In 1978, a graduate student, Lisa Marshall, who was a passionate believer in the biological role of 18:3w3, entered my research group. There followed a series of papers illustrating that increased dietary 18:3w3 not only changed dramatically the fatty acid composition of immune cells in terms of the w6/w3 ratio but also changed the production of the 2-series prostaglandins. Several other graduate students pursued this avenue of research as did other researchers interested in the role of the dietary ratio of w6/w3 in human diseases, particularly those involving uncontrolled inflammatory responses. These earlier studies are covered in reviews (Gurr, 1983; Johnston, 1985, 1988). Collectively, these studies showed that dietary w3 fatty acids modulated the secretion of the inflammatory eicosanoids and cytokines by competitive inhibition of the eicosanoid synthase systems. Eicosapentaenoic (20:5w3) appeared to divert the synthase to less inflammatory products from those produced form arachidonic acid (20:4w6). This, however, was clearly not the whole story particularly when one tried to explain the effects of w3 fatty acids on activities of lymphocytes, cancer incidence, and metastasis (Fritsche and Johnston, 1989, 1990), The third mechanism by which dietary w3 could modulate immune and inflammatory is via alteration in membrane phospholipid fatty acid composition which could alter membrane proteins, receptor function, enzyme activities, and cytokine production. Much recent research has therefore concentrated on altered membrane structure and function when the long chain metabolite of 18:3w3, docosahexaenoic acid, 22:6w3 (DHA), is incorporated into cells of the immune system.

In a brief article it is impossible to do justice to all researchers who are contributing in this area. A few articles which include generous reference lists will, however, provide readers with leads to this burgeoning area of research. Jenski and associates have provided substantial evidence for the role of w3 fatty acid modification of membrane structure and function in the spontaneous release of cytosolic components from tumor cells (Jenski et al., 19911), the alteration of tumor cell sensitivity to immune cytolysis (Pascale et al., 1993); the 22:6w3-induced alteration of Thy-1 and CD8 expression in splenocytes (Jenski et al., 1995), and the role of phospholipid class as a determinant in the effect of 22:6w3's role in tumor cell viability (Zerouga et al., 1996).

Immunity cont....

Our venture to initiate an online newsletter covering developments in omega 3 and omega 6 essential fatty acid studies may be somewhat bold for one who began his career with the advanced technologies of a portable typewriter and a 12" slide-rule (slipstick), and who must now cope with incomprehensible systems such as the internet and Windows. However, as one who grew up in the North Star State learned quite early; to learn to swim one must jump in!

We have made that decision, and this is our first issue of "Omega 3 & 6 News Online". I was encouraged in this direction by a recent experience, which is the major news emanating recently from the Nutritional Biochemistry Section of the Hormel Institute.

A decade ago, we were interested in the study of the fatty acid profiles of normal Minnesotans as the controls in the study of vegetarians (1) and in a variety of studies of both "normal" and diseased groups (2), many of which have not yet been fully published. In general, we found that national "control" groups varied widely, and that Americans suffering from diseases associated with neuropathy or immune deficiency were generally very deficient in total omega 3 essential fatty acids (EFA), as measured in the fatty acids of plasma phospholipids.

We recently learned of the existence of a World Wide Web Journal of Biology, and being interested in the electronic revolution, we submitted one of our manuscripts, which should be of world-wide interest, to that journal. The handling of the manuscript, from submission to publication, including peer review, took less than two months. No charges were made, and there is no need for reprints. At the time of submission, the WWWJB first issue had been visited about 10,000 times during the first ten months of 1996. Since the second issue, which was published November 1, already there have been an additional 13400 visits by the public.

Our publication (3) raises the question of the adequacy of w3 EFA in one group of Americans, in contrast to several other "normal" populations around the world. Normal adult Minnesotans were found to be at the 20th percentile in the range of "normal" populations we have been able to analyze. A group of American infants was found to be the lowest "normal" group studied. We have found patients with a wide variety of neuropathies and immune-deficiencies to be very significantly deficient in total w3, compared to "normal" Minnesotans. We are currently emphasizing research in this area.

The accompanying Figure summarizes our work on "normal" human populations thus far. The total w3 polyunsaturated fatty acids (PUFA) of several populations sampled is plotted versus the total w6 PUFA therein, and these two variables show an inverse relationship, as was demonstrated in this laboratory in animal studies using single competing purified w6 and w3 dietary fatty acids, prior to 1964 (4). High levels of w6 suppress the incorporation of w3 fatty acids into tissue lipids, and high levels of w3 suppress the w6 fatty acids. It appears that in human nutrition, w3 EFA are often in low supply, and that w6 EFA may be overly abundant. There must be an optimum ratio of w3/w6, and this has been found to be 1/4 (0.25) for learning ability of rats (5). In the Figure, the ratios of w3/w6 ranged from a very low 0.09 in American infants, to a very high 0.44 for Nigerians. If learning is best at a ratio of 0.25, it is not surprising that many American children now have difficulty with school.

Fatty Acids Are Essential continued.....

Hard copies of the newsletter will also be available. To receive a hard copy of the newsletter contact Doug Bibus by email or call at 507-433-8804.