Joint Pain Drug Glucosamine Gains Scientific Attention
BOSTON (Boston Globe) - This isn't the way medical science is supposed to work. A remedy used to treat creaky bones in horses and dogs works so well that humans start taking it. It gets hyped in a best-selling book on arthritis and the number of users skyrockets. Doctors get glowing testimonials from patients, so they tell other patients to try it. Finally, with about 5 million Americans taking the concoction of crab shells and cow cartilage, enough begin asking how it works - and enough doctors wonder whether it really does - that scientists finally begin studying its safety and effectiveness.
That's what happened with glucosamine and chondroitin, which taken together or separately are now America's top-selling joint supplements. The early results of research, including one study just published and another due out soon, suggest the treatment actually does ease joint pain and may even forestall further cartilage damage.
The promising research is bound to make the hard-to-pronounce potions, which are available over the counter, even more wildly popular.
"This is a strange, inverted application of the traditional scientific model," said Dr. Timothy McAlindon, an associate professor of medicine at Boston University who has analyzed the evidence on glucosamine and chondroitin sulfate, here and abroad. "The science isn't black or white. We're building a case trying to figure out if this works or not, and at the moment the evidence is favoring these products."
Dr. Roland Moskowitz, a professor at Case Western Reserve University who next week will help initiate the biggest Study ever of glucosamine and chondroitin for the National Institutes of Health, also is bemused by the treatment's unconventional history. But he said "enough people are using it that if it works, we ought to know about it. And if it doesn't, we should know it doesn't and stop people from spending money on it. "If it works, we'll have lucked out." Luck has little to do with it if you ask the hordes of horsemen and pet owners across America who have been giving their animals the glucosamine-chondroitin pill since the early 1990s and swear that it quickens the animals' gait and eases their agony.
Ditto for millions of people in Europe who for even longer have been using the two compounds, which occur naturally in human cartilage and are synthesized in the treatment capsules. The Europeans even have scientific studies, more than three dozen of them, saying the medicine works.
American researchers have been slower to show an interest, which is largely a function of the way things work here with herbal therapies, dietary supplements and other nonpharmaceutical products. Given the medicine's natural derivation, drug companies find it difficult to take out patents on the products, so they have no incentive to sponsor the expensive research to ensure they are effective or safe. The Food and Drug Administration also steers clear of such remedies.
In the last couple of years, however, American researchers have become curious. It was partly because of the publication in 1997 of a popular book called "The Arthritis Cure," and the way it triggered an avalanche of interest in glucosamine-chondroitin among America's 20 million sufferers of the degenerative joint disease called osteoarthritis.
Many were frustrated with the side effects of other medicines and were thrilled with results they got with the new treatment. Doctors were not about to object since their patients were so convinced and the treatment seemed safe, although over time they started pressing for more concrete evidence. McAlindon, the BU arthritis specialist, set out to see whether all the European studies held up. His conclusion, outlined in an article earlier this year in the Journal of the American Medical Association, was that the overseas clinical trials do show that glucosamine and chondroitin reduce pain in osteoarthritis sufferers and are safe. But nearly all the European trials were supported by manufacturers of the supplements who had the most to gain from positive publicity. And "in general they were not that well done," McAlindon said last week. "They seem to exaggerate the treatments' efficacy."
A series of US studies is trying to weed out those quality problems and come up with definitive answers. The largest of its kind, published this month in the journal Osteoarthritis and Cartilage, looked at how glucosamine-chondroitin affected pain and movement in 93 patients with arthritic knees. "The treatment was significantly more effective than a placebo for pain and function," said Dr. Amal Das, a joint replacement surgeon in Hendersonville, N.C., and the lead author.
That finding is consistent with reports from private physicians nationwide and with the results of other, smaller studies, including one published last year involving 34 Navy personnel suffering from knee or lower back pain. While the effects on back pain were unclear, that study found, the aching in knees clearly was relieved.
The next question everyone is asking is whether the treatment does more than mask the pain. Does it actually cure the underlying disease of osteoarthritis? And can it help the thousands of young athletes with cartilage damage? Logic suggests it might. Glucosamine in its natural form stimulates cells that make cartilage, while chondroitin sulfate blocks enzymes that break down old cartilage. The question is whether the same effects are produced by the capsules people take, which generally get glucosamine from crab, lobster, or clam shells and chondroitin from the cartilage in a cow's trachea. And, even trickier, can the glucosamine and chondroitin in the pill work their way from the stomach to the blood to the aching knee?
Animal tests in Arizona offer hope. Cartilage was removed from rabbits to mimic an injury of the kind humans get, and they were fed glucosamine, chondroitin, and a combination of the two. After several months, researchers examined the injured area. "We found the severity of the arthritis process was less in those given the treatment," and the combination of compounds worked best, said Dr. Robert R. Karpman, one of the researchers who oversaw the study in Phoenix, which is due to be published next month. "It seems to slow the arthritic process, but it doesn't repair the joint surface."
However, the Arizona study raises questions. For instance: could humans tolerate the megadoses given to rabbits? Were the beneficial effects a result of stopping further erosion of the cartilage or making new proteins to replace what was gone? And can glucosamine and chondroitin really find their way around the stomach and liver not just to a knee or other joint, but to the particular joint that is damaged?
The fact that cartilage does not have blood vessels, and gets its only nutrition by seepage through the surrounding membrane, probably makes it easier for substances like glucosamine and chondroitin to work their way there, said Dr. Lou Lippiello, director of laboratory research at Nutramax Laboratories, one of the leading manufacturers of the treatment and a partial sponsor of the Hendersonville and Phoenix studies. "Apparently it doesn't affect normal joints," he added. "It seems to have an affinity for joints that are undergoing some kind of trauma or stress."
Further studies clearly are needed, which is why the NIH next week is scheduled to begin a $10 million project involving 1,500 patients. It will look at glucosamine, chondroitin and the two together to see whether they help control arthritis pain and whether they actually attack the underlying disease.
What should patients do in the meantime? Most orthopedic surgeons advise their patients to try it, under a doctor's guidance. But it is expensive - $1 or so a day for the eight weeks it takes to begin working, at which point the dosage is lowered and the cost falls to about 60 cents a day. Insurance generally does not cover the treatment, and physicians caution children and pregnant women not to use it. Anyone who has diabetes or is taking the blood-thinning drug heparin also should be careful. And researchers warn that many of the low-cost concoctions being marketed today do not contain quality products.
Copyright 2000 The Boston Globe. All rights reserved.
BOSTON (Boston Globe) - This isn't the way medical science is supposed to work. A remedy used to treat creaky bones in horses and dogs works so well that humans start taking it. It gets hyped in a best-selling book on arthritis and the number of users skyrockets. Doctors get glowing testimonials from patients, so they tell other patients to try it. Finally, with about 5 million Americans taking the concoction of crab shells and cow cartilage, enough begin asking how it works - and enough doctors wonder whether it really does - that scientists finally begin studying its safety and effectiveness.
That's what happened with glucosamine and chondroitin, which taken together or separately are now America's top-selling joint supplements. The early results of research, including one study just published and another due out soon, suggest the treatment actually does ease joint pain and may even forestall further cartilage damage.
The promising research is bound to make the hard-to-pronounce potions, which are available over the counter, even more wildly popular.
"This is a strange, inverted application of the traditional scientific model," said Dr. Timothy McAlindon, an associate professor of medicine at Boston University who has analyzed the evidence on glucosamine and chondroitin sulfate, here and abroad. "The science isn't black or white. We're building a case trying to figure out if this works or not, and at the moment the evidence is favoring these products."
Dr. Roland Moskowitz, a professor at Case Western Reserve University who next week will help initiate the biggest Study ever of glucosamine and chondroitin for the National Institutes of Health, also is bemused by the treatment's unconventional history. But he said "enough people are using it that if it works, we ought to know about it. And if it doesn't, we should know it doesn't and stop people from spending money on it. "If it works, we'll have lucked out." Luck has little to do with it if you ask the hordes of horsemen and pet owners across America who have been giving their animals the glucosamine-chondroitin pill since the early 1990s and swear that it quickens the animals' gait and eases their agony.
Ditto for millions of people in Europe who for even longer have been using the two compounds, which occur naturally in human cartilage and are synthesized in the treatment capsules. The Europeans even have scientific studies, more than three dozen of them, saying the medicine works.
American researchers have been slower to show an interest, which is largely a function of the way things work here with herbal therapies, dietary supplements and other nonpharmaceutical products. Given the medicine's natural derivation, drug companies find it difficult to take out patents on the products, so they have no incentive to sponsor the expensive research to ensure they are effective or safe. The Food and Drug Administration also steers clear of such remedies.
In the last couple of years, however, American researchers have become curious. It was partly because of the publication in 1997 of a popular book called "The Arthritis Cure," and the way it triggered an avalanche of interest in glucosamine-chondroitin among America's 20 million sufferers of the degenerative joint disease called osteoarthritis.
Many were frustrated with the side effects of other medicines and were thrilled with results they got with the new treatment. Doctors were not about to object since their patients were so convinced and the treatment seemed safe, although over time they started pressing for more concrete evidence. McAlindon, the BU arthritis specialist, set out to see whether all the European studies held up. His conclusion, outlined in an article earlier this year in the Journal of the American Medical Association, was that the overseas clinical trials do show that glucosamine and chondroitin reduce pain in osteoarthritis sufferers and are safe. But nearly all the European trials were supported by manufacturers of the supplements who had the most to gain from positive publicity. And "in general they were not that well done," McAlindon said last week. "They seem to exaggerate the treatments' efficacy."
A series of US studies is trying to weed out those quality problems and come up with definitive answers. The largest of its kind, published this month in the journal Osteoarthritis and Cartilage, looked at how glucosamine-chondroitin affected pain and movement in 93 patients with arthritic knees. "The treatment was significantly more effective than a placebo for pain and function," said Dr. Amal Das, a joint replacement surgeon in Hendersonville, N.C., and the lead author.
That finding is consistent with reports from private physicians nationwide and with the results of other, smaller studies, including one published last year involving 34 Navy personnel suffering from knee or lower back pain. While the effects on back pain were unclear, that study found, the aching in knees clearly was relieved.
The next question everyone is asking is whether the treatment does more than mask the pain. Does it actually cure the underlying disease of osteoarthritis? And can it help the thousands of young athletes with cartilage damage? Logic suggests it might. Glucosamine in its natural form stimulates cells that make cartilage, while chondroitin sulfate blocks enzymes that break down old cartilage. The question is whether the same effects are produced by the capsules people take, which generally get glucosamine from crab, lobster, or clam shells and chondroitin from the cartilage in a cow's trachea. And, even trickier, can the glucosamine and chondroitin in the pill work their way from the stomach to the blood to the aching knee?
Animal tests in Arizona offer hope. Cartilage was removed from rabbits to mimic an injury of the kind humans get, and they were fed glucosamine, chondroitin, and a combination of the two. After several months, researchers examined the injured area. "We found the severity of the arthritis process was less in those given the treatment," and the combination of compounds worked best, said Dr. Robert R. Karpman, one of the researchers who oversaw the study in Phoenix, which is due to be published next month. "It seems to slow the arthritic process, but it doesn't repair the joint surface."
However, the Arizona study raises questions. For instance: could humans tolerate the megadoses given to rabbits? Were the beneficial effects a result of stopping further erosion of the cartilage or making new proteins to replace what was gone? And can glucosamine and chondroitin really find their way around the stomach and liver not just to a knee or other joint, but to the particular joint that is damaged?
The fact that cartilage does not have blood vessels, and gets its only nutrition by seepage through the surrounding membrane, probably makes it easier for substances like glucosamine and chondroitin to work their way there, said Dr. Lou Lippiello, director of laboratory research at Nutramax Laboratories, one of the leading manufacturers of the treatment and a partial sponsor of the Hendersonville and Phoenix studies. "Apparently it doesn't affect normal joints," he added. "It seems to have an affinity for joints that are undergoing some kind of trauma or stress."
Further studies clearly are needed, which is why the NIH next week is scheduled to begin a $10 million project involving 1,500 patients. It will look at glucosamine, chondroitin and the two together to see whether they help control arthritis pain and whether they actually attack the underlying disease.
What should patients do in the meantime? Most orthopedic surgeons advise their patients to try it, under a doctor's guidance. But it is expensive - $1 or so a day for the eight weeks it takes to begin working, at which point the dosage is lowered and the cost falls to about 60 cents a day. Insurance generally does not cover the treatment, and physicians caution children and pregnant women not to use it. Anyone who has diabetes or is taking the blood-thinning drug heparin also should be careful. And researchers warn that many of the low-cost concoctions being marketed today do not contain quality products.
Copyright 2000 The Boston Globe. All rights reserved.