Acetyl Glucosamine Fills a Critical Need

The group most affected by knee osteoarthritis is helped by 
a supplement with no real competition

By Dr. Edward R. Rosick

As the only practitioner of complementary and alternative medicine in a multicenter practice in central Pennsylvania (an area not known, at least in terms of its medical community, for embracing change), it can be frustrating to try to educate my colleagues on the usefulness of supplements in maintaining optimal health. One of the most common arguments I hear from them is, “Those supplements don’t have any type of research backing them up.” Although that’s certainly true for some of the more esoteric, and frankly questionable, products on the market, it’s not at all true for a great many supplements (such as those featured in this magazine).

Among the supplements that rest on rock-solid scientific foundations are two that are often found combined in one product for use in osteoarthritis: glucosamine and chondroitin. We’ll get to them shortly, but first, let’s have a quick look at the disease they help alleviate.

Osteoarthritis—Disabler of Millions

Osteoarthritis (OA) is one of the most common and debilitating diseases to afflict middle-aged and elderly people. Among the 13% of the U.S. population 65 years of age or older—some 35 million people—it’s estimated that at least 13 million suffer from OA. Despite decades of research on the origins and characteristics of OA, scientists are still not sure what causes this debilitating condition—and there is still no cure. Remarkably, there is not even a drug that does anything more than relieve the pain of OA. Pain relief is a huge plus, of course, but it does nothing to improve the underlying condition.

Victims of OA have progressive degeneration of the joints. Although all the body’s joints can be attacked, the disease is most commonly seen in the knees; the hands are also often affected. Up to the age of about 50, OA of the knees is more prevalent in men than in women; in the more elderly population, however, the incidence of knee OA increases more rapidly in women. Both men and women with severe OA suffer not only from pain and stiffness caused by joint destruction, but also from significant loss of mobility, which can greatly interfere with every aspect of their lives.

Conventional Therapy Does Not Stop OA’s Progression

When patients with OA walk (or hobble) into a doctor’s office today, they can pretty much count on getting a prescription for a nonsteroidal anti-inflammatory drug—an NSAID. Some NSAIDs, such as aspirin, acetaminophen, ibuprofen, and naproxen, are sold over-the-counter, but other, more powerful ones are prescription drugs that can be quite expensive. Although they can help ease the inflammation and pain of OA, they do nothing to retard the progression of this disabling disease. In addition, NSAIDs can have significant and potentially life-threatening side effects, such as gastrointestinal bleeding. Even more distressing is that some studies show that NSAIDs may actually hasten the progression of OA.1

So if a patient with OA can’t tolerate the side effects commonly associated with NSAIDs, what else can mainstream medicine offer? The answer, sadly, is very little. Physical therapy can be used to try to regain some of the mobility lost to the ravages of joint degradation, and surgery is sometimes used to replace joints that have been severely damaged. A relatively new therapy entails a series of injections of a lubricating fluid directly into the knee joint. These methods are of limited use, however, and can be very expensive—and, as with painkillers, they do not affect the disease itself.

Glucosamine and Chondroitin Do Stop It

One of the Holy Grails of conventional medicine is to find a drug that can stop the progression of OA. Ironically, such a substance exists and is in use throughout the world—but it’s not a drug. It’s glucosamine, which is commonly formulated together with its chemical relative, chondroitin. These are safe, effective, natural compounds that are used as nutritional supplements. Although glucosamine and chondroitin are helpful in relieving the symptoms of OA, their primary benefit lies in improving the structure of the affected joints, i.e., in retarding the progression of the disease.*

Glucosamine, an amino sugar, is a fundamental biochemical building block for a variety of important substances in the body, including compounds called glycosaminoglycans,of which chondroitin is an example.† The glycosaminoglycans are components of large molecular complexes called proteoglycans, which, together with the protein collagen, form the structural framework of cartilage, a resilient, slippery material found in all our joints.

†Although glucosamine is a sugar, it does not impair blood sugar control and is safe for diabetics to use at doses recommended by the manufacturer.2

Cartilage Needs Glucosamine and Chondroitin

Together with synovial fluid (the lubricant in our joints), cartilage acts as a shock absorber and buffer to prevent our bones from rubbing against each other—when it’s young and healthy. If cartilage becomes worn or degraded, however, as often occurs in aging joints (especially the knees, which take relentless pounding throughout our lives), there can be hell to pay. Bone rubs against bone, inflammation ensues, and the pain can be debilitating. What our joints need (preferably long before this scenario has had a chance to occur) is an abundant supply of proteoglycans in order to maintain healthy cartilage.

That’s where glucosamine and chondroitin come in, because they’re proteoglycan precursors. In our bodies, they’re found primarily in the form of their sulfate derivatives, and it is these sulfates that are most commonly used as nutritional supplements. Whereas glucosamine sulfate is a single chemical compound, chondroitin sulfate is actually a mixture of closely related compounds, consisting mainly of two forms called chondroitin 4-sulfate and chondroitin 6-sulfate—a combination called chondroitin 4,6-sulfates for short. Some researchers believe that the beneficial effects of chondroitin sulfate supplements may depend in part on the ratio of the 4-sulfate to the 6-sulfate in the mixture, with a preference for a 60:40 ratio.

Scientific Evidence for Glucosamine and Chondroitin Piles Up

In the field of nutritional supplements, few substances have been as well documented for their intended purpose as glucosamine and chondroitin. A series of clinical trials by a research group in Belgium (with international collaborators) have given convincing evidence that these compounds, in addition to providing symptomatic relief, favorably alter the structure of the joint, thereby retarding the disease’s progression.3,4,5 Dr. Tim McAlindon, of the Arthritis Center at Boston University Medical Center, hailed the first of these studies as “a landmark in OA research,”1 and he published a meta-analysis of the literature on the subject, concluding that glucosamine and chondroitin had the potential for “considerable utility in OA treatment.”6

Despite abundant evidence of the safety and efficacy of glucosamine and chondroitin, however, many physicians (who may not be familiar with the literature on them) are skeptical, because they tend to be skeptical of supplements in general. The literature keeps on coming, however, and these arthritis-fighting agents are sure to become more widely accepted by mainstream medicine as time goes on.

Glucosamine Protects Women’s Knees and Relieves Symptoms

The latest study from the Belgian scientists (actually, two 3-year studies, conducted as randomized, double-blind, placebo-controlled trials, and published in one paper) shows again why glucosamine should be an integral part of every treatment plan for patients with OA.7 The researchers examined the effects of glucosamine sulfate (1500 mg daily) in 319 postmenopausal women (average age 64) who had OA of the knees. This is the population most affected by OA. X-ray images of the women’s knees were taken at the beginning and the end of the studies to assess any changes—particularly in the joint-space width, a measure of joint deterioration—that might have occurred during the 3-year period. The researchers also measured the primary symptoms of OA—pain, stiffness, and impaired mobility—using a standardized test, the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index.

The results were most gratifying. After 3 years, the women who had been taking glucosamine sulfate showed no narrowing of the joint-space width in their knees—indicating no progression of the disease—whereas the women on placebo had a narrowing of 0.33 mm (which might not sound like much, but in the knee joint, it’s significant). As for subjective complaints, the treated women showed significant improvement: a 14% reduction in the WOMAC score, vs. a 5.4% increase for the controls. Women in the glucosamine sulfate group reported improvements in pain and mobility, but not in stiffness.

The authors stated,

Results of the present study suggest that long-term oral administration of glucosamine sulfate for 3 years can delay the natural symptomatic and structural course of knee osteoarthritis in postmenopausal women.

A Little Knowledge Is a Wonderful Thing

I know all too well how frustrating it can be when it comes to educating those who are not well versed in alternative medicine about the significant benefits that many types of supplements can have in combating debilitating illnesses, such as osteoarthritis. I also believe, however, that patients are well advised to take the time to educate themselves and their physicians about the scientific validity and practical value of safe, natural supplements, such as glucosamine and chondroitin, in treating illnesses for which conventional medicine can do little.


  1. McAlindon T. Glucosamine for osteoarthritis: dawn of a new era? Lancet 2001 Jan 27;357:247-8.
  2. Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Arch Intern Med 2003;163:1587-90.
  3. Reginster J-Y, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE, Gossett C. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001 Jan 27;357:251-6.
  4. Reginster J-Y, Bruyere O, Lecart M-P, Henrotin Y. Naturocetic (glucosamine and chondroitin sulfate) compounds as structure-modifying drugs in the treatment of osteoarthritis. Curr Opin Rheumatol 2003;15:651-5.
  5. Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster J-Y. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 2003;163:1514-22.
  6. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000 Mar 15;283(11):1469-75.
  7. Bruyere O, Pavelka K, Rovati LC, Deroisy R, Olejarova M, Gatterova J, Giacovelli G, Reginster J-Y. Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies. Menopause 2004;11(2):138-43.

 Chondroitin Helps with Arthritis of the Hands

While OA often wreaks havoc on a person’s knees, it can affect other joints as well. Erosive osteoarthritis (EOA) of the hands causes significant inflammation and pain in its victims, and it can severely limit their ability to perform even the most basic tasks of everyday life. As with OA of the knees, conventional medicine can offer pain relief, but no real protection against progression of the disease. Studies have shown, however, that chondroitin may decrease the rate of progression of the disease in addition to providing symptomatic relief.

In a recent study, researchers in Italy gave patients with EOA of the hands (22 women and 2 men, average age 53) either 500 mg of naproxen (a commonly used NSAID) or naproxen plus 800 mg of chondroitin sulfate, daily; both groups took naproxen when necessary for pain relief.1 The patients’ condition was assessed via questionnaires and x-rays, at baseline and again at 12 and 24 months.

All the patients in this study showed progressive worsening of their EOA, with increases in the number of joints affected, but the rate of worsening was slightly slower in those taking chondroitin sulfate. On the other hand, the global assessment of disease activity, carried out by the patients and the physicians, showed no changes from baseline in the treated group, but a significant worsening in the untreated group. The authors concluded, “… we believe that oral chondroitin sulfate is currently the drug of choice for diminishing joint damage in erosive osteoarthritis.”

  1. Rovetta G, Monteforte P, Molfetta G, Balestra V. A two-year study of chondroitin sulfate in erosive osteoarthritis of the hands: behavior of erosions, osteophytes, pain, and hand dysfunction. Drugs Exp Clin Res 2004;XXX(1):11-6.



Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master’s degree in healthcare administration.