Effects of Supplemental Calcium and Vitamin D on Circulating Biomarkers of Gut Barrier Function in Colorectal Adenoma Patients: A Randomized Controlled Trial Open Access

Ganesan, Divya (Spring 2019)

Permanent URL: https://etd.library.emory.edu/concern/etds/sj139291t?locale=en%5D
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Abstract

Disruption of epithelial barrier integrity leading to translocation of bacterial components [lipopolysaccharide (LPS) and flagellin] and associated inflammation may promote colorectal carcinogenesis. LPS-binding protein (LBP) and intestinal fatty-acid binding protein (IFABP) are potential markers of exposure to bacterial products due to impaired gut barrier function. Experimental evidence supports vitamin D and calcium as chemopreventive agents that could improve gut barrier function in part due to their anti-inflammatory actions. We conducted a pilot adjunct biomarker study on 118 patients from the Vitamin D/Calcium Polyp Prevention Study randomized to 1,200 mg/day calcium, 1,000 IU/day vitamin D3 or both over 1 year to estimate the effects of vitamin D and calcium supplementation on plasma levels of these two biomarkers. We found no appreciable effects of calcium and/or vitamin D on LBP or IFABP levels over a 12-month treatment period, with a suggestion for a possible 25% reduction in LBP (p=0.04) in the vitamin D group compared to placebo. There was no evidence of synergy between vitamin D and calcium effects on investigated biomarkers. Secondary analyses suggested that reductions in LBP (20%; p=0.09) and IFABP (28%; p=0.02) following vitamin D supplementation could be limited to individuals with low baseline circulating levels of vitamin D (< 22.52 ng/ml). At baseline, women had 60% higher IFABP levels compared to men (p=0.001) and study participants with BMI ≥30 kg/m2 had a 12% higher level of LBP compared to those with BMI <25 kg/m2 (p=0.16). The study findings support further research into the role of vitamin D supplementation on gut barrier function and colorectal carcinogenesis, and continued investigation of potentially modifiable risk factors for colorectal cancer prevention.

Table of Contents

Chapter 1: Introduction                                                                                                        1

         Background and Significance…………………………………………………………...2

Chapter 2: Manuscript                                                                                                          13

Effects of Supplemental Calcium and Vitamin D on Circulating Biomarkers of Gut Barrier Function in Colorectal Adenoma Patients: A Randomized Controlled Trial……………………………………………………………………………………...............14

References……………………………………………………………………………...............29

Tables…………………………………………………………………………………...............33

Supplementary Materials……………………………………………………………...........38

Chapter 3: Conclusions and Future Directions                                                              43

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