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Resveratrol

Resveratrol featured article

Resveratrol is a natural compound found primarily in the skin of red grapes and the root of Polygonum cuspidatum (also known as Japanese knotweed). It is also present to a lesser degree in peanuts and blueberries. Resveratrol protects the plants in which it is present from fungal attack and the damaging effects of ultraviolet radiation.

Originally extracted in the 1940s, resveratrol attracted little interest in terms of human health until 1992 when research suggested that it could mediate some of the cardioprotective effects of red wine. Since then, numerous studies have demonstrated resveratrol's ability to slow or prevent various illnesses, including cancer and cardiovascular disease, as well as extend the lifespan of organisms ranging from yeast to vertebrates. These protective effects are likely due to resveratrol's anti-inflammatory and antioxidant properties and its capacity to activate sirtuin 1, or SIRT1, a type of enzyme that plays a role in aging and longevity.

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Posted on January 15th 2024 (over 1 year)

Dr. Rhonda Patrick explores iodine supplementation, choline & TMAO, curcumin safety, and red yeast rice in her latest Q&A.

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Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.

Topic Pages

  • Resveratrol

    Resveratrol, a polyphenolic stilbene, activates SIRT1, modulates AMPK and NF-κB pathways, conferring antioxidant and anti-inflammatory effects.

  • Sirtuins

    Resveratrol allosterically enhances mammalian SIRT1 deacetylase activity by decreasing Km for NAD⁺ and specific acetyl-lysine substrates.

News & Publications

  • From the article:

    They have tested 21 different compounds in Alzheimer’s-afflicted neural cells in the lab, measuring the compounds’ effect on the growth of sticky beta amyloid plaques. These plaques develop in the brains of people with Alzheimer’s.

    […]

    The initial screening was done in simpler models, and compounds that had a positive effect were then tested in the 3D neural tissue model. That model is created using a nonreactive silk sponge seeded with human skin cells that, through genetic reprogramming, are converted into neural stem cell progenitors.

    Those cells grow and populate the sponge, “which allows for 3D network formation of neurons similar to what you’d see in the human brain,” Cairns says.

    The initial screen found five compounds had “really robust prevention of these plaques,” she says. In addition to the green tea compounds and resveratrol, they found curcumin from turmeric, the diabetic medication Metformin, and a compound called citicoline prevented plaques from forming and did not have anti-viral effects.

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  • From the article:

    The researchers looked to the rostral ventrolateral medulla (RVLM), a critical region in the brain stem known to be involved with the maintenance of blood pressure and thought to be associated with hypertension and heart failure. They theorized that chronic exposure to low levels of estrogen (in the form of estradiol-17β, also called E2) could influence this area of the brain.

    […]

    To test their hypotheses they conducted a two-phase experiment using rats. In phase 1, animals were divided into groups and used as either controls or implanted with E2. After 90 days of E2 exposure the animals were examined and key data collected. In phase 2, the animals were used as either controls or implanted with E2 and, in addition, fed resveratrol-laced chow for 90 days. As with phase 1, RVLM was subsequently isolated from each animal and examined for increases in superoxide, hypertension and other key health markers.

    Results

    The researchers found that chronic E2 exposure caused a significant increase in superoxide in the RVLM, and in blood pressure. In addition they determined that the increases in both indicators were reversed with resveratrol. Taken together, the findings demonstrate that chronic exposure to low levels of E2 is capable of causing hypertension, possibly by increasing superoxide generation in the RVLM.

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  • Abstract

    “Cerebrovascular endothelial cells (CEC) comprise the blood-brain barrier (BBB). In a previous study, we showed that oxidized LDL (oxLDL) can induce apoptosis of mouse CEC. Resveratrol possesses chemopreventive potential. This study aimed to evaluate the effects of resveratrol on oxLDL-induced insults to mouse CEC and its possible mechanisms. Exposure of mouse CEC to 200 μmol/L oxLDL for 1 h did not cause cell death but significantly altered the permeability and transendothelial electrical resistance of the cell monolayer. However, resveratrol completely normalized such injury. As for the mechanisms, resveratrol completely protected oxLDL-induced disruption of F-actin and microtubule cytoskeletons as well as occludin and zona occludens-1 (ZO-1) tight junctions. The oxLDL-induced decreases in the mitochondrial membrane potential and intracellular ATP levels were normalized by resveratrol. Exposure of mouse CEC to 200 μmol/L oxLDL for 24 h elevated oxidative stress and simultaneously induced cell apoptosis. However, resveratrol partially protected against oxLDL-induced CEC apoptosis. The oxLDL-induced alterations in levels of Bcl-2, Bax, and cytochrome c were completely normalized by resveratrol. Consequently, resveratrol partially decreased oxLDL-induced activation of caspases-9 and -3. Therefore, in this study, we show that resveratrol can protect against oxLDL-induced damage of the BBB through protecting disruption of the tight junction structure and apoptotic insults to CEC.”

  • “The largest nationwide clinical trial to study high-dose resveratrol long-term in people with mild to moderate Alzheimer’s disease found that a biomarker that declines when the disease progresses was stabilized in people who took the purified form of resveratrol. Resveratrol is a naturally occurring compound found in foods such as red grapes, raspberries, dark chocolate and some red wines.”

    Abstract “Resveratrol is a natural polyphenolic compound that activates nicotinamide adenosine dinucleotide-dependent deacetylase SIRT1. Resveratrol has recently been shown to exert potent antidiabetic actions when orally delivered to animal models of type 2 diabetes. However, the tissue(s) mediating these beneficial effects is unknown. Because SIRT1 is expressed in central nervous system (CNS) neurons known to control glucose and insulin homeostasis, we hypothesized that resveratrol antidiabetic effects are mediated by the brain. Here, we report that long-term intracerebroventricular infusion of resveratrol normalizes hyperglycemia and greatly improves hyperinsulinemia in diet-induced obese and diabetic mice. It is noteworthy that these effects are independent of changes in body weight, food intake, and circulating leptin levels. In addition, CNS resveratrol delivery improves hypothalamic nuclear factor-κB inflammatory signaling by reducing acetylated-RelA/p65 and total RelA/p65 protein contents, and inhibitor of nuclear factor-κB α and IκB kinase β mRNA levels. Furthermore, this treatment leads to reduced hepatic phosphoenolpyruvate carboxykinase 1 mRNA and protein levels and ameliorates pyruvate-induced hyperglycemia in this mouse model of type 2 diabetes. Collectively, our results unveiled a previously unrecognized key role for the CNS in mediating the antidiabetic actions of resveratrol.”

  • Currently selected for this coming member’s digest by team member Melisa B.

    Adequate exercise is one of the most effective lifestyle interventions to improve aging, but many people, especially older adults, can find it difficult to exercise. In a study published this month, researchers tested the effects of resveratrol as an adjuvant therapy to exercise for older adults with physical limitations.

    The word “adjuvant” has roots in Latin that mean “helping toward.” Adjuvant therapies are add-ons that may improve the effectiveness of other interventions. Resveratrol is known to activate mitochondria through a protein called PGC-1α, the master regulator of mitochondrial biogenesis. Therefore, resveratrol may boost the benefits of exercise by enhancing mitochondrial adaptation in skeletal muscle.

    The purpose of this randomized controlled pilot study was to determine the safety and feasibility of chronic exercise combined with resveratrol supplementation. The investigators split a group of 60 adults (average age, 71 years) with physical limitations into three groups. All three groups completed supervised walking and whole-body resistance training twice weekly for 12 weeks. One group took 500 milligrams of resveratrol daily, another took 1,000 milligrams of resveratrol daily, and the third group took a placebo. The participants completed a battery of physical function tests and gave blood so the researchers could measure markers of cardiovascular risk.

    On average, participants completed 82 percent of their exercise sessions and took 85 percent of their resveratrol doses, indicating that the intervention was acceptable for most participants. The rate of adverse events was similar between groups with an average of nine events, indicating that the intervention was safe. Pilot studies are not designed to evaluate the effect of the study intervention on health; however, the authors reported some promising early results. Participants in the 1,000 milligram group exhibited a clinically-significant increase of 449 meters in their 6-minute walk test and increased levels of citrate synthase, a common marker of mitochondrial volume.

    The authors are planning a large-scale clinical trial to build on these preliminary results.