Associations between intake of fish and n-3 long-chain polyunsaturated fatty acids and plasma metabolites related to the kynurenine pathway in patients with coronary artery disease.
OBJECTIVE
Enhanced tryptophan degradation via the kynurenine pathway has been related to several pathological conditions. However, little is known about the effect of diet on individual metabolites of this pathway. We investigated cross-sectional associations between reported intake of fish and omega-3 (n-3) long-chain PUFA (LC-PUFA) and plasma metabolites related to the kynurenine pathway.


METHODS
Participants were 2324 individuals with coronary artery disease from the Western Norway B Vitamin Intervention Trial. Fish and n-3 LC-PUFA intakes were assessed using a food frequency questionnaire. Plasma concentrations of tryptophan, kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid, neopterin, and kynurenine-to-tryptophan ratio (KTR) were analyzed. Associations were investigated using partial Spearman's rank correlations and multiple linear regressions.


RESULTS
Median age at inclusion was 62 years (80 % males), and 84 % had stable angina pectoris. Intake of fatty fish and n-3 LC-PUFA was inversely associated with plasma 3-hydroxykynurenine. Consumption of total fish, lean fish, and n-3 LC-PUFA was inversely associated with plasma neopterin. Intake of total fish, fatty fish, and n-3 LC-PUFA was inversely associated with KTR. All these correlations were weak (ρ between -0.12 and -0.06, P < 0.01). In 306 patients with diabetes, lean fish intake was positively associated with plasma 3-hydroxyanthranilic acid (ρ = 0.22, P < 0.001, P for interaction = 0.01), and total fish intake was inversely associated with KTR (ρ = -0.17, P < 0.01, P for interaction = 0.02).


CONCLUSIONS
Fish intake was not an important determinant of individual metabolites in the kynurenine pathway. However, some correlations were stronger in patients with diabetes. The inverse associations of fish or n-3 LC-PUFA with neopterin and KTR may suggest a slightly lower IFN-γ-mediated immune activation with a higher intake.
Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Laboratory Building 8th Floor, P.O. Box 7804, 5020, Bergen, Norway. therese.karlsson@uib.no.
Therese
T
Karlsson
Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Laboratory Building 8th Floor, P.O. Box 7804, 5020, Bergen, Norway.
Elin
E
Strand
Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, P.O. Box 7804, 5020, Bergen, Norway.
Jutta
J
Dierkes
Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0372, Oslo, Norway.
Christian A
CA
Drevon
National Institute of Nutrition and Seafood Research, P.O. Box 2029, Nordnes, 5817, Bergen, Norway.
Jannike
J
Øyen
Bevital AS, Laboratory Building, Jonas Lies veg 87, 5021, Bergen, Norway.
Øivind
Ø
Midttun
Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Laboratory Building 8th Floor, P.O. Box 7804, 5020, Bergen, Norway.|Laboratory of Clinical Biochemistry, Haukeland University Hospital, 5021, Bergen, Norway.
Per M
PM
Ueland
Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, P.O. Box 7804, 5020, Bergen, Norway.
Oddrun A
OA
Gudbrandsen
Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Laboratory Building 8th Floor, P.O. Box 7804, 5020, Bergen, Norway.
Eva Ringdal
ER
Pedersen
Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Laboratory Building 8th Floor, P.O. Box 7804, 5020, Bergen, Norway.|Department of Heart Disease, Haukeland University Hospital, 5021, Bergen, Norway.
Ottar
O
Nygård
D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D002149:Energy Intake; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000097:blood*; D005260:Female; D005399:Fishes; D006801:Humans; D007736:Kynurenic Acid / Q000097:blood; D007737:Kynurenine / Q000031:analogs & derivatives / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D009664:Norway; D015596:Nutrition Assessment; D017747:Seafood; D014280:Triglycerides / Q000097:blood; D014364:Tryptophan / Q000097:blood; D014977:Xanthurenates / Q000097:blood; D062367:ortho-Aminobenzoates / Q000097:blood
D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D014280:Triglycerides; D014977:Xanthurenates; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D015095:3-Hydroxyanthranilic Acid; C005045:3-hydroxykynurenine; D007737:Kynurenine; C028330:xanthurenic acid; D019798:Neopterin; D014364:Tryptophan; D002784:Cholesterol; D007736:Kynurenic Acid
Fish intake; Kynurenine pathway; Neopterin; Omega-3 polyunsaturated fatty acid