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Efficacy of glucosamine, chondroitin, and methylsulfonylmethane for spinal degenerative joint disease and degenerative disc disease: A systematic review


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Nutritional supplements are commonly used for a variety of musculoskeletal conditions, including knee and hip degenerative joint disease. Although these supplements are occasionally recommended for patients with degenerative disc disease and spinal degenerative joint disease, the evidence supporting this use is unknown. To systematically search and assess the quality of the literature on the use of glucosamine, chondroitin sulfate, and methylsulfonylmethane for the treatment of spinal osteoarthritis / degenerative joint disease, and degenerative disc disease. The Index of Chiropractic Literature, AMED, Medline, and CINAHL were searched for randomized controlled trials in English from 1984 to July 2009. Data from studies meeting the inclusion criteria was extracted and reviewed by three reviewers. The Jadad scale was used to assess study quality. No attempts were made at meta-analysis due to variation in study design. Two articles met the inclusion criteria. One study was found to have good quality but reported negative results for the supplemented group compared with placebo, the other study had low quality but reported significant positive results for the supplemented group when compared with a no intervention control group. There was little literature found to support the use of common nutritional supplements for spinal degeneration, making it difficult to determine whether clinicians should recommend them.
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0008-3194/2011/47–55/$2.00/©JCCA 2011
J Can Chiropr Assoc 2011; 55(1) 47
Effi cacy of glucosamine, chondroitin, and
methylsulfonylmethane for spinal degenerative
joint disease and degenerative disc disease:
a systematic review
Kent Stuber, BSc, DC, MSc*
Sandy Sajko, BPHE, DC, MSc, RCCSS(C)†
Kevyn Kristmanson, BSc, DC§
* Canadian Memorial Chiropractic College; Private Practice, Calgary Alberta
† Private practice, Oakville, Ontario.
§ Private practice, Swift Current, Saskatchewan.
Primary contact: Kent Stuber DC, MSc, 19–8 Weston Drive SW, Calgary, Alberta, 403.685.5252.
The authors attest that there are no disclaimers or confl icts of interest.
No funding or support was received in conducting this study or preparing the manuscript.
© JCCA 2011
Contexte : Les suppléments alimentaires sont
couramment utilisés dans une variété de troubles
musculosquelettiques, y compris les maladies
dégénératives des articulations des genoux et
des hanches. Bien que ces suppléments soient
occasionnellement recommandés pour les patients
atteints de discarthrose et d’arthrose cervicale, aucune
preuve ne vient à l’appui de cette utilisation.
Objectif : Rechercher systématiquement et évaluer
la qualité de la littérature concernant l’utilisation
de la glucosamine, du sulfate de chondroïtine et du
méthylsulfonylméthane pour le traitement de l’ostéo-
arthrite et l’ostéoarthrose cervicale ainsi que de la
Sources : Des essais cliniques aléatoires en anglais
menés entre 1984 et juillet 2009 ont été recherchés dans
l’Index of Chiropractic Literature, AMED, Medline, et
Extraction et synthèse des données : Les données des
études respectant les critères d’inclusion ont été extraites
et examinées par trois réviseurs. L’échelle de Jadad a
été utilisée pour évaluer la qualité des études. Il n’a pas
été tenté de procéder à une méta-analyse en raison de la
diversité des modèles d’étude.
Résultats : Deux articles ont respecté les critères
d’inclusion. Une étude était de bonne qualité, mais
indiquait des résultats négatifs du groupe supplémenté
par rapport au groupe placebo. L’autre étude était de
moindre qualité mais indiquait des résultats positifs
Background: Nutritional supplements are commonly
used for a variety of musculoskeletal conditions,
including knee and hip degenerative joint disease.
Although these supplements are occasionally
recommended for patients with degenerative disc disease
and spinal degenerative joint disease, the evidence
supporting this use is unknown.
Objective: To systematically search and assess the
quality of the literature on the use of glucosamine,
chondroitin sulfate, and methylsulfonylmethane for the
treatment of spinal osteoarthritis / degenerative joint
disease, and degenerative disc disease.
Data Sources: The Index of Chiropractic Literature,
AMED, Medline, and CINAHL were searched for
randomized controlled trials in English from 1984 to
July 2009.
Data Extraction and Synthesis: Data from studies
meeting the inclusion criteria was extracted and
reviewed by three reviewers. The Jadad scale was used
to assess study quality. No attempts were made at meta-
analysis due to variation in study design.
Results: Two articles met the inclusion criteria. One
study was found to have good quality but reported
negative results for the supplemented group compared
with placebo, the other study had low quality but
reported signifi cant positive results for the supplemented
group when compared with a no intervention control
Conclusion: There was little literature found to
48 J Can Chiropr Assoc 2011; 55(1)
Effi cacy of glucosamine, chondroitin, and methylsulfonylmethane
Osteoarthritis is a pathology that affects approximately
15% of the world’s population.1 It is a chronic condition
that is most prevalent in the elderly and three times more
common in women than in men.2 Its characterizing fea-
ture is the progressive destruction of the articular cartilage
of joint surfaces which can result in impaired joint bio-
mechanics, swelling, pain, and disability.
Typically, the literature surrounding osteoarthritis is
categorized according to the affected body region. Spinal
osteoarthritis is one area that has garnered attention due
to its relatively high prevalence and the impact that it
can have on those affected. As individuals age, spinal os-
seous degeneration and age-related changes occur in the
macroscopic, histologic and biochemical composition
and structure of the nucleus pulposus and the annulus
brosus. It has been suggested that these changes occur
more frequently in the lumbar spine than the thoracic re-
gion due to the “splinting” by the costovertebral joints,
and again less frequently in the cervical spine due to the
relatively low need for weight-bearing.3
A common medicinal treatment for individuals
suffering from spinal osteoarthritis is nonsteroidal anti-
infl ammatory drugs (NSAIDs), but with the associated
serious gastrointestinal side effects many patients look
towards complementary and alternative medicine to gain
symptomatic relief and avoid iatrogenic illness.4
Glucosamine and chondroitin sulfate have been util-
ized medicinally in Europe for over 40 years and have
gained in popularity in North America since the late
1990’s.5 Glucosamine and chondroitin sulfate, studied
alone or in combination, appear to be somewhat effective
for osteoarthritis of the knee6–8 or hip7,8 but there is no
consensus with respect to a specifi c biochemical rationale
or reasoning behind the results. It has been suggested that
osteoarthritis is associated with a local defi ciency in some
key natural substances and that glucosamine acts as a
substrate for cartilage repair by stimulating proteoglycan
synthesis by chondrocytes.9 In the case of chondroitin, it
has been contended that since it constitutes the majority
of the glycosaminoglycans (GAGs) in articular cartilage,
it helps to maintain the viscosity in joints, stimulates car-
tilage repair and inhibits enzymes that lead to degenera-
tion of cartilage.10
More recently, methylsulfonylmethane or MSM has
been promoted as a possible supplement for osteoarth-
ritis due to its suggested anti-infl ammatory and anal-
gesic effects.11 Similar to glucosamine and chondroitin
sulfate, most MSM research has evaluated the effects of
MSM supplementation on knee osteoarthritis, as Usha
and Naidu12 and Kim et al13 both looked at the effects
of 12-weeks of supplementation with methylsulfonyl-
methane on knee osteoarthritis. In both studies, there was
a signifi cant difference between the supplementation and
placebo group with the supplementation group showing
decreased pain levels. In the study by Usha and Naidu12
specifi cally, when methylsulfonylmethane and glucosa-
mine were combined there was a signifi cant difference in
swelling index, joint function, walking time, joint mobil-
ity index, and overall function ability when compared to
the placebo and the supplements when taken individually.
The objective of this paper was to systematically
search and assess the quality of the literature on the use
of glucosamine, chondroitin sulfate, and methylsulfonyl-
support the use of common nutritional supplements for
spinal degeneration, making it diffi cult to determine
whether clinicians should recommend them.
(JCCA 2011; 55(1):47–55)
key words: systematic review, glucosamine,
chondroitin, methylsulfonylmethane, osteoarthritis,
degenerative joint disease, spine
du groupe supplémenté par rapport à un groupe de
Conclusion : Peu de littérature était disponible à
l’appui de l’utilisation de suppléments alimentaires
communs dans le traitement de la dégénérescence
cervicale. Il est par conséquent diffi cile de déterminer si
les cliniciens doivent les recommander.
(JCCA 2011; 55(1):47–55)
mots clés : examen systématique, glucosamine,
chondroïtine, méthylsulfonylméthane, ostéo-arthrite,
ostéoarthrose cervicale, discarthrose, colonne vertébrale
J Can Chiropr Assoc 2011; 55(1) 49
K Stuber, S Sajko, K Kristmanson
methane, alone or in combination, for the treatment of
spinal osteoarthritis / degenerative joint disease, and de-
generative disc disease.
An electronic search for relevant literature was conducted
on the Index of Chiropractic Literature, AMED, Med-
line, and CINAHL up to and including July 2009. Search
terms consisted of combinations of glucosamine sulfate
(GS), chondrotin sulfate (CS), or methylsulfonylmethane
(MSM) with terms for spinal arthritis or osteoarthritis,
spinal degenerative joint disease, or degenerative disc dis-
ease (the exact search terms and strategies employed are
available from the authors). Relevant MeSH terms were
employed whenever possible. The Cochrane Library was
also searched for relevant reviews or articles using similar
search terms. The authors also hand searched their per-
sonal libraries. Two of the authors (KS and SS) scrutin-
ized the electronic search results, titles and abstracts in
particular, to determine which full manuscripts should be
obtained and evaluated. Each of these authors composed
a list of studies from the electronic search results that they
felt may be clinical studies using GS, CS, or MSM, these
lists were compared and any differences were resolved by
discussion to obtain a fi nal list of manuscripts to obtain.
The full manuscripts that were obtained were for any clin-
ical studies on spinal arthritis, osteoarthritis, degenerative
joint disease, or degenerative disc disease using GS, CS
or MSM.
The inclusion criteria used for this review are indicated
in Table 1, but consisted of studies that were randomized
controlled trials conducted on patients with spinal degen-
erative joint disease, spinal osteoarthritis/osteoarthrosis,
and/or degenerative disc disease. Interventions could in-
clude glucosamine (sulfate or HCl), chondroitin sulfate,
and methylsulfonylmethane (MSM) in any combination
or dosage with co-interventions being allowed; these
could be compared to a do nothing control group, pla-
cebo, or another active intervention. Outcome measures
of interest had to include at least one validated and reli-
able assessment of pain (such as a visual analog scale or
numerical pain rating scale) or disability due to pain (such
as the Oswestry Low Back Disability Index). Only articles
published in a peer-reviewed journal in English within the
past 25 years (1984–2009) were considered. These cri-
teria were applied to all of the obtained full manuscripts.
Reference searching was conducted from the reference
lists of all retrieved studies.
One of the authors (KS) initially extracted data (such as
sample details, interventions, outcome measures, results,
adverse events, withdrawals/dropouts) from the studies
meeting the inclusion criteria into a data extraction sheet
that was checked and edited by the other authors (SS, KK).
The Jadad scale (or Oxford quality scoring system) was
used to assess study quality.14 The Jadad scale is among
the most referenced and widely used of all quality scoring
systems and considered valid and reliable.14,15 The Jadad
scale asks questions about three different aspects of study
design: double blinding, randomization, and the handling
of withdrawals and dropouts.14 There are seven questions
which lead to a score that out of fi ve, with zero being the
lowest score and fi ve being the highest.14 We applied the
classifi cation developed by Abraham et al to determine
whether included trials were of good or poor quality,
where they defi ned a good quality trial as receiving four
or higher on the Jadad scale and a poor quality trial as one
Table 1 Review Inclusion Criteria
Published in English
Published in a peer-reviewed journal
Published in the past 25 years (1984–2009)
Randomized controlled trial
Patients must have spinal osteoarthritis / osteoarthrosis / degenerative joint disease and/or degenerative disc disease proven
via diagnostic imaging
Use glucosamine sulfate (or glucosamine HCl) and/or chondroitin sulfate and/or methylsulfonylmethane (MSM)
Use of other medications, supplements, or interventions tolerable
Comparison group could consist of a do nothing control, placebo, or a different active treatment
Outcome measures include an assessment of pain and/or disability due to pain
50 J Can Chiropr Assoc 2011; 55(1)
Effi cacy of glucosamine, chondroitin, and methylsulfonylmethane
earning three or less.16 All three authors independently re-
viewed the included studies and resolved any differences
by discussion. No attempts were made at meta-analysis
as it was felt there would be too much variation in study
parameters to allow for suitable synthesis.
Figure 1 depicts the fl ow of trials through the review.
The electronic database search initially yielded 17 arti-
cles from Medline, 2 from CINAHL, 2 from the Index
to Chiropractic Literature, 1 from AMED, and none from
the Cochrane Library, for a total or 21 articles excluding
overlap. These search results were scrutinized and only
three articles were obtained for full manuscript review.
Upon review of these three manuscripts, two were found
to be RCTs17,18 and one was a case report19 and thus ex-
cluded. One article was identifi ed by reference searching
from a previous systematic review of glucosamine for
osteoarthritis8 but was excluded as it was not published
in the peer-reviewed literature.20 Thus only two articles
were accepted for analysis.17,18 Table 2 depicts the qual-
ity rating of the two articles included in the review using
the Jadad scale. There was complete (100%) agreement
between the authors on the rating of these articles.
The paper by Leffl er et al17 received a score of 4/5 which
corresponds with a good quality article16, with the only
point missing being for the description of randomization
method. Leffl er et al compared the use of a combination
of glucosamine, chondroitin, and manganese ascorbate
with placebo for patients with degenerative joint disease
of the knee or low back. The subjects were 34 males in
the United States Navy with x-ray proven degenerative
changes in the knees or low back. The 23 subjects with
low back DJD were 43.6 years old on average. The sub-
jects received either oral Cosamin (at a dosage of 1500
mg/day of glucosamine HCl, 1200 mg/day of chondroitin
sulphate, and 228 mg/day of manganese ascorbate) or
a matching placebo, each taken three times daily. Sub-
Figure 1 Literature Search Flow
21 articles identified through the electronic search,
1 article identified through reference searching(20)
3 articles retrieved for more detailed evaluation
2 studies included in the review(17,18)
2 articles excluded that were not published in English,
16 were not clinical studies, 1 article excluded because
it was not published in the peer-reviewed literature(20)
1 article excluded because it was not an RCT(19)
J Can Chiropr Assoc 2011; 55(1) 51
K Stuber, S Sajko, K Kristmanson
jects spent three weeks in a baseline period, then received
either 8 weeks of Cosamin or placebo, then crossed over
to the other group for a fi nal 8 weeks. Subjects were not
permitted to take NSAIDs during the trial but they could
take acetaminophen as necessary.
Outcome measure assessment occurred after weeks 2
and 3 of the baseline period and after weeks 7 and 8 of
each treatment period (thus 6 times in total); there was
no long term follow-up. Outcome measures for the low
back degenerative joint disease subjects included the
Roland-Morris questionnaire for back disability, patient
subjective assessment of handicap (from 0 to 5), phys-
ician assessment of severity (from 0 to 3), an 11 point
visual analog scale, tenderness with movement of the low
back (from 0 to 3), a sprint and stair run, Pavelka physical
examination maneuvers, the Modifi ed Schober technique
for assessing lumbar fl exion, and patient’s subjective as-
sessment of results of treatment (from –3 to +3) (Leffl er).
All of these assessments were totalled to provide an over-
all summary score.
By the end of the trial, four patients withdrew from the
low back degenerative joint disease group. There were
no statistically signifi cant changes in the low back group
when considering the overall summary score or individ-
ual outcome measures. However, the summary score and
patient assessment of treatment effect did show wide 95%
Confi dence Interval’s indicating that clinically meaning-
ful results may have been obtained. No statistically sig-
nifi cant differences were identifi ed between groups with
respect to reported adverse effects.
Fujita et al’s paper18 scored 1/5 which corresponds
with a low quality article,16 with the only point allocated
for the study being described as randomized. This study
compared the use of a combination of glucosamine (1800
mg/day), active absorbable algal calcium (900 mg/day),
porcine skin collagen (10,500 mg/day), composite muco-
polysaccharide (600 mg/day), and vitamin C (600 mg/
day) with control for 80 patients with knee or low back
pain. The number of subjects in this trial with low back
degenerative joint disease was not indicated. The subjects
were randomly divided into two groups: one that would
receive three daily doses of the glucosamine combination
treatment over a four month time period (after a suitable
washout period) and a second group that did not receive
supplements. Subjects were not permitted analgesics dur-
ing the trial. The average age of the subjects was approxi-
mately 65 years old and 75 out of 80 were female. The
supplement group had an average of 1.47/3 in terms of
radiographic degree of spondylosis deformans, compared
with 1.65 in the control group (not a signifi cant differ-
Outcome measures were assessed at baseline and after
Table 2 Jadad Scale Scoring Results
Jadad Scale Item
Leffl er CT, et al. Military
Med 1999; 164(2): 85–91.
Fujita T, et al. J Bone
Miner Metab 2002; 20:
Study described as randomized? 11
Randomization method described and appropriate? 00
Study described as double blind? 10
Double blinding method described and appropriate? 10
Description of withdrawals and dropouts? 10
Subtract 1 point if the randomization method was
described but was inappropriate.
Subtract 1 point if the double blinding method was described
but was inappropriate.
Total Score (/5) 4 1
52 J Can Chiropr Assoc 2011; 55(1)
Effi cacy of glucosamine, chondroitin, and methylsulfonylmethane
the 4 month trial period and included a subjective pain
rating (from 0–3). Pain levels were also measured by skin
impedance when quietly sitting (the basal value), when
standing up, walking, squatting, climbing up and down
stairs (which were all expressed in terms of percentage
change from the basal value). Lumbar spinal radiographs
and bone mineral densities were performed prior to and
following the trial. The supplement group had a signifi cant
decrease in skin impedance from the beginning to conclu-
sion of the trial; this change was not seen in the control
group. Signifi cant decreases in skin impedance during
various tasks (standing up, walking, squatting, climbing
up and down stairs) when compared with rest were again
noted in the supplement group. Subjective pain values de-
creased signifi cantly in the supplement group, but not the
control group. The lumbar bone mineral density increased
signifi cantly in the supplement group; however the degree
of vertebral deformity did not change in either group.
Only two papers met the inclusion criteria for this review
and these articles by Leffl er et al17 and Fujita et al18 are
contradictory in their fi ndings. Leffl er et al17 examined
the effects of glucosamine, chrondroitin sulfate, and man-
ganese ascorbate on degenerative joint disease of the
low back or knee. These authors found no discernable
improvements or change in the supplemented group when
compared to the control group. The article was rated as
having good quality.16 Fujita et al18 looked at the effect
of glucosamine, active absorbable algal calcium, porcine
skin collage, composite mucopolysaccharide, and vita-
min C on back or knee pain. The results indicated that the
group assigned to supplements had signifi cant decreases
in skin impedance and pain over the duration of the study
when compared to the control group. This article was rat-
ed as having poor quality.16
The supplements used by the active treatment (i.e. non-
control) groups in both Leffl er et al’s17 and Fujita et al’s18
studies each had several components, thus it cannot be
ascertained which component(s) of the supplements pro-
duced the improvements (if any) in those subjects. For the
purposes of this review, it cannot be discerned whether the
glucosamine or chondroitin sulfate produced any benefi -
cial effects in the study by Leffl er et al17 or if glucosamine
was responsible for any improvements noted in the study
by Fujita et al.18 The methods of randomization used
in both of the included studies were not revealed. Both
studies indicated that randomization of subjects did take
place, but the exact methods were not disclosed and thus
we cannot discern if the methods were appropriate. The
follow-up periods of 7 to 8 weeks employed by Leffl er et
al17 and 4 months by Fujita et al18 were likely inadequate,
given that spinal osteoarthritis is a long-term condition. It
would seem more suitable for researchers to utilize longer
follow-up periods of at least one year and preferably to
ve years or more. Both of the involved studies had mixed
populations with Leffl er et al including patients with low
back and/or knee degenerative joint disease17 and Fujita
et al including patients with back or knee pain.18 In the
case of Fujita et al18 the average degree of spondylosis
deformans on a scale of zero to three was noted at base-
line indicating that there was some amount of radiograph-
proven spinal osteoarthritis present on average, however
the number of subjects diagnosed with spinal degenera-
tion was not indicated.18
Thus, for the clinician there is contradictory evidence
to support the use of glucosamine in the treatment of spin-
al osteoarthritis or disc degeneration based on the results
of one positive study with low quality and one negative
study with good quality. We identifi ed no articles to sup-
port the use of chondroitin sulfate based on one negative
study with good quality, or MSM based on no identifi ed
studies. Regardless, use of these supplements and their
recommendation in practice is widespread.
In a recent randomized clinical trial analyzing the use
of alternative therapies by individuals with osteoarthritis,
the authors found that 47% of their participants reported
utilizing at least one type of alternative care with the most
common types being massage therapy (57% of alterna-
tive care users), chiropractic (20.7%) and non-prescribed
alternative medications (17.2%).21 A survey of over 2,500
full-time chiropractors in the United States revealed that
on average they treat patients with osteoarthritis/degen-
erative joint disease “often” which was equivalent to one
to two times per week.22 The specifi c anatomic locations
of the osteoarthritis/degenerative joint disease were not
indicated in that survey. The specifi c methods of treat-
ment for a patient with osteoarthritis/degenerative joint
disease was not assessed, however 89% of the chiroprac-
tors surveyed utilized nutritional counselling, therapy,
or supplementation in their practices over the previous
year and on average they indicated that 34.6% of their
J Can Chiropr Assoc 2011; 55(1) 53
K Stuber, S Sajko, K Kristmanson
patients would receive this type of passive adjunctive
A prospective cohort study of a random sample of 9423
Canadians found that 11.5% of their participants were
taking glucosamine fi ve years into the trial compared with
1.6% at baseline.23 This increased usage was associated
with several factors including age, presence of arthritis
and or back pain, calcium intake, regular physical activ-
ity, and use of glucosamine previously.23 The authors felt
that some participants use glucosamine to manage the
symptoms of arthritis and/or back pain, while others use
it on a preventive basis.23 In 2007 glucosamine was the
second most commonly used natural health product, used
by 19.9% of participants over the previous thirty days in
a survey of adults in the general population of the United
States who used nonvitamin, nonmineral health prod-
ucts.24 In the same survey chondroitin was used by 11.9%
of the participants, ranking eighth, while MSM was used
by 4.1% of the participants, ranking eighteenth.24
For clinicians who do choose to recommend these
supplements, it is important to bear in mind that there are
some potential side-effects or contraindications to their
use. It has been proposed that glucosamine sulfate could
potentially alter glucose control, specifi cally interfering
with the hexosamine biosynthesis pathway,25 and as such
down-regulating cellular glucose uptake and leading to
hypergylcemia and insulin resistance. To date, no effects on
glucose concentrations were documented in studies evalu-
ating the use of long-term oral glucosamine for osteoarth-
ritis.9,26 Although no specifi c glucosamine sulfate induced
changes in glycemic control are found in the literature, it
should be noted that the subjects in these studies had well-
controlled type II diabetes and it is unclear how glucosa-
mine sulfate would affect individuals with type I diabetes
who are unable to secrete additional endogenous insulin
to compensate for the potential glucosamine-induced in-
sulin resistance.27 Recently, a case report by Knudsen and
Sokol addressed the effects of glucosamine sulfate on an
individual utilizing warfarin.28 The authors suggested that
the supplementation of glucosamine or glucosamine com-
bined with chondroitin sulfate in individuals consuming
warfarin could potentiate the anticoagulant effects of war-
farin and thereby increase the risk of bleeding.28 Although
this was only a case report, chiropractors should be cogni-
zant of this potential glucosamine-warfarin interaction as
some of the patients for whom they may consider a recom-
mendation for glucosamine may be currently taking war-
farin as an anti-coagulant.
The literature regarding possible contraindications for
MSM is limited, as no formal safety data or long-term
assessment was available. Animal toxicity studies have
shown only minor adverse effects in levels that are 5 to 7
times the proposed maximum recommended human dose
of 6 grams per day.29 The only proposed adverse effects
regarding human supplementation with MSM include al-
lergic gastrointestinal disruptions and skin rashes.30
This review has some possible limitations including
the limitations of the literature itself as there were only
two articles that met our inclusion criteria. This calls into
question whether there may be some publication bias in
this area. It is striking that there have only been two RCTs
published on these supplements for spinal osteoarthritis
when compared with the number of available studies for
these supplements on hip and knee osteoarthritis. Ref-
erence searching of the Cochrane systematic review by
Towheed et al8 yielded an additional short term pilot RCT
article pertaining to the use of glucosamine for osteoarth-
ritis of the spine.20 However, this article was excluded
from the review by Towheed et al8 and did not meet the
inclusion criteria for this review as it was not published in
the peer-reviewed literature; it was an unpublished tech-
nical report by a pharmaceutical company.20
From this limited evidence base fi rm conclusions can-
not be drawn with respect to the effectiveness of glu-
cosamine, chondroitin, or MSM for spinal osteoarthritis,
because their effectiveness is still largely untested. It is
diffi cult to generalize the fi ndings from systematic re-
views pertaining to topics that are as poorly studied as this
one and if more studies had been eligible for this review
it would have led to a stronger conclusion. However it is
still important to present the results of such systematic
reviews so that clinicians can make evidence-based deci-
sions; there have even been systematic reviews published
that had zero articles meet their inclusion criteria.31 From
this overt lack of studies it can be easily stated that there
is a defi nite need for more research in this area.
Another possible limitation of this review is by way of
a language bias as we only permitted articles published in
English. Furthermore we did not search the “grey” litera-
ture or additional electronic databases such as EMBASE.
However, we conducted a multi-modal search strategy
using several electronic databases with hand reference
54 J Can Chiropr Assoc 2011; 55(1)
Effi cacy of glucosamine, chondroitin, and methylsulfonylmethane
searching of obtained articles, thus numerous steps were
taken to thoroughly evaluate the literature.
It could also be argued that a weakness in the meth-
ods of this systematic review was only including RCTs
according to the inclusion criteria employed. However,
in looking at the results of the literature search as seen
in Figure 1, the only other clinical study identifi ed in the
electronic literature search, which was not limited by
study type, was a case report by van Blitterswijkk et al19
that would have been excluded from the review regardless
as it did not employ suitable outcome measures of pain
and/or disability due to pain, along with the single study
found through reference searching, the aforementioned
pilot RCT20 which was excluded as it was not published
in a peer-reviewed journal. As such, use of this particular
inclusion criterion did not affect the outcome of the re-
view.” The use of the Jadad scale may be questioned as it
is a relatively simple tool for rating the quality of RCTs.14
The Jadad scale only evaluates randomization, blinding,
and withdrawals and dropouts, and does not look at other
areas to assess study quality.15 However the Jadad scale is
the most frequently used health care literature quality as-
sessment tool and it has been tested extensively and found
to be valid and reliable.15
Future research in this area should take place to de-
termine the rates at which health care professionals rec-
ommend or prescribe nutritional supplements such as
glucosamine sulfate, chondroitin sulfate, and MSM to pa-
tients with spinal arthritis and disc degeneration, as well
as the consumer usage rates of these supplements. Further
clinical research by way of randomized controlled trials
on the effects of these supplements is also suggested as
there have been only two RCTs in this area using vastly
different supplements and without solely examining pa-
tients with spinal osteoarthritis and/or disc degeneration.
Given the paucity of evidence surrounding the use of glu-
cosamine, chondroitin, and MSM for spinal arthritis and
disc degeneration and the confl icting results in the two
studies that were identifi ed, it would be diffi cult for evi-
dence-based practitioners to justify the recommendation
of these supplements for the pain and resultant disabil-
ity from spinal degenerative conditions. There is an in-
adequate amount of literature examining the use of these
supplements for lumbar spinal degenerative conditions in
comparison with the volume available pertaining to their
use for knee or hip osteoarthritis. Further research is ne-
cessary to clarify if these supplements are of any potential
benefi t for patients with spinal degenerative conditions.
The authors would like to thank and acknowledge Ms.
Anne Taylor-Vaisey, reference librarian at the Canadian
Memorial Chiropractic College for her assistance with the
literature search.
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... These medications can be supplied via oral administration or via intradiscal injections, whose aim is to decrease the local inflammation and provide temporary anaesthesia to relieve the pain [108]. Among supplements, omega-3 fatty acids, glucosamine, and chondroitin are usually administered due to their minimal side effects, but there is a lack of evidence and conflicting findings on their therapeutic effect [110,111]. Although these treatments can offer temporary pain relief, these medications do not target the process of the disease (NP matrix degradation, NP cell senescence and death, or altered cell function), but only target the symptoms of LBP. ...
Full-text available
Low back pain (LBP), caused by intervertebral disc (IVD) degeneration, is a major contributor to global disability. In its healthy state, the IVD is a tough and well-hydrated tissue, able to act as a shock absorber along the spine. During degeneration, the IVD is hit by a cell-driven cascade of events, which progressively lead to extracellular matrix (ECM) degradation, chronic inflammation, and pain. Current treatments are divided into palliative care (early stage degeneration) and surgical interventions (late-stage degeneration), which are invasive and poorly efficient in the long term. To overcome these limitations, alternative tissue engineering and regenerative medicine strategies, in which soft biomaterials are used as injectable carriers of cells and/or biomolecules to be delivered to the injury site and restore tissue function, are currently being explored. Self-assembling peptide hydrogels (SAPHs) represent a promising class of de novo synthetic biomaterials able to merge the strengths of both natural and synthetic hydrogels for biomedical applications. Inherent features, such as shear-thinning behaviour, high biocompatibility, ECM biomimicry, and tuneable physiochemical properties make these hydrogels appropriate and functional tools to tackle IVD degeneration. This review will describe the pathogenesis of IVD degeneration, list biomaterials requirements to attempt IVD repair, and focus on current peptide hydrogel materials exploited for this purpose.
... There is poor evidence on glucosamine and chondroitin having any effect on the pain or regeneration of DDD from very few literature reports, with conflicting findings [61]. ...
Full-text available
With an aging population, there is a proportional increase in the prevalence of intervertebral disc diseases. Intervertebral disc diseases are the leading cause of lower back pain and disability. With a high prevalence of asymptomatic intervertebral disc diseases, there is a need for accurate diagnosis, which is key to management. A thorough understanding of the pathophysiology and clinical manifestation aids in understanding the natural history of these conditions. Recent developments in radiological and biomarker investigations have potential to provide noninvasive alternatives to the gold standard, invasive discogram. There is a large volume of literature on the management of intervertebral disc diseases, which we categorized into five headings: a) Relief of pain by conservative management, b) restorative treatment by molecular therapy, c) reconstructive treatment by percutaneous intervertebral disc techniques, d) relieving compression and replacement surgery, and e) rigid fusion surgery. This review article aims to provide an overview on various current diagnostic and treatment options and discuss the interplay between each arms of these scientific and treatment advancements, hence providing an outlook of their potential future developments and collaborations in the management of intervertebral disc diseases.
... El primero es un amino-monosacárido de origen natural, precursor de los glicosaminoglicanos, considerado un componente importante de la formación del cartílago de las articulaciones. Se ha propuesto que lograba inhibir la IL-1 β presente en los discos lumbares; sin embargo, esta es una teoría que no se ha demostrado científicamente (5). Otro mecanismo de acción descrito se basa en la reparación del cartílago mediante la síntesis de proteoglicanos en los condrocitos (5). ...
... 18 It is important to note that there is some variability in agreement on which treatments within this list should be considered low-value. For example, it is widely agreed that the evidence for the efficacy of glucosamine is limited 19 and it is not recommended by the National Institute for Health and Care Excellence. 3 Liothyronine, conversely, has been restricted largely due to high cost rather than lack of efficacy. ...
Objectives NHS England recently announced a consultation seeking to discourage the use of treatments it considers to be low-value. We set out to produce an interactive data resource to show savings in each NHS general practice and to assess the current use of these treatments, their change in use over time, and the extent and reasons for variation in such prescribing. Design Cross-sectional analysis. Setting English primary care. Participants English general practices. Main outcome measures We determined the cost per 1000 patients for prescribing of each of 18 treatments identified by NHS England for each month from July 2012 to June 2017, and also aggregated over the most recent year to assess total cost and variation among practices. We used mixed effects linear regression to determine factors associated with cost of prescribing. Results Spend on low-value treatments was £153.5 m in the last year, across 5.8 m prescriptions (mean, £26 per prescription). Among individual treatments, liothyronine had the highest prescribing cost at £29.6 m, followed by trimipramine (£20.2 m). Over time, the overall total number of low-value prescriptions decreased, but the cost increased, although this varied greatly between treatments. Three treatment areas increased in cost and two increased in volume, all others reduced in cost and volume. Annual practice level spending varied widely (median, £2262 per thousand patients; interquartile range £1439 to £3298). Proportion of patients over 65 was strongly associated with low-value prescribing, as was Clinical Commissioning Group. Our interactive data tool was deployed to where monthly updated figures and graphs can be viewed. Conclusions Prescribing of low-value treatments is extensive but varies widely by treatment, geographic area and individual practice. Despite a fall in prescription numbers, the overall cost of prescribing for low-value items has risen. Prescribing behaviour is clustered by Clinical Commissioning Group, which may represent variation in the optimisation efficiency of medicines, or in some cases access inequality.
... Subjects with lower back pain undergoing conventional physical therapy with supplementation of a glucosamine complex containing MSM reported an improvement in their quality of life [156]. A 2011 systematic review of GCM supplements as a treatment for spinal degenerative joint disease and degenerative disc disease failed to come to a conclusion on efficacy due to the scarcity of quality literature [157]. ...
Full-text available
Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption.
... It is a major component of the extracellular matrix. As a component of cartilage, chondroitin sulfate helps cushion the joints (Stuber et al., 2011). Chondroitin sulfate is believed to provide structure, hold water and nutrients, and promote elasticity in cartilage. ...
Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested.
... Chondroitin is found attached to proteoglycan and serves as a building block for joint cartilage. Several studies have shown chondroitin sulfate taken orally have no benefits over placebo [43]. Although a study done by Block and team [42] has reported that glucosamine could alleviate the pain of osteoarthritis in vivo, there is a lack of evidence to support its symptomatic benefits in patients with OA [44]. ...
Full-text available
Articular cartilage is prone to damage from sports injuries/aging, which often progresses to osteoarthritis, an inflammatory and degenerative joint disease characterized by degradation of the entire joint, leading to pain and disability. Current pharmaceutical and surgical interventions relieve pain and improve joint function, but the long-term results are not satisfactory. More recently, stem cell-based strategies that include direct intraarticular injection of mesenchymal stem cells and implantation of tissue-engineered cartilage grafts have been developed. This chapter will first review the cartilage structure, composition, and pathology, and then summarize the most recent advances in applying mesenchymal stem cells for treatment of cartilage defects and osteoarthritis.
Conference Paper
Целью нашей работы было изучение влияния метоклопра мида на нейрогенную дилатацию менингеальных сосудов в условиях экспериментального моделирования ГБ у крыс, позволяющего имитировать патофизиологические события, происходящие в периферическом звене тригемино-васкулярной системы во время приступа мигрени
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The current study designed to determine the effect of Glucosamine sulfate in the spleen organ of Albino mice .the study included (24) mice divided in to 3groups (control group had distilled water orally).The other groups treated with (1500, 2500) ml/kg .respectively for (2, 3) months .the spleen have been taken from dissected animal for microscopic preparation to study. Statistical results showed that the average weight of the spleen gradually decreased as the concentration and duration of the drug increased ,The histopathologicale changes appeared in the spleen of the exposure groups during (2,3) month ,the effects were Congestion,hyperplasia,atrophy, amyloid and necrosis.
Management of persistent pain in older adults is challenging given the prevalence of multiple comorbid painful conditions, polypharmacy, age-related changes restricting pharmacological options, and socioeconomic factors. The influences of these factors along with current concern for the use of opioid analgesics highlight the importance of incorporating complementary and integrative medicine approaches. Evidence suggests efficacy and satisfaction with integrating complementary pain management strategies for older adults, especially yoga, massage, and natural products. Nurses and other providers, given their emphasis on holistic care, are in a unique position to lead the transformation of pain management to a patient-centered, self-management style that integrates complementary therapies. [Journal of Gerontological Nursing, 42(12), 40-48.].
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Objective Conventional treatment of osteoarthritis (OA) with non-steroidal anti-inflammatory drugs is associated with serious gastrointestinal side effects and in view of the recent withdrawal of some cyclo-oxygenase-2 inhibitors, identifying safer alternative treatment options is needed. The objective of this systematic review is to evaluate the existing evidence from randomised controlled trials of two chemically related nutritional supplements, dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of OA to determine their efficacy and safety profile. Methods The electronic databases [Cochrane Library, Medline, Embase, Amed, Cinahl and NeLH (1950 to November 2007)] were searched. The search strategy combined terms: osteoarthritis, degenerative joint disorder, dimethyl sulfoxide, DMSO, methylsulfonylmethane, MSM, clinical trial; double-blind, single blind, RCT, placebo, randomized, comparative study, evaluation study, control. Inclusion and exclusion criteria were applied. Data were extracted and quality was assessed using the JADAD scale. Results Six studies were included [evaluating a total of 681 patients with OA of the knee for DMSO (N = 297 on active treatment); 168 patients for MSM (N = 52 on active treatment)]. Two of the four DMSO trials, and both MSM trials reported significant improvement in pain outcomes in the treatment group compared to comparator treatments, however, methodological issues and concerns over optimal dosage and treatment period, were highlighted. Conclusion No definitive conclusion can currently be drawn for either supplement. The findings from all the DMSO studies need to be viewed with caution because of poor methodology including; possible unblinding, and questionable treatment duration and dose. The data from the more rigorous MSM trials provide positive but not definitive evidence that MSM is superior to placebo in the treatment of mild to moderate OA of the knee. Further studies are now required to identify both the optimum dosage and longer-term safety of MSM and DMSO, and definitive efficacy trials.
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This paper examines the associations between chronic disease, age, and physical and mental health-related quality of life (HRQOL), using data collected in 10 studies representing five chronic conditions. HRQOL was measured using the SF-36 or the shorter subset, SF-12. Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were graphed by condition in age increments of 10 years, and compared to age- and sex-adjusted normative data. Linear regression models for the PCS and MCS were controlled for available confounders. The sample size of 2418 participants included 129 with renal failure, 366 with osteoarthritis (OA), 487 with heart failure, 1160 with chronic wound (leg ulcer) and 276 with multiple sclerosis (MS). For the PCS, there were large differences between the normative data and the mean scores of those with chronic diseases, but small differences for the MCS. Female gender and comorbid conditions were associated with poorer HRQOL; increased age was associated with poorer PCS and better MCS. This study provided additional evidence that, while physical function could be severely and negatively affected by both chronic disease and advanced age, mental health remained relatively high and stable.
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This report presents selected estimates of complementary and alternative medicine (CAM) use among U.S. adults and children, using data from the 2007 National Health Interview Survey (NHIS), conducted by the Centers for Disease Control and Prevention's (CDC) National Center for Health Statistics (NCHS). Trends in adult use were assessed by comparing data from the 2007 and 2002 NHIS. Estimates were derived from the Complementary and Alternative Medicine supplements and Core components of the 2007 and 2002 NHIS. Estimates were generated and comparisons conducted using the SUDAAN statistical package to account for the complex sample design. In 2007, almost 4 out of 10 adults had used CAM therapy in the past 12 months, with the most commonly used therapies being nonvitamin, nonmineral, natural products (17.7%) and deep breathing exercises (12.7%). American Indian or Alaska Native adults (50.3%) and white adults (43.1%) were more likely to use CAM than Asian adults (39.9%) or black adults (25.5%). Results from the 2007 NHIS found that approximately one in nine children (11.8%) used CAM therapy in the past 12 months, with the most commonly used therapies being nonvitamin, nonmineral, natural products (3.9%) and chiropractic or osteopathic manipulation (2.8%). Children whose parent used CAM were almost five times as likely (23.9%) to use CAM as children whose parent did not use CAM (5.1%). For both adults and children in 2007, when worry about cost delayed receipt of conventional care, individuals were more likely to use CAM than when the cost of conventional care was not a worry. Between 2002 and 2007 increased use was seen among adults for acupuncture, deep breathing exercises, massage therapy, meditation, naturopathy, and yoga. CAM use for head or chest colds showed a marked decrease from 2002 to 2007 (9.5% to 2.0%).
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Osteoarthritis (OA) is a common, chronic disease that most frequently affects the knees and is a major cause of disability in the elderly. It is characterized by progressive cartilage loss, accompanied by secondary changes such as osteophyte formation and calcium deposition. Inflammatory processes are also involved, leading to stiffness and pain, for which patients seek treatment. Conventional treatment includes analgesics or non-steroidal anti-inflammatory drugs, however life-style changes should also be recommended, such as weight reduction and specific exercises. Glucosamine and chondroitin, classed as over-the-counter supplements or nutraceuticals, are regularly self-administered by patients with OA. Both agents are produced endogenously in the human body and are essential components of cartilage. This review discusses the evidence that supports the use of these agents either alone or in combination for pain relief and as disease-modifying agents in OA.
Background Osteoarthritis (OA) is the most common form of arthritis, and it is often associated with significant disability and an impaired quality of life. Objectives To review all randomized controlled trials (RCTs) evaluating the effectiveness and toxicity of glucosamine in OA. Search strategy We searched MEDLINE, PREMEDLINE, EMBASE, AMED, ACP Journal Club, DARE, CDSR, and the CCTR. We also wrote letters to content experts, and hand searched reference lists of identified RCTs and pertinent review articles. All searches were updated in January 2005. Selection criteria Relevant studies met the following criteria: 1) RCTs evaluating the effectiveness and safety of glucosamine in OA, 2) Both placebo controlled and comparative studies were eligible, 3) Both single blinded and double blinded studies were eligible. Data collection and analysis Data abstraction was performed independently by two investigators and the results were compared for degree of agreement. Gotzsche's method and a validated tool (Jadad 1996) were used to score the quality of the RCTs. Continuous outcome measures were pooled using standardized mean differences (SMD) as the measure of effect size. Dichotomous outcome measures were pooled using relative risk ratios (RR). Main results Analysis restricted to eight studies with adequate allocation concealment failed to show benefit of glucosamine for pain and WOMAC function. Collectively, the 20 analyzed RCTs found glucosamine favoured placebo with a 28% (change from baseline) improvement in pain (SMD - 0.61, 95% CI - 0.95, - 0.28) and a 21% (change from baseline) improvement in function using the Lequesne index (SMD - 0.51 95% CI - 0.96, - 0.05). However, the results are not uniformly positive, and the reasons for this remain unexplained. WOMAC pain, function and stiffness outcomes did not reach statistical significance. In the 10 RCTs in which the Rotta preparation of glucosamine was compared to placebo, glucosamine was found to be superior for pain (SMD - 1.31, 95% CI - 1.99, - 0.64) and function using the Lequesne index (SMD - 0.51, 95% CI - 0.96, - 0.05). Pooled results for pain (SMD - 0.15, 95% CI - 0.35, 0.05) and function using the WOMAC index (SMD 0.03, 95% CI - 0.18, 0.25) in those RCTs in which a non-Rotta preparation of glucosamine was compared to placebo did not reach statistical significance. In the four RCTs in which the Rotta preparation of glucosamine was compared to an NSAID, glucosamine was superior in two, and equivalent in two. Two RCTs using the Rotta preparation showed that glucosamine was able to slow radiological progression of OA of the knee over a three year period (SMD 0.24, 95% CI 0.04, 0.43). Glucosamine was as safe as placebo in terms of the number of subjects reporting adverse reactions (RR= 0.97, 95% CI, 0.88, 1.08). Authors' conclusion This update includes 20 studies with 2570 patients. Pooled results from studies using a non-Rotta preparation or adequate allocation concealment failed to show benefit in pain and WOMAC function while those studies evaluating the Rotta preparation show that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA. WOMAC outcomes of pain, stiffness and function did not show a superiority of glucosamine over placebo for both Rotta and non-Rotta preparations of glucosamine. Glucosamine was as safe as placebo.
Objective To examine the rates of use and expenditures on alternative therapies by adults with osteoarthritis (OA).Methods Adults with OA recruited from the community to participate in a randomized clinical trial recorded alternative and traditional health care use on postcard diaries. General and arthritis-specific quality of life was assessed by questionnaires.ResultsMore than 47% of participants reported using at least one type of alternative care during the 20-week intervention period. Among alternative care consumers, the most commonly used treatments were massage therapy (57%), chiropractic services (20.7%), and nonprescribed alternative medications (17.2%). Four percent of subjects reported using only alternative care during the study period. Expenditures for alternative therapy averaged $1,127 per year, compared with $1,148 for traditional therapies.Conclusion Use of and expenditures for alternative care were high among this cohort of older adults with OA. Clinicians may want to inquire about use of these therapies before recommending treatments for this condition.
The investigation of disease-modifying treatment options for osteoarthritis (OA) has become an important aspect of orthopaedic care. The purpose of this review is to critically evaluate the evidence for the use of glucosamine and chondroitin sulfate for knee OA with the goal of elucidating their indications for clinical use. The published clinical studies of glucosamine and chondroitin sulfate on OA are reviewed within the context of evidence-based medicine. Almost every included trial has found the safety of these compounds to be equal to placebo. In the literature satisfying our inclusion criteria, glucosamine sulfate, glucosamine hydrochloride, and chondroitin sulfate have individually shown inconsistent efficacy in decreasing OA pain and improving joint function. Many studies confirmed OA pain relief with glucosamine and chondroitin sulfate use. The excellent safety profile of glucosamine and chondroitin sulfate therapy should be discussed with patients, and these supplements may serve a role as an initial treatment modality for many OA patients.
Glucose is an important regulator of cell growth and metabolism. Thus, it is likely that some of the adverse effects of hyperglycemia are reflections of normal regulation by abnormal concentrations of glucose. How the cell senses glucose, however, is still incompletely understood. Evidence has been presented that the hexosamine biosynthesis pathway serves this function for regulation of aspects of glucose uptake, glycogen synthesis, glycolysis, and synthesis of growth factors. Excess hexosamine flux causes insulin resistance in cultured cells, tissues, and intact animals. Further evidence for the possible role of this pathway in normal glucose homeostasis and disease is that the level of activity of the rate-limiting enzyme in hexosamine synthesis, glutamine:fructose-6-phosphate amidotransferase, is correlated with glucose disposal rates (GDRs) in normal humans and transgenic mice.