Today we’re going to be taking a look at what many consider to be resveratrol’s first claim to fame: the French paradox. The French paradox is the observation that despite eating a lot of saturated fat, the French people have relatively low rates of cardiovascular disease. Resveratrol, a phytonutrient found in red wine, may be part of the reason why.

History

The phrase “French paradox” is largely attributed to the French scientist Serge Renaud. In 1992, he published a paper titled “Wine, alcohol, platelets, and the French paradox for coronary heart disease,” in which he hypothesized that red wine may help to prevent atherosclerosis. Since Renaud’s findings, a large body of evidence relating resveratrol to an improved cardiovascular profile has been published.

Physiological mechanisms

To really understand how resveratrol works in the body, we need to start with a little chemistry. Resveratrol belongs to a class of compounds called stilbenoids, which are produced in nature by plants and bacteria. Synthetic versions can also be created in the lab. When we ingest it, it is quickly broken down to metabolites that our bodies use in different ways. Humans and other mammals break down resveratrol differently; the predominant metabolite that remains in the body of rats is not the same as the one found in people. This is why it’s extremely important to be careful when extrapolating animal findings to humans.

As resveratrol is known as an antioxidant, a lot of the biochemical research that has been done has looked at its relationship to free radicals. Free radicals are atoms or molecules with unpaired electrons in their outer shells, and are thought to be very important to heart disease because they can damage the structure of the cell. When studying heart disease, we’re particularly concerned with the effects that free radicals have on our blood vessels. The chemical structure of resveratrol (specifically its aromatic rings) allows it to serve as an antioxidant to counteract the actions of free radicals. As Renaud proposed, it could prevent platelets from building up in blood vessels by lowering cholesterol. It may also prevent the buildup of collagen and other fibers around the heart that reduce the strength of its contractions.

Large-scale human studies

A lot of the human data related to resveratrol and cardiovascular health comes from cohort studies, which look at the relationship between a variable (i.e. how much red wine someone drinks) and the risk of developing a certain condition over time. The data have largely shown that light to moderate consumption of alcoholic beverages, defined by the Dietary Guidelines for Americans as up to 1 drink a day for women and 2 for men, can reduce the risk of death from cardiovascular disease. Heavy drinking can negatively impact many organs and systems and is associated with increased all-cause mortality. It’s important to step back and point out here that many of these studies have looked at alcohol in general rather than focusing specifically on red wine. Since spirits and white wine contain little to no resveratrol, this raises the question of how alcohol may be protective independent of resveratrol. Studies that have been done with dealcoholized red wine, grape juice, and resveratrol in pure form have shown that they have positive effects on heart health indicators, which tells us that resveratrol is biologically important. We’ll be focusing specifically on resveratrol’s impact in the body in this review, but it’s important to consider all potential variables when interpreting the research.

Lifestyle influences

When speaking of variables, it’s also necessary to consider lifestyle. People who drink a moderate amount of red wine may also buy healthier food, exercise more, or have a higher socioeconomic status than those who don’t, all of which have been independently associated with a lower risk of heart disease. Any of these factors may be what is known in epidemiology as confounding variables, variables that are associated with both the independent variable (red wine) and the outcome of interest (heart disease). For example, people who drink red wine may also eat more fruits and vegetables. Increased fruit and vegetable intake is related to a lower risk of heart disease independent of red wine intake.

Conclusions

Is the French paradox valid, and is resveratrol responsible? It’s hard to say. The research has definitively shown that resveratrol can have a positive influence on risk factors for heart disease such as high blood pressure, cholesterol, and oxidative damage to tissues from free radicals. However, we need to keep in mind that most of the clinical research has been done with animals, and metabolism of nutrients varies between species. Research has also shown that humans are unlikely to get a significant amount of resveratrol from diet alone. The French may love their wine, but they probably aren’t drinking close to the 450 glasses (translating to approximately 450 mg of resveratrol) a day that has been determined to be the average dose needed to have a clinically significant effect. When considering the findings in the context of human health, we must also consider lifestyle factors such as diet and exercise patterns. French portion sizes tend to be smaller than those of many other Western cultures, which could also play a role in some of their improved health outcomes. Red wine consumed in moderation does seem to positively impact health, but we will need more research (particularly human clinical trials) to see exactly how much credit we can give resveratrol.

References

Bertelli, Alberto AA, and Dipak K. Das. “Grapes, wines, resveratrol, and heart health.” Journal of cardiovascular pharmacology 54.6 (2009): 468-476.

Biagi, Marco, and Alberto AE Bertelli. “Wine, alcohol and pills: What future for the French paradox?.” Life sciences 131 (2015): 19-22.

Catalgol, Betul, et al. “Resveratrol: French paradox revisited.” Frontiers in pharmacology 3 (2012): 141.

Havranek, Edward P., et al. “Social determinants of risk and outcomes for cardiovascular disease a scientific statement from the American Heart Association.” Circulation 132.9 (2015): 873-898.

Lippi, Giuseppe, et al. “Moderate red wine consumption and cardiovascular disease risk: beyond the “French paradox”.” Seminars in thrombosis and hemostasis. Vol. 31. No. 01. © Thieme Medical Publishers, 2010.

Movva, Rajesh, and Vincent M. Figueredo. “Alcohol and the heart: to abstain or not to abstain?” International journal of cardiology 164.3 (2013): 267-276.

Renaud, S. de, and Michel de Lorgeril. “Wine, alcohol, platelets, and the French paradox for coronary heart disease.” The Lancet 339.8808 (1992): 1523-1526.

Smoliga, James M., Joseph A. Baur, and Heather A. Hausenblas. “Resveratrol and health–a comprehensive review of human clinical trials.” Molecular nutrition & food research 55.8 (2011): 1129-1141.

U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015 – 2020 Dietary Guidelines for Americans. 8th Edition, Washington, DC; 2015.

Red Wine and Cardiovascular Disease: Lessons from the French Paradox
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