Purple grape juice and coronary artery disease

Summarized by Robert W. Griffith, MD
October 12, 1999 (Reviewed: January 21, 2005)

Introduction

We have referred elsewhere in these pages to what is known as the answer to the French Paradox - i.e. the rate of coronary heart disease mortality in France is lower than in other countries because of the frequent consumption of red wine. The mechanisms postulated for this have been alcohol-related increases in high-density lipoprotein cholesterol (HDL) and platelet inhibition. , it is not known for sure whether the alcoholic content or flavonoids in the wine confer the advantage. Dietary flavonoids have been associated with a reduced risk of coronary artery disease events.¹

Purple grape juice, a source of flavonoids, has been shown to inhibit platelet aggregation and LDL oxidation in vitro. ² The study summarized here provides evidence linking ingestion of purple grape juice (PGJ) and improvement in endothelial dysfunction and delayed oxidization of LDL in patients with coronary artery disease (CAD).

Method

Fifteen subjects (12 male, 3 female) with coronary artery disease demonstrated by angiography were enrolled. After baseline tests they were required to drink approximately four mL/kg of purple grape juice twice daily for 14 days (this was about 21 ounces for an 80 kg subject).

The brachial artery, in which endothelial function is closely related to endothelial function in the coronary arteries, was examined by ultrasound. After inflation of a blood pressure cuff 50 mm Hg above the systolic pressure for 4.5 minutes, followed by deflation, brachial artery diameter and forearm blood flow scans was measured over a period of one minute. This allowed estimation of the flow-mediated vasodilation (FMD) -- the ratio of the brachial artery diameter after reactive hyperemia to the baseline diameter, expressed as a percent change. A second stimulus to hyperemia, sublingual nitroglycerin, was given 15 minute later, and the same readings made, yielding an estimated nitroglycerin-mediated vasodilation value (NTGMD). Changes in blood flow were expressed as percentages of the resting blood flow.

Full serum lipid analyses were obtained after a 12-hour fast at baseline and two hours after the Day-14 morning PGJ ingestion. LDL particles were isolated by ultracentrifuge and their susceptibility to oxidation determined by addition of freshly prepared copper chloride solution, the rate of conjugated diene formation being monitored. The lag time for formation, expressed in minutes, was measured between adding the copper chloride and reaching the maximum conjugated diene production.

Results

The average age of the subjects was 62.5 years. Ten had a history of hypertension or were on antihypertensive drugs, 11 were dyslipidemic with 10 of these receiving lipid-lowering agents, and all 12 were taking antioxidants (either vitamin E or vitamin C, or both).

Heart rate, resting brachial artery diameter, hyperemic flow at rest and flow after nitroglycerin at rest were unchanged after 14 days of PGJ. The FMD was 2.2% at baseline compared with 6.4% after PGJ (p=0.003). The NTGMD increased from 9.4% at baseline to 12.1% after PGJ (p=0.044).

Stepwise regression analyses were done, showing that intake of antioxidants and baseline LDL levels were positively correlated with the change in FMD, while the use of lipid-lowering drugs was negatively correlated. However, the change in FMD after ingestion of grape juice remained significant after adjusting for these variables (p<0.001). No parameters influenced the change in NTGMD to a relevant extent.

At baseline, the LDL lag time for conjugated diene formation was 87 minutes, which increased to 117 minutes after two weeks of PGJ (p=0.015). Changes in lag time correlated only weakly with changes in FMD (r=0.155).

Comment

This study is the first in vivo demonstration of improved endothelial function after ingestion of purple grape juice. Endothelial dysfunction, which is critical in the causation of coronary artery disease, is probably initiated and perpetuated by oxidized LDL. In these patients there was significant endothelial dysfunction at baseline, which improved with PGJ. The improvement did not correlate well with a decrease in LDL susceptibility to oxidation. It is possible that part of the improvement in FMD might be mediated by lessened platelet aggregation, which has been demonstrated in vitro (or rather ex vivo) after PGJ.² In all events, PGJ clearly has beneficial effects on pathological changes in endothelium function and LDL activity that are likely to result in a reduction of coronary artery disease events. People wishing to have the health advantages of red wine but wanting to avoid the pleasures of alcohol now have a sound alternative.

Source

• Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. JH. Stein, JG. Keevil, DA Wiebe, Circulation, 1999, vol. 100, pp. 1050--1055

Footnotes
1. Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries Studies. MGL. Hertog, D. Kromhout, C. Aravanis, et al. , Arch Int Med, 1995, vol. 155, pp. 381--386
2. Flavonoid intake and coronary mortality in Finland. P. Knekt, R. Jarvinen, A. Reunanen, J. Maatcla, Brit med J, 1996, vol. 312, pp. 478--481

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