Skip to main content

Advertisement

Log in

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

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

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).

Conclusion

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Le Floc’h N, Otten W, Merlot E (2011) Tryptophan metabolism, from nutrition to potential therapeutic applications. Amino Acids 41:1195–1205. doi:10.1007/s00726-010-0752-7

    Article  Google Scholar 

  2. Stevens CO, Henderson LM (1959) Riboflavin and hepatic kynurenine hydroxylase. J Biol Chem 234:1191–1194

    CAS  Google Scholar 

  3. Midttun O, Ulvik A, Ringdal Pedersen E, Ebbing M, Bleie O, Schartum-Hansen H, Nilsen RM, Nygard O, Ueland PM (2011) Low plasma vitamin B-6 status affects metabolism through the kynurenine pathway in cardiovascular patients with systemic inflammation. J Nutr 141:611–617. doi:10.3945/jn.110.133082

    Article  CAS  Google Scholar 

  4. Schroecksnadel K, Frick B, Winkler C, Fuchs D (2006) Crucial role of interferon-gamma and stimulated macrophages in cardiovascular disease. Curr Vasc Pharmacol 4:205–213

    Article  CAS  Google Scholar 

  5. Schrocksnadel K, Wirleitner B, Winkler C, Fuchs D (2006) Monitoring tryptophan metabolism in chronic immune activation. Clin Chim Acta 364:82–90. doi:10.1016/j.cca.2005.06.013

    Article  Google Scholar 

  6. Theofylaktopoulou D, Midttun O, Ulvik A, Ueland PM, Tell GS, Vollset SE, Nygard O, Eussen SJ (2013) A community-based study on determinants of circulating markers of cellular immune activation and kynurenines: the Hordaland Health Study. Clin Exp Immunol 173:121–130. doi:10.1111/cei.12092

    Article  CAS  Google Scholar 

  7. Nilsen RM, Bjorke-Monsen AL, Midttun O, Nygard O, Pedersen ER, Ulvik A, Magnus P, Gjessing HK, Vollset SE, Ueland PM (2012) Maternal tryptophan and kynurenine pathway metabolites and risk of preeclampsia. Obstet Gynecol 119:1243–1250. doi:10.1097/AOG.0b013e318255004e

    Article  CAS  Google Scholar 

  8. Zuo H, Tell GS, Vollset SE, Ueland PM, Nygard O, Midttun O, Meyer K, Ulvik A, Eussen SJ (2014) Interferon-gamma-induced inflammatory markers and the risk of cancer: the Hordaland Health Study. Cancer 120:3370–3377. doi:10.1002/cncr.28869

    Article  CAS  Google Scholar 

  9. Sulo G, Vollset SE, Nygard O, Midttun O, Ueland PM, Eussen SJ, Pedersen ER, Tell GS (2013) Neopterin and kynurenine-tryptophan ratio as predictors of coronary events in older adults, the Hordaland Health Study. Int J Cardiol 168:1435–1440. doi:10.1016/j.ijcard.2012.12.090

    Article  Google Scholar 

  10. Oxenkrug G (2013) Insulin resistance and dysregulation of tryptophan-kynurenine and kynurenine-nicotinamide adenine dinucleotide metabolic pathways. Mol Neurobiol 48:294–301. doi:10.1007/s12035-013-8497-4

    Article  CAS  Google Scholar 

  11. Munipally PK, Agraharm SG, Valavala VK, Gundae S, Turlapati NR (2011) Evaluation of indoleamine 2,3-dioxygenase expression and kynurenine pathway metabolites levels in serum samples of diabetic retinopathy patients. Arch Physiol Biochem 117:254–258. doi:10.3109/13813455.2011.623705

    Article  CAS  Google Scholar 

  12. Pedersen ER, Tuseth N, Eussen SJ, Ueland PM, Strand E, Svingen GF, Midttun O, Meyer K, Mellgren G, Ulvik A, Nordrehaug JE, Nilsen DW, Nygard O (2015) Associations of plasma kynurenines with risk of acute myocardial infarction in patients with stable angina pectoris. Arterioscler Thromb Vasc Biol 35:455–462. doi:10.1161/ATVBAHA.114.304674

    Article  CAS  Google Scholar 

  13. Zheng J, Huang T, Yu Y, Hu X, Yang B, Li D (2012) Fish consumption and CHD mortality: an updated meta-analysis of seventeen cohort studies. Public Health Nutr 15:725–737. doi:10.1017/S1368980011002254

    Article  Google Scholar 

  14. Mozaffarian D, Rimm EB (2006) Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 296:1885–1899. doi:10.1001/jama.296.15.1885

    Article  CAS  Google Scholar 

  15. Zhou Y, Tian C, Jia C (2012) Association of fish and n-3 fatty acid intake with the risk of type 2 diabetes: a meta-analysis of prospective studies. Br J Nutr 108:408–417. doi:10.1017/S0007114512002036

    Article  CAS  Google Scholar 

  16. Wu JH, Micha R, Imamura F, Pan A, Biggs ML, Ajaz O, Djousse L, Hu FB, Mozaffarian D (2012) Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis. Br J Nutr 107:S214–S227. doi:10.1017/S0007114512001602

    Article  CAS  Google Scholar 

  17. Ebbing M, Bleie O, Ueland PM, Nordrehaug JE, Nilsen DW, Vollset SE, Refsum H, Pedersen EK, Nygard O (2008) Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA 300:795–804. doi:10.1001/jama.300.7.795

    Article  CAS  Google Scholar 

  18. Andersen LF, Solvoll K, Johansson LR, Salminen I, Aro A, Drevon CA (1999) Evaluation of a food frequency questionnaire with weighed records, fatty acids, and alpha-tocopherol in adipose tissue and serum. Am J Epidemiol 150:75–87

    Article  CAS  Google Scholar 

  19. Nes M, Frost Andersen L, Solvoll K, Sandstad B, Hustvedt BE, Lovo A, Drevon CA (1992) Accuracy of a quantitative food frequency questionnaire applied in elderly Norwegian women. Eur J Clin Nutr 46:809–821

    CAS  Google Scholar 

  20. Den store matvaretabellen (1995) The Norwegian food composition table. National Nutrition Council and The Food Control Authority, Oslo (in Norwegian)

    Google Scholar 

  21. Andersen LF, Solvoll K, Drevon CA (1996) Very-long-chain n-3 fatty acids as biomarkers for intake of fish and n-3 fatty acid concentrates. Am J Clin Nutr 64:305–311

    CAS  Google Scholar 

  22. Andersen LF, Veierod MB, Johansson L, Sakhi A, Solvoll K, Drevon CA (2005) Evaluation of three dietary assessment methods and serum biomarkers as measures of fruit and vegetable intake, using the method of triads. Br J Nutr 93:519–527

    Article  CAS  Google Scholar 

  23. Verification SSoB (2002) Biochemical verification of tobacco use and cessation. Nicotine Tob Res 4:149–159. doi:10.1080/14622200210123581

    Article  Google Scholar 

  24. Strand E, Pedersen ER, Svingen GF, Schartum-Hansen H, Rebnord EW, Bjorndal B, Seifert R, Bohov P, Meyer K, Hiltunen JK, Nordrehaug JE, Nilsen DW, Berge RK, Nygard O (2013) Dietary intake of n-3 long-chain polyunsaturated fatty acids and risk of myocardial infarction in coronary artery disease patients with or without diabetes mellitus: a prospective cohort study. BMC Med 11:216. doi:10.1186/1741-7015-11-216

    Article  Google Scholar 

  25. Midttun O, Hustad S, Ueland PM (2009) Quantitative profiling of biomarkers related to B-vitamin status, tryptophan metabolism and inflammation in human plasma by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 23:1371–1379. doi:10.1002/rcm.4013

    Article  CAS  Google Scholar 

  26. Ueland PM, Midttun O, Windelberg A, Svardal A, Skalevik R, Hustad S (2007) Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry. Clin Chem Lab Med 45:1737–1745. doi:10.1515/CCLM.2007.339

    Article  CAS  Google Scholar 

  27. Koenker R (2005) Quantile regression. Cambridge University Press, New York

    Book  Google Scholar 

  28. Willett WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65:1220S–1228S

    CAS  Google Scholar 

  29. Hiratsuka C, Fukuwatari T, Sano M, Saito K, Sasaki S, Shibata K (2013) Supplementing healthy women with up to 5.0 g/d of l-tryptophan has no adverse effects. J Nutr 143:859–866. doi:10.3945/jn.112.173823

    Article  CAS  Google Scholar 

  30. Campbell BM, Charych E, Lee AW, Moller T (2014) Kynurenines in CNS disease: regulation by inflammatory cytokines. Front Neurosci 8:12. doi:10.3389/fnins.2014.00012

    Article  Google Scholar 

  31. Adkins Y, Kelley DS (2010) Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids. J Nutr Biochem 21:781–792. doi:10.1016/j.jnutbio.2009.12.004

    Article  CAS  Google Scholar 

  32. Calder PC (2014) Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta 1851:469–484. doi:10.1016/j.bbalip.2014.08.010

    Article  Google Scholar 

  33. Soyland E, Nenseter MS, Braathen L, Drevon CA (1993) Very long chain n-3 and n-6 polyunsaturated fatty acids inhibit proliferation of human T-lymphocytes in vitro. Eur J Clin Invest 23:112–121

    Article  CAS  Google Scholar 

  34. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R (2006) Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 83:754–759

    CAS  Google Scholar 

  35. Gallai V, Sarchielli P, Trequattrini A, Franceschini M, Floridi A, Firenze C, Alberti A, Di Benedetto D, Stragliotto E (1995) Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol 56:143–153

    Article  CAS  Google Scholar 

  36. Dawczynski C, Massey KA, Ness C, Kiehntopf M, Stepanow S, Platzer M, Grun M, Nicolaou A, Jahreis G (2013) Randomized placebo-controlled intervention with n-3 LC-PUFA-supplemented yoghurt: effects on circulating eicosanoids and cardiovascular risk factors. Clin Nutr 32:686–696. doi:10.1016/j.clnu.2012.12.010

    Article  CAS  Google Scholar 

  37. Miles EA, Banerjee T, Wells SJ, Calder PC (2006) Limited effect of eicosapentaenoic acid on T-lymphocyte and natural killer cell numbers and functions in healthy young males. Nutrition 22:512–519. doi:10.1016/j.nut.2005.11.011

    Article  CAS  Google Scholar 

  38. Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC (2001) Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. J Nutr 131:1918–1927

    CAS  Google Scholar 

  39. Trebble TM, Wootton SA, Miles EA, Mullee M, Arden NK, Ballinger AB, Stroud MA, Burdge GC, Calder PC (2003) Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation. Am J Clin Nutr 78:376–382

    CAS  Google Scholar 

  40. Murr C, Winklhofer-Roob BM, Schroecksnadel K, Maritschnegg M, Mangge H, Bohm BO, Winkelmann BR, Marz W, Fuchs D (2009) Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease. Atherosclerosis 202:543–549. doi:10.1016/j.atherosclerosis.2008.04.047

    Article  CAS  Google Scholar 

  41. Theofylaktopoulou D, Ulvik A, Midttun O, Ueland PM, Vollset SE, Nygard O, Hustad S, Tell GS, Eussen SJ (2014) Vitamins B2 and B6 as determinants of kynurenines and related markers of interferon-gamma-mediated immune activation in the community-based Hordaland Health Study. Br J Nutr 112:1065–1072. doi:10.1017/S0007114514001858

    Article  CAS  Google Scholar 

  42. Murr C, Talasz H, Artner-Dworzak E, Schroecksnadel K, Fiegl M, Fuchs D, Denz HA (2007) Inverse association between serum selenium concentrations and parameters of immune activation in patients with cardiac disorders. Clin Chem Lab Med 45:1224–1228. doi:10.1515/CCLM.2007.264

    Article  CAS  Google Scholar 

  43. Wennberg M, Vessby B, Johansson I (2009) Evaluation of relative intake of fatty acids according to the Northern Sweden FFQ with fatty acid levels in erythrocyte membranes as biomarkers. Public Health Nutr 12:1477–1484. doi:10.1017/S1368980008004503

    Article  Google Scholar 

  44. Rylander C, Sandanger TM, Engeset D, Lund E (2014) Consumption of lean fish reduces the risk of type 2 diabetes mellitus: a prospective population based cohort study of Norwegian women. PLoS ONE 9:e89845. doi:10.1371/journal.pone.0089845

    Article  Google Scholar 

  45. Totland TH, Mehæs B, Lundberg-Hallén N, Helland-Kigen KM, Lund-Blix NA, Myhre J, Johansen AM, Løken E, Frost Andersen L (2012) Norkost 3. En landsomfattande kostholdsundersøkelse blant menn og kvinner i Norge i alderen 18-70 år, 2010-11. (Norkost 3. A national dietary survey among males and females aged 18–70 years in Norway, 2010–11.). Helsedirektoratet, Oslo, Norway (in Norwegian)

  46. Agostoni C, Bresson J-L, Fairweather-Tait S, Flynn A, Golly I, Korhonen H, Lagiou P, Løvik M, Marchelli R, Martin A, Moseley B, Neuhäuser-Berthold M, Przyrembel H, Salminen S, Sanz Y, Strain S, Strobel S, Tetens I, Tomé D, van Loveren H, Verhagen H (2010) Scientific opinion on dietary reference values for fats, including fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol. EFSA J 8:1461. doi:10.2903/j.efsa.2010.1461

    Article  Google Scholar 

Download references

Acknowledgments

We wish to thank Reinhard Seifert for valuable statistical advice. This work was supported by the Norwegian Seafood Research Fund (FHF). The funder had no role in the study design, in analysis or interpretation of data, or in the writing of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Therese Karlsson.

Ethics declarations

Conflict of interest

None of the authors reported a conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 52 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karlsson, T., Strand, E., Dierkes, J. et al. 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. Eur J Nutr 56, 261–272 (2017). https://doi.org/10.1007/s00394-015-1077-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-015-1077-9

Keywords

Navigation