Resveratrol is a SAF nutrient pholyphenol produced by several plants in response to stress such as from radiation, heat shock, or microbial attack. It has been shown to increased survivability and life-span of the consuming organisms by activating the same genes as those activated by calorie restriction.
Resveratrol is found in ripe berries, grapes (primarily the skin), peanuts (sprouted, boiled or roasted), red wine, Japanese knotweed, dark chocolate and white pine.
Mechanisms of action
Resveratrol activates the SIRT-1 gene in animals along with AMPK and the transcriptional coactivator PGC-1α, which altogether exert similar health and fitness effects as calorie restriction and exercise. It has shown to increase insulin sensitivity, reduce IGF-1 (insulin like growth factor 1), increase mitochondrial biogenesis, prevent mitochondrial damage, increase fat oxidation, improve motor function and reduce body fat.
In vitro, resveratrol has shown to increase SOD levels, which act to reduce superoxide O2, a major oxidative radical byproduct of mitochondrial energy production. (These effects have been observed via the pathway resveratrol → SIRT-1/NAD → FOXO30 → MnSOD.)
- Calorie restriction and exercise like effects (activation of SIRT-1 and AMPK, inhibition of mTOR, increased mitochondrial biogenesis, increased fat oxidation)
- Anti-aging (activation of SIRT-1, increased cellular NAD dependent deacetylase, increased cellular factor cAMP, increased AMPK and inhibition of mTOR)
- Anti-neoplastic (inhibition of mTOR and growth, apoptotic effects on cancer cells, anti-angiogenic activity, increased resistance to oxidative damage)
- Increased resistance to aging (decreased organ pathology, improved motor function, increased insulin sensitivity, reduced inflammation)
- Immune support (increased expression of the transcriptional coactivator PGC-1a, increased mitochondrial biogenesis, reduction of superoxide O2, upregulation of glutathione peroxidase GPX)
- Neuro-protection (protection against neuronal cell dysfunction and cell death in vitro)
- Testosterone support (increased testosterone production via selective inhibition of the aromatase enzyme that converts testosterone to estrogen)
- Increased cellular repair (increased autophagy and cellular renovation via inhibition of mTOR)
- Skin protection (protection against ultraviolet radiation related damage)
Given the evidence that resveratrol is an estrogen inhibitor (due to its anti-aromatase activity) and a potent topoisomerase inhibitor (enzyme that’s essential for the survivability of the fetus), it should not be used by women who are pregnant or intent to be pregnant. It should not be taken by children as there isn’t sufficient evidence on how it affects the growing young.
SAF Stress-Response Complex
SAF Stress-Response Complex combines the most potent SAF nutrients specifically selected to mimic the effects of fasting and exercise on the body. These hard to find nutrients are specially sourced from barks, roots, rhizomes and leaves into one exclusive package. The formula includes berberine, salicin, green tea, resveratrol and turmeric to yield the right nutritional complexity at the right biological potency.
Jump start your SAF experience with SAF Stress-Response Complex.
Tomé-Carneiro, J; Gonzálvez, M; Larrosa, M; Yáñez-Gascón, MJ; García-Almagro, FJ; Ruiz-Ros, JA; Tomás-Barberán, FA; García-Conesa, MT; Espín, JC (Jul 2013). “Resveratrol in primary and secondary prevention of cardiovascular disease: a dietary and clinical perspective.”. Annals of the New York Academy of Sciences 1290: 37–51.
Athar M, Back JH, Tang X, Kim KH, Kopelovich L, Bickers DR, Kim AL (November 2007). “Resveratrol: a review of preclinical studies for human cancer prevention”. Toxicol. Appl. Pharmacol. 224 (3): 274–83.
Poulsen, MM; Jørgensen, JO; Jessen, N; Richelsen, B; Pedersen, SB (Jul 2013). “Resveratrol in metabolic health: an overview of the current evidence and perspectives.”. Annals of the New York Academy of Sciences 1290: 74–82.
Fernández, AF; Fraga, MF (Jul 2011). “The effects of the dietary polyphenol resveratrol on human healthy aging and lifespan.”. Epigenetics : official journal of the DNA Methylation Society 6 (7): 870–4.
Agarwal, B; Baur, JA (Jan 2011). “Resveratrol and life extension.”. Annals of the New York Academy of Sciences 1215: 138–43.
Marchal, J; Pifferi, F; Aujard, F (Jul 2013). “Resveratrol in mammals: effects on aging biomarkers, age-related diseases, and life span.”. Annals of the New York Academy of Sciences 1290: 67–73.
Jo JY, Gonzalez de Mejia E, Lila MA (March 2006). “Catalytic inhibition of human DNA topoisomerase II by interactions of grape cell culture polyphenols”. Journal of Agricultural and Food Chemistry 54 (6): 2083–7.
Paolini M, Sapone A, Valgimigli L (June 2003). “Avoidance of bioflavonoid supplements during pregnancy: a pathway to infant leukemia?”. Mutat. Res. 527 (1–2): 99–101.
Baur JA, Sinclair DA (June 2006). “Therapeutic potential of resveratrol: the in vivo evidence”. Nature Reviews Drug Discovery 5 (6): 493–506.
Asensi M, Medina I, Ortega A, Carretero J, Baño MC, Obrador E, Estrela JM (August 2002). “Inhibition of cancer growth by resveratrol is related to its low bioavailability”. Free Radic. Biol. Med. 33 (3): 387–98.
Wenzel E, Soldo T, Erbersdobler H, Somoza V (May 2005). “Bioactivity and metabolism of trans-resveratrol orally administered to Wistar rats”. Mol Nutr Food Res 49 (5): 482–94.
Wenzel E, Somoza V (May 2005). “Metabolism and bioavailability of trans-resveratrol”. Mol Nutr Food Res 49 (5): 472–81.
Alcaín FJ, Villalba JM (April 2009). “Sirtuin activators”. Expert Opin Ther Pat 19 (4): 403–14.
Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (December 2006). “Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha”. Cell 127 (6): 1109–22.
Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, DiStefano PS, Fields S, Bedalov A, Kennedy BK (April 2005). “Substrate-specific activation of sirtuins by resveratrol”. J. Biol. Chem. 280 (17): 17038–45.
Robb EL, Page MM, Wiens BE, Stuart JA (March 2008). “Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD”. Biochem. Biophys. Res. Commun. 367 (2): 406–12.
Sun J, Folk D, Bradley TJ, Tower J (June 2002). “Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster”. Genetics 161 (2): 661–72.
Stefani M, Markus MA, Lin RC, Pinese M, Dawes IW, Morris BJ (October 2007). “The effect of resveratrol on a cell model of human aging”. Annals of the New York Academy of Sciences 1114: 407–18.
Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME (March 2004). “Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase”. Science 303 (5666): 2011–5.
Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM (September 2002). “Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress”. Nature 419 (6904): 316–21.
Khan MA, Chen HC, Wan XX, Tania M, Xu AH, Chen FZ, Zhang DZ (March 2013). “Regulatory effects of resveratrol on antioxidant enzymes: a mechanism of growth inhibition and apoptosis induction in cancer cells”. Mol Cells 35 (3): 219–25.
Chun YJ, Kim MY, Guengerich FP (August 1999). “Resveratrol is a selective human cytochrome P450 1A1 inhibitor”. Biochem. Biophys. Res. Commun. 262 (1): 20–4.
Benitez DA, Pozo-Guisado E, Alvarez-Barrientos A, Fernandez-Salguero PM, Castellón EA (2007). “Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines”. J. Androl. 28 (2): 282–93.
Faber AC, Chiles TC (December 2006). “Resveratrol induces apoptosis in transformed follicular lymphoma OCI-LY8 cells: evidence for a novel mechanism involving inhibition of BCL6 signaling”. Int. J. Oncol. 29 (6): 1561–6.
Tang HY, Shih A, Cao HJ, Davis FB, Davis PJ, Lin HY (August 2006). “Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells”. Mol. Cancer Ther. 5 (8): 2034–42. doi:10.1158/1535-7163.MCT-06-0216. PMID 16928824.
Aziz MH, Nihal M, Fu VX, Jarrard DF, Ahmad N (May 2006). “Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3′-kinase/Akt pathway and Bcl-2 family proteins”. Mol. Cancer Ther. 5 (5): 1335–41.
Cao Y, Fu ZD, Wang F, Liu HY, Han R (June 2005). “Anti-angiogenic activity of resveratrol, a natural compound from medicinal plants”. J Asian Nat Prod Res 7 (3): 205–13.
Hung LM, Chen JK, Huang SS, Lee RS, Su MJ (August 2000). “Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes”. Cardiovasc. Res. 47 (3): 549–55.
Marambaud P, Zhao H, Davies P (November 2005). “Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides”. J. Biol. Chem. 280 (45): 37377–82.
Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM (October 2001). “Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models”. Cancer Res. 61 (20): 7456–63.
Wang Y, Lee KW, Chan FL, Chen S, Leung LK (July 2006). “The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in breast cancer cells”. Toxicol. Sci. 92 (1): 71–7.
Kode A, Rajendrasozhan S, Caito S, Yang SR, Megson IL, Rahman I (March 2008). “Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells”. Am. J. Physiol. Lung Cell Mol. Physiol. 294 (3): L478–88.
Ghosh HS, McBurney M, Robbins PD (2010). “SIRT1 negatively regulates the mammalian target of rapamycin”. In Blagosklonny, Mikhail V. PLoS ONE 5 (2): e9199.
Morselli E, Galluzzi L, Kepp O, Criollo A, Maiuri MC, Tavernarakis N, Madeo F, Kroemer G (December 2009). “Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol”. Aging (Albany NY) 1 (12): 961–70.
Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H, Taussig R, Brown AL, Kim MK, Beaven MA, Burgin AB, Manganiello V, Chung JH (February 2012). “Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases”. Cell 148 (3): 421–33.
Mattivi F, Reniero F, Korhammer S (1995). “Isolation, characterization, and evolution in red wine vinification of resveratrol monomers”. Journal of Agricultural and Food Chemistry 43 (7): 1820–3.
Gatto P, Vrhovsek U, Muth J, Segala C, Romualdi C, Fontana P, Pruefer D, Stefanini M, Moser C, Mattivi F, Velasco R (December 2008). “Ripening and genotype control stilbene accumulation in healthy grapes”. Journal of Agricultural and Food Chemistry 56 (24): 11773–85.
Wang KH, Lai YH, Chang JC, Ko TF, Shyu SL, Chiou RY (January 2005). “Germination of peanut kernels to enhance resveratrol biosynthesis and prepare sprouts as a functional vegetable”. Journal of Agricultural and Food Chemistry 53 (2): 242–6.
Stewart JR, Artime MC, O’Brian CA (July 2003). “Resveratrol: a candidate nutritional substance for prostate cancer prevention”. J. Nutr. 133 (7 Suppl): 2440S–2443S.
Hurst WJ, Glinski JA, Miller KB, Apgar J, Davey MH, Stuart DA (September 2008). “Survey of the trans-resveratrol and trans-piceid content of cocoa-containing and chocolate products”. Journal of Agricultural and Food Chemistry 56 (18): 8374–8.
(1999). “Resveratrol In Peanuts”. Kids Food for Thought (The Peanut Institute) 1 (4). Archived from the original on August 24, 2000.
Gocze T (2008-09-08). “Japanese Knotweed a Resilient Invader”. Bangor Daily News.
Simini B (January 2000). “Serge Renaud: from French paradox to Cretan miracle”. Lancet 355 (9197): 48.
Olas B, Wachowicz B (August 2005). “Resveratrol, a phenolic antioxidant with effects on blood platelet functions”. Platelets 16 (5): 251–60.
“‘Longevity gene’ may be dead end: study”. The Raw Story. Agence France-Presse. September 12, 2011.
Ledford H (September 2011). “Longevity genes challenged. Do sirtuins really lengthen lifespan?”. Nature.
Lombard DB, Pletcher SD, Cantó C, Auwerx J (September 2011). “Ageing: longevity hits a roadblock”. Nature 477 (7365): 410–1.
Pathak, L; Agrawal, Y; Dhir, A (Jul 2013). “Natural polyphenols in the management of major depression.”. Expert opinion on investigational drugs 22 (7): 863–80.