Research Studies- New Zealand Green Lipped Mussel

Glasgow Homeopathic Hospital Study (1980)

Gibson, RG. Gibson. S.L.M, Conway, V., et al. Perna Canaliculus on the treatment of Arthritis.

Introduction

This was the first long-term double-blind clinical study examining the effect of Biolane® Extract on 66 patients with arthritis. The results showed that Biolane® Extract was effective in treating patients with both rheumatoid arthritis (RA) or osteoarthritis (OA). The proportion of patients benefiting from treatment with Biolane® Extract was higher in the RA than the OA group.

In a preliminary test carried out with 86 patients, 55 had rheumatoid arthritis and 31 had osteo arthritis. The trial results indicated that 67.9% of the rheumatoid patients and 39.5% of the osteo patients benefited from GLM supplementation . An interesting point relating to these figures is that they agreed with those compiled from unsolicited anecdotal reports originating from people in countries all around the world.

This was followed by a double blind, placebo controlled study involving an additional 66 patients. Of these, 28 had rheumatoid and 38 had clinical and radiological evidence of osteo arthritis. All patients were taking some form of NSAIDs.

Clinical assessments like the ones mentioned below were monitored before and after a 3-month trial period where the test group received 1050mg of GLM extract per day and the control group received the placebo:

• Joint Mobility
• Pain Index
• Swelling
• Function Tests
• Laboratory Indices

Results

Results of the study, after removing eight patients who dropped out due to unrelated reasons, were as follows: 76% of the rheumatoid and 45% of the osteo arthritis group reported improvement in the form of reduced pain/ stiffness. A total of 23 out of 58 (40%) in the study showed no improvement.

Grip strength did not significantly improve in the in the treatment group. Side- effects were minimal, apart from initial exacerbation of symptoms experienced by six of the 66 patients in the trial from two to four weeks after starting the study. This increased sensitivity lasted from one to two weeks after which the individuals generally reported improvement in their symptoms. Dosage of GLM Extract dropped to 750mg per day once a positive response was seen.

Advisory: This is not intended for the diagnosis or treatment of medical complaints. It is for information purposes only.

French Study involving Osteo Arthritis of the Knee (1986)

Audeval, B., Bouchacourt, P., Double blind, placebo-controlled study of the mussel (New Zealand green-lipped mussel) in Gonarthrosis (arthritis of the knee) .

Introduction

This double blind clinical study was conducted to the full European protocol as detailed in the European Directive on clinical trials of New Drugs Against Rheumatism. It was a very well conducted trial, involving 53 carefully matched patients over a period of six months. The trial was conducted at two Rheumatology centers in Paris and produced positive results indicating the effectiveness of the mussel extract for this condition.

The patient′s conditions were confirmed by a radiographic analysis and they had clinically experienced a steady pain for several weeks. The study lasted 6 months using 6 capsules (2100mg of GLM Extract per day) versus a matched placebo.

Ten efficacy measures were employed and patients were examined monthly. Results showed that the GLM Extract group was statistically superior to the placebo group in 4 of the 10 test areas:

• Pain and discomfort
• Functional index ARA
• Patient′s opinion on results of treatment
• Treatment effectiveness judged by the doctor

The placebo group showed a greater reduction in ′morning stiffness′ as compared to the GLM extract group.

Results

The researchers concluded that GLM was effective by influencing the evolution of the arthritic illness – stopping the deterioration and enhancing the repair mechanism rather than by just working as an analgesic or purely as symptomatic anti-inflammatory agent.

Advisory: This is not intended for the diagnosis or treatment of medical complaints. It is for information purposes only.

A USA Pilot Study done on Gonarthrosis (Osteo-arthritis of the knee) (2000)

Kendall R, Lawson J and Hurley LA. New research and a clinical report on the use of Perna canaliculus in the management of arthritis. Townsend Letter for Doctors and Patients, 2000; 204:98-111

Introduction

This paper includes the results of a laboratory research into the mechanisms of action of the mussel extract and also those from a 4-year clinical study involving 120 patients suffering osteo arthritis. The results, which originate from a university and also a clinical practice in the USA are once again excellent and fully support all the earlier positive data for the product.

Sixty-four males and fifty-six females made up this group with most patients in the age group of 60-70. Several of them had been referred total knee replacement. All patients in the study were provided information on the use of Green Lipped Mussel (GLM) for degenerative joint disease. They were advised that GLM Extract had been shown to have an anti-inflammatory effect equal to that of Indocin but more importantly it had a nutritive metabolic effect. The importance of mucopolysacharrides (glycosaminoglycans) in the formation of basic proteoglycans cartilage was stressed.

Patients with a known allergy to seafood, shellfish and alfalfa were excluded from the study but patients who were taking some form of NSAIDs or pain medication were allowed to continue but were requested to keep a record of all medications required.

Pain Assessment

The Huskinson visual analogue pain scale was used to assess pain where the pain intensity ranged from ” no pain” to “worst possible pain “. (Intensity Scale Fig. 1.)

Inflammatory Index

An estimate of overall inflammatory activity of the joints based upon clinical evidence of swelling, trauma, redness, heat and pain was made. A history of ” minutes of morning stiffness” as well as daily activity, participation in sports etc. was recorded by the patients.

The patient′s opinion of their condition in comparison to their initial state (same, a little better, a lot better, worse, much worse) was recorded. The physician′s evaluation was also made at the time of each visit (excellent, good, no change).

Notes were made as to tolerance of GLM Extract and compliance. Notes were also made in reference to the use of NSAID′s, pain medication, tropical cream and ointments.

The patients were prescribed 3 GLM Extract capsules (a total of 1500mg extract) per day taken with food and then 2 capsules daily as a permanent maintenance dose. The product used in the study contained 500mg GLM and 100mg alfalfa. The study was designed to last one year and out of 120 patients, only eleven were eventually elected for total knee replacement.

X-RAY evaluation

X-Rays of the patients were graded on the basis of a scale of I to IV using the Kellgren and Lawrence system – degree of osteoarthritis progressing by grade from grade I (minimal, least, severe) to grade IV (bone on bone).

The response to management in these groups of patients studied became evident at the time of the first follow-up visit. Many grade I & II patients who had presented with an initial analogue of 7 reported a 0 – 2. These patients continued to remain comfortable and active during the rest of the study.

Evidence of pain, heat and swelling was noted to be significantly diminished or absent during the remaining visits.

The two patients who were using canes no longer required them. A significant number of patients were able to reduce their NSAID intake by 50% or more. Most patients reported that their condition was much improved. No patient complained that his condition was worse.

Patient′s and Practitioner′s Assessments

95 patients reported of much improvement and 16 reported of some improvement. 9 patients reported of no change.

According to the practitioner, 19 patients (27%) had shown no improvement, 38 patients (31%) had shown good improvement and 63 patients (52%) had made excellent progress.

11 patients did eventually come for joint replacement therapy but felt that GLM protocol had bought them some more time.

Advisory: This is not intended for the diagnosis or treatment of medical complaints. It is for information purposes only.

Study on recovery of soft tissue damage in South Africa (1998)

In this study, conducted at the UCT Medical School in South Africa, the effects of Seatone GLME on recovery from muscle injury were compared with those of placebo in 20 highly trained athletes (cyclists). The cyclists took Seatone GLME for 3 weeks before muscle injury was induced. Peak power was greater and recovery of peak power faster in the group who were taking Seatone GLME than in those taking placebo. This is the first study to suggest that Seatone GLME can aid in the recovery of soft tissue injury in healthy individuals.

This preliminary clinical trial did not show any benefit of Biolane® Extract in patients with rheumatoid arthritis. However, the study included only 6 patients, and treated them for only 6 weeks, so the patient population was too small and the study duration too short to find any therapeutic benefit. Also, the study used a crossover design in which patients received a placebo or Biolane® Extract for 6 weeks, and then crossed over to the other treatment for a further 6 weeks. This type of study design is not appropriate for assessing the effect of long-term treatment, and may be confounded by carryover effects from one treatment phase to the next.

This double-blind clinical trial was conducted at Auckland Hospital in 47 patients with rheumatoid arthritis. Patients were randomised to receive Naproxen (an anti-inflammatory drug) + Biolane® Extract, or Naproxen + placebo for the first 6 weeks. Then for the following 5 weeks, the Naproxen was replaced with placebo, so that the groups were taking Biolane® Extract + placebo or two forms of placebo. This study assessed the effectiveness of Biolane® Extract by measuring how many patients stayed on the treatment. Biolane® Extract was slightly more effective than placebo in this study (but not statistically significantly so). However, when the powerful anti-inflammatory drug was withdrawn, many patients stopped treatment because of their worsening condition. This is not a surprising finding. A potential confounding factor is that patients withdrew from the study for reasons unrelated to their treatment.

This double-blind study, conducted at the Centre for Rheumatic Disease in Glasgow, compared Biolane® Extract with a placebo in 35 patients with rheumatoid arthritis. The study was conducted in patients with serious rheumatic disease, whose disease was not adequately controlled with anti-inflammatory drugs. It is no surprise that they found Biolane® Extract was not effective.

In-vitro laboratory study of Biolane: A Comparative Study of Biolane versus other agents. Austrlia (2005)

Cheras PA. Vascular Mechanisms in Osteo-arthritis: Rationale for Treatment with a Marine-Based Complementary Medicine, Osteo-arthritis and Cartilage 2005, Volume 13, page S95.

Cheras PA, Stevenson L, Myers SP. In-vitro Biological Activities of Biolane: A comparative study. ACCMER (Australia), Sep 2005

Study Aim

In vitro laboratory studies were undertaken by the Australian Centre for Complementary Medicine Education and Research (ACCMER), a joint venture of the University of Queensland and Southern Cross University. The aim of the studies was to compare selected biological activities of Healtheries′ Biolane™ (Green Lipped Mussel Extract) versus the biological activities in a range of well known complementary anti-arthritic agents.

Sample Preparation

All samples were subjected to two enzyme digestions to simulate in vivo digestive processes. Various components of gastrointestinal secretions may have an impact on potential actives within a product. In this study we used a two stage in vitro model based on gastric and duodenal secretions. The digests prepared from the samples were a pepsin digest containing the prominent gastric enzyme pepsin and a complete digest where the sample was exposed to pepsin followed by pancreatic enzymes.

Assays

Assays assessed:

• Cholesterol synthesis inhibition
• Anti oxidant capacity

Inhibition of the following components of inflammatory pathways

• tissue necrosis factor alpha (a)
• Cox-2 expression
• prostaglandin E2 (PGE2)
• phospholipase A2 (PLA 2) – also associated with platelet aggregabillity
• platelet aggregation inhibitory activity
• fibrinolytic activity

Synopsis of Results

Comparison of aggregate in vitro data – Chondroitin Sulphate (CS) vs Glucosamine Sulphate (GS) vs Glucosamine sulphate:Chondroitin sulphate (GS/CS) vs Lyprinol™ vs Healtheries Biolane™ (Green Lipped Mussel Extract).

Note ● denotes activity present ○ denotes activity not found

â—‹* denotes activity not found at low concentration but present at higher concentration

ND = not done (test unable to be performed due to assay artefact)

The results show that Healtheries Biolane™ (Green Lipped Mussel Extract) demonstrates the most comprehensive range of activities across the suite of in vitro tests performed when compared with the other agents that were tested.

Relevance of the in vitro Biolane green lipped mussel extract (GLME) findings to putative Osteoarthritis pathomechanisms

The vascular theory of osteoarthritis causation is based on epidemiological, laboratory, experimental and clinical findings that support the concept that compromised microcirculation in affected joints initiated through a combination of inflammation and imbalance between coagulation and fibrinolysis can initiate and perpetuate the disease. One implication of this theory is that in order to treat more than just painful symptoms ie to slow or halt the disease process will require a range of biochemical activities to effectively break the web of pathology. It has been proposed that these should include a number of key activities such as anti-inflammatory, anticoagulant, fibrinolytic and lipolytic activities. If these are realised then chondroprotection is likely to ensue.

The use of highly potent anti-inflammatory agents, particularly the Cox-2 inhibitors would appear to be at odds with the known data showing that patients with osteoarthritis are at greater risk of thrombotic episodes than those without the disease. Cox-2 inhibitors pose a theoretical risk of increased thrombotic complications in many patients with osteoarthritis who already have cardiovascular risk factors. The recent removal of Vioxx from the market and restrictions governing the use of Celebrex – the Cox-2 market leaders, based on these concerns would appear to support this proposition.

A successful anti-arthritic agent should have multiple low level activities that address a range of disease drivers while avoiding the serious side effects that frequently accompany massive disruption of major biochemical pathways such as total Cox-2 inhibition.

The current in vitro study has shown that GLME has a range of activities that the vascular theory of osteoarthritis causation predicts as desirable for disease treatment. These include anti-inflammatory activity through its inhibition of TNFa, PGE2, Cox-2 and PLA2 in addition to its anti-oxidant activity. It is not critical for these activities to be at extremely high levels. In fact it is advantageous from the perspective of a low side effect profile that they should not be so. It is the multiplicity of activities that is of greater importance. In addition to anti-inflammatory activity, GLME also has in vitro activities that can reduce thrombotic risk (decreased PLA2 and cholesterol biosynthesis inhibition activity in addition to decreased platelet aggregability – that is also assisted through cholesterol biosynthesis inhibition) and enhance the removal of blood clots (mild fibrinolytic activity).

The results obtained in this study indicate that GLME has in vitro activities in key areas associated with arthritis pathophysiology. In addition, across the range of in vitro tests performed in this comparative study, Healtheries Biolane™ green lipped mussel extract demonstrated a more extensive range of potential anti-arthritic activities in comparison to the other agents tested.

It is important to note that these results apply specifically to Biolane™ (Green Lipped Mussel Extract) and can not be extrapolated to include other green lipped mussel extracts.

Advisory: This is not intended for the diagnosis or treatment of medical complaints. It is for information purposes only.

Researchers from the University of Auckland, New Zealand, demonstrated that intraperitoneal administration (administering through the peritoneum) of Biolane® Extract significantly reduced inflammation in rats with induced arthritis. The study found that lower doses of the extract were effective if administered for several days before administering the arthritis-inducing agent. This was possibly the first indication that Biolane® Extract has a systemic effect on the course of the disease, rather than simply relieving the symptoms.

This study demonstrated that Biolane® Extract had anti-inflammatory activity in rats with arthritis. The study also tested isolated fractions of Biolane® Extract for anti-inflammatory activity, but each of these fractions alone had no effect. This supports the argument that it is the combination of elements in Biolane® Extract (rather than a single compound) that confers its anti-inflammatory activity.

Australian scientists showed that Biolane® Extract mussel extract has a protective effect on the stomach lining; unlike common pharmaceutical agents for treating arthritis, which actually promote stomach ulceration. In addition, these scientists found that the lipid component of the extract, which was responsible for this protective effect on the stomach lining, also demonstrated a mild anti-inflammatory activity.

This study, conducted at the University of Auckland, investigated the relative anti-inflammatory activity of isolated fractions of the mussel extract. The study concluded that the principal activity was due to water-soluble fractions of the extract, with secondary activity due to the lipid fraction.

This study provided valuable evidence for the immunomodulatory (immune system changing) effect of Biolane® Extract, in particular its suppression of T-lymphocyte (a kind of white blood cell) function. It provided further evidence of the systemic effect of the mussel extract in treating arthritic disorders.

This study was the first to demonstrate that Biolane® Extract inhibited prostaglandin production, providing compelling evidence that this was a primary mechanism for its anti-inflammatory effect. Inhibition of prostaglandin production was demonstrated through delayed parturition (giving birth) in rats, a well-established scientific model for investigating effects on prostaglandin production.

This laboratory study, conducted at the Shizuoka College of Pharmacy, successfully demonstrated that a substance in Biolane® Extract has positive antihistamine and anti-inflammatory activity. The active fraction isolated by these scientists was naturally-occurring lysolecithin.

This study investigated the properties of glycogen extracted from the green-lipped mussel, blue mussel and other bivalve shellfish. The anti-inflammatory activity was shown to be unique to the green-lipped mussel glycogen: glycogen from the blue mussel actually exacerbated inflammation in this animal model.

Scientists extracted a polysaccharide (glycogen) from Biolane® Extract, and found that it has anti-inflammatory activity in rats with arthritis. The glycogen from Biolane® Extract also substantially reduced the migration of neutrophils (a kind of white blood cell) to the site of the inflammation.

This small preliminary study showed no effect of Biolane® Extract on arthritis in rats. However, in this study, Biolane® Extract was added to the rats’ food, and therefore scientists were unable to regulate the dosage the animals received. It is probable that the animals did not receive sufficient Biolane® Extract to demonstrate an effect.

Study on dogs diagnosed with degenerative joints disease (DJD) in New Zealand (2006)

81 dogs diagnosed with DJD were treated orally daily with either GLME or placebo for 56 days in a double blind, placebo-controlled study.

In conclusion, the results of this study suggest that Seatone containing treatment used was well tolerated and had a significant beneficial effect on the clinical signs of dogs diagnosed with DJD.

Study of the Teratogenic & Toxicological Potential of Seatone® (Biolane Extract) Auckland. (1981)

Author: TE Miller, HWu..

Dept of Medicine, University of Auckland, New Zealand. May 1981

The study monitored the teratogenic effects of Seatone using 20 breeding pairs of Dark Agouti rats for each of the test and control groups over a period of 6 months. The rats were fed either a standard diet or the diet containing Seatone for 90 days prior to mating.

The control animals were fed powdered pellets of a standard diet, and active group animals were fed Seatone blended in to a formulation that was estimated to equate to 50 time the recommended dosage for humans. Subsenquent analysis indicated that the formulation represented 54 times the recommended human dosage.

Autopsies were carried out on progeny from both groups at 21 days of age, test group, control group with rats from both groups also being processed for histological examination. Additionally, examination of near term (20 days) foetuses from the second litters of both groups, were examined for skeletal abnormalities and malformations.

No teratogenic effects were observed at the doses consumed (54 times normal)

The litter sizes in the Seatone fed group were significantly smaller although the average weight of the Seatone progeny was greater at both 4 and 21 days.

The study concluded that Seatone delayed conception. There were no skeletal abnormalities or malformations in either group but delayed skeletal development was observed in a greater number of animals in the Seatone group to those in the control group.

Study on Acute and sub Acute Toxicity on Seatone® (Biolane Extract) Auckland (1981)

Author: TE Miller.

Dept of Medicine, University of Auckland New Zealand, February 1981

The study was conducted in two phases using four groups of five male and female Fischer rats.

Phase one involved monitoring the response of the rats to a single high dose (8g per kg bodyweight) of Seatone. No signs of toxicity were found and all amimals were alive and healthy 2 weeks after administration of the Seatone.

In phase two the rats were fed Seatone at a daily dose of 2g per kg bodyweight per day administered orally for 14 day. No signs of toxicity were found

The animals were examined daily over a period of fourteen days. At the end of fourteen days the animals were euthanized and a post mortem conducted with heart, lungs, stomach and intestines being examined. Blood samples were also taken from the animals involved in the phase two experiment for determination of haematological parameters.

After two weeks all animals in both phases of the experiments were alive and healthy and it was found that Seatone did not exhibit acute toxicity. Due to the absence of toxic effects it was not possible to establish the LD50 for Seatone and the author concluded that the experiments demonstrated the Seatone does not exhibit acute toxicity when tested in rats.

In body weight terms of a 70 kg human, this would be equivalent to 120 gram per day. The recommended human dose in humans is 1 -1.2 gram per day.

FOOTNOTE: Long Term Toxicity.

The absence of toxic effects due to daily ingestion of Seatone over the long term has since been demonstrated by the fact that the product has been subjected to a number of clinical studies of duration up to six months in human subjects with no incidence of adverse events. In addition, widespread international use of the product by humans for more than 30 years has not resulted in any reports of toxic events.