UC Davis

Cardiovascular disease (CVD) is the leading cause of death worldwide. Menopause represents a key cardiometabolic shift for women. Estrogen loss leads to visceral fat accumulation, dyslipidemia, insulin resistance, and vascular dysfunction, accelerating CVD risk. The aim of this dissertation was to examine how specific Mediterranean dietary components influence cardiometabolic outcomes in postmenopausal women. I integrated clinical, mechanistic, and translational perspectives. Chapter 1 reviews CVD pathophysiology, vascular function, and menopause as a sex-specific CVD risk factor. It details surrogate vascular outcomes, such as flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT), alongside epidemiological and clinical evidence for Mediterranean diet (MedDiet) adherence in CVD prevention. Mechanistic pathways, including oxylipin signaling, flavonoid metabolism, and gut microbiome interactions, are also discussed. Chapters 2 and 3 focus on walnuts as a Mediterranean nut source rich in alpha-linolenic acid (ALA) and ellagitannins. Chapter 2 reports a short-term intervention showing that walnut consumption improved microvascular function and altered oxylipin profiles. Particularly, epoxides support endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation. Chapter 3 demonstrates that walnuts modify lipoprotein composition to suppress tumor necrosis factor (TNF)- α-stimulated cytokine production in diabetic adipocytes. This study suggests that dietary modification may attenuate adipose tissue-driven inflammation. Chapter 4 reports randomized, crossover trials of Oligonol, a flavanol-rich lychee and green tea extract, in postmenopausal women (100-600 mg/day for 2 weeks) and healthy adults (acute 2 g). No significant improvements were observed in any measured outcomes, likely due to factors such as healthy baseline vascular status and lower extract epicatechin content than reported. Chapter 5 integrates observational and clinical findings in a narrative review of Mediterranean style dietary components related to menopausal staging and women-specific cardiometabolic changes. It highlights specific diet-responsive pathways, including oxylipin formation, urolithin production, short-chain fatty acid production, and estrobolome, with emphasis on individual gut microbiome-driven variability. Collectively, the studies in this dissertation demonstrate that Mediterranean dietary components, particularly walnuts, can benefit microvascular function and lipoprotein-associated inflammation, whereas polyphenol extracts show limited short-term vascular effects in low-risk groups. Mediterranean dietary patterns emerge as adaptable strategies for postmenopausal CVD prevention. Future work should prioritize menopause-staged trials with multi-omics to identify responders and refine precision nutrition strategies.