Are these two fashionable supplements any good as a remedy?
Glucosamine and chondroitin (chondroitin sulphate) supplements have grown in popularity with athletes, because the two compounds are thought to soothe painful joints and decrease the risk of osteoarthritis. Glucosamine and chondroitin are commonly believed to prevent the breakdown of joint cartilage and/or stimulate the production of new cartilage, preserving joint integrity in the face of heavy training. Sales of the two compounds are brisk, reaching an estimated one billion (!) dollars in the United States.
Glucosamine is made from glucose (sometimes called 'blood sugar' because of its ubiquitous presence in the blood) and a crystalline amino acid called glutamine. In the human body, it is often incorporated into proteoglycans, which are basically proteins that contain long chains of sugar (glucose) molecules. Proteoglycans are found throughout the body, but they seem to be concentrated mainly in the spaces between cells, including the joints, and they have a strong ability to attract water. As I've said, glucosamine advocates have suggested that the chemical may inhibit the breakdown of joint cartilage and/or stimulate new cartilage formation.
Chondroitin sulphate is a 'glycosaminoglycan' (basically, a compound which contains an amino acid attached to a chain of carbohydrate) and is a key component of cartilage. Like glucosamine, chondroitin has a strong affinity for water, and it seems to be able to 'pull' water into joints and thus keep them lubricated. As part of the aging process, the quantity of chondroitin sulphate in joint cartilage tends to decline, and joints become stiffer and less resilient.
Both glucosamine and chondroitin sulphate are manufactured readily by the human body, so the basic strategy underlying supplementation is to magnify the body's basic levels of the two compounds. Advertisements for glucosamine and chondroitin sulphate typically proclaim that the compounds relieve pain and increase range of motion. Supplement makers use sea shells and animal cartilage (including shark cartilage) to produce their chondroitin-sulphate and glucosamine products, and they market the compounds to two basic groups of people:
(1) individuals suffering from osteoarthritis, and
(2) athletes experiencing 'overuse' injuries.
Symptoms of osteoarthritis
Let's look at those two groups for a moment (naturally, there is some overlap, since many athletes also have osteoarthritis), and think about whether glucosamine and chondroitin would really be helpful to them. Osteoarthritis is a degenerative, debilitating disease; it is widespread (about one in 12 Americans suffers from it), and the risk of developing it increases with age. Symptoms of osteoarthritis also tend to be magnified by the aging process
In osteoarthritis, joint cartilage breaks down, and there is a narrowing of the space between the bones which meet at a joint. The joint bones themselves undergo deleterious chemical change, and considerable pain can be produced. The space-narrowing effect, in addition to the pain, tend to reduce range of motion, especially in the hands, knees, and hips.
Both elite and recreational athletes of any age may suffer from osteoarthritis, and they are at increased risk for the disease in any joint which has been injured during sporting activity (a common belief is that the normal wear and tear of sporting activity leads to osteoarthritis, particularly in the knees, but this concept has not been supported by research). Athletes who do not suffer from osteoarthritis none the less tend to have a high frequency of joint pain in response to strenuous training.
It is interesting to note that the biochemical cause of osteoarthritis is actually unknown; however, the basic course of the disease is well-documented. Glucosamine-containing proteoglycans naturally found in cartilage are broken down faster than they can be repaired. As a result, the cartilage begins to show physical signs of wear and tear, and new bone begins to move into the joint. As mentioned, pain (and inflammation) result.
Getting at the source
Non-steroidal anti-inflammatory drugs (NSAIDs) are the 'classic' treatment for osteoarthritis, in part because they tend to tone down the inflammation. However, NSAIDS do nothing to arrest the basic source of the disease, and thus there is increased interest in glucosamine and chondroitin sulphate. As mentioned earlier, it is often hypothesised that the two compounds might actually prevent the
breakdown of cartilage and/or stimulate the production of new cartilage, in effect stopping osteoarthritis in its tracks.
For any supplement to work, however, it must first be absorbed across the wall of the small intestine. Glucosamine passes this test readily, with about 90% of ingested glucosamine making its way through
the intestinal wall into the bloodstream. Of the glucosamine which is absorbed, experts believe that just 8 to 12% is retained in the tissues, while 20 to 30% is dumped into the urine; the remainder is exhaled as carbon dioxide. The absorption of chondroitin sulphate is much more limited; perhaps less than 10% of what is ingested actually makes it into the blood.
An important footnote to the body's usage of glucosamine and chondroitin is that the synthesis of glycosaminoglycans requires a substantial amount of sulphate. In addition, it is known that sulphate depletion leads to a decrease in glycosaminoglycan synthesis. Thus, the sulphate found in either glucosamine-sulphate or chondroitin-sulphate supplements may be an important element in their usefulness.
What the research says
Like osteoarthritis itself, glucosamine and chondroitin sulphate remain a bit mysterious; their mechanisms of action within the body are not well understood. However, the basic hypotheses are that each chemical might inhibit 'lysosomal enzymes' (powerful degradative chemicals which break down tissues) and stimulate proteoglycan synthesis. As noted earlier, these are entirely different actions, compared with the ones associated with NSAIDS, which basically inhibit the chain of chemical reactions which produce inflammation.
There is both good and bad news about scientific research concerning glucosamine and chondroitin sulphate. The first bit of good news is that there are a lot of studies. At least 18 clinical studies involving over 3000 individuals have been carried out with glucosamine, and eight chondroitin studies with almost 800 subjects have been published. Taken as a whole, these investigations suggest that either glucosamine or chondroitin is better than a placebo at relieving joint discomfort. There is not strong evidence that they are better than NSAIDS, but they have a much lower toxicity than NSAIDS, with far fewer negative side effects.
Now for the bad news. Strangely enough, although the two compounds are often sold together, there are no clinical studies in humans in which glucosamine and chondroitin sulphate have been administered together. In addition, glucosamine and chondroitin sulphate have a slower 'response time' and do not offer the immediate pain relief associated with NSAIDs (in fairness, though, the effects of glucosamine and chondroitin are probably longer-lasting; some studies indicate that the effects of glucosamine and chondroitin sulphate may persist for up to four weeks after withdrawal (Delafuente, J.C., 'Glucosamine in the treatment of osteoarthritis,' Rheumatic Disease Clinics of North America. 2000;26(1):1-11).
No study has demonstrated a protective effect against the breakdown of cartilage in living animals, but 'test-tube' studies have shown potentially positive changes in cartilage cells in response to glucosamine and chondroitin administration. Basically, the addition of glucosamine or chondroitin sulphate to human chondrocytes (cartilage cells) has been linked with the synthesis of proteoglycan and a decrease in the release of lysosomal enzymes.
Rubbishing the studies
The really bad news is that many of the 'pro-glucosamine' and 'pro-chondroitin' studies have been rather harshly criticised because of methodological flaws. Small sample sizes, short trial durations, the lack of randomisation of subjects, an absence of double-blinding, and the use of hospitalised patients rather than free-living subjects have raised real questions about the reliability and validity of the results.
In fact, an analysis of studies conducted between 1980 and 1998 found that just 15 of 37 glucosamine or chondroitin investigations were randomised, double-blind, placebo-controlled studies of adequate time duration. Of these 15 studies, 14 were supported by or performed by the manufacturer of the supplements used in the research.
The authors of the analysis used statistical applications to evaluate the 15 studies, judging the effectiveness of treatments on a scale of 0.2 (small effect) to 0.8 (large effect). The calculated effect of glucosamine turned out to be 0.44 (0.5 is considered moderate effect), while chondroitin sulphate checked in with a more impressive 0.78. Unfortunately, the effectiveness was decreased when only high-quality or large sample size studies were considered (McAlindon, T.E., LaValley, M.P., Gulin, J.P. and Felson, D.T, 'Glucosamine and chondroitin for treatment of osteoarthritis: A systemic quality assessment and meta-analysis,' Journal of the American Medical Association. 2000;283(11):1469-1475).
Preventing structural changes
Based on this research, it does not seem unreasonable to suggest that glucosamine and chondroitin might have moderately positive effects on joint health. And a more recent study, not included in the above analysis, has shown that glucosamine sulphate can prevent structural changes that occur with osteoarthritis. This double-blind, randomised, placebo-controlled study had a beautiful duration (three years), and it actually measured the narrowings of joint spaces within the subjects' knees. The researchers concluded that glucosamine sulphate modified the structure of the tissue, causing individuals taking glucosamine sulphate to experience less pain and greater range of motion over a three-year period, compared with those receiving a placebo (Reginster, J.Y., Deroisy, R., Rovati, L.C., Lee, R.L., Lejeune, E., Bruyere, O., Giacovelli, G., Henrotin, Y., Dacre, J.E., and Gossett, C., 'Long-term effects of glucosamine sulphate on osteoarthritis progression: A randomised, placebo-controlled trial,' Lancet. 2001;357:251-256).
An exciting development in the glucosamine and chondroitin-sulphate story is that the National Institute of Health in the United States is currently funding a study of 1,500 subjects who will receive one of four treatments - glucosamine, chondroitin sulphate, a combination of glucosamine and chondroitin sulphate, or a 'COX-2 inhibitor' (COX-2 inhibitors represent a relatively new treatment for joint distress; they carry with them a lower risk of gastrointestinal bleeding, compared to the traditional NSAIDs); naturally, there will also be a placebo group. The results of this well-designed study should be available by March 2002.
How much to take?
Purchasers of the supplements are generally advised to take 1,500mg of glucosamine daily and 1,200mg of chondroitin sulphate per day. After 60 days, daily maintenance doses of 750mg glucosamine and 600mg of chondroitin sulphate are often called for. Sadly, no 'dose-response' studies have been published in the scientific literature to gain a better understanding of how much of each compound might really be needed for maximum benefit. Most clinical studies use 1,500mg of glucosamine and 1,200mg of chondroitin sulphate daily over four- to 12-week periods and these doses have been used to judge short-term safety of the compounds.
Of course, a key problem has been that certain brands of the supplements are 'cheating'; some products have been independently tested and found to have full potency, while other brands have significantly less of the compound, compared with what is stated on the label (check this out on the web at www.consumerlab.com). An additional problem in the United States is that glucosamine and chondroitin may be packaged together with other ingredients which may or may not be listed on the product label. Fortunately, in Europe glucosamine sulphate is a prescription drug and must meet quality-control standards.
There are no apparent contraindications for glucosamine and chondroitin sulphate, and short-term studies indicate that the two compounds are safe. 'Short-term' is the key phrase, however, as no long-term work has looked into safety of the substances over periods lasting more than 12 weeks or so. Individuals who are allergic to shellfish should be cautious of supplements derived from seashells; there might be residual fish left after the cleaning process. Environmentalists also point out that - since shark cartilage is an important source of the two compounds - we may be obliterating shark populations in our efforts to control joint inflammation.
So what's the bottom line? Few glucosamine/chondroitin studies have been carried out with athletes, and there is really no solid evidence that glucosamine or chondroitin supplementation can reduce normal joint pain in athletes, boost recovery from strenuous workouts, and thus improve the overall quality of training. That doesn't mean that glucosamine or chondroitin will never be found to be effective in these areas, however. Our best guess, though is that further, high-quality research will indicate that glucosamine and chondroitin supplementation are moderately helpful to 'normal individuals' and athletes suffering from osteoarthritis, and perhaps even to athletes who have some wear and tear going on in their joints, without possessing true osteoarthritis.