RESVERATROL BENEFITS AND SIDE EFFECTS
In 1956, the “Grape Stomping” episode of  “I Love Lucy,”  showed Lucille Ball
jumping in a vat of grapes trying to create red wine. And now, laboratory tests
have shown resveratrol, an ingredient from red wine, have anti-aging, anti-
oxidant and anti-coagulant properties.[14]

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.

Resveratrol is considered as a dietary phytoalexin. Phyto comes from the word
phyton which means a plant, while alexin means to defend. Phytoalexin means
plant antibiotic produced by a plant in response to the entry of a disease-
producing substance. [8]

RESEARCH FINDINGS

Arthritis
Resveratrol, one of the key ingredients in Yucca, is believed to contribute a
part of the health benefits of Yucca. Yucca schidigera Roezl. (Agavaceae) has
been traditionally used to treat a variety of diseases including arthritis and
rheumatism. Researchers demonstrated that resveratrol inhibited the
expression of VEGF, MMP-3, MMP-9 and COX-2 in human
articularchondrocytes stimulated with the pro-inflammatory cytokine IL- 1beta.
Furthermore, resveratrol suppressed apoptosis and
inflammatory signaling through its actions on the NF-kappaB pathway in
human chondrocytes.  Resveratrol possessed COX-1 inhibition, COX-2
inhibitory potential and an LTB 4 formation inhibitory activity in an in vitro study.

Cytokine macrophage migration inhibitory factor as a crucial factor in the
pathogenesis of rheumatoid arthritis while resveratrol was a potent inhibitor as
the antipyretic-analgeticdrug acetaminophen.

Intra-articular injections of resveratrol on cartilage and synovium could
significantly decreased cartilage destruction in an experimental rabbit
inflammatory arthritic model.
http://www.zhion.com/phytonutrients/Resveratrol_Arthritis.html

CANCER
As early as 1997, researchers have proposed to use resveratrol as a cancer-
preventive agent. Resveratrol was shown to have 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]

Researchers from researchers at Cook County Hospital found that 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]

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. Researchers found that high-doses of resveratrol
triggered apoptosis in five out of six uterine cancer cell lines. Resveratrol
exhibited a variety of molecular events in etoposide-based combination
therapy in HT-29 colon cancer cells. Resveratrol also induced growth inhibition
in T47D human breast cancer cells. Researchers from China Medical
University, Taiwan, found resveratrol significantly inhibited growth factor
heregulin-beta1 (HRG-beta1)-mediated Matrix metalloproteinase (MMP-9)
expression in human breast cancer cells. Resveratrol significantly reduced the
incidence of poorly differentiated prostatic adenocarcinoma by 7.7-fold in an
animal study. A microarray gene expression study suggested that resveratrol
is a potent inhibitor of A549 lung cancer cell growth. However, a phase I study
suggests that consumption of high-dose resveratrol might be insufficient to
elicit systemic levels commensurate with cancer preventive efficacy.
http://www.zhion.com/phytonutrients/Resveratrol_Cancers.html

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]

Diabetes
In 2001, Naderali EK and co-workers from University of Liverpool found
resveratrol (5-35 micromol/l) induced concentration-dependent relaxation of
mesenteric arteries preconstricted with noradrenaline (8 micromol/l) or KCl
(125 mmol/l) from both lean and dietary-obese rats.

Hyperglycemia, a symptom of diabetes mellitus, induces hyperosmotic
responses, including apoptosis, in vascular endothelial cells and leukocytes.
Hyperosmotic shock elicits a stress response in mammalian cells, often leading
to apoptotic cell death. Moreover, resveratrol was found to attenuate high
glucose-induced apoptotic changes by virtue of its antioxidant property.

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.

Researchers, at Boston University Medical Center, revealed 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). They showed that resveratrol could lower lipid levels
by activating AMP-activated protein kinase. It was about 200 times the potency
of Metformin!
http://www.zhion.com/phytonutrients/Resveratrol_Diabetes.html

Fatty Liver
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.
http://www.zhion.com/phytonutrients/Resveratrol_Diabetes.html

PANCREATITIS
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]

LIVER TRANSPLANT
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]

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

SPERM PRODUCTION
In a study, researchers administered 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]

Stability of Resveratrol
Resveratrol is a potent antioxidant, oxidation may occur during the
manufacturing process or/and storage of the finished products. It has long
been thought that resveratrol supplements were not very effective in
comparison with wine. Recently, some manufacturers have developed a
technique to solve the stability issues of resveratrol supplements during
manufacturing and storage. [1]

DOSE Resveratrol has been suggested to be safe at doses equivalent to 500
mg./day. [1]

TOXICITY / SIDE EFFECTS
Researchers administered rats 0, 300, 1000, and 3000 mg trans-resveratrol
per kilogram body weight per day for 4 weeks. Most of the adverse or side
events occurred in the rats administered 3000 mg per kilogram body weight
per day. Signs of toxicity included reduced final body weights and food
consumption; elevated BUN, creatinine, alkaline phosphatase, alanine
aminotransferase, total bilirubin, and albumin; reduced hemoglobin,
hematocrit, and red cell counts; and increased white cell counts. They also
observed renal lesions. No adverse or side effects were observed at 300 mg
resveratrol per kilogram body weight per day in rats. [12]

However, resveratrol was found to affect the activity of P450 and increase the
absorption of certain drugs such as diltiazem. The intake of high doses of
resveratrol can offer serious unwanted side effects for patients on certain
types of medications. Resveratrol was also found to delay the recovery of
gastric ulcer in an animal study. Finally, resveratrol is also known as a metal
chelator, high doses of resveratrol may prevent the absorption of copper or
other metals. Copper deficiency can cause muscle issues and even heart
failure. Its side effect can be serious!

Finally, resveratrol may also interact multiple drugs such as statins, erectile
dysfunctions meds, calcium channel blockers and more. Please, check my
article of
resveratrol side effects for details.

Resveratrol Cream
So far, only Decherty JJ and co-workers, Ohio Universities College of
Medicine, have conducted study on resveratrol cream. When topically applied,
resveratrol cream were shown to limit HSV-1 lesion formation in the skin of
mice. They also found that resveratrol cream could also inhibit or reduce HSV
replication in the vagina of mice and limits extravaginal disease. Resveratrol
Diabetes Resveratrol Cancers

References
[1] Neil E Levin et al, Pomeratrol™ Fact Sheet, NowFoods Online Publication, September
20, 2005 [2] Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al.
Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.
Science 1997;275:218-20 [3] Signorelli P and Ghidoni R Resveratrol as an anticancer
nutrient: molecular basis, open questions and promises. J Nutr Biochem. 2005 Aug;16(8):
449-66. [4] Olas B, Wachowicz B. Resveratrol, a phenolic antioxidant with effects on blood
platelet functions. Platelets. 2005 Aug;16(5):251-60. [5] Ma ZH, Ma QY. Resveratrol: a
medical drug for acute pancreatitis. World J Gastroenterol. 2005 Jun 7;11(21):3171-4. [6]
Atten MJ, Godoy-Romero E, Attar BM, Milson T, Zopel M, Holian O., Resveratrol regulates
cellular PKC alpha and delta to inhibit growth and induce apoptosis in gastric cancer cells.
Invest New Drugs. 2005 Mar;23(2):111-9. [7] Dong HH Ren HL New progression in the
study of protective properties of resveratrol in anticardiovascular disease. Bratisl Lek Listy.
2004;105(5-6):225-9. [8] Phytoalexin, Medfriendly.com Online Publication, September 20,
2005. [9] Juan ME et al, trans-Resveratrol, a natural antioxidant from grapes, increases
sperm output in healthy rats. J Nutr. 2005 Apr;135(4):757-60. [10] Bertelli AA et al,
Resveratrol, a component of wine and grapes, in the prevention of kidney disease. Ann N Y
Acad Sci. 2002 May;957:230-8. [11] Wu SL et al, Resveratrol prolongs allograft survival after
liver transplantation in rats. World J Gastroenterol. 2005 Aug 14;11(30):4745-9. [12] Crowell
JA et al, Resveratrol-associated renal toxicity. Toxicol Sci. 2004 Dec;82(2):614-9. Epub
2004 Aug 25. [13] Resveratrol - Read This Before You Buy Resveratrol Nurido.at July 2009
[14] The Balancing Act on Lifetime Television wants to lift your "spirits" along with
Chews4Health—as we discover the health benefits of red wine.  Transworld News, July
2009.
Resveratrol is a polyphenol compound that may have health benefits on various chronic diseases.  [1]
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