QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barham, J. B. Articles by Chilton, F. H. Search for Related Content PubMed PubMed Citation Articles by Barham, J. B. Articles by Chilton, F. H.

---

Article

Addition of Eicosapentaenoic Acid to -Linolenic Acid–Supplemented Diets Prevents Serum Arachidonic Acid Accumulation in Humans¹

J. Brooke Barham^*, Michelle B. Edens^*, Alfred N. Fonteh^*, Margaret M. Johnson, Linda Easter^** and Floyd H. Chilton^*,,2

Departments of ^* Internal Medicine (Section on Pulmonary and Critical Care Medicine), Biochemistry and Physiology/Pharmacology, and ^** General Clinical Research Center Wake Forest University School of Medicine, Winston-Salem, NC 27157 and Department of Medicine, Mayo Clinic Jacksonville, Jacksonville, FL 32224

²To whom correspondence should be addressed.

Previous studies reveal that supplementation of human diets with -linolenic 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) levels, a potentially harmful side effect. The objective of this study was to design a supplementation strategy that maintained the capacity of GLA to reduce lipid mediators without causing elevations in serum AA levels. Initial in vitro studies utilizing HEP-G2 liver cells revealed that addition of eicosapentaenoic acid (EPA) blocked -5-desaturase activity, the terminal enzymatic step in AA synthesis. To test the in vivo effects of a GLA and EPA combination in humans, adult volunteers consuming controlled diets supplemented these diets with 3.0 g/d of GLA and EPA. This supplementation strategy significantly increased serum levels of EPA, but did not increase AA levels. EPA and the elongation product of GLA, dihomo--linolenic acid (DGLA) levels in neutrophil glycerolipids increased significantly during the 3-wk supplementation period. Neutrophils isolated from volunteers fed diets supplemented with GLA and EPA released similar quantities of AA, but synthesized 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 proinflammatory AA metabolites, and importantly, not induce potentially harmful increases in serum AA levels.

KEY WORDS: • arachidonic acid • -linolenic acid • inflammation • leukotrienes • neutrophils • humans

This article has been cited by other articles:

				M. van Eijsden, G. Hornstra, M. F van der Wal, T. G. Vrijkotte, and G. J Bonsel Maternal n-3, n-6, and trans fatty acid profile early in pregnancy and term birth weight: a prospective cohort study Am. J. Clinical Nutrition, April 1, 2008; 87(4): 887 - 895. [Abstract] [Full Text] [PDF]

				F. H Chilton, L. L Rudel, J. S Parks, J. P Arm, and M. C Seeds Mechanisms by which botanical lipids affect inflammatory disorders Am. J. Clinical Nutrition, February 1, 2008; 87(2): 498S - 503S. [Abstract] [Full Text] [PDF]

				A. M. Monjazeb, K. P. High, A. Connoy, L. S. Hart, C. Koumenis, and F. H. Chilton Arachidonic acid-induced gene expression in colon cancer cells Carcinogenesis, October 1, 2006; 27(10): 1950 - 1960. [Abstract] [Full Text] [PDF]

				R. J. Flower and M. Perretti Controlling inflammation: a fat chance? J. Exp. Med., March 7, 2005; 201(5): 671 - 674. [Abstract] [Full Text] [PDF]

				D. R. Hoffman, R. C. Theuer, Y. S. Castaneda, D. H. Wheaton, R. G. Bosworth, A. R. O'Connor, S. E. Morale, L. E. Wiedemann, and E. E. Birch Maturation of Visual Acuity Is Accelerated in Breast-Fed Term Infants Fed Baby Food Containing DHA-Enriched Egg Yolk J. Nutr., September 1, 2004; 134(9): 2307 - 2313. [Abstract] [Full Text] [PDF]

				M. E. Surette, M. Edens, F. H. Chilton, and K. M. Tramposch Dietary Echium Oil Increases Plasma and Neutrophil Long-Chain (n-3) Fatty Acids and Lowers Serum Triacylglycerols in Hypertriglyceridemic Humans J. Nutr., June 1, 2004; 134(6): 1406 - 1411. [Abstract] [Full Text] [PDF]

				P. D. Burns, T. E. Engle, M. A. Harris, R. M. Enns, and J. C. Whittier Effect of fish meal supplementation on plasma and endometrial fatty acid composition in nonlactating beef cows J Anim Sci, November 1, 2003; 81(11): 2840 - 2846. [Abstract] [Full Text] [PDF]

				C. Song, X. Li, B. E. Leonard, and D. F. Horrobin Effects of dietary n-3 or n-6 fatty acids on interleukin-1{beta}-induced anxiety, stress, and inflammatory responses in rats J. Lipid Res., October 1, 2003; 44(10): 1984 - 1991. [Abstract] [Full Text] [PDF]

				P. Grandjean and P. Weihe Arachidonic acid status during pregnancy is associated with polychlorinated biphenyl exposure Am. J. Clinical Nutrition, March 1, 2003; 77(3): 715 - 719. [Abstract] [Full Text] [PDF]

				M. Laidlaw and B. J Holub Effects of supplementation with fish oil-derived n-3 fatty acids and {gamma}-linolenic acid on circulating plasma lipids and fatty acid profiles in women Am. J. Clinical Nutrition, January 1, 2003; 77(1): 37 - 42. [Abstract] [Full Text] [PDF]

				P. Tso, K. Ding, S. DeMichele, and Y.-S. Huang Intestinal Absorption and Lymphatic Transport of a High {gamma}-Linolenic Acid Canola Oil in Lymph Fistula Sprague-Dawley Rats J. Nutr., February 1, 2002; 132(2): 218 - 221. [Abstract] [Full Text] [PDF]