For those interested in more of the biochemical detail of why Green-lipped Mussel Oil and therefore Pernoil works we give the following summary . Also below is a list of suggested links and papers. We don’t want to cherry pick particular parts of each paper, so we leave it to you to draw your own conclusions. It is far from a complete list but hopefully it will give you a start to help answer more complex questions.

 What is inflammation?

Inflammation is an adaptive response to infection or injury, which involves the orchestrated delivery of leukocytes to the initiating site. In addition to the classic acute and chronic inflammatory responses, there is also a para-inflammatory response which is induced by tissue stress. Classic inflammatory responses are triggered by toll-like receptors (TLRs) and nucleotide-binding oligomerization-domain protein(NOD)-like receptors (NLRs). TLR/NLR signalling results in the secretion of potent inflammatory mediators , such as cytokines and chemokines. The underlying goal of this response is to facilitate neutrophil invasion of the extravascular site of infection or injury. Activated neutrophils release the toxic contents of their granules and eliminate the initiating trigger. If this cascade of events is successful, the acute inflammatory response ends, and is followed by phases of repair and recovery. However, if removal of the initiating factor is not complete, inflammation can persist prompting the replacement of neutrophils by macrophages and T cells. If this response fails, chronic state of inflammation can develop. Thus , the inflammatory response comprises physiological pathways that must be tightly controlled to avoid evolution into chronic inflammatory states that exist during disease conditions such as type-2 diabetes, Alzheimer’s disease and cardiovascular disease.

Two of the very important pro inflammatory agents are prostaglandin E2 and leukotriene B4 (LTB4) which are derived from the breakdown of arachidonic acid (a n-6 fatty acid) , are important from a modern western diet view point. Other important pro inflammatory compounds are cytokines, tumor necrocis alpha factor and interleukin 1 beta. All of these have been shown to be reduced by the intake of seafood oils. ( 1) This diagram from the Gibson et al paper (1) illustrates the pathways involved


FIGURE 2. Effect of n23 and n29 fatty acids on the production of lipid and peptide inflammatory mediators. The solid arrows indicate synthesis and the dashed arrows indicate inhibition. ETA, eicosatrienoic acid, LT,leukotriene; AA, arachidonic acid; PG,prostaglandin; TX,thromboxane; EPA, eicosapentaenoic acid; TNF-a, tumornecrosi factor a; IL-1b, interleukin 1b.


If these inflammatory mediators can be inhibited from being produced then some benefit is achieved. The diagram shows, in outline, the chemical pathways showing where ETA and EPA are effective in inhibiting the formation of these mediators. It is thought that ETA also has an effect on the cyclooxygenase but it's actions are not clearly understood.

Other evidence of ETA’s effect has been shown. The results of research into the effect of dietary supplementation of ETA in rats established that ETA effectively inhibits synthesis of the mediator LBT4 and suggest that ETA may confer anti inflammatory benefits similar to those observed with essential fatty acid deficiency or fish oil containing EPA. Because ETA is less unsaturated than EPA it can be expected to have greater chemical stability, thus giving practical advantages in products it is involved in.

ETA is used by doctors and medical researchers as an indicator of essential fatty acid deficiency in the body. The higher the level of ETA the more fatty acid deficient the patient is. This is because the more fatty acid deficient cells in the body react by breaking down oleic acid to produce (via a long biochemical pathway) more ETA. A reason for this appears to be that key organs in the body will become inflamed due to a reduction in essential fatty acids. That is, in effect, ETA is a key natural anti inflammatory compound in the body. So the presence of ETA in Green-lipped Mussels , helps explain why mussel oil is a stronger anti inflammatory agent than ordinary fish oil. This may not be the complete story as it is likely that it is the same as most natural materials which give health benefits, in that there are number of smaller compounds that all interact with the main active compounds to produce the overall benefit.

Research discovered that with oleocanthal in olive oil,it can be shown that “ like iboprofen both enantiomers of oleocanthal caused dose dependent inihibition of COX-1 and COX-2 activities but had no effect on lipoxygenase in vitro” (2).

The cytokines are implicated in the later destructive phases of joint disease where as eicosanoids have their effect in the early stages ( 3 ).

The Omega3 fatty acids can suppress the production of TNF and il-1beta . Also it has been shown that young cartilage have high concentrations of ETA showing the importance it has in joints.

Therefore Pernoil capsules have the natural chemical components to assist the control of early stages of arthritic conditions (ie. inhibition of LBT4 synthesis ) and also the later stages through cyclooxygenase inhibition (COX1 & COX2 inihibition).

Clearly one of the implications of this information is that any supplementation of the diet with n-3/n-9 rich oils to prevent or reduce inflammation in joint disease (or any other diseases where inflammation is negatively involved ) would be best associated with changes in other aspects of your diet. The diet must be monitored to ensure there is not an excess of n-6 fats that will reduce the effect of the supplementation.


  1. “Dietary polyunsaturated fatty acids and inflammatory mediator production”
     MJ James, RA Gibson, LG Cleland
    American Journal of Clinical Nutrition Vol  71  343-348

  1. “Phytochemistry: Ibuprofen like activity in extra virgin olive oil”
     Gary Beauchamp et al
     Nature 437 45-46

  1. "Inhibition of human neutrophil leukotriene B4 synthesis in essential fatty acidsdeficiency:role of leukotriene A hydrolase”
     Cleland LG, James MJ, Proudman SM, Neuman MA, Gibson RA.
     Lipids 1994 March 29(3)151-5


Further Reading

Anti-inflammatory activity of an oil derived from perna canaliculus ( New Zealand Green-lipped Mussel), Greenhill NS , Davis PF., including a list of relevant papers.

Functional Performance Systems website – review of published papers on Mead Acid ( ETA)

“Invitro modulation of inflammatory cytokines and IgG levels by extracts of Perna Canaliculus “  Sachin Mani  & John  W Lawson

 "Leukotrienes & Lipoxins"  St Edwards University. Department Chemistry & Biochemistry.

“Leukotrienes & Lipoxins”  -- Chemistry and Biology . The AOCS Lipid Library

“Lipid loop instigates arthritis”  ( highlights importance of LBT4). Journal of Experimental Medicine.

“Lipoxins and other arachidonate derived mediators in bronchial asthma” C Chavis, I Vachier, P Godard, J Bousquet ,P Chanez

“Reducing Inflammation with Diet and Supplements : The story of Eicosonoid Inhibition.”  Subhuti Dharmananda PhD  director Institute of Traditional Medicine. Portland Oregon

“Resolution of inflammation: state of the art, definitions and terms”
Charles N. Serhan, Sue D. Brain, Christopher D. Buckley, Derek W. Gilroy, Christopher Haslett, Luke A. J. O’Neill, Mauro Perretti, Adriano G. Rossi, John L. Wallace

“Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients”
PC Calder

“Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs clinical and immune correlates"
“Do n-3 fatty acids prevent osteoporosis?”
Chaim Vanek,   William E Connor

“New research and Clinical Trial report on the Use of Perna Canaliculus in the Management of Arthritis”
Roger V Kendall , John W Lawson, Lloyd A Hurley.

“Fatty acids from lipids of marine organisms: molecular biodiversity, roles as biomarkers, biologically active compounds, and economical aspects”
Jean-Pascal Bergé and Gilles Barnathan