|Efficacy of Glucosamine and Chondroitin Sulfate May Depend
on Level of Osteoarthritis Pain
In a study published in the New England Journal of Medicine*,
the popular dietary supplement combination of glucosamine plus chondroitin sulfate
did not provide significant relief from osteoarthritis pain among all participants.
However, a smaller subgroup of study participants with moderate-to-severe pain
showed significant relief with the combined supplements. This research was funded
by the National Center for Complementary and Alternative Medicine (NCCAM) and
the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS),
components of the National Institutes of Health (NIH). Researchers led by rheumatologist
Daniel O. Clegg, M.D., of the University of Utah, School of Medicine, Salt Lake
City, conducted the 4-year study known as the Glucosamine/chondroitin Arthritis
Intervention Trial (GAIT) at 16 sites across the United States.
“GAIT is another example of NIH’s commitment to exploring the potential of complementary
and alternative medicine to prevent and treat disease in a manner that is fair,
unbiased, and scientifically rigorous,” said Elias A. Zerhouni, M.D., NIH Director.
GAIT enrolled nearly 1,600 participants with documented osteoarthritis of the
knee. Participants were randomly assigned to receive one of five treatments daily
for 24 weeks: glucosamine alone (1500 mg), chondroitin sulfate alone (1200 mg),
glucosamine and chondroitin sulfate combined (same doses), a placebo, or celecoxib
(200 mg). Celecoxib is an FDA-approved drug for the management of osteoarthritis
pain and served as a positive control for the study. (A positive control is a
treatment that investigators expect participants to respond to in a predictable
way; it helps validate study results.) A positive response to treatment was defined
as a 20 percent or greater reduction in pain at week 24 compared to the start
of the study.
The researchers found that participants taking celecoxib experienced statistically
significant pain relief, as expected, versus placebo — about 70 percent
of those taking celecoxib versus 60 percent taking placebo had a 20 percent or
greater pain reduction. For all participants, there were no significant differences
between the other treatments tested and placebo. However, for participants in
the moderate-to-severe pain subgroup, glucosamine combined with chondroitin sulfate
provided statistically significant pain relief compared to placebo — about
79 percent in this group had a 20 percent or greater pain reduction compared
to 54 percent for placebo. In the subgroup of participants with mild pain, glucosamine
and chondroitin sulfate together or alone did not provide statistically significant
relief compared to placebo.
“This rigorous, large-scale study showed that the combination of glucosamine
and chondroitin sulfate appeared to help people with moderate-to-severe pain
from knee osteoarthritis, but not those with mild pain,” said Stephen E. Straus,
M.D., NCCAM Director. “It is important to study dietary supplements with well-designed
research in order to find out what works and what does not.”
“Because of the small size of the moderate-to-severe pain subgroup, the findings
in this group for glucosamine plus chondroitin sulfate should be considered preliminary
and need to be confirmed in a study designed for this purpose,” said Dr. Clegg,
Professor of Medicine and Chief of Rheumatology at the University of Utah, School
On entering the study, a participant’s level of pain was assessed as either
mild or moderate to severe using standard pain assessment tools and scales, such
as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
Of the 1,583 study participants, 78 percent were in the mild pain subgroup and
the other 22 percent were in the moderate-to-severe pain subgroup. Level of pain
was evaluated at weeks 4, 8, 16, and 24 using the WOMAC scale and other tools.
In addition to taking their daily study treatment, participants could take up
to 4000 mg of acetaminophen daily for pain, except for the 24 hours before they
were assessed by study staff. The use of acetaminophen, however, was low, overall
averaging fewer than two 500 mg tablets per day. Participants could not take
other non-steroidal anti-inflammatory medicines or narcotic (opioid-based) pain
relievers during the study.
“More than 20 million Americans have osteoarthritis, making it a frequent cause
of physical disability among adults,” said Stephen I. Katz, M.D., Ph.D., NIAMS
Director. “We are excited to support studies looking at new treatment options
that could improve the symptoms and quality of life of people with osteoarthritis.”
GAIT was conducted under an Investigational New Drug application filed with
the U.S. Food and Drug Administration. Thus, all of the products used in the
study were subject to the FDA’s pharmaceutical regulations and evaluated and
manufactured by an FDA-licensed clinical research pharmacy center. The glucosamine
and chondroitin sulfate used were tested for purity, potency, quality, and consistency
among batches. Products were retested for stability throughout the study. The
dosages selected were based on the prevailing doses in the scientific literature.
Few side effects from any of the treatments were reported. Those reported were
generally mild, such as upset stomach, and distributed evenly across the treatment
“The GAIT team’s goal was to assess whether glucosamine and chondroitin sulfate,
which we saw our osteoarthritis patients using, provided pain relief,” said Dr.
Clegg. “I urge people with osteoarthritis to follow a comprehensive plan for
managing their arthritis pain — eat right, exercise, lose excess weight,
and talk to your physician about appropriate treatment options.”
The GAIT team continues their research with a smaller study to see whether glucosamine
and chondroitin sulfate can alter the progression of osteoarthritis, such as
delaying the narrowing of the joint spaces. About one-half of the participants
in the larger GAIT study were eligible to enroll in this ancillary study. The
results are expected in about a year.
To view a detailed Question and Answer (Q&A) backgrounder on the NIH Glucosamine/Chondroitin
Arthritis Intervention Trial (GAIT), please see http://nccam.nih.gov/research/results/gait/qa.htm.
The National Center for Complementary and Alternative Medicine’s mission
is to explore complementary and alternative medical practices in the context
of rigorous science, train CAM researchers, and disseminate authoritative information
to the public and professionals. For additional information, call NCCAM’s Clearinghouse
toll free at 1-888-644-6226, or visit the NCCAM Web site at nccam.nih.gov.
NCCAM is 1 of 27 institutes and centers at the National Institutes of Health,
the Federal focal point for medical research in the United States.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases,
a component of the National Institutes of Health, DHHS, supports research into
the causes, treatment, and prevention of arthritis and musculoskeletal and
skin diseases; the training of basic and clinical scientists to carry out this
research; and the dissemination of information on research progress in these
diseases. For additional information, call NIAMS’s clearinghouse at (301) 495-4484
or visit NIAMS’s Web site at www.niams.nih.gov.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services. It is the primary Federal
agency for conducting and supporting basic, clinical, and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.