New Zealand Green-Lipped Mussel

Scientific Name(s): Perna canaliculus . Family: Mytilidae

Common Name(s): New Zealand Green-Lipped Mussel ( NZGLM )

Clinical Overview

Uses of New Zealand Green-Lipped Mussel

Limited clinical studies suggest that NZGLM may have efficacy in the treatment of diseases with inflammatory components such as arthritis and asthma. However, conflicting trial results have been reported. Animal studies have investigated use for dysmenorrhea and inflammatory bowel disease.

New Zealand Green-Lipped Mussel Dosing

The typical dose used in trials for asthma and arthritis is 200 mg/day, calculated as the dose of polyunsaturated fatty acids. Standardized products include Lyprinol and Seatone . Although the US Food and Drug Administration (FDA) has issued Import Alerts attempting to stop importation of the extract, it persists in the marketplace.

Contraindications

Hypersensitivity to shellfish.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Animal studies have suggested that this product could be dangerous to a fetus.

New Zealand Green-Lipped Mussel Interactions

None well documented.

New Zealand Green-Lipped Mussel Adverse Reactions

GI discomfort and transient worsening of arthritic pain have been noted. However, incidence appears to be low. Long-term exposure has resulted in occupational asthma in people working as mussel openers.

Toxicology

None well documented.

History

Shellfish supplements have been used as a traditional remedy for arthritis in humans, in particular by the New Zealand Maoris. Early reports suggested that the daily ingestion of NZGLM extract alleviated the symptoms of arthritis in humans. Supported by a worldwide media campaign, claims were made that the extract was safe and effective in treating rheumatic diseases. 1 The Arthritis Foundation responded by calling these claims unfounded and feared that the campaign could delude arthritis sufferers and raise false hopes. Although the FDA has issued Import Alerts attempting to stop importation of the extract, 2 it still is available.

Chemistry

Although composition of the lipid fraction varies (possibly because of differing methods of collection, transport, and storage time), it usually is about 8% of freeze-dried weight. 3 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 acid, eicosapentaenoic acid, and palmitic acid. Cholesterol is the major sterol (31% of total sterols) with smaller proportions of desmosterol/brassicasterol, 24-methylenecholesterol, trans-22-dehydrocholesterol, nordehydrocholesterol, and occelastrol. 3 Glycosaminoglycans, a group of long, unbranched carbohydrates, also are present; chondroitin sulfate is of particular interest. Freeze-dried NZGLM powder contains the amino acids glutamine and methionine, vitamins E and C, and minerals zinc, copper, and manganese. 4

New Zealand Green-Lipped Mussel Uses and Pharmacology

Interest in NZGLM has focused mostly on its use in diseases with inflammatory components. Anti-inflammatory activity has been associated with omega-3 fatty acids, which inhibit the metabolism of arachidonate and reduce the formation of leukotrienes and prostaglandins. In vitro reduction in leukotriene production has been demonstrated. 5 Data are conflicting, possibly because NZGLM extracts are available in several formulations, including stabilized and nonstabilized powders, and heat-treated materials.

P. canaliculus extract reduced carrageenan-induced rat footpad edema following high-dose (500 mg/kg) intraperitoneal injection. 6 Effects were noted within 2 hours. Carrageenan-induced rat footpad swelling was 3% after injection with mussel extract compared with 26% after injection with aspirin, ibuprofen, or indomethacin. 7 Oral administration of the crude mussel preparation and its lipid extracts slightly reduced carrageenan-induced edema; however, the changes were not statistically significant. 8

Research reveals no clinical data regarding the anti-inflammatory effects of NZGLM.

In addition to the possible anti-inflammatory effects of NZGLM, the content of chondroitin sulfate, a major component of cartilage matrix and synovial fluid, is of interest. Dietary supplementation with chondroitin is reputed to stimulate cartilage matrix production and may have therapeutic benefits in osteoarthritis. 4

In dogs with signs of arthritis, reduction in total arthritic scores for joint pain and swelling was observed after 6 weeks of treatment with an extract of NZGLM. 4 Dogs received the extract with their standard diet or as a component of a proprietary dog food. Dosage was calculated according to weight (450, 750, or 1,000 mg/day for weights of less than 25 kg, 25 to 34 kg, or more than 34 kg, respectively). Method of administration had no impact on efficacy.

Generally, clinical trials investigating the use of NZGLM in arthritis have been small and poorly designed. A highly publicized 1980 trial reported benefits in patients with rheumatoid arthritis and osteoarthritis. 9 Improvement was observed in 39% and 18% of NZGLM and placebo recipients, respectively, after 3 months of treatment. The FDA and the National Institute for Arthritis, Metabolism, and Digestive Diseases (now the National Institute of Diabetes and Digestive and Kidney Diseases) regarded the study as small and poorly described, concluding that the extract was no more effective than placebo. A more recent study demonstrated apparent efficacy, but methodological flaws limit the usefulness of these findings. 10

Leukotrienes are mediators of airway inflammation in asthma. They induce bronchoconstriction and increase mucus secretion and microvascular permeability, allowing infiltration of inflammatory cells (eg, eosinophils, neutrophils) into the airway. NZGLM extract is thought to prevent this cascade by inhibiting leukotriene production. 5

Research reveals no animal data regarding the use of NZGLM in asthma.

Daytime wheeze was reduced in corticosteroid-naive patients with mild to moderate atopic asthma who received stabilized NZGLM extract. 5 Morning peak expiratory flow (PEF) was increased in patients receiving the mussel extract compared with those receiving placebo. However, mean forced expiratory volume in 1 second and evening PEF did not differ between the 2 groups.

In an ex vivo dysmenorrhea model, NZGLM extract modified the spontaneous and oxytocin-induced contractions of the uterus. 11 Mice with induced colitis, who had received NZGLM extract, had less weight loss, lower disease activity index scores, smaller crypt area losses in the distal colon, and lower caecum and colon weights than placebo recipients. 12 In rats, oral administration of the mussel lipid fraction concomitantly with aspirin, indomethacin, tolmetin, or diclofenac reduced gastric mucosal damage caused by these drugs up to 100%. 8 NZGLM may act synergistically with other agents. Coadministration of NZGLM with pentoxifylline or prednisone for arthritis and with nonsteroidal anti-inflammatory drugs for dysmenorrhoea has been suggested. 11

Dosage

Clinical studies of NZGLM extracts have used 100 mg twice daily. 5 The dose was calculated on the omega-3 polyunsaturated fatty acid content of the extract.

Pregnancy/Lactation

An extract of NZGLM has been shown to modify spontaneous and oxytocin-induced contractions of the uterus. 11 Proprietary preparation of NZGLM fed to pregnant rats retarded fetal development and delayed parturition (the action of giving birth), suggesting that the product contains an orally active prostaglandin inhibitor. 13 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 NZGLM and its extracts have reported a low incidence of adverse effects, generally consisting of GI symptoms (eg, diarrhea, flatulence, nausea). 14 One study reported 2 patients with a transient worsening of arthritic pain for the first 2 to 3 days of the trial. 10 In another study, no significant changes in blood pressure or laboratory tests were observed. 5 Symptoms suggestive of occupational asthma and lung-function abnormalities have been associated with work as an opener in green-lipped mussel processing plants. 15 About one third of the mussel openers studied demonstrated work-related respiratory symptoms. The length of time working as a mussel opener was independently linked to respiratory symptoms. The risk was higher in those who had worked for more than 7 years. It has been suggested that, like most seafood-related asthma, the mechanism is an immunoglobulin E-mediated allergic reaction associated with sensitization to high molecular weight-proteins. The relationship between duration of work and the presence of asthma symptoms supports this theory.

Toxicology

One case report describes granulomatous hepatitis, jaundice, colicky epigastric pain, anorexia, and malaise in a 64-year-old woman taking NZGLM. Liver biopsy and presence of eosinophil were suggestive of a drug reaction. Liver function tests were normal 3 months after discontinuation of all medications. 16

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