Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma.
OBJECTIVE
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.
Pufulete
M
M
Nitritional Sciences Research Division, Department of Nutrition and Dietetics, King's College London, Franklin Wilkins Building, 150 Stamford St, London SE1 9NH, UK. maria.pufulete@kcl.ac.uk
Al-Ghnaniem
R
R
Khushal
A
A
Appleby
P
P
Harris
N
N
Gout
S
S
Emery
P W
PW
Sanders
T A B
TA
D000236:Adenoma / Q000235:genetics*; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000235:genetics; D019587:Dietary Supplements; D004311:Double-Blind Method; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000494:pharmacology*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012007:Rectum / Q000187:drug effects / Q000378:metabolism
D004273:DNA, Neoplasm; D006710:Homocysteine; D005492:Folic Acid