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GLUCOSAMINE FOR TREATMENT OF OSTEOARTHRITIS
Mikio Kato, MD, FACS, FACOG Gene Mazzocco, MD, FACP Robert Cendo, MD , Edward O. Dingilan, PE
Some people suffering from mild to moderate osteoarthritis claim relief when taking orally glucosamine alone or with chondroitin sulfate. A research published in the Journal of American Medical Association reviews existing studies on glucosamine, and concludes past trials demonstrate claims of moderate to large effect, but suggests quality of the trials have to be reviewed. Nevertheless, the review suggests there exists some degree of probable effectiveness in glucosamine with or without chondrotin supplementation.1
A recent randomized double blind placebo-controlled clinical trial was conducted in Europe over 3 years on 212 patients with knee osteoarthritis. The 102 patients taking 1500mg/day glucosamine sulfate showed in addition to pain relief, no significant joint space loss compared to the patients on placebo who had significant progressive joint-space narrowing. The report published in The Lancet suggests further studies, and an expanded protocol to determine if the present findings of the study will be of clinical importance in the longer term.2
The Arthritis Foundation suggests osteoarthritis suffers to try glucosamine supplementation along with current medications for a period six to eight weeks, and if no improvement of the symptoms within few months, then in all probability the patient will not feel any relief from using the glucosamine supplementation.
The National Center for Complementary and Alternative Medicine (NCCAM) initiated a multi-center, three phase clinical study to determine conclusively whether glucosamine or chondrotin are more effective than placebo for treating knee pain associated with osteoarthritis. The final report is due in March 2005.3
Osteoarthritis is one of the leading ageless disabling diseases in the world, and in United States alone 21 million people suffer from it. By age 65 most people have some form of osteoarthritis.4 It is a disease that causes gradual failure of the entire bone joint including loss of joint space. In a healthy joint, the bone endings have elastic cartilage that acts as a shock cushion, providing a smooth bearing surface, distributes and transmits the body load and motion , thereby reducing joint stress.
The body naturally produces glucosamine from digested carbohydrate to glucose, and the amino acid glutamine that donates the amine to glucose. The glucosamine is further synthesized to proteoglycans which form a component of the joint cartilage matrix, and the synovial fluid that wets the cartilage. With age, the body produces less glucosamine, causing the cartilage to lose its elasticity. Over time, this loss in elasticity results to cartilage degradation, ulceration, eventual narrowing of the space between bone endings, and painful bone to bone contact with inflammation of the joints.
Prevailing cases of osteoarthritis are related to age, the likely consequence of metabolic changes as the body ages. It is believed daily oral supplementation of glucosamine over time may compensate, with varying individual results the body glucosamine deficiency, thereby maintaining a healthy joint endings. This probable explanation has yet to be established by clinical research.
Men before the age 50 have higher incidence of osteoarthritis, and after age 50 the incidence increases with women.5 Estrogen replacement is associated with reduction of incidents of knee and hip osteoarthritis.6 Obesity is also associated with knee and hip osteoarthritis. It is likely body weight increases resulting to osteoarthritis is caused by reduced mobility.7 Obesity and knee osteorthritis is more prevalent with women5. Individuals with osteoporosis exhibit a lower than expected osteoarthritis8.
Occupations requiring repetitive impact labor, shock loading activity on joints, knee trauma from sports, or improper footwear affect progression of osteoarthritis, often manifesting after years.9 Studies show with certain individuals enzymatic degradation of cartilage, blood serum electrolyte imbalances can be potential causes of osteoarthritis.
Commercially glucosamine hydrochloride is manufactured by reacting natural chitin from shrimp, crab, lobster shells with hydrochloric acid, followed by crystallizing and purifying. Glucosamine sulfate is prepared by dissolving and recrystalizing glucosamine hydrochloride with sodium or potassium sulfate salt. On equal weight basis, glucosamine hydrochloride has on the average 26% more available glucosamine compared to the glucosamine sulfate. Experts comment both perform equally well.
Effectiveness of glucosamine varies with quality and purity. It is recommended to purchase glucosamine supplements from established manufacturers who back their product with verifiable certificates of analysis. Often glucosamine supplements are found to include herbal products. There is no scientific published data that demonstrates for, or against the effectiveness of glucosamine when taken with these herbal products.
A European study with a small group showed the body absorbs over 90% of the orally taken glucosamine.10 Limited studies indicate glucosamine appears to be generally safe, and most common side effect being intestinal gas. Glucosamine supplements are not recommended for people with shellfish allergies. Pregnant, lactating women, individuals less than 14 years old, or persons on other medications are recommended to consult first their physician prior to using glucosamine. The effects of chondrotin sulfate on the body are lesser studied. The bioavailability mechanism and effectiveness of glucosamine salts, and chondroitin sulfate supplements related to osteoarthritis is still not well defined and requires further clinical long term studies. Glucosamine has been shown to possess anti-inflammatory properties11, and in vivo studies have demonstrated beneficial effects on cartilage metabolism12
There is a growing body of evidence from osteoarthitis suffers showing some degree of pain relief when using glucosamine with or without chondroitin sulfate. In certain cases the symptom relief described to be comparable to that from aspirin or ibuprofen. The difference being in the case of glucosamine it may actually be a contributing factor to slowing cartilage damage compared to nonsteroidal anti-inflammatory drugs (NSAID) such as aspirin or ibuprofen that only relieve the pain and inflammation associated with osteoarthritis. Glucosamine is being used in Europe for over a decade.
More physicians are recommending osteoarthritis patients use of glucosamine as an alternative choice.
Nevertheless, until formal clinical research conclusively demonstrates statistically significant long term effectiveness of glucosamine, science will view the symptom relief claims made by glucosamine users as anecdotal
1. McAlindon TE et al: Glucosamine and chondroitin for treatment of osteoarthritis. JAMA 2000, 283:1469-147
2. Reginster JY et al: Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001, 357:251-256
3. National Institute of Health, news release: Glucosamine/Chondroitin Arthritis Intervention Trial. http://nccam.nih.gov/nccam/ne/press-releases/121100
4. Meyers SL et al: Prevalence of cartilage shards in synovium and their association with synovitis in patients with early and endstage osteoarthritis.J Rheumatol 19:1247-1251, 1992
5. Van Sasse JLCM et al: Epidemiology of osteoarthritis.., Ann Rheum Dis 48:271-280, 1989
6. Mankin HJ et al: Biochemical and metabolic abnormalities articulator cartilage from osteoarthritis hips. J
Bone Joint Surg 52A: 424, 1970
7. Felson DT et al: Obesity and knee osteoarthritis. The Framingham study Ann Intern Med 109:18-24, 1988
8. Hart DJ et al: The relationship between osteoarthritis and osteopororis in the general population. Ann
Rheum Dis 53:158-162, 1994
9. Lindberg H et al: Heavy labor and the occurance of gonarthritin Clin Orthop 214:235-236, 1987
10. Setnikar I, et al: Pharmacokinetics of glucosamine in man.Drug Res 43(H):10, 1993
11. Sentikar I, et al: Antireactive properties of glucosamine sulfate Arzenmittelforschung 41:542-545, 1991
12. Bassleer CT, et al: Stimulation of protoglycan production by glucosamine sulfate in chondrocytes isolated
from human osteoarthritic cartilage in vitro. Osteoarthritis Cartilage 6:427-434, 1998
Supplemental readings:
1. “Glucosamine, Nature’s Arthritis Remedy”. Ray Sahelian,MD ISBN:0-9639755-2-8
2. “The Arthritis Cure”. Jason Theodosakis, MD, MS, MPH et al ISBN: 0-312-96453-6
Mikio Kato, MD, FACS, FACOG, Gene Mazzocco, MD, FACP,
Robert Cendo, MD,
Edward O. Dingilian, PE, President, United Chitotechnologies, Inc. USA
Correspondence to: Edward O. Dingilian, PE, (e-mail:Edingilian@aol.com)
November 29, 2001