Resveratrol
See also: Resveratrol Studies
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Food Sources: Grape skins and seeds Peanuts, pistachios Mulberries, blueberries, cranberries Polygonum cuspidatum or Japanese knotweed.
Concentration of the **phytoalexin** resveratrol in wine
Resveratrol is a polyphenol stilbenoid and an antifungal phytoalexin made by a few plants including Japanese Knotweed (Polygonum cuspidatum) and Grape (seeds and skins), and is found in lesser amounts in many blue/red/purple berries, including Mulberries (Morus rubra); Peanuts are also a minor source. It has numerous antimutagenic, antioxidant, and cardioprotective benefits for humans. In addition, it is an anti-inflammatory COX-1 modulator with venotonic effects, inhibits platelet aggregation, induces apoptosis in certain cancer cells, and acts as a beneficial phytoestrogen that may help to prevent or treat breast cancer. Resveratrol is ethanol-soluble, so significant amounts are found in red wine where it is hypothesized to contribute to the cardioprotective effect of the Mediterranean diet and to help explain the 'French paradox.” Many resveratrol supplements are made from the roots of Japanese Knotweed, which is the richest known practical source of the compound – and being an invasive weed, it's also an ecologically sustainable choice. (-Ganora)
The simple phenol resveratrol is probably the most actively researched phytochemical worldwide, with many properties demonstrated in pharmacological models. There are more than 4000 studies on resveratrol. It’s a phytoalexin produced by several plants in response to fungal attack...
One of the issues with resveratrol is that its rapidly metabolized and has limited bioavailability. However, resveratrol metabolites (mainly phase II conjugates) might also be bioactive, or act as a reservoir of resveratrol at target tissues. One study found that to maximize plasma resveratrol levels it should be taken with a standard breakfast and not with a high fat meal. The high fat breakfast was observed to reduce its bioavailability by about 45%
Since phytochemicals can causehormeticresponses and may act as environmental signals to shift into survival mode ahead of an environmental decline, Dr. David Sinclair’s team investigated whether simple phytochemicals might increase the SIRT1 protein. Resveratrol, found in grapes and several other foods and herbs, was identified to be the most active natural agent at activating SIRT1
(Mill & Bone)
Take 4 capsules of resveratrol with dinner. Circadian rhythm research shows that it’s better to take antioxidants during the night, not the day.
Resveratrol-3,4',5-trihydroxy-trans-stillbene (resveratrol; RSV), a natural non-flavonoid polyphenol compound, provides protection against stress injury, excessive sunlight, ultraviolet radiation, infections, and invading fungi. There is increasing evidence that resveratrol, a sirtuin1 activator, plays a pivotal role in neuroprotection and neuronal differentiation - See Study
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Uses
To prevent or treat heart disease
There is limited scientific evidence to support this use.
To treat arthritis
A few studies suggest resveratrol may help as an add-on to some medications, but more studies are needed.
To prevent or treat diabetes
A few studies suggest resveratrol may improve some markers and symptoms of type 2 diabetes, but it did not appear to improve metabolic syndrome in obese patients.
To improve memory
Although one study showed that resveratrol may affect some markers of Alzheimer’s disease, other trials found no significant impact on memory or cognitive function in older adults.
For cancer prevention or as add-on treatment
Several laboratory studies suggest resveratrol may prevent the growth of cancer cells. However, some of these experiments used very high doses, which in one human study caused serious adverse events. Other studies in humans were too small to draw any conclusions. In addition, resveratrol has hormone-like properties that may stimulate some types of cancer cells.
To reduce radiation side effects
Although a few lab experiments suggest utility, no human studies have been conducted.
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 . 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 , but a meta-analysis did not find any significant effect on memory or cognitive performance . Recent double-blind trials have also not found benefit with resveratrol on cognitive function in older adults.
Resveratrol is also thought to have cardioprotective effects. Earlier studies found it reduces low density lipoprotein (LDL) oxidation, inhibits platelet aggregation, and may protect against atherogenesis . Consumption of wine or a resveratrol-rich grape supplement is associated with reduced risk of cardiovascular disease and may help promote circulatory system health . However, it does not decrease risk of all-cause mortality in older adults . Data on effectiveness of resveratrol against non-alcoholic fatty liver disease are conflicting.
Resveratrol may increase insulin sensitivity in diabetic patients , and supplementation improved arterial stiffness and reduced oxidative stress . However, it did not improve metabolic patterns or reduce C-reactive protein , and data on whether it controls metabolic syndrome in obese subjects are inconclusive . Other studies suggest benefit with resveratrol in diabetic patients on bone density and levels of SIRT-1, a key protein in metabolism and inflammation . It may also help as adjunctive therapy to improve symptoms in rheumatoid and osteoarthritis.
Preclinical experiments suggest that resveratrol has antiproliferative and antioxidant effects . In combination with radiation exposure, it exhibited dose-dependent radioprotective , radiomodulatory , radiosensitizing , cytotoxic , and neuroprotective effects. Other experiments suggest effects including chemotherapeutic potentiation and protection against chemo-induced cardiotoxicity.
However, data on use of resveratrol in cancer patients are quite limited. In phase 1 pilots of colorectal cancer patients, one study suggests resveratrol may decrease tumor cell proliferation while another suggests utility may be limited to prevention rather than established cancers . Study of a high-dose micronized formula in multiple myeloma patients was stopped due to serious adverse events that included renal failure . In addition, resveratrol exhibits estrogen-like properties and activates transcription by both estrogen and androgen receptors that can lead to the stimulation of cancer cell proliferation . Therefore, larger well-designed trials are needed to determine the circumstances under which resveratrol might demonstrate utility and safety.
Whereas resveratrol appears to be well tolerated in some studies, high doses can cause gastrointestinal side effects such as diarrhea. It also inhibits cytochrome P450 enzymes and may increase the risk of adverse effects of certain drugs. Given its phytoestrogenic properties and potential for interactions, use of this supplement should be discussed with the treating physician.
Mechanism of Action
Resveratrol acts as an antioxidant and inhibits oxidation of low density lipoproteins (LDL) , platelet aggregation, and eicosanoid synthesis ; induces nitric oxide (NO) production and increases arterial blood flow . These actions may contribute to its purported cardiovascular health benefits. Resveratrol also acts as an anti-inflammatory agent by inhibiting cyclooxygenase (COX) activity . 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 . Other effects include decreasing oxidative stress and improving insulin sensitivity by increasing protein kinase activities . Resveratrol was also shown to decrease circulating insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels 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 , inhibiting human Sirt3 along with stimulating Sirt5 and Sirt1 . The neuroprotective effects of resveratrol were shown to be via regulating autophagy and apoptosis mediated by the Akt/mTOR pathway.
Resveratrol has also been investigated for its anticancer potential. It was found to inhibit proliferation of cancer cells via apoptosis and by exerting antiestrogenic effects . Trans-resveratrol appears to decrease methylation of the tumor suppressor gene RASSF-1alpha in women at increased breast cancer risk . In addition, reductions in breast cancer cell migration and invasion were observed after supplementation . Resveratrol growth factor heregulin-beta1 (HRG-beta1) mediated matrix metallopeptidase 9 (MMP-9) expressions in human breast cancer cells . However, contradictory data show that resveratrol mimics phytoestrogens and could activate genes that are normally regulated by estrogens or androgens . 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 ; and modulated steroid hormone-dependent pathways to inhibit prostate cancer cell growth. However, it also increases angiogenesis and inhibits apoptosis in vivo . 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 . 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 . Protective effects of resveratrol against doxorubicin-induced cardiotoxicity are due to upregulation of SIRT1-mediated p53 deacetylation . Also, it protects against cisplatin-induced cardiotoxicity by suppressing oxidative stress,
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