Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors

J Nutr. 2019 May 1;149(5):770-775. doi: 10.1093/jn/nxz001.

Abstract

Background: A frequent observation in inflammatory conditions, including rheumatoid arthritis (RA), is low circulating amounts of pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B-6. Recently, a functional marker of vitamin B-6 status, the ratio of 3-hydroxykynurenine (HK): xanthurenic acid (XA) in plasma (HK: XA), was proposed.

Objective: We investigated vitamin B-6 status in patients with RA before and after established treatment with TNFα inhibitors.

Methods: We performed a longitudinal study of RA patients (n = 106, 36% men, median age 54 y) starting first treatment with a TNFα inhibitor (infliximab, etanercept, adalimumab, golimumab, or certolizumab). Clinical assessment (Disease Activity Score for 28 standard joints, DAS28), joint ultrasonography, and blood draw were performed at baseline and after 3 mo treatment. Plasma concentrations of PLP, HK, and XA were measured by liquid chromatography-tandem mass spectrometry. Associations of changes in vitamin B-6 markers with change in DAS28 were assessed by generalized additive models regression and with European League Against Rheumatism (EULAR) response categories by linear regression.

Results: At baseline PLP was inversely correlated with CRP (ρ = -0.27, P = 0.007), whereas HK: XA correlated with DAS28 (ρ = 0.46, P < 0.001), CRP (ρ = 0.36, P < 0.001), and ultrasonography scores (ρ = 0.29-0.35, P ≤ 0.003). After 3 mo treatment, the change (a 33% overall reduction) in DAS28 was related to changes in both PLP (ß = -0.28, P = 0.01) and HK: XA (ß = 0.33, P < 0.001). Good responders (45%) according to EULAR criteria experienced a 31% increase in PLP (P = 0.003) and an 11% decrease in HK: XA (P = 0.1), whereas nonresponders (24%) experienced a 25% increase in HK: XA (P = 0.02).

Conclusion: Two independent measures of vitamin B-6 status confirm an association with disease activity in RA patients. The association of HK: XA with disease activity may also imply perturbations in kynurenine metabolism in RA. This trial was registered at helseforskning.etikkom.no as 2011/490.

Keywords: 3-hydroxykynurenine: xanthurenic acid ratio; TNFα inhibitors; functional vitamin B-6 status; pyridoxal 5′-phosphate; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Female
  • Humans
  • Kynurenine / analogs & derivatives
  • Kynurenine / blood
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Nutritional Status*
  • Pyridoxal Phosphate / blood
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / therapeutic use*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / blood
  • Vitamin B 6 / blood*
  • Vitamin B 6 Deficiency / blood
  • Vitamin B 6 Deficiency / complications*
  • Xanthurenates / blood

Substances

  • Biomarkers
  • TNF protein, human
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factor-alpha
  • Xanthurenates
  • 3-hydroxykynurenine
  • Kynurenine
  • xanthurenic acid
  • Pyridoxal Phosphate
  • Vitamin B 6
  • C-Reactive Protein