Antagonistic effects of aspirin and folic acid on inflammation markers and subsequent risk of recurrent colorectal adenomas.
The Aspirin/Folate Polyp Prevention Trial found that aspirin, but not folic acid, reduced recurrence of colorectal adenomas. This study examined whether treatment effects on inflammation markers explained the trial results. The trial had a factorial design with three aspirin (placebo, 81, and 325 mg/d) and two folic acid (placebo and 1 mg/d) groups. There were 884 subjects who had colonoscopic evaluation for adenomas at year 3 and plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNF-R2), and IL-1 receptor antagonist (IL-1Ra) measured at baseline and year 3. Among individuals not receiving folic acid, there was a 4% decrease (mean ratio of year 3 to baseline levels = 0.96, 95% confidence interval [CI] = 0.82 to 1.14) in CRP for a period of 3 years in the 325 mg of aspirin group vs a 20% increase (mean ratio = 1.20, 95% CI = 1.03 to 1.41) in the placebo group (P = .027). By contrast, the reverse was observed among individuals who also received folic acid (P(interaction) = .013). Changes in inflammation markers were not associated with adenoma recurrence. Low-dose aspirin (325 mg/d) is beneficial in stabilizing CRP levels, which may be abrogated by folate. Nevertheless, inflammation markers do not mediate the chemopreventive effect of aspirin on colorectal adenomas.
Ho
Gloria Y F
GY
Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. gloria.ho@einstein.yu.edu
Xue
Xiaonan
X
Cushman
Mary
M
McKeown-Eyssen
Gail
G
Sandler
Robert S
RS
Ahnen
Dennis J
DJ
Barry
Elizabeth L
EL
Saibil
Fred
F
Bresalier
Robert S
RS
Rohan
Thomas E
TE
Baron
John A
JA
D000236:Adenoma / Q000517:prevention & control*; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000517:prevention & control; D004334:Drug Administration Schedule; D004336:Drug Antagonism; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D005492:Folic Acid; D001241:Aspirin