School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 7 Sassoon Road, Pokfulam, Hong Kong, China.
Graduate School of Public Health and Health Policy, City University of New York, 55 W 125th Street, New York, NY, 10017, USA.
Eur J Clin Nutr. 2020 Apr;74(4):613-621. doi: 10.1038/s41430-020-0588-5. Epub 2020 Mar 4.
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.
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.
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.
背景/目的：色氨酸是一种必需氨基酸，必须从富含色氨酸的食物中摄取，如乳制品、鸡蛋、坚果、豆类和谷物。它也被建议作为一种膳食补充剂来改善心理健康。观察发现，血浆色氨酸与缺血性心脏病（IHD）呈负相关，然而，其主要代谢产物 5-羟色胺和犬尿氨酸与 IHD 呈正相关，这使得色氨酸的作用难以推断。本研究旨在获得较少受干扰的色氨酸及其生理相关因素（5-羟色胺和犬尿氨酸）与 IHD、其危险因素和抑郁症关联的估计值。
受试者/方法：我们使用两样本 Mendelian Randomization 研究设计。我们使用与色氨酸、5-羟色胺和犬尿氨酸代谢物独立相关的遗传工具，应用于 UK Biobank SOFT CAD 研究与 CARDIoGRAMplusC4D 联盟（病例 n≤76014，对照 n≤264785）的荟萃分析，以及其他用于危险因素（包括糖尿病、脂质和血压）和抑郁症的联盟。我们使用逆方差加权法对遗传变异特异性估计值进行了组合，同时使用 MR-Egger、加权中位数和 MR-PRESSO 作为敏感性分析。
色氨酸和 5-羟色胺与 IHD 无关。犬尿氨酸名义上与 IHD 呈正相关（每标准差的比值比为 1.57，95%置信区间为 1.05-2.33），但在进行多次比较校正后则无相关性。与 IHD 危险因素和抑郁症的关联均为无效。
我们不能排除色氨酸的主要代谢产物之一犬尿氨酸可能与 IHD 呈正相关的可能性。需要进一步的研究来证实任何关联和潜在机制。
