Resveratrol: How Much Wine Do You Have to Drink to Stay Healthy?

Abstract

Resveratrol is a naturally occurring stilbene endowed with multiple health-promoting effects. It is produced by certain plants including several dietary sources such as grapes, apples, raspberries, blueberries, plums, peanuts, and products derived therefrom (e.g., wine). Resveratrol can be isolated and purified from these biological sources or synthesized in a few steps with an overall high yield. This compound and its glucoside, the trans-polydatin piceid, have received worldwide attention for their beneficial effects on cardiovascular, inflammatory, neurodegenerative, metabolic, and age-related diseases. These health-promoting effects are particularly attractive given the prevalence of resveratrol-based nutraceuticals and the paradoxical epidemiologic observation that wine consumption is inversely correlated to the incidence of coronary heart disease. However, the notion of resveratrol as a "magic bullet" was recently challenged by clinical trials showing that this polyphenol does not have a substantial influence on health status and mortality risk. In the present review, we discuss the proposed therapeutic attributes and the mode of molecular actions of resveratrol. We also cover recent pharmacologic efforts to improve the poor bioavailability of resveratrol and influence the transition between body systems in humans. We conclude with some thoughts about future research directions that might be meaningful for resolving controversies surrounding resveratrol.

Keywords: French paradox; SIRT1; human trials; liver; nanotechnology; pharmacology; therapy.

FIGURE 1

Biological sources of resveratrol. (A) Resveratrol was first isolated from the roots of the white hellebore Veratrum album var. grandiflorum (Veratrum grandiflorum). The phenotype of this plant is characterized by strong and leafy stems arranged in inflorescences (left). The 6 petals of that plant are spread, not adherent, and of white or greenish color (right). (B) The highest concentrations of resveratrol are found in the Japanese knotweed Polygonum japonicum (synonym Fallopia japonica, formerly Polygonum cruspdatum). Originally this herbaceous perennial plant was endemic in East Asia (Japan, China, and Korea) and nowadays can be found in Europe classified as one of the worst invasive plant species. It belongs to the genus Fallopia and its stems hold lots of distinct raised nodes (left). The small white or cream flowers are arranged in erect racemes (right). (C) The content of resveratrol in wines originating from different grape varieties is highly variable. Typically, white wines (e.g., those produced from the varieties White Burgunder, Riesling, Ortega, and Gewürztraminer) contain ∼10 times lower resveratrol quantities than wines made from red grapes varieties [such as Cabernet Mitos, Cabernet Cubin, Syrah, Spätburgunder (Pinot noir), Cabernet Sauvignon, and Merlot]. The photos in panels A and B were reproduced from reference with permission. All grape images were taken in Martinsried, Pfalz, Germany. For typical resveratrol concentrations in depicted wines, please refer to Supplemental Table 1.

FIGURE 2

Some of the reported beneficial effects of resveratrol on organ function.

FIGURE 3

Quantities of food and beverages that must be consumed to reach therapeutic doses. Based on animal studies, daily resveratrol doses in the range of hundreds of milligrams to several grams for therapeutic intervention have been proposed. If a person intends to ingest 1 g resveratrol each day, this would require consuming the depicted quantities of foods or beverages. The calculation is based on typical resveratrol contents found in peanuts without seed coats (0.03–0.14 μg/g) (126), red wine (Pinot noir from France, 0.362–1.979 mg/L) (127), white wine (Riesling from Spain, 0.057–0.390 mg/L) (128), rosé wine from Serbia (0.29 mg/L) (129), beer (1.34–77.0 μg/L) (130), skin of tomato (∼19 μg/g dry weight) (131), dark chocolate (350 μg/kg), milk chocolate (100 μg/kg) (132), Itadori tea (68 μg/100 mL, when prepared by infusing 1 g of the commercial root prepared with 100 mL of boiling water for 5 min) (37), red Merlot grapes from Japan (1259 μg/kg fresh weight) (133), white Riesling grapes from Japan (387 μg/kg fresh weight) (133), and cultivated apples (estimating a mean total content of 400 μg/kg fresh weight found in 150 different cultivars) (4).