Glucosamine Sulfate Scores, Again, Against Arthritis

Glucosamine Sulfate Scores,
Again, Against Arthritis

New study adds weight to the already solid case for the benefits of this supplement
By Will Block

This here spot is more than hot—in fact, this joint is jumping!
Fats Waller, in “The Joint Is Jumping”

Artist-enhanced x-ray of a healthy knee and one afflicted with advanced osteoarthritis, showing deterioration of both the cartilage and the bones. (See footnote below.)

umping joints! When was the last time your joints could be described that way? If you’re of a certain age, chances are those days are a distant memory, rekindled when you watch your grandchildren bounce around the house like rubber balls. Don’t you envy them their effortless flexibility and resiliency? Ah, youth! Ah, cartilage! Ah, synovial fluid! Where did you all go?

If this rings a bell, odds are that it’s your knees that are giving you the most trouble. Although the human knee is a masterpiece of biomechanical engineering (credit God or evolution—your choice), it is, alas, highly vulnerable to injury. It’s also the number one target of osteoarthritis, a disease with a perverse love of knees (followed by hips and then various other joints). That may not be surprising, though, considering the constant pounding that our knees take when we walk—and our hips too, although less so. (Curiously, however, our feet are seldom affected by arthritis. How come?)

Worldwide, osteoarthritis (OA) is a leading cause of physical disability, the need for health care, and an impaired quality of life. The impact of osteoarthritis of the knee on disability statistics is similar to that of cardiovascular disease, and it’s greater than that caused by any other medical condition in the elderly.1

Excess Weight Can Hurt Your Knees

It doesn’t help, of course, that so many people are overweight, thus adding to the stresses and strains on their poor, beleaguered knees. Think of every extra pound of fat you may be carrying around as a tiny jackhammer, grinding away at your knees with every step you take.*

*For you anatomy buffs, the point of maximum pressure in the knee, and thus maximum potential loss of cartilage due to osteoarthritis, is the medial compartment of the tibiofemoral joint. That’s a spot on the inner side of the joint between the shinbone (tibia) and the thighbone (femur).

Let’s say you walk a mile, using about 2000 steps, and let’s say you’re 10 pounds overweight, so that with every step, your knee has to bear 10 more pounds of force than nature intended. That’s 20,000 pounds, or 10 tons, of extra force—in only 1 mile! It’s a wonder your knees didn’t disintegrate long ago. Admittedly, this example is an oversimplification (the physics of walking is more complex than that), but you get the idea: being overweight makes those extra stresses and strains on your knees add up fast.

Walk, or Swim

Should any of this, however, be construed as an argument against walking? No! On the contrary, regular exercise-walking is one of the best things you can do for the health of your whole body—starting, of course, with your heart and lungs and including, in most cases, your knees. It depends, though, on what condition they’re in to begin with. If you can walk without pain, chances are the exercise will do your knees good, even if you’re overweight, because the strengthening benefits will outweigh (so to speak) the stress damage. If in doubt, ask your doctor. And if walking is out, then swim—it’s probably the best overall form of exercise there is, with virtually zero stress on your lowdown joints.

No Cure for Osteoarthritis

Even if you’re not overweight, age can take its toll on your joints, especially if you don’t exercise regularly to stay in shape. Use it or lose it! Genetics is also a factor in osteoarthritis—some people are just unlucky in that department and must do that much more (and perhaps many years sooner than others) to resist the effects of OA on their joints.

But how do you resist a disease that’s so cruel and relentless? There is, after all, no cure, despite research spanning generations of dedicated scientists. The, uh, knee-jerk answer is to take drugs to relieve the pain. That’s a good answer, actually, because alleviating the pain of OA pretty much trumps all other considerations, at least to begin with, and drugs definitely help. Bear in mind that we’re using the term drugs loosely here to include nonprescription (over-the-counter) drugs, notably NSAIDs (nonsteroidal anti-inflammatory drugs), which, ironically, are the most widely prescribed by doctors for relieving the symptoms of OA. (For more on this confusing matter, see the sidebar, “When Is a Drug Not a Drug?”)

When Is a Drug Not a Drug?

The easy answer is: When it’s available without a prescription—like glucosamine and its chemical derivatives. The trouble is, we tend not to distinguish between prescription and nonprescription drugs in ordinary speech. We refer to countless over-the-counter remedies as drugs, and we go to the drugstore to buy them. Some examples are antiseptics, antacids, cough medicines, laxatives, nonsteroidal anti-inflammatory drugs, and even some steroidal anti-inflammatory drugs, such as hydrocortisone.

This blurs the important distinction between “real” drugs, i.e., prescription pharmaceuticals, and medicinal preparations that anyone can buy anytime, including nutritional supplements. As two distinct classes of products, they have much in common, but they also have enormous differences, and it behooves informed consumers to understand those similarities and differences.

So when medical researchers call glucosamine (or one of its chemical derivatives) a drug, they’re correct, in terms of common usage. But so are we when we say that it’s not a drug in the strict sense—it’s a nutritional supplement. The beauty of glucosamine is that it has the benefits of being a “real” drug, in terms of scientific validation, but none of the liabilities: it’s available to anyone, anytime.

NSAIDs Don’t Get at the Cause of OA

Until recently, pain relief was virtually the only orthodox treatment for osteoarthritis. Most of the analgesic (pain-killing) and anti-inflammatory drugs used—NSAIDs, mainly—are nonspecific, i.e., they’re general-purpose drugs not targeted at any disease in particular. Furthermore, their chronic use is fraught with harmful side effects, and they may even worsen the osteoarthritic process.2 The newest and somewhat safer NSAIDs, called COX-2 inhibitors, are used primarily for pain relief in osteoarthritis, although they have some other uses as well. In any case, all these drugs are short-term symptom modifiers, i.e., they alleviate the symptoms of the disease without improving the underlying structural problems that cause those symptoms.

That’s fine as far as it goes, but what we really want are drugs (whether prescription or nonprescription) or nutritional supplements that are long-term structure modifiers, i.e., agents that affect the actual disease, not just the symptoms it causes. Even if the Holy Grail of a cure for OA continues to elude us, we want at least to be able to retard or halt, or even reverse, the progress of the disease. That goal has been a prime focus of arthritis research for decades. Many pharmaceutical companies have sought in vain for a drug that will work, all the while trying to overlook the fact that two nutritional supplements, glucosamine and chondroitin, have been widely and successfully used for this purpose.

Glucosamine Sulfate Alters Joint Structure

A breakthrough occurred in 2001 with the publication, in the esteemed British medical journal The Lancet, of a 3-year-long Belgian study on the use of glucosamine sulfate for treatment of osteoarthritis of the knee.3 Various chemical derivatives of glucosamine (which is called a drug in the medical literature) had been used for many years, but solid scientific evidence of their safety and efficacy was lacking. As we reported in the April 2001 issue of Life Enhancement (Landmark in Osteoarthritis Research Validates Glucosamine Sulfate), the Belgian study remedied that deficiency in convincing fashion.

The research was excellent, and the results were positive and credible. Most importantly, they showed that glucosamine sulfate (1500 mg/day, the standard dose in many European and other countries, where it has long been a prescription medication), does indeed alter the joint structure favorably, thus interfering with the progress of the disease. The latter can be assessed accurately by measuring the width of the joint space on x-ray images. (See the sidebar, “What Is OA, and How Does GS Help?”)

What Is OA, and How Does GS Help?

In the normal knee joint, there is a healthy cushion of cartilage (along with a lubricant called synovial fluid) that acts as a shock absorber and insulator, keeping the ends of the bones at a safe distance from each other. In osteoarthritis (OA), however, the cartilage deteriorates and becomes thinner, eventually allowing the bones to rub against each other, causing inflammation and pain.

Glucosamine sulfate (GS), a derivative of the natural glucosamine found in the human body, is obtained by synthesis from chitin, the tough, protective substance that is the principal component of the outer shell of arthropods, such as crabs and shellfish. It is believed that glucosamine and several of its derivatives can help repair cartilage, to which they are chemically related, through various mechanisms that are too complex to be described here.

Kneecap to GS: “What’s a nice molecule like you doing in a joint like this?”

Another substance that is beneficial for OA is the related compound chondroitin, which has also been the subject of much research.1 This compound is most often used in the form of two of its sulfate derivatives: chondroitin 4-sulfate and chondroitin 6-sulfate; these are often referred to collectively as chondroitin 4,6-sulfates.

If you’re into biochemistry, you’ll want to know (or perhaps you already know) that glucosamine is an aminomonosaccharide and a precursor of glycosaminoglycans and proteoglycans, the principal constituents of cartilage. Chondroitin is itself a glycosaminoglycan, so there are some obvious connections there.

  1. 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.

Glucosamine Sulfate Halts OA in Its Tracks

Of the 212 patients who started the 3-year treatment program, 139 completed it, and the ones who were lucky enough to be in the treatment group (as opposed to the control group, which received placebo) must have been glad they did. As a group, they had no significant loss of joint space compared to baseline (i.e., when the treatment began), meaning that the disease was effectively halted in its tracks. By contrast, the control group suffered a significant loss: 0.31 mm, on average. This rate of loss—about 0.1 mm/year—is typical of those measured in long-term studies of OA.

The treatment group also felt better. Based on a standardized symptom-assessment index for OA (the questions pertain to pain, stiffness, and limitations of physical function), their scores were 24.3% better than at baseline, whereas those in the control group had scores that were 9.8% worse—a very significant spread. Furthermore, the side effects reported by the patients (mostly gastrointestinal complaints) were transient and mild to moderate, and there was no substantial difference between the treatment group and the control group in this regard, which means that, for all practical purposes, glucosamine sulfate has no side effects.

But Are the Results Reproducible?

The Belgian study was hailed by an authority in the field as “a landmark in OA research.”2 Conducted by scientists from Belgium, the United States, the United Kingdom, and Italy, it was carefully designed as a randomized, placebo-controlled, double-blind study, with uncommon attention to every detail, and the results were statistically significant—an important factor that sometimes gets overlooked in otherwise well-designed studies in which the patient population is too small.

So—was that good enough to satisfy the medical establishment that glucosamine sulfate is a safe and effective treatment for osteoarthritis? Not on your life! And bravo for that. Good scientists are always skeptical, and a crucial element was missing: reproducibility. Clinical trials are so difficult to do well, so fraught with complexity and the possibility of errors subtle enough to escape the notice of even the most experienced researchers, that one can never be sure their results are valid unless they can be independently reproduced by other researchers under more or less similar conditions.

That, however, is a tall order indeed, because clinical trials are complicated, time-consuming, and expensive. Little wonder, then, that they’re seldom repeated, unless there’s a lot of money to be made on the outcome. Thus, reproducibility is rarely established. We’re left to accept, or not, the results of a given study based on considerations that only other experienced researchers in the field in question could possibly understand and evaluate competently. For everyone else, it’s a matter of faith: you believe the results or you don’t, based largely on subjective criteria.

Reproducibility Is Documented

What a pleasant surprise it was, then, to see in the Archives of Internal Medicine that the Belgian study has been substantially reproduced, in a study conducted in the Czech Republic by researchers at the Charles University in Prague, which has a long history of excellence in medical research.4 Together with colleagues in Italy, the Czech group set out to perform the same kind of 3-year trial of the safety and efficacy of glucosamine sulfate, using the same dosage of 1500 mg/day and following similar experimental protocols. They did this in parallel with the Belgian study, in the hope that the two studies would produce similar results.

Glory be—the results were similar in every major respect (we’ll spare you the details). The important thing is that the much-desired reproducibility of results was achieved, lending greater credibility to both studies. In the authors’ words:

These results are of particular relevance in that they independently confirm and extend the results of another recent study. Glucosamine sulfate, therefore, is the first agent that meets the current requirements to be classified as a symptom- and structure-modifying drug in osteoarthritis, according to the definition of scientific organizations, as acknowledged by regulatory agencies.

The Pharmaceutical Connection

That is most gratifying, and it’s great news—again—for anyone with osteoarthritis, because they can be sure that with glucosamine sulfate, they’re getting the best medicinal agent currently available for retarding the progress of the disease, and thus the pain and disability it can inflict.

It must be frustrating for the pharmaceutical companies to know that glucosamine sulfate is a nutritional supplement and not a prescription drug that they can sell at inflated prices. Well, perhaps it’s not all that frustrating. First of all, glucosamine sulfate is a prescription drug throughout most of the world—but not, fortunately, in the United States, where it is a reasonably priced nutritional supplement.

Furthermore, the Belgian and Czech studies may not have been quite as independent as they at first seemed. In each of the studies, two Italian scientists were among the authors, and they were the same two scientists. Both of them are affiliated with Rotta Research Laboratorium/Rottapharm in Monza, Italy, a multinational pharmaceutical company that is a major manufacturer of . . . you guessed it: glucosamine sulfate. And who was the sole source of funding for both studies? Right again: that same company.

Glucosamine Sulfate Works

Now, does all that mean that the research results are tainted? Not necessarily, and there is no direct evidence that they are. Still, it would be more reassuring if the studies had been truly independent and free of the appearance of financial interest. Bear in mind, on the other hand, that the studies were published in distinguished, peer-reviewed medical journals whose reputations depend on scientific integrity and the avoidance of conflicts of interest—as do the reputations of the other researchers involved, who are affiliated with universities in four countries.

It’s also important to realize that the results of these studies merely provide scientific confirmation of what was already widely accepted—but never proved—by the medical community (especially in Europe) through years of clinical experience: that glucosamine sulfate alleviates the pain and retards the progress of osteoarthritis. So if your joints aren’t jumping, perhaps you should try glucosamine sulfate. It won’t make you a kid again, but it can help stop the clock on osteoarthritis.


  1. Guccione AA, Felson DT, Anderson JJ, et al. The effects of specific medical conditions on the functional limitations of elders in the Framingham Study. Am J Public Health 1994;84:351-8.
  2. McAlindon T. Glucosamine for osteoarthritis: dawn of a new era? Lancet 2001 Jan 27;357:247-8.
  3. Reginster JY, 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. Pavelká K, Gatterová J, Olejarová M, Machacek S, Giacovelli G, Rovati LC. Glucosamine sulfate use and delay of progression of knee osteoarthritis. Arch Int Med 2002 Oct 14;162:2113-23.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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