RESVERATROL

INTRODUCTION
Cancer is the most commonly diagnosed disease, and its related
morbidity and mortality pose a significant health problem
worldwide[1]. Despite great efforts to find a cure, cancer
continues to be a substantial cause of death in humans, and
efficient treatment remains a formidable challenge[1]. Despite
several advancements in diagnosis and monitoring, the overall
cancer survival rate has not improved[1].
Prevailing cancer therapies, e.g., chemotherapy, targeted agents,
radiation therapy, cancer surgery etc., have boundaries resulting
from the development of resistance to the therapy[1].
Since ancient times, natural products have been utilized to
prevent many chronic diseases, including cancer[1]. A revived
interest in phytochemicals acquired from dietary or medicinal
plant sources has given an alternative source of bioactive
compounds that can be utilized as preventive or therapeutic
agents against a variety of diseases[1]. Resveratrol is growing in
demand because it has cancer-preventive and anticancer
properties[1].
It is a polyphenol compound found in grapes, red wine, berries,
and peanuts[1-2]. It is also a component of some Chinese and
Japanese traditional medicines in its extract forms, such as those
that come from Polygonum cuspidatum, which can treat
inflammation, headaches, cancers, and amenorrhea[1-2].
Resveratrol may help to protect against the thickening of arterial
walls and heart disease, but consuming a diet rich in Resveratrol
does not reduce the risk of dying from cancer or heart
disease[3].
It is available in solid/powder, liquid and in pill forms.

USES


(A) Hay Fever
Using a nasal spray of Resveratrol three times daily for four
weeks appears to lessen allergy symptoms in adults with
seasonal allergies[4]. Using Resveratrol and beta-glucans nasal
spray three times daily for two months also decreases allergy
symptoms in children with allergies[4].


(B) Diabetes
Resveratrol has exhibited many benefits for diabetes, at least in
animal studies[5].
These advantages include increased insulin sensitivity and
preventing complications from diabetes[5].
Resveratrol works by stopping a specific enzyme from turning
glucose into sorbitol which is sugar alcohol[5].
When too much sorbitol starts to build up in people with
diabetes, it creates cell-damaging oxidative stress[5].
Other benefits of Resveratrol on diabetes includes protection
against oxidative stress, decreasing inflammation, and activation
of AMPK, which aids to metabolize glucose[5]
Researchers state that the compound could treat diabetes and
its complications, but more research is needed to prove this[5].


(C) Lowering of blood pressure
By escalating the expression and activity of eNOS, Resveratrol
could be an assuring supplement for lowering blood pressure[6].

A 2015 review mentioned that high doses might help decrease
the pressure exerted on artery walls when the heart beats [5].
This pressure is called systolic blood pressure[5].
Systolic blood pressure usually goes up with age[5]. When
systolic blood pressure is high, it becomes a risk factor for heart
disease[5].
Resveratrol may achieve this blood-pressure-lowering effect by
producing more nitric oxide, which causes blood vessels to
relax[5].
But, the authors of that study state that more research is
required before making any specific recommendations about the
most suitable dose of Resveratrol to maximize blood pressure
benefits[5].


(D) Positive Effect on blood fat
Numerous studies have suggested that resveratrol supplements
may healthily change blood fats[7].
Resveratrol seems to regulate cholesterol levels by decreasing
the effect of an enzyme that controls cholesterol production[5].
Because Resveratrol is an antioxidant, it may decrease the
oxidation of “bad” LDL cholesterol, which otherwise will cause
plaque to build up in artery walls[5].
In a study, participants were given grape extract that has extra
Resveratrol [5].
After six months of their prophylaxis with Resveratrol, their LDL
had dropped by 4.5%, and oxidized LDL had decreased by 20%

compared to participants who took an unenriched grape extract
or a placebo[5].
(E) Protects the brain
Due to antioxidant and anti-inflammatory activities, Resveratrol
helps to protect the brain[5].
It seems to interfere with beta-amyloids, essential for
developing the plaques that are signs of Alzheimer’s disease[5].
Also, the compound may produce a chain of events that defends
brain cells from damage[5].
While this research is fascinating, scientists still have questions
about how well the human body can use supplemental
Resveratrol, limiting its immediate use as a supplement to
protect the brain[5].


(F) Cancer
Resveratrol has been studied in-vivo for its ability to stop and
treat cancer[5]. However, mixed results are achieved[5].
In-vitro and in-vivo studies have shown to fight many types of
cancer, including gastric cancer, colon cancer, skin cancer,
breast cancer and prostate cancer[5].
Resveratrol may combat cancer cells by changing the gene
expression, which inhibits the growth of cancer tumours [5].
Also, it may interfere with certain hormones and prevent
hormone-dependent cancers[5].
Because studies have been carried out in test tubes and animals,
more research is required to check if and how this compound
might be utilized for human cancer therapy[5].

MECHANISM OF ACTION
Resveratrol has been examined for its anticancer potential[3]. It
was seen to inhibit the proliferation of cancer cells through
apoptosis and by exerting anti-estrogenic effects[3]. Trans-
resveratrol appears to decrease methylation of the tumour
suppressor gene RASSF-1alpha in women at increased breast
cancer risk[3]. In addition, breast cancer cell movement and
invasion reductions were seen after supplementation[3].
Resveratrol growth factor heregulin-beta1 mediated matrix
metallopeptidase 9 expressions in human breast cancer cells[3].
But, contradictory data show that Resveratrol mimics
phytoestrogens and could stimulate genes usually regulated by
estrogens or androgens[3]. In other studies, Resveratrol helped
reduce prostate tumorigenesis by decreasing prostatic levels of
mTOR complex activity and enhanced expression of SIRT1; and
modulated steroid hormone-dependent pathways to inhibit
prostate cancer cell growth[3]. However, it also enhances
angiogenesis and inhibits apoptosis in vivo[3]. Further research
is required.
Additional findings show that Resveratrol downregulates p21 and
upregulates cyclin E causing S-phase accumulation and
apoptosis in neuroblastoma cells[3]. It also inhibits CYP1A1,
CYP1A2, and CYP1B1 enzymes in tumour cells, perhaps exerting
antitumor effects as some of these enzymes are known to be
involved in activating procarcinogens and toxins[3]. Protective
effects of Resveratrol against doxorubicin-induced
cardiotoxicity are because of upregulation of SIRT1-mediated
p53 deacetylation[3]. Also, it protects against cisplatin-induced
cardiotoxicity by suppressing oxidative stress[3].

DOSAGE

Resveratrol is available under different brands and other names:
cis-resveratrol, kojo-kon, Stilbene phytoalexin, and trans-
resveratrol.
Evidence from clinical studies is inadequate to give dosing
guidelines[8]. Single-dose studies advise that a safe daily dosage
for a person weighing 70 kg may be 450 mg/day[8]. Dosages
above 1 g/day seem to have been well-tolerated in a short-term
(2-week) trial but reported adverse reactions in another
study[8]. In a meta-analysis estimating the effects of Resveratrol
on glucose control and insulin sensitivity, dosing extends from
8- 1,500 mg/day, and the span varied between 2 weeks to 6
months; these studies centred on patients with type 2 diabetes
mellitus, cardiovascular diseases, or metabolic syndrome, or
healthy participants[8]. High-dose of Resveratrol (1,000 mg
twice daily) has been utilized for up to 1 year in patients with
mild and moderate Alzheimer’s disease and 500 mg 3 times daily
for 6 months in non-alcoholic fatty liver disease[8]. For exercise
capacity, the beginning dose was 500 mg twice a day for 1 week,
then raised to 1,000 mg twice a day for the remaining 3
weeks[8].


SIDE EFFECTS
Orally:
Resveratrol is LIKELY SAFE when used in the same
quantity found in foods[4]. When consuming in doses up to 1500
mg daily for up to 3 months, Resveratrol is POSSIBLY SAFE[4].
Higher doses ranging from 2000-3000 mg per day have been
used safely for 2-6 months[4]. However, these larger doses of
Resveratrol are more likely to produce stomach problems[4].


Application on skin: Resveratrol is POSSIBLY SAFE when
applied to the skin for approx 30 days[4].

Precautions/Warnings
Pregnant and Lactating women: Resveratrol is LIKELY SAFE
when taken in the exact amounts found in some foods[4].
However, during pregnancy and breastfeeding, the source of
Resveratrol is essential[4]. Wine should not be taken as a source
of Resveratrol during pregnancy and lactation[4].
Bleeding disorders: Resveratrol might reduce blood clotting and
increase the risk of bleeding in people with bleeding
disorders[4].
In various hormone sensitive cancers such as breast cancer,
uterine cancer, ovarian cancer, endometriosis etc.: Resveratrol
might act the same as estrogen[4]. So beware before taking
Resveratrol in such conditions[4].
Surgery: Resveratrol might increase the chance of bleeding
during and after surgery[4]. Stop using Resveratrol approx two
weeks before a scheduled surgery[4].

Interaction
Antiplatelet drugs: Although clinical significance is yet to
be determined, Resveratrol inhibits platelet aggregation in
vitro, so concomitant use with antiplatelet medications may
develop bleeding risk[3]. Therefore, one should consult a
health physician before consuming it[3].
Cytochrome P450 substrates: Resveratrol inhibits CYP3A4,
CYP2D6 and induced CYP1A2 in healthy volunteers
following daily consumption of one gram of Resveratrol for

four weeks[3]. Hence, it can affect the levels of drugs that
are metabolized by these enzymes[3].
Carbamazepine: Polygonum cuspidatum, an herbal
supplement rich in Resveratrol, raised carbamazepine
blood levels due to CYP3A inhibition and multidrug
resistance-associated protein 2 in a murine model[3].
Clinical significance is yet to be determined[3].