Clinical use of cyclooxygenase inhibitors impairs vitamin B-6 metabolism

• Published in: The American journal of clinical nutrition Vol. 98; no. 6; pp. 1440 - 1449
• Main Authors: Chang, Hsin-Yueh, Tang, Feng-Yao, Chen, Der-Yuan, Chih, Hui-Min, Huang, Shih-Ting, Cheng, Hung-Dian, Lan, Joung-Liang, Chiang, En-Pei Isabel
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 01.12.2013; American Society for Nutrition
• Subjects: Animals; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; Biological and medical sciences; cardiovascular diseases; Celecoxib; clinical nutrition; Cricetinae; Cross-Sectional Studies; Cyclooxygenase Inhibitors - adverse effects; Cyclooxygenase Inhibitors - therapeutic use; Drug Monitoring; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; golden hamsters; Humans; inflammation; Kidney - drug effects; Kidney - metabolism; Liver - drug effects; Liver - metabolism; long term effects; Male; Mesocricetus; Mesocricetus auratus; metabolism; Mice; Mice, Inbred C57BL; Middle Aged; Naproxen - adverse effects; Naproxen - therapeutic use; nonsteroidal anti-inflammatory agents; patients; prostaglandin synthase; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyridoxal Phosphate - blood; Pyridoxal Phosphate - deficiency; Pyridoxal Phosphate - metabolism; pyridoxine; rheumatoid arthritis; risk factors; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin B 6 - metabolism; Vitamin B 6 Deficiency - blood; Vitamin B 6 Deficiency - chemically induced; Vitamin B 6 Deficiency - metabolism; Prostaglandin-endoperoxide synthase; Nutrition; Enzyme; Inhibitor; B-Vitamins; Oxidoreductases; Metabolism
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.3945/ajcn.113.064477

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. This trial was registered at clinicaltrials.gov as NCT00944866.