GREEN-LIPPED MUSSEL OIL (GLMO)

The most powerful natural anti-inflammatory agent known

GLMO is a natural marine oil, a lipid extract of the New Zealand green-lipped mussel Perna canaliculus. The Maoris who live in New Zealand have claimed for centuries that consuming local green-lipped mussels has helped them maintain good health. Statistics show that the reported incidence of arthritis is much lower in the coastal-welling Maoris than in the Maoris who reside in the interior. Coastal-dwelling Maoris are known to consume large amounts of green-lipped mussels.

To investgate its reported anti-inflammatory activity, researchers in the United Kingdom, Australia and Japan started in the 1970's a number of clinical trials with various oral preparations of the New Zealand green-lipped mussel. However, the majority of these studies proved unsatisfactory. During the 1970's McFarlane Laboratories Pty. Ltd., which later became part of the MacLab Group of Companies in Melbourne, was established to distribute freeze-dried green-lipped mussel powder in Australia.

In the early 1980's McFarlane became concerned over criticism which had been voiced by certain medical and scientific commentators challenging the value of freeze-dried green-lipped mussel powder for the treatment of arthritis. In 1982, following discussions with RMIT University in Melbourne, McFarlane decided to fund research in the Natural Products Chemistry Unit of RMIT's department of Applied Biology. The challenge for RMIT was to seek and identify the active component(s) that was believed to exist in the green-lipped mussel. In 1983 the research team at RMIT was joined by a Japanese research group headed by professor Takuo Kosuge, head of the Shizuoka College of Pharmacy at Shizuoka University, Japan and one of Japan's most respected research chemists.

Early 1984 professor Kosuge formulated there was a major problem with the mussel powder produced by MacFarlane. The mussel powder was found to be exremely unstable and lacking in potency due to rapid oxygen degradation (oxidation). Professor Kosuge determined that unless some method could be eveloped to stabilise the mussel powder and prevent its oxidation, there would be little or no value for use as a serious treatment for arthritis, which was the commercial aim of MacFarlane. After testing all known anti-oxidants without success, professor Kosuge turned to research that he had conducted twenty years earlier on a traditional mehod used by Japanese fisherman to preserve their stored fish for future consumption with the help of tartaric acid. This method appeared to work for the geen-lipped mussel as well. As a result of this work, MacFarlane patented and developed a natural stabilisation process for green-lipped mussel powder with tartaric acid, which prevented its oxidation and allowed it to be researched without degrading in potency.

In the early 1990's the RMIT group approached Dr. Henry Betts, who was the Principal Scientist of the Rheumatology Research Laboratory at the Queen Elisabeth Hospital in Adelaide, South Australia. Dr. Betts had perfected a technique for testing anti-inflammatory compounds in an in vitro system. The MIT/McFarlane group asked Dr. Betts to test various fractions extracted from the New Zealand green-lipped mussel. It was through this research the discovery was made the lipid fraction of the green-lipped mussel are the biological most active anti-inflammatory compounds.

Since this discovery, most research on the green-lipped mussel has been conducted on its lipid fractions, the green-lipped mussel oil (GLMO). It has recently been discovered that a completely new group of fatty acids, the so-called Furan fatty acids, form the most important anti-inflammatory fraction in green-lipped mussel oil. In the early 2000s, the first green-lipped mussel oil (GLMO) was commercially available as a softgel capsule, stabilized with vitamin E to prevent oxidation. In the early 2000's the first commercial GLMO became availble as soft gel capsules, stabilised with vitamin E to prevent oxidation.

The production process

Green-lipped mussels are cultured in the pristine wilderness of the New Zealand coastal waters, feeding on natural plankton. The culture is controlled and regulated by the New Zealand Ministry of Agriculture and Forestry. After harvesting, the mussels are transported in refrigerated trucks to the manufacturing plant where they are crushed and centrifuged. The mussel extract is stabilised with tartaric acid and freeze-dried, after which the mussel oil is extracted. The mussel oil is further stabilised with vitamin E to prevent oxidation in the capsules. Only GLMO produced in this way has kept its full potency of anti-inflammatory properties. 

GLMO with stabilised lipids is much more potent than unstabilised oil and powder The NZ green-lipped mussel, ranked among the top 'eco-friendly seafoods' according to the US environmental agency Blue Ocean Institute's list, is already used a source of nutraceuticals. The extract has gained a reputation amongst consumers as a natural product with anti-inflammatory properties - an effect that has been attributed to a body of science to its lipid factions.

- Nutraingredients 27/09/2007: Studies support green-lipped mussel's anti-inflammatory properties

GLMO inhibits inflammations and allergic reactions in a safe way

GLMO moderately inhibits ovine COX-1 and COX-2 pure enzymes in vitro. The free fatty acid fraction of GLMO and to a lesser extent the triglyceride fraction are the most active anti-inflammatory compounds. Hydrolysis of the extracts using potassium hydroxide or protease enzymes increased COX inhibition by up to ten-fold. Both COX-1 and COX-2 pathways are involved with inflammatory processes and allergic reactions. Although inhibition of COX-2 is beneficial to the reduction of the inflammatory response, there is debate concerning the safe usage of NSAIDs and selective COX-2 inhibitors as anti-inflammatory agents in relation to gastrointestinal and cardiovascular events. In the present study, GLMO exhibited no inhibition selectivity or preference for either COX-1 or COX-2, and this was apparent for the extracts at various concentrations. This observation is in contrast to the NSAID's which are non-selective inhibitors of COX that show preferential activity against COX-1. The researchers concluded these results support the use of GLMO as an alternative for conventional [non-steroidal anti-inflammatory drugs] NSAIDs and fish oil treatment in the relief of the symptoms of arthritis.

- S. McPhee, L.D. Hodges, P.F.A. Wright, P.M. Wynne, N. Kalafatis, D.W. Harney, T.A. Macrides (2007) Anti-cyclooxygenase effects of lipid extracts from the New Zealand green-lipped mussel, Perna canaliculus. Comparative Biochemistry and Physiology, Part B, Volume 146, Pages 346-356.

Furan fatty acids form the most biologically active part of the green-lipped mussel

GLMO contains a fairly rare group of fatty acids, the so-called furan fatty acids. These fatty acids are produced by specific algae that occur in the clean, cold, deep New Zealand coastal waters in which the green-lipped mussel is farmed. The mussels filter these algae from the water, and the furan fatty acids accumulate in the mussel tissue. Furan fatty acids are the most biologically active component in the mussel fraction and contribute largely to the powerful anti-inflammatory effect of the green-lipped mussel.

- Toshiyuki Wakimotoa,1, Hikaru Kondob , Hirohiko Niia , Kaori Kimurab , Yoko Egamia , Yusuke Okab , Masae Yoshidab , Eri Kidab , Yiping Yeb , Saeko Akahoshib , Tomohiro Asakawab , Koichi Matsumurac , Hitoshi Ishidab , Haruo Nukayab , Kuniro Tsujib , Toshiyuki Kanb , and Ikuro Abea (2011): Furan fatty acid as an anti-inflammatory component from the green-lipped mussel Perna canaliculus. PNAS | October 18, 2011 | vol. 108 | no. 42 | 17533–17537 / https://www.pnas.org/doi/full/10.1073/pnas.1110577108

GLMO contains a novel and unique omega-3 fatty acid that imitates arachidonic acid (AA)

The free fatty acid fraction of GLMO contains novel omega 3 polyunsaturated fatty acids (ω-3 PUFA), originating from the algae and other micro organisms unique to New Zealand waters. The most bioactive fractions were identified as C18:4, C19:4, C20:4, and C21:5. The C20:4 (an ETA-like molecule) was the predominant PUFA in the extract, and was a structural isomer of arachidonic acid (AA). The inflammatory precursor AA is an ω-6 PUFA of 20 carbons in length and has 4 unsaturated double bonds (positions 5, 8, 11 and 14) with each double bond being separated by one methylene group. The predominant bioactive PUFA of GLMO identified in this study is similar to AA in that it also possesses 20 carbons with four double bonds. However, the first double bond is located at the seventh position, and the second double bond is interrupted from the first by two methylene groups resulting in the double bonds at positions 7, 11, 14 and 17. The interrupted bond positioning of these structural analogues of AA may account for their anti-inflammatory behaviour, by competitively inhibiting the active site of enzymes which use AA as a substrate, i.e., LO and COX, thereby reducing the production of leukotriene (LT) and prostaglandin (PG) metabolites. The novel compounds may be biologically significant as anti-inflammatory agents, as a result of their in vitro inhibition of lipoxygenase products of the AA pathway.

- Nutraingredients 27/08/2007: Studies support green-lipped mussel's anti-inflammatory properties
- A.P. Treschow, L.D. Hodges, P.F.A. Wright, P.M. Wynne, N. Kalafatis, T.A. Macrides (2007): Novel anti-inflammatory ω-3 PUFAs from the New Zealand green-lipped mussel, Perna canaliculus" Comparative Biochemistry and Physiology, Part , Volume 147, Pages 645-656.

GLMO reduces inflammation by modulating specific cytokines and proteins

A pioneering research by the Hong Kong Polytechnic University has uncovered a previously unknown complex anti-inflammatory mechanism for easing the pain of arthritis as well as confirming the effectiveness of GLMO's ability to alleviate conditions associated with inflammation. In a series of studies conducted by professor Samuel Lo and his team, GLMO was shown to relieve pain in adjuvant-induced rats; modulate cytokines with a decrease in cytokines associated with inflammations, and increase IL-10 (a cytokine that controls inflammation). Moreover, GLMO decreased the synthesis of some proteins associatd with inflammation, while increasing the synthesis of the anti-inflammatory enzyme MDH.

- Halpern G.M. (2008): Novel anti-inflammatory mechanism of Lyprinol in the AIA rat model. Progress in Nutrition Vol. 10, N.3, 146-152.
- Chi-Ho Lee, John Hon-Kei Lum, Curtise Kin-Cheung Ng, Janice McKay, Yoki Kwok-Chu Butt, Man-Sau Wong, Samuel Chun-Lap Lo (2007): Pain controlling and cytokine-regulating effects of a lipid extract of Perna canaliculus, in a rat adjuvant-induced arthritis model. eCam Advanc Access, September 26, 2007
- Hong Kong Polytechnic University Press Release, issued January 22, 2009   

GLMO is over 200 to 350 times more potent than other oils

Research has shown GLMO is over 200 to 350 times more potent than other oils (fish oil, salmon oil, flax oil, evening prmrose oil) in preventing the swelling associated with adjuvant-induced polyarthritis.

- Halpern G.M. (2000): Anti-Inflammatory effects of Greenlip mussel oil. All. et Immun. 32(7);272-278.
- Whitehouse MW, Macrides TA, et al: Anti-Inflammatory activity of a lipid fraction (GLMO) from the NZ greenlip mussel. Inflam Pharmacol 1997(5):237-246

GLMO is more poten than NSAID's (non-steroidal anti-inflammatory drugs)

In a study the effects of GLMO, aspirin and ibuprofen were compared in a carageenan-induced inflammation in rodents. Results showed that aspirin reduced inflammatory swelling by 40%, ibuprofen by 60% and GLMO by 90%.

- Halpern G.M. (2000): Anti-Inflammatory effects of Greenlip mussel oil. All. et Immun. 32(7);272-278.

GLMO is safe and effective in the management of arthritis

Several studies show GLMO is safe and effective in the management of arthritis: 

• Eighty patients with knee OA were randomized to receive either GLMO or placebo for six months. All were allowed paracetamol rescue treatment during the study and were reviewed at week 0, 2, 4, 8, 12, 18 and 24 for arthritis assessment and safety evaluation. Assessment of the patients’ arthritis included the use of a100 mm visual analog scale (VAS) for pain, patient’s and physician’s global assessment of arthritis, a validated Chinese version of the Oxford Knee Score (COKS), a validated Chinese version of the Arthritis Impact Measurement Scale 2-short form (CAIMS2-SF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Improvement in almost all of the arthritis assessment parameters was observed in both groups of patients studied. However, there was a greater improvement in the perception of pain as measured by the VAS, and patients’ global assessment of arthritis in those who took GLMO when compared with controls from week 4 following adjustment for the change in the amount of paracetamol used between study visits. Patients who took GLMO but not placebo also had improved scores in the CAIMS2-SF physical function and psychological status domains from week 4. However, changes in these scores did not differ significantly between the two groups at various study visits.When used over six months, GLMO was safe and well tolerated with no serious side-effects reported. Further, there were no significant differences in the overall incidence of adverse reactions or withdrawal from study as a result of trial drug toxicity between GLMO and placebo treated patients.
  - Lau CS et al (2004): Treatment of Knee Osteoarthritis with a lipid extract of the green-lipped mussel, a double blind placebo-controlled study. Prog in Nutr 6(1),N;17-31.
  
  
• A 12 week drug monitoring study evaluated the effects of GLMO on 50 adult men and women suffering from inflammatory rheumatoid arthritis. 34 of the 50 patients required medicinal treatment before and during the study. Upon completion of the study, for 21 of the 34 subjects (64 %) current drug therapy could be reduced or terminated. 13 of those did not even require further therapy. At the end of the treatment period, 38 % of all subjects were regarded as being free from disorders and the number of subjects suffering from severe pain was significantly decreased from 60% (at baseline) to 25 % (at completion of the trial). A significant positive effect was observed for all investigated parameters. GLMO was generally very well tolerated, with only one, non-serious adverse event (mild nausea) observed, which can probably be related to the study medication. GLMO therefore, proved to be an effective and very well tolerated dietary supplement for the treatment of inflammatory rheumatoid arthritis.
  - Gruenwald J. et al (2004): Efficacy and Tolerability of a combination of Greenlip Mussel Oil and high concentrations of EPA and DHA in Inflammatory Rheumatoid Disorders. Adv. Ther. 21(3);197-200
   
• In a multicenter trial, 54 patients with symptomatic osteoarthritis of the knee and hip were to receive GLMO at a dose of 2 capsules twice a day. After 4 and 8 weeks treatment period, the following parameters were analyzed ; Visual analogue scale, Lequesne index, Global assessment by patients, Global assessment by doctors and Adverse effects. GLMO treatment led to significant improvement in the signs and symptoms of osteoarthritis as determined by all efficacy measures. After 4 and 8 weeks treatment period, 53% and 80% of patients experienced significant pain relief and improvement of joint function. There was no proven adverse effect during this clinical trial.
  - Cho CS et al (2002): Korean Multi-Centre Study of Greenlip Mussel Oil for Patients with Osteoarthritis of the Hip and Knee. The New. Med. J. 45 (5);27-33.
   
  
•  In a series of clinical studies, the efficacy of GLM powder was evaluated in alleviating arthritic signs in dogs. The performance of GLM was investigated as a powdered supplement on top of a standard diet and when incorporated into one of two processed dietary products, a semimoist treat and a dry main meal diet. Both of these products used low-temperature manufacturing processes designed to retain the efficacy of the GLM. Total arthritic scores and scores for joint pain and joint swelling were significantly reduced following 6 wk of GLM supplementation in all three forms.
  - Bierer T.L. and L.M. Bui (2002): Improvement of Arthritic Signs in Dogs fed Green-Lipped Mussel. J. Nutr. 132:1634S-1636S.
   
• A double-blind 3-month parallel comparison of stabilized green-lipped mussel powder and green-lipped mussel oil was conducted at the Glasgow Homeopathic Hospital. Sixty patients wee invited to take part in this trial, 30 patients with classical rheumatoid arthritis and 30 with clinical and radiological evidence of osteoarthritis. Pogress was monitored by means of the articular index (AI), morning stiffness (limbering up time LUT), grip strength in each hand, pain as associated by the visual analogue scale (VA), functional index (FI) and the presence or absence of night pain. The 30 patients in each category were randomly assigned to stabilized green-lipped mussel powder (1150 mg/day) or stabilized green-lipped mussel oil (210 mg/day). Results: 76% of rheumatoid and 70% of osteoartritic patients benefited. AI, LUT and FI improved significantly by 3 months. The two preparations appaeared equally efficacious.
  - Gibson SLM, Gibson RG (1998): The treatment of arthritis with a lipid extract of Perna canaliculus: a randomized trial. Compl Ther Med 6:122-126.

GLMO is safe and effective in he management of asthma

Asthma is a chronic inflammatory disease of the airways mediated at least in part by leukotrienes and other lipid mediators. Experimental studies have shown that lipid extract of New Zealand green-lipped mussel, Perna canaliculus, is effective in inhibiting 5-lipoxygenase and cyclo-oxygenase pathways responsible for production of eicosanoids, including leukotrienes and prostaglandins. The aim of this study was to assess its effect on symptoms, peak expiratory flow (PEF) and hydrogen peroxide (H2O2) in expired breath condensate as a marker of airway inflammation in patients with steroid-naïve atopic asthma in a double-blind randomised, placebo-controlled clinical trial. Forty six patients with atopic asthma received two capsules of lipid extract or placebo b.i.d. for 8 weeks. Each capsule of lipid extract contained 50 mg v-3 polyunsaturated fatty acids and 100 mg olive oil, whereas placebo capsules ontained only 150 mg olive oil. There was a significant decrease in daytime wheeze, the concentration of exhaled H2O2 and an increase in morning PEF in the lipid extract group compared to the placebo group. There were no significant side-effects. The authors conclude that lipid extract of New Zealand green-lipped mussel may have some beneficial effect in patients with atopic asthma.

- Emelyanov E, Fedoseev G et al (2002): Treatment of asthma with a lipid extract of New Zealand green-lipped mussel: a randomised clinical trial. Eur Respir J 20; 1-5.

GLMO reduces inflammation and improves lung function in mouse model of allergic airway disease

Asthma is an inflammatory airway disease that is characterized by an influx of eosinophils to the lungs, mucus hypersecretion and T helper type 2 cytokine production. Recent dietary changes, including a decreased o-3 polyunsaturated fatty acid (PUFA) intake, may have contributed to increased asthma rates and dietary supplementation with marine oil could have clinical benefits.

To assess the effects of dietary supplementation with o-3 PUFAs on allergic inflammation and lung function using a mouse model of ovalbumin (OVA)-induced allergic airway disease (AAD).

BALB/c mice received a daily supplement of either fish oil (rich in o-3 PUFA) or lyprinol (a complex mixture of various marine lipids plus vitamin E and olive oil) before and during AAD. The effects of supplementation on AAD were assessed.
Lyprinol but not fish oil treatment reduced eosinophil influx into the bronchoalveolar lavage fluid, the lung tissue surrounding the airways and the blood, decreased mucus hypersecretion in the lung and reduced airway hyperresponsiveness (AHR). The effects of lyprinol were not associated with changes in serum IgG1 or IgG2a, or the release of IL-4, IL-5, IL-13 and IFN-g.

Conclusions Lyprinol suppresses the development of allergic inflammation and AHR in AAD. The therapeutic potential of dietary supplementation with lyprinol for asthma warrants further investigation.

- Wood LG, Hazlewood JC, Foster PS and Hansbro PM (2010): Lyprinol reduces inflammation and improves lung function in a Mouse model of allergic airways disease. Clinical & Experimental allergy 1-9

GLMO has the potential to reduce the severity and onset of Inflammatory Bowel Disease (IBD)

Twenty-three IMale C57BL/6 mice, aged 6 weeks were assigned to three treatment groups and administered GLMO, fish oil or extra virgin olive oil  via daily oral gavage, for 13 days. This study shows GLMO has the potential to reduce the severity and onset of IBD. GMO was more beneficial for treatment of colonic inflammation than fish oil , even though the optimal dose for GLMO administration may not have been achieved.

- Tenikoff D, Murphy KJ, Le M, Butler RN, Howard GS, Howe PR (2005): Greenlip Mussel Oil, a potential preventive treatment for Inflammatory Bowel Disease (IBD)?. J. Gastroenterol 2005; 40:361-365.

Why is Green-Lipped mussel OIL (GLMO) superior to Green-Lipped mussel POWDER?

•  GLMO is made according to patented processes of stabilization and extraction, which ensure a stable and standardized oil of consistently high quality.
• GLMO contains a unique complex of furan fatty acids and omega-3 fatty acids that are active against inflammation.
• The oil form makes it possible to stabilize GLMO by adding a fat-soluble antioxidant, such as vitamin E. This means that the active ingredient, the unique blend of furan fatty acids and omega-3 fatty acids, remains biologically active, even after several years.
• Green-lipped mussel powder consists of dried and ground mussels, and is therefore especially rich in proteins. In some products the shell has also been ground, which provides no benefit because the shell contains few valuable substances. In addition, much mussel powder is 'defatted', the valuable oil has largely been removed beforehand through extraction. 'Defatted' mussel powder is usually used in (supplementary) animal feeds and is much less suitable for human use.
• In powder form, the furan fatty acids and omega-3 fatty acids cannot be properly stabilized with an antioxidant. As a result, these fatty acids quickly oxidize and green-lipped mussel powder quickly loses its biological activity.
• Green-lipped mussel powder mainly contains mussel proteins, which can trigger allergic reactions in people. Asthma, for example, is primarily an allergic reaction, which puts asthma patients at greater risk of allergic reactions.
• It is often said that green-lipped mussel powder is a rich source of the so-called Glycoaminoglycans (GAGs), such as glucosamine and chondroitin. However, this is demonstrably nonsense, analysis has shown that green-lipped mussel powder contains no more than 2% of GAGs, of which probably less than 0.2% is biologically active.
• GLMO is considered a modulator of the LOX and COX pathways. The enzymes 5-lipoxygenase (LOX) and cyclooxygenase (COX) of these pathways are involved in, for example, inflammatory reactions and allergic reactions. GLMO modulates the action of these enzymes, thus calming and preventing chronic inflammatory reactions and allergic reactions.
• GLMO is therefore safe to use and has no side effects. Adults, children and animals can therefore use it safely and it does not make them drowsy or sleepy.

In short: only stabilized green-lipped mussel OIL (GLMO) contains the powerful anti-inflammatory fatty acid fractions, the biologically active component of the green-lipped mussel. Because the oil fraction contains no protein, it can also be used by people who are hypersensitive to shellfish and crustaceans. Therefore, always use green-lipped mussel OIL and never green-lipped mussel POWDER.