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resveratrol

What Is It?
Health Benefits
Forms

Dosage Information

Guidelines for Use

General Interaction

Possible Side Effects

Cautions

References

Evidence Based Rating Scale

 

What Is It?

Resveratrol is touted by nutritionists and biochemists especially for its potential as an anticancer and cardioprotective compound. Resveratrol belongs to the phytoalexin class of phytochemicals, which are produced by several plants when under attack by fungi, infection, injury, or stress. As such, resveratrol functions as a moderate Antioxidant, quenching free radical damage linked to multiple diseases. The compound has also demonstrated anti-inflammatory properties that help it to block reactions associated with the cancer process.

Resveratrol is found in the skins of red grapes and is, therefore, a component of red wine. It is also found in purple grape juice, berries such as blueberries, cranberries, and raspberries, and in smaller amounts in peanuts. In the 1990s, the compound began to garner scientific attention as a possible explanation for the “French paradox” of a low incidence of heart disease among French people despite a diet high in saturated fats. Resveratrol is often marketed as “the French paradox in a bottle,” though preliminary research indicates the amount of resveratrol found in wine is not sufficient to corroborate these claims.

Health Benefits

While resveratrol may not be responsible for the “French paradox,” preliminary in vitro and in vivo studies, and some human studies, have demonstrated that it may have anti-infective, antioxidant and anti-inflammatory properties important in treating cancer and heart disease. Some scientists also believe resveratrol may extend lifespan, but studies have been limited to animals.

Specifically, resveratrol may help to:

Prevent and treat cancer. Scientists suggest that resveratrol is unique because it has the ability to battle cancer at all three steps of the cancer process: initiation, promotion, and progression. Preliminary animal studies have shown resveratrol may reduce the risk of developing cancer by inhibiting tumor growth and by promoting apoptosis (programmed cell death), which can result in cancer if it doesn’t occur. A 1997 study in cancer-prone mice found that resveratrol acted as an antioxidant, anti-mutagen, and anti-inflammatory agent to inhibit the occurrence of skin tumors. (1) And another study in 1999 found resveratrol seemed to induce apoptosis through the activation of tumor protein 53, which acts as a tumor suppressor to prevent cancer. (2) Also in 1999, a study of cancerous rats found resveratrol decreased tumor growth. In the study, rats that had been inoculated with fast-growing tumors showed a significant decrease (25%) in tumor cell content after being treated with resveratrol due to apoptosis of the tumor cells. (3) A 2004 study comparing the effects of several compounds, including resveratrol, found them to be more effective in suppressing cancer than conventional medications. The comparison focused on the ability to suppress activation of nuclear factor-kappa B (NF-kappaB), leading to decreased multiplication of tumor cells. All compounds tested, including resveratrol, suppressed NF-kappaB thereby inhibiting the proliferation of tumor cells. Resveratrol, as well as curcumin, celecoxib (Celebrex), and tamoxifen, were found to be the most potent anti-inflammatory and anti-proliferative agents of those tested. (4) Additional in vivo studies have shown that resveratrol inhibits growth and induces death of ovarian and breast cancer cells, that it may prevent liver cancer cells from invading adjacent tissues, and also that it has positive effects on several other cancers, including leukemia and colon, esophageal, gastric, pancreatic, and prostate cancers. A 2006 review of these studies indicates efficacy in all of these areas. (5)

Results in humans have not been as conclusive, however. Several studies have found that resveratrol is most effective on tumors it can come into direct contact with – such as skin and gastrointestinal tract tumors, but that, even high doses, may not be enough for the systemic prevention of cancer in humans. For example, a 2007 study of 10 healthy volunteers testing the plasma levels of resveratrol after a single oral dose of 0.5g, 1g, 2.5g, or 5 g found that urinary excretion of resveratrol and its metabolites was rapid, and that plasma levels of resveratrol were not high enough for systemic cancer prevention even at the highest dosage. (6) A 2005 review of similar studies found that about 75 percent of resveratrol is excreted through feces and urine, and the overall oral bioavailability of resveratrol is almost zero because of its rapid and extensive metabolism. (7) However, a 2006 review of the chemopreventive effects of resveratrol indicates the enterohepatic recirculation (when secretions from the liver to the intestine are reabsorbed into the blood and returned to the liver) of the compound may contribute to delayed elimination of it, thereby increasing plasma levels to a level sufficient for cancer protection. (8) A 2007 review of studies evaluating phytochemicals, including resveratrol, in treating prostate cancer concluded that its efficacy cannot be rated in humans yet because of differences in study designs, small patient numbers, short treatment duration and lack of a standardized drug formulation. (9)

Improve cardiovascular health. Epidemiologic and clinical studies suggest that high consumption of resveratrol-rich foods may result in lowered total cholesterol, lowered LDL (bad) cholesterol, and reduced cardiovascular disease risk. Researchers believe that resveratrol is partially responsible for the cholesterol-lowering effects of red wine, and resveratrol's antioxidant properties may be the mechanism at work in reducing the oxidation of LDL cholesterol. When LDL undergoes oxidation, this chemical alteration causes it to stick to arterial walls and gradually form plaque. The plaque build-up narrows the arteries that supply the heart with blood carrying oxygen and nutrients in a condition, called atherosclerosis. So the potential of resveratrol to reduce the oxidation of LDL cholesterol may have important implications in heart disease. Also important for cardioprotection is resveratrol’s ability to inhibit platelet aggregation, the clumping together of blood platelets, which can lead to potentially deadly blood clots. Several studies have shown that resveratrol inhibits this process.

A 1995 study at the University of Toronto comparing the effects of resveratrol to other phenolics (quercetin, catechin and epicatechin), to antioxidants (alpha-tocopherol, hydroquinone and butylated hydroxytoluene), and to ethanol found that resveratrol inhibited thrombin-induced and ADP-induced platelet aggregation, whereas ethanol inhibited only thrombin-induced aggregation and the other compounds tested were inactive. Additionally, resveratrol inhibited the oxidation of lipids more effectively than the other compounds. (10) A similar study by Polish researchers in 1999 examined the effect of resveratrol on the production of free radicals in pig blood platelets and showed that resveratrol inhibited the production of different reactive oxygen species that can lead to heart disease. (11) In studies at the University of Connecticut School of Medicine, the cardioprotective action of resveratrol was tested in rats whose hearts were experimentally damaged by decreased blood flow and oxygen levels for thirty minutes followed by two hours of reperfusion. Five groups of rats were compared. One received an ethanol-free red wine extract for 15 minutes before ischemia.. Three of the rat groups received resveratrol, ethanol, or ethanol plus resveratrol; and one served as a control group. Both red wine extract and resveratrol were significantly more cardioprotective than control in improving post-ischemic ventricular (heart muscle) functions and reducing infarct size: however the red wine extract appeared superior to resveratrol alone. Improvement in the ethanol plus resveratrol group was equivalent to resveratrol alone, while there was minimal benefit to ethanol alone. (12, 13) More in vitro and in vivo studies followed these with similar results. A 2004 review of these animal studies found that resveratrol efficiently modulates vascular cell function, inhibits LDL oxidation, suppresses platelet aggregation and reduces myocardial damage during ischemia-reperfusion. However, the review called for further studies to establish its bioavailability and cardioprotective effects in humans. (14)

In one 2005 study in women, 24 pre-menopausal and 20 post-menopausal women were randomly divided into two groups: one group received a grape powder supplement containing resveratrol and other compounds (flavans, anthocyanins, quercetin, myricetin, and kaempferol), and the other group received placebo for four weeks. After a three-week washout period, subjects were assigned to the alternate treatment for an additional four weeks. Plasma triglyceride levels were reduced by an average 15% and 6% in pre-menopausal and post-menopausal women, respectively, after taking the supplement. Plasma LDL cholesterol also was lower after treatment, but LDL oxidation was not changed by supplementation. However, whole-body oxidative stress was significantly reduced as a result of supplementation. The grape powder supplement, which contained resveratrol, beneficially affected key risk factors for coronary heart disease in both pre- and post-menopausal women via altering lipoprotein metabolism, oxidative stress, and inflammatory markers. (15) A 2005 study of 30 men with coronary heart disease evaluated the effect of a grape extract on brachial artery dilation (an experimental model using the upper arm vessels to mimic how the heart might respond). The men received either a grape extract containing resveratrol and other polyphenolic compounds or placebo and were monitored 30, 60 and 120 minutes after treatment. Treatment with the grape extract resulted in a significant increase in dilation, which peaked at 60 minutes. No changes were observed in the control group. The polyphenolic compounds improved brachial artery function in these male patients with coronary heart disease and may help to explain the beneficial effects of red wine on the cardiovascular system. (16)

Expand lifespan. Preliminary research in animals indicates resveratrol improves factors associated with longer lifespan, including increasing insulin sensitivity and decreasing insulin-like growth factor-1. In 2006, a study at the Harvard Medical School showed that resveratrol counteracted the effects of a high-calorie, high-fat diet in mice. The mice were divided into groups and were fed either a standard diet or a high-fat diet that added hydrogenated coconut oil to the standard diet. The mice on the high-fat diet consumed about 30% more calories than those on the standard diet. Some mice also received resveratrol, which along with either diet led to a 30% lower risk of death than the mice on the high-fat diet without resveratrol. Upon examining gene expression, researchers noted that adding resveratrol opposed the effects of the high-calorie diet in 144 out of 153 known longevity gene pathways. Insulin and glucose levels in mice on the high-fat plus resveratrol diet were closer to those in the mice on a standard diet than to the mice on the high-fat diet without resveratrol. However, the addition of resveratrol to the high-fat diet did not change the levels of free fatty acids and cholesterol, which were much higher than in the mice on a standard diet. (17)

Researchers at the Institute of Genetics and Molecular and Cellular Biology in France subsequently found resveratrol may also increase physical endurance. In this 2006 study, mice given resveratrol ran twice as far as ordinary laboratory mice before collapsing from exhaustion. The mice treated with resveratrol also had energy-charged muscles and reduced heart rates similar to trained athletes. The researchers also examined the effects of resveratrol in a group of Finnish subjects and found the same gene regulatory mechanism may work in humans. (18) While previous studies used dosages in mice that would require humans to drink more than 100 bottles of red wine a day to achieve the same results, a 2008 study by researchers at the University of Wisconsin found that lower doses of resveratrol (the equivalent to 35 bottles of day in humans) produced the same beneficial effects in mice. In supplement form, researchers say, resveratrol may be able to mimic the effects of a calorie-restricted diet at safe and effective doses for humans. (19)

Prevent osteoarthritis. Preliminary studies indicate the anti-inflammatory properties of resveratrol may prevent the age-related deterioration of joint cartilage associated with osteoarthritis (OA). In a 2005 Turkish study, a group of rabbits with OA received intra-articular injections containing resveratrol once a day for two weeks: a control group did not receive it. The treatment group showed a significantly reduced average cartilage tissue destruction score (1.7), compared to the control group (2.8). Researchers concluded that injections of resveratrol at the onset of disease may slow of cartilage deterioration protect cartilage from developing and advancing OA. (20) Further in vitro studies of human articular cartilage cells have shown that resveratrol blocks the effects of pro-inflammatory cytokine (IL-1beta), which plays a role in the pathogenesis of OA, via inhibiting apoptosis in these cells. (21-23) More research is needed.

Forms

  • Capsule

  • Extract

  • Tablet

Dosage Information

Because studies in humans are limited, a standard dosage has not been determined. However, doses up to 5 grams have been used.

Guidelines for Use

Cooking or heating foods that contain resveratrol, such as blueberries or peanuts, reduces the content of resveratrol by up to half. Eating the raw source will provide a higher concentration of resveratrol.

General Inteaction

  • Taking resveratrol along with anticoagulant/antiplatelet herbs or medications may increase the risk of bleeding in some people.

  • There are no known interactions with foods associated with the use of resveratrol. 

Possible Side Effects

There are no known side effects associated with the use of resveratrol.

 Cautions

Resveratrol may act as a phytoestrogen (plant based substance that can bind with estrogen receptors in the body). In general, these substances are 1000 times weaker than hormonal estrogen. For women with hormone-sensitive conditions, such as breast, uterine, and ovarian cancers and endometriosis and uterine fibroids, it is unclear whether this effect is a risk or a benefit. Women with these conditions should discuss use of resveratrol with their physicians.

 References

 1. Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997 Jan 10;275(5297):218-20.
2. Huang C, Ma WY, Goranson A, Dong Z. Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway. Carcinogenesis. 1999 Feb;20(2):237-42.
3. Carbó N, Costelli P, Baccino FM, et al. Resveratrol, a natural product present in wine, decreases tumor growth in a rat tumor model. Biochem Biophys Res Commun. 1999 Jan 27;254(3):739-43.
4. Takada Y, Bhardwaj A, Potdar P, Aggarwal BB. Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene. 2004 Dec 9;23(57):9247-58.
5. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5(6):493-506.
6. 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. June 2007;16(6):1246-52.
7. Wenzel E, Somoza V. Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res. 2005 May;49(5):472-81.
8. Delmas D, Lançon A, Colin D, et al. Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer. Curr Drug Targets. 2006 Apr;7(4):423-42.
9. Von Löw EC, Perabo FG, Siener R, Müller SC. Review. Facts and fiction of phytotherapy for prostate cancer: a critical assessment of preclinical and clinical data. In Vivo. 2007 Mar-Apr;21(2):189-204.
10. Pace-Asciak CR, Hahn S, Diamandis EP, et al. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta. 1995 Mar 31;235(2):207-19.
11. Olas B, Zbikowska HM, Wachowicz B, et al. Inhibitory effect of resveratrol on free radical generation in blood platelets. Acta Biochim Pol. 1999;46(4):961-6.
12. Ray PS, Maulik G, Cordis GA, et al. The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radic Biol Med. 1999 Jul;27(1-2):160-9.
13. Sato M, Ray PS, Maulik G, et al. Myocardial protection with red wine extract. J Cardiovasc Pharmacol. 2000 Feb;35(2):263-8.
14. Bradamante S, Barenghi L, Villa A. Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev. 2004 Fall;22(3):169-88.
15. Zern TL, Wood RJ, Greene C, et al. Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr. 2005 Aug;135(8):1911-7.
16. Lekakis J, Rallidis LS, Andreadou I, et al. Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur J Cardiovasc Prev Rehabil. 2005 Dec;12(6):596-600.
17. Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42.
18. Lagouge M, Argmann C, Gerhart-Hines, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006 Dec 15;127(6):1109-22.
19. Barger JL, Kayo T, Vann JM, et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PloS ONE. 2008 Jun 4;3(6):e2264.
20. Elmali N, Esenkaya I, Harma A, et al. Effect of resveratrol in experimental osteoarthritis in rabbits. Inflamm Res. 2005 Apr;54(4):158-62.
21. Shakibaei M, John T, Seifarth C, Mobasheri A. Resveratrol inhibits IL-1 beta-induced stimulation of caspase-3 and cleavage of PARP in human anticular chondrocytes in vitro. Ann NY Acad Sci. 2007 Jan;1095:554-63.
22. Csaki C, Keshishzadeh N, Fischer K, Shakibaei M. Regulation of inflammation signaling by resveratrol in human chondrocytes in vitro. Biochem Pharmacol. 2008 Feb 1;75(3):677-87.
23. Shakibaei M, Csaki C, Nebrich S, Mobasheri A. Resveratrol suppresses interleukin-1beta-induced inflammatory signaling and apoptosis in human articular chondrocytes: Potential for use as a novel nutraceutical for the treatment of osteoarthritis. Biochem Pharmacol. 2008 Jun 3.

Evidence Based Rating Scale 

The Evidence Based Rating Scale is a tool that helps consumers translate the findings of medical research studies with what our clinical advisors have found to be efficacious in their personal practice. This tool is meant to simplify which supplements and therapies demonstrate promise in the treatment of certain conditions. This scale does not take into account any possible interactions with any medication/ condition/ or therapy which you may be currently undertaking. It is therefore advisable to ask your doctor before starting any new treatment regimen.

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Arthritis

 

 

 

 

 

Date Published: 04/19/2005
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