Higher vitamin B6 status is associated with improved survival among patients with stage I–III colorectal cancer

Andreana N. Holowatyj, Jennifer Ose, Biljana Gigic, Tengda Lin, Arve Ulvik, Anne J.M.R. Geijsen, Stefanie Brezina, Rama Kiblawi, Eline H. van Roekel, Andreas Baierl, Jürgen Böhm, Martijn J.L. Bours, Hermann Brenner, Stéphanie O. Breukink, Jenny Chang-Claude, Johannes H.W. de Wilt, William M. Grady, Thomas Grünberger, Tanja Gumpenberger, Esther HerpelMichael Hoffmeister, Eric T.P. Keulen, Dieuwertje E. Kok, Janna L. Koole, Katharina Kosma, Ewout A. Kouwenhoven, Gry Kvalheim, Christopher I. Li, Peter Schirmacher, Petra Schrotz-King, Marie C. Singer, Fränzel J.B. van Duijnhoven, Henk K. van Halteren, Kathy Vickers, Jeroen Vogelaar, Christy A. Warby, Evertine Wesselink, Per M. Ueland, Alexis B. Ulrich, Martin Schneider, Nina Habermann, Ellen Kampman, Matty P. Weijenberg, Andrea Gsur, Cornelia M. Ulrich*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


Background: Folate-mediated 1-carbon metabolism requires several nutrients, including vitamin B6. Circulating biomarker concentrations indicating high vitamin B6 status are associated with a reduced risk of colorectal cancer (CRC). However, little is known about the effect of B6 status in relation to clinical outcomes in CRC patients. Objectives: We investigated survival outcomes in relation to vitamin B6 status in prospectively followed CRC patients. Methods: A total of 2031 patients with stage I–III CRC participated in 6 prospective patient cohorts in the international FOCUS (folate-dependent 1-carbon metabolism in colorectal cancer recurrence and survival) Consortium. Preoperative blood samples were used to measure vitamin B6 status by the direct marker pyridoxal 5'-phosphate (PLP), as well as the functional marker HK-ratio (HKr)[3'hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3'-hydroxy anthranilic acid + anthranilic acid)]. Using Cox proportional hazards regression, we examined associations of vitamin B6 status with overall survival (OS), disease-free survival (DFS), and risk of recurrence, adjusted for patient age, sex, circulating creatinine concentrations, tumor site, stage, and cohort. Results: After a median follow-up of 3.2 y for OS, higher preoperative vitamin B6 status as assessed by PLP and the functional marker HKr was associated with 16–32% higher all-cause and disease-free survival, although there was no significant association with disease recurrence (doubling in PLP concentration: HROS, 0.68; 95% CI: 0.59, 0.79; HRDFS, 0.84; 95% CI: 0.75, 0.94; HRRecurrence, 0.96; 95% CI: 0.84, 1.09; HKr: HROS, 2.04; 95% CI: 1.67, 2.49; HRDFS, 1.56; 95% CI: 1.31, 1.85; HRRecurrence, 1.21; 95% CI: 0.96,1. 52). The association of PLP with improved OS was consistent across colorectal tumor site (right-sided colon: HROS, 0.75; 95% CI: 0.59, 0.96; left-sided colon: HROS, 0.71; 95% CI: 0.55, 0.92; rectosigmoid junction and rectum: HROS, 0.61; 95% CI: 0.47, 0.78). Conclusion: Higher preoperative vitamin B6 status is associated with improved OS among stage I–III CRC patients. Am J Clin Nutr 2022;116:303–313.

Original languageEnglish
Pages (from-to)303-313
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Issue number2
Publication statusPublished - 1 Aug 2022


  • colon cancer
  • colorectal cancer
  • HKr
  • one-carbon metabolism
  • PAR
  • PLP
  • rectal cancer
  • recurrence
  • survivorship
  • vitamin B6


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