Clinical use of cyclooxygenase inhibitors impairs vitamin B-6 metabolism
Hsin-Yueh Chang, Feng-Yao Tang, Der-Yuan Chen, Hui-Min Chih, Shih-Ting Huang, Hung-Dian Cheng, Joung-Liang Lan, En-Pei Isabel Chiang, Hsin-Yueh Chang, Feng-Yao Tang, Der-Yuan Chen, Hui-Min Chih, Shih-Ting Huang, Hung-Dian Cheng, Joung-Liang Lan, En-Pei Isabel Chiang
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.
Source: PubMed