Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms

Abstract

This brief review, based on an invited presentation at the 17th Workshop on Vitamin D, is to summarize a line of the author’s research that has been directed at the intertwined missions of clarifying and/or developing vitamin D and calcium and as preventive agents against colorectal cancer in humans, understanding the mechanisms by which these agents may reduce risk for the disease, and developing ‘treatable’ biomarkers of risk for colorectal cancer. The biological plausibility and observational and clinical trial evidence for vitamin D and calcium in reducing risk for colorectal neoplasms, the development of pre-neoplastic biomarkers of risk for colorectal neoplasms, and the clinical trial findings from the author’s research group on the efficacy of vitamin D and calcium in modulating these biomarkers are summarized. Regarding the latter, we tested the efficacy of 800 IU (20 µg) of vitamin D3 and 2.0g of calcium daily, alone and combined vs. placebo over 6 months on modulating normal colon tissue and circulating hypothesis-based biomarkers of risk for colorectal neoplasms in a randomized, double-blind, placebo-controlled, 2×2 factorial design clinical trial (n = 92). The tissue-based biomarkers were measured in biopsies of normal-appearing rectal mucosa using immunohistochemistry with quantitative image analysis, and a panel of circulating inflammation markers was measured using enzyme-linked immunoassays (ELISA). Statistically significant proportional tissue increases in the vitamin D group relative to the placebo group were found in bax (51%), p21 (141%), APC (48%), E-cadherin (78%), MSH2 (179%), the CaSR (39%), and CYP27B1 (159%). In blood, there was a 77% statistically significant decrease in a summary inflammation z-score. The findings for calcium were similar to those for vitamin D. These findings indicate that supplemental vitamin D3 or calcium can favorably modulate multiple normal colon tissue and circulating hypothesis-based biomarkers of risk for colorectal neoplasms in sporadic colorectal adenoma patients.

Effects of supplemental calcium and vitamin D on tight‐junction proteins and mucin‐12 expression in the normal rectal mucosa of colorectal adenoma patients

“…[33][34][35][36] In our previous pilot studies, vitamin D or calcium supplementation alone, but not in combination, had the strongest observed effects on CRC risk biomarkers in the normal colorectal mucosa. 37 As vitamin D promotes calcium absorption in the intestine, 38 Our estimated calcium supplementation effects on CLDN1 and OCLD expression are consistent with findings from at least one previous cancer cell-culture study in which incubation of Caco-2 epithelial cells in a calcium-free solution rapidly decreased transepithelial resistance and increased paracellular permeability, indicating decreased TJ tightness. These effects were reversed by replenishing extracellular calcium.…”

“…A synergistic effect of these two exposures was seen in two large cohort studies however, not in several smaller observational studies . In our previous pilot studies, vitamin D or calcium supplementation alone, but not in combination, had the strongest observed effects on CRC risk biomarkers in the normal colorectal mucosa . As vitamin D promotes calcium absorption in the intestine, it is possible that it decreases luminal calcium concentrations in the colorectum.…”

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

“…Vitamin D has been found to have antitumour effects, suggesting that it might inhibit the progression of rectal cancer 10 , breast cancer 11 , pancreatic cancer 12,13 , head and neck cancers 14 and other cancers. Urashima 15 suggested that the higher the serum level of vitamin D is, the better is the prognosis of rectal cancer patients.…”

Differentiation of human colon tissue in culture: Effects of calcium on trans-epithelial electrical resistance and tissue cohesive properties

“…The findings presented here may help explain how an adequate daily intake of calcium contributes to health, despite there being little change in colonic histological features over a widerange of calcium intake amounts [57][58][59][60]. While having an adequate daily intake of calcium is important to health, most individuals are calcium deficient.…”