Abstract
BACKGROUND: The relative availability of the essential amino acid tryptophan in the brain, as indicated by the tryptophan index, which is the ratio of tryptophan to its competing amino acids (CAAs) in circulation, has been related to major depression. However, it remains unknown whether tryptophan availability is involved in the pathogenesis of ischemic stroke. AIMS: We aimed to investigate the relationship between the tryptophan index and the risk of ischemic stroke. METHODS: We performed a nested case-control study within a community-based cohort in eastern China over the period 2013 to 2018. The analysis included 321 cases of ischemic stroke and 321 controls matched by sex and date of birth. The plasma levels of tryptophan and CAAs, including tyrosine, valine, phenylalanine, leucine, and isoleucine, were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. Conditional logistic regression analyses were employed to determine incidence rate ratios (IRRs) and their 95% confidence intervals (CIs). RESULTS: After adjustment for body mass index, current smoking status, educational attainment, physical activity, family history of stroke, hypertension, diabetes, hyperlipidemia, and estimated glomerular filtration rate, an elevated tryptophan index was significantly associated with a reduced risk of ischemic stroke in a dose-response manner (IRR, 0.76; 95% CI, 0.63-0.93, per standard deviation increment). The plasma tryptophan or CAAs were not separately associated with the risk of ischemic stroke. CONCLUSIONS: The tryptophan index was inversely associated with the risk of ischemic stroke. Our novel observations suggest that the availability of the essential amino acid tryptophan in the brain is involved in the pathogenesis of ischemic stroke.