UC Davis

Cardiovascular disease (CVD) is the number one cause of death in the U.S. Traditional risk factors include sex, age, genetics, hypertension, dyslipidemia, diabetes mellitus, smoking, physical inactivity, sub-optimal nutrition, and overweight and obesity. In addition to these predictive risk factors, endothelial dysfunction is an early indicator of atherosclerosis. Inflammation is also involved at each step of the atherogenic process and plays a critical role in the progression of CVD. Although CVD is commonly perceived as a disease of adulthood, studies suggest that atherosclerosis begins in childhood or adolescence and culminates over the course of the lifespan. Cardiovascular risk factors, for example obesity and dyslipidemia, often develop in childhood, and are directly associated with the severity of early atherosclerotic lesions in adolescents and young adults. According to the U.S. Dietary Guidelines Advisory Committee, a healthy diet is higher in fruits, vegetables, whole grains, low-fat or nonfat dairy, seafood, legumes, and nuts and lower in red meat, refined grains and added sugars. Diets that adhere to these guidelines are deemed some of the healthiest and are associated with reduced risk of a myriad of chronic diseases. Research suggests that the observed benefits of such diets can largely be attributed to habitual consumption of plant foods or following a plant-based diet. Frequent consumption of both nuts and berries is associated with a decreased risk for the development of cardiovascular disease. Along with protein, fiber and micronutrients, nuts provide essential fatty acids, such as linoleic and alpha-linolenic acids, and bioactive phenolics, including ellagic acid and ellagitannins. Berries are also significant contributors of fiber and micronutrients to the diet, and are similarly rich in phytonutrients, including anthocyanins, flavan-3-ols, flavonols, in addition to ellagic acid and ellagitannin. The aforementioned bioactive phytonutrients may elicit vasculoprotective effects through a variety of mechanisms, mediating the health benefits associated with a diet rich in plants. Therefore, this dissertation focuses on the role of plant-based diets and associated phytonutrients, particularly those present in walnut and strawberry, in promoting vascular health.

Chapter I provides an in-depth discussion of both the fundamental challenges and promising future directions in research with nuts and berries. New understanding of the bioactive compounds found in both nuts and berries has reinforced their role for use in personalized nutrition efforts. Chapters II, III, and IV shift into research on individual foods. Chapter II is a comprehensive review of recent literature on the effects of strawberry intake on human health. Recent advances in research related to the gut microbiome and microbial metabolism have established a new understanding of the phytonutrients in strawberries and the potential mechanisms by which strawberry intake may promote health. Chapter III details a dietary intervention trial in postmenopausal women with overweight or obesity supplementing with 40g/d walnuts for 12-weeks. This work sought to extend previous findings of improved microvascular function in a similar cohort for four weeks but did not yield the same level of improvement. Twelve weeks of 40g/day walnut intake did, however, improve lipid profile, particularly in those with hyperlipidemia at baseline. Pending metabolomic analysis will help elucidate the mechanisms underlying the described physiological changes related to walnut intake, which may be related to circulating and lipoprotein-esterified oxylipins. Chapter IV reviews clinically relevant studies on the effects of freeze-dried strawberry powder (FDSP) on vascular health, with focus on a dietary intervention trial conducted in overweight or obese adolescent males. One week of supplementation with 50 g/d FDSP improved microvascular function only in participants with a ‘responder’ phenotype, or who experienced increases in fasting nitrate levels with FDSP intake. These results emphasize the importance of inter-individual variability and personalized approaches in nutrition. The appendices are representative of a broader body of work pertaining to cardiovascular health within the context of both the lacto-ovo-vegetarian diet and adolescent obesity. Appendix A describes a cross-sectional study evaluating vascular function in individuals following either a vegetarian or omnivorous diet containing red meat. Appendix B discusses adolescent obesity, which has increased dramatically in recent years and is coupled with increased prevalence of chronic cardiometabolic diseases. Unique consequences, such as those related to psychosocial health, and intervention opportunities are also addressed. Finally, concluding remarks and future research directions are presented in Chapter VI.

This dissertation focuses on the role of plant-based diets and associated nutrients and phytonutrients in promoting vascular health. To a significant extent, this work reflects my research interests in health promotion and chronic disease prevention through the bioactivity of phytonutrients. Plant foods provide an array of bioactive metabolites, which regulate a number of physiological processes. A particular emphasis was placed on nuts and berries, specifically, walnuts and strawberries. Work within this dissertation demonstrates the benefits and explores proposed mechanisms of plant foods in vascular health. This work also supports the importance of consideration of interindividual variability and multiomics in the novel but growing field of personalized nutrition. This information can be used to inform personalized nutrition recommendations and promote vascular health over the lifespan.