Effects of Vitamin D and Calcium Supplementation on Leukocyte Telomere Length in Colorectal Adenoma Patients: A Randomized Clinical Trial Open Access

Abstract

Abstract

Effects of Vitamin D and Calcium Supplementation on Leukocyte Telomere Length in Colorectal Adenoma Patients: A Randomized Clinical Trial

By Evelyn Wang
Background:

Epidemiologic studies have shown that calcium and vitamin D are associated with decreased risk for colorectal cancer. However, data on this association in the context of leukocyte telomere length is limited. This study investigates the efficacy of a calcium and vitamin D intervention in persons at increased risk for colorectal cancer - leukocyte telomere length is used as a proxy for chemoprevention success. Baseline associations between leukocyte telomere length and patient lifestyle characteristics are also investigated.

Methods:

Blood specimens were collected before and after supplementation with calcium and vitamin D, alone and in combination, in a 6-month, pilot, double-blinded, placebo controlled, randomized clinical trial in 92 patients previously diagnosed with sporadic colorectal adenoma. Real-time qPCR was performed to measure relative leukocyte telomere length, then translated into base-pair length. Fisher's exact test for categorical variables and ANOVA for continuous variables were used to test for differences among treatment groups. Linear mixed effects models were used to estimate the treatment effects for leukocyte telomere length and plasma 25-OH-vitamin D, the best indicator of vitamin D exposure.

Results:

After 6 months of treatment, among 24 participants that had both baseline and follow-up leukocyte telomere length data, 25-OH-vitamin D increased 43%, 75%, and 3% in the calcium, vitamin D3, and calcium plus vitamin D3 groups relative to the placebo group, respectively. Relative to the placebo group, mean telomere length decreased by 16%, 18%, and 10% in the calcium, vitamin D, and calcium plus vitamin D groups, respectively. Analysis of 46-baseline participants and 37 follow-up participants that had at least one telomere length measurement revealed numbers consistent with the 24 participants (except for the calcium plus vitamin D3 group, in which telomere length increased). Several lifestyle and dietary factors for colorectal cancer were associated with baseline leukocyte telomere length in the hypothesized direction.

Conclusion:

Our preliminary results suggest that calcium and vitamin D, individually or together, may not have an effect on leukocyte telomere length after 6 months of treatment.

Key Words: Leukocyte Telomere Length, Vitamin D, Calcium, Colorectal Neoplasms, Randomized Clinical Trial

Table of Contents

Table of Contents BACKGROUND.....................................................................................1 METHODS............................................................................................7

STUDY DESIGN......................................................................................7

SAMPLE SIZE.........................................................................................7

LABORATORY TEST..................................................................................9

STATISTICAL ANALYSIS...........................................................................11

RESULTS.............................................................................................12

STUDY PARTICIPANTS.............................................................................12

PLASMA VITAMIN D AND TELOMERE LENGTH...............................................13

ASSOCIATION BETWEEN TELOMERE LENGTH AND TREATMENT GROUP.............14

ASSOCIATIONS BETWEEN LIFESTYLE FACTORS AND TELOMERE LENGTH...........16

DISCUSSION.......................................................................................17 FUTURE DIRECTIONS...........................................................................19 REFERENCES.......................................................................................20 TABLES...............................................................................................25 FIGURES.............................................................................................30 APPENDIX..........................................................................................32

About this Master's Thesis

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• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Nutrition Biology, General Health Sciences, Epidemiology
Keyword	Nutrition Intervention Calcium Randomized Clinical Trial Colorectal adenoma Vitamin D Telomere length
Committee Chair / Thesis Advisor	Fedirko, Veronika, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs

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