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Glucosamine: A Review

Allison Tannis M.Sc.                                                                                                               September, 2002

Recently there has been a boom in the supplement industry. Dietary supplement sales grew from $8.8 billion dollars in 1994, to an estimated $15.7 billion dollars in 2000.1 Supplements are topics of television shows, newspaper articles and everyday discussions. The recent boom in consumer interest in natural supplements has not been accompanied by consumer education. For example, glucosamine is reportedly incorrectly taken by some of the public to heal general joint pain. However, it has only been shown to be effective against hip and knee pain caused by osteoarthritis. This article will briefly review glucosamine, including its biochemistry, structure, efficacy and potential side effects.

Glucosamine is a natural amino-monosaccharide (i.e. amino-sugar compound), which is normally present in the human body.2 Glucosamine is found in everyday foods such as meat, fish and poultry.3  In the body, glucosamine can be phosphorylated into glucosamine-6-phosphate through a complex pathway that eventually leads to glycosaminoglycans. Glycosaminoglycans then form large aggregating proteoglycans with hylauronic acid to form the matrix in cartilage. Therefore, glucosamine is a fundamental molecule for the synthesis of cartilage.4

Currently, there are many available forms of glucosamine on the market. In Canada, glucosamine is sold as a nutritional supplement and is available in capsule form at pharmacies and health food stores.5 The supplements come from crushed shells of lobster and crab. The exoskeleton is a rich source of chitin, which is a repeating polymer of glucosamine units.6 Glucosamine is sold in various forms including sulfated, hydrochlorinated, iodinated and N-acetylated.7 It has been suggested that sulfated glucosamine is most effective because sulfate is needed in the synthesis of cartilage compounds.8 Glucosamine is also available in combination with other compounds, most commonly chondroitin sulfate. Research shows positive results with the use of both glucosamine and chondroitin to treat osteoarthritis; however, fewer clinical trials have been carried out with chrondroitin.

Osteoarthritis affects about 300,000 Canadians.9 Side effects of current pharmaceutical treatments have propelled the investigation of alternative treatments, including natural supplements like glucosamine and chondroitin. Since the 1960s there have been a number of human trials investigating glucosamine, in various forms and combination with other supplements, on knee and hip osteoarthritis. Most of the studies have suggested a beneficial effect with supplementation.10 However, flaws have been identified in some of these studies including small subject numbers and lack of adequate diagnostic testing for osteoarthritis. Many valid studies found that glucosamine sulfate, at a dose of 500mg, three times per day, is superior to placebo and as effective as ibuprofen in reducing pain due to osteoarthritis of the knee.11 All in all, the research seems to indicate that glucosamine (1500mg a day) is an effective treatment for knee and hip osteoarthritis. In fact, glucosamine may be a superior treatment, according to some studies that suggest it may help regenerate the damaged cartilage in osteoarthritic joints.12

Clinical trials have reported a few side effects attributed to glucosamine supplementation. In doses far in excess of those used in human clinical trials, glucosamine exhibits no known toxicities.13 Side effects reported in clinical trials include heartburn, epigastric pain, nausea,14 drowsiness, skin reactions and headaches.15 However, the hypothesis that glucosamine may cause insulin resistance is of concern. The metabolic steps that glucosamine goes through in the body can be overloaded and block the normal movement of glucose. This can cause insulin resistance in cells exposed to large doses of glucosamine. However, the research in this area is contradictory, as some studies show evidence that this interaction occurs while others do not.16 Regardless, the studies that suggest that glucosamine causes insulin resistance have used higher doses than would ever be used clinically or be available from recommended doses of over-the-counter products. Unfortunately, these studies are difficult to extrapolate into a clinical setting. Currently, the Human Nutraceutical Research Unit at the University of Guelph is investigating the effects of normal, recommended doses of glucosamine in healthy adults. Preliminary results show no incidence of insulin resistance.

Over the past 20 years, studies have demonstrated that oral glucosamine decreases pain and improves mobility in osteoarthritis without serious side effects.17 A typical dose of 1500mg over a day has the potential to reduce pain and swelling, and to increase joint movement. However, clinical science only supports the use of glucosamine for knee and hip osteoarthritis. Caution should be exercised by type II diabetic individuals in case glucosamine does, in fact cause insulin resistance. With regards to the chemical forms of glucosamine the point to note is that all have shown similar positive results in the treatment of osteoarthritis. Therefore, osteoarthritis sufferers desiring to use glucosamine are only advised to choose supplements from reputable companies with demonstrated product quality control in place.

References:

1. Scott, G.N. and G.W. Elmer. 2002. Update on natural product-drug interactions. Am J Health-Syst Pharm. 59:339-346.

2. Piperno, M., Reboul, P., Hellio le Graverand, M.P., Peschard, M.J., Annefield, M., Richard, M. and Vignon, E. 2000. Glucosamine sulfate modulates dysregulated activities of human osteoarthriticchondrocytes in vitro. Osteo Cart. 8:207-212.

3. Runkel, D.R., and Cupps, M.J. 1999. Glucosamine sulfate use in osteoarthritis. Am J Health-Syst Pharm. 56:267-269.

4. Piperno, M., Reboul, P., Hellio le Graverand, M.P., Peschard, M.J., Annefield, M., Richard, M. and Vignon, E. 2000. Glucosamine sulfate modulates dysregulated activities of human osteoarthritic chondrocytes in vitro. Osteo Cart. 8:207-212.

5. Wlock, K. 1997. Glucosamine sulfate in the treatment of osteoarthritis. CPJ/RPC. October:34-5.

6. Stryer, L. 1995. Biochemistry-4th Edition. W.H. Freeman & Company, New York, NY. pp474.

7. Clark, D.M. 1991. Current concepts in the treatment of degenerative joint disease. Comp Cont Ed Pract Vet. 13:1439-1445.

8. Pirohamned, R. and R. Garris. 1998. Glucosamine sulfate in the treatment of osteoarthritis. Pharmacist.August, 66-74.

9. Anonymous. 1998. Glucosamine Sulfate and Chondroitin Sulfate. The Arthritis Foundation. http://www.arthritis.org/resource/statements/glucosamine.asp.

10. Delafuente, J.C. 2000. Glucosamine in treatment of osteoarthritis. Rheum Dis Clin North Am. 26:1-11.

11. Runkel Runkel, D.R., and Cupps, M.J. 1999. Glucosamine sulfate use in osteoarthritis. Am J Health-Syst Pharm. 56:267-269.

12. Piperno, M., Reboul, P., Hellio le Graverand, M.P., Peschard, M.J., Annefield, M., Richard, M. and

Vignon, E. 2000. Glucosamine sulfate modulates dysregulated activities of human osteoarthritic chondrocytes in vitro. Osteo Cart. 8:207-212.

13. AbdelFattah, W., and Hammad, T. 2001. Chondroitin sulfate and glucosamine: a review of their safety profile. JANA. 3:16-23.

14. Delafuente, J.C. 2000. Glucosamine in treatment of osteoarthritis. Rheum Dis Clin North Am. 26:1-11.

15. Barclay, T.S., Tsourounis, C. and McCart, G.M. 1998. Glucosamine: a critical review of the literature. Ann Pharmacother. 32:574-9.

16. Virkamaki, A., Daniels, M.C., and Hamalainen, S. 1997. Activation of the hexosamine pathway by glucosamine in vivo insulin resistance in multiple insulin sensitive tissues. Endocrinology. 138:2501-2507.

17. McAldindon, T. 2001. Glucosamine and chondroitin for osteoarthritis? Bull Rheum Dis. 50:1-4.

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