Biomarkers of one-carbon metabolism are associated with biomarkers of inflammation in women

J Nutr. 2014 May;144(5):714-21. doi: 10.3945/jn.113.183970. Epub 2014 Mar 19.


Folate-mediated one-carbon metabolism is essential for DNA synthesis, repair, and methylation. Perturbations in one-carbon metabolism have been implicated in increased risk of some cancers and may also affect inflammatory processes. We investigated these interrelated pathways to understand their relation. The objective was to explore associations between inflammation and biomarkers of nutritional status and one-carbon metabolism. In a cross-sectional study in 1976 women selected from the Women's Health Initiative Observational Study, plasma vitamin B-6 [pyridoxal-5'-phosphate (PLP)], plasma vitamin B-12, plasma folate, and RBC folate were measured as nutritional biomarkers; serum C-reactive protein (CRP) and serum amyloid A (SAA) were measured as biomarkers of inflammation; and homocysteine and cysteine were measured as integrated biomarkers of one-carbon metabolism. Student's t, chi-square, and Spearman rank correlations, along with multiple linear regressions, were used to explore relations between biomarkers; additionally, we tested stratification by folic acid fortification period and multivitamin use. With the use of univariate analysis, plasma PLP was the only nutritional biomarker that was modestly significantly correlated with serum CRP and SAA (ρ = -0.22 and -0.12, respectively; P < 0.0001). Homocysteine (μmol/L) showed significant inverse correlations with all nutritional biomarkers (ranging from ρ = -0.30 to ρ = -0.46; all P < 0.0001). With the use of multiple linear regression, plasma PLP, RBC folate, homocysteine, and cysteine were identified as independent predictors of CRP; and PLP, vitamin B-12, RBC folate, and homocysteine were identified as predictors of SAA. When stratified by folic acid fortification period, nutrition-homocysteine correlations were generally weaker in the postfortification period, whereas associations between plasma PLP and serum CRP increased. Biomarkers of inflammation are associated with PLP, RBC folate, and homocysteine in women. The connection between the pathways needs to be further investigated and causality established. The trial is registered at as NCT00000611.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Carbon / immunology*
  • Carbon / metabolism*
  • Chronic Disease
  • Cross-Sectional Studies
  • Cysteine / blood
  • Erythrocytes / immunology
  • Erythrocytes / metabolism
  • Female
  • Folic Acid / immunology
  • Folic Acid / metabolism
  • Homocysteine / metabolism
  • Humans
  • Inflammation / epidemiology*
  • Inflammation / metabolism*
  • Linear Models
  • Middle Aged
  • Nutritional Status / immunology*
  • Risk Factors
  • Serum Amyloid A Protein / metabolism
  • Vitamin B 12 / blood
  • Vitamin B 6 / blood


  • Biomarkers
  • Serum Amyloid A Protein
  • Homocysteine
  • Carbon
  • Vitamin B 6
  • C-Reactive Protein
  • Folic Acid
  • Cysteine
  • Vitamin B 12

Associated data