Biochemistry and physiology of eicosanoid precursors in cell membranes

Excessive action of omega-6 eicosanoids formed from the body's omega-6 esse ntial fats occurs in many health disorders, and it can be diminished with d ietary omega-3 fats. The current abundance of omega-6 (n-6) eicosanoid-medi ated disorders (e.g. thrombotic heart attack and stroke, cardiac arrhythmia , atherogenesis, arthritis, asthma, osteoporosis, tumour metastases, etc.) accompanies n-6 acid intakes that are more than ten times than the adequate level of 0.5% of energy. The n-3 and n-6 highly unsaturated fatty acids (H UFAs) are maintained in tissue phospholipids in a competitive, hyperbolic r elationship to the dietary abundance of their, 18-carbon polyunsaturated fa tty acid (PUFA) precursors. In contrast, 18:2n-6 and 18:3n-3 acids are main tained in tissue triacylglycerols in a linear proportion to their dietary a bundance expressed as percentage of daily caloric energy. The near absence of 20:3n-9 acid in plasma phospholipids in the U.S.A. population reflects v ery high intakes of polyunsaturated fats that compete with oleate for conve rsion to tissue HUFAs. The ethnic food combinations for Greenland, Japanese , Mediterranean, and American populations give proportions of omega-6 isome rs in the body long-chain acids near 30%, 50% 60% and 80%, respectively. It is of interest that these values mimic clinical outcomes associated with c ardiovascular mortalities ranging from 20 to 50 to 90 to 200 per 100 000, r espectively. Therapeutic treatment to cut excessive omega-6 eicosanoid sign alling has involved billions of dollars being spent to develop and market n ew pharmaceutical agents while a preventive nutrition approach to cut exces sive omega-6 eicosanoid signalling has yet to be applied systematically in dietetics, clinical nutrition and public health. Voluntary choices of food combinations can produce proportions of omega-6 HUFAs and of omega-3 plus o mega-6 HUFAs in the total body ranging from 30% to 90%, respectively. Adver se effects of excessive omega-6 eicosanoid signalling can be lowered by two interdependent dietary changes: first, reduce the daily intake of foods ov erly rich in the precursors of 20:4n-6 acid; and second, simultaneously inc rease the omega-3 PUFAs in the diet to competitively inhibit the conversion of LA into tissue omega-6 HUFAs. An inter active computer software applica tion has been developed to combine the complex biomedical information on co mpetitive interactions among essential fats and eicosanoids, and to interpr et and display the finding in terms of multiple daily food choices understa ndable by the general public. (C) 2001 The European Society of Cardiology.