|FAQs | Safety Info | Contact Us|
>Glycomarine COX Inhibition
GlycoMarine� SCIENTIFIC and TECHNICAL SUMMARY
Inflammation causes the pain associated with arthritis. This pain prevents sufferers from freely using affected joints, and results in reduced mobility and quality of life. The only permanent cure for arthritis is to replace damaged joints. However, many joints cannot be replaced, the severity of the arthritis may not warrant surgical intervention, or the patient may be too old, and thereby medically compromised by undergoing surgery. The current medical treatment of arthritis relies heavily on non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin and phenylbutazone. These can provide significant relief, but individuals respond differently to different drugs. Finding the right agent for a particular patient is a case of trail and error, and many do not respond at all. A further complication is that the NSAIDs cause damage to the gastric mucosa, which can lead to ulceration. Some patients are more susceptible to gastric damage than others, and hence, cannot take NSAIDs - leaving them without adequate pain control.
There is a clear need for an anti-inflammatory agent that can provide relief from the symptoms of arthritis without causing gastric damage. Worldwide, tens of thousands of individuals have found that McFarlane Laboratories' green-lipped mussel extract, GlycoMarine�, can meet this need. An added benefit is that the product is actually gastroprotective and can safeguard the stomach from the ulcerogenic effects of NSAIDs, which might be taken in combination with GlycoMarine. GlycoMarine is classified as a natural remedy, and no specific medical claims are made. However, more than 20 years of laboratory and clinical research strongly supports the view that GlycoMarine is a natural, gentle, anti-inflammatory, which provides relief from the painful symptoms of osteo and rheumatoid arthritis.
Please note that GlycoMarine is referred to under the name Seatone� in most of the clinical studies. Seatone� is synonymous with GlycoMarine.
Background and Development
GlycoMarine is the trade name for an extract of the New Zealand green-lipped mussel (Perna canaliculus) produced by McFarlane Laboratories of Auckland, New Zealand. The original version of this product was first introduced for general use in 1972, and is currently marketed as a food supplement/natural remedy in pharmacies and health food outlets. Over 95% of the production is exported, and the extract is sold in over 30 countries under the Seatone� brand name.
A McFarlane Laboratories company was founded to pursue the hypothesis that green-lipped mussel had anti-inflammatory properties. As a first step, it was necessary to establish a secure supply of fresh, healthy mussels. Mussel farming requires pollution free inshore seawater, with little variation in temperature. New Zealand provides ideal conditions for mussel farming and the world's first Perna canaliculus mussel farms were established in 1972 by McFarlane. In the 1980s, the present McFarlane Company acquired the business whereupon it changed and improved the earlier product.
Early research indicated that simply drying and encapsulating mussels did not produce a consistent product. Additionally, non-active components of the mussels diluted the activity. Two processes were combined to overcome this problem:
While the initial decision to process in this way was made on largely intuitive grounds, more recent research has shown that mussels processed using less sympathetic manufacturing techniques have greatly reduced anti-inflammatory activity. It is important to note that McFarlane Laboratories' product, GlycoMarine and Seatone� are the only mussel extract products manufactured using this unique and proprietary process.
The only thing that goes into GlycoMarine is New Zealand green lipped mussel extract.
In the early days, McFarlane owned their own mussel farms. As demand for Seatone� increased, McFarlane assisted individuals in establishing independent mussel farms, which now supply mussels for GlycoMarine. Mussels are farmed in several parts of New Zealand, but McFarlane Laboratories obtains its mussels exclusively from the Coromandel Coast. This isolated peninsula (east of Auckland) produces some of the highest-grade mussels in New Zealand. Both the water quality and shellfish quality is regularly monitored in Government laboratories. In addition to this, McFarlane Laboratories carries out further microbiological and physical testing to ensure that the final product meets the highest standards. Typical analysis profiles are appended at the end of this section.
When the mussels reach peak condition, at around eighteen months of age, they are harvested and shipped live in refrigerated trucks to McFarlane's factory in Auckland. (This multimillion-dollar facility is constructed to pharmaceutical industry standards, and has New Zealand Ministry of Agriculture, USDA, and EU registration.) On arrival, the mussels are transferred to cool storage and processed through McFarlane's unique hydroextraction equipment. The liquid extract is then immediately transferred to trays and snap frozen in preparation for freeze drying in one of four microprocessor-controlled, high capacity freeze dryers. The dry extract is milled to produce a fine powder and is then ready for bulk packaging or encapsulation. This start-to-finish in-house processing is proprietary to McFarlane, and total control over product quality is one of the reasons GlycoMarine sales continue to grow while imitators come and go.
When Seatone� was first sold in 1972, there was very little research-based evidence of its efficacy as an anti-inflammatory. However, as the anecdotal reports accumulated, McFarlane Laboratories funded a program of research projects in universities and hospitals; this, in an effort to obtain clinical and laboratory support for the claims of benefit made by arthritis sufferers who used the product. This ongoing research is presented in more detail in the RESEARCH section. One of McFarlane's aims was to establish an index of bioactivity that would allow individual batches of extract to be graded and standardized according to anti-inflammatory activity. This proved difficult for many years, but the company persevered and a sensitive bioactivity assay was eventually established. This breakthrough was the result of a New Zealand Government-funded co-operation between scientists at McFarlane Laboratories and The University of Auckland School of Medicine.
The internationally accepted, pharmaceutical industry standard for the assessment of activity of non-steroidal anti-inflammatory drugs, is the carrageenin assay. The assay was improved and refined by Ormrod and Miller at the University of Auckland as part of a research project supported by McFarlane Laboratories. This assay forms the basis of the test for activity in GlycoMarine.
The anti-inflammatory effects of GlycoMarine take several weeks to become apparent. In order to circumvent this problem, we have developed a proprietary and confidential extraction technique. This process has resulted in the anti-inflammatory activity of GlycoMarine being concentrated in a soluble injectable fraction.
The activity of the mussel extract is expressed in terms of suppression of oedema relative to a non-treated control group. Our purified mussel extract routinely suppresses oedema by 60-70%. In order to provide a meaningful indicator of activity between assays, an anti-inflammatory index (AI-index) is calculated. The AI-index is based on suppression of oedema relative to the mean control value. The assay has been standardized using the non-steroidal, anti-inflammatory drugs: aspirin, phenyllbutazone and indomethacin.
McFarlane Laboratories has set the minimum specification for the AI-index at 1.5 (100%) and most batches have an AI-index of 2-2.5, i.e. 33-66% above specification. Batches of mussel extract with an AI-index below 1.5 are rejected.
1. Winter CA, Risley EA & Nuss GW, Carrageenin-Induced Oedema in Hind Paw of the Rat as an Assay for Anti-inflammatory Drugs. Proc Soc Exp Biol Med 111:544-547 (1962).
2. Ormrod DJ & Miller TE, Assessment of Anti-inflammatory Agents Using 1251 Labeled Human Serum Albumin to Quantify Footpad Oedema Volume in the Rat. Pharm Res, 8: 1270-1273 (1991).
Published peer-reviewed papers and commissioned reports are appended in order of publication. A brief summary of the findings of these studies is given below.
Published Scientific Papers
1. Gibson RG, Gibson SLM, Conway V & Chappell D. Perna canalliculus in the treatment of arthritis. The Practitioner, 224, 995-999, (1980)
This double blind clinical study, carried out at The Victoria Infirmary, Glasgow, was a follow up to an encouraging preliminary therapeutic trial in 86 patients. Sixty-six patients took part, 28 of whom suffered from rheumatoid arthritis and 38 from osteoarthritis. These patients were evaluated at baseline and at monthly intervals over a six-month period. The initial dose was 3 x 350mg Seatone� capsules per day (1050mg total), but several patients in the treatment group found they could maintain a positive effect at a dose of 700mg/day. Overall there was a good response to treatment and 68% of rheumatoid patients and 40% of osteoarthritis sufferers gained significant relief from the symptoms of their disease. These were generally older individuals with advanced arthritis and the gains were in quality of life (pain relief, stiffness and coping with the environment) rather than in joint function. That these patients were able to gain benefit was of great significance to the researchers and they concluded, " �Perna canaliculus is an effective supplement or possible alternative to orthodox therapy in the treatment of both rheumatoid arthritis and osteoarthritis."
2. Rainsford KD & Whitehouse MW. Gastro-protective and Anti-inflammatory Properties of Green Lipped Mussel.(Perna canaliculus) Preparation. Arzneim-Forsch. /Drug Research, 30(11), 2128-2132, (1980).
To different degrees, all non-steroidal anti-inflammatory drugs (NSAIDs) cause damage to the gastric lining. It was therefore important to determine if Seatone�, which could be considered a natural NSAID, was ulcerogenic. This detailed study also measured the anti-inflammatory effects of mussel extract and found it to be moderately anti-inflammatory in the rat carrageenin footpad assay following oral administration. This anti-inflammatory activity was found to be specific to Perna canaliculus and was not found in New Zealand scallops, oyster, abalone or blue mussels. However, the main thrust of the study was the evaluation of the effect of mussel extract on the gastric mucosa. Seatone� itself had no effect on the stomach lining and, more importantly, it was found to actually protect the lining from damage by NSAIDs such as aspirin and indomethacin. This was seen in both rats and pigs - the latter being considered the closest non-primate to man. Thus as well as providing relief from arthritis, these result s suggest that Seatone� will also protect the stomach from the ulcerogenic effects of NSAIDs that might be taken in combination with mussel extract. Fractionation experiments suggested that the activity was associated with one or more lipid components of the mussel extract. The gastroprotective properties of Seatone� are the subject of a NZ patent.
3. Miller TE & Ormrod D. The anti-inflammatory activity of Perna canaliculus (NZ green lipped mussel). New Zealand Medical Journal, 667, 187-193 (1980).
This was the first paper in an ongoing Seatone� research program carried out by Drs Miller and Ormrod of the Department of Medicine, University of Auckland. In this study they first evaluated the anti-inflammatory activity of known NSAIDs on the carrageenin rat footpad assay. This allowed them to compare the relative effects of mussel extract. Seatone�, injected intraperitoneally was found to significantly suppress carrageenin-induced oedema and a dose response effect was established. Oral administration was not effective, but the authors suggest that longer-term administration or a different model may be more appropriate. They conclude, "The results, however, provide an encouraging start by characterizing some of the pharmacological properties of the material�"
4. Couch RAF, Ormrod DJ, Miller TE & Watkins WB. Anti-inflammatory activity in fractionated extracts of the green-lipped mussel. New Zealand Medical Journal, 720, 803-806 (1982).
This study, also from the laboratory of Miller and Ormrod, extended the previous study by fractionating the mussel and determining anti-inflammatory activity in this fraction. "A two step aqueous fractionation process resulted in an extract, which although only 16% 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." These results added to the mounting evidence that Seatone� did possess genuine anti-inflammatory activity.
5. Miller TE & Wu H. In vivo evidence for prostaglandin inhibitory activity in New Zealand green-lipped mussel extract. New Zealand Medical Journal, 755, 355-357 (1984).
This interesting research grew out of an earlier study designed to assess the teratogenic (foetal damaging) properties of Seatone�. Although no teratogenic effects were noted, and pups born to Seatone� fed rats were normal in every way, delivery of the litters (parturition) was delayed. parturition and inflammation are both controlled to some extent by prostaglandins, and most NSAIDs act on prostaglandins. Drs. Miller and Wu hypothesised that delayed parturition might "provide a novel test bed for the assessment of agents with prostaglandin biosynthesis inhibitory activity." This idea proved to be correct and feeding female rats with Seatone� both delayed parturition and inhibited foetal development. This is consistent with material inhibiting prostaglandin activity. It is important to note that Seatone� did not cause foetal deformities and that pups allowed to go to full term were normal. However, it is suggested that Seatone� should not be consumed during pregnancy.
6. Billard H. Extract of Perna Canaliculus (New Zealand green-lipped mussel) in rheumatology. La Gazette Medicale, 92(7), 1-5, 1985.
This is essentially a review article covering the research to 1985. It provides a very useful overview and suggests possible modes of action of the mussel extract.
7. Audeval B & Bouchacourt P. Double blind, placebo controlled study of the mussel Perna canaliculus (New Zealand Green-lipped mussel) in gonarthritis (arthritis of the knee). La Gazette Medicale, 93 (38), 1986.
This carefully executed double blind trial provides some of the most compelling data supporting the use of Seatone� to relieve the symptoms of arthritis in humans. By concentrating on patients with arthritis in just one joint - the knee- the researchers were able to eliminate the variables associated with diffuse arthritis and study a greater number of indices of disease in more detail. Four of the 10 criteria studied showed statistically significant improvement and three others tended towards the positive, but did not reach significance. The two most debilitating features of arthritis - pain and loss of function - both responded well to treatment. Interestingly, those with moderate disease showed greater improvement than those with advanced arthritis. The authors concluded "The results of this preliminary trial support the effective action of Seatone� in subjects suffering from mild arthritis of the knee."
8. Kosuge T, Tsuji K, Ishida H & Yamaguchi T. Isolation of an Anti-histamine Substance from Green-Lipped Mussel (Perna canaliculus). Chem. Pharm. Bull, 34, 4825-4828, 1986.
Histamine is an important component of the acute, mediator-driven, phase of inflammation. Although not generally used in the treatment of arthritic conditions anti-histamine drugs are important in the control of allergic reactions. Kosuge and colleagues used sophisticated isolation techniques to look for anti-histamine agents in the lipid component of the mussel. They found an active phospholipid and identified it as lysolethicin. As well as inhibiting histamine release, lysolecithin was found to inhibit the carrageenin footpad assay.
9. Miller TE, Dodd J., Ormrod D & Geddes R. Anti-inflammatory activity of glycogen extracted from Perna canaliculus (NZ green-lipped mussel). Agents and actions, 38, C139-C142, 1993.
10. Ormrod DJ, Dodd JR, Geddes R & Miller TE. Demonstration and characterization of Anti-inflammatory activity in a carbohydrate (glycogen) extract of the New Zealand green-lipped mussel (Perna canaliculus). Proceedings of the 6th International Congress of the European Association for Veterinary Pharmacology and Therapeutics, Blackwell Scientific Publications, p160, 1994.
This research, reported in these two papers, represented a new direction in the search for active component/s in Seatone�. A graduate student, Ulla Knaus, at the Ludwig Maximilians University in Munich had reported bioactivity in the glycogen (carbohydrate) fraction of Perna canalliculus. In cooperation with biochemists Professor Geddes and Joanna Dodd, Miller and Ormrod extracted the glycogen from fresh green-lipped mussels and evaluated its anti-inflammatory activity. It was found that this component was highly anti-inflammatory and was so low in toxicity that it could be injected intravenously. None of the NSAIDs can be routinely used in this way due to adverse reactions. The extract was also effective following oral, subcutaneous, intramuscular and intraperitoneal administration. It was further found that treating the extract with carbohydrate enzymes destroyed the activity. Treating with protease or lipase did not have the same effect, indicating that the activity was associated with a carbohydrate m oiety. Further experiments demonstrated that the carbohydrate extract inhibited neutrophil emigration from the blood vessels to an extra-vascular site of inflammation. Neutrophils are a key white blood cell in the inflammatory pathway and inhibiting their ability to participate in the response may be one of the mechanisms of action of the parent compound. This research is ongoing, and as detailed earlier, the carbohydrate extraction technique is used as a basis for an activity index for Seatone.
Recent Research Not Yet Published
1. Horimitsu Orimh, Michio Fujita, Tomoyuki Omura, Nobuyuki Kirihara (Division of Veterinary Radiology, Nippon Veterinary and Animal Science University) and Kenjiro Shimada. Clinical Effects of the New Zealand Green Lipped Mussel on Dogs and Cats with Joint Diseases. Research was conducted from September 1, 1997 - July 31, 1998 in veterinaries in the Tokyo district.
(These research findings were written in Japanese, and were translated into English.)
Clinical testing of a commercially prepared extract of the New Zealand green-lipped mussel (Green Mussel E Kyowa, GMEK. We used New Zealand green-lipped mussel manufactured by McFarlane Laboratories Ltd.). Research conducted on several different kinds of joint diseases of dogs and cats. The experimental animals were 43 dogs and 6 cats with pain and/or lameness, which was thought to be caused by joint diseases. GMEK was remarkably effective in 18, effective in 21, slightly effective in 7, and ineffective in 1 case. The clinical symptoms aggravated in 2 cases. No adverse effects were clinically observed except temporary diarrhea in 4 cases. GMEK was confirmed to be an excellent nutritional supplement for dogs and cats with joint diseases. In summary, the researchers concluded: GMEK as a nutritional supplement is safe and effective for dogs and cats suffering from joint diseases.
2. Pollard Brendan, Slacek Brigitte, Ankenbauer-Perkins Kim; Animal Health Services Centre, Massey University, Palmerstown North, New Zealand. Draft Double Blind Pharmacological Efficacy Trial: Final Report of the Efficacy of Green-Lipped Mussel Extract in the Management of Degenerative Joint Disease in Dogs. Conducted between 4 June 1997 - 12 October 1998.
The objective of the trial was to compare the efficacy of green-lipped mussel (GLM) extract with a placebo in the relief of clinical signs of canine degenerative joint disease.
The trial was conducted in two phases. The first phase was a double-blind, placebo controlled study of 80 dogs, randomly allocated to receive GLM extract or a placebo for 56 days. At the conclusion of this phase, all owners were offered the choice of continuing the trial (90% of the owners (72 dogs) elected to enter the second phase of the trial) by administering the GLM extract in an uncontrolled open-label fashion for a further 56 days. Response to treatment was evaluated by both owner assessments and physical examinations performed by a veterinarian. Complete blood counts and serum chemistry profiles were used to screen for evidence of toxicosis. In conclusion, it was said that: This trial provides objective evidence that Green Lipped Mussel extract has a clinically significant beneficial effect on the signs of degenerative joint disease in dogs.
The research to date provides strong evidence that GlycoMarine is anti-inflammatory and can alleviate the symptoms of arthritis in both animals and humans. However, in spite of more than 20 years of research, it has not been possible to identify the active component(s). Some clues to the reason for this are contained in these papers. Some experiments support the view that a protein or proteins are responsible for the activity, while others suggest that the activity resides with lipids or carbohydrates. The truth may well be that all three (or perhaps other, as yet untested, components) are required for maximum benefit. In time this question will be resolved, but in the meantime, arthritis sufferers have access to a well-researched, safe and effective natural anti-inflammatory that, in many cases, will help them to lead a more active and less painful life.
Copyright © 2006 Marine Ingredients, All Rights Reserved.