title: Association between Circulating Vitamin D Metabolites and Fecal Bile Acid Concentrations.
abstract: Although hydrophobic bile acids have been demonstrated to exhibit cytotoxic and carcinogenic effects in the colorectum, ursodeoxycholic acid (UDCA) has been investigated as a potential chemopreventive agent. Vitamin D has been shown to play a role in both bile acid metabolism and in the development of colorectal neoplasia. Using a cross-sectional design, we sought to determine whether baseline circulating concentrations of the vitamin D metabolites 25(OH)D and 1,25(OH)2D were associated with baseline fecal bile acid concentrations in a trial of UDCA for the prevention of colorectal adenoma recurrence. We also prospectively evaluated whether vitamin D metabolite concentrations modified the effect of UDCA on adenoma recurrence. After adjustment for age, sex, BMI, physical activity, and calcium intake, adequate concentrations of 25(OH)D (≥30 ng/mL) were statistically significantly associated with reduced odds for high levels of total [OR, 0.61; 95% confidence interval (CI), 0.38-0.97], and primary (OR, 0.61; 95% CI, 0.38-0.96) bile acids, as well as individually with chenodeoxycholic acid (OR, 0.39; 95% CI, 0.24-0.63) and cholic acid (OR, 0.56; 95% CI, 0.36-0.90). No significant associations were observed for 1,25(OH)2D and high versus low fecal bile acid concentrations. In addition, neither 25(OH)D nor 1,25(OH)2D modified the effect of UDCA on colorectal adenoma recurrence. In conclusion, this is the first study to demonstrate an inverse relationship between circulating levels of 25(OH)D and primary fecal bile acid concentrations. These results support prior data demonstrating that vitamin D plays a key role in bile acid metabolism, and suggest a potential mechanism of action for 25(OH)D in colorectal cancer prevention. Cancer Prev Res; 9(7); 589-97. ©2016 AACR.
authors.affiliation: Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona. University of Arizona Cancer Center, Tucson, Arizona. jacobse@email.arizona.edu.
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Jacobs
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, Arizona.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Haussler
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona.
authors.forename: David S
authors.initials: DS
authors.lastname: Alberts
authors.affiliation: Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona.
authors.forename: Lindsay N
authors.initials: LN
authors.lastname: Kohler
authors.affiliation: Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona.
authors.forename: Peter
authors.initials: P
authors.lastname: Lance
authors.affiliation: Department of Family and Preventive Medicine, University of California San Diego, La Jolla, California.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Martínez
authors.affiliation: Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona. University of Arizona Cancer Center, Tucson, Arizona.
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Roe
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona. Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, Arizona. School of Mathematical and Natural Sciences, Arizona State University, Phoenix, Arizona.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Jurutka
mesh_terms: D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000032:analysis*; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D003430:Cross-Sectional Studies; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use; D014807:Vitamin D / Q000097:blood*
chemical_list: D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D014807:Vitamin D; D014580:Ursodeoxycholic Acid