Mengyu Li1, Man Ki Kwok1, Shirley Siu Ming Fong1, Catherine Mary Schooling2,3. 1. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong, China. 2. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong, China. cms1@hku.hk. 3. Graduate School of Public Health and Health Policy, City University of New York, 55 W 125th Street, New York, NY, 10017, USA. cms1@hku.hk.
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.
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.
Authors: Edward Yu; Miguel Ruiz-Canela; Marta Guasch-Ferré; Yan Zheng; Estefania Toledo; Clary B Clish; Jordi Salas-Salvadó; Liming Liang; Dong D Wang; Dolores Corella; Montse Fitó; Enrique Gómez-Gracia; José Lapetra; Ramón Estruch; Emilio Ros; Montserrat Cofán; Fernando Arós; Dora Romaguera; Lluis Serra-Majem; Jose V Sorlí; Frank B Hu; Miguel A Martinez-Gonzalez Journal: J Nutr Date: 2017-02-08 Impact factor: 4.798
Authors: Gillian M Mackay; Caroline M Forrest; John Christofides; Michala A Bridel; Susan Mitchell; Richard Cowlard; Trevor W Stone; L Gail Darlington Journal: Clin Exp Pharmacol Physiol Date: 2008-10-31 Impact factor: 2.557
Authors: Karen Mei-Ling Tan; Mya-Thway Tint; Narasimhan Kothandaraman; Navin Michael; Suresh Anand Sadananthan; S Sendhil Velan; Marielle V Fortier; Fabian Yap; Kok Hian Tan; Peter D Gluckman; Yap-Seng Chong; Mary F F Chong; Yung Seng Lee; Keith M Godfrey; Johan G Eriksson; David Cameron-Smith Journal: J Clin Endocrinol Metab Date: 2022-05-17 Impact factor: 6.134