Preface

Chapter 7 **Vitamin D, Its Receptor Gene Polymorphism and**

Chapter 8 **Vitamin D3 and Neurofibromatosis Type 1 161**

**Section 4 Therapeutic Measurements of Vitamin D 179**

Chapter 9 **Pathogenic and Therapeutic Role of Vitamin D in Antiphospholipid Syndrome Patients 181**

Chapter 10 **Therapeutic and Prophylactic Potential of Vitamin D for**

Chapter 11 **Nanoparticles for Delivery of Vitamin D: Challenges and**

Svetlana Jelic, Dejan Nikolic, Dragomir Marisavljević and Ljudmila

Sofia F.G. Zorzella-Pezavento, Larissa L.W. Ishikawa, Thais F.C. Fraga-Silva, Luiza A.N. Mimura and Alexandrina Sartori

Maria J. Ramalho, Manuel A.N. Coelho and Maria C. Pereira

Mehir un Nisa Iqbal and Taseer Ahmed Khan

**Breast Cancer 135**

**VI** Contents

Juichiro Nakayama

Stojanovich

**Multiple Sclerosis 205**

**Opportunities 231**

Vitamin D, a fat-soluble vitamin also known as the "sunshine vitamin," is derived mostly from sun exposure and food. For normal activation, it has to undergo two hydroxylation reactions. Vitamin D affects more than 2000 genes in the body. A serum concentration of 25(OH) D indicates the ideal level of vitamin D in our bodies. The primary function of vita‐ min D is to regulate calcium and phosphorous absorption. Vitamin D deficiency leads to several diseases. From the therapeutic point of view, vitamin D helps in the treatment of many diseases. Lifestyle has an impact on our bodies' systems of getting sufficient amounts of vitamin D. In this context, due to industrialization and also changes in the environmental factors, any further study or work on vitamin D would be helpful for our society. I believe it offers a more than ample opportunity for me to present this book, *A Critical Evaluation of Vitamin D - Clinical Overview*, to the audience.

The book targets the principles, mechanisms and clinical significance of vitamin D. It covers four sections: "Vitamin D in Cardiovascular and Renal Diseases", "Vitamin D in Age and Neu‐ rological Diseases", "Vitamin D and Cancer" and "Therapeutic Measurements of Vitamin D". Each of these sections is interwoven with the theoretical aspects and experimental techniques of basic and clinical sciences. This book will be a significant source to students, scientists, physicians, healthcare professionals and also other members of this society who are interested in exploring the role of vitamin D in human life.

In the first section, the authors have disclosed the association of vitamin D deficiency in the pathogenesis and complications of cardiovascular disease—beneficial effects of vitamin D in renal patients, including end-stage renal patients and kidney transplant recipients and the pleiotropic effects of vitamin D in patients with kidney disease. In the second section, the authors have disclosed the prevalence of vitamin D deficiency and the associated risk factors among the geriatric population and the binding effects of vitamin D to amyloidogenic pepti‐ des in the brain. In the third section, we can notice information on the relationship between the vitamin D levels in the blood and the histological type and grade of colorectal tumors the role of vitamin D and its receptor gene polymorphisms in the development of breast cancer and the topical or systemic application of vitamin D or its analogs to treat skin lesions for patients with neurofibromatosis type 1. In the last section, the authors reviewed the in‐ terrelationship between vitamin D status and the two well-known prothrombotic states, an‐ tiphospholipid syndrome and metabolic syndrome—therapeutic and prophylactic potential of vitamin D and the application of nanosystems for the encapsulation of vitamin D for dif‐ ferent applications, such as food and pharmaceutical industries.

I appreciate the support of our higher authorities. I extend my gratitude toward my late mother and late father and my brothers for introducing me to higher education. I am contin‐ uously indebted to my wife Anitha for her emotional and technical support throughout this project. The smiles of my daughter, Humsiha, encouraged me to finish this task in an easy way. I must acknowledge the interest and commitment from the Publishing Processing Manager of InTech Mr. Edi Lipovic, whose patience and focus were a fantastic support in this project. Finally, I express deep and sincere appreciation to all the authors for their val‐ uable contributions and scholarly cooperation for the timely completion of this book.

> **Dr. Sivakumar Gowder** Qassim University, Saudi Arabia

**Vitamin D in Cardiovascular and Renal Diseases**

uously indebted to my wife Anitha for her emotional and technical support throughout this project. The smiles of my daughter, Humsiha, encouraged me to finish this task in an easy way. I must acknowledge the interest and commitment from the Publishing Processing Manager of InTech Mr. Edi Lipovic, whose patience and focus were a fantastic support in this project. Finally, I express deep and sincere appreciation to all the authors for their val‐

**Dr. Sivakumar Gowder**

Qassim University, Saudi Arabia

uable contributions and scholarly cooperation for the timely completion of this book.

VIII Preface

#### **Vitamin D and Cardiovascular Diseases Vitamin D and Cardiovascular Diseases**

Claudia Lama von Buchwald and Seth I. Sokol Claudia Lama von Buchwald and Seth I. Sokol

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/65080

#### **Abstract**

Vitamin D deficiency is highly prevalent worldwide and has been implicated in the pathogenesis and complications of cardiovascular disease (CVD). Defining this relationship has been challenging, and the clinical application of vitamin D screening and supplementation for CVD risk prevention and modification remain uncertain. The available evidence includes large observational studies and smaller randomized trials mostly evaluating surrogate endpoints and scarcely directed at CV outcomes as a primary endpoint. Methodological heterogeneity is present among most of these trials. Clarification of the clinical application of this relationship through ongoing large randomized trials should have important implications for public health.

**Keywords:** vitamin D deficiency, cardiovascular disease, endothelial function, hyper‐ tension, vitamin D

## **1. Introduction**

Cardiovascular disease (CVD) is the leading cause of death in the developed world and is projectedto be the leading cause ofmorbidity andmortality indeveloping countries by 2020 [1]. In the United States, one in three adults lives with CVD resulting in disability and losses of billionsofdollarseachyear[2].CVDisamultifactorialdiseasethatembodiesacomplexinterplay between genetic predisposition, environmental factors, and risk factors that tend to be more prevalentincertainethnicgroupsandthosewithlowersocioeconomicstatus.Despitesubstantial gains in CVD prevention, a significant amount of risk remains despite adequate control and modification of traditional risk factors. Identification of novel risk factors that are easily modifiable has been eagerly sought over the past decade.

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The discovery of the vitamin D receptor (VDR) in multiple cell types, including cardiomyocytes and vascular cells [3, 4], has led to increasing interest in vitamin D's role in human health, including cardiovascular, beyond its well‐known role in bone health. Deficient vitamin D levels (<20 ng/ml) have been independently linked to increased morbidity and mortality [5–7].

Experimental evidence has linked vitamin D to regulation of multiple pathways involved in the pathogenesis of CVD. Several ecological and epidemiological studies have suggested a relationship between CVD and vitamin D status, as CVD events are higher in the winter, a period when vitamin D levels are lowest [8, 9]. Additionally, certain populations with poor cutaneous production of vitamin D and subsequently lower plasma levels, such as African Americans, tend to be at greater risk for hypertension and cardiovascular disease [3, 8, 10, 11]. These lines of evidence do not prove causality but support a hypothesis for further study.

Randomized controlled trials have mostly been based on surrogate or secondary endpoints for CV risk reduction [12]. Study methodology has been heterogeneous and results are often conflicting. To date, large well‐powered randomized trials of vitamin D featuring CV outcomes as a primary endpoint are still ongoing [13, 14]. In the absence of results from these trials, regular supplementation cannot be recommended for cardiovascular risk modulation. Despite the lack of recommendations, use of vitamin D supplements for this purpose has risen dramatically.

The following chapter will provide an overview on the biologic plausibility and current evidence linking vitamin D to CV health and disease. But first, a brief review of the prevalence and definition of vitamin D deficiency and description of vitamin D synthesis and metabolism is necessary.
