Glucosamine - Medicinal Uses, Interactions, Side Effects, Dosage

Glucosamine - Uses and Benefits, Preparations and Dosage

<p><strong>Glucosamine</strong></p> <p>Glucosamine (2-amino-2-deoxy beta-D-glucopyranose) is a substrate for the production of articular cartilage and is present in most human tissue. Commercial products are prepared from the shells of crabs and other crustaceans. </p> <p><strong>Uses and Benefits:</strong></p> <p> Glucosamine is commonly employed for musculoskeletal and other types of chronic pain. It has been studied primarily for pain due to osteoarthritis. </p> <p><strong>Pharmacology: </strong></p> <p>Endogenous glucosamine is used to produce pycosaminoglycans and other proteoglycans within articular cartilage. In osteoarthritis, the rate of production of new cartilage is (:xceeded by the rate of degradation of existing cartilage, resul in a net loss. Administration of exogenous glucosamine pro­vides a greater supply of "building blocks," and stimulates production of glycosaminoglycans, resulting in an increase in, or maintenance of, existing cartilage. Animal and human studies of glucosamine given orally or by injection into affected large joints have demonstrated increases in thickness and histological normalization of damaged cartilage. In addition, some mild anti-inflammatory action by non-prostaglandin-related mecha­nisms has been observed in both <em>in vitro </em>and animal studies. Oral glucosamine is 90% absorbed, but undergoes a significant hepatic first-pass effect of up to 70%.</p> <p><strong>Clinical Trials: </strong></p> <p>See Chondroitin for discussion of combined glucosamine and chondroitin trials. </p> <p> Osteoarthritis (OA)-Early European and Asian trials in patients with found some benefits with intra-articular, intra­venous, and intramuscular glucosamine, as well as combinations of injectable and oral doses. More recent, controlled trials using oral doses relied on objective comparison scales that provide reliable measures of clinical benefits. For example, a high-quality, randomized, placebo-controlled trial that met statistical power used glucosamine sulfate (GS) 500 mg or placebo three times daily for 4 weeks, in 252 patients with knee OA. Significant diffeences were found in favor of GS in the change in Lequesne index (a validated disability scale used in OA trials) as well as outcomes as defined by physician assessment of global efficacy.</p> <p>A number of controlled clinical studies of glucosamine have re­ported similar benefits for pain or disability due to knee OA. A meta-analysis of randomized, double-blind, placebo-controlled trials found six (five oral and one intraarticular dosing) that lasted at least 4 weeks; study size varied from 20 to 329 patients. The treatment effect size of glucosamine was calculated to be 0.44, a moderate effect. However, methodological limitations common to most of the trials (e.g., inadequate allocation concealment, ab­sence of intent-to-treat analysis) tended to overestimate effects, and therefore the actual treatment effect size is likely to be smaller than the calculated value. A Cochrane Review identified 16 double-blind, randomized, controlled trials . placebo, using oral glucosamine), mostly in patients with knee but also one trial each with spine and multiple OA sites. Glucosamine was found to be superior to placebo in all but one study; a moderate effect size was also calculated</p> <p>Other Uses-Another oral form, N-acetyl-D-glucosamino, was evaluated in a recent pilot study of 12 children with chronio inflammatory bowel disease. A reduction in symptoms was roported in eight patients. Nine additional children received rectal doses: improvement was noted in three, and remission occurrer in two. Biopsies (not done in all cases) showed histological im" provement. However, this pilot study was not controlled. </p> <p><strong>Adverse Effects: </strong></p> <p>Glucosamine is well tolerated. Mild nausen and diarrhea are most commonly reported; frequency is similar to placebo in some controlled trials. One trial (n = 1200) noted thai gastrointestinal side effects occurred at a higher rate in patients with pre-existing gastroduodenal illnesses or those taking diuretics. There is one case report each of an immediate hypersensitivity reaction and of photosensitivity recurring on rechallenge. </p> <p><strong>Side Effects and Interactions:</strong></p> <p>There are no known drug interactions with glucosamine. </p> <p><strong>Cautions:</strong></p> <p>A common caution based on animal studies is that glucosamine may increase blood glucose. One human study using intravenous glucosamine did find slight (5.4-9.0 mg/dl) increases in plasma fasting glucose levels. However, clinical effects of oral glucosamine on blood glucose have not been reported, and one study found no changes in fasting glucose over a 3-year period. Safety during pregnancy and lactation has not been determined. </p> <p><strong>Preparations </strong><strong>& </strong><strong>Doses: </strong></p> <p>The recommended dose, used in almost all of the clinical trials, is 500 mg three times daily. Theoretically, all salt forms should dissolve and allow glucosamine absorption, but there is some evidence that the sulfate moiety is necessary for clinical efficacy. Animal and human studies <em>have </em>shown a decrease in glycosaminoglycan synthesis in sulfate depletion conditions. No trials comparing the different salt forms <em>have </em>been conducted; <em>however, </em>results of the one clinical trial of glucosamine HCI did not show benefits. Another form, N-acetyl­D-glucosamine, has been shown to increase serum glucosamine <em>levels, </em>but has not been adequately tested clinically.Until more data is <em>available, </em>the recommended form is glucosamine sulfate. </p> <p><strong>Summary Evaluation </strong></p> <p>The clinical evidence is sufficient to support the use of oral glucosamine sulfate for symptoms of mild to moderate osteoarthritis. Symptom reduction appears to be similar to that of analgesic doses of NSAIDs. Glucosamine has a longer onset of action than <em> </em> but fewer adverse effects. Evidence of positive effects on joints structure is promising. There is no evidence at this time that glucosamine amine is beneficial for disorders other than osteoarthritis.</p>

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