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RESVERATROL BENEFITS SIDE EFFECTS, REVIEWS

Aug 16, 2017

Resveratrol Reviews
Resveratrol (3,4',5-trihydroxystilbene) is a polyphenol, belongs to a class of stilbenes. Resveratrol is a fat-soluble compound that occurs in a trans 
and a cis configuration. Resveratrol also occur as glucosides, such as resveratrol-3-O-beta-glucoside (also called as piceid).
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.Resveratrol was interested by scientists, as it might have health benefits on various 
chronic diseases.Some marketers promote resveratrol as an anti-aging remedy. Resveratrol exhibits a wide range of biological effects, including 
antiplatelet, anti-inflammatory, anticancer, antimutagenic and antifungal properties.
 

Resveratrol was also believed responsible for some of the beneficial effects of moderate red wine drinking on the cardiovascular system. However, 
one liter of red wine contains only 1.5-3 mg of resveratrol, Consequently, resveratrol becomes popular in the US and other places in the world.
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.

Metabolism and Absorption of Resveratrol
Oral dosage of trans-reveratrol is well-absorbed in the body, but it has a rapid metabolism and elimination leading to a low bioavailability. 
Bioavailability is the fraction of an orally-administrated compound that reaches the circulatory system. A group of 6 subjects took 25 mg of 
trans-resveratrol orally, only traces of the unchanged resveratrol were detected in blood stream. Plasma concentrations of resveratrol and 
metabolites peaked around 60 minutes (T max) later. 

Resveratrol Biological Activities and Potential Health Benefits

Arthritis
Yucca schidigera Roezl. (Agavaceae) has been traditionally used to treat arthritis and rheumatism and some other diseases. Later on, resveratrol 
was found to be one of its key ingredients. [a3] Arthritis is the inflammation of the joints, it 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 agent 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. 
Resveratrol was found be an inhibitor or a mediator for some of these compounds in our body. Thus, resveratrol may benefit people suffered from 
arthritis.
Cancer
Resveratrol may have benefits on those at risk of certain cancers. As early as 1997, researchers have proposed to use resveratrol as a 
cancer-preventive agent. Resveratrol potentiates 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]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. Resveratrol 
is also able to activate apoptosis, to arrest the cell cycle or to inhibit kinase pathways. [2,3, c2]

In addition to potentiate the benefit of anti-cancer drugs, resveratrol itself can be an anti-cancer agent. In a study, resveratrol inhibited 
cyclooxygenase (COX) expression and/or activity; in endometrial cancer cells, COX-2 is overexpressed and confers cellular resistance to 
apoptosis. High-doses of resveratrol triggered apoptosis in five out of six uterine cancer cell lines. [c4] Resveratrol also 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] In another 
study, resveratrol-induced growth inhibition in T47D human breast cancer cells. Resveratrol-induced apoptosis is found to be associated with the 
activation of the p53 in a dose- and a time-dependent manner. [c6] In another study, resveratrol significantly inhibited growth factor heregulin-beta1 
(HRG-beta1)-mediated Matrix metalloproteinase 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 (dosage- 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] Finally, resveratrol was shown as a potent 
inhibitor of A549 lung cancer cell growth based on a microarray gene expression study. [c10]

The studies on the potential health benefits of resveratrol on cancer were done in animals. One may ask what dosage needed for a human to 
achieve such therapeutic effects? A phase I study of oral resveratrol (single dosages- 0.5, 1, 2.5, or 5 g) was conducted by Leicester University, 
UK, 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 dosage 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 the requirement of consumption of very high-dose 
resveratrol to elicit systemic levels commensurate with cancer preventive efficacy. [c7] However, it is also found that resveratrol has hormesis 
properties. Frequently, low doses of toxins and other stressors not only are harmless but also activate an adaptive stress response that raise the 
resistance of the organism against high doses of the same agent. This phenomenon, which is known as "hormesis" When high doses of these 
chemicals are employed, cells undergo mitochondrial outer membrane permeabilization and die. In contrast, low doses of such cytotoxic 
chgemicals can activate hormesis in several paradigms, and this may explain the lifespan-prolonging potential of autophagy inducers including 
resveratrol and caloric restriction. 

Cardiovascular Diseases
Resveratrol is a phytoestrogen, potent antioxidant, reactive oxygen species scavenger and metal chelators.  Thus, resveratrol 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.Thus, 
resveratrol may benefit people at risk of certain cardiovascular conditions.

Diabetes
Studies showed that resveratrol increased life span in lower organisms by activating the NAD (+)-dependent histone deacetylase Sirt1. And, it was 
found that that resveratrol promoted longevity and improved glucose homeostasis in mice by stimulating the Sirt1-mediated deacetylation of the 
transcriptional coactivator PGC-1alpha.  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. 
Hyperglycemia, a symptom of diabetes mellitus, induces hyperosmotic responses, including apoptosis, in vascular endothelial cells and 
leukocytes. Hyperosmotic shock often leads to apoptotic cell death. Resveratrol was found to attenuate high glucose-induced apoptotic changes 
by virtue of its antioxidant property.  Diabetic nephropathy is a serious vascular complication and one of the main causes of end-stage renal 
disease. Increased oxidative stress plays an important role in the etiology of diabetic nephropathy. Treatment with resveratrol significantly 
attenuated renal dysfunction and oxidative stress in diabetic rats.

Most of type 2 diabetes mellitus patients eventually become insulin dependent when insulin secretion by the islets of Langerhans is exhausted. 
Resveratrol was found to possess 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. In nicotinamide-treated diabetic rats, the plasma glucose oncentration on day 14 was reduced only by 20.3 %, and 
the triglyceride concentration was reduced by 33 %. 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. Thus, resveratrol may benefit people at risk of type 2 diabetes.

Fatty liver / liver protection
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. Oral administration of resveratrol (dosage 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.  Thus, resveratrol may have benefits of liver protection.

Skin
When topically applied, resveratrol cream limited the HSV-1 lesion formation in the skin of mice, resveratrol cream also reduced HSV replication in 
the vagina of mice and limits extravaginal disease. Thus, resveratrol cream may have some potential benefits on skin health, but more studies are 
needed to support this health benefit-claim.


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