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.

中文翻译：

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色氨酸，5-羟色胺和犬尿氨酸对缺血性心脏病及其危险因素的影响：孟德尔随机研究

背景/目标

色氨酸是必需氨基酸，必须从富含色氨酸的饮食中获得，例如乳制品，鸡蛋，坚果，豆类和谷物。也有人建议将其作为改善精神健康的饮食补充。观察到血浆色氨酸与缺血性心脏病（IHD）呈负相关，但是其主要代谢产物5-羟色胺和犬尿氨酸与IHD正相关，这使得色氨酸的作用难以推断。这项研究旨在获得色氨酸和生理相关因素（5-羟色胺和犬尿氨酸）与IHD，其危险因素和抑郁症之间的关联的混杂证据。

主题/方法

我们使用了两个样本的孟德尔随机研究设计。我们使用独立地被色氨酸，血清素相关的遗传工具，并且犬尿氨酸的代谢物施加到英国生物库SOFT CAD研究与CARDIoGRAMplusC4D财团的荟萃分析（例Ñ  ≤76014和对照Ñ  ≤264785），以及其它财团风险因素，包括糖尿病，脂质，血压以及抑郁症。我们使用逆方差加权结合遗传变量特定的估计，并结合MR-Egger，加权中位数和MR-PRESSO作为敏感性分析。

结果

色氨酸和5-羟色胺与IHD无关。Kynurenine在名义上与IHD正相关（正比1.57 /标准偏差，95％置信区间1.05-2.33），但经过多次比较校正后没有。与IHD危险因素和抑郁症的关联为零。

结论

我们不能排除色氨酸的主要代谢物之一犬尿氨酸可能与IHD正相关的可能性。需要进一步研究以确认任何关联和潜在机制。