Glucosamine

Glucosamine is a glucose derivative that naturally occurs in connective and cartilage tissues. It is a precursor of antioxidant-like glycosaminoglycan (GAG) and proteoglycans found in the body. Studies have shown glucosamine may affect subchondral bone turnover, structure and mineralization;1 inhibit COX-2 and inducible nitric oxide synthase (iNOS) activity;2,3 and decrease collagen degradation by inhibiting advanced lipoxidation reactions, thereby protecting the chondrocyte matrix.4 Such effects, coupled with clinical trials, have led researchers to conclude glucosamine may have positive effects on OA symptoms and disease progression.5

National Institutes of Health (NIH) sponsored a $12.5 million, multicenter clinical trial involving Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT). 6 In the double blind GAIT study, 1,583 patients were divided into five treatment groups and given either: glucosamine alone, chondroitin sulfate alone, the two supplements in combination, celecoxib, a prescription drug to treat OA pain, or placebo. The patients were monitored over 24 weeks and were separated into two pain subgroups—those with mild pain (78 percent) and those with moderate-to-severe pain (22 percent). The study’s primary outcome was defined as at least a 20-percent reduction in pain at 24 weeks.

At the study’s end, the study concluded glucosamine and chondroitin taken alone or in combination did not effectively reduce knee pain in OA patients with mild pain. However, the researchers, led by Daniel O. Clegg, M.D., from the University of Utah, Salt Lake City, did find a significantly higher response rate to the nutrient combination in patients with moderate-to-severe pain at baseline, aiding almost 80 percent of study participants; the abstract further noted all treatments were well tolerated.

The GAIT trial was also the primary piece of evidence considered by reviewers from the U.S. Agency for Healthcare Research and Quality (AHRQ), which concluded there is no demonstrable clinical benefit to the use of oral glucosamine/chondroitin for knee OA.7 They did note six study-level meta-analyses found statistically significant differences between treatment and placebo, but suggested more trials are necessary.

Such trials are underway, and have their own positive findings to build on. The Europeansponsored Glucosamine Unum In Die Efficacy (GUIDE) trial compared the effect of 1,500 mg/d glucosamine sulfate, 3,000 mg/d acetaminophen and placebo on various osteoarthritis pain and mobility indices in 318 OA patients (88 percent women) over 24 weeks.8  Ibuprofen (400 mg/d) was permitted as a rescue medication. Glucosamine sulfate was efficacious in reducing scores on various OA symptom indices. There were no differences in safety among treatments. The researchers concluded 1,500 mg/d glucosamine sulfate might be the preferred symptomatic medication in knee OA. Similarly, researchers out of Poland reported 12 weeks of supplementation with glucosamine sulfate (500 mg tid) improved functional status and pain in patients with knee or hip OA.9

Glucosamine is often paired with chondroitin, the most prevalent GAG found in joint cartilage, and research has shown the supplement might have long-term benefit to the symptoms and progression of OA. Studies suggest it may reduce the activity and production of matrix metalloproteinases (MMPs), which play a key role in degradation of cartilage matrix.10

References:
1.  Wang SX et al. “The effects of glucosamine hydrochloride on subchondral bone changes in an animal model of osteoarthritis.” Arthritis Rheum. 2007 May;56(5):1537-48.

2. Jang BC et al. “Glucosamine hydrochloride specifically inhibits COX-2 by preventing COX-2 N-glycosylation and by increasing COX-2 protein turnover in a proteasome-dependent manner.” J Biol Chem. 2007 Sep 21;282(38):27622-32.

3. Rafi MM, Yadav PN, Rossi AO. “Glucosamine inhibits LPS-induced COX-2 and iNOS expression in mouse macrophage cells (RAW 264.7) by inhibition of p38-MAP kinase and transcription factor NF-kappaB.” Mol Nutr Food Res. 2007 May;51(5):587-93.

4. Tiku ML et al. “Glucosamine prevents in vitro collagen degradation in chondrocytes by inhibiting advanced lipoxidation reactions and protein oxidation.” Arthritis Res Ther. 2007 Aug 8;9(4):R76.

5.  Reginster JY, Bruyere O, Neuprez A. “Current role of glucosamine in the treatment of osteoarthritis.” Rheumatology (Oxford). 2007 May;46(5):731-5.

6. Clegg DO et al. “Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.” N Engl J Med. 2006 Feb 23;354(8):795-808.

7. Samson DJ et al. “Treatment of Primary and Secondary Osteoarthritis of the Knee.” AHRQ, Publication No. 07-E012, September 2007.

8. Herrero-Beaumont G et al. “Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator.” Arthritis Rheum. 2007 Feb;56(2):555-67.

9. Dudek A et al. “[Efficacy of glucosamine sulfate treatment in patients with osteoarthritis][Article in Polish].” Pol Merkur Lekarski. 2007 Mar;22(129):204-7.

10. Sandya S, Sudhakaran PR. “Effect of glycosaminoglycans on matrix metalloproteinases in type II collagen-induced experimental arthritis.” Exp Biol Med (Maywood). 2007 May;232(5):629-37.