Resveratrol

Resveratrol is a compound that is found in grapes. It is a potent anti-oxidant and anti-inflammatory agent and has gained a great deal of attention as it may boost longevity. Interest in this compound arose from the "French paradox" - that despite high intake of cholesterol and saturated fat, France has a low incidence of death from certain cancers or heart disease. It was postulated that resveratrol, which is found in wine, may be responsible for this.1

Over 20 years of research has suggested many beneficial effects of resveratrol, including longevity benefits, improved insulin sensitivity and weight loss, and neuroprotection. However, controlled trials have yet to demonstrate strong evidence for longevity or cognitive enhancement by resveratrol.2,3

Molecular Actions of Resveratrol

At a cellular level resveratrol action has been linked to SIRT1. SIRT1 is in the family of NAD-dependent deacetylases, and it is increased during fasting periods. As caloric restriction has a very strong link with longevity, these molecular consequences of fasting have gained a great deal of attention.

At a molecular level, the actions of resveratrol appear to depend on SIRT1 signaling. However, what exactly the interaction entails is unclear at present. Overall, resveratrol appears to increase mitochondrial function - the cell's energy generator.4

Effect on Cognition

Resveratrol can cross the blood brain barrier, and at doses of 250 and 500 mg, increases cerebral blood flow.5However, acute or chronic resveratrol administration has not been shown to improve cognition, as measured by psychometric testing batteries.5It has been observed that resveratrol blood levels increase when taken chronically, indicating that other benefits, such as neuroprotection, may be enhanced by chronic intake.

There is evidence from work in neural cell culture that resveratrol may act synergistically with melatonin, to reduce oxidative damage induced by treatment with amyloid beta, a toxic protein implicated in Alzheimer's Disease.6In a study of cerebral ischemia (a model for strokes), resveratrol was shown to reverse cell death and glial cell activation (hallmarks of cell death and detrimental inflammation that occur after ischemia).7

Editorial Opinion

At a molecular level and in controlled studies resveratrol appears to have powerful protective properties against oxidative stress. However, studies demonstrating clear longevity benefits, or cognitive benefits in healthy adults are lacking. So we do not recommend resveratrol supplementation. Studies demonstrating tangible benefits of chronic resveratrol administration are necessary.

  1. Poulose, S. M., Thangthaeng, N., Miller, M. G., & Shukitt-Hale, B. (2015). Effects of pterostilbene and resveratrol on brain and behavior. Neurochem Int, 89, 227-233. doi:10.1016/j.neuint.2015.07.017

  2. Kasiotis, K. M., Pratsinis, H., Kletsas, D., & Haroutounian, S. A. (2013). Resveratrol and related stilbenes: their anti-aging and anti-angiogenic properties. Food Chem Toxicol, 61, 112-120. doi:10.1016/j.fct.2013.03.038

  3. McCormack, D., & McFadden, D. (2013). A review of pterostilbene antioxidant activity and disease modification. Oxid Med Cell Longev, 2013, 575482. doi:10.1155/2013/575482

  4. Price, N. L., Gomes, A. P., Ling, A. J., Duarte, F. V., Martin-Montalvo, A., North, B. J., . . . Sinclair, D. A. (2012). SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab, 15(5), 675-690. doi:10.1016/j.cmet.2012.04.003

  5. Kennedy, D. O., Wightman, E. L., Reay, J. L., Lietz, G., Okello, E. J., Wilde, A., & Haskell, C. F. (2010). Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr, 91(6), 1590-1597. doi:10.3945/ajcn.2009.28641

  6. Kwon, K. J., Kim, H. J., Shin, C. Y., & Han, S. H. (2010). Melatonin Potentiates the Neuroprotective Properties of Resveratrol Against Beta-Amyloid-Induced Neurodegeneration by Modulating AMP-Activated Protein Kinase Pathways. J Clin Neurol, 6(3), 127-137. doi:10.3988/jcn.2010.6.3.127

  7. Wang, Q., Xu, J., Rottinghaus, G. E., Simonyi, A., Lubahn, D., Sun, G. Y., & Sun, A. Y. (2002). Resveratrol protects against global cerebral ischemic injury in gerbils. Brain Res, 958(2), 439-447.

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