For centuries, Curcuma has been used in Ayurvedic medicine for the treatment of digestive and painful disorders. Its indications have been enlarged to include multiple myeloma, pancreatic cancer, myelodysplasic syndromes, colon cancer, and psoriasis, among other disease conditions [1]. Investigators have isolated a series of curcuminoids containing 90% curcumin or diferuloylmethane, a polyphenolic pigment from the rhizoma of the plant with demonstrated antioxidant properties [2]. Epidemiological studies have suggested that curcumin possesses anti-inflammatory, hypolipemic, anti-thrombotic, anti-tumor, anti-diabetic, and neuroprotective properties [3]. Today, with more than 5,600 pharmacological studies, the potential applications of curcumin is documented in rheumatic, traumatic, and sport-related conditions, as well as Alzheimer’s disease, gastric ulcer, irritable colon disorder, and Crohn disease [4].

Curcumin acts at various levels of the inflammation cascade; it modulates pro-inflammatory interleukin production and decreases the action of phospholipase A2, cyclooxygenase-2, and 5-lipoxygenase. Curcumin does not affect Cox-1 activity, which contributes to its excellent tolerance. Its anti-inflammatory action is due to its modulation of NFκB (anti-catabolic activity) and other transcription factors [5]. In vitro studies have revealed a protective effect of curcumin on cartilage [6]. Taken together, these lines of evidence support the use of curcumin for the treatment of rheumatic conditions.

However, the use of curcumin is limited by its low bioavailability. After oral administration, only a limited amount of the molecule penetrates the intestinal barrier to reach the circulation and the periphery of the body; the use of the native form of curcumin is therefore limited [7] To overcome these obstacles, Tilman SA, a Belgian pharmaceutical company, patented a new curcumin formulation called Flexofytol^®. This innovative and licensed galenic form of curcumin uses a very thin dispersion of curcumin in a specific excipient and in the presence of emulsifiers that facilitate penetration through the intestinal barrier. Accordingly, the administration of 42 mg of this optimized curcumin preparation in a small capsule is equal to the ingestion of 57 g of native curcumin or 1 kg of Curcuma powder [6].

This new curcumin preparation has been marketed in Belgium for more than 3 years and is one of the most frequently prescribed compounds for osteoarthritis. It is recommended for maintaining articular flexibility, preserving the joints, limiting cartilage ageing, and improving articular function, particularly for sensitive joints and tendons. Flexofytol^® is registered not as a drug, but as a food supplement.

We sought to perform a real-life evaluation of patient satisfaction with Flexofytol^®. The present study was performed in 2013 with the help of general practitioners, with the goal of assessing their personal experience with patients suffering various manifestations of osteoarthritis. This investigation also aimed to evaluate the potential benefits of Flexofytol^® on joint function, to identify the treatment period required before clinical improvement becomes apparent, to pinpoint undesirable effects, and to determine whether better results could be achieved in some locations versus others in terms of pain severity, flexibility, and quality of life.

In the present investigation, the experience of 110 Belgian general practitioners suggests that 2 capsules of Flexofytol^® taken twice daily can significantly improve the pain, articular flexibility, and quality of life of osteoarthritic patients, nearly without undesirable effects and within 6 weeks (Fig. 1). Flexofytol^® also reduced the consumption of concomitant therapies for osteoarthritis, such as anti-inflammatory drugs, analgaesic drugs, and chondroprotective agents, and was associated with a high degree of patient satisfaction (Fig. 4). The clinical improvement was maintained at least up to 6 months despite the statistical reduction of concomitant analgesic and anti-inflammatory therapies at 6 weeks suggesting that the benefit was not related to the concomitant therapies. The best indications of Flexofytol^® suggested from this study are painful osteoarthritis of the knee or of the hip, although benefits were also reported in other degenerative joint conditions (Fig. 2). The weakest point of this study is that it is observational, not randomized, not double blind and not placebo controlled; yet the data come from a collection of real-life information that reflects the experiences of 110 physicians over 1 year and of 820 patients over 6 months of therapy. This approach is quite different from a randomized, controlled, double blind study with a reference molecule, but includes a large number of physicians and patients and covers a relatively long period of observation. It is also important to stress the good compliance of the treated patients and the proportion of patients who wished to continue Flexofytol^® therapy longer than 6 months. The observed benefits at 6 weeks may be due to the anti-inflammatory mode of action and/or analgaesic effect of curcumin, while patient satisfaction at 6 months may result from additional regenerating effects of curcumin on articular structures. A series of in vitro studies previously uncovered an anti-catabolic effect of curcumin that inhibits metalloproteases and stimulates the production of glycosaminoglycans, which play a role in the accumulation of aggrecans in the cartilage and reinforce the matrix; curcumin also promotes the formation of chondrocytes [4, 6].

Curcumin is relatively stable in the intestine, but to detect curcumin in circulating plasma, dosages as high as 10-12 g daily are necessary. Once in the blood, curcumin can persist for a long time, and can penetrate the peripheral tissue due to its polyphenol structure [6, 7]. The curcumin extract in Flexofytol^® is a micro-emulsion that is 1350 times more assimilable than native curcumin powder. In Flexofytol^® capsules, curcumin is present in the centre of a 200-nm micelle constituted of polysorbate with a hydrophilic extremity on the periphery and a hydrophobic extremity oriented toward the centre. This formulation differentiates Flexofytol^® from the other available preparations of curcumin, which for example use black pepper or piperidine as supports, or are combined with other plant extracts. The benefits of curcumin in osteoarthritis have been reported in other studies as well [6] The administration of 1 g Meriva (a curcumin extract coated in a phytosome to facilitate its resorption by the intestine) over 3-8 months also improved symptoms, articular function, and quality of walking; these benefits were associated with reductions in the levels of inflammation mediators such as Interleukin 1(, Interleukin 6, the ligand of CD40, and other adhesion molecules, as well as reductions in the blood sedimentation rate [8-10].

Other clinical trials with different curcumin preparations in osteoarthritis have been recently published in the literature; accordingly, a double blind prospective randomized clinical trial has suggested a benefit of curcumin as an adjuvant therapy to diclofenac (75 mg daily) in primary knee osteoarthritis but no statistical significance [11]. First in a 3 month study, Meriva (a curcumin phytosome phosphatidyl complex) decreased pain and improved joint function in 50 osteoarthritis patients. In a following study in 100 patients, Meriva also improved a series of inflammatory markers and sedimentation rate as well [12]. A curcuma domestica extract seems to be as effective as ibuprofen for the treatment of osteoarthritis but with fewer gastrointestinal adverse events [13]. A randomized double blind placebo control parallel group clinical trial conducted among patients with mild-moderate knee osteoarthritis showed a greater reduction of Womac, Visual analogue score and Lequesne pain functional index than in placebo and also on pain and physical function [14].

In rheumatoid arthritis, BCM-95, another curcumin formulation, improved the disease articular score more than the anti-inflammatory drug diclofenac, suggesting that curcumin could be considered as an alternative to non-steroidal anti-inflammatory drugs, with better tolerance; note that in animal models, curcumin exerts an analgaesic effect [15].

In conclusion, Flexofytol^® like other curcumin extracts is appropriate for the care of patients complaining of joint problems. Flexofytol^® may not only address painful joints, but may also contribute to the regeneration of cartilage.