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Nutrigenomics and molecular nutrition

Effects of tryptophan, serotonin, and kynurenine on ischemic heart diseases and its risk factors: a Mendelian Randomization study

European Journal of Clinical Nutrition volume 74, pages 613–621 (2020)Cite this article

Subjects

Abstract

Background/objectives

Tryptophan is an essential amino acid that must be obtained from dietary items, such as dairy products, eggs, nuts, legumes, and grains, which are rich in tryptophan. It has also been suggested as a dietary supplement to improve mental health. Observationally plasma tryptophan is inversely associated with ischemic heart disease (IHD), however, its main metabolites, serotonin, and kynurenine are positively associated with IHD, which makes the effects of tryptophan difficult to infer. This study aimed to obtain less-confounded estimates of the associations of tryptophan and physiologically related factors (serotonin and kynurenine) with IHD, its risk factors and depression.

Subjects/methods

We used a two-sample Mendelian Randomization study design. We used genetic instruments independently associated with tryptophan, serotonin, and kynurenine metabolites applied to a meta-analysis of the UK Biobank SOFT CAD study with the CARDIoGRAMplusC4D consortium (cases n ≤ 76,014 and controls n ≤ 264,785), and other consortia for risk factors including diabetes, lipids, and blood pressure, as well as for depression. We combined genetic variant-specific estimates using inverse variance weighting, with MR-Egger, the weighted median and MR-PRESSO as sensitivity analyses.

Results

Tryptophan and serotonin were not associated with IHD. Kynurenine was nominally and positively associated with IHD (odds ratio 1.57 per standard deviation, 95% confidence interval 1.05–2.33) but not after correction for multiple comparisons. Associations with IHD risk factors and depression were null.

Conclusions

We cannot exclude the possibility that one of the main metabolites of tryptophan, kynurenine, might be positively associated with IHD. Further studies are needed to confirm any association and underlying mechanism.

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Acknowledgements

Data on coronary artery disease/myocardial infarction have been contributed by the CARDIoGRAMplusC4D and UK Biobank CardioMetabolic Consortium CHD working group who used the UK Biobank Resource (application number 9922). Data have been downloaded from www.CARDIOGRAMPLUSC4D.ORG. Data on diabetes have been contributed by DIAGRAM investigators and have been downloaded from http://www.diagram-consortium.org. Data on lipids have been contributed by GLGC investigators and have been downloaded from http://csg.sph.umich.edu/willer/public/lipids2013/. Data on blood pressure have been contributed by UK Biobank Ben Neale files and have been downloaded from http://www.nealelab.is/uk-biobank. Data on depression related phenotypes have been contributed by UK Biobank and have been downloaded from https://datashare.is.ed.ac.uk/handle/10283/3036.

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Authors and Affiliations

  1. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong, China

    Mengyu Li, Man Ki Kwok, Shirley Siu Ming Fong & Catherine Mary Schooling

  2. Graduate School of Public Health and Health Policy, City University of New York, 55 W 125th Street, New York, NY, 10017, USA

    Catherine Mary Schooling

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Contributions

CMS designed the study; ML conducted the analysis and drafted the paper; CMS directed the analytic strategy and supervised the study from conception to completion; MKK, SSMF, and CMS revised drafts of the paper. All the authors contributed to the interpretation of the data and critically revising the paper.

Corresponding author

Correspondence to Catherine Mary Schooling.

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The authors declare that they have no conflict of interest.

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This MR study only uses published or publicly available data. No original data were collected for the MR study. Ethical approval for each of the studies included in the investigation can be found in the original publications (including informed consent from each participant).

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Li, M., Kwok, M.K., Fong, S.S.M. et al. Effects of tryptophan, serotonin, and kynurenine on ischemic heart diseases and its risk factors: a Mendelian Randomization study. Eur J Clin Nutr 74, 613–621 (2020). https://doi.org/10.1038/s41430-020-0588-5

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