by Christian Finn
If you've ever suffered from any form of joint pain, you know how miserable it can make your life. Most people take their joints for granted. When they're working smoothly, they demand little attention. But once they begin to ache, they take center stage.
Joint pain is like a constant throbbing ache that never seems to go away. Pain killers, such as aspirin or ibuprofen, are usually prescribed to treat these symptoms. Although they're safe to use in the short term, long-term use of pain killers can cause serious damage to the lining of your stomach. However, it is possible to dramatically reduce joint pain without relying on pain killers.
Every time that you move a joint (such as your knee), there is a tremendous pressure imposed on it. To reduce some of this stress, your joints are protected by cartilage, which is an extremely "tough" tissue. Think of cartilage like a shock absorber. It acts like a "cushion" between bones. Unfortunately, cartilage can wear away leaving the heads of the bone making painful contact with each other.FIGURE 1: Cartilage acts like a "cushion" between bones such as the femur (the bone in the top of your thigh) and the tibia (also known as the shin bone).
Cartilage is helped in the process of shock absorption by synovial fluid. Synovial fluid helps to keep a joint lubricated (a little like the oil in your car engine), and contains an important substance known as hyaluronic acid (pronounced high-al-your-onik) .
When hyaluronic acid has been applied to wounds following surgery, it results in faster healing, reduces scarring, and can also preserve cartilage. Interestingly, arthritic joints appear to be deficient in hyaluronic acid [17, 18].
Arthritis literally means inflammation of a joint. It often begins subtly, with a little aching and stiffness. However, arthritis can also announce its presence far more dramatically, with swollen joints that literally cry out with pain.
If you've ever suffered from a joint injury especially to the knee your chances of developing arthritis are greatly increased. In fact, a previous joint injury is one of the strongest predictors that you'll end up with arthritis later in life [13, 24].
Of course, just because you're suffering from joint pain doesn't mean that you have arthritis. However, arthritis is the most common chronic disease in the world. The two most common types are osteoarthritis and rheumatoid arthritis, which affect millions of people across the world [9, 10].
Usually, the pain in the early stages of arthritis is due to inflammation. As the disease progresses and the cartilage is worn away, most of the pain comes from the friction of raw bones rubbing against each other. In the normal knee (shown below in the image on the left), cartilage is represented by the black space between the thigh bone and shin bone. However, the arthritic knee on the right shows black space on only one side of each knee indicating a loss of cartilage.
FIGURE 2: A comparison between a normal (left) and an arthritic (right) knee.
There are various treatments that deal with the symptoms of arthritis. For instance, new injections known as Hyalgan and Synvisc have been approved by the FDA. Both contain derivatives of hyaluronic acid. In theory, restoring hyaluronic acid to diseased joints will reduce both inflammation and pain. Unfortunately, the injections have to be repeated regularly, which makes this option very expensive.
While surgical procedures (cartilage transplantation and joint resurfacing) do show some promise, the most popular treatments are pain killers, such as aspirin and ibuprofen. But what most don't realize is that over-the-counter pain killers may actually be doing them more harm than good.
The truth is, taking aspirin, ibuprofen or acetaminophen is perfectly safe for the short term. But they can lead to serious, often irreversible, side effects.
One of the ways in which pain killers work is by inhibiting the production of prostaglandins in joints. This relieves the symptoms of arthritis. However, it creates problems in the gut where these very same prostaglandins are beneficial. Take pain killers long enough, or in high doses, and you could end up with "holes" in the lining of your stomach.
That's why COX-2 inhibitors such as Celebrex and Vioxx have become so popular since they entered the market back in 1999. Also known as the "super" aspirins, COX-2 inhibitors inhibit the activity of an enzyme called cyclo-oxygenase 2, which is linked with pain and inflammation.
Their advantage over traditional pain killers is that they have no effect on cyclo-oxygenase 1 (also known as COX-1), the enzyme involved in protecting your stomach. In other words, COX-2 inhibitors are just as effective as other pain killers, but much less likely to cause stomach ulcers or bleeding.
However, while the selective COX-2 inhibitors serve to interrupt inflammation early on, it appears they may make the inflammation worse later. Concerns about the long-term safety of COX-2 inhibitors, together with the rise in popularity of "natural" food supplements, have led to an increase in the use of preparations containing glucosamine and chondroitin sulfate.
Glucosamine and chondroitin sulfate
Glucosamine and chondroitin sulfate are popular supplements that claim to contribute to healthy joints. Used to treat osteoarthritis in horses and dogs for decades, both glucosamine and chondroitin occur naturally in your body. Both play a key role in the construction of cartilage
Glucosamine, for example, stimulates the production of glycosaminoglycans (the structural components of cartilage) as well as the incorporation of sulfur into cartilage. Sulfur is necessary for making and repairing cartilage. Chondroitin works a little differently. It helps to keep cartilage resilient by drawing fluid (particularly water) into the connective tissue. It may also inhibit enzymes that break down cartilage, as well as providing the building blocks that cartilage needs to repair itself.
The supplements are extracted from animal tissue. Glucosamine comes from crab, lobster or shrimp shells. Chondroitin sulfate is often derived from cattle tracheas.
A number of studies show that both glucosamine and chondroitin sulfate can reduce joint pain without the side effects often seen with commonly prescribed medication .
For example, a group of 34 men from the elite special warfare group of the U.S Navy were assigned to one of two groups . The men in the first group, all of whom suffered from osteoarthritis of the knee or hip, were given Cosamin®DS a combination of glucosamine hydrochloride (1500 mg daily), chondroitin sulfate (1,200 mg daily) and manganese ascorbate (228 mg) for four months. Group two was given a fake supplement. Four months later, the men given Cosamin®DS reported a large drop in knee pain. Their score in a physical examination also improved. A similar study, again using Cosamin®DS, showed an improvement in joint function in patients with mild or moderate degeneration of knee cartilage .
In a comprehensive review of 15 clinical trials, carried in the Journal of the American Medical Association, researchers conclude that glucosamine and chondroitin sulfate, "demonstrate moderate to large effects, but quality issues and likely publication bias suggest that these effects are exaggerated" .
Publication bias is the tendency to publish research with positive outcomes much more frequently than research with negative outcomes. Negative outcome refers to finding nothing of consequence, not to finding that something affects us negatively.
Although lead author of the JAMA review Dr. Timothy McAlindon, an Associate Professor of Medicine at Boston University, admits that glucosamine and chondroitin may have some efficacy in osteoarthritis, their benefits may be "exaggerated".
"I don't actively discourage my patients from trying these substances, as long as they are prepared to take the financial impact and are aware of the possibility that they may not work at all", says Dr. McAlindon.
Moreover, one of the problems with glucosamine sulfate is the possibility of a link to a condition known as insulin resistance. Someone with insulin resistance has cells that respond sluggishly to the action of insulin. It's a condition that is a precursor to a sinister-sounding condition called Syndrome X.
The term was coined by researchers at Stanford University to describe a cluster of symptoms, including high blood pressure, elevated plasma triglycerides, and obesity, which tend to appear together in some individuals and increase their risk for type II diabetes and heart disease.
Scientists have known for some time that glucosamine causes insulin resistance in both animals and human skeletal muscle cultures [1, 3, 22]. Glucosamine, when infused directly into the bloodstream, has also been shown to cause a mild degree of insulin resistance in healthy non-diabetic males . Because people with osteoarthritis are often elderly (and overweight), the use of glucosamine may increase their risk of developing one or more of the conditions associated with Syndrome X.
That said, it's important to note that the study linking glucosamine with insulin resistance in healthy male subjects infused glucosamine straight into the blood, rather than providing it orally. However, it does point to the need for research tracking the long-term effect of oral glucosamine supplementation on insulin resistance. One alternative is to use chondroitin alone, rather than in combination with glucosamine sulfate. Chondroitin hasnt been shown to affect insulin sensitivity, yet still provides the same benefits to cartilage as glucosamine.
Chondroitin sulfate is useful for the treatment of osteoarthritis, both as an agent that progressively reduces joint pain and as a compound that reduces the need for the use of pain killers .
Chondroitin sulfate has an extremely powerful capacity to attract and retain water molecules. The presence of water within cartilage makes it highly resistant to both friction and impact forces. That's why cartilage is so good at protecting your joints from damage.
Bones can't rub against each other when they are "capped" properly with cartilage. Unfortunately, as the cartilage loses some of its fluid-retaining properties, much of the protective effect is lost. Adding chondroitin sulfate to your diet might help to "restore" cartilage to its previous "healthy" state.
One of the main criticisms of chondroitin sulfate is that it's degraded in your digestive system long before it can reach your joints. However, research shows that chondroitin sulfate IS absorbed from the small intestine into the bloodstream . In fact, after just 10 days of oral supplementation with chondroitin sulfate (800 mg daily), hyaluronic acid concentration and the viscosity of synovial fluid is significantly increased .
Much like glucosamine, chondroitin has been shown to significantly reduce the pain of arthritic joints. In a study carried out at the University of Siena in Italy, 146 patients with osteoarthritis of the knee were divided into two groups . Patients in one group were given 150 mg of diclofenac each day (diclofenac is a non-steroidal anti-inflammatory medication often used to treat arthritis). A second group used 1200 mg of chondroitin sulfate.
Patients treated with diclofenac experienced prompt and effective relief from their symptoms. However, their pain and discomfort returned quickly when they stopped using it. Although it took longer for the subjects using chondroitin sulfate to get relief from their symptoms, the benefits lasted for up to three months after they stopped taking the chondroitin.
A French research team report similar results. Test subjects with osteoarthritis of the knee were given one gram of chondroitin sulfate daily for three months . Joint pain was significantly reduced both during and for 30 days AFTER the treatment period. The ability of chondroitin sulfate to keep working even after you stop taking it suggests that you don't need to use chondroitin sulfate all the time.
An additional benefit of chondroitin sulfate is that some (but not all) of the anti-inflammatory drugs prescribed for osteoarthritis may lead to a more rapid "closing" of joints . When a joint closes, the cartilage covering bones gradually disappears. As the bones edge closer together, joint flexibility is lost. In contrast, chondroitin sulfate has been shown to actually slow the loss of cartilage. Some evidence for this comes from a placebo-controlled trial carried in the journal Osteoarthritis and Cartilage.
Researchers at the University Hospital of Geneva in Switzerland tracked a group of 42 patients given 800 mg chondroitin sulfate daily for 12 months . Subjects were aged between 35-78, and all had symptoms of osteoarthritis in the knee.
Chondroitin sulfate significantly reduced joint pain, confirming its effectiveness as a safe slow-acting treatment for osteoarthritis of the knee. More interesting still, treatment with chondroitin sulfate was also associated in some of the patients with a stabilization of joint width in the knee. Joint-space narrowing did occur in patients treated with the placebo. This suggests that chondroitin sulfate was slowing the loss of cartilage.
Unfortunately, there's no real evidence to support the use of chondroitin sulfate as a way to protect against future injury. To date, the only studies linking chondroitin sulfate with a reduction in joint pain have been carried out with osteoarthritis patients. However, the idea of using chondroitin as a way to keep your joints healthy certainly merits serious consideration. If you have suffered from cartilage damage in the past, chondroitin sulfate supplementation is certainly worth a try. One single daily dose of chondroitin sulfate (1200 mg) appears to be equally as effective as three doses of 400 mg .
The bottom line
The majority of the research to date shows that both glucosamine (in both sulfate and hydrochloride form) and chondroitin sulfate either alone or as a combination appear to have a beneficial effect on joint function. The reduction in joint pain is also comparable (albeit not quite as rapid) to prescribed medication. The benefits usually show after one or two months of use, and last for up to three months after you stop using it.
Unfortunately, one of the main problems associated with glucosamine and chondroitin products is that you can never be sure about exactly what you're getting. The supplement industry is poorly regulated, and discrepancies in some of the study findings may relate to the quality of the supplements used . For example, research from the University of Maryland shows that many glucosamine and chondroitin preparations don't contain what they're supposed to. Cosamin®DS [http://www.nutramaxlabs.com/] is a reliable glucosamine/chondroitin product used successfully in several human trials [7, 15].
However, the long-term effect of oral glucosamine on insulin resistance isn't well understood. If there is an increased risk of developing one or more of the "cluster" of symptoms associated with Syndrome X, it's likely to be greater in people who are overweight, or who already suffer from diabetes. In addition, anyone with an allergy to shellfish (from which glucosamine is extracted) can't use it.
If you want to use chondroitin sulfate alone, one of the few products tested in human trials is Condrosulf® [http://www.ibsa.ch/], which appears to be available on a prescription-only basis. Consumer Lab has tested various glucosamine and chondroitin blends [http://www.consumerlab.com/results/gluco.asp], with only one chondroitin-only product (made by Now Foods [http://www.nowfoods.com/]) passing the test. Avoid chondroitin made from shark cartilage, as it contains many other ingredients besides chondroitin sulfate, and the quality is extremely inconsistent.
As with all dietary supplements, there is the potential for side effects and interactions with medications. For a list of drugs that may interact with chondroitin, visit http://www.healthandage.com/html/res/com/ConsSupplements/Chondroitincs.html
For a list of drugs that may interact with glucosamine, visit http://www.healthandage.com/html/res/com/ConsSupplements/Glucosaminecs.html.
If glucosamine or chondroitin sulfate don't appeal to you, there is some early (though far from conclusive) evidence to show that a milk-based product called NuVim [http://www.nuvim.com/WhatIsNuvim.asp] can alleviate some of the symptoms of osteoarthritis over a six-week period .
1. Baron, A.D., Zhu, J.S., Zhu, J.H., Weldon, H., Maianu, L., & Garvey, W.T. (1995). Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity. Journal of Clinical Investigation, 96, 2792-2801
2. Bourgeois, P., Chales, G., Dehais, J., Delcambre, B., Kuntz, J.L., & Rozenberg, S. (1998). Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 x 400 mg/day vs placebo. Osteoarthritis and Cartilage, 6, S25-S30
3. Ciaraldi, T.P., Carter, L., Nikoulina, S., Mudaliar, S., McClain, D.A., & Henry, R.R. (1999). Glucosamine regulation of glucose metabolism in cultured human skeletal muscle cells: divergent effects on glucose transport/phosphorylation and glycogen synthase in non-diabetic and type 2 diabetic subjects. Endocrinology, 140, 3971-3980
4. Colker, C.M., Swain, M., Lynch, L., & Gingerich, D.A. (2002). Effects of a milk-based bioactive micronutrient beverage on pain symptoms and activity of adults with osteoarthritis: a double-blind, placebo-controlled clinical evaluation. Nutrition, 18, 388-392
5. Conte, A., Volpi, N., Palmieri, L., Bahous, I., & Ronca, G. (1995). Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate. Arzneimittelforschung, 45, 918-925
6. da Camara, C.C., Dowless, G.V. (1998). Glucosamine sulfate for osteoarthritis. Annals of Pharmacotherapy, 32, 580-587
7. Das, A., & Hammad, T.A. (2000). Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and manganese ascorbate in the management of knee osteoarthritis. Osteoarthritis and Cartilage, 8, 343-350
8. Deal, C.L., & Moskowitz, R.W. (1999). Nutraceuticals as therapeutic agents in osteoarthritis, chondroitin sulfate, and collagen hydrolysate. Rheumatic Diseases Clinics of North America, 25, 379-395
9. Felson, D.T., Lawrence, R.C., Dieppe, P.A., Hirsch, R., Helmick, C.G., Jordan, J.M., Kington, R.S., Lane, N.E., Nevitt, M.C., Zhang, Y., Sowers, M., McAlindon, T., Spector, T.D., Poole, A.R., Yanovski, S.Z., Ateshian, G., Sharma, L., Buckwalter, J.A., Brandt, K.D., & Fries, J.F. (2000). Osteoarthritis: new insights. Part 1: the disease and its risk factors. Annals of Internal Medicine, 133, 635-646
10. Felson, D.T., Lawrence, R.C., Hochberg, M.C., McAlindon, T., Dieppe, P.A., Minor, M.A., Blair, S.N., Berman, B.M., Fries, J.F., Weinberger, M., Lorig, K.R., Jacobs, J.J., & Goldberg, V. (2000). Osteoarthritis: new insights. Part 2: treatment approaches. Annals of Internal Medicine, 133, 726-737
11. Huskisson, E.C., Berry, H., Gishen, P., Jubb, R.W., & Whitehead, J. (1995). Effects of antiinflammatory drugs on the progression of osteoarthritis of the knee. LINK Study Group. Longitudinal Investigation of Nonsteroidal Antiinflammatory Drugs in Knee Osteoarthritis. Journal of Rheumatology, 22, 1941-1946
12. Kelly, G.S. (1998). The role of glucosamine sulfate and chrondoitin sulfates in the treatment of degenerative joint disease. Alternative Medicine Reviews, 3, 27-39
13. Lau, E.C., Cooper, C., Lam, D., Chan, V.N., Tsang, K.K., & Sham, A. (2000). Factors associated with osteoarthritis of the hip and knee in Hong Kong Chinese: obesity, joint injury, and occupational activities. American Journal of Epidemiology, 152, 855-862
14. Leeb, B.F., Schweitzer, H., Montag, K., & Smolen, J.S. (2000). A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. Journal of Rheumatology, 27, 205-211
15. Leffler, C.T., Philippi, A.F., Leffler, S.G., Mosure, J.C., & Kim, P.D. (1999). Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Military Medicine, 164, 85-91
16. Mazieres, B., Combe, B., Phan Van, A., Tondut, J., & Grynfeltt, M. (2001). Chondroitin sulfate in osteoarthritis of the knee: a prospective, double blind, placebo controlled multicenter clinical study. Journal of Rheumatology, 28, 173-181
17. McCarty, M.F. (1996). Glucosamine for wound healing. Medical Hypotheses, 47, 273-275
18. McCarty, M.F., Russell, A.L., & Seed, M.P. (2000). Sulfated glycosaminoglycans and glucosamine may synergize in promoting synovial hyaluronic acid synthesis. Medical Hypotheses, 54, 798-802
19. McAlindon, T.E., LaValley, M.P., Gulin, J.P., & Felson, D.T. (2000). Glucosamine and chrondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. Journal of the American Medical Association, 283, 1469-1475
20. Monauni, T., Zenti, M.G., Cretti, A., Daniels, M.C., Targher, G., Caruso, B., Caputo, M., McClain, D., Del Prato, S., Giaccari, A., Muggeo, M., Bonora, E., & Bonadonna, R.C. (2000). Effects of glucosamine infusion on insulin secretion and insulin action in humans. Diabetes, 49, 926-935
21. Morreale, P., Manopulo, R., Galati, M., Boccanera, L., Saponati, G., & Bocchi, L. (1996). Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. Journal of Rheumatology, 23, 1385-1391
22. Patti, M.E., Virkamaki, A., Landaker, E.J., Kahn, C.R., & Yki-Jarvinen, H. (1999). Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle. Diabetes, 48, 1562-1571
23. Ronca, F., Palmieri, L., Panicucci, P., & Ronca, G. (1998) Anti-inflammatory activity of chondroitin sulfate. Osteoarthritis and Cartilage, 6, 14-21
24. Sutton, A.J., Muir, K.R., Mockett, S., & Fentem, P. (2001). A case-control study to investigate the relation between low and moderate levels of physical activity and osteoarthritis of the knee using data collected as part of the Allied Dunbar National Fitness Survey. Annals of the Rheumatic Diseases, 60, 756-764
25. Uebelhart, D., Thonar, E.J., Delmas, P.D., Chantraine, A., & Vignon, E. (1998). Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarthritis and Cartilage, 6, S39-S46
Copyright © 2000-2002. Christian Finn. All rights reserved. No part of this website may be reproduced or transmitted in any form or by any means without written permission from the author.