Maria Virginia Aloi Deheza

MariaVirginia.AloiDeheza@lc.cuny.edu
DFN 445
Prof Andrea P. Boyar
Final Submission Date: 04/23/2015

Can the antioxidant resveratrol in red wine reduce the

risk of coronary heart disease/cardiovascular disease
in subjects at increased risk?

References:
1. Wong RHX, Howe PRC, Buckley JD, Coates AM, Kunz I, Berry NM. Acute resveratrol
supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly
elevated blood pressure. Nutr Metab Cardiovas 2011; 21, 851-856.
2. Tom-Carneiro J, Gonzlvez M, Larrosa M, Yez-Gascn MJ, Garca-Almagro FJ, Ruiz-Ros
JA, et al. One-Year Consumption of a Grape Nutraceutical Containing Resveratrol Improves the
Inflammatory and Fibrinolytic Status of Patients in Primary Prevention of Cardiovascular
Disease. Am J Cardiol 2012;110:356363.

Introduction
Resveratrol, an antioxidant present in red wine, is known to have properties that protect
the heart. Is this claim indeed true? Many studies have been conducted in the past to investigate
the effects of resveratrol and its role in the prevention and treatment of cardiovascular disease.
These studies have mostly been done on test tubes or in animals but very few have been done on
humans. That is why this research paper will investigate resveratrol human trials. One of the
studies chosen claims to be the first one ever performed on humans, which is an extremely
fascinating find. The studies selected in this research paper aim to investigate the action of
resveratrol in patients with increased risk of cardiovascular disease. The importance of these
discoveries are of great interest in the health care community because they may open a whole
new era in the prevention and treatmentcardiovascular of disease.

Methods and results

In 2011 researchers performed a study with the goal of finding out if flow-mediated
dilatation was acutely effected after the consumption of resveratrol from red wine (1). They also
wanted to investigate if the effect was related to the amount of resveratrol consumed. Flowmediated dilatation is a process by which blood vessels dilate in the presence of increased blood
flow and it is also an important biomarker for cardiovascular health. If this function is absent or
diminished it indicates cardiovascular risk. The team performed a randomized, placebocontrolled, double-blind, crossover human intervention trial that consisted of four weekly visits
from the patients to the facility. The population studied were 19 nonsmoking (or those on
nicotine replacement therapy) overweight and obese Australian adults aged 30 to 70 who

suffered from elevated blood pressure but did not have history of cardiovascular disease, diabetes
or renal disease and were not taking medications for diabetic or blood pressure. The women who
participated in the study were required to be postmenopausal.
During the study participants were asked not to change their diet habits before visits, not
to alter their physical activity, nor to consume polyphenols. One of three doses of resveratrol (30
mg, 90 mg and 270 mg) or a placebo were provided to the volunteers every week. The placebo
capsules were exactly the same in appearance as the active capsules and they contained a filler of
Calcium Hydrogen Phosphate and microcrystalline cellulose which was inert. Each patient,
having fasted for 4 hours, consumed a single dose consisting of 6 capsules every visit. After a 45
min rest, the researcher performed an assessment of endothelial function via flow-mediated
dilatation by ultrasound. The ultrasound videos obtained from the session were analyzed using
specialized software. Next, the change in the diameter of the artery was computed in percentages
(% Flow-Mediated Dilatation). Following this, a blood sample was obtained each visit and tested
for resveratrol concentration. During the analysis of the data obtained from the participants the
researchers observed that when the resveratrol doses increased there was a significant
proportional increase in the concentrations of resveratrol in plasma. They also observed an
increase in Flow-Mediated Dilatation after consumption of the doses of resveratrol which
demonstrated that resveratrol improved Flow-Mediated Dilatation in a dose-related way. The
researchers concluded that resveratrol may indeed provide the claimed cardiovascular benefits of
red wine, though more research is suggested to ensure the validity of the findings.(1)
A 2012 study aimed to assess, for the first time, the effects of resveratrol supplementation
on inflammation and fibrinolysis in patients at high risk for cardiovascular disease currently

following primary prevention of cardiovascular disease (2). Fibrinolysis is the natural process by
which blood clots are prevented from growing and becoming problematic. The researchers
recruited 75 patients who were from 18 to 80 years of age, had been taking statins for over three
months, and had risk factors for cardiovascular disease such as diabetes, high cholesterol, arterial
hypertension, smoking, and overweight and obesity. Patients who were pregnant, over or under
the age range designated, consumed food supplements often, or had had history of cardiovascular
or cerebrovascular, infectious, or neoplastic diseases, or other chronic pathology were excluded.
The study was triple-blinded, meaning that besides the researchers and the participants not
knowing who participated in which group, the statisticians were not

aware of the group

placements either. It was also a placebo-controlled parallel follow-up trial that lasted one year.
Three parallel groups were offered pills: a supplement with 8 mg of resveratrol, a grape
supplement without resveratrol, and a placebo. The placebo contained maltodextrin and was
identical in appearance to the active pills. The first 6 months the patients took a single dose and
the last 6 months they took a double dose in order to test for dose-related results. The data
collected was in the form of blood tests and questionnaires. The blood testing was done at the
beginning, at six months, and at the end of the study. Participants were required to fast the day
before the blood drawing. They were also asked to take notes of their food consumption 3 days
prior to the tests (including red wine and grape products). Blood was tested for levels of Creactive protein, tumor necrosis factor-alpha, plasminogen activator inhibitor type 1, interleukin6/interleukin-10 ratio, increased anti-inflammatory interleukin-10, adiponectin, and soluble
intercellular adhesion molecule-1. In order to check for possible incidences concerning tolerance
and compliance, questionnaires were provided at the beginning of the study and retrieved at the

six and twelve months visits. After analyzing the data, the researchers found that the patients
who consumed the resveratrol pill slightly differed from the ones who consumed the placebo and
the regular grape supplement after 6 months in the following blood components: antiinflammatory interleukin-10 (Placebo group no significant change, No Resveratrol Grape no
significant change, Resveratrol group increased 10.4% from baseline), tumor necrosis factoralpha (Placebo group no significant change, No Resveratrol Grape no significant change,
Resveratrol group no significant change), high-sensitivity C-reactive protein (Placebo group no
significant change, No Resveratrol Grape no significant change, Resveratrol group no significant
change), interleukin-6/interleukin-10 ratio (Placebo group no significant change, No Resveratrol
Grape no significant change, Resveratrol group no significant change), and plasminogen
activator inhibitor type 1 (Placebo group no significant change, No Resveratrol Grape no
significant change, Resveratrol group no significant change). However, they noted significantly
greater changes after 12 months in the same blood components: anti-inflammatory interleukin-10
(Placebo group decreased 11.2%, No Resveratrol Grape no significant change, Resveratrol group
increased 19.8%), tumor necrosis factor-alpha (Placebo group no significant change, No
Resveratrol Grape no significant change, Resveratrol group decreased 19.8%), high-sensitivity
C-reactive protein (Placebo group no significant change, No Resveratrol Grape no significant
change, Resveratrol group decreased 26.0%), interleukin-6/interleukin-10 ratio (Placebo group
no significant change, No Resveratrol Grape no significant change, Resveratrol group decreased
24.0%), and plasminogen activator inhibitor type 1 (Placebo group no significant change, No
Resveratrol Grape no significant change, Resveratrol group decreased 16.8%). Less significant
changes were observed in the adiponectin and soluble intercellular adhesion molecule-1 which

increased and decreased, respectively. The researchers concluded that resveratrol consumption
over the course of an year improved the inflammation and fibrinolysis state in subjects with high
risk of cardiovascular disease who were taking statins as a primary prevention for the same
condition. This outcome makes it safe to say that resveratrol could be adequate as a complement
for primary prevention of cardiovascular disease in the gold standard therapy.(2)

Conclusion
An analysis of the peer-reviewed articles showed many similarities in the results as well
as in the designs of the studies. They were both randomized, double-blind (one was triple-blind),
placebo-controlled, crossover human intervention trials with focus on dose differentiation. They
both aimed at the treatment of cardiovascular disease symptoms and prevention, specifically
endothelial function, inflammation, and fibrinolysis. Both studies demonstrated a significant
improvement regarding the risk factors for cardiovascular disease. These results prove that the
hypothesis stated at the beginning of the paper is indeed true because in both studies the patients
consuming the resveratrol pill showed statistically significant differences from the patients who
took the placebo. It is safe to say, therefore, that resveratrol may be considered to be included in
the gold standard for prevention and treatment of cardiovascular disease.