Effects of Supplemental Vitamin D and Calcium on Biomarkers of Inflammation in Colorectal Adenoma Patients: A Randomized, Controlled Clinical Trial

Vitamin D and calcium affect several pathways involved in inflammation, tumor growth, and immune surveillance relevant to carcinogenesis. Also, epidemiologic evidence indicates that calcium and vitamin D may reduce risk for developing colorectal adenomas and cancer. To investigate the effects of calcium and vitamin D on biomarkers of inflammation in colorectal adenoma patients, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial (n = 92) of 2 g/d calcium and/or 800 IU/d vitamin D-3 supplementation versus placebo over 6 months. Plasma concentrations of proinflammatory markers [C-reactive protein (CRP), TNF-alpha, interleukin (IL)-6, IL-1 beta, and IL-8] and an anti-inflammatory marker (IL-10) were measured using ELISAs. After 6 months of treatment, in the vitamin D-3 supplementation group, CRP decreased 32% overall (P = 0.11), 37% in men (P = 0.05), and 41% among non-nonsteroidal anti-inflammatory drug (NSAID) users (P = 0.05) relative to placebo. In the vitamin D-3 supplementation group, TNF-alpha decreased 13%, IL-6 32%, IL-1 beta 50%, and IL-8 15%; in the calcium supplementation group, IL-6 decreased 37%, IL-8 11%, and IL-1 beta 27%. Although these changes were not statistically significant, a combined inflammatory markers z-score decreased 77% (P = 0.003) in the vitamin D-3 treatment group overall, 83% (P = 0.01) among men, and 48% among non-NSAID users (P 0.01). There was no evidence of synergy between vitamin D-3 and calcium or effects on IL-10. These preliminary results are consistent with a pattern of reduction in tumor-promoting inflammation biomarkers with vitamin D-3 or calcium supplementation alone and support further investigation of vitamin D-3 as a chemopreventive agent against inflammation and colorectal neoplasms. Cancer Prev Res; 4(10); 1645-54. (C)2011 AACR.