Dietary and serum levels of vitamins and minerals in relation to metabolic outcomes in observational and randomized settings

A growing body of evidence suggests that chronic, suboptimal intake and low body stores of essential vitamins and minerals are quite common in the U.S. population and may potentially contribute to underlying metabolic and inflammatory abnormalities, ultimately leading to the clinical expression of type 2 diabetes (T2D), metabolic syndrome, and CVD. Vitamin D and magnesium (Mg), two essential micronutrients, have been inversely associated with the presence of metabolic disease in diverse epidemiologic settings, and there is plausible biological evidence linking inadequate intake and low body stores of these nutrients to risk of metabolic disorders.;This dissertation examines the role of vitamin D and Mg on intermediate metabolic and inflammatory biochemical markers involved in the pathogenesis of complex metabolic disorders. Chapter 1 introduces general background on metabolic disease and summarizes available literature linking Mg and vitamin D to intermediate biochemical markers for these disorders. Chapter 2 examines serum concentrations of vitamin D in relation to metabolic biomarkers, measures of adiposity, and prevalent metabolic syndrome among postmenopausal women enrolled in the Women's Health Initiative Calcium-Vitamin D trial (WHI-CaD). Chapter 3 investigates the association of dietary Mg intake with biomarkers of inflammation and endothelial dysfunction among postmenopausal women enrolled in the WHI Observational Study (WHI-OS). Chapter 4 examines the effects of four weeks of Mg supplementation on metabolic markers and differential gene expression in a randomized crossover trial of overweight and obese individuals at UCLA.;Our main findings indicate that serum 25(OH)D concentrations may be inversely associated with levels of triglycerides, measures of adiposity including BMI, waist circumference, and waist-hip ratio, as well as prevalent metabolic syndrome among women enrolled in the WHI. We also observed that dietary Mg intake was independently and inversely associated with hs-CRP and IL-6, two markers of underlying systemic inflammation known to be associated with T2D risk. Findings from our randomized trial indicate that four weeks of Mg supplementation among overweight and obese individuals may improve insulin and glucose homeostasis as reflected by levels of fasting insulin and C-peptide. We also observed systemic changes in genomic expression in response to Mg supplementation. Overall, this series of observations are consistent with a growing body of literature linking serum vitamin D and dietary Mg to metabolic intermediates and support the need for future, large-scale trials to quantify the potential beneficial effects Mg and vitamin D supplementation on metabolic outcomes and fully evaluate the balance of benefits or risk.