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Effect of combined folic acid, vitamin B(6), and vitamin B(12) on colorectal adenoma.

ABSTRACT: Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma.The Women's Antioxidant and Folic Acid Cardiovascular Study was a randomized, double-blind, placebo-controlled trial of 5442 female health professionals at high risk for cardiovascular disease from April 1998 through July 2005. Participants were randomly assigned to receive a combination pill of folic acid (2.5mg), vitamin B(6) (50mg), and vitamin B(12) (1mg) or placebo. This study included 1470 participants who were followed up for as long as 9.2 years and underwent an endoscopy at any point during follow-up. We estimated relative risks using a generalized linear model with a natural logarithm link function and Poisson distributed errors. All statistical tests were two-sided.The risk of colorectal adenoma was similar among participants receiving treatment (24.3%, 180 of 741 participants) vs placebo (24.0%, 175 of 729 participants) (multivariable adjusted relative risk = 1.00, 95% confidence interval = 0.83 to 1.20). Treatment was not associated with the risk of adenoma when data were analyzed by subsite, size, stage, and the number of adenomas. There was no statistically significant effect modification by alcohol intake, history of cancer or adenoma, or baseline plasma levels or intakes of folate, vitamin B(6), or vitamin B(12).Our results indicate no statistically significant effect of combined folic acid, vitamin B(6), and vitamin B(12) treatment on colorectal adenoma among women at high risk for cardiovascular disease.

SUBMITTER: Song Y

PROVIDER: S-EPMC3611818 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Effect of combined folic acid, vitamin B(6), and vitamin B(12) on colorectal adenoma.

Song Yiqing Y Manson Joann E JE Lee I-Min IM Cook Nancy R NR Paul Ligi L Selhub Jacob J Giovannucci Edward E Zhang Shumin M SM

Journal of the National Cancer Institute 20121012 20

<h4>Background</h4>Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma.<h4>Methods</h4>The Women's Antioxidant and Folic Acid Cardiovascular Study was a randomized, double-blind, placebo-controlled trial of 5442 female health professionals at high risk for cardiovascular disease from April 1998 through July 2005. Particip ...[more]

PMID: 23066166

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Project description:The cholesterol-oxidized metabolite 27-hydroxycholesterol (27-OHC) is synthesized by CYP27A1, which is a key factor in vitamin D and oxysterol metabolism. Both vitamin D and 27-OHC are considered to play important roles in Alzheimer's disease (AD). The study aims to research the effects of co-supplementation of vitamin D, folic acid, and vitamin B12 on learning and memory ability in vitamin D-deficient mice, and to explore the underlying mechanism. In this study, C57BL/6J mice were fed a vitamin D-deficient diet for 13 weeks to establish a vitamin D-deficient mice model. The vitamin D-deficient mice were then orally gavaged with vitamin D (VD), folic acid (FA), and vitamin B12 (VB12) alone or together for eight weeks. Following the gavage, the learning and memory ability of the mice were evaluated by Morris Water Maze and Novel object recognition test. The CYP27A1-related gene and protein expressions in the liver and brain were determined by qRT-PCR. The serum level of 27-OHC was detected by HPLC-MS. Serum levels of 25(OH)D, homocysteine (Hcy), and S-Adenosylmethionine (SAM) were measured by ELISA. After feeding with the vitamin D-deficient diet, the mice performed longer latency to a platform (p < 0.001), lower average speed (p = 0.026) in the Morris Water Maze, a lower time discrimination index (p = 0.009) in Novel object recognition, and performances were reversed after vitamin D, folic acid and vitamin B12 supplementation alone or together (p < 0.05). The gene expressions of CYP27A1 in the liver and brain were upregulated in the vitamin D-deficiency (VDD) group compared with the control (CON) group (p = 0.015), while it was downregulated in VDD + VD and VDD + VD-FA/VB12 groups compared with the VDD group (p < 0.05), with a similar trend in the protein expression of CYP27A1. The serum levels of 27-OHC were higher in the VDD group, compared with CON, VDD + VD, and VDD + VD-FA/VB12 group (p < 0.05), and a similar trend was found in the brain. The serum 25(OH)D levels were significantly decreased in the vitamin D-deficiency group (p = 0.008), and increased in the vitamin D-supplemented group (p < 0.001). The serum levels of SAM were higher in the B vitamins-supplemented group, compared with CON and VDD groups (p < 0.05). This study suggests that CYP27A1 expression may be involved in the mechanism of learning and memory impairment induced by vitamin D deficiency. Co-supplementation with vitamin D, folic acid, and vitamin B12 significantly reverses this effect by affecting the expression of CYP27A1, which in turn regulates the metabolism of 27-OHC, 25(OH)D, and SAM.

Dataset Information

Effect of combined folic acid, vitamin B(6), and vitamin B(12) on colorectal adenoma.

Publications

Effect of combined folic acid, vitamin B(6), and vitamin B(12) on colorectal adenoma.

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