Introduction
Osteoarthritis continues to be a painful and disabling condition
for many of our patients. Medical treatments remain limited
primarily to pain-control medication and surgery. Fortunately,
certain promising alternative therapies have received a good
deal of attention from the scientific research community. In
the WSCC Clinics Protocol on Glucosamine and Chondroitin Sulfate1,
adopted in 2001, the case was made for selecting either glucosamine
sulfate, 1500 mg per day, or chondroitin sulfate, 800-1200 mg
per day, as the initial choice of dietary supplement therapy
for osteoarthritis. This recommendation was based on the strength
of evidence from several randomized controlled trials (RCTs)
and two meta-analyses. Since then new studies have been published
that improve our understanding of the value of these supplements.
New Glucosamine Research
One of the most promising results discussed in the WSCC Clinics
Protocol were the findings reported early in 2001 of a three-year
Belgian RCT of glucosamine sulfate, in which the treatment
group did not experience the deterioration of radiographic
knee changes seen in the placebo group at the end of the trial2.
In 2002, a second long-term RCT was published reporting similar
benefits in a group of Czech subjects3. In addition to experiencing
significant symptom relief, subjects receiving 1500 mg per
day of glucosamine sulfate averaged no progressive joint space
narrowing after three years, while in comparison the placebo
group lost a significant amount of joint space and had only
a modest reduction in pain. While a few subjects taking glucosamine
sulfate did not experience these protective joint space effects,
almost three times as many in the placebo group developed
severe narrowing, defined as greater than 0.5 mm in three
years. A follow-up analysis revealed that subjects with initially
milder joint narrowing received the greatest protection from
glucosamine sulfate4. As in the prior long-term study, no
significant side effects from the supplement were reported.
Osteoarthritis of the temporomandibular joint (TMJ) was treated
with glucosamine sulfate in a recent Canadian RCT5. Glucosamine
therapy (1500 mg per day) was compared to ibuprofen (1200
mg per day) in this 90-day trial, which resulted in equal
improvement in both groups measured by assessments of pain
and TMJ function. As reported in other trials, subjects treated
with glucosamine sulfate did not experience a return of pain
for 30 days after treatment was stopped, which represents
a remarkable "carry-over" effect. This study also
demonstrates that glucosamine sulfate may benefit patients
with osteoarthritis in areas other than the knee.
A recent short-term study conducted in Great Britain did
not report significant pain reduction from glucosamine sulfate
therapy for osteoarthritis of the knee6. After six months
of supplementation with 1500 mg per day, the glucosamine group
had a small but significant improvement in knee flexion, but
self-assessment of pain was not different from that in the
placebo group, many of whom experienced pain reduction as
well. These patients had more severe osteoarthritis than those
in most of the successful trials of glucosamine sulfate, and
other reports suggest glucosamine is more effective in mild
to moderate cases4. This study is only the second RCT to report
disappointing results from glucosamine sulfate therapy, compared
with at least sixteen double-blind studies reporting significant
positive outcomes.
Clinicians and patients alike are interested to learn whether
glucosamine might be helpful in joint disorders other than
osteoarthritis, but until recently this type of investigation
had not been attempted. An Australian group has just reported
results of a RCT of glucosamine hydrochloride therapy on people
with "regular" knee pain7. Subjects,
who averaged 42-43 years of age, were selected for the presence
of knee pain "more often than not" while pursuing
the activities of daily living. About half of the subjects
had prior medical workups for their knee pain that indicated
some degree of cartilage damage, but this study did not perform
any further diagnostic evaluations on any subject. Deviating
from most prior glucosamine studies, this three-month trial
supplied glucosamine as the hydrochloride rather than the
sulfate salt. Until this study appeared, only one trial of
glucosamine hydrochloride monotherapy had been published,
and the earlier study reported only marginal effects of glucosamine
hydrochloride against osteoarthritis discomfort8.
Glucosamine-treated subjects in the new study reported some
significant improvements compared to the placebo group in
discomfort relief and quality of life, but performance of
either a "duck-walk" or a stair climb did not improve.
It is tempting to speculate that glucosamine sulfate, having
a more impressive record of significant benefit, may have
had greater potential to improve both discomfort and function
had it been used in this study.
As described in the WSCC Protocol, animal studies have questioned
whether glucosamine is safe for use in patients with diabetes
or other glucose intolerance disorders. To date no formal
human investigations have been carried out to determine whether
this concern is valid. It appears from the long-term studies
described above that glucosamine sulfate produces no significant
changes in plasma glucose among healthy subjects, but anecdotal
reports of elevated blood glucose readings by diabetics taking
glucosamine suggest that patients with that disease monitor
their glucose levels carefully while using glucosamine.
Continue
to Chondroitin Sulfate Research
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Be sure to visit the Glucosamine Product Guide for a review of commercially available glucosamine products broken down by 9 different categories such as price per month, quality and type. Learn what the best products out there are and what criteria was used to ranked each.
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