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NIHR Signal Resveratrol supplements do not improve cardiovascular risk markers

Published on 21 August 2015

doi: 10.3310/signal-000112

This systematic review of trials found that resveratrol supplements do not improve the results of tests that indicate risk of heart disease, including levels of blood pressure, blood glucose, cholesterol or C-reactive protein.

Resveratrol is found naturally in red grapes, other fruits, and nuts. Some researchers think resveratrol in red wine may lower the risk of cardiovascular disease in moderate drinkers, as seen in France. Resveratrol is currently available to buy as a supplement. This review aimed to find out whether resveratrol supplementation might help reduce cardiovascular disease risk markers. The findings suggest they don’t.

Share your views on the research.

Why was this study needed?

Cardiovascular disease is a very common and serious problem in the UK. It causes a quarter of deaths in the UK, and an estimated seven million people are currently living with it. Being physically active and eating healthily lowers the risk of cardiovascular disease. The researchers wanted to see if taking a resveratrol supplement would also reduce the risk. Past trials have given contradictory findings and a 2013 systematic review of seven trials and 236 participants gave inconclusive results. The aim of this larger, more up to date systematic review, was to better understand whether resveratrol supplements improve markers of cardiovascular disease risk.

What did this study do?

This was a systematic review and meta-analysis of randomised controlled trials involving participants taking purified or standard-strength resveratrol supplements. Trial participants took reservatrol supplements for between 2 and 12 months, at doses ranging between 8 mg/day to 1500 mg/day. Trials were included only if they measured a blood protein called C-reactive protein (CRP), which is raised when there is inflammation in the body, including in cardiovascular disease. Other tests for cardiovascular disease risk included: cholesterol level, blood pressure and blood glucose. Studies were excluded for reasons such as using a low strength of resveratrol (below 5mg per day) or for using extracts with variable or unknown strength, such as in grape juice.

The results of 10 trials were pooled in a meta-analysis. The systematic review was rigorously carried out which provides confidence in the results, although the RCTs were relatively small in size.

What did it find?

  • The systematic review found 10 relevant RCTs from around the world. They included 600 participants and were rated as moderate to high quality.
  • Overall, taking resveratrol supplements was linked to a lower average CRP level (-0.144 mg/l) but this was not statistically significant (95% confidence interval -0.968 to 0.680).
  • Most trials measured cholesterol and half measured blood pressure. There was no significant effect of taking resveratrol supplements on cholesterol or blood pressure.

What does current guidance say on this issue?

There is no guidance available on resveratrol supplementation. Neither NICE public health guidance on prevention of cardiovascular disease for the population (2010), nor a NICE guideline on maintaining a healthy weight (2015), provides recommendations for the use of resveratrol.

NICE public health guidance on prevention of cardiovascular disease does make recommendations on what can be done to reduce risk in the population and there are well known steps that individuals can take to reduce their own risk, summarised in other NICE guidance on cardiovascular risk, cholesterol and blood pressure treatment.

What are the implications?

This study only looked at the effect of resveratrol on laboratory test results, not actual heart disease.  Nevertheless there is nothing in the research on the test results that suggests this supplements of this dietary component might be protective against heart disease.

The messages about preventing heart disease are unchanged by this study.  Stopping smoking, eating and exercising healthily and getting treatment for any raised blood pressure or cholesterol, remain the main things individuals can do.  Adding resveratrol supplements won’t help.

Bibliography

Cardiovascular disease statistics [internet].  London; British Heart Foundation; 2015.

Maintaining a healthy weight and preventing excess weight gain among adults and children. NG7. London: National Institute for Health and Care Excellence; 2015.

Nabili, SN. C-reactive protein measurement [internet]. New York; Emedicine health; 2014.

Prevention of cardiovascular disease. PH25. London: National Institute for Health and Care Excellence; 2010.

Sahebkar A. Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trials. Nutrition reviews. 2013;71(12):822-35.

Why was this study needed?

Cardiovascular disease is a very common and serious problem in the UK. It causes a quarter of deaths in the UK, and an estimated seven million people are currently living with it. Being physically active and eating healthily lowers the risk of cardiovascular disease. The researchers wanted to see if taking a resveratrol supplement would also reduce the risk. Past trials have given contradictory findings and a 2013 systematic review of seven trials and 236 participants gave inconclusive results. The aim of this larger, more up to date systematic review, was to better understand whether resveratrol supplements improve markers of cardiovascular disease risk.

What did this study do?

This was a systematic review and meta-analysis of randomised controlled trials involving participants taking purified or standard-strength resveratrol supplements. Trial participants took reservatrol supplements for between 2 and 12 months, at doses ranging between 8 mg/day to 1500 mg/day. Trials were included only if they measured a blood protein called C-reactive protein (CRP), which is raised when there is inflammation in the body, including in cardiovascular disease. Other tests for cardiovascular disease risk included: cholesterol level, blood pressure and blood glucose. Studies were excluded for reasons such as using a low strength of resveratrol (below 5mg per day) or for using extracts with variable or unknown strength, such as in grape juice.

The results of 10 trials were pooled in a meta-analysis. The systematic review was rigorously carried out which provides confidence in the results, although the RCTs were relatively small in size.

What did it find?

  • The systematic review found 10 relevant RCTs from around the world. They included 600 participants and were rated as moderate to high quality.
  • Overall, taking resveratrol supplements was linked to a lower average CRP level (-0.144 mg/l) but this was not statistically significant (95% confidence interval -0.968 to 0.680).
  • Most trials measured cholesterol and half measured blood pressure. There was no significant effect of taking resveratrol supplements on cholesterol or blood pressure.

What does current guidance say on this issue?

There is no guidance available on resveratrol supplementation. Neither NICE public health guidance on prevention of cardiovascular disease for the population (2010), nor a NICE guideline on maintaining a healthy weight (2015), provides recommendations for the use of resveratrol.

NICE public health guidance on prevention of cardiovascular disease does make recommendations on what can be done to reduce risk in the population and there are well known steps that individuals can take to reduce their own risk, summarised in other NICE guidance on cardiovascular risk, cholesterol and blood pressure treatment.

What are the implications?

This study only looked at the effect of resveratrol on laboratory test results, not actual heart disease.  Nevertheless there is nothing in the research on the test results that suggests this supplements of this dietary component might be protective against heart disease.

The messages about preventing heart disease are unchanged by this study.  Stopping smoking, eating and exercising healthily and getting treatment for any raised blood pressure or cholesterol, remain the main things individuals can do.  Adding resveratrol supplements won’t help.

Bibliography

Cardiovascular disease statistics [internet].  London; British Heart Foundation; 2015.

Maintaining a healthy weight and preventing excess weight gain among adults and children. NG7. London: National Institute for Health and Care Excellence; 2015.

Nabili, SN. C-reactive protein measurement [internet]. New York; Emedicine health; 2014.

Prevention of cardiovascular disease. PH25. London: National Institute for Health and Care Excellence; 2010.

Sahebkar A. Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trials. Nutrition reviews. 2013;71(12):822-35.

Lack of efficacy of resveratrol on C-reactive protein and selected cardiovascular risk factors - Results from a systematic review and meta-analysis of randomized controlled trials

Published on 18 April 2015

Sahebkar, A.,Serban, C.,Ursoniu, S.,Wong, N. D.,Muntner, P.,Graham, I. M.,Mikhailidis, D. P.,Rizzo, M.,Rysz, J.,Sperling, L. S.,Lip, G. Y.,Banach, M.

Int J Cardiol Volume 189 , 2015

INTRODUCTION: Numerous studies have suggested that oral supplementation with resveratrol exerts cardioprotective effects, but evidence of the effects on C-reactive protein (CRP) plasma levels and other cardiovascular (CV) risk factors is inconclusive. Therefore, we performed a meta-analysis to evaluate the efficacy of resveratrol supplementation on plasma CRP concentrations and selected predictors of CV risk. METHODS: The search included PUBMED, Cochrane Library, Web of Science, Scopus, and EMBASE (up to August 31, 2014) to identify RCTs investigating the effects of resveratrol supplementation on selected CV risk factors. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence intervals (CI) as summary statistics. RESULTS: Meta-analysis of data from 10 RCTs (11 treatment arms) did not support a significant effect of resveratrol supplementation in altering plasma CRP concentrations (WMD: -0.144mg/L, 95% CI: -0.968-0.680, p=0.731). Resveratrol supplementation was not found to alter plasma levels of total cholesterol (WMD: 1.49mg/dL, 95% CI: -14.96-17.93, p=0.859), low density lipoprotein cholesterol (WMD: -0.31mg/dL, 95% CI: -9.57-8.95, p=0.948), triglycerides (WMD: 2.67mg/dL, 95% CI: -28.34-33.67, p=0.866), and glucose (WMD: 1.28mg/dL, 95% CI: -5.28-7.84, p=0.703). It also slightly reduced high density lipoprotein cholesterol concentrations (WMD: -4.18mg/dL, 95% CI: -6.54 to -1.82, p=0.001). Likewise, no significant effect was observed on systolic (WMD: 0.82mmHg, 95% CI: -8.86-10.50, p=0.868) and diastolic blood pressure (WMD: 1.72mmHg, 95% CI: -6.29-9.73, p=0.674). CONCLUSIONS: This meta-analysis of available RCTs does not suggest any benefit of resveratrol supplementation on CV risk factors. Larger, well-designed trials are necessary to confirm these results.

Resveratrol is one of a group of naturally occurring substances called polyphenols. It is found in plants, particularly fruit and nuts. Grapes contain the highest levels (3,540 ng/g), peanuts contain about half as much, and blueberries contain much less. Researchers had noticed that a relatively small proportion of French people have cardiovascular disease, compared to people from other Western countries that eat a similar high fat diet. Resveratrol is particularly abundant in red wine, which is commonly drunk in France. Therefore researchers have tried to discover how resveratrol may improve measures of cardiovascular disease risk.

Expert commentary

Although it would be helpful to identify a substance that would magically improve cardiovascular risk factors, it is difficult to find something that works as effectively as a statin. If resveratrol were to be such a magic bullet, one would expect the red wine drinking countries to have a very significant increment in longevity over other parts of the world where red wine is not the tipple of choice. It is therefore not surprising that giving a resveratrol supplement on its own is not effective. Perhaps the small benefits of the Mediterranean/red wine diet that have been identified come from other elements of the source of resveratrol: i.e. increased HDL due to moderate alcohol consumption, and a lower stress lifestyle.

Professor Tim Reynolds, Consultant Chemical Pathologist, Divisional Medical Director and R&D Lead, Burton Hospitals NHS Foundation Trust