One-carbon metabolites, B vitamins and associations with systemic inflammation and angiogenesis biomarkers among colorectal cancer patients: results from the ColoCare Study

Rama Kiblawi, Andreana N. Holowatyj, Biljana Gigic, Stefanie Brezina, Anne J. M. R. Geijsen, Jennifer Ose, Tengda Lin, Sheetal Hardikar, Caroline Himbert, Christy A. Warby, Juergen Boehm, Martijn J. L. Bourse, Fraenzel J. B. van Duijnhoven, Tanja Gumpenberger, Dieuwertje E. Kok, Janna L. Koole, Eline H. van Roekel, Petra Schrotz-King, Arve Ulvikl, Andrea GsurNina Habermann, Matty P. Weijenberg, Per Magne Ueland, Martin Schneiders, Alexis Ulrich, Cornelia M. Ulrich*, Mary Playdon*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r -0·33, Plinear < 0·0001), serum amyloid A (SAA) (r -0·23, Plinear = 0·003), IL-6 (r -0·39, Plinear < 0·0001), IL-8 (r -0·20, Plinear = 0·02) and TNFα (r -0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r -0·14), SAA (r -0·14) and TNFα (r -0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.

Original languageEnglish
Article numberPII S0007114520000422
Pages (from-to)1187-1200
Number of pages14
JournalBritish Journal of Nutrition
Issue number10
Publication statusPublished - 28 May 2020


  • One-carbon metabolism
  • B vitamins
  • Folate
  • Vitamin B-6
  • Inflammation
  • Colorectal cancer
  • Angiogenesis
  • RISK


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