Dietary Supplementation with γ-Linolenic Acid Alters Fatty Acid Content and Eicosanoid Production in Healthy Humans ,

Abstract

To understand the in vivo metabolism of dietary gamma-linolenic acid (GLA), we supplemented the diets of 29 volunteers with GLA in doses of 1.5-6.0 g/d. Twenty-four subjects ate controlled eucaloric diets consisting of 25% fat; the remaining subjects maintained their typical Western diets. GLA and dihomo-gamma-linolenic acid (DGLA) increased in serum lipids of subjects supplemented with 3.0 and 6.0 g/d; serum arachidonic acid increased in all subjects. GLA supplementation with 3.0 and 6.0 g/d also resulted in an enrichment of DGLA in neutrophil phospholipids but no change in GLA or AA levels. Before supplementation, DGLA was associated primarily with phosphatidylethanolamine (PE) of neutrophil glycerolipids, and DGLA increased significantly in PE and neutral lipids after GLA supplementation. Extending the supplementation to 12 wk did not consistently change the magnitude of increase in either serum or neutrophil lipids in subjects receiving 3.0 g/d. After GLA supplementation, A23187-stimulated neutrophils released significantly more DGLA, but AA release did not change. Neutrophils obtained from subjects after 3 wk of supplementation with 3.0 g/d GLA synthesized less leukotriene B4 (P < 0.05) and platelet-activating factor. Together, these data reveal that DGLA, the elongase product of GLA, but not AA accumulates in neutrophil glycerolipids after GLA supplementation. The increase in DGLA relative to AA within inflammatory cells such as the neutrophil may attenuate the biosynthesis of AA metabolites and may represent a mechanism by which dietary GLA exerts an anti-inflammatory effect.

Nutrient supplementation with polyunsaturated fatty acids and micronutrients in rheumatoid arthritis: clinical and biochemical effects

“…Furthermore, downmodulatory effects on proinflammatory cytokines have been described. Similar clinical results have been published with the omega-6 fatty acid gamma-linolenic acid (GLA), isolated from certain plant and seed oils (Zurier et al, 1996;Johnson et al, 1997;Belch & Hill, 2000). Administration of GLA leads to an increased incorporation of its metabolite dihomogammalinolenic acid (DGLA) in cell membranes, thus blocking the metabolism of AA and changing the balance of lipid mediators towards the production of lesspotent eicosanoids.…”

Anti-Atherosclerotic Effects of Dihomo-.GAMMA.-Linolenic Acid in ApoE-Deficient Mice

“…Dietary GLA-containing seed oils increased PGE1 in macrophages 7) . PGE1 is converted from DGLA by COX 7) ; therefore, GLA may be elongated to DGLA, and its metabolite PGE1 may contribute to the anti-atherosclerotic effect of GLA 10,11) , although the inhibitory mechanism of the seed oils was not clear. Since plant seed oils contain many other components, including GLA, it is unclear whether DGLA shows direct anti-atherosclerotic action.…”

“…However, the conversion of LA to GLA is limited in rodents and humans, and a supplemental diet of GLA-enriched seed oils may be needed to increase tissue GLA concentration. GLA is rapidly elongated to DGLA, and the conversion of DGLA to arachidonic acid (AA) occurs slowly due to the limited activity of 5 desaturase in rodents and humans 10,11) . In mouse macrophages, DGLA is mainly converted to prostaglandin (PG) E1 by cyclooxygenase (COX) 7) .…”

Investigations of human platelet-type 12-lipoxygenase: role of lipoxygenase products in platelet activation

“…The extinction coeffi cient of phospholipase A 2 (cPLA 2 ) ( 25 ). The composition of the phospholipids in the platelet membrane is dynamic in nature, and because many of the fatty acids that make up the phospholipid bilayer are not produced in the body, their content is primarily regulated by dietary intake (26)(27)(28)(29). Although AA makes up a large proportion of the phospholipid content, other fatty acids are also available from the platelet membrane, and their content, relative to AA, has been shown to fl uctuate depending on diet ( 27,29,30 ).…”