ABSTRACT
I. Introduction and Historical Perspectives .......................................................................... 792 A. Essential Fatty Acids ................................................................................................... 792 B. De ciency Symptoms .................................................................................................. 793 C. Desaturation/Elongation of EFA ................................................................................. 793 II. The Biological Signi cance of γ-Linolenic Acid .............................................................. 794 A. Sources of γ-Linolenic Acid ........................................................................................ 794 B. Metabolism and Generation of Potent Biological Modulators .................................... 794 III. Generalized Functional Roles of γ-Linolenic Acid ........................................................... 795 IV. Nutritional/Biological Signi cance of γ-Linolenic Acid .................................................. 795 A. Signi cance of Dose of Dietary Intake of γ-Linolenic Acid ....................................... 796 B. In Vivo Role of γ-Linolenic Acid in Normal Skin ....................................................... 796 C. In Vivo Role of γ-Linolenic Acid-Enriched Diet in the Induction of the
Biosynthesis of Potent Biologically Active Mediators ................................................ 796 V. Dietary Role of γ-Linolenic Acid in Disease Situations: Modulation of
In5 ammatory/Immunological Disorders ........................................................................... 797 A. In Vivo Dietary Role in Rheumatoid Arthritis ............................................................. 797 B. In Vivo Dietary Role in a Model of Lupus Erythematosus .......................................... 798 C. In Vivo Dietary Role in Cardiovascular Disorders ...................................................... 798 D. In Vivo Dietary Role in Bleomycin-Induced Lung Fibrosis ........................................ 799 E. In Vivo Dietary Role in the Management of Type I and Type II Diabetes ................... 799 F. In Vivo Dietary Role in the Management of Bronchial Asthma .................................. 800 VI. Role of γ-Linolenic Acid-Enriched Diet in Hyperproliferative Processes ........................ 801 A. In Vivo Dietary Role in a Guinea Pig Model of Normal Skin Epidermis:
Generation of Biologically Potent Metabolites ........................................................... 801 B. In Vivo Dietary Role in a Rodent Hyperproliferative Skin Model .............................. 802 VII. Role of γ-Linolenic Acid-Enriched Diet in Carcinogenesis: Models, Mechanisms,
and Speculative Pathways ................................................................................................. 802 A. In Vivo Role in Animal Models of Human Breast Cancer ........................................... 802 B. In Vivo Role of γ-Linolenic Acid as an Adjunct to Tamoxifen in Chemotherapeutic
Management of Human Breast Cancer ....................................................................... 803
The rst indication that dietary fat may be essential for healthy growing animals was presented in 1918 by Aron (1918) who proposed that butter has a nutrient value that cannot be provided by other dietary components. This report suggested that there was a special nutritive value inherent in fat apart from its caloric contribution and that this possibly was related to the presence of certain lipids. In 1929, Burr and Burr (1929) presented the rst series of articles outlining a “new de - ciency disease produced by the rigid exclusion of fat from the diet.” In the series of conclusions put forth, they developed the hypothesis that warm-blooded animals, in general, cannot synthesize appreciable quantities of certain fatty acids. In 1930, both investigators signi cantly added to their earlier work by presenting evidence that the dietary inclusion of linoleic acid alone could reverse all de ciency symptoms resulting from a fat-free diet and thus linoleic acid (LA or 18:2n-6)1 was heralded as an essential fatty acid (EFA) (Burr and Burr, 1930; Burr et al., 1940). The recognition that some unsaturated fatty acids could not be synthesized from endogenous precursors by mammals and were essential dietary elements led to the designation of essential and nonessential fatty acids. It was originally thought that there are only two EFAs, linoleic acid (9,12-octadecadienoic acid, LA, 18:2n-6) and γ-linolenic acid (9,12,15-octadecatrienoic acid, GLA, 18:3n-6), but continued nutritional studies revealed positive essential growth responses not only for linoleic acid and GLA, but also for arachidonic acid (AA) as well as the long-chain highly unsaturated fatty acids in sh oil [eicosapentaenoic acid (EPA), 20:5n-3 and docosahexaenoic acid (DHA), 22:6n-3]. More recent reports on the biological signi cance of the longer-chain n-3 polyunsaturated fatty acids (PUFAs) do qualify these long-chain fatty acids as essential PUFAs.
