A standardized Boswellia serrata extract shows improvements in knee osteoarthritis within five days-a double-blind, randomized, three-arm, parallel-group, multi-center, placebo-controlled trial

Abstract

Background: Boswellin^® Super is a standardized extract of Boswellia serrata Roxb gum resin, standardized to contain 30% 3-acetyl-11-keto-β-boswellic acid along with other β-boswellic acids (BSE). A randomized, double-blind, placebo-controlled clinical trial was conducted at two doses of BSE to understand its safety and efficacy in supporting joint health and improving mobility and symptoms of osteoarthritis (OA) of the knee.

Methods: Based on the inclusion/exclusion criteria, 105 newly diagnosed participants with degenerative hypertrophy OA were recruited and randomized into Placebo, BSE-150 mg or BSE-300 mg (n = 35 in each group) to receive either 150 mg or 300 mg BSE or a placebo tablet twice a day for 90 days. All the participants were evaluated for pain and physical function using the standard tools including the Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne Functional Index (LFI), EuroQol- 5 Dimension (EQ-5D) quality of life, 6-min walk test at day 0, days 5, 30, 60 and 90 of treatment. Additionally, the circulating levels of inflammatory biomarkers, tumor necrosis factor-α (TNFα), high-sensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were evaluated. Safety was evaluated by blood biochemical, hematological analysis, urinary analyses and by monitoring adverse events throughout the study.

Results: Ninety-eight subjects completed the study. Improvements in pain scores were observed as early as 5 days after the start of the supplement in the BSE-150 and BSE-300 groups. By 90 days, the VAS pain score reduced by 45.3% and 61.9%, WOMAC- total score improved by 68.5% and 73.6% in the BSE-150 and BSE-300 groups respectively. WOMAC pain (70.2%, 73.9%, WOMAC stiffness (65.6%,68.9%), WOMAC function (68.8%,74.2%), LFI severity (50%,53.3%), decreased and EQ5D (56.9%, 62.9%) and distance walked in 6 minutes (21.2%, 21.9%) improved in the BSE-150 and BSE-300 groups in 90 days. Further, the levels of TNFα, hs-CRP, and IL-6 were found to decrease in the serum in BSE-supplemented participants. No significant adverse events were recorded during the study.

Conclusion: The study confirms that Boswellin® Super can be used as a safe and effective supplement to support joint health and mobility in the management of osteoarthritis.

Clinical trial registration: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NzU2Nzc=&Enc=&userName=CTRI, identifier CTRI/2022/11/047397.

Keywords: 3-acetyl-11-keto-β-boswellic acid; Boswellia serrata extract; Boswellin Super; WOMAC; lequesne functional index quality of life; osteoarthritis; visual analog scale.

FIGURE 1

Consort Diagram: Consort flow chart showing the enrolment, allocation, follow-up, and analysis of participants.

FIGURE 2

VAS and WOMAC total scores (A): Visual analog scale for pain (VAS), (B): Western Ontario McMaster Index (WOMAC) total scores at different time points day 0, day 30, day 60 and day 90 in placebo, BSE-150 and BSE-300 groups. (Day 105 included for VAS scores). Each point represents Mean ± SEM. The decrease in VAS score was significant (p = 0.002) on day 60 in comparison to day 0 in placebo, and from day 30 to 105 compared to day 0 (p < 0.001) in BSE-150 and BSE-300 compared to day 0.

FIGURE 3

VAS and WOMAC total scores in age and gender specific groups: Visual analog scale for pain (VAS) in (A): Male, (B): Female, (C): Age <55 years, (D): > 55 years, Western Ontario McMaster Index (WOMAC) total scores in (E): Male, (F): Female, (G): Age < 55 years, (H): > 55 years in a gender and age specific analysis, in placebo, BSE-150 and BSE-300 groups. Each point represents Mean ± SEM. Study participants were grouped into two age groups <55 years (40–55 years) and >55 years (56–70 years). The parameters are analyzed in male and female participants and in the two age groups.

FIGURE 4

WOMAC pain, stiffness and difficulty in physical activity scores WOMAC pain, stiffness and difficulty in physical activity scores of placebo, BSE-150 and BSE-300 groups at different time points day 0, day 30, day 60 and day 90. Each bar represents Mean ± SEM. In comparison with Day 0, the mean scores in the treatment groups were tested for significance using Dunnett’s multiple comparisons test. The decrease in WOMAC pain and physical activity scores were significant (p < 0.05) on days 60 and 90 in comparison to day 0 in placebo, and from day 30 to 90 compared to day 0 (p < 0.001) in BSE-150 and BSE-300 compared to day 0. The stiffness improvement was significant only in BSE-150 and BSE-300 from day 30 onwards. The sub scores showed significant (p < 0.05) in BSE-300 on day 5 compared to day 0.

FIGURE 5

LFI pain, severity, and daily activity scores LFI pain, severity and daily activity scores of placebo, BSE-150 and BSE-300 groups at different time points day 0, day 30, day 60 and day 90. Each bar represents Mean ± SEM. In comparison with Day 0, the mean scores in the treatment groups were tested for significance using Dunnett’s multiple comparisons test. The decrease in LFI pain and daily activity and severity scores were significant (p < 0.05) on days 90 in comparison to day 0 in placebo, and from day 30 to 90 compared to day 0 (p < 0.001) in BSE-150 and BSE-300 compared to day 0. The pain and severity improvement was significant (p < 0.05) in BSE-150 on day 5 compared to day 0.

FIGURE 6

Radiological X-ray image. Radiological X-ray images of the knee of participants captured on screening and end of the study. Significant improvements in osteoarthritis was observed in the knee joint. The gap between the knee joints (white arrow) increased significantly in BSE-150 and BSE-300 supplemented participants.