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

Clinical use of cyclooxygenase inhibitors impairs vitamin B-6 metabolism.

Author information

1
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.

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.

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:

ClinicalTrials.gov NCT00944866.

PMID:
24153347
DOI:
10.3945/ajcn.113.064477
[Indexed for MEDLINE]
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