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Clinical efficacy and tolerance of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease

  • Animal Health Australia

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To evaluate the efficacy and tolerance of an extract of green-lipped mussel (GLME) in the management of mild-to-moderate degenerative joint disease (DJD) in dogs. Eighty-one dogs presumptively diagnosed with DJD were treated orally daily with either GLME or a placebo for 56 days, in a double-blind, placebo-controlled study. In an uncontrolled open-label extension to the study, all dogs were treated with GLME for an additional 56 days (from Days 57-112). Clinical signs were subjectively scored by the owners, and findings of detailed musculoskeletal examinations were scored by one veterinarian. Efficacy was assessed from a qualitative comparison of the proportion of dogs with improved clinical signs, and a quantitative comparison of the scores of the musculoskeletal examinations, between groups. Haematological and biochemical analyses and reports by owners of possible adverse drug reactions were used to screen for evidence of toxicity. There was close agreement between assessments by the veterinarian and owners. The clinical signs of DJD in both GLME-treated and placebo groups improved significantly over baseline by Day 28; this improvement continued over the entire course of the study. There were no significant differences between groups on Day 28. On Day 56, a higher proportion of dogs in the GLME-treated group had improved clinical signs (p=0.018), and GLME-treated dogs had marginally better (p=0.053) musculoskeletal scores than dogs in the placebo group. The differences between the groups were no longer apparent by Day 112, by which time the former placebo group had been receiving GLME for 56 days in the open-label phase of the study. The proportion of dogs in the former placebo group that had improved by Day 112 (29/32; 91%) was significantly greater (p=0.012) than the proportion improved at Day 56 (15/37; 41%). No signs of toxicity were apparent. GLME had a beneficial effect on the clinical signs of dogs presumptively diagnosed with mild-to-moderate DJD. Long-term therapy may be required before improvement is apparent.
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Clinical efficacy and tolerance of an extract of
green-lipped mussel (Perna canaliculus) in dogs
presumptively diagnosed with degenerative joint
B Pollard a , WG Guilford a , KL Ankenbauer-Perkins b & D Hedderley c
a Institute of Veterinary, Animal and Biomedical Sciences , Massey University , Private
Bag 11222, Palmerston North, New Zealand E-mail:
b Estendart Ltd , Palmerston North, New Zealand
c New Zealand Institute of Crop and Food Research Ltd , Palmerston North, New Zealand
Published online: 18 Feb 2011.
To cite this article: B Pollard , WG Guilford , KL Ankenbauer-Perkins & D Hedderley (2006) Clinical efficacy and tolerance
of an extract of green-lipped mussel (Perna canaliculus) in dogs presumptively diagnosed with degenerative joint disease,
New Zealand Veterinary Journal, 54:3, 114-118, DOI: 10.1080/00480169.2006.36622
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Scientifi c Article
Clinical ef cacy and tolerance of an extract of green-lipped mussel
(Perna canaliculus) in dogs presumptively diagnosed with
degenerative joint disease
B Pollard*, WG Guilford, KL Ankenbauer-Perkins and D Hedderley
AIM: To evaluate the effi cacy and tolerance of an extract of
green-lipped mussel (GLME) in the management of mild-to-
moderate degenerative joint disease (DJD) in dogs.
METHODS: Eighty-one dogs presumptively diagnosed with
DJD were treated orally daily with either GLME or a placebo
for 56 days, in a double-blind, placebo-controlled study. In an
uncontrolled open-label extension to the study, all dogs were
treated with GLME for an additional 56 days (from Days 57–
112). Clinical signs were subjectively scored by the owners, and
ndings of detailed musculoskeletal examinations were scored
by one veterinarian. Effi cacy was assessed from a qualitative
comparison of the proportion of dogs with improved clinical
signs, and a quantitative comparison of the scores of the mus-
culoskeletal examinations, between groups. Haematological and
biochemical analyses and reports by owners of possible adverse
drug reactions were used to screen for evidence of toxicity.
RESULTS: There was close agreement between assessments by
the veterinarian and owners. The clinical signs of DJD in both
GLME-treated and placebo groups improved signifi cantly over
baseline by Day 28; this improvement continued over the en-
tire course of the study. There were no signifi cant differences
between groups on Day 28. On Day 56, a higher proportion
of dogs in the GLME-treated group had improved clinical
signs (p=0.018), and GLME-treated dogs had marginally bet-
ter (p=0.053) musculoskeletal scores than dogs in the placebo
group. The differences between the groups were no longer ap-
parent by Day 112, by which time the former placebo group
had been receiving GLME for 56 days in the open-label phase of
the study. The proportion of dogs in the former placebo group
that had improved by Day 112 (29/32; 91%) was signifi cant-
ly greater (p=0.012) than the proportion improved at Day 56
(15/37; 41%). No signs of toxicity were apparent.
a benefi cial effect on the clinical signs of dogs presumptively di-
agnosed with mild-to-moderate DJD. Long-term therapy may
be required before improvement is apparent.
KEY WORDS: Green-lipped mussel extract, Perna canaliculus, de-
generative joint disease, arthritis, dog
Degenerative joint disease (DJD) or osteoarthritis is the most fre-
quently diagnosed arthropathy of animals (Pedersen et al 2000).
The cause of DJD is unknown but numerous predisposing factors
have been recognised. These include obesity, instability, laxity or
malalignment of joints, trauma, excessive work, and genetic fac-
tors (Smith et al 1995, 2001; Pedersen et al 2000). The predispos-
ing factors result in accelerated turnover of the articular cartilage
matrix, which eventually leads to localised degeneration of articu-
lar cartilage, exposure and sclerosis of underlying bone, formation
of osteophytes, and thickening of the synovia (Manley 1995; Ped-
ersen et al 2000). Damage to the articular cartilage is mediated
by cytokines, prostaglandins, proteinases and oxygen-derived free
radicals (Manley 1995). Eventually, the cumulative damage to the
joints leads to clinical signs such as unwillingness to exercise, re-
stricted joint movement, pain, stiffness, lameness, and crepitation
or joint thickening (Manley 1995; Pedersen et al 2000).
The diagnosis of DJD is based on the history and clinical signs,
as well as radiography of affected joints. Radiography will not
detect early cartilage degeneration but will reveal more advanced
degenerative changes such as osteophyte formation, subchondral
sclerosis, attrition of subchondral bone, joint deformity and sub-
luxation (Pedersen et al 2000). In certain clinical presentations,
other diagnostic steps such as evaluation of joint fl uid, synovial
biopsy and tests for rheumatoid factor are indicated to diagnose
less common forms of joint disease such as septic arthritis, im-
mune-mediated polyarthritis and rheumatoid arthritis. However,
evaluation of synovial fl uid per se does not have suffi cient sensitiv-
ity or specifi city to allow clinicians to reach a defi nitive diagnosis
of DJD (Gibson et al 1999; Pedersen et al 2000).
Traditionally, treatment of DJD has centred on rest, controlled
exercise, management of predisposing factors, and periodic use of
non-steroidal anti-infl ammatory agents to reduce synovial infl am-
mation and pain (Manley 1995; Pedersen et al 2000). The search
for compounds to relieve the symptoms and alter the course of
osteoarthritis has ranged across a wide spectrum of botanical,
zoological, chemical and manufactured materials. This search for
compounds showing the ideal balance between effi cacy, side-ef-
fects and cost continues unabated. Recently, there has been an
upsurge in interest in chondro-protective agents and alternative
therapies such as parenterally-administered polysulphated gly-
cosaminoglycans, and a variety of dietary supplements including
* Institute of Veterinary, Animal and Biomedical Sciences, Massey University,
Private Bag 11222, Palmerston North, New Zealand.
Estendart Ltd, Palmerston North, New Zealand.
New Zealand Institute of Crop and Food Research Ltd, Palmerston North,
New Zealand.
§ Author for correspondence. Email:
ANOVA Analysis of variance
DJD Degenerative joint disease
GLME Green-lipped mussel extract
SD Standard deviation
New Zealand Veterinary Journal 54(3), 114-118, 2006 114
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anti-oxidants, chondroitin sulphate, glucosamine, omega-3 fatty
acids, milk protein concentrate, and GLME (De Haan et al 1994;
Gingerich and Strobel 2003).
GLMEs are derived from the New Zealand green-lipped mus-
sel (Perna canaliculus). Various types of GLME have been em-
ployed in the management of arthritis. These include stabilised
freeze-dried powdered preparations of the mussel tissue and oily
extracts. Some authors observed a benefi cial effect of GLME on
rheumatoid arthritis and osteoarthritis in humans (Gibson et al
1980; Gibson 2000) but others did not (Larkin et al 1985; Dar-
lington and Stone 2001). In dogs, recent studies by Bui and Bierer
(2001) demonstrated that the addition of a green-lipped mussel
powder to a dry diet resulted in signifi cant clinical improvement
in arthritis by the end of 6 weeks of treatment. In contrast, a lower
dose of green-lipped mussel powder did not result in clinical im-
provement in another study of arthritis in dogs (Dobenecker et
al 2002).
The purpose of the placebo-controlled phase of the study present-
ed here was to compare the effi cacy of a GLME with a placebo
in alleviating the clinical signs of mild-to-moderate canine DJD.
A secondary objective was to evaluate the tolerance of the GLME
by dogs. The objective of the open-label phase of the study was to
provide the manufacturer of the GLME-containing product with
commercially-relevant information on the effi cacy of the product
as perceived by pet owners.
Materials and methods
The 81 dogs (43 in the treated group and 38 in the placebo group)
used in the study were selected from lame dogs presenting over a
10-month period to the Veterinary Teaching Hospital, Massey
University, Palmerston North, New Zealand, or to private veteri-
nary clinics in the lower North Island of New Zealand. The dogs
all had clinical histories consistent with DJD, including intermit-
tent or continuous lameness, stiffness on rising, and diffi culty
walking up or down stairs. The dogs remained in their owners’
care for the duration of the study. The study was approved by the
Massey University Animal Ethics Committee, Palmerston North,
New Zealand.
Diagnostic procedures
The dogs were confi rmed as generally healthy, following physical
examination and routine urine, haematological and biochemical
analyses. All dogs underwent a musculoskeletal examination con-
ducted by the same veterinarian, to identify the affected joint(s).
Radiography was performed to help confi rm the diagnosis of DJD
and rule out other causes of lameness. Joint taps were not per-
formed on the dogs selected into the study because the procedure
was not considered to be clinically indicated. Specifi cally, the dogs
did not have a history or clinical signs suggestive of polyarthritis
or septic arthritis, and there are no known tick-borne arthroses in
dogs in this geographic region.
Criteria for selection and allocation of cases
Dogs presumptively diagnosed with mild-to-moderate DJD of
more than 1 month’s duration were considered for inclusion.
Results of musculoskeletal examinations were graded using a
scale of 1–5 (score increasing with increasing severity) proposed
by Holtsinger et al (1992) for each of fi ve parameters: lameness,
weight-bearing, joint mobility/palpation, willingness to hold up
the contra-lateral limb, and pain (Table 1). Dogs were excluded
if they had a score >4 in one or more of these lameness grading
categories, or if they had clinical evidence of septic or immune-
mediated arthritis, neurological disorders, bleeding disorders, or
were pregnant. Dogs were also excluded if they had been treated
with topical or systemic anti-infl ammatory agents (including oral
nutritional supplements containing GLME) within the previ-
ous 2 weeks, with intra-articular injections within the previous
3 months, or had undergone orthopaedic surgery of any type
within the previous month.
Dogs entering the study were grouped according to the joint(s)
primarily affected (hip, shoulder, stifl e, or other) and randomly
allocated to one of two groups, viz treatment with a product con-
taining GLME, or treatment with a placebo.
The GLME treatment (SF4 Dog; McFarlane Laboratories New
Zealand Ltd, Auckland, NZ) contained 125 mg GLME per tab-
let, 52.86 mg brewer’s yeast, 191.50 mg lactose and 10.64 mg tab-
Table 1. Grading scale used by a veterinarian to assess the severity
of musculoskeletal dysfunction in dogs presumptively diagnosed with
degenerative joint disease (modifi ed from Holtsinger 1992).
Parameter Grade Signs/assessment
1 Stands and walks normally
2 Stands and walks normally, slight lameness
at the walk
3 Stands normally, severe lameness at the walk
4 Abnormal posture when standing, severe
lameness at the walk
5 Reluctant to rise and will not walk >5 strides
Willingness to hold up contra-lateral limb
1 Readily accepts for >2 min
2 Mild resistance, accepts for >1min
3 Moderate resistance, replaces it in <30 sec
4 Strong resistance, replaces it in <10 sec
5 Refuses to raise contra-lateral limb
1 Normal weight-bearing
2 Normal weight-bearing at rest, favours limb
when walking
3 Partial weight-bearing at rest and at the walk
4 Partial weight-bearing at rest, non-weight-
bearing at the walk
5 Non-weight-bearing at rest and when walking
1 No pain elicited on palpation of affected joint
2 Mild pain on palpation, e.g. turns head
3 Moderate pain on palpation, e.g. pulls limb away
4 Severe pain on palpation, e.g. vocalises,
attempts to bite
5 Will not allow examiner to palpate joint
Joint mobility/palpation
1 No limitation of joint motion, no crepitus
2 Mild (10–20%) decreased range of motion, no
3 Mild (10–20%) decreased range of motion,
4 Moderate (20–50%) decreased range of motion,
5 Severe (>50%) decreased range of motion,
115 New Zealand Veterinary Journal 54(3), 2006 Pollard et al
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leting aid (magnesium stearate, acacia and aerosil). The placebo
contained the same ingredients except for the GLME which was
replaced by dried fi n-fi sh (McFarlane Laboratories Ltd), and was
of similar size, shape, colour, and odour to the GLME treatment.
Both types of tablet were provided in identical plastic screw-top
bottles identifi ed only by code numbers. Both tablets were of a
size easy to administer, were highly palatable to the dogs, and were
administered daily according to bodyweight, viz 5–15 kg (three
tablets), 16–20 kg (fi ve tablets), 21–25 kg (six tablets), 26–45 kg
(eight tablets), and 46–65 kg (nine tablets). Owners recorded the
treatment and any observations of note in a daily log. Treatment
continued for 56 days. Owner compliance was checked by re-
viewing the daily log and counting the tablets remaining in the
bottles at the end of the treatment period.
At the conclusion of the placebo-controlled study, the owners
were offered an open-label extension to the trial during which
all dogs were treated with the GLME-containing product for 56
days. Thus, at the conclusion of the open-label phase of the trial,
half the dogs had received GLME for 112 days and half had re-
ceived GLME for 56 days.
Clinical examinations and sampling
The dogs were evaluated by the same veterinarian prior to com-
mencement of treatment and after approximately 28, 56, and 112
days. Assessments at those intervals included a general physical
examination and a musculoskeletal examination, scored as de-
scribed above.
Blood samples were collected prior to treatment and on Day 56,
by cephalic or jugular venepuncture. Samples collected into tubes
containing EDTA were used for a complete blood count, includ-
ing numbers of platelets. Serum was harvested in plain blood
collection tubes, for analysis of the concentrations of calcium,
phosphorus, sodium, potassium, bicarbonate, chloride, urea, cre-
atinine, bilirubin, cholesterol, total protein, albumin, and globu-
lin; the anion gap and albumin/globulin ratio; and the activity
of creatine phosphokinase, aspartate aminotransferase, alanine
aminotransferase, amylase, and lipase. Urinalysis was performed
on free-catch urine. All analyses were performed by a commercial
animal health laboratory (Batchelar Animal Health Laboratory,
Palmerston North, New Zealand), and data were compared to the
established reference ranges of that laboratory.
Assessments by owners
The general health of the dogs (appetite, attitude, level of activity,
faecal consistency, and the presence of vomiting or any other ab-
normalities) and severity of lameness were assessed by their own-
ers on Days 0, 26, 52 and 112. These assessments were recorded
on forms using visual analogue and ordinal grading scales. Own-
ers were also asked for an overall assessment as to whether or not
their animal’s condition had or had not improved.
Musculoskeletal assessment by the veterinarian
The severity of each dog’s musculoskeletal dysfunction was as-
sessed in both quantitative and qualitative manners. The fi ve
musculoskeletal parameters considered were assessed in a stand-
ardised way at each examination and a score for each parameter
was allocated (Table 1). The scores of the individual parameters
were added to give a cumulative score for each musculoskeletal
examination. The cumulative score at each assessment during the
trial was used as the quantitative clinical assessment. At each ex-
amination, the quantitative clinical assessment was qualitatively
categorised as ‘improved’ (i.e. cumulative score lower than previ-
ous examination) or ‘not improved’. This qualitative clinical as-
sessment was based on the change (if any) in the cumulative score
over baseline (Day 0).
Assessment of tolerance
Tolerance of the treatment was assessed by a comparison of the
owners’ reports of any adverse effects of the GLME treatment and
placebo, and a review of the haematological, serum biochemistry
and urinalysis data.
Statistical analysis
All statistical analyses were performed using SAS for Windows,
v6.12 (SAS Institute Inc, Cary NC, USA). The degree of agree-
ment between the owners’ assessments of improvement and the
veterinarian’s qualitative assessment of improvement on Days
0, 28, 56 and 112 were analysed using the Kappa statistic. The
veterinarian’s qualitative assessments of improvement of the two
groups of dogs on Days 0, 28, 56 and 112 were compared using
logistic regression.
The cumulative musculoskeletal scores of the two groups were
compared over Days 0, 28, 56 and 112, using repeated measures
analysis of variance (ANOVA). Only complete datasets from dogs
that had been examined on all four occasions were used for this
analysis. The distribution of the residuals was checked for normal-
ity and homogeneity of variance; these checks confi rmed that the
assumptions of ANOVA applied to the cumulative scores. Con-
trasts were used to test whether there was any signifi cant change
between successive observations.
Case recruitment
One hundred and forty-two dogs were presented for this study
and of these 84 met the inclusion criteria. Data from three of
these were eventually excluded from analysis as one dog was di-
agnosed with osteosarcoma of the scapula towards the end of the
trial and the owners of the other two dogs failed to comply with
the experimental protocol. Thus, data from 81 dogs were includ-
ed in statistical analyses.
The mean age of the dogs was 8.5 (SD 3.3) years and mean
weight was 32.6 (SD 11.1) kg. There were 48 females (59%), and
the most common breeds were Labrador Retriever (26%), Ger-
man Shepherd dog (12%), Border Collie (11%), and Rottweiler
The majority of the 81 dogs included in the data analysis com-
pleted the study. Seven of the 81 dogs did not complete the study
for the following reasons, but partial datasets from these dogs were
available. Three dogs were euthanised during the study: a 13-year-
old dog in the GLME-treated group and an 11-year-old dog in
the placebo group were euthanised due to overall poor quality of
life, and an 11-year-old dog in the placebo group was euthanised
for renal failure. Two dogs in the GLME-treated group and two
in the placebo group were formally withdrawn from the study.
Of these four, one owner believed the treatment caused the dog’s
coat to smell (this dog was in the placebo group), one dog in
the treated group required anti-infl ammatory treatment, and two
owners were unable to continue to participate in the study. Data
were incomplete from another four dogs because one dog was not
presented for examination on Day 28, one was not presented on
Day 56, and two animals were not presented on Day 112.
Pollard et al New Zealand Veterinary Journal 54(3), 2006 116
Downloaded by [FU Berlin] at 04:34 03 December 2014
The DJD of the dogs included in the study most frequently af-
fected the hip joint (43%) followed by the stifl e (16%) and shoul-
der (10%).
Agreement between assessments by the veterinarian and
Agreement between the owners’ assessments of improvement and
the veterinarian’s qualitative clinical assessments was 78% on Days
28 and 56, and 91% on Day 112, when both groups were treated
with the GLME-containing product. The corrected coeffi cient of
agreement (Kappa) was 0.546 on Day 28, 0.547 on Day 56, and
0.698 on Day 112, and there was no sign of systematic bias.
Qualitative clinical assessment
Results of the qualitative clinical assessments are shown in Table 2.
On Day 28, there was no signifi cant difference between the pro-
portion of dogs showing improvement in the GLME-treated
and placebo groups. In contrast, on Day 56 a higher proportion
of dogs in the GLME-treated group (28/42; 67%) showed im-
provement than in the placebo group (15/37; 41%, p=0.018).
On Day 112, when all dogs had been receiving GLME for either
56 (former placebo group) or 112 days (former GLME-treated
group), 29/32 (91%) dogs in the former placebo group and 29/37
(78%) dogs in the former GLME-treated group had improved
(p>0.05). The proportion of dogs in the former placebo group
that had improved by Day 112 (91%) was greater than the pro-
portion that had improved in that group by Day 56 (41%) on the
placebo treatment (p=0.012). In contrast, the proportion of dogs
in the GLME-treated group that improved was not signifi cantly
different (p>0.05) at Days 56 and 112.
Quantitative clinical assessment
Complete datasets for the repeated measures ANOVA were avail-
able from 70 dogs (32 from the placebo group and 38 from the
GLME-treated group). The cumulative scores from the mus-
culoskeletal examinations of both groups improved signifi cantly
from Days 0 to 28 (Figure 1). Between Days 28 and 56, cumula-
tive scores of the GLME-treated group improved signifi cantly but
those of the placebo group did not, resulting in a marginally sig-
nifi cant (p=0.053) difference between the scores of the two groups
on Day 56. Between Days 56 and 112, the cumulative scores of
both groups improved signifi cantly, and by Day 112 there was no
longer a signifi cant difference between the groups.
Evaluation of haematological, serum biochemical and urinalysis
data in relation to the testing laboratory’s reference ranges for each
parameter did not demonstrate any evidence of toxicity. No ad-
verse effects that were attributable to the GLME treatment were
described by the owners or the veterinarian.
The results of this study suggest that long-term administration,
i.e. 8 weeks or longer, of GLME alleviated the clinical signs of
dogs presumptively diagnosed with mild-to-moderate DJD. The
reason for the lag period between the start of treatment with green-
lipped mussel products and clinical improvement is unknown,
but this has been reported previously (Bui and Bierer 2001).
The underlying process by which GLME has its benefi cial ef-
fects on the clinical manifestations of DJD is unknown. Extracts
of green-lipped mussel have been known for some time to have
modest anti-infl ammatory properties (Miller and Ormrod 1980;
Rainsford and Whitehouse 1980; Couch et al 1982), and the ac-
tive ingredient has variously been attributed to a proteinaceous
macromolecule (Couch et al 1982), a prostaglandin inhibitor
(Miller and Wu 1984), a glycogen extract or glycoprotein (Miller
et al 1993), or a polyunsaturated fatty acid (Whitehouse et al
1997; Halpern 2000).
The high proportion of dogs (15/47; 41%) that improved in the
placebo group during the fi rst 56 days of the trial is noteworthy
and similar to that seen in another recent trial of a nutraceutical
in dogs with arthritis (Gingerich and Strobel 2003). The present
trial was commenced in the middle of winter and most of the
recruitment into the trial was completed within 6–9 months. Ac-
cordingly, some of the improvement seen in both the GLME-
treated and placebo groups may be attributable to warmer weath-
er conditions as the trial progressed. Increased focus by owners
on appropriate rest, diet and exercise, factors already known to
infl uence the course of DJD, may also have contributed to the
improvement, as may have a ‘placebo-like effect’.
The continued improvement of the musculoskeletal scores of the
GLME-treated group during the open-label phase of the study
may have been due to the prolonged duration of administration,
which may have resulted in further clinical improvement. Alter-
natively, the perceived improvement may have been a placebo-
like effect due to the ‘unblinding’ of the owners and veterinarian.
Further research is required to establish the duration of treatment
required for optimal therapeutic effect.
Table 2. Qualitative clinical assessment of the percentage of dogs that
had or had not improved on a placebo or green-lipped mussel extract
(GLME) treatment by Day 28 and Day 56 of the placebo-controlled
phase of a trial.
Day Placebo GLME-treated
Improved 16 (42%) 19 (45%)
Not improved 22 (58%) 23 (55%)
Improved 15 (41%) 28 (67%)
Not improved 22 (60%) 14 (33%)
a Placebo and GLME-treated groups differ signifi cantly (p=0.018)
Figure 1. Cumulative musculoskeletal examination scores of dogs
treated with either green-lipped mussel extract (GLME; ) or placebo
() for 56 days, then with GLME for another 56 days. The standard
errors (SE) for the individual datapoints were similar (0.37–0.43), and
the pooled estimate (0.39) is shown here. There was a marginally
signifi cant (p=0.053) difference between the groups at Day 56. A least
signifi cant difference (LSD) bar is shown for comparisons between
times within a group.
Cumulative clinical score
Days of treatment
20 60 80 100 12040
LSD within
117 New Zealand Veterinary Journal 54(3), 2006 Pollard et al
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A high proportion of dogs in the placebo group improved from
Day 56 (41%) to Day 112 (91%) after the placebo had been dis-
continued and replaced with open-label administration of the
GLME. This particular comparison suggests that open-label ad-
ministration of GLME to dogs with mild-to-moderate DJD is
highly likely to produce a perceived benefi cial clinical response,
but does not separate placebo effects from direct effects of the
In conclusion, the results of this study suggest that the GLME-
containing treatment used was well tolerated and had a signifi -
cant benefi cial effect on the clinical signs of dogs presumptively
diagnosed with DJD, but that long-term therapy may be required
before improvement is apparent.
We would like to thank the staff of the Veterinary Teaching
Hospital of the Institute of Veterinary, Animal and Biomedical
Sciences, Massey University; and Estendart Ltd, for their invalu-
able nursing, technical and administrative input. The advice and
encouragement of Mr John Croft of Healtheries Ltd, Auckland,
New Zealand, is gratefully acknowledged. McFarlane Laborato-
ries NZ Ltd, Avondale, Auckland, New Zealand, provided fi nan-
cial support.
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Pollard et al New Zealand Veterinary Journal 54(3), 2006 118
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... In a number of studies, Green lipped mussel (Perna canaliculus) extract (GLME) alone or in combination with other ingredients has been found to be a therapeutically effective and safe nutraceutical for OA dogs [9,10,11,4,47,25,50,60]. GLME is a source of glucosamine, chondroitin, omega-3 fatty acids, vitamins (C and E), minerals (such as zinc, copper, iodine and manganese), enzymes and peptides/proteins. ...
... In contrast to Rimadyl TM , the apparent anti-inflammatory effect of BVP-01 took longer to occur. This is consistent with a longer period required for an anti-inflammatory nutraceutical to have an effect than NSAID's [24,47,37,20,31,17,12,43,60]. However, serious adverse effects with the long-term use of the COX inhibiting NSAIDs have been associated with hepatic, renal, cardiovascular and GI systems [42,44,40,3,48,29,46,53,6]. ...
... An extract from New Zealand green-lipped mussel (Perna canaliculus) known as greenshell mussel TM (GSM) was found to be beneficial for joint health and symptom-relieving of OA in animal (17) and human clinical trials (18). The inhibitory effect of omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) present in GSM on cyclooxygenase-2 (COX-2) and the 5-lipoxygenase (5-LOX) cascade suppress synthesis of Prostaglandin E2 (PGE2) and reduce the inflammatory response (19). ...
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Objective To investigate the effect of whole greenshell mussel (GSM) powder on biomarkers of cartilage metabolism, inflammatory cytokines, and joint symptoms in postmenopausal women with overweight/obesity and joint discomfort.DesignFifty-five postmenopausal women with overweight/obesity were randomly assigned to receive 3 g/day whole GSM powder or placebo for 12 weeks. Cartilage turnover biomarkers urinary C-telopeptide of type II collagen (CTX-II) and serum cartilage oligomeric matrix protein (COMP) were measured at baseline, week 6 and 12. Plasma cytokines were measured at baseline and week 12. Joint pain and knee-related problems were assessed at baseline and week 12 using a 100 mm Visual Analogue Scale (VAS) and the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, respectively.ResultsForty-nine participants completed the study (GSM n = 25, placebo n = 24). After 12 weeks, urinary CTX-II showed no significant change over time or between the groups (interaction effect P = 0.1). However, in women with symptomatic knees, a significant difference was noted between the group (treatment effect P = 0.04), as it was lower in the GSM group compared to placebo group at week 6 (P = 0.04) and week 12 (P = 0.03). Serum COMP and plasma cytokines were not affected. GSM supplementation showed greater reduction in the VAS pain score than placebo (−13.2 ± 20.3 vs. −2.9 ± 15.9; P = 0.04). No significant change in KOOS domains between the two groups was observed.Conclusion Oral supplementation of whole GSM powder at 3 g/day may slow down the degradation of type II collagen in postmenopausal women with symptomatic knees. GSM treatment conferred clinical benefit on overall joint pain. No significant effect was noted for inflammatory cytokines, suggesting that GSM may act within the joint microenvironment rather than at the systemic level.Clinical trial registration[], identifier [ACTRN12620000413921p].
... GLM contains abundant long-chain omega-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA), and many minor fatty acids (including 5, 9, 12, 16-nonadecatetraenoic acid, 5, 9, 12, 15-octadecatetraenoic acid, and 5, 9, 12, 15, 18-heneicosapentaenoic acid) [14]. Many animal and clinical studies have shown that GLM exhibits anti-inflammatory, antiarthritic, and gastro-protective properties [15][16][17][18]. Specifically, long-chain omega-3 polyunsaturated fatty acids such as EPA and DHA are known to exert anti-inflammatory effects. ...
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The green-lipped mussel (GLM) contains novel omega-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and joint-protecting properties. Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage; oxidative stress plays a role in the pathogenesis of OA. The objectives of this study were to investigate the in vivo effects of the GLM on pain severity and cartilage degeneration using an experimental rat OA model, and to explore the mode of action of GLM. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) into the knee. Oral GLM was initiated on the day after 3dyas of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed both macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1β (IL-1β), IL-6, nitrotyrosine, and inducible nitric oxide synthase (iNOS) in knee joints. Also, the GLM was applied to OA chondrocyte, and the expression on catabolic marker and necroptosis factor were evaluated by real-time polymerase chain reaction. Administration of the GLM improved pain levels by preventing cartilage damage and inflammation. GLM significantly attenuated the expression levels of mRNAs encoding matrix metalloproteinase-3 (MMP-3), MMP-13, and ADAMTS5 in IL-1β-stimulated human OA chondrocytes. GLM decreased the expression levels of the necroptosis mediators RIPK1, RIPK3, and the mixed lineage kinase domain-like protein (MLKL) in IL-1β-stimulated human OA chondrocytes. Thus, GLM reduced pain and cartilage degeneration in rats with experimentally induced OA. The chondroprotective properties of GLM included suppression of oxidative damage and inhibition of catabolic factors implicated in the pathogenesis of OA cartilage damage. We suggest that GLM may usefully treat human OA.
... Concussion has been aim of several studies among sports sciences and sport scientists around the world (Crocetta, Dominski, & Andrade, 2015). Throughout many years, the cerebral concussion (CC), a type of minor or mild head injury or trauma, was undervalued by western medicine, even though some neurologists and researchers highlight that major brain traumas would be able to be recovered, whereas minor and mild brain injuries could lead to death (Pollard, Guilford, Ankenbauer-Perkins, & Hedderley 2006). ...
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A Psicologia do esporte é uma área de conhecimento que visa estudar e compreender técnicas que ajudem no desenvolvimento humano nas suas quatro esferas de atuação: iniciação, atividade física, reabilitação e alto rendimento. Focalizando nossa atenção no alto rendimento, o manejo das emoções parece constituir um dos pontos nevrálgicos na melhora da performance e do bem-estar do atleta. O conhecimento adquirido através da psicoeducação é fator fundamental para o empoderamento do desportista acerca das próprias emoções e de como usá-las a seu favor. Propomos nesse estudo bibliográfico levantar de maneira exploratória na literatura científica baseada em evidência como as intervenções de psicoeducação podem auxiliar o atleta de alto rendimento no desenvolvimento de habilidades de manejo eficaz das emoções que potencializem suas valências psicológicas voltadas para seu esporte.
Le but de cette revue systématique et métanalyse était d’examiner les évidences d’efficacité clinique analgésique des diètes enrichies et nutraceutiques testés chez des chiens arthrosiques. À partir de quatre bases de données bibliographiques électroniques, 1096 publications ont été retracées, en plus de 20 publications provenant de sources internes. Cinquante-quatre articles ont été inclus, comprenant 69 essais et permettant d’établir 9 catégories de traitement. L’évaluation d’efficacité, modulée par le niveau de qualité des essais, établit une évidence analgésique, avec effet clinique, pour les diètes enrichies et les suppléments à base d’oméga-3, ainsi que ceux à base de cannabidiol (à moindre degré). Nos analyses démontrent aussi une faible efficacité du collagène, et un non-effet marqué des nutraceutiques à base de chondroïtine – glucosamine qui nous pousse à recommander que ces derniers produits ne soient plus conseillés pour la gestion des douleurs en arthrose canine. Mots-Clés : Arthrose, Nutraceutiques, Compléments alimentaires, Diètes thérapeutiques, Douleur, Animal, Locomotion, Qualité méthodologique, Évidences scientifiques, Validation métrologique
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With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.
The typical canine rehabilitation patient with orthopedic disease may differ in its nutritional needs, with the assumption that most patients will be on a complete and balanced commercial dog food that is not enriched with agents for ameliorating their condition. For a significant number of rehabilitation patients, obesity is a major issue where hypocaloric diet plans are often implemented and are covered extensively elsewhere (VCNA Small Animal Practice May 2021). The focus of this article will be implementation of physical activity or structured physical exercise protocols and how they might be used in combination with a typical hypocaloric diet plan, a diet low in calories. Considering the limited information regarding physical activity or structured exercise programs in dogs, a human comparative assessment of efficacy is fundamental as a baseline of information regarding typical interventions. In addition, many of these long-term rehabilitation cases typically exhibit osteoarthritis (OA) and as part of case management, there is a need to implement nutrient or nutraceutical intervention to either diminish the progression of OA or help with pain control measures, particularly for the nonsteroidal anti-inflammatory intolerant patient. Nutraceutical intervention comes in many forms from botanicals to nutritional enhancement; botanicals will be covered elsewhere in this issue. This overview of nutraceuticals will cover nonbotanical interventions including fish oil, glucosamine/chondroitin, avocado/soybean unsaponifiables, undenatured collagen, green lipped mussel, and egg shell membrane supplementation.
Currently, more than 46 million adults in the United States suffer from some form of arthritis. Arthritis is also prevalent in other species, including canine and equine. Among all forms of arthritis, osteoarthritis (OA) is the most common form, afflicting nearly 27 million adults. The other common form of arthritis is rheumatoid arthritis. Among animal species, canine and equine are more prone to arthritis than other species. A large number of factors, such as aging, excessive exercise, obesity, genetic predisposition, immune disorders, poor nutrition, injury, and infection, can lead to OA. Presently, the use of nutraceuticals appears to be a good option to treat or manage OA, because they are taken orally, well-tolerated, and safe. However, some nutraceuticals exert adverse effects. This chapter describes, in brief, the characteristics of OA, pathophysiology of OA, and efficacy, safety, and toxicity of some commonly used nutraceuticals.
Veterinary pet supplements and nutraceuticals are widely used by dog, cat and horse owners across the United States, generating millions of dollars in revenue for manufacturers. Despite the widespread use of these veterinary products, oversight and regulation remain limited as compared to human dietary supplement regulations. This review describes the current regulation, quality control, safety and efficacy of pet supplements and nutraceuticals targeted towards the dog, cat and horse.
Carprofen (D,L-6-chlor-alphamethylcarbazole-2-acetic acid) is a nonsteroidal anti-inflammatory drug with demonstrated therapeutic activity in the relief of clinical signs of degenerative joint disease in laboratory animal models and in human trials. The double-blind clinical study, reported herein, compared the therapeutic efficacy of carprofen with that of a placebo, in the acute relief of clinical canine degenerative joint disease. Twohundred and nine cases were collected from 10 studies in three geographic regions of the USA. The results of logistic analysis showed that dogs treated with carprofen were 24.8 times more likely to receive a positive evaluation by the veterinarian than those treated with a placebo (p <0.01). The odds of showing improvement, when evaluated by the owners, were 13.4 times greater than placebo (p <0.01). The evaluation from the veterinarian and the owner had excellent agreement (Kappa = 0.997) for dogs treated with carprofen and good agreement (Kappa = 0.667) for those treated with the placebo. Regional differences in response rate were not found in these studies. This trial demonstrated that carprofen is efficacious, across geographic regions, in the acute relief of clinical signs associated with canine degenerative joint disease. Carprofen is a new anti-inflammatory drug (NSAID) with analgesic potency. Side effects reported are few. Dogs with degenerative joint disease (DSD) treated with carprofen were 24.8 times more likely to respond favourably than placebo-treated dogs (p <0.01). This study concluded that carprofen is an effective NSAID in relieving the clinical signs of DSD in dogs.
Thirty-five patients with rheumatoid arthritis were randomly allocated to either Seatone (green-lipped mussel extract) or placebo in order to assess the former's claimed effectiveness in rheumatoid disease. After six months there was no significant improvement in any laboratory or clinical measurement of disease activity in the Seatone group. The patients on active drug fared no better than those on placebo. These results suggest that Seatone is not effective in rheumatoid arthritis.
Prostaglandin synthetase inhibitors (eg, aspirin, indomethacin and naproxen) interfere with ovulation and prolong the gestation period in the rat. These properties could provide a novel test bed for the assessment of agents with prostaglandin biosynthesis inhibitory activity. Rats were fed green-lipped mussel extract and the effects on conception and the subsequent gestation period were determined. Parturition was delayed and fetal development was retarded in the Seatone-fed animals. The observations were consistent with the known effects of nonsteroidal anti-inflammatory drugs, suggesting that Seatone does contain pharmacologically active material inhibiting prostaglandin biosynthesis.
The anti-inflammatory effect of a crude fraction of the New Zealand green lipped mussel (Perna canaliculus) has been investigated. A carrageenan-induced inflammatory oedema of the rat hind footpad was used as the experimental model. Non-steroidal anti-inflammatory agents were first shown to be capable of reducing the inflammatory oedema and in the subsequent experiments a representative agent was included as a reference substance. The preparation, Perna canaliculus, effectively reduced the footpad oedema but only if injected into the peritoneal cavity. Decreasing amounts were given IP and 500 mg/kg of the crude preparation was found to be the lowest single dose that would produce a significant reduction in the inflammatory response to carrageenan. Lower doses were effective if the substance was first administered daily for several days, prior to the challenge. Oral administration was not effective in reducing the inflammatory response.
The New Zealand green-lipped mussel (Perna canaliculus) is the source of a para-pharmaceutical called Seatone. Claims have been made that the preparation may be helpful in the management of inflammatory joint disease but results of clinical studies to date have been contradictory. An earlier experimental study demonstrated anti-inflammatory activity in the crude preparation and further experiments to isolate and characterise the active fraction were indicated. A two-step fractionation procedure resulted in an extract, which although only 16 percent by weight of the parent material, retained anti-inflammatory activity. Experiments involving alternative routes of administration, with heat or enzyme treatment of the active extract and a comparative analysis of fractions from related bivalves, all demonstrated that the anti-inflammatory effect was genuine and did not result from counter-irritancy. The initial results suggest that the active agent is a proteinaceous macromolecule.
This trial suggests that the extract of the green lipped mussel, Perna canaliculus is an effective supplement or possible alternative to orthodox therapy in the treatment of both rheumatoid arthritis and osteoarthritis. It reduces the amount of pain and stiffness, improves the patient's ability to cope with life, and apparently enhances general health. Added to these benefits is the low incidence of side effects. It would therefore seem that this substance could be of considerable value to patients suffering from these two chronic and disabling conditions.
Freeze-dried powdered preparations of whole (i.e. without shell) green-lipped mussel (Perna canaliculus) from New Zealand given orally to rats showed some modest anti-inflammatory activity (carrageenan paw oedema). This material strikingly reduced the gastric ulcerogenicity of several non-steroid anti-inflammatory drugs in rats and pigs. The gastroprotective activity in rats was primarily associated with particular lipid fractions, which exhibited differential protective activity against acetylsalicylic acid on the one hand and indometacin on the other.
Passive coxofemoral joint laxity of dogs, as quantitated by a distraction-stress radiographic method, may have important prognostic value in determining susceptibility to hip dysplasia. Data from 151 dogs, representing 13 breeds, were included in a logistic regression model to evaluate the contribution of factors such as age, breed, weight, sex, distraction index, and Norberg angle to the risk of developing degenerative joint disease (DJD) of the coxofemoral joint. Of the factors studied, the amount of passive hip laxity, as quantitated by the distraction index, was the most significant (P < 0.0001) determinant of the risk to develop DJD of the coxofemoral joint. In the longitudinal and cross-sectional components of the study, distraction index was a significant (P < 0.001) risk factor for DJD, irrespective of age at evaluation (4, 12, or 24 months). The strength of the hip laxity:DJD correlation increased with the age of dog. In contrast, the Norberg angle, a measure of hip laxity on the standard hip-extended radiograph, was not found to be a significant risk factor for DJD, either in the longitudinal or cross-sectional analyses. Breed-specific probability curves of DJD susceptibility indicated that German Shepherd Dogs had a significantly (P < 0.05) greater risk of developing DJD than did the pool of non-German Shepherd Dogs. The information derived from this statistical model will help to scientifically characterize the role of passive hip laxity as a component in the pathogenesis of DJD of the coxofemoral joint.
A double-blinded, controlled clinical study was performed to compare the response of adult dogs affected with hip dysplasia to a placebo and three different dosages of polysulfated glycosaminoglycan (PSGAG): 2.2 mg/kg, 4.4 mg/kg, and 8.8 mg/kg. Dogs were randomly assigned to treatment groups. The drug was administered intramuscularly every 3 to 5 days for a total of eight injections. Response to treatment was analyzed based on changes in lameness, range of motion (ROM), and pain on manipulation of the hip joints. Evaluation for adverse reactions included complete blood cell (CBC) count, blood urea nitrogen (BUN), creatinine, and physical examination. Data were collected on a total of 111 dogs. Eighty-four met all criteria for inclusion in the study. Dogs that were given 4.4 mg/kg of PSGAG showed the greatest improvement in orthopedic scores, whereas dogs in the placebo group showed the smallest improvement; however, the differences in clinical improvement between the four treatment groups were not statistically significant. No local or systemic adverse reactions related to the drug were observed.