Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2005 May;54(5):648-53.
doi: 10.1136/gut.2004.054718.

Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma

M Pufulete  1 , R Al-Ghnaniem, A Khushal, P Appleby, N Harris, S Gout, P W Emery, T A B Sanders
Affiliations
Clinical Trial

Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma

M Pufulete et al. Gut. 2005 May.

Abstract

Background and aims: A low dietary folate intake can cause genomic DNA hypomethylation and may increase the risk of colorectal neoplasia. The hypothesis that folic acid supplementation increases DNA methylation in leucocytes and colorectal mucosa was tested in 31 patients with histologically confirmed colorectal adenoma using a randomised, double blind, placebo controlled, parallel design.

Methods: Subjects were randomised to receive either 400 microg/day folic acid supplement (n = 15) or placebo (n = 16) for 10 weeks. Genomic DNA methylation, serum and erythrocyte folate, and plasma homocysteine concentrations were measured at baseline and post intervention.

Results: Folic acid supplementation increased serum and erythrocyte folate concentrations by 81% (95% confidence interval (CI) 57-104%; p<0.001 v placebo) and 57% (95% CI 40-74%; p<0.001 v placebo), respectively, and decreased plasma homocysteine concentration by 12% (95% CI 4-20%; p = 0.01 v placebo). Folic acid supplementation resulted in increases in DNA methylation of 31% (95% CI 16-47%; p = 0.05 v placebo) in leucocytes and 25% (95% CI 11-39%; p = 0.09 v placebo) in colonic mucosa.

Conclusions: These results suggest that DNA hypomethylation can be reversed by physiological intakes of folic acid.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Trial profile.
See this image and copyright information in PMC

Comment in

References

    1. Giovannucci E, Stampfer MJ, Colditz GA, et al. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst 1993;85:875–84. - PubMed
    1. Giovannucci E, Rimm EB, Ascherio A, et al. Alcohol, low-methionine-low folate diets, and risk of colon cancer in men. J Natl Cancer Inst 1995;87:265–73. - PubMed
    1. Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Intern Med 1998;129:517–24. - PubMed
    1. Bird CL, Swendseid ME, Witte JS, et al. Red cell and plasma folate, folate consumption, and the risk of colorectal adenomatous polyps. Cancer Epidemiol Biomarkers Prev 1995;4:709–14. - PubMed
    1. Kato I, Dnistrian AM, Schwartz M, et al. Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study. Br J Cancer 1999;79:1917–22. - PMC - PubMed

Publication types

MeSH terms