Title

Cardioprotective effects of grape polyphenols on the post-menopausal state

Date of Completion

January 2005

Keywords

Health Sciences, Nutrition

Degree

Ph.D.

Abstract

The French Paradox is an unusual biological phenomenon because a diet high in saturated fats is associated with low coronary heart disease (CHD) occurrences. The regular intake of red wine has been accepted as the link between low CHD incidences and this paradox. Although alcohol has been documented to be cardioprotective, it is the grape polyphenols that drive the French Paradox. Polyphenols are well known inhibitors of low density lipoprotein oxidation (LDL-ox) a promoter of atherosclerosis. However, recent studies indicate that polyphenols may alter lipoprotein metabolism. ^ It is well accepted that post-menopausal women have an increased CHD risk due to increased triglycerides (TG), low density lipoprotein (LDL), and apolipoprotein (apo) B concentrations. Due to their elevated risk, post-menopausal women are an excellent model for studying the effects of grape polyphenols. The purpose of this dissertation was to investigate the effects of grape polyphenols on lipoprotein metabolism in ovariectomized guinea pigs and post-menopausal women. ^ Study 1 evaluated lyophilized grape preparation (LGP) effects on plasma lipids, lipoprotein metabolism, and atherosclerotic development in ovariectomized guinea pigs. Guinea pigs were fed either control (n = 11) or LGP diet (n = 10) for 12 wk. LGP treatment significantly decreased TG and VLDL-C concentrations. Cholesteryl ester (CE) concentrations and ACAT activity were also significantly decreased due to LGP. Furthermore, modifications in hepatic cholesterol metabolism altered LDL composition, thereby decreasing atherosclerotic development. ^ Due to the previous results, Study 2 evaluated LGP effects on plasma lipids, lipoprotein metabolism, LDL oxidation, whole body oxidative stress and inflammation in pre- and post-menopausal women. Pre- (n = 24) and post-menopausal (n = 20) women consumed the LGP or control for 4 wks followed by a washout period after which they consumed the alternate treatment for 4 wks. Similar to previous results, LGP significantly decreased TG and LDL-C in pre- and post-menopausal women. Lipoprotein metabolism was further altered with decreases in apo B, apo E and CETP activity. Although there was no change in ox-LDL, LGP significantly decreased oxidative stress and inflammation in pre- and post-menopausal women. ^ Through these modifications of lipoprotein metabolism, inflammation, and oxidative stress in the post-menopausal state, grape polyphenols may be considered cardioprotective. ^