Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with OA

Analyze & Realize AG, Berlin, Germany.
Advances in Therapy (Impact Factor: 2.27). 09/2009; 26(9):858-71. DOI: 10.1007/s12325-009-0060-3
Source: PubMed


A total of 177 patients with moderate-to-severe hip or knee osteoarthritis (OA) were tested over a period of 26 weeks in a two-center, two-armed, randomized, double-blind, comparison study. The aim was to see if a combination of glucosamine sulfate (1500 mg/day) and the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (group A), showed equivalence (noninferiority) or superiority as opposed to glucosamine sulfate alone (group B).
The primary therapy evaluation was performed using the Western Ontario and McMaster Universities Arthrosis index (WOMAC) score. At the end of the study, a reduction in the pain score of > or =20% was required (primary target criterion) and the quantitative difference in the WOMAC subscores pain, stiffness, and function were analyzed (secondary target criteria).
When a minimal pain reduction of > or =20% was chosen, there was no statistically significant difference in the number of responders between the two groups (92.2% group A, 94.3% group B). A higher responder criterion (> or =80% reduction in the WOMAC pain score) was chosen. Therefore, the frequency of responders showed a therapeutic and statistical superiority for the combination product of glucosamine sulfate and the omega-3 polyunsaturated fatty acids in patients who complied with the study protocol (group A 44%, group B 32%; P=0.044). OA symptoms (morning stiffness, pain in hips and knees) were reduced at the end of the study: by 48.5%-55.6% in group A and by 41.7%-55.3% in group B. The reduction was greater in group A than in group B. There was a tendency toward superiority shown in the secondary target criteria and concurrent variables. In the global safety evaluation, both products have been demonstrated to be very safe in long-term treatment over 26 weeks. To our knowledge, this is the first clinical trial in which glucosamine was given in combination with omega-3 fatty acids to patients with OA.

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    • "Skin irritation Gruenwald et al. 2009 [42] "
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    ABSTRACT: Background Omega-3 (n-3) fatty acid supplementation is becoming increasingly popular. However given its antithrombotic properties the potential for severe adverse events (SAE) such as bleeding has safety implications, particularly in an older adult population. A systematic review of randomized control trials (RCT) was conducted to explore the potential for SAE and non-severe adverse events (non-SAE) associated with n-3 supplementation in older adults. Methods A comprehensive search strategy using Medline and a variety of other electronic sources was conducted. Studies investigating the oral administration of n-3 fish oil containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or both against a placebo were sourced. The primary outcome of interest included reported SAE associated with n-3 supplementation. Chi-square analyses were conducted on the pooled aggregate of AEs. Results Of the 398 citations initially retrieved, a total of 10 studies involving 994 older adults aged ≥60 years were included in the review. Daily fish oil doses ranged from 0.03 g to 1.86 g EPA and/or DHA with study durations ranging from 6 to 52 weeks. No SAE were reported and there were no significant differences in the total AE rate between groups (n-3 intervention group: 53/540; 9.8%; placebo group: 28/454; 6.2%; p = 0.07). Non-SAE relating to gastrointestinal (GI) disturbances were the most commonly reported however there was no significant increase in the proportion of GI disturbances reported in participants randomized to the n-3 intervention (n-3 intervention group: 42/540 (7.8%); placebo group: 24/454 (5.3%); p = 0.18). Conclusions The potential for AEs appear mild-moderate at worst and are unlikely to be of clinical significance. The use of n-3 fatty acids and the potential for SAE should however be further researched to investigate whether this evidence is consistent at higher doses and in other populations. These results also highlight that well-documented data outlining the potential for SAE following n-3 supplementation are limited nor adequately reported to draw definitive conclusions concerning the safety associated with n-3 supplementation. A more rigorous and systematic approach for monitoring and recording AE data in clinical settings that involve n-3 supplementation is required.
    BMC Geriatrics 05/2013; 13(1):41. DOI:10.1186/1471-2318-13-41 · 1.68 Impact Factor
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    • "Also here validated scores were used (WOMAC and Lequesne) and showed that the treatment reduced symptoms of pain and stiffness significantly and improved physical function both between groups and in the treatment group but not in the placebo group [32]. A third study compared glucosamine alone and glucosamine plus a combination of fish oil and other ω-3 oils, where the combined group gave significantly better results [33]. As the products used in the human studies were different from the ones used in the canine studies, it is of course possible that the added nettle, lemon verbena, zinc or glucosamine might have made these products superior. "
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    ABSTRACT: Background An un-commissioned randomized, double-blinded, placebo controlled clinical study was planned using a deep sea fish oil product for pets. Seventy-seven client-owned dogs with osteoarthritis were randomly assigned to supplement the food with either the fish oil product or corn (=placebo) oil. Our main outcome variables were force platform variables peak vertical force (PVF) and impulse, the validated Helsinki Chronic Pain Index (HCPI) and the use of rescue NSAIDs. Secondary outcome variables were a locomotion visual analog scale (VAS), a Quality of life VAS, a comparative questionnaire, a veterinary assessment, owners’ final assessment of outcome and guessing the product given. Results When comparing the two test groups at the end of the trial (16 weeks) there was no significant difference in any of the main outcome variables but owners of dogs that had taken fish oil were significantly happier with the treatment at the end visit and did significantly better at guessing what group their dogs had been in, compared to the placebo group. When comparing variables within the fish oil group as change from baseline to trial end, there were significant positive changes in PVF, HCPI, NSAID use, Quality of life VAS, as well as in all three scores in the comparative questionnaire (locomotion, every-day situations, and skin & coat). There were similar positive trends in force platform impulse and in the veterinary assessment variables, although they did not reach significance. Within the placebo group there were significant positive changes only in the HCPI and a significant deterioration according to veterinary assessment. Conclusions When compared to placebo, there was not a major statistically significant benefit in using deep sea fish oil as a pain reliever in our study population of dogs suffering from osteoarthritis. However, the fish oil treated patients improved significantly in many of the variables, when comparing baseline values to the study-end values within the group, indicating a true but small relief in symptoms. Deep sea fish oil supplementation could be considered a part of the multimodal pain relieving approach currently recommended for dogs suffering from OA, especially for individuals that do not tolerate anti-inflammatory drugs.
    BMC Veterinary Research 09/2012; 8(1):157. DOI:10.1186/1746-6148-8-157 · 1.78 Impact Factor
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    • "The use of glucosamine associated with the monitoring of response using an appropriate biomarker could improve the efficiency and the cost/benefit ratio of the treatment. Finally, we should consider the use of glucosamine as a combination therapy with other drugs or other nutraceuticals, such as omega-3 fatty acid or manganese ascorbate [79,80]. This would open up a new horizon in this field but the combinations would need to be rigorously assessed. "
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    ABSTRACT: Glucosamine in its acetylated form is a natural constituent of some glycosaminoglycans (for example, hyaluronic acid and keratan sulfate) in the proteoglycans found in articular cartilage, intervertebral disc and synovial fluid. Glucosamine can be extracted and stabilized by chemical modification and used as a drug or a nutraceutical. It has been approved for the treatment of osteoarthritis (OA) in Europe to promote cartilage and joint health and is sold over the counter as a dietary supplement in the United States. Various formulations of glucosamine have been tested, including glucosamine sulfate and glucosamine hydrochloride. In vitro and in vivo studies have uncovered glucosamine's mechanisms of action on articular tissues (cartilage, synovial membrane and subchondral bone) and justified its efficacy by demonstrating structure-modifying and anti-inflammatory effects at high concentrations. However, results from clinical trials have raised many concerns. Pharmacokinetic studies have shown that glucosamine is easily absorbed, but the current treatment doses (for example, 1,500 mg/day) barely reach the required therapeutic concentration in plasma and tissue. The symptomatic effect size of glucosamine varies greatly depending on the formulation used and the quality of clinical trials. Importantly, the effect size reduces when evidence is accumulated chronologically and evidence for the structure-modifying effects of glucosamine are sparse. Hence, glucosamine was at first recommended by EULAR and OARSI for the management of knee pain and structure improvement in OA patients, but not in the most recent NICE guidelines. Consequently, the published recommendations for the management of OA require revision. Glucosamine is generally safe and although there are concerns about potential allergic and salt-related side effects of some formulations, no major adverse events have been reported so far. This paper examines all the in vitro and in vivo evidence for the mechanism of action of glucosamine as well as reviews the results of clinical trials. The pharmacokinetics, side effects and differences observed with different formulations of glucosamine and combination therapies are also considered. Finally, the importance of study design and criteria of evaluation are highlighted as new compounds represent new interesting options for the management of OA.
    Arthritis research & therapy 01/2012; 14(1):201. DOI:10.1186/ar3657 · 3.75 Impact Factor
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