Folic acid and prevention of colorectal adenomas: A combined analysis of randomized clinical trials

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
International Journal of Cancer (Impact Factor: 5.09). 07/2011; 129(1):192-203. DOI: 10.1002/ijc.25872
Source: PubMed


Observational data suggest that lower folate status is associated with an increased risk of colorectal neoplasia, implying that folate may be useful as a chemopreventive agent. We conducted a combined analysis of three large randomized trials of folic acid supplementation for the prevention of metachronous adenomas in patients with an adenoma history. Participants included 2,632 men and women who had a history of adenomas randomized to either 0.5 or 1.0 mg/day of folic acid or placebo and who had a follow-up endoscopy 6 to 42 months after randomization [mean = 30.6 (standard deviation = 8.1) months]. We used random-effects meta-analysis to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The RR comparing folic acid versus placebo was 0.98 (95% CI = 0.82-1.17) for all adenomas and 1.06 (95% CI = 0.81-1.39) for advanced lesions. Folic acid was associated with a nonsignificant decreased risk of any adenoma among subjects in the lowest quartile of baseline plasma folate (≤ 11 nmol/L) and no effect among individuals in the highest quartile (> 29 nmol/L, p for trend = 0.17). There was a nonsignificant trend of decreasing risk of any adenoma associated with folic acid supplements with increasing alcohol intake. During the early follow-up reported here, more deaths occurred in the placebo group than in the folic acid group (1.7% vs. 0.5%, p = 0.002). In conclusion, after up to 3.5 years of folic acid use, there is no clear decrease or increase in the occurrence of new adenomas in patients with a history of adenoma.

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Available from: Jane C Figueiredo, Sep 26, 2014
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    • "[21], [22] Dietary supplement use and colorectal adenoma risk have been extensively investigated in the general population. No convincing evidence for an association between multivitamin supplement use, [23] folic acid supplement use, [24] and antioxidant supplement use and adenoma occurrence was found, [25], [26] whereas calcium supplement use might contribute to a lower risk of colorectal adenomas. [27] MMR gene mutation carriers might have a higher use of dietary supplements compared to the general Dutch population based on their health status and risk. "
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    ABSTRACT: Individuals with Lynch syndrome have a high lifetime risk of developing colorectal tumors. In this prospective cohort study of individuals with Lynch syndrome, we examined associations between use of dietary supplements and occurrence of colorectal adenomas. Using data of 470 individuals with Lynch syndrome in a prospective cohort study, associations between dietary supplement use and colorectal adenoma risk were evaluated by calculating hazard ratios (HR) and 95% confidence intervals (CI) using cox regression models adjusted for age, sex, and number of colonoscopies during person time. Robust sandwich covariance estimation was used to account for dependency within families. Of the 470 mismatch repair gene mutation carriers, 122 (26.0%) developed a colorectal adenoma during an overall median person time of 39.1 months. 40% of the study population used a dietary supplement. Use of any dietary supplement was not statistically significantly associated with colorectal adenoma risk (HR = 1.18; 95%CI 0.80-1.73). Multivitamin supplement use (HR = 1.15; 95%CI 0.72-1.84), vitamin C supplement use (HR = 1.57; 95%CI 0.93-2.63), calcium supplement use (HR = 0.69; 95%CI 0.25-1.92), and supplements containing fish oil (HR = 1.60; 95%CI 0.79-3.23) were also not associated with occurrence of colorectal adenomas. This prospective cohort study does not show inverse associations between dietary supplement use and occurrence of colorectal adenomas among individuals with Lynch syndrome. Further research is warranted to determine whether or not dietary supplement use is associated to colorectal adenoma and colorectal cancer risk in MMR gene mutation carriers.
    Full-text · Article · Jun 2013 · PLoS ONE
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    • "This is thought to occur in folate replete populations when an unnaturally high folate status accelerates cell proliferation in early cancers. However, supplementation with folic acid and other B vitamins in folate deficient populations and populations where there is a high incidence of the gene for slow folate metabolism (MTHFR C677T) may decrease the risk of these cancers (Le Marchand et al., 2002; Figueiredo et al., 2011). "

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