title: Clinical use of cyclooxygenase inhibitors impairs vitamin B-6 metabolism.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Food Science and Biotechnology (H-YC, H-MC, S-TH, H-DC, and E-PIC), the National Chung Hsing University-UCD Plant and Food Biotechnology Program and Agricultural Biotechnology Center (E-PIC), and the Agricultural Biotechnology Center (E-PIC), National Chung Hsing University, Taichung, Taiwan ; the Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung, Taiwan (F-YT); and the Division of Allergy Immunology Rheumatology (D-YC and J-LL) and the Department of Nursing and Pediatrics (H-MC), Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Hsin-Yueh
authors.initials: HY
authors.lastname: Chang
authors.forename: Feng-Yao
authors.initials: FY
authors.lastname: Tang
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Chih
authors.forename: Shih-Ting
authors.initials: ST
authors.lastname: Huang
authors.forename: Hung-Dian
authors.initials: HD
authors.lastname: Cheng
authors.forename: Joung-Liang
authors.initials: JL
authors.lastname: Lan
authors.forename: En-Pei Isabel
authors.initials: EP
authors.lastname: Chiang
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000068579:Celecoxib; D006224:Cricetinae; D003430:Cross-Sectional Studies; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D011732:Pyridoxal Phosphate / Q000097:blood / Q000172:deficiency / Q000378:metabolism; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use; D025101:Vitamin B 6 / Q000378:metabolism*; D026681:Vitamin B 6 Deficiency / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D009288:Naproxen; D011732:Pyridoxal Phosphate; D025101:Vitamin B 6; D000068579:Celecoxib