title: Menaquinone-7 as a novel pharmacological therapy in the treatment of rheumatoid arthritis: A clinical study.
abstract: Menaquinones (MKs) have been reported to induce apoptosis in rheumatoid arthritis (RA) synovial cells. Recently, menaquinone-4 (MK-4) was proven as a new potential agent for the treatment of RA. However, menaquinone-7 (MK-7) has greater bioavailability and efficacy than MK-4 after oral administration. Yet, the therapeutic benefits of MK-7 in the management of patients with RA have never been addressed. This study was designed to clarify the therapeutic role of MK-7 added to normal therapeutic regimen of RA in patients with different stages of the disease with a clinical follow up through a randomized clinical trial. In a cross sectional study, 84 RA patients (24 male, 60 female) (average age=47.2 years) were enrolled in this study. The patients were divided into MK-7 treated group (n=42) and MK-7 naïve group (n=42). MK-7 capsules were administered in a dose of 100µg/day for three months in the first group without changing in other medications. The clinical and biochemical markers on RA patients treated with MK-7 and naïve group were assessed. In MK-7 treated group, serum concentrations of MK-7 were monitored before and after three months of MK-7 administration. In the cross sectional study, a significant decrease in MK-7 treated group for the levels of undercarboxylated osteocalcin (ucOC), erythrocyte sedimentation rate (ESR), disease activity score assessing 28 joints with ESR (DAS28-ESR), C-reactive protein (CRP) and matrix metalloproteinase (MMP-3) was found. In MK-7 treated group, a marked decrease in RA clinical and biochemical markers for moderate and good response compared to non-responders was observed in ucOC, ESR and DAS28-ESR. A marked increase in the levels of MK-7 for the moderate and good responders compared to non-responders was observed. The results suggest that MK-7 improves disease activity in RA patients. Therefore, MK-7 represents a new promising agent for RA in combination therapy with other disease modifying antirheumatic drugs.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al Madinah AlMunawarah 30001, Saudi Arabia; Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt. Electronic address: mahran44@hotmail.com.
authors.forename: Mahran S
authors.initials: MS
authors.lastname: Abdel-Rahman
authors.affiliation: Department of Rheumatology & Rehabilitation, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Eman A M
authors.initials: EA
authors.lastname: Alkady
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al Madinah AlMunawarah 30001, Saudi Arabia; Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
authors.forename: Sameh
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002214:Capsules; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004534:Egypt; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D024482:Vitamin K 2 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D002214:Capsules; D024482:Vitamin K 2; C062629:menaquinone 7
keywords: DAS28-ESR; Matrix metalloproteinase.; Menaquinone-7; Rheumatoid arthritis; ucOC