Biochemistry and physiology of eicosanoid precursors in cell membranes
National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA
* Correspondence: William E. M. Land, PhD, National Institute on Alcohol Abuse and Alcoholism, 6000 Executive Blvd., Suite 400, Bethesda, MD, 20892-7003, USA
Abstract
Excessive action of omega-6 eicosanoids formed from the body's omega-6 essential fats occurs in many health disorders, and it can be diminished with dietary omega-3 fats. The current abundance of omega-6 (n-6) eicosanoid-mediated disorders (e.g. thrombosic 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 (HUFAs) are maintained in tissue phospholipids in a competitive, hyperbolic relationship to the dietary abundance of their 18-carbon polyunsaturated fatty acid (PUFA) precursors. In contrast, 18:2n-6 and 18:3n-3 acids are maintained in tissue triacylglycerols in a linear proportion to their dietary abundance 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 very high intakes of polyunsaturated fats that compete with oleate for conversion to tissue HUFAs. The ethnic food combinations for Greenland, Japanese, Mediterranean, and American populations give proportions of omega-6 isomers 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 cardiovascular mortalities ranging from 20 to 50 to 90 to 200 per 100 000, respectively.
Therapeutic treatment to cut excessive omega-6 eicosanoid signalling has involved billions of dollars being spent to develop and market new pharmaceutical agents while a preventive nutrition approach to cut excessive 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 omega-6 HUFAs in the total body ranging from 30% to 90%, respectively. Adverse effects of excessive omega-6 eicosanoid signalling can be lowered by two interdependent dietary changes: first, reduce the daily intake of foods overly rich in the precursors of 20:4n-6 acid; and second, simultaneously increase the omega-3 PUFAs in the diet to competitively inhibit the conversion of LA into tissue omega-6 HUFAs. An inter active computer software application has been developed to combine the complex biomedical information on competitive interactions among essential fats and eicosanoids, and to interpret and display the finding in terms of multiple daily food choices understandable by the general public.
Key Words: arrhythmia • eicosanoids • food choices • thrombosis