Bioavailability of Vitamin D and Impact of Supplementation on Clinical and Inflammatory Outcomes in Cystic Fibrosis Open Access

Grossmann, Ruth Elizabeth (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/vq27zp35j?locale=en
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Abstract

Cystic fibrosis (CF) is the most common, heritable disease that significantly shortens life expectancy among Caucasians in the United States. Morbidity and mortality in CF is primarily related to respiratory failure, the result of chronic pulmonary infection and inflammation.

Vitamin D insufficiency may affect up to 90% of individuals with CF and may be related to the high prevalence of fat malabsorption in CF. Vitamin D insufficiency has been associated with an increased risk for low bone mineral density, diabetes, respiratory infection, reduced lung function and inflammation; as well as, mortality. Therefore, repletion of vitamin D may impact the primary causes of morbidity and mortality in CF and should be evaluated.

The study of the clinical impact of vitamin D supplementation in CF has been complicated by the identification of a reliable vitamin D repletion strategy. We conducted a systematic review to determine whether the vehicle of the supplement impacted bioavailability both in CF and non-CF populations. We concluded that vehicle substance does not appear to have an impact on supplement bioavailability in non-CF subjects, and there was inadequate research to determine whether vehicle substance impacts supplement bioavailability in CF subjects.

In a pilot study of vitamin D supplementation in CF, we randomized adults with CF, hospitalized for a pulmonary exacerbation, to either a high-dose, oral bolus of vitamin D in a non-lipid vehicle or placebo. Subjects were followed for up to 1-year and were evaluated for changes in vitamin D status, vitamin D toxicity, and clinical outcomes. We found a significant increase in vitamin D status; as well as, improved clinical outcomes in the vitamin D group compared to placebo without signs vitamin D toxicity. We also evaluated changes in markers of inflammation and the antimicrobial peptide, LL-37 for 12-weeks after randomization. We found a significant decrease in systemic concentrations of TNF-α and a trend for decreased IL-6 concentrations in the vitamin D group compared to placebo.

We have also shown that vitamin D supplementation in a non-lipid vehicle may improve clinical outcomes and markers of inflammation in CF.

Table of Contents

CHAPTER 1: INTRODUCTION................................................................................... 1
CHAPTER 2: LITERATURE REVIEW ........................................................................... 6
VITAMIN D ........................................................................................................... 6
Vitamin D: History, structure and metabolism ........................................................ 6
History of discovery ............................................................................................... 6
Structure, synthesis and forms ................................................................................. 7
Bioavailability of vitamin D ....................................................................................... 8
Metabolism of vitamin D .......................................................................................... 9
Genomic and non-genomic actions ........................................................................... 11
Genomic actions of vitamin D .................................................................................. 11
Non-genomic actions of vitamin D ............................................................................ 12
Functions of Vitamin D ........................................................................................... 12
Calcium metabolism ............................................................................................... 12
Hormone secretion ................................................................................................ 13
Proliferation and differentiation ................................................................................ 14
Immune function ................................................................................................... 14
Evaluating and correction vitamin D status ............................................................ 17
Definition of vitamin D status and vitamin D intake ....................................................... 17
Evaluation of vitamin D status ................................................................................. 19
Prevalence of vitamin D deficiency and insufficiency ................................................... 20
Causes of vitamin D deficiency and insufficiency.......................................................... 21
Dietary sources .................................................................................................... 23
Vitamin D repletion ................................................................................................ 23
Vitamin D and health outcomes ........................................................................... 24
Health outcomes related to vitamin D nutriture .......................................................... 24
Health disparities associated with vitamin D .............................................................. 25
CYSTIC FIBROSIS .............................................................................................. 26
Etiology of cystic fibrosis ................................................................................... 26
Pulmonary pathophysiology in CF ........................................................................... 27
Gastrointestinal pathophysiology in CF .................................................................... 30
Vitamin D in Cystic Fibrosis ................................................................................ 31
Prevalence and causes of vitamin D Insufficiency ...................................................... 31
Vitamin D status and clinical outcomes .................................................................... 32
Vitamin D repletion ............................................................................................... 35
CHAPTER 3: EVALUATION OF VEHICLE SUBSTANCES ON VITAMIN D
BIOAVAILABILITY: A SYSTEMATIC REVIEW ........................................................... 37

Introduction to chapter 4 ................................................................................... 38

CHAPTER 4: PILOT STUDY OF VITAMIN D SUPPLEMENTATION IN

ADULTS WITH CYSTIC FIBROSIS PULMONARY EXACERBATION: A RANDOMIZED,

CONTROLLED TRIAL ............................................................................................ 40
Introduction to chapter 5 ................................................................................... 41
CHAPTER 5: Impact of vitamin D supplementation on markers of inflammation in

adults with CYSTIC FIBROSIS hospitalized FOR a pulmonary exacerbation ..............43
ABSTRACT ......................................................................................................... 44
INTRODUCTION .................................................................................................. 45
METHODS .......................................................................................................... 45
Study design ...................................................................................................... 45
Analytical Methods .............................................................................................. 46
Statistical analysis .............................................................................................. 46
RESULTS ........................................................................................................... 47
DISCUSSION ..................................................................................................... 48

Tables .............................................................................................................. 50
Figures ............................................................................................................. 51
CHAPTER 6: CONCLUSIONS ................................................................................ 53
Key Findings ..................................................................................................... 53
Implications for vitamin D repletion in the CF population ............................................ 54
Implications for the evaluation of vitamin D supplementation in CF ............................... 56
Implications for the evaluation of systemic inflammation in CF..................................... 59
Implications for public health ................................................................................ 62
Implications for future research ............................................................................. 63
SUMMARY ........................................................................................................ 66
REFERENCES .................................................................................................... 68

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