Efficacy and Safety of a Novel Low-Dose Water-Dispersible Turmeric Extract in the Management of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Overview

Purpose

Turmeric extract is a well-known nutraceutical ingredient recognized for its benefits in managing musculoskeletal health. This study evaluated the efficacy and safety of a novel low-dose water-dispersible turmeric extract containing 60% natural curcuminoids (WDTE60N) in participants with mild-to-moderate knee osteoarthritis.

Patients and Methods

This double-blind, randomized, placebo-controlled trial was conducted at two orthopedic centers in Uttar Pradesh, India (July 2023–November 2023). Participants aged 45– 75 years with unilateral or bilateral OA of the knee for > 3 months were randomized in 1:1 ratio to receive WDTE60N (250 mg) or placebo capsules once daily for three months. Study endpoints included assessment of changes from baseline to day 90 in pain intensity (visual analog scale [VAS], knee injury and osteoarthritis outcome score [KOOS]), inflammatory biomarkers, and safety profile. Data were analyzed using independent t-test, chi-square test, and analysis of co-variance test.

Results

In total, 139 participants (WDTE60N, n = 70; placebo, n = 69) with mean age and BMI of 56.35 years and 23.89 kg/m², respectively, were included. The mean reduction (95% CI) in VAS score from baseline to day 90 was significantly higher in the WDTE60N group than in the placebo group (14.41 [13.08, 15.75] vs 6.02 [5.00, 7.05]; p < 0.0001). In the WDTE60N group, the mean change in VAS scores was significantly reduced from as early as day 07 (p = 0.0076), which continued until day 90 (p < 0.0001), compared to the placebo group. Improvement in the mean KOOS scores (baseline-Day 90) was evident, with significantly higher mean scores for each domain (pain, symptoms, activities of daily living, function in sport and recreation, and knee-related quality of life [QoL]) on Day 90 in the WDTE60N group than in the placebo group (p < 0.05). Inflammatory biomarkers (hsCRP, TNF-α, IL-6, and IL-1β) were significantly reduced from baseline to day 90 in the WDTE60N group compared to the placebo group (p < 0.0001). Four mild adverse events were reported during the study period.

Conclusion

Supplementation with the low-dose water-dispersible turmeric extract containing 60% natural curcuminoids for three months was safe and effective in alleviating pain, improving functional status and quality of life and reducing inflammation in participants with mild-to-moderate knee osteoarthritis.

Introduction

Knee osteoarthritis (OA), the most prevalent form of OA, is a degenerative joint disease of the knee that typically results from wear and tear and progressive loss of articular cartilage. According to the International Classification of Diseases (ICD) classification, knee OA is classified as unilateral or bilateral primary knee OA, unilateral or bilateral post-traumatic knee OA, and other unilateral or bilateral secondary knee OA.¹ Clinically, it is characterized by progressive worsening of symptoms such as pain, inflammation, stiffness-related discomfort, and reduced mobility over the course of the disease. If left untreated, the disease can advance, potentially resulting in disability and impaired quality of life (QoL).^2,3 According to the latest Global Burden of Disease Study (GBD) report, approximately 7.6% of the global population was diagnosed with OA in 2020. Knee OA was a major contributor to this global burden, affecting 4307 individuals per 100,000 population. Furthermore, it is anticipated that the prevalence of knee OA will increase by 74.9% from 2020 to 2050, indicating a substantial increase in the disease burden that will pose a critical challenge for healthcare systems worldwide.³

Given that knee pain is the central cause of disability in patients with OA and adversely affects their functional abilities and QoL, the primary goal of treatment is to alleviate the intensity of knee pain.^4–6 Among the currently available management strategies including pharmacological, non-pharmacological, and surgical interventions, pharmacological treatments (such as non-steroidal anti-inflammatory drugs [NSAIDs], acetaminophen, naproxen, selective cyclooxygenase-2 [COX-2] inhibitor, glucosamine, capsaicin, steroids, etc) are the most commonly used.^2,7,8 Despite various advancements in the available management strategies over the past few decades, no cure exists for knee OA; treatments primarily aim to delay disease progression.² In particular, due to the safety concerns associated with the long-term use of these pharmacological treatments, there is growing interest in exploring safer natural therapies. In the past decade, supplementation with nutraceuticals for the management of OA has gained attention owing to their promising role in alleviating pain, inflammation, oxidative stress, and joint discomfort while also promoting cartilage formation.⁹

The potential of turmeric to offer a myriad of health benefits has been well recognized since ancient times in Asian countries. Curcuminoids are the major phytochemicals found in the rhizome of the turmeric plant (Curcuma longa L.) of which curcumin is the major phytoactive and the other two are demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids, also commonly called curcumin, have several pharmacological effects, such as anti-inflammatory, antitumor, antioxidant, lipid-regulating, and anticoagulant effects.^10,11 Within the wide range of dietary supplements evaluated, curcumin has been reported as one of the most potent and effective nutraceutical ingredients in reducing the severity of pain in patients with OA.^12,13 A strong wall of evidence supports the efficacy and safety of curcumin in alleviating pain and improving functional abilities in individuals with OA.^14–17 However, its poor absorption and low bioavailability, which necessitate the administration of multiple daily doses, might affect treatment adherence, especially during long-term use. In addition, high doses of turmeric extract and curcumin (>4000 mg/day) are associated with an increased risk of adverse events such as gastrointestinal symptoms, liver enzyme abnormalities, and urticaria.^18–20 Currently, most bioavailable turmeric extracts in the market are formulated with synthetic excipients and contain up to 20% active ingredients, still requiring higher doses to achieve clinical efficacy.²¹ Thus, there exists a gap in developing a turmeric formulation that can deliver therapeutic benefits at lower doses. To address these limitations, a novel low-dose, water-dispersible turmeric extract containing 60% natural curcuminoids (WDTE60N of Nutriventia Limited and Laila Nutraceuticals, India) was developed. This novel formulation was designed to deliver optimal benefits with a single daily low dose of 250 mg, containing 150 mg of curcuminoids.

Robust evidence from previous pharmacokinetic studies demonstrated a higher bioavailability of WDTE60N compared to the commercially available standard turmeric extract formulations, both with and without the bioavailability enhancer – piperine.^21,22 In particular, once a day, administration of WDTE60N can provide the clinical benefits of curcumin at a ten-fold lower dose of 150 mg of curcuminoids compared to multiple daily doses of the standard 95% turmeric extract, which contains 1500 mg of curcuminoids.²¹ This was demonstrated in two clinical trials. A randomized, double-blind, placebo-controlled trial conducted among healthy adults with chronic knee pain demonstrated the efficacy of WDTE60N, administered for 3 months, in terms of significant improvements in joint function and mobility and alleviation of chronic knee pain.²³ Another similarly designed clinical trial was conducted on the delayed onset muscle soreness in recreationally active healthy adults after a bout of acute exercise. The WDTE60N was well tolerated in these studies.²⁴

These promising outcomes, along with multiple clinical studies evaluating other curcumin supplements in patients with knee OA,^{14,16,25–28} highlight the growing body of evidence supporting the use of curcumin supplements in the management of knee OA. However, to date, none of these studies have assessed the efficacy of curcumin at shorter time intervals after the initiation of product administration. In view of this lacuna, the present study aimed to assess the efficacy and safety of a WDTE60N in participants with mild-to-moderate knee OA, with a focus on understanding its effects at earlier timepoints, starting as early as day 03 following administration.

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Efficacy and Safety of a Novel Low-Dose Water-Dispersible Turmeric Extract in the Management of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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Thanawala S, Shah R, Alluri KV, Bhupathiraju K, Prasad N, Agarwal Y. Efficacy and Safety of a Novel Low-Dose Water-Dispersible Turmeric Extract in the Management of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Pain Res. 2025;18:411-427
https://doi.org/10.2147/JPR.S501505