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

Br J Nutr. 2020 May 28;123(10):1187-1200. doi: 10.1017/S0007114520000422. Epub 2020 Feb 5.


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.

Keywords: Angiogenesis; B vitamins; Colorectal cancer; Folate; Inflammation; One-carbon metabolism; Vitamin B6.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloid / blood
  • Biomarkers, Tumor / blood
  • C-Reactive Protein / metabolism
  • Carbon / blood*
  • Colorectal Neoplasms / blood*
  • Cross-Sectional Studies
  • Female
  • Folic Acid / metabolism
  • Glutamates / blood
  • Humans
  • Inflammation
  • Inflammation Mediators / blood*
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Intestines / blood supply
  • Linear Models
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / blood*
  • Phosphoric Monoester Hydrolases / blood
  • Prospective Studies
  • Statistics, Nonparametric
  • Tetrahydrofolates / blood
  • Tumor Necrosis Factor-alpha / blood
  • Vitamin B Complex / blood*
  • Young Adult


  • Amyloid
  • Biomarkers, Tumor
  • Glutamates
  • Inflammation Mediators
  • Interleukin-6
  • Interleukin-8
  • Tetrahydrofolates
  • Tumor Necrosis Factor-alpha
  • Vitamin B Complex
  • Carbon
  • C-Reactive Protein
  • Folic Acid
  • 4-aminobenzoylglutamic acid
  • pyridoxal-5-phosphatase
  • Phosphoric Monoester Hydrolases
  • 5-methyltetrahydrofolate