 52 , and control of the production of inflammatory lipid mediators 38 , , However, the concentrations of resveratrol required to produce these effects are often higher than those measured in human plasma after oral consumption of resveratrol 9.
Some animal studies also suggested that high oral doses of resveratrol could decrease the risk of thrombosis and atherosclerosis , , although one study found increased atherosclerosis in animals fed resveratrol Other protective effects of resveratrol in vivo include the reduction of cardiac hypertrophy and the lowering of blood pressure in various models, as well as the limitation of infarct size in post myocardial infarction rats reviewed in Resveratrol supplementation resulted in improved values of flow-mediated dilation FMD of the brachial artery, a surrogate marker of vascular health.
Yet, FMD returned to baseline values within three months after discontinuing resveratrol One study limitation was that the resveratrol formulation contained additional compounds i. In a few additional studies, resveratrol was shown to improve endothelial function by reducing vascular inflammation and endothelial activation. A randomized, double-blind , placebo-controlled study in 41 healthy subjects found that daily supplementation with resveratrol mg , grapeseed extract mg , and quercetin mg , for one month significantly reduced the expression of interleukin-8 IL-8 and cell adhesion molecules ICAM-1 and VCAM-1 in endothelial cells, suggestive of a protective effect against endothelial dysfunction The daily intake of a resveratrol-rich grape supplement was compared to resveratrol-free grape supplement in a year-long, randomized, double blind, placebo-controlled study in 75 individuals at high risk for cardiovascular disease CVD.
The decreased concentrations of two CVD risk markers, oxidized low-density lipoprotein oxLDL and apolipoprotein B ApoB after six months further suggested a cardioprotective effect of resveratrol Supplementation of patients with stable coronary heart disease with the same regimen also improved the profile of circulating inflammatory markers and reduced the expression of proinflammatory genes in peripheral blood mononuclear cells PBMCs The expression of microRNAs and cytokines specifically involved in atherogenic and pro-inflammatory signals were also found to be downregulated in the PBMCs of supplemented patients While preliminary human studies suggest that resveratrol may have beneficial effects on cardiovascular health, there is currently no convincing evidence that these effects can be achieved in the amounts present in one to two glasses of red wine see Sources.
For more information regarding resveratrol and cardiovascular disease, see Caloric restriction is known to extend the lifespan of a number of species, including yeast, worms, flies, fish, rats, and mice In yeast Saccharomyces cerevisiae , caloric restriction stimulates the activity of an enzyme known as Silent information regulator 2 protein Sir2 or sirtuin Yeast Sir2 is a nicotinamide adenine dinucleotide NAD -dependent deacetylase enzyme that removes the acetyl group from acetylated lysine residues in target proteins see the article on Niacin.
Resveratrol feeding also extended the lifespan of worms Caenorhabditis elegans and fruit flies Drosophila melanogaster by a similar mechanism Additionally, resveratrol dose-dependently increased the lifespan of a vertebrate fish Nothobranchius furzeri Resveratrol was also found to extend the lifespan of mice on a high-calorie diet such that their lifespan was similar to that of mice fed a standard diet Although resveratrol increased the activity of the Sir2 homologous human sirtuin 1 SIRT1 in the test tube , there are no epidemiological data to link resveratrol, SIRT1 activation, and extended human lifespan.
Moreover, the supraphysiological concentrations of resveratrol required to increase human SIRT1 activity were considerably higher than concentrations that have been measured in human plasma after oral consumption. Based on a lack of correlation with baseline inflammatory markers, cardiovascular disease and cancer incidence, and all-cause mortality, the authors concluded that higher versus lower quartiles of urinary resveratrol metabolite concentrations did not predict risk of chronic disease or mortality.
However, key experts identified several limitations regarding the quality of the research , Specifically, the use of single measures of total urinary resveratrol metabolites at baseline has been highlighted as being unlikely to reflect lifetime consumption of wine or exposure to dietary resveratrol Resveratrol has also exhibited additional neuroprotective properties in cultured cells and animal models see Biological Activities.
Although resveratrol bioavailability to the brain is uncertain 78 , a randomized , double-blind , placebo -controlled study has reported an increase in cerebral blood flow in the prefrontal cortex of healthy young subjects ages, years following a single oral dose of mg of resveratrol.
However, resveratrol intake did not improve performance in cognitively demanding tasks undertaken during the post-administration period Additional evidence of the potential of resveratrol to mimic the metabolic benefits of caloric restriction on cognitive health may come from ongoing clinical trials in both healthy older individuals and AD patients More than one out of three American adults has impaired glucose tolerance also known as prediabetes , which places them at increased risk of developing type 2 diabetes Muscle insulin resistance, which is thought to be the earliest stage in the development of type 2 diabetes, is characterized by excess lipid exposure, impaired insulin receptor signaling , impaired glucose uptake, mitochondrial dysfunction, reduced fatty acid oxidation , and increased expression of pro-inflammatory cytokines.
In humans, short-term supplementation with resveratrol has been associated with beneficial effects on glucose and lipid metabolism in individuals with type 2 diabetes.
Comparison of changes between baseline and end-of-study measures between placebo and intervention groups showed that resveratrol significantly lowered both fasting glucose and fasting insulin concentrations and improved measures of glycemic control HbA1c level and insulin sensitivity HOMA-IR. In addition, the level of HDL -cholesterol was increased while the level of LDL -cholesterol and systolic blood pressure were significantly reduced. No changes were found in measures of diastolic blood pressure , total cholesterol , triglycerides , and markers of liver function During the three-month study period, changes in biochemical and clinical parameters, including fasting glucose concentration, HbA1c level, systolic and diastolic blood pressure, total cholesterol, and LDL-cholesterol, were significantly improved with resveratrol compared to control i.
A few clinical studies have evaluated the effects of resveratrol on key metabolic variables in overweight or obese subjects with no overt metabolic dysfunction and found little or no metabolic benefits following resveratrol treatment Yet, at present, there is no available evidence to suggest whether overweight or obese individuals with impaired glucose tolerance could benefit from resveratrol supplements and reduce their risk of developing type 2 diabetes Current data suggest that resveratrol could improve specific metabolic variables in individuals with type 2 diabetes , , but more research is needed to assess its effect in individuals at risk for diabetes, including obese subjects with impaired glucose tolerance.
Resveratrol is found in grapes, wine, grape juice, peanuts, cocoa, and berries of Vaccinium species, including blueberries, bilberries, and cranberries In grapes, resveratrol is found only in the skins The amount of resveratrol in grape skins varies with the grape cultivar, its geographic origin, and exposure to fungal infection The amount of fermentation time a wine spends in contact with grape skins is also an important determinant of its resveratrol content.
Therefore, because of variations between types of wine, vintages, and regions, it is very difficult to provide accurate estimates of resveratrol content in the thousands of wines from worldwide wineries. Yet, it appears that resveratrol content in wine is usually low, highly variable and unpredictable, and resveratrol is only a minor compound in the complete set of grape and wine polyphenols Many wines also contain significant amounts of cis -resveratrol see Figure 1 above , which may be produced during fermentation or released from viniferins resveratrol polymers Red wine is a relatively rich source of resveratrol, but other polyphenols are present in red wine at considerably higher concentrations than resveratrol see the article on Flavonoids Estimates of resveratrol content of some beverages and foods are listed in Table 1 and Table 2.
These values should be considered approximate since the resveratrol content of foods and beverages can vary considerably. Most resveratrol supplements available in the US contain extracts of the root of Polygonum cuspidatum , also known as Fallopia japonica , Japanese knotweed, or Hu Zhang Red wine extracts and grape extracts from Vitis vinifera containing resveratrol and other polyphenols are also available as dietary supplements. Resveratrol supplements may contain anywhere from less than 1 milligram mg to mg of resveratrol per tablet or capsule, but it is not known whether there is a safe and effective dosage for chronic disease prevention in humans also see the section on Safety.
Resveratrol is not known to be toxic or cause significant adverse effects in humans, but there have been only a few controlled clinical trials to date reviewed in A trial evaluating the safety of oral trans -resveratrol in 10 subjects found that a single dose of 5, mg resulted in no serious adverse effects Mild diarrhea was also reported in six out of eight individuals who consumed 2, mg of resveratrol twice daily for two periods of eight days in an open-label and within subject-control study The safety of resveratrol-containing supplements during pregnancy and lactation has not been established Because there is no known safe amount of alcohol consumption at any stage of pregnancy , pregnant women should avoid consuming wine as a source of resveratrol.
Until more is known about the estrogenic activity of resveratrol in humans, women with a history of estrogen-sensitive cancers , such as breast, ovarian, and uterine cancers, should avoid resveratrol supplements see Estrogenic and anti-estrogenic activities Resveratrol has been found to inhibit human platelet aggregation in vitro 53 , Theoretically, high intakes of resveratrol i.
Cytochrome P CYP enzymes are phase I biotransformation enzymes involved in the metabolism of a broad range of compounds, from endogenous molecules to therapeutic agents. Resveratrol has been reported to inhibit CYP3A4 activity in vitro , and in healthy volunteers Therefore, high intakes of resveratrol i. Some of the many drugs metabolized by CYP3A4 include HMG-CoA reductase inhibitors statins , calcium channel antagonists felodipine, nicardipine, nifedipine, nisoldipine, nitrendipine, nimodipine, and verapamil , anti-arrhythmic agents amiodarone , HIV protease inhibitors saquinavir , immunosuppressants cyclosporine and tacrolimus , antihistamines terfenadine , benzodiazepines midazolam and triazolam , and drugs used to treat erectile dysfunction sildenafil.
Of note, a recently completed clinical trial NCT examined the potential for single and multiple doses of resveratrol 1, mg to interfere with the metabolism of midazolam in healthy volunteers, and results are soon to be published Other CYP enzymes e. Finally, resveratrol was found to be a weak inducer of the expression and activity of CYP1A2, which catalyzes the metabolism of several drugs, including acetaminophen paracetamol and the antidepressant drugs, clomipramine and imipramine 28 , This suggests that resveratrol may interfere with CYP1A2-mediated drug metabolism by increasing drug clearance, possibly lowering circulating drug concentrations below therapeutic levels.
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