Plasma β-Alanine is Positively Associated With Risk of Ischemic Stroke: a Nested Case-Control Study

Background: Previous studies suggested that beta-alanine as a neurotransmitter could affect the pathogenesis of ischemic damage. However, the association between circulating beta-alanine and risk of ischemic stroke (IS) has not been evaluated in populations. Objectives: We aimed to examine the association between beta-alanine and IS risk in a nested case-control study. Methods: We performed a case-control study nested within a prospective community-based cohort (n =16457; median follow-up time: 5.3 y), which included 321 incident IS cases and 321 controls matched by age and sex..-alanine and other metabolites were measured in plasma after overnight fasting by LC-MS/MS. The association of beta-alanine with risk of IS was evaluated by conditional logistic regression. BMI, current smoking, educational attainment, physical activity, total energy intake, family history of stroke, hypertension, diabetes, hyperlipidemia, and estimated GFR were adjusted in multivariable models. Results: There was a significant Spearman partial correlation between beta-alanine and 4-pyridoxic acid (p= 0.239; P < 0.001). Participants with elevated beta-alanine levels were more likely to develop IS with an adjusted OR of 1.26 (95% CI: 1.06-1.51; P= 0.011) (per standard deviation increment). This association remained significant after excluding the first 2 y of follow-up, and after further adjustment for red meat intake, total protein intake, medication use, or vitamin B6 indicators. Conclusions: Our novel findings revealed that plasma beta-alanine at baseline were positively associated with risk of IS and may function as an early biomarker of IS risk.