Resveratrol and health - A comprehensive review of human clinical trials

Molecular Nutrition and Food Research

Volumn 55, Issue 8, 2011, Pages 1129-1141

  Smoliga, James M ^a   Baur, Joseph A ^b   Hausenblas, Heather A ^c  

^a MARYWOOD UNIVERSITY   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF FLORIDA   (United States)

Author keywords

Grapes; Nutraceutical; Sirtuins; Stilbenes; Wine

Indexed keywords

RESVERATROL; STILBENE DERIVATIVE;

ANIMAL; BIOAVAILABILITY; CARDIOVASCULAR DISEASE; CLINICAL TRIAL (TOPIC); DIABETES MELLITUS; DIET SUPPLEMENTATION; HUMAN; LIVER; METABOLISM; OBESITY; OXIDATIVE STRESS; REVIEW; WINE;

ANIMALS; BIOLOGICAL AVAILABILITY; CARDIOVASCULAR DISEASES; CLINICAL TRIALS AS TOPIC; DIABETES MELLITUS; DIETARY SUPPLEMENTS; HUMANS; LIVER; OBESITY; OXIDATIVE STRESS; STILBENES; WINE;

ANIMALIA; VITACEAE;

EID: 79961047423     PISSN: 16134125     EISSN: 16134133     Source Type: Journal    
DOI: 10.1002/mnfr.201100143     Document Type: Review

References (95)

1. US Department of Health and Human Services. Aging Statistics 2010, .
2. vel Szic, K. S., Ndlovu, M. N., Haegeman, G., Vanden Berghe, W., Nature or nurture: let food be your epigenetic medicine in chronic inflammatory disorders. Biochem. Pharmacol. 2010, 80, 1816-1832.
3. Beavers, K. M., Brinkley, T. E., Nicklas, B. J., Effect of exercise training on chronic inflammation. Clin. Chim. Acta 2010, 411, 785-793.
4. Baur, J. A., Resveratrol, sirtuins, and the promise of a DR mimetic. Mech. Ageing Dev. 2010, 131, 261-269.
5. Baur, J. A., Sinclair, D. A., Therapeutic potential of resveratrol: the in vivo evidence. Nat. Rev. Drug Discov. 2006, 5, 493-506.
6. Liu, B. L., Zhang, X., Zhang, W., Zhen, H. N., New enlightenment of French Paradox: resveratrol's potential for cancer chemoprevention and anti-cancer therapy. Cancer Biol. Ther. 2007, 6, 1833-1836.
7. Jang, M., Cai, L., Udeani, G. O., Slowing, K. V. et al., Cancer chemoprotective activity of resveratrol, a natural product derived from grapes. Science 1997, 275, 218-220.
8. Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A. et al., Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006, 444, 337-342.
9. Labbe, A., Garand, C., Cogger, V. C., Paquet, E. R. et al., Resveratrol improves insulin resistance hyperglycemia and hepatosteatosis but not hypertriglyceridemia, inflammation, and life span in a mouse model for Werner syndrome. J. Gerontol. A Biol. Sci. Med. Sci. 2011, 66, 264-278.
10. Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A. et al., Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J. Gerontol. A Biol. Sci. Med. Sci. 2011, 66, 191-201.
11. Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L. et al., Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008, 8, 157-168.
12. Barger, J. L., Kayo, T., Vann, J. M., Arias, E. B. et al., A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in Mice. PLoS One 2008, 3, e2264.
13. Halliwell, B., Dietary polyphenols: good, bad, or indifferent for your health? Cardiovasc. Res. 2007, 73, 341-347.
14. Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H. et al., Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006, 127, 1109-1122.
15. Zang, M., Xu, S., Maitland-Toolan, K. A., Zuccollo, A. et al., Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes 2006, 55, 2180-2191.
16. Bordone, L., Cohen, D., Robinson, A., Motta, M. C. et al., SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 2007, 6, 759-767.
17. Feige, J. N., Lagouge, M., Canto, C., Strehle, A. et al., Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab. 2008, 8, 347-358.
18. Um, J. H., Park, S. J., Kang, H., Yang, S. et al., AMPK-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes 2009.
19. Jang, M., Cai, L., Udeani, G. O., Slowing, K. V. et al., Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997, 275, 218-220.
20. Buryanovskyy, L., Fu, Y., Boyd, M., Ma, Y. et al., Crystal structure of quinone reductase 2 in complex with resveratrol. Biochemistry 2004, 43, 11417-11426.
21. Athar, M., Back, J. H., Kopelovich, L., Bickers, D. R., Kim, A. L., Multiple molecular targets of resveratrol: anti-carcinogenic mechanisms. Arch. Biochem. Biophys. 2009, 486, 95-102.
22. Baur, J. A., Sinclair, D. A., Therapeutic potential of resveratrol: the in vivo evidence. Nat. Rev. 2006, 5, 493-506.
23. Vang, O., Ahmad, N., Baile, C. A., Baur, J. A. et al., What is new for an old Molecule? Systematic Review and Recommendations on the use of Resveratrol. PLoS One 2011, in press. DOI: 10.1371/journal.pone.0019881.
24. Block, G., Jensen, C. D., Norkus, E. P., Dalvi, T. B. et al., Usage patterns, health, and nutritional status of long-term multiple dietary supplement users: a cross-sectional study. Nutr. J. 2007, 6, 30.
25. Goldberg, D. M., Yan, J., Soleas, G. J., Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin. Biochem. 2003, 36, 79-87.
26. Calamini, B., Ratia, K., Malkowski, M. G., Cuendet, M. et al., Pleiotropic mechanisms facilitated by resveratrol and its metabolites. Biochem. J. 2010, 429, 273-282.
27. Yu, C., Shin, Y. G., Kosmeder, J. W., Pezzuto, J. M., van Breemen, R. B., Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Commun. Mass Spectrom. 2003, 17, 307-313.
28. Patel, K. R., Scott, E., Brown, V. A., Gescher, A. J. et al., Clinical trials of resveratrol. Ann. NY Acad. Sci. 2011, 1215, 161-169.
29. Boocock, D. J., Faust, G. E. S., Patel, K. R., Schinas, A. M. et al., Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemoprotective agent. Cancer Epidemiol. Biomarkers Prev. 2007, 16, 1246-1252.
30. Brown, V. A., Patel, K. R., Viskaduraki, M., Crowell, J. A. et al., Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res. 2010, 70, 9003-9011.
31. Chow, H. H., Garland, L. L., Hsu, C. H., Vining, D. R. et al., Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev. Res. 2010, 3, 1168-1175.
32. Almeida, L., Vaz-da-Silva, M., Falcao, A., Soares, E. et al., Pharmacokinetic and safety profile of transresveratrol in a rising multiple-dose study in healthy volunteers. Mol. Nutr. Food Res. 2009, 53, S7-S15.
33. Patel, K. R., Brown, V. A., Jones, D. J., Britton, R. G. et al., Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Res. 2010, 70, 7392-7399.
34. Goldberg, D. M., Yan, J., Ng, E., Diamandis, E. P. et al., A global survey of trans-resveratrol concentrations in commercial wines. Am. J. Enol. Viticulture 1995, 46, 159-165.
35. Gresele, P., Pignatelli, P., Guglielmini, G., Carnevale, R. et al., Resveratrol, at concentrations attainable with moderate wine consumption, stimulates human platelet nitric oxide production. J. Nutr. 2008, 138, 1602-1608.
36. Vitaglione, P., Sforza, S., Galaverna, G., Ghidini, C. et al., Bioavailability of trans-resveratrol from red wine in humans. Mol. Nutr. Food Res. 2005, 49, 495-504.
37. Pignatelli, P., Ghiselli, A., Buchetti, B., Carnevale, R. et al., Polyphenols synergistically inhibit oxidative stress in subjects given red and white wine. Atherosclerosis 2006, 188, 77-83.
38. Wallerath, T., Deckert, G., Ternes, T., Anderson, H. et al., Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 2002, 106, 1652-1658.
39. Wallerath, T., Li, H., Godtel-Ambrust, U., Schwarz, P. M., Forstermann, U., A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide 2005, 12, 97-104.
40. Leikert, J. F., Rathel, T. R., Wohlfart, P., Cheynier, V. et al., Red wine polyphenols enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release from endothelial cells. Circulation 2002, 106, 1614-1617.
41. Walle, T., Hsieh, F., DeLegge, M. H., John E Oatis, J., Walle, U. K., High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Dispos. 2004, 32, 1377-1382.
42. Abd El-Mohsen, M., Bayele, H., Kuhnle, G., Gibson, G. et al., Distribution of [3H]trans-resveratrol in rat tissues following oral administration. Br. J. Nutr. 2006, 96, 62-70.
43. Roberts, R. A., Laskin, D. L., Smith, C. V., Robertson, F. M. et al., Nitrative and oxidative stress in toxicology and disease. Toxicol. Sci. 2009, 112, 4-16.
44. Finkel, T., Holbrook, N. J., Oxidants, oxidative stress and the biology of ageing. Nature 2000, 408, 239-247.
45. Kaneto, H., Katakami, N., Matsuhisa, M., Matsuoka, T. A., Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis. Mediators Inflamm. 2010, 2010, 453892.
46. Ciencewicki, J., Trivedi, S., Kleeberger, S. R., Oxidants and the pathogenesis of lung diseases. J. Allergy Clin. Immunol. 2008, 122, 456-468; quiz 469-470.
47. Bayir, H., Kagan, V. E., Bench-to-bedside review: mitochondrial injury, oxidative stress and apoptosis - there is nothing more practical than a good theory. Crit. Care 2008, 12, 206.
48. Robb, E. L., Page, M. M., Wiens, B. E., Stuart, J. A., Molecular mechanisms of oxidative stress resistance induced by resveratrol: specific and progressive induction of MnSOD. Biochem. Biophys. Res. Commun. 2008, 367, 406-412.
49. Nigdikar, S. V., Williams, N. R., Griffin, B. A., Howard, A. N., Consumption of red wine polyphenols reduces the susceptibility of low-density lipoproteins to oxidation in vivo. Am. J. Clin. Nutr. 1998, 68, 258-265.
50. Fuhrman, B., Lavy, A., Aviram, M., Consumption of red wine with meals reduces the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. Am. J. Clin. Nutr. 1995, 61, 549-554.
51. Ghanim, H., Sia, C. L., Abuaysheh, S., Korzeniewski, K. et al., An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J. Clin. Endocrinol. Metab. 2010, 95, E1-E8.
52. Ghanim, H., Sia, C. L., Korzeniewski, K., Lohano, T. et al., A Resveratrol and Polyphenol Preparation Suppresses Oxidative and Inflammatory Stress Response to a High-Fat, High-Carbohydrate Meal. J. Clin. Endocrinol. Metab. 2011, 96, 1409-1414.
53. Dal-Pan, A., Blanc, S., Aujard, F., Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity. BMC Physiol. 2010, 10, 11.
54. Dal-Pan, A., Terrien, J., Pifferi, F., Botalla, R. et al., Caloric restriction or resveratrol supplementation and ageing in a non-human primate: first-year outcome of the RESTRIKAL study in Microcebus murinus. Age (Dordr.) 2010.
55. Yoshizaki, T., Schenk, S., Imamura, T., Babendure, J. L. et al., SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity. Am. J. Physiol. Endocrinol. Metab. 2010, 298, E419-E428.
56. Sun, C., Zhang, F., Ge, X., Yan, T. et al., SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab. 2007, 6, 307-319.
57. Brasnyo, P., Molnar, G. A., Mohas, M., Marko, L., Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br. J. Nutr. 2011, 1-7.
58. Sirtris Announces SRT501 Lowers Glucose In Twice-Daily Dosing Clinical Trial. Medical News Today 2008, .
59. Crandall, J. P., Oram, V., Trandafirescu, G., Hawkins, M. et al., American Diabetes Association, Orlando, 2010, pp. 736-P.
60. Vislocky, L. M., Fernandez, M. L., Biomedical effects of grape products. Nutr. Rev. 2010, 68, 656-670.
61. Bertelli, A. A., Das, D. K., Grapes, wines, resveratrol, and heart health. J. Cardiovasc. Pharmacol. 2009, 54, 468-476.
62. Dohadwala, M. M., Vita, J. A., Grapes and cardiovascular disease. J. Nutr. 2009, 139, 1788S-1793S.
63. Leifert, W. R., Abeywardena, M. Y., Cardioprotective actions of grape polyphenols. Nutr. Res. 2008, 28, 729-737.
64. Yeboah, J., Crouse, J. R., Hsu, F. C., Burke, G. L., Herrington, D. M., Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation 2007, 115, 2390-2397.
65. Witte, D. R., Westerink, J., de Koning, E. J., van der Graaf, Y. et al., Is the association between flow-mediated dilation and cardiovascular risk limited to low-risk populations? J. Am. Coll. Cardiol. 2005, 45, 1987-1993.
66. Wong, R. H. X., Howe, P. R. C., Buckley, J. D., Coates, A. M. et al., Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr. Metab. Cardiovasc. Di. 2010, in press, DOI: 10.1016/j.numeed.2010.03.003.
67. Smoliga, J. M., Vang, O., Baur, J. A., Challenges of translating basic research into therapeutics: resveratrol as an example. J. Gerontol. A Biol. Sci. Med. Sci. 2011, in press.
68. Gupta, S. C., Kannappan, R., Reuter, S., Kim, J. H., Aggarwal, B. B., Chemosensitization of tumors by resveratrol. Ann. NY Acad. Sci. 2011, 1215, 150-160.
69. Ndiaye, M., Kumar, R., Ahmad, N., Resveratrol in cancer management: where are we and where we go from here? Ann. NY Acad. Sci. 2011, 1215, 144-149.
70. Shukla, Y., Singh, R., Resveratrol and cellular mechanisms of cancer prevention. Ann. NY Acad. Sci. 2011, 1215, 1-8.
71. Giovannelli, L., Pitozzi, V., Jacomelli, M., Mulinacci, N. et al., Protective effects of resveratrol against senescence-associated changes in cultured human fibroblasts. J. Gerontol. A Biol. Sci. Med. Sci. 2011, 66, 9-18.
72. Xia, L., Wang, X. X., Hu, X. S., Guo, X. G. et al., Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms. Br. J. Pharmacol. 2008, 155, 387-394.
73. Demidenko, Z. N., Blagosklonny, M. V., At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence. Cell Cycle 2009, 8, 1901-1904.
74. Abraham, J., Johnson, R. W., Consuming a diet supplemented with resveratrol reduced infection-related neuroinflammation and deficits in working memory in aged mice. Rejuvenation Res. 2009, 12, 445-453.
75. Oomen, C. A., Farkas, E., Roman, V., van der Beek, E. M. et al., Resveratrol preserves cerebrovascular density and cognitive function in aging mice. Front. Aging Neurosci. 2009, 1, 4.
76. Chiavaroli, A., Brunetti, L., Orlando, G., Recinella, L. et al., Resveratrol inhibits isoprostane production in young and aged rat brain. J. Biol. Regul. Homeost. Agents 2010, 24, 441-446.
77. Csiszar, A., Labinskyy, N., Pinto, J. T., Ballabh, P. et al., Resveratrol induces mitochondrial biogenesis in endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 2009, 297, H13-H20.
78. Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H. et al., Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell 2006, 127, 1109-1122.
79. Lopez-Lluch, G., Irusta, P. M., Navas, P., de Cabo, R., Mitochondrial biogenesis and healthy aging. Exp. Gerontol. 2008, 43, 813-819.
80. Lin, J., Wu, H., Tarr, P. T., Zhang, C. Y. et al., Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 2002, 418, 797-801.
81. Ryan, M. J., Jackson, J. R., Hao, Y., Williamson, C. L. et al., Suppression of oxidative stress by resveratrol after isometric contractions in gastrocnemius muscles of aged mice. J. Gerontol. A Biol. Sci. Med. Sci. 2010, 65, 815-831.
82. Jackson, J. R., Ryan, M. J., Hao, Y., Alway, S. E., Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2010, 299, R1572-R1581.
83. Murase, T., Haramizu, S., Ota, N., Hase, T., Suppression of the aging-associated decline in physical performance by a combination of resveratrol intake and habitual exercise in senescence-accelerated mice. Biogerontology 2009, 10, 423-434.
84. Jackson, J. R., Ryan, M. J., Alway, S. E., Long-term supplementation with resveratrol alleviates oxidative stress but does not attenuate sarcopenia in aged mice. J. Gerontol. A Biol. Sci. Med. Sci. 2011, in press, DOI: 10.1093/gerona/glr047.
85. Kennedy, D. O., Wightman, E. L., Reay, J. L., Lietz, G. et al., Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am. J. Clin. Nutr. 2010, 91, 1590-1597.
86. Wallenborg, K., Vlachos, P., Eriksson, S., Huijbregts, L. et al., Red wine triggers cell death and thioredoxin reductase inhibition: effects beyond resveratrol and SIRT1. Exp. Cell Res. 2009, 315, 1360-1371.
87. Lekakisa, J., Rallidisa, L. S., Andreadoub, I., Vamvakoua, G. et al., Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur. J. Cardiovasc. Prev. Rehab. 2005, 12, 596-600.
88. Smoliga, J. M., Bost, J., Maroon, J. C., Resveratrol, 2011, conference of resveratrol 2nd health, Copenhagen, Denmark 2010.
89. Steigerwald, M. D., Fisk, M. M., Smoliga, J. M., Rundell, K. W., Resveratrol 2010, conference of resveratrol and health, Copenhagen, Denmark 2010.
90. Kehlenbrink, S., Li, W., Koppaka, S., Zhang, K. et al., American Diabetes Association, Orlando, 2010, pp. 310-OR.
91. Marques, L., Bargut, T., Pires, L., Lopes, G. et al., Resveratrol supplementation, immunological indices and total antioxidant capacity in athletes. Med. Sci. Sports Exerc. 2009, 41, S229.
92. Schreiber, L., McAnulty, S., McAnulty, L., Rowe, B. et al., Resveratrol and catechin administration blunts exercise-induced oxidative stress and cytokine IL-8. Med. Sci. Sports Exerc. 2009, 41, S246.
93. U.S. National Institutes of Health, .
94. Vang, O., Das, D. K., Resveratrol and health. Ann. NY Acad. Sci. 2011, 1215, 1-170.
95. Nguyen, A. V., Martinez, M., Stamos, M. J., Moyer, M. P. et al., Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer. Cancer Manag. Res. 2009, 1, 25-37.