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Resveratrol is a phytoalexin polyphenolic compound found in various plants, primarily grape skins, mulberries, raspberries, blueberries, and peanuts. Resveratrol has antioxidant, estrogenic, antiplatelet, anti-cancer, and anti-inflammatory properties and effects quite a number of processes in animals. It has a large number of exciting laboratory studies on cell cultures and animal studies especially on cancer and heart disease. Unfortunately, as of Ocotber, 2006, I have been unable to locate one single random assignment, controlled study in human beings for any disease state, other than a very preliminary study on hyperlipidemia, which I consider more of a lab finding rather than a clinical disease. There are some favorable epidemiological studies on grape consumption, but many of the statements praising resveratrol are really statements promoting the consumption of red wine. Many of the claims for red wine are grossly exaggerated. For instance, the evidence that red wine has any better effect on heart disease than a similar amount of other alcoholic beverages is disproven by several studies. Also, since the alcohol research finds that one drink of alcohol (4 ounces of 12% red wine or 12 ounces of beer or one ounce of whiskey) is the optimal intake for cardiac and circulatory disease prevention, and since 4 ounces of the average red wine contains less than 1 mg. of resveratrol, it seems unlikely that this very small amount of resveratrol is likely to have a major impact. In fact, for individuals wanting to increase their consumption of resveratrol despite the present paucity of human research, drinking grape juice and eating peanuts would seem much wiser. Also, much larger doses of resveratrol are readily available in supplement form, e.g. a 60 mg tablet, equal to the amount in 18 liters or 24 bottles of the average red wine, can be purchased for about 40 cents (www.iherb.com ). Some of the animal research uses massive doses even larger for this when corrected for body weight and some studies inject the resveratrol intraperitoneally or IV. Resveratrol is very rapidly metabolized by the liver when consumed orally, but its metabolized forms may be just as effective. Of course, humans may not need as much resveratrol per body weight to receive substantial benefit, but that is totally unknown at the present time. Research specific to grape consumption rather than resveratrol per se can be found at Grapes and Resveratrol. I am excited by the resveratrol research and it is certainly harmless, but it sure would be nice to have human studies. Even animal studies are not large in number. Most research to date is based on effects on cell cultures. All of the same benefits can be obtained from melatonin, which has considerably more animal and human research. Human Research Cancer: Breast Cancer Lower with High Resveratrol Consumption: In a case-control study of 369 breast cancer cases and 602 controls, cmpared with the lowest tertile of total resveratrol intake, the multivariate odds ratios (OR) were 0.50 for the intermediate and 0.39 for the highest tertile, and the trend in risk was significant. A significant inverse association was observed for resveratrol from grapes (OR = 0.64 and 0.55), but not for wine. Resveratrol and breast cancer risk. Levi F, et al. Lausanne, Switzerland. . Eur J Cancer Prev 2005 Apr;14(2):139-42. Animal Research Alcohol: Peroxidation Damage Reduced in Rats: Alcohol Alcohol 2006 Mar 3. Alcohol Liver Damage and Mortality Reduced in Mice: Mice were randomly distributed into four groups (control, resveratrol-treated control, alcohol and resveratrol-treated alcohol). Chronic alcohol intoxication was induced by progressively administering alcohol in drinking water up to 40% v/v. The mice administered resveratrol received 10 mg/ml in drinking water. Transaminase concentration was significantly higher in the alcohol group than in the rest of the groups (p < 0.05). IL-1 levels were significantly reduced in the alcohol plus resveratrol group compared with the alcohol group (p < 0.05). Mortality in the alcohol group was 78% in the seventh week, versus 22% in the alcohol plus resveratrol group (p < 0.001). ffect of resveratrol on alcohol-induced mortality and liver lesions in mice. Bujanda L, et al. San Sebastian, Spain. . BMC Gastroenterol 2006 Nov 15. Arthritis: In a rabbit study, intraarticular injections of resveratrol starting at the onset of disease may protect cartilage against the development of experimentally induced OA. Inflam Res 2005 Apr;54(4):158-62. Arthritis: Protected Against Induced Rabbit Knee Arthritis: Effects of Resveratrol in Inflammatory Arthritis. Elmali N, et al. Inonu University, Malatya, Turkey, . Inflammation 2006 Nov 4. Brain: Protects Against Colchicine Toxicity: Neuroprotective Effects of Resveratrol against Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress in Rats. Kumar A, et al. Panjab University, Chandigarh, India. Pharmacol Nov 28, 2006 Brain: Resveratrol Helped the cognitive ability of Alzheimer mice. Luo L, et al. Central South University, Changsha, China. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2006 Aug;31(4):566-9. Brain Neuroprotection from resveratrol against traumatic brain injury in rats: Ates O, et al. Inonu University, Malatya, Turkey. Mol Cell Biochem 2006 Aug 19. Cancer: No Help for Cachexia: R Cancer: Slows Metastases In Rat Lung: Resveratrol didn't effect implanted Lewis lung carcinoma in rats but did decrease metastases by 40%. Other studies have found impact on the implanted cancer itself. Cancer Letter 2006 Feb 5; However, it didn't help A/J mice from cancer induced by benzopyrene. Br J Cancer 2004 Oct 4;91(7):1380-3. Cancer: Breast: Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro. Lanzilli G, et al. Rome. Int J Oncol 2006 Mar;28(3):641-648. Resveratrol has anticancer properties, as suggested by its ability to suppress proliferation of a wide variety of tumor cells, including lymphoid and myeloid cancers; multiple myeloma; cancers of the breast, prostate, stomach, colon, pancreas, and thyroid; melanoma; head and neck squamous cell carcinoma; ovarian carcinoma; and cervical carcinoma. The growth-inhibitory effects of resveratrol are mediated through cell-cycle arrest; upregulation of p21Cip1/WAF1, p53 and Bax; down-regulation of survivin, cyclin D1, cyclin E, Bcl-2, Bcl-xL and clAPs; and activation of caspases. Resveratrol has been shown to suppress the activation of several transcription factors, including NF-kappaB, AP-1 and Egr-1; to inhibit protein kinases including IkappaBalpha kinase, JNK, MAPK, Akt, PKC, PKD and casein kinase II; and to down-regulate products of genes such as COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA. These activities account for its suppression of angiogenesis. Anticancer Res 2004 Sep-Oct;24(5A):2783-840. Cancer: Slowed Human Breast Cancer Xenografts in Nude Mice: Resveratrol, but not EGCG, in the diet suppresses DMBA-induced mammary cancer in rats. Whitsett TG Jr et al. 2006 Jan 8;231(1):113-22. Cancer: Gastric: Human Transplanted Cells Destroyed: Resveratrol is able to induce apoptosis of transplanted tumor cells into rats. This apoptosis may be mediated by down-regulating apoptosis-regulated gene bcl-2 and up-regulating the expression of apoptosis-regulated gene bax. World J Gastroent 2005 Jan 14;11(2):280-4. Cancer: Helps Many Types of Cancer in Lab Studies: Resveratrol suppresses proliferation of tumor cells, including lymphoid and myeloid cancers; multiple myeloma; cancers of the breast, kidney, prostate, stomach, colon, pancreas, and thyroid; melanoma; head and neck squamous cell carcinoma; neuroblastoma, leukemia, ovarian carcinoma; and cervical carcinoma. The growth-inhibitory effects of resveratrol are mediated through cell-cycle arrest; upregulation of p21Cip1/WAF1, p53 and Bax; down-regulation of survivin, cyclin D1, cyclin E, Bcl-2, Bcl-xL and clAPs; and activation of caspases. Resveratrol suppresses the activation of several transcription factors, including NF-kappaB, AP-1 and Egr-1; to inhibit protein kinases including IkappaBalpha kinase, JNK, MAPK, Akt, PKC, PKD and casein kinase II; and to down-regulate products of genes such as COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA. These activities account for the suppression of angiogenesis. Resveratrol also potentiates the apoptotic effects of cytokines (e.g., TRAIL), chemotherapeutic agents and gamma-radiation. Anticancer Res 2004 Sep-Oct;24(5A):2783-840. Cancer: Liver 5-FU Treatment Enhanced: RES could induce the S phase arrest of H22 cells and enhance the anti-tumor effect of 5-FU on murine hepatoma22 and antagonize its toxicity markedly. World J Gastroent 2004 Oct 15;10(20):3048-52. Colitis: Resveratrol reduces the damage in chronic experimentally induced colitis, alleviates the oxidative events, returns PGE(2) production to basal levels and stimulates apoptosis in colonic cells. British Journal of Pharmacology, 13 February 2006 Diabetes: Nephropathy Helped: Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats. Sharma S, et al. India. Pharmacol 2006;76(2):69-75; Similar, Kumar, et al. Life Sci. 2007 Jan 20. Diabetes: Resveratrol Helped Neuropathic Pain in Mice: Sharma S, et al. Panjab University, India. Exercise Tolerance Increased in Mice: Mice treated with resveratrol significantly increased their aerobic capacity, as evidenced by their increased running time and consumption of oxygen in muscle fibers. RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in PGC-1alpha acetylation and an increase in PGC-1alpha activity. This mechanism is consistent with RSV being a known activator of the protein deacetylase, SIRT1, and by the lack of effect of RSV in SIRT1(-/-) MEFs. Importantly, RSV treatment protected mice against diet-induced-obesity and insulin resistance. These pharmacological effects of RSV combined with the association of three Sirt1 SNPs and energy homeostasis in Finnish subjects implicates SIRT1 as a key regulator of energy and metabolic homeostasis. Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1alpha. Lagouge M, et al. Illkirch, France. Cell 11/15/06. Heart: Statin and resveratrol in combination better cardioprotection against myocardial infarction in hypercholesterolemic rat than either alone: Penumathsa SV, et al. University of Connecticut. J Mol Cell Cardiol 2006 Dec 22. Heart: Helps Reduce Arrythmias and MI Mortality: Antiarrhythmic effect of resveratrol on aconitine induced rat arrhythmia, ouabain induced guinea pig arrhythmia, and coronary ligation induced rat arrhythmia animal models. Resveratrol significantly and dose-dependently increased the doses of aconitine and ouabain required to induce the arrhythmia indexes. In coronary ligation induced rat arrhythmia model, resveratrol shortened duration of arrhythmia, decreased incidence of ventricular tachycardia and mortality. Biochem Biophys Res Commun 2006 Feb 24;340(4):1192-9 Heart: Resveratrol Does as Well as Wine, Alcoholized or Dealcoholized in Reducing Atherosclerosis: Rabbits fed a high cholesterol (1.5%) diet were simultaneously given water containing resveratrol (3 mg/kg/day) or red wine (4 ml/kg/day) containing 3.98 mg/l and 3.23 mg/l resveratrol for regular and dealcoholized red wine, respectively, for a 12-week duration. All groups did equally better than the control group with less atherosclerosis without effecting lipids. Int J Mol Med 2005 Oct;16(4):533-40. Heart Attack Damage Reduced: In rats given 20 mg/kg/d of oral resveratrol for 14 days, less heart damaged occurred when given ischemic heart attacks. Scand Cardio J 2004 Aug;38(4):245-54. Heart: Catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation. Auger C, et al. Universite Montpellier, France. J Agric Food Chem 2005 Mar 23;53(6):2015-21. Inflammation: COX-2 Favored: In a lab study of COX-1 and COX-2 inhibition with ibuprofen, rofecoxib, naproxen, and indomethacin used used for comparison, more COX-2 selective inhibition occurred with ipriflavone, resveratrol, MSV-60, amentoflavone, ruscus extract and notoginseng. Glucosamine, nexrutine, and berberine did not inhibit either isoform. Inhibition of COX isoforms by nutraceuticals. Seaver B, et al. University of Montana. J Herb Pharmacother 2004;4(2):11-8. Kidney: Resveratrol protects against cyclosporine-induced nephrotoxicity through nitric oxide dependent mechanism. Chandler V, et al. Punjab University. Toxicology 2005 May 15;210(1):55-64. Kidney Ischemia, Transplant Helped: Protective effect of nitric oxide pathway in resveratrol renal ischemia-reperfusion injury in rats. Chander V, et al. Panjab University, Chandigarh, India. Arch Med Res 2006 Jan;37(1):19-26. Similar: Ischemia is an inciting factor in 50% of acute renal failure, increases the risk of organ rejection after renal transplantation. It reduces ischemia-reperfusion (I/R) injury of rat kidney both by antioxidant and anti-inflammatory mechanisms. Univ Milan. Ann NY Acad Sci 2002 May;957:230-8. Similar: Resveratrol improves ischemia/reperfusion-induced oxidative renal injury in rats. Sener G, et al. Marmara University, Istanbul, Turkey. . Arch Med Res 2006 Oct;37(7):822-9. Kidney: Gentamicin-induced nephrotoxicity in rats ameliorated and healing effects of resveratrol: Silan C, et al. Duzce University. Biol Pharm Bull 2007 Jan;30(1):79-83. Liver: Resveratrol prolongs allograft survival after liver transplantation in rats. RES has an immuno-suppressive property as well as protective effect on hepatocytes under allograft rejection. Wu SL, et al. First Hospital of Xi'an Jiaotong University, China. . World J Gastroenterol 2005 Liver: Resveratrol protects against acetaminophen-induced toxicity in mice. Sener G, et al. Marmara University, Istanbul, Turkey. Hepatol Res 2006 Apr 1. Longevity: Resveratrol Increased Lifespan in Small Fish: Using the short-lived seasonal fish Nothobranchius furzeri with a maximum recorded lifespan of 13 weeks in captivity, resveratrol added to the food starting in early adulthood caused a dose-dependent increase of median and maximum lifespan. It reduces the expression of neurofibrillary degeneration in the brain. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Valenzano DR, et al. Pisa, Italy. Curr Biol 2006 Feb 7;16(3):296-300. Longevity: Resveratrol Helped Mice on Fatty Diet Live Longer: Resveratrol (24 mg/kg) elped mice on a 60% fat diet live almost as long as mice on standard lab diets. The fatty-diet mice without resveratrol died about 22% earlier than standard diet mice. Sinclair D, et al. Harvard, NYT 11/2/06. Sinclair takes 5 mg/kg or 350 mg of resveratrol per day assuming he's the average 70 kg man. He is also the founder of Sirtris Pharmaceuticals and is developing chemicals to mimic resveratrol. He hopes to get FDA approval for his medications. Sinclair worked in the Sir-2 lab of Guarente at Harvard. The Sir-2 gene makes sirtuin. Resveratrol activates the Sir-2 gene but has many other biological effects. Lungs: Resveratrol alleviates bleomycin-induced lung injury in rats: Sener G, et al. Marmara University, Istanbul, Turkey. Pulm Pharma Ther 2006 Sep 3. Muscle: Protects Against Ischemic Damage: Protective effects of resveratrol in ischemia-reperfusion injury of skeletal muscle: A clinically relevant animal model for lower extremity ischemia. Ikizler M, et al. Osmangazi University, Eskisehir, Turkey. . Chin J Physiol 2006 Aug 31;49(4):204-9. Neonatal Exposure Via Nursing Mother (Rat): May Be Harmful: Resveratrol (RES) is able to bind to estrogen receptors and evoke biological effects that parallel those exerted by endogenous and synthetic estrogens. Adult female rats acutely exposed to RES exhibit estrous cycle irregularity, ovarian hypertrophy, and alterations in sociosexual behavior. In a study of the prolonged effects of maternal RES exposure throughout the lactational period on subsequent behavior, reproductive tissues, and brain morphology of the adult offspring, female offspring exposed to RES throughout nursing exhibited reduced body weight and increased ovarian weight, but exhibited normal estrous cyclicity and sociosexual behavior, without changes in the volume of the sexually dimorphic nucleus of the preoptic area or the anteroventral periventricular nucleus of the hypothalamus. During adulthood, males exposed to RES throughout nursing exhibited decreased body weight and plasma testosterone concentration, increased testicular weight, and reduced sociosexual behavior. These males also had significantly smaller sexually dimorphic nucleus of the preoptic area volumes and larger anteroventral periventricular nucleus volumes compared to male controls. These data suggest that postnatal exposure to RES may affect estrogenic activity in specific peripheral tissues (e.g., the gonads), while inducing antiestrogenic effects in the brain. Thus, the present study supports recent in vitro and in vivo findings that RES differs from most other phytoestrogens by acting as a possible mixed ER agonist/antagonist, depending on the tissue-specific availability of ER subtypes that are preferentially localized in specific brain regions and throughout the reproductive tract. More importantly these data indicate that maternal consumption of phytoestrogens during lactation can have lasting effects on the offspring that may not become apparent until they reach adulthood. Effects of neonatal resveratrol exposure on adult male and female reproductive physiology and behavior. Henry LA, et al. Binghamton University (SUNY). . Devel Neurosci 2006;28(3):186-95. Pancreatitis: RESV may exert its therapeutic effect on SAP by lowering pancreatic oxidative free radicals and reducing pancreatic tissue infiltration of neutrophils. World J Gastroent 2006 Jan 7 Sepsis: Resveratrol, a phenolic compound, reduces sepsis-induced remote organ injury, at least in part, through its ability to balance oxidant-antioxidant status, to inhibit neutrophil infiltration and to regulate the release of inflammatory mediators. J Surg Res 2006 Feb 17. Stroke: Spinal Cord Helped: Resveratrol, a natural red wine polyphenol, reduces ischemia-reperfusion-induced spinal cord injury. Kaplan S, et al. Columbia University. . Ann Thor Surg 2005 Dec;80(6):2242-9. Similar: Vasc Surg 2004 Jul;40(1):138-45. Stroke: Reduced Damage From Middle Cerebral Artery Infarct in Rats: Treatment with trans resveratrol prevented motor impairment, rise in levels of MDA and reduced glutathione and also significantly decreased the volume of infarct as compared to control. Life Sci 2002 Jun 28;71(6):655-65. Testes: Resveratrol reduces ischemia reperfusion injury after experimental testicular torsion. Uguralp S, et al. Inonu University, Malatya, Turkey. . Eur J Pediatr Surg 2005 Apr;15(2):114-9. Testes: Trans-Resveratrol increases sperm output in healthy rats. Juan ME, et al. Universitat de Barcelona. J Nutr 2005 Apr;135(4):757-60. Toxicity: None Found: There were no observed adverse effect level with 300 mg resveratrol per kilogram body weight per day in rats. Toxicol Sci 2004 Dec;82(2):614-9. Vaginal Herpes in Mice Suppressed by 19% Resveratrol Cream: It was effective against both HSV-1 and HSV-2, but not at lower strengths. Effect of resveratrol on herpes simplex virus vaginal infection in the mouse. Docherty JJ, et al. Northeastern Ohio Universities College of Medicine, Rootstown, OH. . Antiviral Res 2005 Sep;67(3):155-62. Viral: Cytomegalovirus Inhibited: Human cytomegalovirus DNA replication was reduced to undetectable levels by treatment with resveratrol, as were the second (late) phases of virus-induced phosphatidylinositol-3-kinase signaling and transcription factor activation. Resveratrol lost substantial antiviral activity when its addition was delayed until 4 h postinfection. It likely operated during attachment and entry. Antivirus Res 2004 Aug;63(2):85-95. Resveratrol suppresses IL-6-induced Intracellular Adhesion Molecule-1 gene expression in endothelial cells: effects on the inhibition of STAT3 phosphorylation. Wung BS, et al. Taiwan. Life Sci 2005 Dec 12;78(4):389-97. Concentrations of total resveratrol were 0.84 - 7.33 mg/L in eleven dry red wines and 0.12 - 6.00 mg/L in three grape juices. Se Pu 2004 Jul;22(4):424-7. Letter to the Editor: Published in part March 4, 2006, New Scientist p. 25. Thomas E. Radecki, M.D., J.D. |