Folate fortification, plasma folate, homocysteine and colorectal adenoma recurrence

Abstract

In 1996, the US Food and Drug Administration mandated the fortification of grain products with folic acid, a nutrient that has been associated with lower risk of colorectal neoplasia. We assessed the relation of plasma folate and homocysteine and colorectal adenoma recurrence separately in 2 studies: the first involved an intervention of a cereal supplement that contained folic acid, wheat bran fiber (WBF), and the second was conducted primarily during postfortification of the food supply using ursodeoxycholic acid (UDCA). Analyses were stratified for multivitamin use. Results show that plasma folate and homocysteine concentrations were associated with adenoma recurrence among nonusers of multivitamins only. Among nonmultivitamin users, the odds ratio [OR] (95% confidence interval [CI]) for those in the highest versus the lowest folate quartile was 0.65 (0.40-1.06) for the WBF study and 0.56 (0.31-1.02) for the UDCA; likewise, individuals in the highest versus the lowest quartile of homocysteine had higher odds of adenoma recurrence, in both the WBF (OR 5 2.25; 95% CI 5 1.38-3.66) and UDCA (OR 5 1.93; 95% CI 5 1.07-3.49) populations. Analyses comparing multivitamin users to different plasma folate concentrations among nonusers show that odds of recurrence for supplement users was lower only when compared to nonusers who had lower concentrations. Our results show that higher plasma folate or lower homocysteine levels are associated with lower odds of recurrence among nonusers of multivitamins in both studies. Our finding, suggesting that multivitamins or supplemental folate only benefit individuals with lower plasma folate concentrations, should be taken into consideration when designing and interpreting results of intervention studies. ' 2006 Wiley-Liss, Inc.Key words: colorectal adenoma; folate; homocysteine Colorectal cancer is thought to be the result of a multistep evolutionary process that involves a precursor lesion, the adenomatous polyp. Among individuals who undergo removal of their adenoma(s), recurrence of these lesions at surveillance colonoscopy is common, making adenoma recurrence an important endpoint to study in relation to lifestyle and other risk factors.Folate is a water soluble B-vitamin that functions as a coenzyme in single-carbon transfer in nucleic and amino acid metabolism. Folic acid is the fully oxidized monoglutamyl form of folate that is used in supplements and fortified foods. A recent meta analysis showed a significant 20-25% lower risk of developing colorectal cancer among individuals in the highest compared to those in the lowest category of dietary folate 1 ; inverse associations between blood folate and colorectal neoplasia (i.e., cancer and adenoma) have also been shown. [2][3][4] Mechanisms responsible for the inverse association of folate on risk of colorectal cancer are not entirely understood and may involve disturbances in DNA synthesis, methylation and repair, 5-7 albeit alternate mechanisms have been proposed. 8 Homocysteine, a biochemical marker of folate status, is an...

Folic Acid Prevents the Initial Occurrence of Sporadic Colorectal Adenoma in Chinese Older than 50 Years of Age: A Randomized Clinical Trial

“…We believe the effects of a chemopreventive agent, especially one based on a dietary component, may vary depending on the baseline state of sufficiency. Previous results showed that folate supplementation may protect against adenoma or cancer only in those with low baseline folate levels (30). Our data strongly support this theory; therefore, people with low plasma folate should be encouraged to take adequate folate supplements based on the potential perceived risk of CRCs.…”

The Metabolic Syndrome Is Associated with an Increased Risk of Colorectal Polyps Independent of Plasma Homocysteine

“…Hyperhomocysteinemia, a well-known risk factor for cardiovascular diseases, can increase the production of oxygen free radicals through homocysteine oxidation and can diminish the DNA methylation in critical tissues through a simultaneous increase in intracellular S-adenosylhomocysteine and is thus a risk factor for cancer [46,47]. Although some previous studies did not show that high plasma homocysteine was significantly associated with the development of colorectal polyps [48,49], the present study, in agreement with other studies [19,20,21,22], demonstrated that an increased plasma homocysteine concentration was associated with the development of colorectal polyps. …”

“…In the last decade, much attention has also been paid to the relationship between high plasma homocysteine levels and the risk of colorectal polyps [19,20,21,22]. Besides the many known risk factors (i.e.…”

Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas

“…There was a weak inverse association between dietary folate intake and colorectal cancer risk (14), and blood folate levels were inversely associated in some (15)(16)(17)(18), but not all (10,(19)(20)(21)(22)(23)(24) studies. Vitamin B12 status was not associated with colorectal cancer in the majority of the studies (21,(24)(25)(26).…”