Supplements May Help Knee Arthritis

New Studies Give Mixed Signals About Glucosamine, Chondroitin Benefits

Medically Reviewed by Louise Chang, MD on November 14, 2005
From the WebMD Archives

Nov. 14, 2005 -- Arthritis sufferers may -- or may not -- benefit from a pair of popular dietary supplements, two new clinical trials suggest.

One supplement is glucosamine, derived from the shells of crabs and lobsters. The other is chondroitin, usually derived from animal cartilage. These supplements are said to help relieve arthritis pain. They are also said to prevent the arthritic joint narrowing that causes one bone to grind against another.

Do these supplements really work? That is what two clinical trials -- a 1,583 patient study in the U.S. and a 318 patient study in Europe -- tried to find out. Researchers reported results from both studies at this week's annual scientific meeting of the American College of Rheumatology in San Diego.

"The supplements were not better than the placebo," Daniel O. Clegg, MD, tells WebMD. Clegg, chief of rheumatology at the University of Utah in Salt Lake City, led the NIH-sponsored U.S. study.

Arthritis Foundation spokesman Erin Arnold, MD, has a different interpretation. Arnold, a rheumatologist with the Illinois Bone and Joint Institute in Morton Grove, Ill., notes that Clegg is focusing on the study's overall results. She says she is more impressed with the study's finding that patients with more severe arthritis pain got significant relief from the glucosamine-chondroitin combination.

"I am very encouraged by the results of this study," Arnold tells WebMD. "The data presented certainly does not deter me from encouraging patients to try glucosamine and chondroitin."

There is less controversy over the smaller, European study led by Gabriel Herrero-Beaumont, MD, of the Jiminez Diaz Foundation in Madrid, Spain.

"Our results confirm previous studies," Herrero-Beaumont tells WebMD. "They demonstrate clearly that glucosamine was able to control knee osteoarthritis pain."

Glucosamine + Chondroitin: For Bad Arthritis Pain Only?

The U.S. trial enrolled patients aged 40 and older with knee pain due to osteoarthritis. They were randomly assigned to one of five treatments:

  • Inactive placebo pills
  • Glucosamine hydrochloride at a dose of 500 milligrams three times a day
  • Sodium chondroitin at a dose of 400 milligrams three times a day
  • Combination glucosamine and chondroitin
  • Celebrex at a dose of 200 milligrams per day

It is common for a pain study to show that many patients report relief from inactive placebo pills. And that happened here. Nearly 60% of patients given only placebo pills said they had less pain. So did about 67% of patients treated with combination glucosamine and chondroitin. But that isn't what scientists call a significant difference -- that is, there's more than a 5% chance the findings are just coincidence.

"I really feel the study is a negative study," Clegg says. "I would say to patients that the safety data are really reassuring, the efficacy data are not."

When Clegg's team looked only at patients with moderate to severe pain. Only 54% of these patients got relief from placebo. But 79% reported relief from combination glucosamine and chondroitin. That is a significant difference. But there's a problem, Clegg says. The study wasn't designed to look at just this group. The effect here is based on only a small number of patients.

"About 20% of the study patients have moderate to severe pain," Clegg says. "Interestingly, in that subgroup, the combination of glucosamine and chondroitin appeared to be effective in relieving pain. I think this outcome is really interesting but just from a research standpoint. It is an exploratory, hypothesis-generating finding -- not a finding on which to base treatment."

Different Opinions on U.S. Study

The Arthritis Foundation says that the Clegg study "demonstrates that the combination of glucosamine and chondroitin may be a beneficial part of an overall treatment plan in individuals with moderate to severe knee osteoarthritis."

This conclusion did not change after conversations with Clegg, Arnold says.

"Based on the data we have had -- and on the use of glucosamine and chondroitin in clinical practice -- we think there is enough there to give glucosamine and chondroitin a try," she says. "It is safe."

The study isn't the first to show that glucosamine and chondroitin help arthritis, says Andrew Shao, PhD, vice president for scientific and regulatory affairs at the Council for Responsible Nutrition, a supplement industry trade group.

"There are at least 50 published clinical trials on either one of these supplements or the combination, with various relevant health outcomes, such as improved joint pain and improved joint space," Shao tells WebMD. "It's important to keep in mind these products support joint health. It is not necessary to restrict use to osteoarthritis sufferers. Although the research is not done yet, they might be useful for arthritis prevention, too."

Glucosamine Better Than Tylenol?

A more consistently positive result comes from the European study. This clinical trial randomly treated knee osteoarthritis patients with either glucosamine sulfate (one 1,500-milligram dose daily), acetaminophen (the active ingredient in Tylenol, given at the high dose 1,000 milligrams three times daily), or inactive placebo.

After six months of treatment, patients getting either glucosamine or acetaminophen had significantly less pain than patients getting placebo pills.

But researcher Herrero-Beaumont says that patients treated with glucosamine reported more kinds of improvement than those treated with acetaminophen.

"Glucosamine showed more positive effects than placebo in 10 of 10 measures, whereas acetaminophen was more positive than placebo in only five of the 10," he says. "But there was no statistical significance between glucosamine and acetaminophen."

Things to Know

Herrero-Beaumont says that because glucosamine is extremely safe, he recommends it to patients with arthritis. But since there's some evidence that the supplement accumulates in the body, he says he advises patients to use it in three-month-on, two-month-off cycles.

Arnold says she has yet to see any safety concerns with either glucosamine or chondroitin. She recommends that patients give it a try -- with the advice of their doctors.

"There are things that work for certain patients that don't work for others," she says. "Based on safety, I would continue to encourage my patients to use glucosamine and chondroitin. Some of my patients who use these supplements have been able to use [fewer] anti-inflammatory and pain medications."

Arnold is quick to warn that supplements will not cure arthritis -- and that they are only a part of a multiprong treatment.

What does Arnold tell her patients?

"I recommend first of all that they try only products evaluated by Consumer Laboratories or USP to make sure they have in them what they are supposed to have," she says. "Then I tell them to take half the dose in the morning and half in the evening. And I have them do at least a three-month trial before giving up."

Industry spokesman Shao says patients should be patient.

"Glucosamine and chondroitin are very different from some drugs used to relieve arthritis pain," he says. "Rather than mask pain, they are actually fixing the joint. But that takes time. It does not kick in after a few hours or days. It takes months for the effects to manifest."

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SOURCES: American College of Rheumatology Annual Scientific Meeting, San Diego, Nov. 12-17, 2005. News release, American College of Rheumatology. News release, Arthritis Foundation. News release, Council for Responsible Nutrition. Daniel Clegg, MD, professor and chief, division of rheumatology, University of Utah, Salt Lake City. Gabriel Herrero-Beaumont, MD, Jiminez Diaz Foundation, Madrid, Spain. Erin Arnold, MD, spokesperson, Arthritis Foundation; rheumatologist, Illinois Bone and Joint Institute, Morton Grove, Ill. Andrew Shao, PhD, vice president for scientific and regulatory affairs, Council for Responsible Nutrition, Washington.
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