Singhal S, Hasan N, Nirmal K, et al. Bioavailable turmeric extract for knee osteoarthritis: A randomized, non-inferiority trial versus paracetamol. Trials. January 30, 2021;22(1):105. doi: 10.1186/s13063-021-05053-7.
Osteoarthritis (OA), a progressive, degenerative disease affecting articular joints, is characterized by the breakdown of cartilage, joint lining, ligaments, and bone. Hips, knees, hands, and spine are most often affected; pain and stiffness are common effects. Knee OA, the leading cause of pain and disability in adults and elders, affects 10-15% of people aged ≥ 60 years. There is no cure or effective treatment to halt or reverse OA progression. Many conventional drugs pose risks of gastrointestinal, renal, and/or cardiovascular adverse effects (AEs). Dietary supplements (DS) are among alternative approaches to managing OA.
The most important DS studied for OA are the curcuminoids (curcumin [CU], demethoxycurcumin, and bisdemethoxycurcumin) from turmeric (TM; Curcuma longa, Zingiberaceae) rhizomes. With long use in traditional and alternative medicine, TM is also a valued medicinal food. Thought to suppress pro-inflammatory signaling as well as pro-inflammatory cytokines and mediators of their release, CU has anti-inflammatory, antithrombotic, antioxidant, and antimicrobial effects. Highly lipophilic and poorly bioavailable, attempts to improve oral bioavailability of CU have included combining it with piperine (from numerous peppers [Piper spp., Piperaceae]). Piperine increases CU's bioavailability but boosts absorption of other drugs and/or DS and decreases liver metabolism.
A standardized TM extract (BCM-95®; Arjuna Natural Pvt Ltd.; Kerala, India), marketed in a hard gelatin capsule (Curcugreen®; Arjuna), contains curcuminoids and TM essential oil (TMEO) with sesquiterpene turmerones, BCM-95 is reported to have strong anti-inflammatory effects. Bioavailability of a curcuminoid-TMEO complex was ~ 6.93 times greater than CU alone. Previous clinical and preclinical trials support use of the complex in OA.
The authors conducted a randomized, prospective, non-inferiority, intention-to-treat trial of BCM-95 vs. acetaminophen (ACM) at the Department of Orthopedics, Lok Nayak Jai Prakash Hospital (Maulana Azad Medical College; New Delhi, India). Patients included, presumably recruited sequentially (the process is not described, nor are study dates stated), were diagnosed with knee OA by ACR criteria and were 40-80 years of age. They had chronic (≥ every other day for the previous month) knee pain, grade 2-4 radiologic knee OA (Kellgren-Lawrence scale) and had not used NSAIDs or other analgesics within 24 hours of enrollment. Patients with OA due to metabolic arthropathy, or who had knee trauma or steroid injections < one month before enrollment or serious comorbidities, and any who were pregnant, lactating, or allergic to any study agent were excluded.
Sample size needed based on the main outcome, Western Ontario and McMaster Universities OA Index (WOMAC) pain subscale scores, was 96 patients in each arm. Of 210 assessed, 193 were randomized to BCM (n = 97) or ACM (n = 96). The BCM group took one 500 mg capsule twice daily; the ACM group, one 650 mg tablet thrice daily for six weeks. Randomization and allocation were well-concealed, but neither patients nor investigators could remain blinded due to different shapes of the products used. WOMAC pain, stiffness, and physical function were evaluated at days zero and 42. Blood samples at these points were assessed for C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α). A responder analysis for ≥ 20, 50, and 70% reductions in WOMAC pain and pain + stiffness + function over six weeks was conducted. Statistical significance was set at P < 0.05.
At baseline, demographic characteristics and WOMAC scores were normally distributed between groups; CRP and TNF-α levels were not.* Several methods were used in data analysis. Of 193 patients randomized, 144 completed the study, 73 in BCM; 71, ACM. At six weeks, WOMAC scores had improved but remained equivalent in both groups on all subscales (P < 0.05). Pro-inflammatory factors decreased significantly in both groups but more so with BCM (CRP [P = 0.2589]; TNF-α [P = 0.0529]). Mean change in efficacy parameters after six weeks was not significantly different between groups for WOMAC scores or CRP (P > 0.05) but was significant for TNF-α (P = 0.0095). A ≥ 20% reduction in WOMAC pain and pain + stiffness + function scores was seen by similar percentages in each arm; however, 18.0% in BMC had ≥ 50% lower WOMAC scores; 3.0%, ≥ 70% lower. None in ACM achieved ≥ 50% WOMAC reductions (P = 0.0002). No serious AEs were reported. Mild, self-limiting AEs were reported by 12.68% in the ACM group and 5.48% in BCM, a significant advantage for BCM.
The authors conclude that bioavailable turmeric extract is as effective as ACM in improving function and reducing pain and stiffness in patients with knee OA. The authors declare no conflicts of interest.
*Although baseline WOMAC scores are reported, baseline CRP and TNF-α levels are not.