Monday, February 4, 2013

What is glucosamine as a therapeutic supplement?


Overview

Glucosamine, most commonly used in the form glucosamine sulfate, is a simple
molecule derived from glucose, the principal sugar found in
blood. In glucosamine, one oxygen atom in glucose is replaced by a nitrogen atom.
The chemical term for this modified form of glucose is amino sugar. Glucosamine is
produced naturally in the body, where it is a key building block for making
cartilage.




Requirements and Sources

There is no U.S. Dietary Reference Intake for glucosamine. One’s body makes all the glucosamine it needs from building blocks found in foods. Glucosamine is not usually obtained directly from food. Glucosamine supplements are derived from chitin, a substance found in the shells of shrimp, lobsters, and crabs.




Therapeutic Dosages


Osteoarthritis is a disease in which cartilage in joints
becomes stiffer and may wear away. Glucosamine is used to treat this condition. A
typical dosage of glucosamine is 500 milligrams (mg) three times daily. A 1,500-mg
dose taken once daily is another option.


Glucosamine is available in three forms: glucosamine sulfate, glucosamine
hydrochloride, and N-acetyl glucosamine. All three forms are sold as tablets or
capsules. There is some dispute over which form is best. One study provides some
evidence that glucosamine hydrochloride and glucosamine sulfate are equally
effective. Glucosamine is often sold in combination with chondroitin.
It is not known whether this combination treatment is better than glucosamine
alone, although animal studies suggest that this may be the case.




Therapeutic Uses

Glucosamine is widely accepted as a treatment for osteoarthritis. However, the current evidence from double-blind studies is highly inconsistent, with many of the most recent and best-designed studies failing to find significant benefit. According to the positive studies, glucosamine acts more slowly than conventional treatments, such as ibuprofen, but eventually produces approximately equivalent benefits. In addition, unlike conventional treatments, glucosamine might also help prevent progressive joint damage, thereby slowing the course of the disease. However, both these potential benefits remain controversial in light of the most recent trials. Glucosamine has also shown some promise for osteochondritis of the knee, a cartilage disease related to osteoarthritis.


Some athletes use glucosamine, in the (unproven) belief that it can prevent muscle and tendon injuries. It has also been suggested as a treatment for tendonitis. However, there is no meaningful scientific evidence to support these potential uses. Exercise can also produce short-term muscle soreness. In one study, use of glucosamine not only failed to prove effective for reducing this type of pain but also increased it. However, one study found somewhat inconsistent evidence hinting that glucosamine might aid recovery from acute knee injuries experienced by competitive athletes.


Glucosamine might also be helpful for rheumatoid arthritis, according to a double-blind, placebo-controlled study of fifty-one people. In this study, use of glucosamine at a dose of 1,500 mg daily significantly improved symptoms. It did not, however, alter measures of inflammation as determined through blood tests.




Scientific Evidence


Relieving osteoarthritis symptoms. Inconsistent evidence suggests that glucosamine supplements might relieve pain and other symptoms of osteoarthritis. Two types of studies have been performed, those that compared glucosamine against placebo and those that compared it against standard medications.


In the placebo-controlled category, one of the best trials was a three-year, double-blind study of 212 people with osteoarthritis of the knee. Participants receiving glucosamine showed reduced symptoms, compared with those receiving placebo. Benefits were also seen in other double-blind, placebo-controlled studies, enrolling a total of more than a thousand people and ranging in length from four weeks to three years.


Other double-blind studies, enrolling a total of more than four hundred people, compared glucosamine against ibuprofen. These studies found glucosamine and the drug equally effective. Furthermore, one of the placebo-controlled trials noted above (only reported in abstract form) also included people given the drug piroxicam and again found equivalent benefits.


However, most recent studies have been less promising. In four studies involving a total of about five hundred people, use of glucosamine failed to provide any meaningful improvement in symptoms. The list goes on. In a study involving 222 participants with hip osteoarthritis, two years of treatment with glucosamine was no better than a placebo for pain, function, or X-ray findings. Another trial involving 147 women with osteoarthritis found glucosamine to be no more effective than home exercises over an eighteen-month period.


In a double-blind trial, researchers evaluated the effects of stopping glucosamine after taking it for six months. Involving 137 people with osteoarthritis of the knee, the study found that participants who stopped using glucosamine (and, unbeknownst to them, took a placebo instead) did no worse than people who stayed on glucosamine.


In another, very large (1,583-participant) study, neither glucosamine (as glucosamine hydrochloride) nor glucosamine plus chondroitin was more effective than a placebo. Another trial failed to find benefit with glucosamine plus chondroitin. Finally, in a systematic review including ten randomized trials involving 3,803 patients with osteoarthritis of hip or knee, researchers found that glucosamine alone or with chondroitin did not improve pain. It appears that most of the positive studies were funded by manufacturers of glucosamine products, and most of the studies performed by neutral researchers failed to find benefit.


Many popular glucosamine products combine this supplement with methylsulfonylmethane (MSM). One study published in India reported that both MSM and glucosamine improved arthritis symptoms, compared with a placebo, but that the combination of MSM and glucosamine was even more effective than either supplement separately. However, India has not achieved a reputation for conducting reliable medical trials.



Slowing the course of osteoarthritis. Conventional treatments for
osteoarthritis reduce the symptoms but do not slow the progress of the disease. In
fact, nonsteroidal anti-inflammatory drugs, such as indomethacin,
might actually speed the progression of osteoarthritis by interfering with
cartilage repair and promoting cartilage destruction (though the evidence for this
is weak). In contrast, two studies reported that glucosamine can slow the
progression of osteoarthritis.


A three-year, double-blind, placebo-controlled study of 212 people found indications that glucosamine may protect joints from further damage. Over the course of the study, individuals given glucosamine showed some actual improvement in pain and mobility, while those given placebo worsened steadily. Perhaps even more important, X-rays showed that glucosamine treatment prevented progressive damage to the knee joint. Another large, three-year study enrolling 202 people found similar results. Furthermore, a follow-up analysis, done five years after the conclusion of these two studies, found suggestive evidence that use of glucosamine reduced the need for knee-replacement surgery.


Like the positive studies of glucosamine for reducing symptoms, all of these studies were funded by a major glucosamine manufacturer.



Relieving knee pain due to osteochondritis. A twelve-week, double-blind, placebo-controlled study examined the effectiveness of glucosamine at 2,000 mg daily in fifty people with continuing knee pain, mostly caused by osteochondritis (damage to the articular cartilage of the knee) rather than osteoarthritis. The results were somewhat equivocal but appeared to indicate that glucosamine could improve symptoms. Some participants may have also had osteoarthritis, so the results of this study are a bit difficult to interpret.




Safety Issues

Glucosamine appears to be a generally safe treatment and has not been associated with significant side effects. A few case reports and animal studies raised concerns that glucosamine might raise blood sugar in people with diabetes, but subsequent studies have tended to lay these concerns to rest. Glucosamine does not appear to affect cholesterol levels either. There is one case report of an allergic reaction to a glucosamine/chondroitin product, causing exacerbation of asthma.




Bibliography


Arendt-Nielsen, L., et al. “A Double-Blind Randomized Placebo-Controlled Parallel Group Study Evaluating the Effects of Ibuprofen and Glucosamine Sulfate on Exercise-Induced Muscle Soreness.” Journal of Musculoskeletal Pain 15 (2007): 21-28.



Herrero-Beaumont, G., et al. “Glucosamine Sulfate in the Treatment of Knee Osteoarthritis Symptoms: A Randomized, Double-Blind, Placebo-Controlled Study Using Acetaminophen as a Side Comparator.” Arthritis and Rheumatism 56, no. 2 (2007): 555-567.



Kawasaki, T., et al. “Additive Effects of Glucosamine or Risedronate for the Treatment of Osteoarthritis of the Knee Combined with Home Exercise.” Journal of Bone and Mineral Metabolism 26 (2008): 279-287.



Ostojic, S. M., et al. “Glucosamine Administration in Athletes: Effects on Recovery of Acute Knee Injury.” Research in Sports Medicine 15 (2007): 113-124.



Rozendaal, R. M., et al. “Effect of Glucosamine Sulfate on Hip Osteoarthritis.” Annals of Internal Medicine 148 (2008): 268-277.



Usha, P. R., and M. U. Naidu. “Randomised, Double-Blind, Parallel, Placebo-Controlled Study of Oral Glucosamine, Methylsulfonylmethane, and Their Combination in Osteoarthritis.” Clinical Drug Investigation 24 (2004): 353-363.

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