Research ArticlePycnogenol supplementation reduces pain and stiffness and improves physical function in adults with knee osteoarthritis☆
Introduction
Osteoarthritis is the most common chronic degenerative joint disorder worldwide, affecting over 50% of adults over 65 years of age. A 33% prevalence of radiological knee OA and 10% to 15% prevalence of symptomatic knee OA in persons 60 years and older have been reported recently [1]. Although OA is not considered an inflammatory disease, mediators classically associated with inflammation, such as cytokines, prostaglandins, nitric oxide (NO), and proteases, perpetuate cartilage damage that ensues from repeated mechanical injury. Cartilage destruction, an important pathologic feature and a major cause of joint dysfunction, is mediated by two distinct pathways: intrinsic, in which chondrocytes are responsible for the degradation of the extracellular matrix (ECM); and extrinsic, wherein cells and tissues other than chondrocytes, such as inflamed synovium, pannus tissue, and inflammatory cells affect the ECM via synovial fluids [2]. Matrix metalloproteinases (MMPs) are major proteolytic enzymes involved in ECM turnover. The expression of MMPs in osteoarthritic cartilage and their contribution to the cartilage degradation has been documented [3]. Another suspected mediator of cartilage damage is overproduction of NO, a major catabolic factor produced by chondrocytes in response to proinflammatory cytokines [4].
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used medications for arthritis, accounting for 111 million prescriptions annually and 3% of the American prescription drug market [5], [6]. These medications are associated clinically with significant complications including nonulcer dyspepsia, symptomatic gastric and duodenal ulcers, ulcer hemorrhages, and perforations [5]. Their economic impact includes 100 000 hospitalizations annually, costing $1.6 billion with 17 000 deaths [6]. Complications have increased with the aging of the American population and heightened the use of aspirin for cardioprophylaxis. Therefore, there is an increasing need to develop effective and safe treatment to minimize the adverse events in patients with osteoarthritis.
Pycnogenol, a standardized extract from the bark of French maritime pine (Pinus maritima), is a registered trademark belonging to Horphag Research, Ltd (Geneva, Switzerland). It contains monomeric phenolic compounds (catechin, epicatechin, and taxifolin), condensed flavonoids (procyanidins), and phenolic acids (hydroxy benzoic, protocatechuic, gallic, vanillic, ρ-coumaric, caffeic, and ferulic acid) [7]. Clinical studies indicate that Pycnogenol is effective in the treatment of chronic venous insufficiency, retinal microhemorrhages, and ultraviolet radiation–induced erythema; in alleviating asthma symptoms; improving hypertension and inhibiting platelet aggregation [7]. Pycnogenol has a wide range of anti-inflammatory and antioxidant activities [8], including free radical–scavenging activity against reactive oxygen and nitrogen species [9]. It also modulates the production of NO radicals in activated macrophages by inhibiting inducible NO synthase (iNOS) expression and activity and by quenching the NO radicals [10]. Furthermore, 2 metabolites formed in vivo from Pycnogenol displayed strong inhibitory activity toward MMP-1, MMP-2, and MMP-9 [11].
Dietary antioxidants such as vitamin C, vitamin E, and β-carotene were recently shown to reduce the risk of progression of knee OA [12]. These beneficial health effects are attributed to their antioxidant activities and have attracted considerable attention in recent years for treating oxidative stress–related diseases, including OA. Although the antioxidant activities of some of the Pycnogenol compounds have been studied extensively [8] and other antioxidant therapies have been shown to have beneficial effects on OA, no data are available with respect to the clinical usefulness of Pycnogenol in treating OA. Considering the strong antioxidant and anti-inflammatory profile of Pycnogenol and its inhibitory effects on MMPs and iNOS, this study was conducted for the first time to evaluate the efficacy of Pycnogenol in knee OA.
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Human subjects
Patients were eligible for the study if they were between 25 and 65 years old, fulfilled the American College of Rheumatology criteria [13] for primary knee OA (grade 1 or 2), had a Western Ontario and McMaster Universities (WOMAC) pain subscale index of at least 40 at the baseline, and had intermittent or constant pain in the target knee for at least 50% of the time in last 3 months that required medical treatment in the form of NSAIDs or selective cyclooxygenase 2 (COX-2) inhibitors on most
Results
From a total of 40 subjects who met the inclusion and exclusion criteria, 3 subjects declined to participate for reasons unrelated to the study (travel, relocation, etc) before randomization, 1 subject was withdrawn due to lack of efficacy (in placebo group), and 1 was lost to follow-up (in Pycnogenol group) (Fig. 1). The groups had similar demographics and clinical characteristics at the baseline. No significant differences in baseline characteristics were observed (Table 1). In addition,
Discussion
Dietary supplements with complex mixtures of bioactive nonnutrients are being used to provide nutritional therapy and antioxidant activity. Pycnogenol is becoming another dietary supplement of bioactive nonnutritive molecules with health promoting activities, important in understanding the role of supplements and foods in human diets and nutrition. To our knowledge, this is the first randomized clinical trial to show the effectiveness of Pycnogenol, a dietary supplement with known antioxidant
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This research was supported by a grant from Horphag Research, Inc, which also provided the supplement and placebo pills.