October 30, 2020
Camille Frances Hanginan, MD
The French Paradox
The French have the Eiffel Tower, a prosperous economy, an unparalleled tourism, and a vastly rich history. Even when you talk about cardiovascular health, the French do not fail to give us a reason to envy them.
Worldwide, the number 1 cause of mortality is ischemic heart disease (IHD), accounting for more than 9 million deaths in 2016.1 The European Heart Network reported in 2017 that an average of 20% of deaths in European countries is due to IHD.2
In the Philippines, this figure is unsurprisingly higher at 38%.3 In France, however, only 6% of deaths is due to IHD. This is despite having a diet rich in dietary cholesterol and saturated fat.4 French scientists noticed this in 1980 and branded it as the “French Paradox”. A great number of research papers were hailed in an attempt to explain this phenomenon.
Much focus was given to alcohol consumption in France, particularly red wine. Red wine is processed from grapes, which contains the antioxidant resveratrol in its skin. Resveratrol was thrust into fame, thanks to the French Paradox, and much has been studied on its cardioprotective effects.
What is Resveratrol?
Resveratrol (RES) is a bioactive compound belonging to polyphenol group and is found in over 70 plant species including grapes and blueberries. Apart from its high antioxidant potential, this compound is also believed to possess antithrombotic, anticarcinogenic, antitumor, and estrogenic properties.5
Several human trials have shown that RES can function as a direct free radical scavenger. In a study by Prior et. al., grape powder was shown to produce an area under the curve for hydrophilic antioxidant property.6 A randomized double-blind trial by Janiques and colleagues showed that grape powder increased glutathione peroxidase activity in non-diabetic hemodialysis patients.7
The cardioprotective properties of RES have also been extensively studied. RES improves the release of nitric oxide and prostacyclin promoting better endothelial function.8 Nitric oxide is a major component of endothelium-derived relaxing factor, a vasodilator substance which protects the endothelial lining of arteries and arterioles from shear stress brought by viscous drag of the blood.9
Prostacyclin, on the other hand, inhibits platelet aggregation and therefore decreased thrombogenesis.10 This antithrombotic effect is further enhanced by the action of RES against thromboxane A2, a prostanoid that promotes platelet aggregation.
Magyar et. al. in 2012 launched a double-blind, placebo-controlled trial to determine the effect of RES on left ventricular diastolic function, endothelial function, LDL level, and hemorheological properties like red blood cell(RBC) deformability and platelet aggregation in patients who had a history of myocardial infarction. Forty patients were enrolled in the study, half of whom received 10mg-resveratrol capsule and the other half placebo for 3 months.
Examinations performed before and after the treatment period were physical examination, blood pressure measurement, clinical chemistry, hemorheological measurements, 12-L electrocardiography, and flow-mediated vasodilatation determination (FMD).
FMD was used to measure endothelial function and is defined as the percentage change in brachial artery diameter at rest and at release of a pneumatic cuff inflated to suprasystolic pressure (250mmHg). The researchers found that administration of resveratrol leads to an improved FMD, increased RBC deformability, increased platelet sensitivity to aspirin, decreased LDL cholesterol, and improved diastolic function.11
The question now lies on how much red wine per day is justifiable, if you want a daily splurge of red wine. It is interesting to note that red wine contains an average of 1.9mg of trans-resveratrol per liter.
The resveratrol supplements used in human studies contain 10-100mg administered once daily to meet the desired affects. The American Heart Society recommends moderation of alcohol to two drinks per day for men and one drink for women.
As we all know, too much alcohol can lead to deleterious effects on the body, especially to the liver. But should we forget about the French, their saturated fat-rich diet and impressive cardiovascular health statistics? C’est la vie, maybe they are just lucky.
Several other factors should be taken into account to explain this “luck”—their dietary patterns (close to Mediterranean diet), culture, and their attitude towards health. If you really want to get the best of resveratrol, however, try going back to the basics and add grapes your grocery list. After all, red wine comes from grape skin.
1. Global Health Estimates 2016: Deaths by Cause, Age, Sex, by Country and by Region, 2000- 2016. Geneva, Switzerland: World Health Organization; 2018.
4. Artaud-Wild SM, Connor SL, Sexton G, Connor WE. Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox. Circulation. 1993 Dec; 88(6):2771-9
5. Salehi B, Mishra AP, Nigam M, et al. Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines. 2018;6(3):91. Published 2018 Sep 9.
6. Prior RL, Gu L, Wu X, Jacob RA, Sotoudeh G, Kader AA, Cook RA. Plasma antioxidant capacity changes following a meal as a measure of the ability of a food to alter in vivo antioxidant status. J Am Coll Nutr. 2007 Apr; 26(2):170-81.
7. Janiques AG, Leal Vde O, Stockler-Pinto MB, Moreira NX, Mafra D. Effects of grape powder supplementation on inflammatory and antioxidant markers in hemodialysis patients: a randomized double-blind study. J Bras Nefrol. 2014 Oct-Dec; 36(4):496-501.
8. O. Rakici, U. Kiziltepe, B. Coskun, S. Aslamaci and F. Akar, Effects of resveratrol on vascular tone and endothelial function of human saphenous vein and internal mammary artery. Int J Cardiol 105 (2005), 209–215.
9. Hall, John E.Guyton, Arthur C.Guyton And Hall Textbook Of Medical Physiology. Philadelphia, PA : Saunders/Elsevier, 2011
10. Harvey, R., Ph. D. Lippincott's Illustrated Reviews: Biochemistry. Philadelphia :Wolters Kluwer Health, 2011
11. Magyar, K., Halmosi, R., Palfi, A., Fehér, G., Czopf, L., Fulop, A., ... Szabados, E. (2012). Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. Clinical Hemorheology and Microcirculation, 50(3), 179-187.
12. tervbo U, Vang O, Bonnesen C. A review of the content of the putative chemopreventive phytoalexin resveratrol in red wine. Food Chemistry. 2007;101:449-457.