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They say you can’t buy happiness, but you can buy wine, and that’s kind of the same thing. But could drinking wine also be adding years to your life?

A small compound known as resveratrol might hold the key to this question.

History

Grapes have been hailed as a miracle cure since 1928, when Johanna Brandt published her popular book The Grape Cure[1], in which she claimed that a regime of fasting followed by the consumption of red grapes cured her of cancer, and could prove effective against a host of other diseases such as arthritis, diabetes, and cataracts.

Resveratrol is a compound found in grapes, berries, and nuts, and commonly associated with red wine. It was first isolated in 1939 from white hellebore – a poisonous medicinal plant – by Michio Takaoka[2]. In 1963, Nonomura, another Japanese scientist, isolated it from Japanese knotweed[3], whose roots had been used for centuries in traditional medicine to treat cardiovascular diseases and liver ailments.

Indeed, the presence of resveratrol in grapevines was not elucidated until 1976[4], and its presence in wine was only found as recently as 1992 by Siemann and Creasy of Cornell University[5]. This discovery has led to widespread speculations about wine consumption being a solution to the “French paradox”.

More recently, scientists at the Harvard Medical School, such as David Sinclair and Konrad Howitz, have shown that resveratrol can increase the lifespan of yeast cells and other species such as worms and fruit flies[6]. The evidence for lifespan increases in mammals and humans has been inconclusive and is still largely debated, however.       

Resveratrol in nature

Resveratrol is a stilbenoid existing as two geometric isomers: cis- and trans-. It is synthesized in some plant species as a response to infection, UV radiation, or injury, and is a member of the same family as pterostilbene, another related compound with the same action and superior bioavailability.

Resveratrol can be found in a large variety of natural foods, including grapes, peanuts[7], cocoa, and berries such as blueberries, raspberries, and cranberries[8]. Red wine is thought to have higher levels of resveratrol than white wine, due to its high concentration in the skin of grapes, which are fermented during the production of red wine, giving it its characteristic colour.

The average concentration of resveratrol in red wine is 1.9±1.7 mg/liter of trans-resveratrol, with those made from the Pinot Noir and St Laurent grape varieties boasting the highest levels[9]. Trans-resveratrol is more active than cis-resveratrol, and is thought to have more positive effects on inflammation and cancer proliferation than its isomer[10-11].  

Due to its high reactivity, the bioavailability of resveratrol is very low, and several studies have shown that only around 10% of the average oral dose ends up in the blood serum[12-13]. The good news is that co-ingestion with other flavonoids, particularly quercetin has recently been found to increase resveratrol bioavailability[14-15], due to the competition of these molecules for the same metabolizing enzymes[16].

The presence of other bioflavonoids in wine has also been purported to increase the bioavailability of resveratrol[17], which makes reaching for that extra glass of wine in the evening all the more tempting. 

However, compared to the amount of resveratrol present in typical dietary supplements (100mg and upwards) wine has very small amounts not to mention its poor bioavailability. It should probably not need stating, but we certainly do not recommend drinking excessively as this can lead to serious health problems and is a poor health and longevity strategy.

Potential Health Benefits

Resveratrol is one of the best studied flavonoids, particularly in the context of aging. Most mammal studies to date have been carried out in rats, however, and despite its popularity, only a relatively small number of clinical trials have been conducted in humans.

Due to its interaction with SIRT1 and adipocyte development, resveratrol has been proposed as a possible therapeutic agent for the improvement of cardiovascular disease. In recent years, supplementation with resveratrol has been shown to decrease LDL (bad cholesterol) levels, and apolipoprotein-B in patients with CVD[18-19].

Resveratrol has also been thought to have great therapeutic potential for metabolic syndrome and obesity, and some studies have shown it to have a beneficial effect on glucose metabolism, as well as temporarily increasing insulin sensitivity in diabetics[20-21]. In obese subjects, resveratrol confers a protective and antioxidant effect[22-23], and reduces resting metabolic rate by a mechanism which mimics calorie restriction[24].

Recently, it has been proven to stimulate fat metabolism by increasing cyclic adenosine monophosphate (a derivative of ATP) in cells through a mechanism analogous to that used by known fat burners such as caffeine and green tea catechins[25].

In patients with colorectal cancer treated with resveratrol, tumor cell proliferation seems to be reduced after surgery[26], while chemoprotective effects have also been found for breast cancer[27].

In 1997, a landmark study indicated that the topical application of resveratrol acted as a powerful chemopreventive treatment for skin cancer[28], and recent studies have shown that resveratrol is a very effective UV-filter for use in sunscreens, particularly in combination with other antioxidants[29]

The longevity effects of resveratrol in humans, although potentially appreciable, are still being contested, and the latest reviews have suggested that resveratrol may be enhancing lifespan by reducing the risk of common causes of death such as cardiovascular disease and cancer, rather than extending lifespan per se.

It has also been proposed that it is its interaction with AMPK and NAD+, not SIRT1 as previously thought, that may be the primary cause of its longevity effects[30-32].    

Disclaimer

This article is only a very brief summary, and is not intended as an exhaustive guide and is based on the interpretation of research data, which is speculative by nature. This article is not a substitute for consulting your physician about which supplements may or may not be right for you. We do not endorse supplement use or any product or supplement vendor and all discussion here is for scientific interest.

Literature

[1] Brandt, J., (1928). The Grape Cure. New York: Harmony Centre, Inc., 1928.

[2] Takaoka, M., (1939). Resveratrol, a new phenolic compound, from Veratrum grandiflorum (Title in Japanese). Nippon Kagaku Kaishi 60: 1090-1100.

[3] Nonomura; Kanagawa (1963). Chemical constituents of Polygonaceous plants. I. studies on the components of Ko-jo-kon. Yakugaku Zasshi 83: 988–990.

[4] Langcake P., Pryce R.J., (1976). The production of resveratrol by Vitis vinifera and other members of the Vitaceae as a response to infection or injury. Physiology and Plant Pathology 9: 77–86.

[5] Siemann, E.H., Creasy, L.L., (1992). Concentration of the Phytoalexin Resveratrol in Wine. American Journal of Enology and Viticulture, 43: 49-52.

[6] Howitz, K., Bitterman, K., et al. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425: 191-196.

[8] Higdon, J., Drake, V.J., Steward, W.P., (2016). “Resveratrol”. Micronutrient Information Center. Linus Pauling Institute, Oregon State University, Corvallis, OR.

[7] Sales, J.M., Resurreccion, A.V., (2014). “Resveratrol in peanuts.”. Critical reviews in food science and nutrition. 54 (6): 734–70.

[9] Stervbo, U.,Vang, O., Bonnesen, C., (2007). “A review of the content of the putative chemopreventive phytoalexin resveratrol in red wine”. Food Chemistry. 101 (2): 449–57.

[10] Agarwal, B., Baur, J.A., (2011). Resveratrol and life extension. Annals of the New York Academy of Science.

[11] Howitz, K.T., et al. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425: 191-196.

[12] Walle, T. et al. (2004). High absorption but very low bioavailability of oral resveratrol in humans . Drug Metabolism and Disposition 32(12):1377-82

[13] Cottart, C.H., et al. (2010). Resveratrol bioavailability and toxicity in humans. Molecular Nutrition and Food Research 54(1):7-16.

[14] Pacifici, G.M. (2004). Inhibition of human liver and duodenum sulfotransferases by drugs and dietary chemicals: a review of the literature. International Journal of Clinical Pharmacolology and Therapeutics 42(9): 488-95.

[15] Arias, N., (2016). The combination of resveratrol and quercetin enhances the individual effects of these molecules on triacylglycerol metabolism in white adipose tissue. European Journal of Nutrition, 55(1): 341-348.

[16] Chaudhary, A., et al. (1993). Multiple-dose lorazepam kinetics: shuttling of lorazepam glucuronide between the circulation and the gut during day- and night-time dosing intervals in response to feeding. Journal of Pharmacology and Experimental Therapeutics 267(3):1034-8.

[17] Belguendouz, L., Frémont, L., Gozzelino, M.T., (1998). Interaction of transresveratrol with plasma lipoproteins. Biochemical Pharmacology 55(6): 811-6.

[18] Magyar, K., et al. (2012). Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clinical Hemopheology and Microcirculation, 50(3): 179-187.

[19] Tomé-Carneiro, J., (2012). Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial. Molecular Nutrition and Food Research, 56(5): 810-821.

[20] Baile, C.A., et al. (2011). Effect of resveratrol on fat mobilization. Annals of the New York Academy of Science 1215: 40-7.

[21] Fischer-Posovszky, P., et al. (2010). Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. American Journal of Clinical Nutrition 92(1):5-15.

[22] De Groote, D., et al. (2012). Effect of the intake of resveratrol, resveratrol phosphate, and catechin-rich grape seed extract on markers of oxidative stress and gene expression in adult obese subjects. Annals of Nutrition and Metabolism, 61(1): 15–24.

[23] Wong, R.H., et al. (2011). Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutritional Metabolism and Cardiovascular Disease 21(11): 851–856.

[24] Timmer, S. (2011). Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metabolism 14(5): 612–622.

[25] Vaz-da-Silva M., et al. (2008). Effect of food on the pharmacokinetic profile of trans-resveratrol. International Journal of Clinical Pharmacology and Therapeutics 46(11): 564-70.

[26] Patel, K.R., et al. (2010). Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Research 70(19): 7392–7399.

[27] Zhu, W., et al. (2012). Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer. Nutrition and Cancer 64 (3): 393–400.

[28] Jang, L., et al. (1997). Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275: 218–220.

[29] Freitas et al. (2015). Trans-resveratrol and beta-carotene from sunscreens penetrate viable skin layers and reduce cutaneous penetration of UV-filters. International Journal of Pharmaceutics, 484 (1-2): 131-137.

[30] Pacholec, M., et al. (2010). SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. Journal of Biological Chemistry 285(11):8340-51

[31] Beher, D., et al. (2009). Resveratrol is not a direct activator of SIRT1 enzyme activity. Chemical Biology and Drug Design 74(6):619-24.

[32] Park, S.J., et al. (2012). Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148(3): 421-33.

 

 

 

CategoryBlog, Supplements
About the author
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Kali Carrigan

Kali Carrigan is a freelance research specialist at the Forever Healthy Foundation, and a devoted public advocate for research on aging and longevity.

Her background is in genetics–where she has worked as a cancer researcher– and psychology, where she has carried out several projects on narratives of death, and the effects of mortality salience on health-oriented behavior.

At the moment, she is writing her M.A thesis on the semiotics of death in contemporary Europe and the United States.

Formerly, Kali has worked as a palliative care counselor, an experience which helped shape her views on the need for increased advocacy in the public and legislative spheres.

As a writer and translator, Kali has authored articles on longevity as an imperative both at the individual and global level, bringing together the ethical, scientific, and health aspects of aging in one unified vision. She was one of the first translators of Aubrey de Grey’s groundbreaking book “Ending Aging” into Spanish.

Through consulting and advocacy, Kali hopes to bring the advances of longevity science to the general public by providing clear and accessible information on the benefits of longevity for the pursuit of health and wellbeing.

  1. June 8, 2017

    Also of interest in regards to resveratrol in wine is that those made in warmer climates contain less resveratrol.

    Californian reds (just for example) will contain less resveratrol than those grown in France.

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