More vitamin D makes for better health – dissertation based on Rotterdam studies – Oct 2015

Vitamin D and cardio-metabolic health in the elderly, The Rotterdam study

Dissertation by Anna Vitezova, which includes many of her publications

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Chapter 1 of this thesis introduces the reader to the background of the main topic – vitamin D, its metabolism and physiological effects. Since its discovery vitamin D has been recognized as an important factor in calcium homeostasis and bone metabolism. Recently, there has been extensive research performed on possible extra-skeletal effects of vitamin D. Nowadays vitamin D deficiency has been linked to a higher risk of many prevalent diseases such as cardio-vascular disease or type 2 diabetes mellitus. Based on this new research it is considered that improving vitamin D status may be a cost-effective tool to improve public health. The main objective of this thesis was to investigate the association of vitamin D and cardio-metabolic health.

Chapter 2 presents a systematic review and meta-analysis of observational studies and randomised controlled trials (RCTs) on vitamin D and the risk of mortality. The objective was to evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality under various circumstances. With this meta-analysis we found that the evidence from observational studies shows inverse associations of circulating 25-hydroxyvitamin D with risks of vascular, cancer and nonvascular-noncancer deaths. Further we found that supplementation with vitamin D3 reduces overall mortality among older adults significantly; however, further investigations are required to establish the optimal dose and duration, and whether vitamin D3 affects mortality risk differently than vitamin D2.

In chapter 3 we investigated the associations between vitamin D and metabolic outcomes. More specifically, in chapter 3.1 we focused on possible association between vitamin D status and prevalence of metabolic syndrome in the elderly since the findings on this topic in the elderly are inconsistent. The aim was to evaluate the association between vitamin D status and the metabolic syndrome in the elderly, as well as between vitamin D status and the components of metabolic syndrome (i.e. serum glucose, triglycerides (TG), HDL cholesterol (HDL-C), waist circumference (WC), and blood pressure (BP)). We found higher 25-hydroxyvitamin D concentrations in the elderly to be associated with a lower prevalence of metabolic syndrome and, in particular, with more beneficial HDL-C, TG, WC and serum glucose. Further in this chapter (3.2) we examined the association between vitamin D and body composition in the elderly. We found lower serum 25-hydroxyvitamin D concentrations to be associated with a higher fat mass Vitamin D and Cardio-metabolic Health in the Elderly percentage. We also demonstrated that the association between serum 25-hydroxyvitamin D and differential fat distribution in the elderly was mainly explained by BMI, which deserves further study.

The focus of chapter 4 was on the association of vitamin D and cardiovascular health. Here we investigated the possible association between vitamin D status and the incidence of atrial fibrillation in the elderly. We found vitamin D status not to be associated with atrial fibrillation in any of the 3 multivariate models tested and concluded that this prospective cohort study did not support the hypothesis that vitamin D status is associated with atrial fibrillation.

Chapter 5 introduces new ideas in the vitamin D research. Firstly, we have investigated the possible interaction between serum magnesium levels and vitamin D in relation to incidence of type 2 diabetes mellitus (5.1). We found that the association between 25-hydroxyvitamin D and type 2 diabetes mellitus may depend on adequate serum magnesium levels. These results imply that it may be important in clinical practice to assess serum 25-hydroxyvitamin D and magnesium levels simultaneously to identify people at risk of type 2 diabetes mellitus. In the second part of chapter 5 (5.2), we explored the association between vitamin D and serum lipids. Higher levels of vitamin D have been associated with lower rates of cardiovascular disease perhaps through improved lipid profiles. However, results reported were inconsistent and the direction of the association between vitamin D and lipid levels remained unknown. For that reason the aim of this chapter was to assess the potential bidirectional associations between 25-hydroxyvitamin D and blood lipids using path analyses in cross-lagged models a novel approach in analyzing this kind of data. Our results from path analyses on repeatedly measured 25-hydroxyvitamin D and lipid levels suggest that total cholesterol might be related with a decrease in 25-hydroxyvitamin D concentrations, but not the other way around, whereas the observed inverse association between HDL cholesterol and 25-hydroxyvitamin D may be bidirectional.

Chapter 6 discusses the main findings of this thesis as well as methodological issues arising from the design of our study, public health implications of our findings and future directions in vitamin D research. Repletion of vitamin D status might be considered as a cost-effective public health measure in prevention of certain conditions and improving some aspects of overall human health. However, to prove the causality of the association of vitamin D Vitamin D and Cardio-metabolic Health in the Elderly and different diseases with the certainty, properly designed randomized controlled trials are needed.