Green Mussel Extract
Green Mussel
Mytilidae:Mytilidae
Genus:Perna
Binomial name:Perna Canalicula
Arthritis in one or other of its several forms continues to be a major cause of disability in the UK.
Although many non-steroidal anti-inflammatory drugs are now available, none is wholly effective, and
side effects remain a problem. The search for a safer and more effective anti-inflammatory agent
therefore continues.
Five years ago, a preparation of the New Zealand green lipped mussel, Perna canaliculus, came to our
notice, and a preliminary therapeutic trial was carried out in 86 patients, 55 with rheumatoid arthritis
and 31 with osteoarthritis. The patients were treated for periods ranging from six months to 4.5 years:
67% of those with rheumatoid arthritis and 35% of those with osteoarthritis benefited. Toxic effects
were uncommon and generally mind.
In order to evaluate the efficacy of this preparation more fully, it was decided to carry out a
carefully controlled double-blind trial on similar group of patients. This second trial was also number
osteoarthritis to obtain a more accurate assessment of the effect of the agent in this condition.
Sixty-six patients took part in the trial. Twenty-eight suffered from classical rheumatoid arthritis
and 38 had clinical and radiological evidence of osteoarthritis.
All the patients were on the waiting list of the orthopaedic unit of the Victoria Infirmary, Glasgow,
for joint surgery. All were taking some form of non-steroidal anti-inflammatory therapy. They were
told that they would be taking part in a double-blind trial to assess the value of a new anti-inflammatory
preparation, and all were willing to co-operate. Inquiry was made regarding any known allergy to fish or
shell-fish. The patients were requested to continue all previous therapy unchanged and to tale the trial
materials as an additional treatment.
The mussel extracted was prepared in capsule form, 350mg per capsule. The placebo was a pharmacologically
inactive preparation of fish that was identical in appearance, taste and smell to the active preparation.
Both were prepared by McFarlane Laboratories, New Zealand. The initial dose was three capsules per day
(1050mg). Both materials were given to the hospital pharmacy department where a random code was produced.
Experience during the preliminary study indicated that the effects of the messel preparation could last
for two to three weeks after cessation of the therapy if this had been taken for more than two months.
It was therefore not possible to conducts a full double-blind cross-over trial. The patients were
accordingly kept on their randomly allocated double-blind therapy for a period of three months after
which they were fully reassessed. They were then given the active preparation for a further three months,
thus giving all the patients the opportunity of taking the test material. Since the codes were not broken
until the patients had been in the trial for six months, neither the patients nor the trial knew whether
there had been any change of therapy in the second three month period. The patients were then again
reassessed and the codes broken.
The patients were seen at monthly intervals in the orthopaedic outpatients department. With the
exception of joint movement which were measured at the initial visit, at three months and at six months,
full clinical assessments were made at each visit. Anu previously unnoticed side effects were also recorded.
Rheumatoid patients.- The following measure were used to assess the progress of the patients with
rheumatoid arthritis: articular index of joint tendeness, morning stiffness (limbering up time), grip
strength in each hand, pain as assessed by the visual analogue scale, functional index, and the time
taken to walk a measured distance of 50 feet(15.24m). The patients and the physician also made their own
assessments of whether or not there had been an improvement. The patients was considered to have improved
when both the patient's and the physician's opinion agreed and there was objective supporting evidence.
Patients with osteoarthritis.- The progress of the patients with osteoarthritis was assessed by means of
the following measures: degree of morning stiffness (limbering up time), pain as assessed by the visual
analogue scale, functional index, time taken to walk 50 feet (15.24m), the range of movements of hip and
knee joints, and the patient's and physician's own assessments of improvement. Again improvement was jugged
to have occurred when both the patient and the physician agreed and there was objectibe supporting evidence.
In the four-year pilot study, haemoglobin, white-cell count, ESR, serum biochemistry, rheumatoid
serology and urine analysis were performed at regular intervals. No statistically significant changes
were observed in nay of these parameters although haemoglobin levels tended to rise and in one case a
positive R3 calue became negative, in view of these largely negative results over four years, laboratory
tests were not performed routinely in the six-month trial, although individual tests were done when
clinically indicated
The results were analysed by the Wilcoxon matched-pairs signedranks test.
The age and sex of the patients, the time for which they had been affected and the severity of
their disease are presented for the active and placebo groups of both rheumatoid and osteoarthritic
patients in table 1. The group were comparable.
Of the 66 patients in the trial, eight dropped out before the end of the first three months
- three had rheumatoid arthritis and five had osteroarthritic. Three of these patients were admitted
to hospital for reasons unrelated to their arthritis, two had difficulties with transport, one had
previous dyspepsia and felt the capsules disagreed with her, and two gave no reason.
The of the 17 rheumatoid patients on the active preparation improved during the first three months
compared with three of the 11 patients on the inert preparation. In the osteoarthritis group six of
the 16 patients on the active and three of the 22 patients on the inert preparation, improved. During
the second three months of the trial, a further six rheumatoid and six osteroarthritic patients improved.
At the end of six month, therefore, 19 of the 28 rheumatoid patients (67.8%) and 15 of the 38
osteroarthritic patients (39.5%) felt that they had benefited from being included in the trial.
If the patients who dropped out are disregarded, as in most instances the reason for drop-out was
unrelated to the arthritis, then 76% of the rheumatoid and 45% of the osteroarthritic patients improved.
The mean results for the measurements of pain, stiffness and function in the various groups of
patients before and after treatment are presented in table 2 and 3.
Of the 66 patients in the trial, 46 suffered from night pain. This was relieved in 17 patients
on active treatment and in two on placebo-a 37% response to the active preparation.
Apart from the patients who improved when assessed objectively, seven patients, four on placebo
and three on the active material, showed a temporary response lasting less than two months.
Since previous experience with rheumatoid patients in Glasgow has suggested that a placebo effect
is not maintained for longer than six weeks, these patients were classed as placebo responders.
Six patients experienced an increase in the severity of their symptoms two to four weeks after
starting active treatment. This exacerbation lasted for one to two weeks, after which they made
good progress. It is interesting that a similar flare-up has been observed in other patients one
to five weeks after beginning treatment with this extract.
Apart from the exacerbation of symptoms nine of the 66 patients in the trial experienced side
effects, eight on the active preparation and one on the inert material. Two patients experienced
increased stiffness which disappeared within two to three weeks. One patient had epigastric
discomfort, one suffered from increased flatulence and four, of whom one was on placebo, had
nausea. One patient retained fluid which was reversed by stopping the treatment for a week and
recommencing at a lower dose level.
When patients were seen to be well-maintained on the active preparation for two months or more,
an attempt was made to reduce the dose. It was found that several patients could be satisfactorily
maintained on two capsules (700mg) per day.
It was encouraging that the proportion of patients who responded to treatment with the mussel
extract in the double-blind trial was similar to that obtained in the preliminary study, 67.9%
of rheumatoid patients and 39.5% of osteroarthritic patients benefiting from this form of therapy.
The measure of pain, stiffness and the ability to cope with the environment improved significantly
in those patients who responded to the therapy.
Grip strength did not improve significantly in the short-term double-blind trial although in the
pilot study, which included a number of patients with less severe destruction of the joints of the
hands, there was significant improvement in strength. Many of the rheumatoid patients in the
double-blind trial das marked deformities of the hands and had difficulty in grasping the cuff of
the grip-strength apparatus. It was therefore not surprising that no marked change was seen in this
measure. There were no significant change in joint function as assessed by measurement of the range
of movement in the osteroarthritic group as a whole although individual patients did improve. This
again was not surprising since gross destructive changes requiring joint surgery are unlikely to be
reversible by drug therapy.
Most of the patients in the study were old and had suffered from their disease for many years.
The mean ages were 68.8 and 57.0 years, respectively, for osteoarthtritis and rheumatoid patients and
the mean duration of disease 12.9 and 17.8 years, respectively. All patients were severely affected
and all had deteriorated to the stage where they were on the waiting list for joint surgery for the
relief of pain and disability. They were therefore patients who were nearing the end of the road as
far as orthodox therapy was concerned. While it is unlikely that many will have been improved to the
extent that joint surgery becomes unnecessary, nevertheless the quality of life for about half of them
has been improved considerably. The encouraging fact that improvement could be obtained in such old and
long-standing cases confirmed the impression gained from the preliminary four-year study that benefit
was related neither to age of the patients nor to the extent or severity of the disease.
Toxic effects were uncommon and, with the exception of the one patient who retained fluid, were mild.
The mussel extract used in the present trial was as effective as gold, though not as effective as
levamisole in improving pain, stiffness and grip strength. The drop-out and side-effect rates moreover
were much lower with Perna canaliculus than with either gold or levamisole. These latter are both
second-line drugs with a high incidence of toxic reactions (table 4). It is therefore suggested that
Perna canaliculus may prove to be a safe alternative to second-line drugs when first-line treatment is
failing to maintain the patient in a reasonably comfortable and functional state.
The dose of mussel extract required to maintained improvement varies from patient to patient. In the
four-year pilot study it was possible to reduce the dose in a considerable number of patients to one
capsule per day or less after they had been on the therapy for a period of several months. In the
double-blind trial some patients managed to reduce their dosage from three capsules (1050mg) per day
to two capsules (700mg) per day without experiencing any set-back. None has so far been able to reduce
the dose further, but none has yet been on the therapy for longer than six months.
This trial suggests that the extract of the green lipped mussel, Perna canaliculus is an effective
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 could be of considerable value
to patients suffering from these two chronic and disabling conditions.