This 8-week randomized, double-blind, placebo-controlled study with 100 community adults reporting joint pain showed that Instaflex is efficacious and safe to use, with no adverse symptomology or negative effects on general metabolism and liver and kidney function. Instaflex caused significant reductions in joint pain for the whole group. Among the 74% of subjects with knee pain, difficulties performing daily activities were attenuated. Joint pain reduction effects from Instaflex become apparent by the fourth week of supplementation, and occurred without changes in systemic inflammation or distance walked in six minutes.
The primary outcomes of this study were the pain, stiffness, and function indexes of the WOMAC. The magnitude of decrease in joint pain for all subjects in the Instaflex (↓37%) compared to placebo (↓16%) group, and decrease in difficulties performing daily activities for those with knee pain (↓39% vs. ↓14%), is comparable to or higher than what has been reported in other studies using chondroprotective or anti-inflammatory dietary supplements in subjects with osteoarthritis [8, 12–14, 28–33]. For comparison with a lifestyle change factor, one study of 250 subjects showed that weight loss of 5% and higher (median 11.1 kg) resulted in a 54% decrease in the WOMAC pain index after adjustment for age, sex, and baseline weight .
Most previous studies testing the efficacy of dietary supplements on joint pain reduction have compared placebo to one or two of the chondroprotective components including glucosamine (typical dose, 1,000-1,500 mg/day), chondroitin sulfate (800–1,200 mg/day), methylsulfonylmethane (1,500 mg/day), collagen hydrolysates, and hyaluronic acid [6–8]. Results from these studies have been mixed [6, 8, 12, 13, 15, 23, 28] and the most recent meta-analysis of glucosamine and chondroitin was non-supportive .
There is increasing evidence that nutraceutical-based combinations of chondroprotective and/or anti-inflammatory components are modestly effective in reducing joint pain within 4–16 weeks without measurable side effects [9, 11]. Instaflex (3 capsules daily portion) combines 1500 mg of glucosamine sulfate, 500 mg methylsufonlylmethane, and 4 mg hyaluronic acid with several anti-inflammatory substances including white willow bark extract, ginger root concentrate, boswella serrata extract, turmeric root extract, and cayenne. Other combinations of nutraceuticals, botanicals, and dietary supplements that have shown efficacy in reducing joint pain symptoms in double-blind, placebo-controlled studies include Phellodendron amurense bark and Citrus sinensis peel extracts standardized to berberine and polymethoxylated flavones , lemon verbena extract (14% verbascoside) with fish oil , a product containing dried extracts from six Asian herbs , and a mixture of glucosamine, chondroitin, and quercetin glycoside .
Each of the anti-inflammatory components of Instaflex has been studied separately for influences on joint pain management, but little is known regarding potential synergistic effects when these are combined in smaller amounts than used in single component studies. The active principle in white willow bark extract is salicin, an alcoholic β-glucoside closely related to acetylsalicylic acid in aspirin. The daily dose of Instaflex supplement contains approximately the equivalent of ¼ an aspirin tablet. Studies using larger doses of white willow bark providing about 240 mg/day salicin for periods of up to six weeks generally support modest pain relief [16, 34].
More than 100 compounds have been reported from ginger, including gingerols that possess anti-inflammatory, analgesic, and cardiotonic effects [18, 35]. Ginger has gained considerable attention in developed countries in recent years, especially for its use in the treatment of inflammatory conditions, and a study of patients with osteoarthritis showed a moderate effect of ginger extract in reducing symptomatology . Boswellia serrata is Indian frankincense or Salai, and has been used for centuries as a treatment for arthritis. Animal studies and pilot clinical trials support the potential of Boswellia serrate gum resin extract in the treatment of a variety of inflammatory diseases including osteoarthritis [19, 20, 36], and a study of 75 patients with osteoarthritis showed that Boswella serrate extract safely reduced pain and improved physical functioning .
Turmeric contains over 300 different components including the active ingredient curcumin (3–5%) . In vitro and animal research shows curcumin is a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation . Few human trials have been published, but one study of 107 patients with knee osteoarthritis showed that turmeric extract was as efficacious as ibuprofen in alleviating symptoms . Cayenne or red pepper spice contains capsaicin that activates the transient potential receptor vanilloid 1 (TRPV1) channel involved in some aspects of inflammation control . One review of several studies indicates that cayenne compared to placebo exerts modest effects for pain relief .