Glucosamine is an amino sugar biosynthesized from glucose and used by the body as a building-block of the ground substance of the articular cartilage, the proteoglycans. Osteoarthritis results from continous wear and tear on the joints and progressive catabolic loss of cartilage proteoglycans. An imbalance in proteoglycan biosynthesis and degradation results in breakdown of cartilage and the protective coating that covers the ends of bones in a joint. Glucosamine inhibits the degradation of proteoglycans and is a primary substrate and stimulant of proteoglycan biosynthesis. A number of double-blind studies have demonstrated that oral glucosamine is at least as effective as NSAIDs at decreasing pain and improving mobility in osteoarthritis. Glucosamine is not as potent an anti-inflammatory agent as NSAIDs, but it is much less toxic to the gastrointestinal tract.

Recent research indicates that glucosamine may also help slow the progression of osteoarthritis. In a controlled study, orally administered glucosamine sulfate was shown to prevent "joint space narrowing" and improve symptoms in subjects with knee osteoarthritis. Joint space narrowing is a measure of the loss of joint space due to articular cartilage breakdown. In comparison, the joint space in the placebo group had narrowed significantly and their symptoms worsened by the end of the three-year study. In addition to stimulating proteoglycan synthesis, glucosamine may stimulate synovial production of hyaluronic acid (HA)—a compound responsible for the lubricating and shock-absorbing properties of synovial fluid. HA has anti-inflammatory and analgesic properties, and its concentration is diminished in osteoarthritis.

Pharmacokinetics studies indicate that roughly 90% of glucosamine sulfate is absorbed after oral administration. However, a significant amount is metabolized during first-pass hepatic metabolism and does not reach the blood. In one study, the amount of glucosamine in the blood after oral administration was 26% of that after intravenous or intramuscular administration.

Chitin from shellfish

2-amino-2-deoxy-D-glucose (1)

• Glucosamine sulfate: 500, 750, and 1,000 mg capsules and tablets 
• N-acetyl glucosamine: 500 and 750 mg capsules and tablets 
• Glucosamine hydrochloride (HCL): 500, 750, and 1,000 mg capsules and tablets 
• Glucosamine/chondroitin sulfate combination products 

Most studies have been done on glucosamine sulfate. There is debate as to whether the glucosamine HCL form is effective. Chondroitin sulfate has been shown to be more effective than placebo on osteoarthritis of the knee and hip, but debate exists as to how well it is absorbed by the body. More study is needed on these glucosamine combinations and preparations.

Osteoarthritis

Recommended dosage is 1,500 mg glucosamine per day (500 mg, tid) for one to two months. Ongoing supplementation may be required to prevent progression of osteoarthritis and to reduce pain and inflammation.

The majority of studies indicate that glucosamine is safe, nontoxic, and causes only minor side effects, which include mild gas, diarrhea, and bloating.

Glucosamine sulfate may contain high amounts of sodium or potassium. Individuals on a salt- or potassium-restricted diet, or taking potassium-sparing diuretics, should check labels before taking glucosamine sulfate.

Animal studies suggest that glucosamine may raise insulin resistance. Diabetics should have their blood sugar checked regularly.

Glucosamine is made from chitin—a component of shellfish. Although it is not extracted from the protein component of shellfish, individuals with shellfish allergies may want to check with a health care professional before taking glucosamine.

The combination of glucosamine and NSAIDs may reduce the doses needed for anti-inflammatory activity as well as the side effects associated with these drugs (Zupanets et al. 1991). In an in vitro study, lower doses of diclofenac, indomethacin and piroxicam combined with glucosamine reduced experimentally-induced inflammation in mice.

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