Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation

Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):2136-45. doi: 10.1158/1055-9965.EPI-07-2895.


Background: Folate, other vitamin B cofactors, and genes involved in folate-mediated one-carbon metabolism all may play important roles in colorectal neoplasia. In this study, we examined the associations between dietary and circulating plasma levels of vitamins B(2), B(6), and B(12) and risk colorectal adenomas.

Methods: The Aspirin/Folate Polyp Prevention Study is a randomized clinical trial of folic acid supplementation and incidence of new colorectal adenomas in individuals with a history of adenomas (n = 1,084). Diet and supplement use were ascertained through a food frequency questionnaire administered at baseline. Blood collected at baseline was used to determine plasma B-vitamin levels. We used generalized linear regression to estimate risk ratios (RR) and 95% confidence intervals (95% CI) as measures of association.

Results: We found a borderline significant inverse association with plasma B(6) [pyridoxal 5'-phosphate (PLP)] and adenoma risk (adjusted RR Q4 versus Q1, 0.78; 95% CI, 0.61-1.00; P(trend) = 0.08). This association was not modified by folic acid supplementation or plasma folate. However, the protective association of PLP with adenoma risk was observed only among subjects who did not drink alcohol (P(interaction) = 0.03). Plasma B(2) (riboflavin) was inversely associated with risk of advanced lesions (adjusted RR Q4 versus Q1, 0.51; 95% CI, 0.26-0.99; P(trend) = 0.12). No significant associations were observed between adenoma risk and plasma vitamin B(12) or dietary intake of vitamin B(2) and B(6). When we examined specific gene-B-vitamin interactions, we observed a possible interaction between methylenetetrahydrofolate reductase -C677T and plasma B(2) on risk of all adenomas.

Conclusion: Our results suggest that high levels of PLP and B(2) may protect against colorectal adenomas.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / epidemiology
  • Adenoma / genetics
  • Adenoma / prevention & control*
  • Alcohol Drinking / adverse effects
  • Aspirin / therapeutic use*
  • Chemoprevention
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / prevention & control*
  • Double-Blind Method
  • Female
  • Folic Acid / blood
  • Folic Acid / therapeutic use*
  • Genotype
  • Humans
  • Incidence
  • Linear Models
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Middle Aged
  • Neoplasm Recurrence, Local / prevention & control
  • Poisson Distribution
  • Polymorphism, Genetic
  • Riboflavin / blood
  • Risk
  • Surveys and Questionnaires
  • Vitamin B 12 / blood
  • Vitamin B 6 / blood


  • Vitamin B 6
  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Vitamin B 12
  • Aspirin
  • Riboflavin