A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee

Abstract

Introduction: 5-Loxin is a novel Boswellia serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid (AKBA), which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the efficacy and safety of 5-Loxin in the treatment of osteoarthritis (OA) of the knee.

Methods: Seventy-five OA patients were included in the study. The patients received either 100 mg (n = 25) or 250 mg (n = 25) of 5-Loxin daily or a placebo (n = 25) for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. Additionally, the cartilage degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients. Measurement of a battery of biochemical parameters in serum and haematological parameters, and urine analysis were performed to evaluate the safety of 5-Loxin in OA patients.

Results: Seventy patients completed the study. At the end of the study, both doses of 5-Loxin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA patients. Interestingly, significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-Loxin as early as 7 days after the start of treatment. Corroborating the improvements in pain scores in treatment groups, we also noted significant reduction in synovial fluid matrix metalloproteinase-3. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups.

Conclusion: 5-Loxin reduces pain and improves physical functioning significantly in OA patients; and it is safe for human consumption. 5-Loxin may exert its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators, and it may improve joint health by reducing the enzymatic degradation of cartilage in OA patients.

Trial registration: (

Clinical trial registration number: ISRCTN05212803.).

Figure 1

Flow chart of the patients who participated in the clinical trial. Evaluations of physical activity and pain scores, serum biochemistry, haematology, urine biochemistry and proinflammatory cytokines were done at baseline (day 0) and on days 7, 30, 60 and 90 during follow up. Assessments of matrix metalloproteinase-3 were done on days 0 and 90 only.

Figure 2

Function, pain and stiffness scores. Presented are the mean scores for (a) visual analog scale, (b) Lequesne's Functional Index, (c) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-pain, (d) WOMAC-stiffness, and (e) WOMAC-functional ability in the low-dose (100 mg/day 5-Loxin^®) and high-dose (250 mg/day 5-Loxin^®) groups and placebo group at different time points, as indicated. Each bar represents mean concentration ± standard deviation. In comparison with placebo, the change in scores in the treatment groups was tested for significance using Tukey's multiple comparison test; asterisk indicates statistical significance.

Figure 3

Reduction of Synovial MMP-3 levels. Presented are the matrix metalloproteinase (MMP)-3 levels in synovial fluid collected from 5-Loxin^® treated and placebo patients with osteoarthritis. At day 90 there was no significant change in MMP-3 concentration in the placebo group compared with baseline. In comparison with the placebo group, at the end of the study the groups receiving100 mg/day and 250 mg/day 5-Loxin^® showed 31.37% (P = 0.002) and 46.4% (P < 0.001) reductions in MMP-3 concentration, respectively. Change in MMP-3 concentration between the active treatment groups was not significant (P = 0.213). Each bar represents mean concentration of MMP-3 (ng/ml synovial fluid) ± standard deviation.