Colorectal adenomas in a randomized folate trial: the role of baseline dietary and circulating folate levels.
The Aspirin/Folate Polyp Prevention Study is a randomized, placebo-controlled trial of aspirin use and folic acid supplementation and incidence of colorectal adenomas in individuals with a history of these lesions. The trial showed that folic acid supplementation does not prevent the occurrence of new adenomas and may increase risk. We extend these results by investigating whether the effect of folic acid treatment differed by baseline dietary and circulating folate levels. Diet and supplement use were ascertained at baseline through a food-frequency questionnaire; a blood sample was used to determine plasma and RBC folate levels. Individuals were followed for 3 years (first follow-up) and subsequently for an additional 3 to 5 years (second follow up). We used generalized linear regression to estimate risk ratios and 95% confidence limits as measures of association. There was little evidence that baseline dietary and total folate intake, and plasma and RBC folate modified the association between folic acid treatment and risk of any adenomas or advanced lesions. However, there was a protective association of the highest tertile of dietary and total intake as well as circulating folate with risk of any adenomas among those in the placebo group but no association among individuals in the folic acid group. Our findings support the idea that although moderate doses of folate may be protective compared with deficiency, at some point of sufficiency, supplementation provides no additional benefit.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. janefigu@usc.edu
Jane C
JC
Figueiredo
A Joan
AJ
Levine
Maria V
MV
Grau
Elizabeth L
EL
Barry
Per M
PM
Ueland
Dennis J
DJ
Ahnen
Tim
T
Byers
Robert S
RS
Bresalier
Robert W
RW
Summers
John
J
Bond
Gail E
GE
McKeown-Eyssen
Robert S
RS
Sandler
Robert W
RW
Haile
John A
JA
Baron
D000236:Adenoma / Q000453:epidemiology / Q000517:prevention & control*; D001241:Aspirin / Q000008:administration & dosage; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D016001:Confidence Intervals; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood*; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016012:Poisson Distribution; D012307:Risk Factors; D011795:Surveys and Questionnaires
D010919:Placebos; D005492:Folic Acid; D001241:Aspirin