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New Zealand Green-Lipped Mussel

Scientific Name(s): Perna canaliculus
Common Name(s): Lyprinol (stabilized lipid extract), New Zealand green-lipped mussel, Seatone (freeze-dried preparation)

Clinical Overview

Use

Limited clinical studies suggest that Perna mussel extracts may have efficacy in the treatment of diseases with inflammatory components, such as arthritis and asthma. However, conflicting trial results have been reported.

Dosing

Limited clinical trial data are available to inform therapeutic dosing. In arthritis and asthma trials, various dosages from multi-ingredient commercial preparations have been described, making it difficult to establish dosing recommendations.

Contraindications

Hypersensitivity to shellfish. Use with caution in individuals with hepatic impairment.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Animal studies suggest that components of Perna extracts may have adverse effects on a fetus.

Interactions

None well documented.

Adverse Reactions

GI discomfort and transient worsening of arthritic pain have been noted. Hepatic dysfunction has also been recorded, but the incidence appears to be low. Long-term exposure has resulted in occupational asthma in workers in mussel processing plants.

Toxicology

No data.

Source

There are 2 green mussel species: P. canaliculus is found in the temperate waters of New Zealand, whereas Perna viridis occurs widely throughout the Indo-Pacific region, which includes Japan, Malaysia, Indonesia, and the Philippines. Green mussels are farmed commercially in Thailand and the Philippines, although New Zealand is regarded as the major exporter.FAO 1988

History

Shellfish supplements have been used as traditional remedies for arthritis, in particular by the indigenous Maori people of New Zealand. Initial studies were limited by problems in the extraction processes, as activity is lost in heat treatment or freeze drying.Brien 2008, Doggrell 2011

Chemistry

Although composition of the lipid fraction varies, possibly because of differing methods of collection, transport, and storage time, it is usually approximately 8% of the freeze-dried weight.Murphy 2003 Triglycerides form the largest fraction, followed by free fatty acids, sterols, and phospholipids. Low levels of sterol esters are found in some samples. Fatty acids are predominantly polyunsaturated, mostly in the form of omega-3 (40% of total polyunsaturated fatty acids). Omega-6 fatty acids are present at far lower levels (about 5% of total polyunsaturated fatty acids). The major identified fatty acids are docosahexaenoic, eicosapentaenoic, and palmitic acids. Cholesterol is the major sterol (31% of total sterols), with smaller proportions of desmosterol/brassicasterol, 24-methylenecholesterol, trans-22-dehydrocholesterol, nordehydrocholesterol, and occelastrol.Murphy 2003 Glycosaminoglycans, a group of unbranched carbohydrates of high molecular weight, are also present; chondroitin sulfate is of particular interest.

Pernin, a nonpigmented glycosylated protein, has been identified in the Perna mussel, and is rich in histidine and aspartic acid. Potential functions for this protein may be in binding divalent cations and serine protease inhibition.Scotti 2001 Freeze-dried Perna mussel powder contains the amino acids glutamine and methionine, vitamins E and C, and the minerals zinc, copper, and manganese.Bierer 2002 The preparation Seatone is a freeze-dried, concentrated powder of Perna lipid extract, while Lyprinol is a stabilized, super-critical fluid extract preparation containing the omega-3 essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).Brien 2008, Emelyanov 2002

Uses and Pharmacology

Anti-inflammatory/Arthritis

In vitro studies demonstrate anti-inflammatory activity via inhibition of the metabolism of arachidonate and reduced formation of leukotrienes and prostaglandins. In vitro modulation of leukotrienes, cytokines, and immunoglobulin has been demonstrated. Such effects, as well as the inhibition of lipoxygenase and cyclooxygenase enzymes, are attributed largely to the polyunsaturated fatty acid content.Emelyanov 2002, Mani 2006, McPhee 2007, Treschow 2007 In addition, contribution of the chondroitin sulfate content, a major component of cartilage matrix and synovial fluid, is of interest.Bierer 2002

Animal data

Studies in rats with adjuvant-induced arthritis or with carrageenan-induced footpad swelling have generally demonstrated positive anti-inflammatory effects, as measured by cytokine and splenocyte protein expression, radiology, paw swelling, and pain scores.Lawson 2007, Lee 2008, Lee 2009, Miller 1980, Rainsford 1980, Singh 2008 Methodological issues regarding route of administration and differing preparations used have been noted.

Limited studies in dogs with arthritis have been conducted with P. canaliculus preparations, with reductions in total arthritic scores observed.Bierer 2002, Hielm-Bjorkman 2009 Improvements in long-term pain and radiological assessments suggest efficacy is less than that with traditional nonsteroidal anti-inflammatory drugs (NSAIDs) but greater than with placebo, indicating a possible place in therapy when NSAIDS are contraindicated.Hielm-Bjorkman 2009

Clinical data

Two systematic reviews have been published: one reviewing osteoarthritis and rheumatoid arthritis trials through 2005 and including a highly publicized 1980 trial that reported benefits in patients with rheumatoid arthritis and osteoarthritis,Cobb 2006, Gibson 1980 and the other including only osteoarthritis trials through 2007.Brien 2008, Gibson 1980 Generally, clinical trials investigating the use of Perna mussel extracts in arthritis are small and methodologically weak due to a lack of consistency in product potency and dosing, an absence of placebo or comparator, or use of active placebo. Despite biological plausibility and limited evidence of efficacy in animal studies, there is little compelling evidence to support a therapeutic role for Perna extracts in the treatment or prevention of arthritis. However, the extract may have a place as adjunctive therapy, because some studies report analgesic effects.Brien 2008, Cobb 2006, Doggrell 2011 More recent studies have used a standardized green-lipped mussel lipid extract, PCSO-524; however, results remain equivocal. In a small blinded, randomized, comparator trial, 50 patients older than 50 years with osteoarthritis of the knee and/or hip randomly received Lyprinol (50 mg of PCSO-524 with EPA 5.2% and DHA 3.4%) or fish oil (EPA 18%, DHA 12%) for 12 weeks. Benefit was documented with PCSO-524 for pain scores, subjective health assessment categories, and overall health.Zawadzki 2013 In contrast, a 12-week, randomized, double-blind, placebo-controlled trial in patients with hip or knee osteoarthritis (N=80) demonstrated no benefits (based on pain scores) with use of 600 mg daily of Biolex-GLM, a green-lipped mussel extract enriched with N-acylethanolamine and long-chain omega-3 fatty acids. However, acetaminophen use remained lower in the treatment group during the postintervention phase compared with the placebo group.Stebbings 2017 A small industry-sponsored, uncontrolled pilot study conducted in 23 patients with osteoarthritis of the knee reported improvements in pain, stiffness, and physical function scores at 4 and 8 weeks with daily supplementation of a proprietary blend of freeze-dried P. canaliculus mussel meat (GlycOmega PLUS; 3,000 mg/day). GI function was assessed as a secondary outcome and found to be improved during the first 4 weeks only. Adverse events included 4 cases of reflux, abdominal pain, and/or diarrhea.Coulson 2012 The GlycOmega PLUS proprietary blend was then compared with glucosamine in a 12-week nonblinded, randomized study (N=40); however, the primary outcome of this subsequent trial was assessment of the effects of supplementation with green-lipped mussel or glucosamine sulphate on common GI tract microbial genera in patients with knee osteoarthritis. Furthermore, the study investigated whether bacterial growth patterns could be correlated to therapeutic efficacy outcomes with green-lipped mussel and glucosamine sulphate. No differences were found in microbiota from baseline in either group, but both groups demonstrated improvements in GI symptoms scores, with no difference between groups. Additionally, both groups experienced changes from baseline in arthritis scores for pain, stiffness, and physical function, with glucosamine providing significant improvement in stiffness compared with the green-lipped muscle group (P=0.02).Coulson 2013

Asthma

Leukotrienes are mediators of airway inflammation in asthma that induce bronchoconstriction and increase mucus secretion and microvascular permeability, allowing infiltration of inflammatory cells (eg, eosinophils, neutrophils) into the airway. Perna mussel extract is thought to prevent this cascade by inhibiting leukotriene production.Emelyanov 2002

Animal data

In a mouse model of allergic airways disease, Perna extract improved lung function compared with fish oil, with positive changes in mucus hypersecretion and airway responsiveness.Wood 2010

Clinical data

Daytime wheezing was reduced in corticosteroid-naive patients with mild to moderate atopic asthma who received stabilized Perna mussel extract.Scotti 2001 In a study of 46 patients with atopic asthma, morning peak expiratory flow (PEF) was increased in those receiving mussel extract (Lyprinol) compared with those receiving placebo. However, mean forced expiratory volume in the first second of expiration (FEV1) and evening PEF did not differ between the 2 groups.Doggrell 2011, Emelyanov 2002 A small double-blind, randomized, placebo-controlled, crossover trial enrolled 20 adults with mild to moderate asthma to evaluate the effect of an extract of stabilized marine lipids from New Zealand green-lipped mussels (PCSO-524; Lyprinol/Omega XL) on hyperpnea-induced bronchoconstriction. PCSO-524 (comprised of 50 mg of omega-3 [n-3] fatty acids, including EPA 72 mg and DHA 48 mg plus olive oil 100 mg) or placebo (olive oil 150 mg) was administered for 3 weeks, with a 2-week washout between treatments. Although no difference was observed in bronchodilator use, improvement in mean asthma scores occurred with PCSO-524 compared with usual diet and placebo (P<0.001 each). Similarly, morning and evening peak flow was also increased with treatment (386.3 L/min) compared with both usual diet (370.4 L/min; P=0.001) and placebo (364.5 L/min; P<0.001). Attenuation of hyperpnea-induced bronchoconstriction was reflected by a significantly lower maximum percentage drop in FEV1 with treatment (−8.4%) compared with usual (−19.3%) and placebo diets (−22.5%) (P<0.001 each). Similar results were observed in several other pulmonary function parameters. Rescue medication use was also reduced with PCSO-524.Mickleborough 2013

Cancer

Animal data

A study in rats found a limited effect of Lyprinol in preventing chemotherapy-induced intestinal mucositis.Torres 2008

Clinical data

In a small dose-escalation study (N=17), no evidence of tumor response was observed in advanced breast or prostate cancer patients.Sukumaran 2010 Claims of efficacy in the treatment of cancer are unsubstantiated by clinical trials.Doggrell 2011

Dysmenorrhea

Experimental data

In an ex vivo rat dysmenorrhea model, Perna mussel extract modified the spontaneous and oxytocin-induced contractions of the uterus. Use of Perna mussel as an adjunct to standard therapy with NSAIDs for dysmenorrhea has been suggested.Shiels 2000

GI effects

Animal data

Mice with induced colitis receiving Perna mussel extract showed less weight loss, lower disease activity index scores, smaller crypt area losses in the distal colon, and lower cecum and colon weights than placebo recipients.Tenikoff 2004 In rats, oral coadministration of the mussel lipid fraction with aspirin, indomethacin, tolmetin, or diclofenac reduced gastric mucosal damage caused by these drugs up to 100%.Rainsford 1980

Dosing

Limited clinical trial data are available to inform therapeutic dosing.

In arthritis and asthma trials, various dosages from multi-ingredient commercial preparations have been described, making it difficult to establish dosing recommendations.Coulson 2012, Doggrell 2011, Mickleborough 2013, Stebbings 2017, Zawadzki 2013

Pregnancy / Lactation

An extract of Perna mussel has been shown to modify spontaneous and oxytocin-induced contractions of the uterus.Shiels 2000 Proprietary preparations of mussel extract fed to pregnant rats slowed fetal development and delayed parturition (the action of giving birth), suggesting the presence of an orally active prostaglandin inhibitor.Green 1981 Other prostaglandin inhibitors, such as aspirin, indomethacin, and naproxen, are known to interfere with ovulation and prolong gestation periods in rats. The clinical importance of these findings is unclear.

Interactions

None well documented.

Adverse Reactions

Studies with Perna mussel and its extracts have reported a low incidence of adverse effects, generally consisting of GI symptoms (eg, diarrhea, flatulence, nausea) and transient worsening of arthritic pain.Cho 2003, Green 1981, Sukumaran 2010 In a dose-escalation study with Lyprinol, liver function abnormalities were noted in one patient who had normal liver function at the start of the study.Sukumaran 2010 In an older publication, granulomatous hepatitis, jaundice, colicky epigastric pain, anorexia, and malaise were described in a 64-year-old woman taking Perna mussel.Green 1981

Symptoms suggestive of occupational asthma and lung function abnormalities, possibly an immunoglobulin E–mediated allergic reaction, have been reported in workers in green-lipped mussel processing plants.Glass 1998

Toxicology

Information regarding toxicity is limited. Neurotoxic food poisoning has been reported from the consumption of fresh Perna shellfish; however, immersion for at least 3 minutes in boiling water has been shown to decrease the risks of viral food-borne infections, such as hepatitis A and norovirus.Hewitt 2006, Ishida 2004 Heavy metal exposure from Perna consumption has been estimated to be below accepted maximum limits.Whyte 2009 In a study evaluating the efficacy of Perna extracts in rats, no changes in organ weight or histological or biochemical changes were noted.Singh 2008

References

Bierer TL, Bui LM. Improvement of arthritic signs in dogs fed green-lipped mussel (Perna canaliculus). J Nutr. 2002;132(6)(suppl 2):S1634-S1636.12042477
Brien S, Prescott P, Coghlan B, Bashir N, Lewith G. Systematic review of the nutritional supplement Perna canaliculus (green-lipped mussel) in the treatment of osteoarthritis. QJM. 2008;101(3):167-179.18222988
Cho SH, Jung YB, Seong SC, et al. Clinical efficacy and safety of Lyprinol, a patented extract from New Zealand green-lipped mussel (Perna canaliculus) in patients with osteoarthritis of the hip and knee: a multicenter 2-month clinical trial. Eur AnnAllerg Clin Immunol. 2003;35(6):212-216.12872680
Cobb CS, Ernst E. Systematic review of a marine nutriceutical supplement in clinical trials for arthritis: the effectiveness of the New Zealand green-lipped mussel Perna canaliculus. Clin Rheumatol. 2006;25(3):275-284.16220229
Coulson S, Vecchio P, Gramotnev H, Vitetta L. Green-lipped mussel (Perna canaliculus) extract efficacy in knee osteoarthritis and improvement in gastrointestinal dysfunction: a pilot study. Inflammopharmacology. 2012;20(2):71-76.22366869
Coulson S, Butt H, Vecchio P, Gramotnev H, Vitetta L. Green-lipped mussel extract (Perna canaliculus) and glucosamine sulphate in patients with knee osteoarthritis: therapeutic efficacy and effects on gastrointestinal microbiota profiles. Inflammopharmacology. 2013;21(1):79-90.22821424
Doggrell SA. Lyprinol—is it a useful anti-inflammatory agent? Evid Based Complement Alternat Med. 2011;2011:307121.
Emelyanov A, Fedoseev G, Krasnoschekova O, Abulimity A, Trendeleva T, Barnes PJ. Treatment of asthma with lipid extract of New Zealand green-lipped mussel: a randomised clinical trial. Eur Respir J. 2002;20(3):596-600.12358334
Food and Agriculture Organization of the United Nations. Yearbook of Fishery Statistics: Catches and landings. Vol. 62. Rome, Italy: FAO; 1988.
Gibson RG, Gibson SL, Conway V, Chappell D. Perna canaliculus in the treatment of arthritis. Practitioner. 1980;224(1347):955-960.7003577
Glass WI, Power P, Burt R, Fishwick D, Bradshaw LM, Pearce NE. Work-related respiratory symptoms and lung function in New Zealand mussel openers. Am J Ind Med. 1998;34(2):163-168.9651626
Green-lipped mussel extract in arthritis. Lancet. 1981;1(8211):85.6109130
Hewitt J, Greening GE. Effect of heat treatment on hepatitis A virus and norovirus in New Zealand greenshell mussels (Perna canaliculus) by quantitative real-time reverse transcription PCR and cell culture. J Food Prot. 2006;69(9):2217-2223.16995527
Hielm-Björkman A, Tulamo RM, Salonen H, Raekallio M. Evaluating complementary therapies for canine osteoarthritis part I: green-lipped mussel (Perna canaliculus). Evid Based Complement Alternat Med. 2009;6(3):365-373.18955269
Ishida H, Nozawa A, Nukaya H, Tsuji K. Comparative concentrations of brevetoxins PbTx-2, PbTx-3, BTX-B1 and BTX-B5 in cockle, Austrovenus stutchburyi, greenshell mussel, Perna canaliculus, and Pacific oyster, Crassostrea gigas, involved neurotoxic shellfish poisoning in New Zealand. Toxicon. 2004;43(7):779-789.15284012
Lawson BR, Belkowski SM, Whitesides JF, Davis P, Lawson JW. Immunomodulation of murine collagen-induced arthritis by N, N-dimethylglycine and a preparation of Perna canaliculus. BMC Complement Altern Med. 2007;7:20.17562016
Lee CH, Butt YK, Wong MS, Lo SC. Differential protein expression induced by a lipid extract of Perna canaliculus in splenocytes of rats with adjuvant-induced arthritis. Inflammopharmacology. 2008;16(4):188-194.18759077
Lee CH, Lum JH, Ng CK, et al. Pain controlling and cytokine-regulating effects of Lyprinol, a lipid extract of Perna Canaliculus, in a rat adjuvant-induced arthritis model. Evid Based Complement Alternat Med. 2009;6(2):239-245.18955235
Mani S, Lawson JW. In vitro modulation of inflammatory cytokine and IgG levels by extracts of Perna canaliculus. BMC Complement Altern Med. 2006;6:1.16412227
McPhee S, Hodges LD, Wright PF, et al. Anti-cyclooxygenase effects of lipid extracts from the New Zealand green-lipped mussel, Perna canaliculus. Comp Biochem Physiol B Biochem Mol Biol. 2007;146(3):346-356.17197217
Mickleborough TD, Vaughn CL, Shei RJ, Davis EM, Wilhite DP. Marine lipid fraction PCSO-524 (lyprinol/omega XL) of the New Zealand green lipped mussel attenuates hyperpnea-induced bronchoconstriction in asthma. Respir Med. 2013;107(8):1152-1163.23660397
Miller TE, Ormrod D. The anti-inflammatory activity of Perna canaliculus (NZ green lipped mussel). N Z Med J. 1980;92(667):187-193.6933356
Murphy KJ, Mann NJ, Sinclair AJ. Fatty acid and sterol composition of frozen and freeze-dried New Zealand green lipped mussel (Perna canaliculus) from three sites in New Zealand. Asia Pac J Clin Nutr. 2003;12(1):50-60.12737011
Rainsford KD, Whitehouse MW. Gastroprotective and anti-inflammatory properties of green lipped mussel (Perna canaliculus) preparation. Arzneimittelforschung. 1980;30(12):2128-2132.7194074
Scotti PD, Dearing SC, Greenwood DR, Newcomb RD. Pernin: a novel, self-aggregating haemolymph protein from the New Zealand green-lipped mussel, Perna canaliculus (Bivalvia: Mytilidae). Comp Biochem Physiol B Biochem Mol Biol. 2001;128(4):767-779.11290459
Shiels IA, Whitehouse MW. Lyprinol: anti-inflammatory and uterine-relaxant activities in rats, with special reference to a model for dysmenorrhoea. Allerg Immunol (Paris). 2000;32(7):279-283.11094641
Singh M, Hodges LD, Wright PF, et al The CO2-SFE crude lipid extract and the free fatty acid extract from Perna canaliculus have anti-inflammatory effects on adjuvant-induced arthritis in rats. Comp Biochem Physiol B Biochem Mol Biol. 2008;149(2):251-258.17931921
Stebbings S, Gray A, Schneiders AG, Sansom A. A randomized double-blind placebo-controlled trial to investigate the effectiveness and safety of a novel green-lipped mussel extract -BioLex- for managing pain in moderate to severe osteoarthritis of the hip and knee. BMC Complement Altern Med. 2017;17(1):416.28830491
Sukumaran S, Pittman KB, Patterson WK, et al. A phase I study to determine the safety, tolerability and maximum tolerated dose of green-lipped mussel (Perna canaliculus) lipid extract, in patients with advanced prostate and breast cancer. Ann Oncol. 2010;21(5):1089-1093.19846468
Tenikoff D, Murphy KJ, Le M, Butler RN, Howarth GS, Howe PR. Lyprinol: a potential preventive treatment for experimental inflammatory bowel disease (IBD). Asia Pac J Clin Nutr. 2004;13(suppl):S94.
Torres DM, Tooley KL, Butler RN, Smith CL, Geier MS, Howarth GS. Lyprinol only partially improves indicators of small intestinal integrity in a rat model of 5-fluorouracil-induced mucositis. Cancer Biol Ther. 2008;7(2):295-302.18059190
Treschow AP, Hodges LD, Wright PF, Wynne PM, Kalafatis N, Macrides TA. Novel anti-inflammatory omega-3 PUFAs from the New Zealand green-lipped mussel, Perna canaliculus. Comp Biochem Physiol B Biochem Mol Biol. 2007;147(4):645-656.17543561
Whyte AL, Hook GR, Greening GE, Gibbs-Smith E, Gardner JP. Human dietary exposure to heavy metals via the consumption of greenshell mussels (Perna canaliculus Gmelin 1791) from the Bay of Islands, northern New Zealand. Sci Total Environ. 2009;407(14):4348-4355.19419753
Wood LG, Hazlewood LC, Foster PS, Hansbro PM. Lyprinol reduces inflammation and improves lung function in a mouse model of allergic airways disease. Clin Exp Allergy. 2010;40(12):1785-1793.20412134
Zawadzki M, Janosch C, Szechinski J. Perna canaliculus lipid complex PCSO-524 demonstrated pain relief for osteoarthritis patients benchmarked against fish oil, a randomized trial, without placebo control. Mar Drugs. 2013;11(6):1920-1935.23739042

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

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