Systemic folate status, rectal mucosal folate concentration and dietary intake in patients at differential risk of bowel cancer (The FAB2 Study).

BACKGROUND/OBJECTIVES: Folate has been strongly implicated in the aetiology of colorectal cancer. However, the relationship between dietary folate intake, rectal mucosal folate status and colorectal cancer risk is uncertain. The study aimed to estimate nutrient intakes and measure systemic folate status and rectal mucosal folate concentration in people at differential risk of developing colorectal cancer. METHODS: Two hundred and twenty-eight individuals were recruited from gastroenterology clinics and subdivided into three patient groups: untreated colorectal cancer (n = 43), adenomatous polyps (n = 90) or normal bowel (n = 95). Biopsies from macroscopically normal rectal mucosa and blood were collected and used for the measurement of rectal mucosal 5-methyltetrahydrofolate (5-MeTHF) and systemic markers of folate status, respectively. Nutrient intake was estimated using a validated food frequency questionnaire. RESULTS: Dietary intake variables, plasma 5-MeTHF and red cell folate and plasma homocysteine concentrations were similar in all three subject groups and 95% CI fell within normal range for each variable. Rectal mucosal 5-MeTHF concentration was higher in the normal mucosa of adenomatous polyp patients than in normal subjects (P = 0.055). Rectal mucosal 5-MeTHF was associated significantly with plasma folate (P < 0.001, r = 0.294), red cell folate (P = 0.014, r = 0.305), plasma homocysteine (P = 0.017, r = -0.163) and dietary folate intake (P = 0.036, r = 0.152). CONCLUSIONS: This study demonstrates adequate folate status of patients attending gastroenterology clinics for the investigation of bowel symptoms, with no significant difference in dietary intakes or systemic folate status indices according to diagnosis. Rectal mucosal 5-MeTHF concentrations were elevated in adenomatous polyp patients, but failed to reach significance. Further studies are required to determine the biological significance of this observation.

Responses of biomarkers of folate and riboflavin status to folate and riboflavin supplementation in healthy and colorectal polyp patients (the FAB2 Study).

Epidemiologic data suggest that increasing folate intake may protect against colorectal cancer. Riboflavin may interact with folate to modulate the effect. A double-blind randomized placebo-controlled intervention study (the FAB2 Study) was carried out in healthy controls and patients with colorectal polyps (adenomatous and hyperplastic) to examine effects of folic acid and riboflavin supplements on biomarkers of nutrient status and on putative biomarkers of colorectal cancer risk (DNA methylation and DNA damage; to be reported elsewhere). Ninety-eight healthy controls and 106 patients with colorectal polyps were stratified for the thermolabile variant of methylene tetrahydrofolate reductase, MTHFR C677T, and were randomized to receive 400 microg of folic acid, 1,200 microg of folic acid, or 400 microg of folic acid plus 5 mg of riboflavin or placebo for 6 to 8 weeks. Blood samples and colon biopsy samples were collected for the measurement of biomarkers of folate and riboflavin status. Supplementation with folic acid elicited a significant increase in mucosal 5-methyl tetrahydrofolate, and a marked increase in RBC and plasma, with a dose-response. Measures of riboflavin status improved in response to riboflavin supplementation. Riboflavin supplement enhanced the response to low-dose folate in people carrying at least one T allele and having polyps. The magnitude of the response in mucosal folate was positively related to the increase in plasma 5-methyl tetrahydrofolate but was not different between the healthy group and polyp patients. Colorectal mucosal folate concentration responds to folic acid supplementation to an extent comparable to that seen in plasma, but with a suggestion of an upper limit.