It is unknown exactly how CMO works, but it is worth exploring the many possibilities that have been proposed based on clinical observations of symptom improvement, scientific reviews of the chemistry of CMO and published data on one of the fatty acids in the complex.
A review of the recent literature on fatty acids shows standard polyunsaturated fatty acids (PUFAs) are effective agents for inflammation relief.1-4 Fish oils rich in n-3 fatty acids have demonstrated anti-inflammatory effects against arthritis in numerous studies.5-7 Most studies attributed modulation of immune and inflammatory response to eicosanoids and cytokine-mediated effects.8 Cytokines and certain eicosanoids are implicated in inflammatory conditions. It is thought that CM may work through a similar but as yet unknown mechanism, although there is some evidence that n-5 and n-9 fatty acids form oxygenated metabolites through transcellular processing and that these exert anti-inflammatory effects distinct from eicosanoids.9
A striking difference between the effect of CMO and PUFAs is the longer-lasting effects CMO appears to have. It is thought this may be due to some type of "reprogramming" of T cells. This brings us to another proposed mechanism of action, N-myristoylation.
Cytokine activity is linked to N-myristoylation, a process in which myristic acid is bound to the glycine residues in specific membrane proteins and is responsible for their activation. There is some evidence that human myristoylation may occur with other 14-carbon fatty acids, and perhaps include myristoleic acid.10 And, in fact, a recent study identified myristoleic acid as the cytotoxic component in saw palmetto (Serenoa repens) that induces apoptosis in human prostate cancer cells.11 These receptors bind cytokines with high affinity, which in turn initiates intracellular signals that alter the behaviour of the effector cell.12
Cellular behaviors that can be affected include various secretions, gene transcription, chemotaxis, and proliferation and differentiation of hematopoietic stem cells, including T cells. These behaviors directly affect immune function and inflammatory activities and some affect pain response.13 Research on N-myristolylation and inflammatory cytokines provides some scientific support for a mechanism of action for CMO.
1. Kremer JM. Effects of modulation of inflammatory and immune parameters in patients with rheumatic and inflammatory disease receiving dietary supplementation of n-3 and n-6 fatty acids. Lipids 1996 Mar;31 Suppl:S243-7.
2. James MJ, et al. Dietary polyunsaturated fatty acids and inflammatory mediator preduction. Am J Clin Nutr 2000 Jan;71(1 suppl):343S-8s.
3. Rothman D, et al. Botanical lipids: effects on inflammation, immune responses, and rheumatoid arthritis. Semin Arthritis Rheum 1995 Oct;25(2):87-96.
4. Sperling RI. Eicosanoids in rheumatoid arthritis. Rheum Dis Clin North Am 1995 Aug;21(3):741-58.
5. Kremer JM, et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal anti-inflammatory drugs. Clinical and immune correlates. Arthritis Rheum 1995 Aug;38(8):1107-14.
6. James MJ, Cleland LG. Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin Arthritis Rheum 1997 Oct;27(2):85-97.
7. Ariza-Ariza R et al. Omega-3 fatty acids in rheumatoid arthritis: an overview. Semin Arthritis Rheum 1998 Jun;27(6):366-70.
8. Calder PC. Dietary fatty acids and the immune system. Nutr Rev 1998 Jan;56(1):S70-S83.
9. Serhan CN, et al. Novel functional sets of lipid-derived mediators with anti-inflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal anti-inflammatory drugs and transcellular processing. J Exp Med 2000 Oct;192(8):1197-204.
10. Kishore NS, et al. Comparison of the acyl chain specificities of human myristoyl-CoA synthetase and human myristoyl-CoA:protein N-myristoyltransferase. J Biol Chem 1993;268(7):4889-902.
11. Iguchi K, et al. Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells. Prostate 2001;47:59-65.
12. Raju R, et al. Mammalian myristoyl Co:A protein N-myristoyltransferase. MolCell Biochem 1995;149/150:191-202.
13. Plotnikoff NP, ed. Cytokines stress and immunity. Boca Raton, FL. CRC Press, 1999 pp. 101, 115-121, 188-190, 263.
Reprinted with exclusive permission of Functional Foods & Nutraceuticals Magazine. Originally published March 2002. http://www.ffnmag.com/ASP/articleDisplay.asp?strArticleId=131&strSite=FFNSite