Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans

Previous studies reveal that supplementation of human diets with gamma-lino lenic acid (GLA) reduces the generation of lipid mediators of inflammation and attenuates clinical symptoms of chronic inflammatory disorders such as rheumatoid arthritis. However, we have shown that supplementation with this same fatty acid also causes a marked increase in serum arachidonate (AA) l evels, a potentially harmful side effect. The objective of this study was t o design a supplementation strategy that maintained the capacity of GLA to reduce lipid mediators without causing elevations in serum AA levels, initi al in vitro studies utilizing HEP-G2 liver cells revealed that addition of eicosapentaenoic acid (EPA) blocked Delta-5-desaturase activity, the termin al enzymatic step in AA synthesis. To test the in vivo effects of a GLA and EPA combination in humans, adult volunteers consuming controlled diets sup plemented these diets with 3.0 g/d of GLA and EPA. This supplementation str ategy significantly increased serum levels of EPA, but did not increase AA levels. EPA and the elongation product of GLA, dihomo-gamma-linolenic acid (DGLA) levels in neutrophil glycerolipids increased significantly during th e 3-wk supplementation period. Neutrophils isolated from volunteers fed die ts supplemented with GLA and EPA released similar quantities of AA, but syn thesized significantly lower quantities of leukotrienes compared with their neutrophils before supplementation. This study revealed that a GLA and EPA supplement combination may be utilized to reduce the synthesis of proinfla mmatory AA metabolites, and importantly, not induce potentially harmful inc reases in serum AA levels.