What is Resveratrol

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) was first discovered in the 1940s. Resveratrol is a polyphenol (phytoalexin), a natural chemical compound found naturally several plants in response to injury such as in response to exogenous stimuli such as fungal infections from Botrytis cinerea, lesions or UV radiation ¹. Resveratrol is a natural phytoalexin that accumulates in several vegetables and fruits like in red grape skins including their derived products like red wine and grape juice, blueberries, apples, raspberries, pistachios, plums, peanuts, mulberries, and some Japanese herbs (Japanese knotweed) ². It seems the roots of Japanese knotweed has abundant resveratrol. Since resveratrol was reported to possess strong anticancer properties in tumor initiation, promotion, and progression stages in the well-regarded journal Science in 1997 ³, its bioactivities and health benefits have been intensively investigated. Experimental and preclinical studies have attributed several health-promoting effects to resveratrol, including cardioprotective effects, chemopreventive activity in diverse cancers, and a capacity to extend the lifespan of lower organisms ⁴. The hope and hype concerning resveratrol was initiated by the finding that phenolic compounds such as the stilbenes exhibit radical scavenger and antioxidant properties ⁵. This may account in part for the so-called “French paradox” originally formulated in 1981 by French epidemiologists who observed a lower mortality incidence of coronary heart disease in France despite high levels of dietary saturated fat and cigarette smoking ⁶. It was later assumed that moderate drinking of red wine over a long period of time can protect against coronary heart disease and might be the cause of this paradoxical finding ⁷. Moreover, it was postulated that resveratrol modulates signaling pathways that limit the spread of cancer cells ⁸, protects nerve cells from damage ⁹, helps to prevent diabetes ¹⁰, and acts as an antiaging agent that improves age-related problems ¹¹. Rodent models suggested that this substance might improve consequences of an unhealthy lifestyle resulting from high caloric intake ¹². In addition, resveratrol has been shown to mediate therapeutic hepatic effects in acquired and genetic models of iron overload ¹³.

In the recent years, resveratrol received renewed interest as several findings implicated resveratrol could increase cell survival and slow aging in yeast (and later in mice) by activating a “longevity” gene known as sirtuin 1 (SIRT1) capable of mimicking the effects of calorie restriction, and regulating longevity in lower organisms. But the dose of resveratrol administered in experiments is always much higher than you’d normally consume in a daily diet. You would need to drink a hundred to a thousand glasses of red wine to equal the doses that improve health in mice ².

Given the worldwide increase in age-related metabolic diseases and obesity, resveratrol supplement has been promoted as a treatment for many conditions — including aging. The first real interest in this compound came when in 1992 resveratrol was postulated to explain some of the cardio-protective effects of red wine ¹⁴. Five years later, in 1997, Jang and colleagues reported resveratrol to work as a chemo-preventive agent, by the ability to inhibit carcinogenesis at multiple stages in lab mice ¹⁵. Meanwhile, anti-inflammatory and anti-oxidant properties were identified for resveratrol ¹⁶, ¹⁷.

Resveratrol supplements have not been well studied in people. We don’t really know what benefits and risks they might have. We also don’t know if resveratrol is necessarily more important than some of the other natural substances in wine. Furthermore, although resveratrol is well-tolerated and safe as reported by most of the clinical trials, very few adverse effects (e.g., nausea and diarrhea) were observed, as well as some unfavorable results like an increase in total cholesterol, ApoB, the homeostatic model assessment-insulin resistance (HOMA-IR) score, fasting blood glucose, body fat, and the inflammatory markers ¹⁸. Interestingly, resveratrol was reported to mask the exercise training-induced benefits, blunting the improved cardiovascular health parameters ¹⁹. It might be attributable to the potent antioxidant capability of resveratrol, which could scavenge the free radicals induced by exercise training, because the appropriate number of free radicals is necessary for health maintenance. Therefore, it could be suggested that foods containing resveratrol should not be consumed during exercise.

Nonetheless, resveratrol has become a popular supplement. People use it for many different conditions. Some take resveratrol supplements to try to prevent or treat serious diseases, like cancer or heart disease. Others hope that they will slow the aging process. For now, these uses are unsupported by evidence.

In light of the positive epidemiological evidence and the promising results from experimental studies, resveratrol has been investigated in the human population as a potential nutraceutical ²⁰. A nutraceutical is defined as any substance that is a food or part of a food and provides medical or health benefits, including the prevention and treatment of disease. There are certain encouraging outcomes reported. Specifically, resveratrol intake (500 mg/day for 30 days) was demonstrated to reduce cardiovascular disease risk factors by increasing sirtuin 1 (SIRT1), enhancing total antioxidant capacity in healthy individuals, decreasing low-density lipoprotein cholesterol (LDL-C or “bad cholesterol”), ApoB, and oxidized LDL ¹⁸. Moreover, resveratrol prevented bone density loss (500 mg/day for 6 months) in type-2 diabetic patients ²¹. In addition, resveratrol showed benefits in obesity, non-alcoholic fatty liver disease (NAFLD), and neurodegenerative diseases ²². However, some null outcomes have also been reported. For instance, resveratrol intake (250 mg/day for 8 weeks) did not increase SIRT1 nor improve many cardiovascular risk factors in healthy aged men ¹⁹. In some other studies, no significant improvements were found in metabolic biomarkers in patients with Alzheimer’s disease, obesity or type-2 diabetes, respectively, though their resveratrol intake ranged from 150 to 1000 mg/day with different duration of 4–52 weeks ²³. Therefore, the outcomes of clinical studies are not always consistent. Of note, the health effects of resveratrol as a therapeutic intervention may be affected by many factors, such as baseline health status of the subjects, their demographic profile, lifestyle, eating pattern, resveratrol dose, and intervention period. Nevertheless, a well-designed study, proper sample size, and a scientific evaluation system are also needed.

Resveratrol and weight loss, what is the evidence ?

The anti-obesity effects of resveratrol shown in lab mice are not transposed into an efficient therapy of human obesity ²⁴. Recent peer-reviewed human clinical trials did not show the ability of resveratrol as a weight loss compound.

Resveratrol supplements appeared to aid those with the stiffest blood vessels in small study

The antioxidant resveratrol — found in red wine, peanuts and berries — might improve the health of blood vessels in people with type 2 diabetes, a small study suggests ²⁵.

Some preliminary evidence also suggests that resveratrol in humans may have anti-inflammatory effects, prevent cancer, diminish arterial stiffness, and improve endothelial reactivity in older women ²⁶, ²⁷, ²⁸.

The study ²⁵, ²⁹ found that resveratrol supplements lessened artery stiffness in some people with type 2 diabetes. Stiffening of the arteries, called arteriosclerosis, raises the risk of heart attack and stroke. As you age, your arteries stiffen, which can lead to an increased risk of heart disease. In people with type 2 diabetes and obesity, this process starts earlier and can have more severe consequences.

The body’s largest artery is the aorta, which carries blood from the heart toward the rest of the body. For the study, the researchers measured the aortic thickness of 57 patients with type 2 diabetes (age 56 and obese, on average). The investigators also conducted tests to measure blood-vessel health.

Some patients were given resveratrol supplements, while the others were given a placebo. Overall, the study found a trend toward less aortic stiffness in participants taking resveratrol supplements, but it wasn’t statistically significant.

However, in a subset of 23 patients who had an exceptionally stiff aorta at the start of the study, 100-milligram (mg) daily doses of resveratrol for two weeks reduced stiffness nearly 5 percent. That regimen was followed by 300-mg doses over two weeks, which decreased stiffness by 9 percent, the researchers said.

Aortic stiffness increased among those taking a placebo for four weeks, the researchers found.

In treatment with resveratrol among people with diabetes, there was a trend toward improvement in the stiffness. And in people with higher stiffness there was more of a benefit.

“While the research suggests there might be ways to improve blood vessel abnormalities in people with type 2 diabetes, it’s too soon to recommend resveratrol for that purpose”, said the lead researcher Dr. Naomi Hamburg. She is chief of the vascular biology section at Boston University School of Medicine. The author added that a longer study is needed to look at whether resveratrol is going to reduce heart attacks and stroke. However, Hamburg pointed out that the doses of resveratrol used in the study were much greater than exists in a glass of red wine, a major dietary source of the antioxidant.

For now, the overall recommendation is to have a diet that’s rich in fruits and vegetables.

In animal studies, resveratrol has been shown to activate a “longetivity” gene (SIRT1) that appears to delay aging and development of several diseases ³⁰, ³¹.

To see if the same thing would happen in humans, the same researchers took samples from the blood-vessel linings of seven patients and looked at SIRT1 activity. They found that gene activity increased slightly after resveratrol supplementation. This doesn’t prove that reservatrol activates the longevity gene, only that there was an association.

This study shows that a natural antioxidant in these foods can reverse age-related changes in the arteries.

Impressively, the effect was seen after just a few weeks of treatment. Who knows what more prolonged antioxidant treatment could do to the arteries and other organs. Many people obtain resveratrol in their daily diet.

However, a recent phase 2 study of SRT501, a micronized oral formulation of resveratrol that activates SIRT1, in multiple myeloma patients was halted early owing to a high level of adverse effects and renal failure ³².

Another cloud: a company called Sirtris Pharmaceuticals, which was established to develop drugs from resveratrol, pulled the plug on the program in 2010 when a clinical trial showed that one of these drugs might be linked to kidney damage ³³.

Resveratrol and heart disease

There are a number of reports describing the beneficial effects of resveratrol on improvement of heart dysfunction, failure, calcification, and pressure overload, as well as the attenuation of myocardial hypertrophy by virtue of its antioxidant, antihypertensive, and coronary vasodilating activities ³⁴. At the molecular level, most likely some of these effects are mediated through activation of silent information regulator 1 (SIRT1; also known as Sirtuin 1), 5′-adenosine monophosphate-activated protein kinase, and endogenous antioxidant enzymes ³⁵. A recent study of the pathogenesis of myocardial fibrosis suggested that resveratrol exhibited its therapeutic effects by inhibiting pathways that were driven by reactive oxygen species, extracellular regulated kinases, TGF-β, and periostin ³⁶. In addition, resveratrol was shown to prevent collagen expression in cardiac fibroblasts and to protect against drug-induced cardiotoxicity ³⁷. The therapeutic effects of resveratrol in these models could be attributed to the capacity of resveratrol to protect against drug-induced glutathione depletion and superoxide dismutase activity ³⁸. A recent meta-analysis of 6 randomized controlled trials comprising a total of 247 subjects showed that high levels of resveratrol consumption significantly decreased the systemic blood level, although it had no effect on diastolic blood levels ³⁹.

Resveratrol and Anti-aging and Anti-cancer

Resveratrol is being examined in at least 110 clinical trials on: age-related macular degeneration, aging, Alzheimer’s disease, cancer including colon, follicular lymphoma, liver cancer, multiple myeloma and neuroendocrine tumors, cardiovascular problems including diastolic heart failure, hypertensive heart disease, cerebral blood flow, heart failure, heart failure with preserved ejection fraction, chronic renal insufficiency, cellulite, cognitive disorders, dyslipidemia, diabetes, diabetic nephropathy, endometriosis, eye diseases, Friedreich Ataxia, Huntington disease, memory, metabolic disorders, mood disorders, polycystic ovary syndrome (PCOS), seasonal allergic rhinitis, nonalcoholic fatty liver disease, peripheral arterial disease, obesity, schizophrenia, sedentary lifestyle, sports concussion, and other disorders ⁴⁰.

Resveratrol has demonstrated great potential in the treatment of various cancers due to its capability in targeting various molecular pathways ⁴¹. By inhibition of TNF-receptor associated factor 6 (TRAF6), resveratrol inhibits epithelial-to-mesenchymal transition (EMT) to reduce the invasion of prostate cancer cells ⁴². In colon cancer cells, resveratrol-loaded solid lipid nanoparticles remarkably stimulate apoptotic cell death to diminish the growth and proliferation of cancer cells ⁴³. In addition to apoptosis, resveratrol induces cell cycle arrest in cancer cells ⁴⁴. Due to its demethylation capability, resveratrol enhances the sensitivity of anaplastic thyroid cancer cells to retinoic acid ⁴⁵. Notably, resveratrol can be applied in cancer immunotherapy. Programmed death-1 (PD-1) is associated with reduced severity of the immune system during cancer progression. By administration of resveratrol, PD-1 is accumulated in endoplasmic reticulum and its stabilization is inhibited, leading to the increased anti-tumor activity of T-cells ⁴⁶.

Resveratrol administration is advantageous in the treatment of colon cancer by triggering signaling pathways that can lead to the stimulation of apoptosis. A combination of resveratrol and As2O3 diminishes the expression of hEGR channels on the cell membrane. This results in the dissociation of hERG and integrin β1 to induce apoptosis in colon cancer cells ⁴⁷. Furthermore, resveratrol has shown great potential in the treatment of oral cancer. Thyroxine is associated with enhanced proliferation and progression of oral cancer cells by down-regulation of apoptotic factor BAD and up-regulation of PD-1. Resveratrol exerts an inhibitory effect on the function of thyroxine so that resveratrol supplementation enhances the expression of BAD and inhibits PD-1 to suppress oral cancer cells ⁴⁸. By down-regulation of the snail signaling pathway, resveratrol reduces epithelial-to-mesenchymal transition (EMT) to inhibit the invasion of colon cancer cells ⁴⁹. It is worth mentioning that resveratrol activates tumor suppressor Rad9 to induce premature senescence in lung and breast cancer cells ⁵⁰. Another published article also demonstrates the capability of resveratrol in the regulation of epigenetic factors ⁵¹. These studies reveal the potential activity of resveratrol as an anti-tumor agent.

In summary ⁴⁰, the anti-aging, anti-cancer, anti-neurological effects of resveratrol have been examined in many different diseases and environments. While there have been many beneficial effects postulated to be induced by consumption of resveratrol, the concentrations required to obtain those health benefits may be high. Although, there probably are many beneficial health effects of consumption of products rich in resveratrol. A good, well-balanced diet may prevent certain diseases from occurring ⁴⁰.

In another study published online by JAMA Internal Medicine on May 12, 2014 ⁵², researchers report that dietary resveratrol did not affect health, longevity in the population study. The study participants were men and women, 65 years or older, who participated in the Invecchiare in Chianti, “Aging in the Chianti Area” (InCHIANTI) Study, conducted in 2 small towns in Tuscany, Italy.  Resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study.

Results are based on data collected from 1998 to 2009, as part of the Invecchiare in Chianti Study (“Aging in the Chianti Region”). The team of scientists from America and Italy, including NIA Scientific Director Dr. Luigi Ferrucci, found that resveratrol in the diet was not associated with a reduced incidence of cardiovascular disease, cancer, and inflammation, nor was it associated with longevity.

In the paper ⁵², researchers note the interest in resveratrol supplementation in the U.S. and elsewhere, and they caution against use of such supplements based on animal data thus far. The paper states there is “limited and conflicting human clinical data demonstrating any metabolic benefits of resveratrol, and there is no data concerning its safety in high doses or for long-term supplementation in older people, who often have multiple comorbidities for which they are taking multiple medications.”

The study authors suggest that more research with a larger group of participants is needed to determine whether resveratrol could have benefits in people, especially those who are overweight with health issues like diabetes.

Resveratrol and breast cancer

The impact of resveratrol on breast cancer is controversial. Although some reports showed that resveratrol supplementation prevented experimental mammary carcinogenesis ⁵³, other studies found that low concentrations of resveratrol promoted breast cancer ⁵⁴. Resveratrol decreased breast cancer cell proliferation in a dose-dependent manner ⁵⁵. Novel aza-resveratrol analogues have already been tested for their potential to inhibit the proliferation of breast cancer cells by impacting the expression of estrogen receptors ⁵⁶. In a pilot study conducted in 40 postmenopausal women with high BMI, a resveratrol intervention with 1 g resveratrol/d for 12 wk had favorable effects on estrogen metabolisms and increased the concentrations of the sex steroid hormone-binding globulin, which is inversely associated to breast cancer risk ⁵⁷. Likewise, a randomized double-blind study of 39 adult women with increased breast cancer risk showed decreased methylation of the tumor suppressor gene RASSF-1α (Ras association domain family member 1-α) in resveratrol-treated patients compared with nontreated subjects and suppression of expression of the cancer promoting PGE2 ⁵⁸. However, this study was conducted with a limited sample size and needs to be validated in larger cohorts.

Resveratrol and fertility

With regard to the ovaries, resveratrol was shown to be an effective therapy for conditions associated with androgen excess, thereby protecting against age-dependent decline in fertility by increasing the ovarian follicular reserve, ovarian life span, and preventing oocyte apoptosis ⁵⁹. Other reports have shown that resveratrol restores erectile function in experimental models of rats with diabetes, a finding that was mainly reflected by improvement of intracavernous pressure, mean arterial blood pressure, and modulation of cavernous cyclic GMP levels ⁶⁰. Recently, it was shown that resveratrol supplementation modulates oxidative stress, JNK signaling, and caspase-3 activities, thereby counteracting diabetes-induced decreases in reproductive organ weights, sperm count, and motility ⁶¹. Similar effects on spermatogenesis and general testicular germ cell differentiation of resveratrol were also reported in surgically rendered cryptorchid mice ⁶².

Resveratrol and the kidney

With regard to the kidney, independent reports have shown that resveratrol attenuates renal injury, fibrosis, unwanted drug toxicity, and oxidative and diabetes-associated damage ⁶³. Recently, it was demonstrated that resveratrol potentiates vitamin D and nuclear receptor signaling, possibly elucidating a possible molecular pathway of resveratrol activity ⁶⁴. An inhibitory effect of resveratrol on epithelial-mesenchymal transition, a process that is associated with the progression of fibrosis, was recently demonstrated in the human tubular epithelial cell line HK-2 ⁶³. In the study, it was demonstrated that resveratrol increased expression of SIRT1 and inhibited TGF-β pathway via deacetylation of Smad4, the common intracellular mediator of TGF-β signaling ⁶³.

Resveratrol and the eye

Resveratrol protected lens and corneal epithelium, as well as retinal photoreceptor cells, from diabetic complications and other kinds of damage ⁶⁵. Comparable to the observations that were found in renal cells, epithelial-mesenchymal transition was significantly inhibited in retinal pigment epithelial cells, suggesting that resveratrol is a potential drug suitable for the treatment of proliferative vitreoretinopathy, a disease marked by retinal detachment and ocular trauma ⁶⁶. In this model system, resveratrol also leads to a substantial deacetylation of Smad4, which resulted in reduced fibrotic membrane formation. In a diabetic cataract rat model, a protective effect of resveratrol on lens epithelial cell apoptosis was demonstrated by reduced expression of caspase-3 and lower apoptotic ratios ⁶⁷.

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence.

Insufficient evidence to rate effectiveness of Resveratrol for:

• Acne. Early evidence shows that applying a gel containing resveratrol to the face might reduce the severity of acne.
• Lung disease (chronic obstructive pulmonary disease, COPD). Early research suggests that taking a combination product containing resveratrol, vitamin C, zinc, and flavonoids slightly reduces coughing and mucus production in people with COPD.
• Diabetes. Some research suggests that taking 5 mg of resveratrol twice daily for 4 weeks does not affect insulin levels in people with diabetes. However, other evidence shows that taking a specific product that contains resveratrol (Biofort) daily for 3 months reduces blood sugar, blood pressure and fat levels in the blood.
• “Hardening of the arteries” (atherosclerosis).
• High cholesterol.
• Preventing cancer.
• Other conditions.

More evidence is needed to rate resveratrol for these uses.

How much resveratrol should you take?

Resveratrol is an unproven treatment and there is no standard dose. Given the lack of evidence about their safety, resveratrol supplements are not recommended for children or for women who are pregnant or breastfeeding.

Current recommendations for daily consumption of resveratrol are primarily based on arithmetical animal-to-human dosage conversion ². Unfortunately, the confirmation of therapeutic effectiveness of these calculated resveratrol concentrations in humans is still pending ⁶⁸. Independent studies have shown that resveratrol consumption in a daily range of 700–1000 mg/kg body weight is well tolerated without toxicologic effects and that concentrations ≤2 g/day are harmless when applied in the short term ⁶⁹. Based on these and other findings, various “experts” claim that a daily dosage of 1 g/day is effective for treatment of diverse disorders in humans. In addition, the permanent launch of articles with a lack of scientific background has led to the notion that the consumption of supplements enriched with resveratrol is health-promoting or suitable to alleviate diverse medical conditions. Moreover, the uncritical acceptance and erroneous interpretation of the French paradox, which links a lower incidence of coronary heart disease with the chronic consumption of low doses of red wine or intake of other resveratrol-containing nutrients, have led to the assumption that red wine, grapes, peanuts, chocolate, Itadori tea, or other foods or beverages are a kind of “daily health therapy.”

However, one wonders how much of these nutrients must be consumed to reach the Recommended Dietary Allowance (RDA) of 1 g resveratrol. Recommended Dietary Allowance (RDA) is average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%-98%) healthy people. Typical resveratrol concentrations reported for conventional food products are (see Figure 1 below): peanuts without seed coats, 0.03–0.14 μg/g ⁷⁰; red wines, 0.361–1.972 mg/L ⁷¹; white wines, 0–1.089 mg/L ⁷²; rosé wine from Serbia, 0.29 mg/L ⁷³; beers, 1.34–77.0 μg/L ⁷⁴; skin of tomatoes, ∼19 μg/g dry weight ⁷⁵; dark chocolate, 350 μg/kg; milk chocolate, 100 μg/kg ⁷⁶; Itadori tea (68 μg/100 mL, when prepared by infusing 1 g of the commercial root prepared with 100 mL of boiling water for 5 min) ⁷⁷; red Merlot grapes from Japan (1259 μg/kg fresh weight) ⁷⁸; white Riesling grapes from Japan, 59–1759 μg/kg fresh weight ⁷⁸; and apples, 400 μg/kg fresh weight ⁷⁹. On the basis of these given concentrations, it is not possible to absorb the recommended dose of resveratrol through uptake of any of these nutrients or combinations thereof (see Figure 1). This inevitably raises the question: how can scientists justify the French paradox by drinking red wine or consuming other foods or beverages? The newest annual report on wine published by the Global Agricultural Information Network reveals that France is the world’s biggest wine producer (4.6 billion liters in 2014) and consumer with a per capita consumption of 43.4 L in 2014 ⁸⁰. Assuming ∼73% of these wines are red/rosé wines and 27% are white wines, and further adopting that red/rosé wines contain ∼2 mg/L resveratrol and white wines contain ∼0.5 mg resveratrol/L, the annual consumption of 31.7 L of red wine and 11.7 L of white wine is equal to an uptake of ∼70 mg resveratrol/year (or 0.2 mg/day) or 5000 times less than the proposed therapeutic dose of 1 g/day. Even if further daily resveratrol sources (grapes or peanuts) are considered, these rough calculations clearly document that the consumption of red wine is not a good explanation of the pathologic mechanisms predicting the French paradox.

Taking resveratrol supplements comes with some risks ⁸¹, because no one knows

• the safe, effective dose for humans
• how long-term use will affect us for better or for worse.

That makes taking a resveratrol supplement a bit of an experiment—sort of like the tests on lab mice. A big difference is that mice have researchers assessing their response to resveratrol, but we don’t. If you take a resveratrol supplement, or plan to, let your doctor know so you both can be alert for any possible harms.

If you believe that resveratrol will help you live longer and healthier, get it from food or wine, not by choking down resveratrol pills. Why ? Eating red grapes, blueberries, and pistachios, or having a glass of your favorite red wine, are pleasurable ways to take in resveratrol. Plus you get all the other healthful plant products that come with the resveratrol.

Figure 1. Quantities of food and beverages that must be consumed to reach therapeutic Resveratrol doses

Footnotes: Based on animal studies, daily resveratrol doses in the range of hundreds of milligrams to several grams for therapeutic intervention have been proposed. If a person intends to ingest 1 gram resveratrol each day, this would require consuming the depicted quantities of foods or beverages. The calculation is based on typical resveratrol contents found in peanuts without seed coats (0.03–0.14 μg/g) ⁷⁰, red wine (Pinot noir from France, 0.362–1.979 mg/L) ⁷¹, white wine (Riesling from Spain, 0.057–0.390 mg/L) ⁷², rosé wine from Serbia (0.29 mg/L) ⁷³, beer (1.34–77.0 μg/L) ⁷⁴, skin of tomato (∼19 μg/g dry weight) ⁷⁵, dark chocolate (350 μg/kg), milk chocolate (100 μg/kg) ⁷⁶, Itadori tea (68 μg/100 mL, when prepared by infusing 1 g of the commercial root prepared with 100 mL of boiling water for 5 min) ⁷⁷, red Merlot grapes from Japan (1259 μg/kg fresh weight) ⁷⁸, white Riesling grapes from Japan (387 μg/kg fresh weight) ⁷⁸, and cultivated apples (estimating a mean total content of 400 μg/kg fresh weight found in 150 different cultivars) ⁷⁹.

[Source ⁸² ]

Resveratrol summary

Resveratrol is one of the most investigated bioactive compounds in foods ²⁰, although its use in clinical practice remains very limited. A number of epidemiologic studies have demonstrated that resveratrol is effective in the prevention of some diseases such as cardiovascular diseases and cancer, although the results are sometimes inconsistent ²⁰. In addition, the experimental studies have shown that resveratrol possesses many bioactivities and health benefits like antioxidant, anti-inflammatory, immunomodulatory effects, and improving cardiovascular diseases, cancer, liver diseases, diabetes, obesity, Alzheimer’s disease, and Parkinson’s disease. Furthermore, resveratrol showed some effects in patients with cardiovascular diseases and obesity in clinical trials, although inconsistency has also been reported. In the future, more bioactivities and health benefits of resveratrol should be evaluated, and further clarification of the underlying mechanisms of action is required. In order to develop resveratrol into functional foods and pharmaceuticals, more clinical trials are essential to confirm its efficacy and observe the possible adverse events, and the dose–effect relationship should be paid special attention as well.

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