Clinical use of cyclooxygenase inhibitors impairs vitamin B-6 metabolism

Am J Clin Nutr. 2013 Dec;98(6):1440-9. doi: 10.3945/ajcn.113.064477. Epub 2013 Oct 23.


Background: A low circulating vitamin B-6 concentration, which is an independent risk factor for cardiovascular disease, is commonly seen in human inflammation.

Objective: We investigated whether cyclooxygenase inhibitors alter vitamin B-6 metabolism.

Design: To investigate whether subjects taking a cyclooxygenase inhibitor had an altered vitamin B-6 profile, we conducted a cross-sectional study that involved 150 rheumatoid arthritis patients, with and without cyclooxygenase inhibitor treatments. C57BL/6J mice and hyperlipidemic Syrian hamsters received drug regimens that reflected clinical nonsteroidal antiinflammatory drug (NSAID) uses in treating human inflammation. The impact of long-term physiologic use of selective and nonselective cyclooxygenase inhibitors on vitamin B-6 metabolism was systematically investigated in these independent in vivo models.

Results: Patients who were taking cyclooxygenase inhibitors had lower circulating pyridoxal-5'-phosphate, especially those taking NSAIDs >6 mo. Long-term celecoxib and naproxen use reduced hepatic pyridoxal-5'-phosphate in mice. Nonselective cyclooxygenase inhibitor naproxen significantly decreased vitamin B-6 vitamers in the kidney.

Conclusions: To our knowledge, we show novel findings that long-term physiologic doses of cyclooxygenase inhibitor may impede the synthesis of the coenzymatically active form of vitamin B-6. Because the cause of vitamin B-6 depletion in inflammation remains unknown, this study provides a potential mechanism that could account for the poor vitamin B-6 status in human inflammation. Moreover, this study further raises concerns about the long-term clinical use of antiinflammatory NSAIDs in humans. Vitamin B-6 status should be carefully monitored in long-term NSAID users. Future randomized placebo-controlled studies are needed to determine the impacts of antiinflammatory cyclooxygenase inhibitor use on vitamin B-6 metabolism in humans.

Trial registration: NCT00944866.

Publication types

  • Clinical Trial
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Celecoxib
  • Cricetinae
  • Cross-Sectional Studies
  • Cyclooxygenase Inhibitors / adverse effects*
  • Cyclooxygenase Inhibitors / therapeutic use
  • Drug Monitoring
  • Female
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mesocricetus
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Naproxen / adverse effects
  • Naproxen / therapeutic use
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use
  • Pyridoxal Phosphate / blood
  • Pyridoxal Phosphate / deficiency
  • Pyridoxal Phosphate / metabolism
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use
  • Vitamin B 6 / metabolism*
  • Vitamin B 6 Deficiency / blood
  • Vitamin B 6 Deficiency / chemically induced*
  • Vitamin B 6 Deficiency / metabolism


  • Cyclooxygenase Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Naproxen
  • Pyridoxal Phosphate
  • Vitamin B 6
  • Celecoxib

Associated data