Resveratrol Supplements Shown to Decrease Cardiovascular Disease Risk in the First Long-Term Clinical Research Trial

We’ve all seen evidence time and time again that red wine is good for your health when consumed in moderation.  Scientists have even broken it down to the molecules, and have found that certain compounds are likely most responsible for the increased health benefits of red wine, with the polyphenol resveratrol being the most widely studied.  Resveratrol (and red wine in general) has been shown to benefit many different health issues, including (but certainly not limited to) diabetes, osteoporosis, dementia, and cardiovascular health.  We’ve seen short-term studied in laboratory settings, rodents, and some humans, however, what we seem to be missing are long term clinical research trials confirming what scientists have already found in the laboratory.

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The goal of the short study presented today was to examine the effects of a dietary resveratrol-enriched grape supplement on the inflammatory and fibrinolytic status of patients that were at high risk for cardiovascular disease and who were currently undergoing medical treatment for the prevention of those types diseases.

Methods

This study was a randomized, triple-blinded, placebo-controlled clinical trial with three “parallel arms” (a.k.a. treatments).  The three treatments were a grape extract containing 8mg of resveratrol, a grape extract containing similar polyphenolic content but without resveratrol, and a placebo control (maltodextrin).

Patients currently undergoing cardiovascular disease prevention at the Morales Meseguer University Hospital Cardiology Service in Murcia, Spain were recruited for this study.  To be considered for this study, patients had to be between 18 and 80 years old, have diabetes mellitus or hypercholesterolemia in addition to another cardiovascular disease risk factor including arterial hypertension, tobacco smoking (active), or obesity/overweight.  Patients were not allowed to participate in the study if they were pregnant, outside the age requirement, having documented cardiovascular disease or cerebrovascular disease, regularly intaking food supplements (particularly ones containing antioxidants), or if they had an infectious disease, neoplastic disease, or any other known chronic pathological disease.

There were a total of 75 patients in the study, with 34 men and 41 women.  These patients were randomly assigned to one of three treatment groups (as described above). 

The main factor of study was the change in high-sensitivity C-reactive protein (CRP) levels from baseline to the end of the study (12 months).  CRP rises in response to inflammation, thereby is a good indicator any disease that carries with it inflammation (which can be a large variety of diseases, including cardiovascular diseases).

Treatments were contained within a 370mg hard gelatin capsule which contained 350mg of the product (resveratrol, polyphenols, or placebo) plus 20mg of magnesium stearate and silicon dioxide.

The polyphenol content of the resveratrol and polyphenol treatments were: ~40mg procyanidins, ~25mg anthocyanins, ~1mg flavonols, and ~0.8mg hydroxcinamic acids.  For the resveratrol treatment, in addition to the polyphenols listed about, each capsule contained 8.1+/-0.5mg resveratrol and other derivatives in trace amounts (i.e. piceid and viniferins).

Participants were told to maintain their usual medication schedules and other lifestyle and diet choices throughout the duration of the study.  Participants consumed 1 capsule per day (taken in the morning) for the first 6 months and then 2 capsules per day for the following 6 months to determine if there are any dose-dependent effects.  Patients received 10 boxes of 60 capsules for the entire study.  Any unused capsules were sent back to the site by the patients at the end of the study.

Possible negative side effects were monitored throughout the study by questionnaires and telephone interviews.  Participants were asked to make note of any consumption of grape products (especially red wine) other than their treatment capsules, and also detailed records of their diet 3 days before blood draws.  Questionnaires were taken at 6 months and 12 months time.

Blood samples were collected at baseline, 6 months, and 12 months during the study.  Safety of the capsules were monitored by measuring hepatic, thyroid, and renal functions.

The following serum levels of inflammatory-related markers were measured: IL-6, IL-10, TNF-α, IL-18, sICAM-1, hs-GRP, adiponectin, and PAI-1.  (If you’d like more details on these inflammatory markers, just ask.)

Results

  • There were no significant differences in the inclusion characteristics of participants, except minor but insignificant differences were noticed for age, glucose, glycated hemoglobin.
  • Significant correlations were found between: hs-CRP and PAI-1, IL-6 and hs-CRP, TNF-αand hs-CRP, and adiponectin and sICAM-1 in all treatments.
  • The percentages of patients with greater than 3mg/L at baseline for the placebo group was 54%, for the grape extract with polyphenols only group was 32%, and finally for the grape extract with polyphenols plus resveratrol was 48%.
  • Placebo group:

o   The first 6 months showed a slight increase in IL-6 and was a significant increase by the end of the study.

o   IL-10 (anti-inflammatory) decreased after the 12 month study period.

o   The was a marginally significant (not quite statistically significant) increase in the IL-6/IL-10 ratio (pro-inflammatory) after 12 months.

o   Other inflammatory markers were not significantly different.

o   The percentage of patients with greater than 3mg/L hs-CRP values did not change from baseline to the end of the 12 month period.

  • Grape Extract Plus Polyphenols Only Group:

o   There were no significant changes in any inflammatory markers during the 12 month study period.

o   The percentage of patients with greater than 3mg/L hs-CRP values did not change from baseline to the end of the 12 month period.

  • Grape Extract Plus Polyphenols AND Resveratrol Group:

o   There was a decrease in hs-CRP (the main compound of interest).

§  hs-CRP decreased for 20 out of 25 patients.

§  The percentage of patients with greater than 3mg/L hs-CRP values decreased from 48% at baseline to 30% at the end of the 12 month period.

o   TNF-α and PAI-1 decreased by the end of the study in the resveratrol group.

o   The IL-6/IL-10 ratio decreased, primarily due to an increase in IL-10 levels.

o   sICAM-1 decreased only marginally.

o   Adiponectin significantly increased after 6 months and only marginally increased by 12 months.

o   IL-18 decreased over time, though was not significant.

o   IL-6 did not change over time.

o   Correlations:

§  The decrease in hs-CRP was significantly correlated with the decrease in TNF-α.

§  The decrease in sICAM-1 significantly correlated with the decrease in IL-18.

§  The increase in adiponectin was significantly correlated with the decrease in sICAM-1.

  • Contents of the capsules were deemed safe due to no relevant changes occurring in markers for the hepatic, thyroid, or renal systems.
  • There were no adverse effects noted by any patient in the study.

Conclusions

The results of this study are the first of its kind, according to the authors, to demonstrate that a dietary supplementation of grape extract plus 8mg of resveratrol in capsule form significantly improves the inflammatory and fibrinolytic status of patients that are currently undergoing prevention for cardiovascular diseases.  The authors indicate that the most important finding was the decrease in hs-CRP levels by 26% after 1 year, in addition to a decrease in proinflammatory TNF-a and PAI-1.  As a reminder, CRP rises in response to inflammation, thereby is a good indicator any disease that carries with it inflammation (which can be a large variety of diseases, including cardiovascular diseases).  A decrease in this marker means that inflammation in the system is decreased; which is overall positive result in regards to cardiovascular and other systems health.  It does appear that the higher dose of 2 capsules per day is more effective in reducing the levels of these inflammatory markers, particularly of PAI-1.

It is important to note that the patients in this study were not asked to give up any of their other medications for cardiovascular disease prevention.  Therefore, according to the authors, there is a strong possibility that there is a synergistic effect going on between the statins in the cardiovascular medications and the resveratrol or other compounds in the supplement.  Previous studies have shown that pravastatin and resveratrol are more effective than statins alone in protecting against heart attack in hypercholesterolemic rats, so a synergistic effect in humans should not be ruled out.

The main limitation in this study is that the sample sizes were not very large.  Since participants had to be divided into three treatment groups, therefore the sample size per treatment group was very small.  As a result of this, those results that were found to be marginally significant or not significant may change if more patients were enrolled into the study.  The only way around this is to simply repeat the study with more patients per treatment group.

According to the authors, this is the very first long-term clinical trial examining the effects of a resveratrol supplement on the prevention of cardiovascular disease in humans.  I thought it was a very interesting study, however would certainly like to see it performed with more patients enrolled.  Also, I’d like to see the studied carried out for longer, if possible, in attempt to be able to predict future cardiovascular events in patients consuming resveratrol supplements versus placebo. 

Finally, I’d like to see this study performed using a wider range of demographics.  It was not clear the demographic breakdown of the participants, but with such a low number of subjects, it may have been difficult to analyze these factors regardless.  Would we see these same results in other countries that typically have different diets or lifestyles?  How do these results hold up to the typical American diet and lifestyle? 

What do you all think about this study?  Would you change it?  How so?  Please feel free to leave your comments below!

Source: Tomé-Carneiro, J., Gonzálvez, M., Larrosa, M., Yáñez-Gascón, M.J., Gracía-Almagro, F.J., Ruiz-Ros, J.A., García-Conesa, M.T., Tomás-Barberán, F.A., Espín, J.C. 2012. One-Year Consumption of a Grape Nutraceutical Containing Resveratrol Improves the Inflammatory and Fibrinolytic Status of Patients in Primary Prevention of Cardiovascular Disease. American Journal of Cardiology 110(3): 356-363.

DOI: 10.1016/j.amjcard.2012.03.030.

I am not a health professional, nor do I pretend to be. Please consult your doctor before altering your alcohol consumption habits. Do not consume alcohol if you are under the age of 21. Do not drink and drive. Enjoy responsibly!

2 comments for “Resveratrol Supplements Shown to Decrease Cardiovascular Disease Risk in the First Long-Term Clinical Research Trial

  1. Crystal Gailey
    August 30, 2012 at 2:08 pm

    Resveratrol was said to have many beneficial effects to the human body including increasing life span, preventing brain degeneration, lowering blood sugar, preventing cardiovascular diseases and many others. It is actually a natural phenol that can be extracted from the red skin of grapes thus, the reason why people drink red wine.

  2. August 30, 2012 at 2:11 pm

    I think that's been pretty well established, but thanks for reminding everyone! Cheers!

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