Dietary polyunsaturated fatty acids and inflammatory mediator production.
Many antiinflammatory pharmaceutical products inhibit the production of certain eicosanoids and cytokines and it is here that possibilities exist for therapies that incorporate n-3 and n-9 dietary fatty acids. The proinflammatory eicosanoids prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) are derived from the n-6 fatty acid arachidonic acid (AA), which is maintained at high cellular concentrations by the high n-6 and low n-3 polyunsaturated fatty acid content of the modern Western diet. Flaxseed oil contains the 18-carbon n-3 fatty acid alpha-linolenic acid, which can be converted after ingestion to the 20-carbon n-3 fatty acid eicosapentaenoic acid (EPA). Fish oils contain both 20- and 22-carbon n-3 fatty acids, EPA and docosahexaenoic acid. EPA can act as a competitive inhibitor of AA conversion to PGE(2) and LTB(4), and decreased synthesis of one or both of these eicosanoids has been observed after inclusion of flaxseed oil or fish oil in the diet. Analogous to the effect of n-3 fatty acids, inclusion of the 20-carbon n-9 fatty acid eicosatrienoic acid in the diet also results in decreased synthesis of LTB(4). Regarding the proinflammatory ctyokines, tumor necrosis factor alpha and interleukin 1beta, studies of healthy volunteers and rheumatoid arthritis patients have shown < or = 90% inhibition of cytokine production after dietary supplementation with fish oil. Use of flaxseed oil in domestic food preparation also reduced production of these cytokines. Novel antiinflammatory therapies can be developed that take advantage of positive interactions between the dietary fats and existing or newly developed pharmaceutical products.
James
M J
MJ
Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia, and the Department of Pediatrics and Child Health, Flinders Medical Center, Bedford Park, Australia.
Gibson
R A
RA
Cleland
L G
LG
D016718:Arachidonic Acid / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000628:therapy; D004041:Dietary Fats / Q000378:metabolism*; D015232:Dinoprostone / Q000009:adverse effects / Q000096:biosynthesis; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000096:biosynthesis; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D005395:Fish Oils / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000009:adverse effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000009:adverse effects / Q000096:biosynthesis; D008043:Linseed Oil / Q000627:therapeutic use; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D017962:alpha-Linolenic Acid / Q000378:metabolism
D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D018836:Inflammation Mediators; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D017962:alpha-Linolenic Acid; D007975:Leukotriene B4; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D008043:Linseed Oil; D015118:Eicosapentaenoic Acid; D015232:Dinoprostone