New Zealand green-lipped mussel

New Zealand green-lipped mussel

New Zealand green-lipped mussel

Clinical overview

Use

dosage

Only limited data from clinical studies are available regarding therapeutic dosage. Studies on arthritis and asthma have reported varying dosages from commercial multi-ingredient preparations, making it difficult to establish dosage recommendations.

Contraindications

Hypersensitivity to shellfish. Use with caution in people with impaired liver function.

Pregnancy/breastfeeding

Avoid using. There is a lack of information on safety and effectiveness during pregnancy and breastfeeding. Animal studies suggest that components of Perna extracts may have harmful effects on the fetus.

Interactions

None are well documented.

Side effects

Gastrointestinal discomfort and temporary worsening of arthritic pain were noted. Hepatic impairment has also been observed, but the frequency appears to be low. Long-term exposure has caused occupational asthma in shellfish processing workers.

toxicology

No data.

Scientific family

• Mytilidae

source

There are two species of green mussels: P. canaliculus is found in the temperate waters of New Zealand, while Perna viridis is widespread throughout the Indo-Pacific region, which includes Japan, Malaysia, Indonesia and the Philippines. Green mussels are farmed commercially in Thailand and the Philippines, with New Zealand considered the largest exporter.FAO 1988

Story

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

Chemistry

Although the composition of the lipid fraction varies, possibly due to different collection, transportation and storage time methods, it is usually about 8% of the freeze-dried weight. Murphy 2003 Triglycerides form the largest fraction, followed by free fatty acids, sterols and phospholipids. Small amounts 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 in much smaller amounts (about 5% of total polyunsaturated fatty acids). The main fatty acids identified are docosahexaenoic acid, eicosapentaenoic acid and palmitic acid. Cholesterol is the major sterol (31% of all sterols), with smaller amounts of desmosterol/brassicasterol, 24-methylene cholesterol, trans-22-dehydrocholesterol, nordehydrocholesterol and occelastrol. Murphy 2003 Glycosaminoglycans, a group of high molecular weight unbranched carbohydrates, are also present; Chondroitin sulfate is of particular interest.

Pernin, a non-pigmented glycosylated protein, has been identified in the Perna mussel and is rich in histidine and aspartic acid. Possible functions of this protein could be in the binding of divalent cations and the inhibition of serine protease.Scotti 2001 Freeze-dried Perna mussel powder contains the amino acids glutamine and methionine, the vitamins E and C as well as the minerals zinc, copper and manganese.Bierer 2002 preparation Seatone is a freeze-dried, concentrated powder made from Perna lipid extract, while Lyprinol is a stabilized, is a supercritical liquid extract preparation containing the essential omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).Brien 2008, Jemeljanow 2002

Use and Pharmacology

Anti-inflammatory/arthritis

In vitro studies demonstrate an anti-inflammatory effect by inhibiting the metabolism of arachidonate and reducing the formation of leukotrienes and prostaglandins. Modulation of leukotrienes, cytokines and immunoglobulins has been demonstrated in vitro. Such effects, as well as the inhibition of the enzymes lipoxygenase and cyclooxygenase, are largely attributed to the polyunsaturated fatty acid content. Emelyanov 2002, Mani 2006, McPhee 2007, Treschow 2007 In addition, the content of chondroitin sulfate, a major component of cartilage, contributes to matrix and synovial fluid, of interest.Bierer 2002

Animal data

Studies in rats with adjuvant-induced arthritis or with carrageenan-induced footpad swelling have generally shown 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 problems have been identified regarding the route of administration and the different preparations used.

Limited studies have been conducted in dogs with arthritis using P. canaliculus preparations, with reductions in overall arthritis scores observed. Bierer 2002, Hielm-Bjorkman 2009 Improvements in long-term pain and radiological studies suggest that the effectiveness is less than that of conventional non-steroidal anti-drugs. anti-inflammatory drugs (NSAIDs), but greater than placebo, indicating a possible place in therapy when NSAIDS are contraindicated. Hielm-Bjorkman 2009

Clinical data

Two systematic reviews were published: one that examined studies on osteoarthritis and rheumatoid arthritis up to 2005 and included a high-profile 1980 study reporting benefits in patients with rheumatoid arthritis and osteoarthritis (Cobb 2006, Gibson 1980), and the other that only included studies on osteoarthritis up to 2007, Brien 2008, Gibson 1980 In general, clinical trials investigating the use of Perna mussel extracts in arthritis are small and methodologically weak due to inconsistent product efficacy and dosage, lack of a placebo or comparator, or use of an active placebo. Despite biological plausibility and limited evidence of effectiveness in animal studies, there is little convincing evidence for a therapeutic role for Perna extracts in treating or preventing arthritis. However, the extract can be used as adjunctive therapy as 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, the results remain unclear. In a small, blinded, randomized comparative study, 50 patients over 50 years of age with osteoarthritis of the knee and/or hip were randomly assigned to receive Lyprinol (50 mg PCSO-524 with EPA 5.2% and DHA 3.4%) or fish oil (EPA 18). %, DHA 12%) for 12 weeks. Benefits were documented using PCSO-524 for pain scores, subjective health assessment categories, and general health status. Zawadzki 2013 In contrast, a 12-week, randomized, double-blind, placebo-controlled trial in patients with hip or knee osteoarthritis (N=80) showed no benefits (based on pain scores) from daily ingestion of 600 mg of Biolex-GLM, a green-lipped mussel extract, enriched with N-acylethanolamine and long-chain omega-3 fatty acids. However, acetaminophen consumption remained lower in the treatment group during the postintervention period compared to 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 was found to improve only in the first 4 weeks. Adverse events included 4 cases of reflux, abdominal pain and/or diarrhea. Coulson 2012 The proprietary blend GlycOmega PLUS was then compared to glucosamine in a 12-week, non-blinded, randomized trial (N=40); However, the primary outcome of this subsequent study was to evaluate the effects of green-lipped mussel or glucosamine sulfate supplementation on common gastrointestinal microbial genera in patients with knee osteoarthritis. In addition, the study examined whether bacterial growth patterns could correlate with the therapeutic effectiveness of green-lipped mussel and glucosamine sulfate. No differences in microbiota from baseline were found in either group, but both groups showed improvements in GI symptom scores, with no difference between groups. In addition, there were changes from baseline in arthritis scores for pain, stiffness, and physical function in both groups, with glucosamine resulting in a significant improvement in stiffness compared to 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 the infiltration of inflammatory cells (e.g., eosinophils, neutrophils) into the airways. Perna mussel extract is thought to prevent this cascade by inhibiting leukotriene production. Emelyanov 2002

Animal data

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

Clinical data

Daytime wheezing was reduced in corticosteroid-naïve 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 who received mussel extract (Lyprinol) compared to those who received a placebo. However, mean forced expiratory volume in the first second of expiration (FEV1) and evening PEF did not differ between the two groups.Doggrell 2011, Emelyanov 2002. A small double-blind, randomized, placebo-controlled crossover study enrolled 20 adults with mild to moderate lung disease to evaluate the effects of an extract of stabilized marine lipids from New Zealand green-lipped mussels (PCSO-524; Lyprinol/Omega XL) on bronchoconstriction caused by hyperpnea. PCSO-524 (consisting 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) were administered for 3 weeks, with a 2-week washout period between treatments. Although no difference was observed with bronchodilator use, there was an improvement in mean asthma scores with PCSO-524 compared to regular diet and placebo (both P < 0.001). Likewise, peak morning and evening flow was increased by treatment (386.3 L/min) compared to usual diet (370.4 L/min; p = 0.001) and placebo (364.5 l/min; p < 0.001). The attenuation of bronchoconstriction caused by hyperpnea was reflected in a significantly smaller maximum percentage decrease in FEV1 with treatment (−8.4%) compared to usual (−19.3%) and placebo diets (−22.5%) (both P < 0.001). Similar results were observed for several other pulmonary function parameters. The use of emergency medication was also reduced with PCSO-524.Mickleborough 2013

Cancer

Animal data

A study in rats found a limited effect of lyprinol in preventing intestinal mucosal inflammation caused by chemotherapy.Torres 2008

Clinical data

In a small dose escalation study (N=17), no evidence of tumor response was observed in patients with advanced breast or prostate cancer. Sukumaran 2010 Claims of effectiveness in treating cancer are not supported by clinical trials. Doggrell 2011

Dysmenorrhea

Experimental data

In an ex vivo dysmenorrhea model in rats, Perna mussel extract altered spontaneous and oxytocin-induced uterine contractions. The use of Perna mussels as an adjunct to standard therapy with NSAIDs for dysmenorrhea has been suggested.Shiels 2000

GI effects

Animal data

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

dosage

Only limited data from clinical studies are available regarding therapeutic dosage.

Studies on arthritis and asthma have reported different dosages from multi-ingredient commercial preparations, making it difficult to make dosage recommendations. Coulson 2012, Doggrell 2011, Mickleborough 2013, Stebbings 2017, Zawadzki 2013

Pregnancy/breastfeeding

Perna mussel extract has been shown to alter 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 process of giving birth), indicating the presence of a...orally active prostaglandin inhibitors.Green 1981 Other prostaglandin inhibitors such as aspirin, indomethacin and naproxen are known to impair ovulation and prolong gestation in rats. The clinical significance of these results is unclear.

Interactions

None are well documented.

Side effects

Studies with Perna mussels and their extracts have reported a low frequency of adverse reactions, generally consisting of gastrointestinal symptoms (e.g., diarrhea, bloating, nausea) and a temporary worsening of arthritic pain. Cho 2003, Green 1981, Sukumaran 2010 In a dose escalation study with Lyprinol, liver dysfunction was noted in a patient who had normal liver function at the start of the study. year old woman taking Perna mussel.Green 1981

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

toxicology

Toxicity information is limited. Neurotoxic food poisoning has been reported when consuming fresh Perna shellfish; However, immersion in boiling water for at least 3 minutes has been shown to reduce the risk of viral food-borne infections such as hepatitis A and norovirus. Hewitt 2006, Ishida 2004 Heavy metal contamination from Perna consumption is estimated to be below the accepted maximum limits.Whyte 2009 In a study evaluating the effectiveness of Perna extracts in rats, no changes in organ weight or histological or biochemical changes were found.Singh 2008

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been evaluated for safety or effectiveness by the FDA and is not subject to the quality and safety information collection standards that apply to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not confirm that this product is safe, effective, or approved to treat any patient or medical condition. This is just a brief summary of general information about this product. It does NOT contain all information about the possible uses, instructions, warnings, precautions, interactions, side effects or risks that may apply to this product. This information does not constitute specific medical advice and does not replace the information you receive from your healthcare provider. You should speak to your doctor to get complete information about the risks and benefits of using this product.

This product may interact negatively with certain health and medical conditions, other prescription and over-the-counter medications, foods or other dietary supplements. This product may be unsafe if used before surgery or other medical procedures. It is important to fully inform your doctor about the herbs, vitamins, minerals, or other supplements you are taking before any surgery or medical procedure. With the exception of certain products generally considered safe in normal amounts, including the use of folic acid and prenatal vitamins during pregnancy, this product has not been adequately studied to determine whether it is safe for use during pregnancy, breastfeeding, or in those younger than 2 years of age.

Bierer TL, Bui LM. Improvement in arthritic symptoms in dogs fed green-lipped mussels (Perna canaliculus). J Nutr. 2002;132(6)(suppl 2):S1634-S1636.12042477Brien S, Prescott P, Coghlan B, Bashir N, Lewith G. Systematic review of the dietary supplement Perna canaliculus (green-lipped mussel) in the treatment of osteoarthritis. QJM. 2008;101(3):167-179.18222988Cho SH, Jung YB, Seong SC, et al. Clinical efficacy and safety of Lyprinol, a patented extract of New Zealand green-lipped mussel (Perna canaliculus), in patients with osteoarthritis of the hip and knee: a multicenter two-month clinical trial. Your AnnAllerg Clin Immunol. 2003;35(6):212-216.12872680Cobb CS, Ernst E. Systematic review of a marine dietary supplement in clinical trials for arthritis: the effectiveness of the New Zealand green-lipped mussel Perna canaliculus. Rheumatol Clinic. 2006;25(3):275-284.16220229Coulson S, Vecchio P, Gramotnev H, Vitetta L. Efficacy of green-lipped mussel (Perna canaliculus) extract in knee osteoarthritis and improvement of gastrointestinal dysfunction: a pilot study. Inflammatory pharmacology. 2012;20(2):71-76.22366869Coulson S, Butt H, Vecchio P, Gramotnev H, Vitetta L. Green-lipped mussel extract (Perna canaliculus) and glucosamine sulfate in patients with knee osteoarthritis: therapeutic efficacy and effects on gastrointestinal microbiota profiles. Inflammatory pharmacology. 2013;21(1):79-90.22821424Doggrell 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 New Zealand green-lipped mussel lipid extract: a randomized clinical trial. Eur Respir J. 2002;20(3):596-600.12358334Food and Agriculture Organization of the United Nations. Fisheries Statistics Yearbook: 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):955-960.7003577Glass WI, Power P, Burt R, Fishwick D, Bradshaw LM, Pearce NE. Work-related respiratory symptoms and lung function in New Zealand clam openers. Bin J Ind Med. 1998;34(2):163-168.9651626Green-lipped mussel extract for arthritis. Lancet. 1981;1(8211):85.6109130Hewitt 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 protection. 2006;69(9):2217-2223.16995527Hielm-Björkman A, Tulamo RM, Salonen H, Raekallio M. Evaluation of complementary therapies for canine osteoarthritis Part I: Green-lipped mussel (Perna canaliculus). Evid Based Complement Alternat Med. 2009;6(3):365-373.18955269Ishida H, Nozawa A, Nukaya H, Tsuji K. Comparative concentrations of the brevetoxins PbTx-2, PbTx-3, BTX-B1 and BTX-B5 in cockles, Austrovenus stutchburyi, greenshell mussels, Perna canaliculus and the Pacific oyster Crassostrea gigas caused neurotoxic shellfish poisoning in New Zealand. Toxicone. 2004;43(7):779-789.15284012Lawson BR, Belkowski SM, Whitesides JF, Davis P, Lawson JW. Immunomodulation of murine collagen-induced arthritis by N,N-dimethylglycine and a preparation from Perna canaliculus. BMC Komplement Altern Med. 2007;7:20.17562016Lee CH, Butt YK, Wong MS, Lo SC. Differential protein expression induced by a lipid extract of Perna canaliculus in splenocytes from rats with adjuvant-induced arthritis. Inflammatory pharmacology. 2008;16(4):188-194.18759077Lee CH, Lum JH, Ng CK, et al. Pain-relieving and cytokine-regulating effects of lyprinol, a lipid extract of Perna canaliculus, in an adjuvant-induced arthritis model in rats. Evid Based Complement Alternat Med. 2009;6(2):239-245.18955235Mani S, Lawson JW. In vitro modulation of inflammatory cytokine and IgG levels by extracts of Perna canaliculus. BMC Complement Altern Med. 2006;6:1.16412227McPhee S, Hodges LD, Wright PF, et al. Anti-cyclooxygenase effect of lipid extracts from the New Zealand green-lipped mussel Perna canaliculus. Comp Biochem Physiol B Biochem Mol Biol. 2007;146(3):346-356.17197217Mickleborough TD, Vaughn CL, Shei RJ, Davis EM, Wilhite DP. The marine lipid fraction PCSO-524 (Lyprinol/Omega XL) of the New Zealand green-lipped mussel alleviates bronchoconstriction caused by hyperpnea in asthma. Respir Med. 2013;107(8):1152-1163.23660397Miller TE, Ormrod D. The anti-inflammatory effect of Perna canaliculus (New Zealand green-lipped mussel). NZ Med J 1980;92(667):187-193.6933356Murphy KJ, Mann NJ, Sinclair AJ. Fatty acid and sterol composition of frozen and freeze-dried New Zealand green-lipped mussel (Perna canaliculus) from three locations in New Zealand. Asia Pacific J Clin Nutr. 2003;12(1):50-60.12737011Rainsford KD, Whitehouse MW. Gastroprotective and anti-inflammatory properties of green-lipped mussel preparation (Perna canaliculus). Drug research. 1980;30(12):2128-2132.7194074Scotti PD, Dearing SC, Greenwood DR, Newcomb RD. Pernin: a novel, self-aggregating hemolymph protein from the New Zealand green-lipped mussel Perna canaliculus (Bivalvia: Mytilidae). Comp Biochem Physiol B Biochem Mol Biol. 2001;128(4):767-779.11290459Shiels IA, Whitehouse MW. Lyprinol: anti-inflammatory and uterine relaxant effects in rats, with particular reference to a model of dysmenorrhea. Allerg Immunol (Paris). 2000;32(7):279-283.11094641Singh M, Hodges LD, Wright PF, et al. The CO2-SFE crude lipid extract and free fatty acid extract from Perna canaliculus have anti-inflammatory effects in adjuvant-induced arthritis in rats. Comp Biochem Physiol B Biochem Mol Biol. 2008;149(2):251-258.17931921Stebbings S, Gray A, Schneiders AG, Sansom A. A randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of a novel green-lipped mussel extract - BioLex - for the treatment of pain in moderate to severe osteoarthritis of the hip and knee. BMC Complement Altern Med. 2017;17(1):416.28830491Sukumaran 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):1089-1093.19846468Tenikoff D, Murphy KJ, Le M, Butler RN, Howarth GS, Howe PR. Lyprinol: a potential preventative treatment for experimental inflammatory bowel disease (IBD). Asia Pacific 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):295-302.18059190Treschow 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):645-656.17543561Whyte AL, Hook GR, Greening GE, Gibbs-Smith E, Gardner JP. Human exposure to heavy metals through consumption of green-shell mussels (Perna canaliculus Gmelin 1791) from the Bay of Islands in northern New Zealand. Sci Total Environ. 2009;407(14):4348-4355.19419753Wood LG, Hazlewood LC, Foster PS, Hansbro PM. Lyprinol reduces inflammation and improves lung function in a mouse model of allergic airway disease. Clin Exp Allergy. 2010;40(12):1785-1793.20412134Zawadzki M, Janosch C, Szechinski J. The Perna canaliculus lipid complex PCSO-524 showed pain relief in osteoarthritis patients compared to fish oil, a randomized trial without placebo control. Mar drugs. 2013;11(6):1920-1935.23739042

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