RESVERATROL BENEFITS     October 16, 2011
Resveratrol was first found in 1940 in the roots of a plant called Veratrum grandiflorum. Later on, in 1976,
resveratrol was discovered in grapes, and in 1992, resveratrol was also indentified in wine. [13] Resveratrol is a
polyphenol compound that may have health benefits on various chronic diseases.  [1] It exhibits a wide range of
biological effects, including antiplatelet, anti-inflammatory, anticancer, antimutagenic and antifungal properties. [4]
This compound is also believed responsible for some of the beneficial effects of moderate red wine drinking on the
cardiovascular system. One liter of red wine contains 1.5-3 mg of resveratrol. Resveratrol also exists in grapes.
Resveratrol supplements are popular in the US and other countries. This article reviews resveratrol benefits based
on recent research findings and news.


[1] Scientific Evidence of Resveratrol Benefits on Arthritis
Yucca schidigera Roezl. (Agavaceae) has been traditionally used to treat arthritis and rheumatism. Recently,
researchers found the resveratrol is one of the key ingredients of Yucca. [a3]

Arthritis, an inflammation of the joints, is a chronic disease that results from dysregulation of pro-inflammatory
cytokines (e.g. tumour necrosis factor and interleukin-1beta) and pro-inflammatory enzymes that mediate the
production of prostaglandins (e.g. cyclooxygenase-2) and leukotrienes (e.g. lipooxygenase), together with the
expression of adhesion molecules and matrix metalloproteinases, and hyperproliferation of synovial fibroblasts. All
of these factors are regulated by the activation of the transcription factor nuclear factor-kappaB. Thus, any agents
which can suppress the expression of tumor necrosis factor-alpha, interleukin-1beta, cyclooxygenase-2,
lipooxygenase, matrix metalloproteinases or adhesion molecules, or suppress the activation of NF-kappaB, have
the potential to cure arthritis. [a6]

COX-1 and COX-2
Oxidative stress is related to a number of autoimmune diseases, including cancer and rheumatoid arthritis. The
main source of pathologic “reactive oxygen species” are the activated polymorphonuclear leukocytes. Resveratrol
was found to inhibit isolated polymorphonuclear leukocytes in a dose dependent manner. [a2] Resveratrol is able
to inhibit the expression of VEGF, MMP-3, MMP-9 and COX-2 in human articularchondrocytes stimulated with the
pro-inflammatory cytokine IL-1beta. Resveratrol is also able to suppress apoptosis and inflammatory signaling
through its actions on the
NF-kappaB pathway in human chondrocytes. [a4] Resveratrol was found to possess
COX-1 inhibition, COX-2 inhibitory potential and an LTB 4 formation inhibitory activity in an in vitro study. [a3]

Anabolic Mediator
Resveratrol is found to be a potent anabolic mediator of bovine intervertebral disc cartilage homeostasis from a
vitro study, revealing its potential as a unique biologic treatment to slow the progression of intervertebral disc
degeneration. [a1]

The inflammatory process plays a pivotal role during the pathogenesis of osteoarthritis, dominated by catabolic
processes initiated by pro-inflammatory cytokines such as
IL-1beta. Resveratrol is able to reverse significantly IL-
1beta-reduced cell proliferation and blocked IL-1beta-stimulated cell membrane bound- and mature IL-1beta
synthesis in chondrocytes. Furthermore, resveratrol is able to inhibit the IL-1beta-induced degradation of
mitochondria and apoptosis in chondrocytes in a time-dependent manner. Resveratrol is also able to reverse the
IL-1beta-induced up-regulation of reactive oxygen species (ROS) in chondrocytes. [a5]

Macrophage Migration Inhibitory Factor
Cytokine macrophage migration inhibitory factor is a crucial factor in the pathogenesis of rheumatoid arthritis.
Resveratrol is found to be a potent inhibitor as the antipyretic-analgetic drug acetaminophen. [a7]

Nuclear factor kappa B (NF-kappaB) / Animal Study
Nuclear factor kappa B (NF-kappaB), is a pivotal transcription factor involved inthe activation of the TNF-alpha and
IL-1beta genes. Activation of NF-kappaB insynovial cells is a feature seen in arthritis patients. Resveratrol is potent
and specific inhibitor of
TNF-alpha and IL-1beta induced NF-kappaB activation. Intra-articular injections of
resveratrol on cartilage and synovium could significantly decreased cartilage destruction in an experimental rabbit
inflammatory arthritic model. [a8]

Scientific Evidence of Resveratrol Benefits on Cancers
As early as 1997, resveratrol was proposed to be used as a cancer-preventive agent. Resveratrol has anti-cancer
activities in assays representing three major stages of carcinogenesis. Resveratrol has been shown to inhibit
cancer initiation and promotion [2] It acts as a selective estrogen receptor modulator (SERM) and regulates
proteins involved in DNA synthesis and cell cycle. Resveratrol also affects the activity of transcriptional factors
involved in proliferation and stress responses, such as NF-kB, AP1 and Egr1. [3] In a study, gastric
adenocarcinoma cells respond to resveratrol treatment with suppression of DNA synthesis, activation of nitric oxide
synthase, induction of apoptosis and inhibition of total PKC and PKC alpha activity. [6]

Trans-resveratrol (RSVL; 3,4',5-trihydroxystilbene), a natural compound found in grapes, berries, peanuts and red
wine exerts certain anticancer roles in different human cancer types. Several epidemiological studies have
revealed that resveratrol is probably one of the active ingredients of wine responsible for its health benefits such
as prevention of vaso-coronary diseases and cancer. Resveratrol acts on the process of carcinogenesis by
affecting the three phases: tumor initiation, promotion and progression phases and suppresses the final steps of
carcinogenesis, i.e. angiogenesis and metastasis. It is also able to activate apoptosis, to arrest the cell cycle or to
inhibit kinase pathways. [c2] When, resveratrol adds to the growth inhibitory/anticancer activity of cisplatin and
doxorubicin in vitro and protects against doxorubicin-induced cardiac toxicity both in vitro and in mice. [c3]

Test-tube and animal studies have shown resveratrol benefits on different kinds of cancers. Resveratrol has been
reported to inhibit cyclooxygenase (COX) expression and/or activity in endometrial cancer cells, COX-2 is
overexpressed and confers cellular resistance to apoptosis.  High-doses of resveratrol was found to trigger
apoptosis in five out of six uterine cancer cell lines. [c4] Resveratrol exhibited a variety of molecular events in
etoposide-based combination therapy in HT-29 colon cancer cells including the activation of adenosine
monophosphate (AMP)-activated protein kinase, inhibition of cell growth, induction of apoptosis, and reactive
oxygen species (ROS) generation. [c5] Resveratrol-induced growth inhibition in T47D human breast cancer cells
was caused by apoptosis in a cell study. Resveratrol-induced apoptosis is associated with the activation of the p53
in a dose- and a time-dependent manner. [c6] In another study, resveratrol also inhibited growth factor heregulin-
beta1 (HRG-beta1)-mediated Matrix metalloproteinase (MMP-9) expression in human breast cancer cells.
Resveratrol significantly suppressed HRG-beta1-mediated phosphorylation of ERK1/2 and invasion of breast
cancer cells. [c8] Transgenic Adenocarcinoma Mouse Prostate males were fed with resveratrol (625 mg resveratrol
per kg AIN-76A diet) or phytoestrogen-free, control diet (AIN-76A). Resveratrol in the diet significantly reduced the
incidence of poorly differentiated prostatic adenocarcinoma by 7.7-fold. [c9] Resveratrol is also a potent inhibitor of
A549 lung cancer cell growth based on a microarray gene expression study. [c10]

A phase I study of oral resveratrol (single doses of 0.5, 1, 2.5, or 5 g) was conducted in 10 healthy volunteers per
dose level. Resveratrol and six metabolites were recovered from plasma and urine. Peak plasma levels of
resveratrol at the highest dose were 539 +/- 384 ng/mL (2.4 micromol/L), which occurred 1.5 h post-dose. Cancer
preventive effects of resveratrol in cells in vitro require levels of at least 5 micromol/L. The results suggest that
consumption of high-dose resveratrol might still be insufficient to elicit systemic levels commensurate with cancer
preventive efficacy. [c7]

Potential Resveratrol Benefits On Cardiovascular Diseases
Resveratrol is a phytoestrogen, potent antioxidant, reactive oxygen species scavenger and metal chelators.  [4]
Thus, it may have benefits of protection of the cardiovascular system against ischemic-reperfusion injury; it may
also protect and maintain the intact endothelium, exhibits antiatherosclerotic properties inhibits the LDL oxidation,
suppress the platelet aggregation and exhibits estrogen like action. [4, 7]

Scientific Evidence for Potential Resveratrol Benefits On Diabetes
Resveratrol increased life span in lower organisms by activating the NAD (+)-dependent histone deacetylase Sirt1.
Further, resveratrol promoted longevity and improved glucose homeostasis in mice by stimulating the Sirt1-
mediated deacetylation of the transcriptional coactivator PGC-1alpha. [d7] It could be beneficial if resveratrol can
benefit animals suffered from diabetes.

In 2001, resveratrol (5-35 micromol/l) was found to induce concentration-dependent relaxation of mesenteric
arteries preconstricted with noradrenaline (8 micromol/l) or KCl (125 mmol/l) from both lean and dietary-obese rats.
[d1 Hyperglycemia, a symptom of diabetes mellitus, induces hyperosmotic responses, including apoptosis, in
vascular endothelial cells and leukocytes. Resveratrol was able to attenuate high glucose-induced apoptotic
changes by virtue of its antioxidant property. [d2] Diabetic nephropathy is a serious vascular complication and one
of the main causes of end-stage renal disease. And, resveratrol significantly attenuated renal dysfunction and
oxidative stress in diabetic rats. [d3]

Most of type 2 diabetes mellitus (DM) patients eventually become insulin dependent because insulin secretion by
the islets of Langerhans becomes exhausted. Resveratrol shows hypoglycemic and hypolipidemic effects in
streptozotocin-induced diabetes rats. In resveratrol-treated diabetic rats, the plasma glucose concentration on day
14 was reduced by 25.3%, and the triglyceride concentration was reduced by 50.2% compared with the placebo-
treated rats. Resveratrol administration ameliorates common DM symptoms, such as body weight loss, polyphagia,
and polydipsia. In STZ-nicotinamide DM rats, resveratrol administration significantly decreased insulin secretion
and delayed the onset of insulin resistance. [d4]

Usually, diabetic rats exhibited a significant thermal hyperalgesia and cold allodynia along with increased plasma
glucose and decreased body weights. Allodynia means other pain. It is a painful response to a usually non-painful
stimulus. In a study, treatment with resveratrol (10mg/kg orally) from week 4 to week 6 significantly attenuated the
cold allodynia and thermal hyperalgesia, suggesting the application of resveratrol in diabetes, especially for
diabetic neuropathy. [d5]

Inactivation of hepatic AMP-activated protein kinase was a key event in the pathogenesis of hyperlipidemia in
diabetes (based on a study of in type 1 diabetic LDL receptor-deficient mice). Resveratrol could lower lipid levels
by activating AMP-activated protein kinase. It was about 200 times the potency of Metformin! [d6]

Other studies supporting resveratrol benefits on diabetic animals
Treatment with resveratrol prevented the increase in acetylcholinesterase activity and consequently memory
impairment in diabetic rats. [d8]

Daily oral treatment of resveratrol to diabetic rats for 30 days demonstrated a significant decline in blood glucose
and glycosylated hemoglobin levels and a significant increase in plasma insulin level. The administration of
resveratrol also reverted the altered activities of the key enzymes of carbohydrate metabolism in liver and kidney
tissues of diabetic rats to near normal levels. [d9]

Resveratrol increased mitochondrial mass and mtDNA content, up-regulated protein expression of electron
transport chain constituents and induced mitochondrial biogenesis factors (PGC-1alpha, Nrf-1, Tfam) in cultured
human coronary arterial endothelial cells. Resveratrol treatment normalized impaired mitochondrial biogenesis in
aortas of type 2 diabetic mice. This suggests the potential benefits of resveratrol on diabetes or metabolic
diseases. [d10]

Resveratrol could inhibit the formation of islet amyloid polypeptide (IAPP) fibril. Following preferential partitioning of
IAPP into the fluid lipid phase, the membrane of beta-cells suffered irreversible damage and predominantly
circularly-shaped lipid-containing IAPP amyloid was formed. Deposition of amyloid in the extracellular matrix of beta-
cells commonly occurs in type II diabetes mellitus. Thus, resveratrol may benefit animals suffered from diabetes.

Resveratrol and cobalt protoporphyrin administration increased heme oxygenase-1 protein expression and heme
oxygenase activity in the aorta and significantly increased serum adiponectin levels, compared to untreated
diabetic rats. Increased heme oxygenase-1 expression usually improves vascular function. [d12]

Resveratrol decreased blood glucose, glycosylated hemoglobin, blood urea, serum uric acid, serum creatinine and
diminished activities of pathophysiological enzymes such as aspartate transaminase (AST), alanine transaminase
(ALT) and alkaline phosphatase (ALP) in diabetic rats after 30 days of treatment. [d13]

The prevalence of nonalcoholic fatty liver disease is high.nonalcoholic fatty liver disease is linked to obesity,
diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with nonalcoholic fatty liver disease will
eventually develop cirrhosis. Resveratrol was found to decrease nonalcoholic fatty liver disease severity in rats.
This effect was mediated, at least in part, by tumor necrosis factor alpha (TNF-alpha) inhibition and antioxidant
activities. [d14]

Scientific Evidence of Resveratrol benefits on fatty liver / liver protection, pancreatitiis, liver
transplant, kidney diseases and sperm production

The prevalence of nonalcoholic fatty liver disease is high.nonalcoholic fatty liver disease is linked to obesity,
diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with nonalcoholic fatty liver disease will
eventually develop cirrhosis. Resveratrol was found to decrease nonalcoholic fatty liver disease severity in rats.
This effect was mediated, at least in part, by tumor necrosis factor alpha (TNF-alpha) inhibition and antioxidant

Oral administration of resveratrol (20 mg/kg daily for 4 weeks) also remarkably prevented the DMN-induced loss in
body and liver weight, and inhibited the elevation of serum alanine transaminase, aspartate transaminase, alkaline
phosphatase and bilirubin levels. [LP1]

Because microcirculation occlusion and cytokines over-production is involved in many diseases such as acute
pancreatitis, resveratrol as a platelet and cytokines inhibitor may have benefits on acute pancreatitis. [5]

Resveratrol has been shown to have an immuno-suppressive property as well as protective effect on hepatocytes
under allograft rejection in a study of Wistar rats. [11]

Resveratrol (RSV) has been shown to reduce ischemia-reperfusion (I/R) injury of rat kidney both by antioxidant
and anti-inflammatory mechanisms. [10]

In a study, researchers administered
dosage of 20 mg/(kg . d) of trans-resveratrol for 90 days. Compared to a
control group, the diameter of the seminiferous tubules was significantly reduced from 437.5 +/- 0.1 mum in the
controls to 310.9 +/- 0.1 mum. This decrease was accompanied by a significant increase in tubular density. Sperm
counts were significantly greater in the resveratrol-treated rats than in the control group, but sperm quality did not
differ. [9]

Resveratrol weight loss
A lot of articles suggest resveratrol may help weight loss?  Read: resveratrol weight loss.

Resveratrol may be SAFE for a healthy person when used in the amounts found in foods. But there are potential
side effects if resveratrol is taken in larger amounts. Please click:
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