Effects of Supplemental Calcium and Vitamin D on Circulating Biomarkers of Inflammation in Colorectal Adenoma Patients: a Randomized Clinical Trial Open Access

Abstract

Vitamin D and calcium are known to affect several pathways involved in inflammation and immune surveillance relevant to carcinogenesis, and, in observational studies, were shown to be associated with lower risk for colorectal neoplasms. To investigate the effects of vitamin D and calcium, alone and in combination, on circulating biomarkers of inflammation in colorectal adenoma patients, we conducted a pilot biomarker study within a 2x2 factorial, placebo-controlled, double-blind, randomized controlled trial of 1.2 g/d calcium and/or 1000 UI/d vitamin D3 supplementation over 3 or 5 years. Plasma concentrations of pro-inflammatory markers [tumor necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-1β, IL-2, IL-4, IL-8, IL-12p40, IL12p70, IL-17A, interferon-gamma (IFN-γ)] and an anti-inflammatory marker (IL-10) were measured using multiplex electrochemiluminescence assays. After 12 months, in the vitamin D3 supplementation group, compared to the group that received no vitamin D3, IL-2 and IL-10 increased 27% (p = 0.06) and 16% (p = 0.11), respectively, and IL-1β decreased 23% (p = 0.07). In the calcium supplementation group, compared to the group that received no calcium, IL-1β decreased 79% (P = 0.11); and, in the calcium plus vitamin D supplementation group, compared to the calcium group, IL-2 increased 30% (p = 0.13). A combined inflammatory markers z-score decreased by 51% (p = 0.03) in the calcium treatment group overall, and 73% (p = 0.09) among those with higher baseline total calcium, when compared to the group that received no calcium. These results suggest that supplemental vitamin D and calcium may influence colorectal neoplasms development through inflammatory pathways.

Table of Contents

Introduction…….….…………………………………………………………………………….….   1

           Colorectal Cancer…………………………………………………………………….........   1

           Vitamin D, Calcium and Colorectal Carcinogenesis………………....................     1

           Vitamin D, Calcium and Inflammation………………………….…………...........…   3

Methods……………………………………….….……………………………………………………  5

           Study Population and Data Collection……………………………………............…..  5

           Blood Collection………………………………………..……………………………......….  6

           Inflammation Biomarker Assays……………………………………………….............  6

           Statistical Analysis………………………………………..…………………………........   7

Results…………….………………………..…………………………………………………….….   10

Discussion……….………………………..………………………………………………………….  12

References…….………………………..………………………………………………………...….  15

Table 1……………………………………….………………………………………………………….  21

Table 2……………………………………..……………………………………………………..…….  24

Table 3..……………..……………………..……………………………………………………..……  31

Table 4..…………………………………….…………………………………………………………… 32

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology
Keyword	Calcium Inflammation Vitamin D Colorectal Cancer Colorectal Adenoma
Committee Chair / Thesis Advisor	Veronika Fedirko MPH PHD, Emory University

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