Dietary amino acids and risk of stroke subtypes: Results from three large prospective cohort studies.

Background: Differences in dietary protein have been associated with stroke risk, with possible heterogeneity in associations by stroke type or food sources of protein.

Objective: We examined the associations of individual dietary amino acids, as the constituents of dietary protein, with risks of ischemic, hemorrhagic and total stroke.

Methods: We analysed data from 73,830 women in the Nurses' Health Study (1984-2012), 92,333 women in the Nurses' Health Study II (1991-2013), and 43,268 men in the Health Professionals Follow-Up Study (1986-2016). Dietary intakes of 22 (20 standard and two non-standard) amino acids were assessed using validated food frequency questionnaires, administered typically every four years. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischemic, hemorrhagic and total stroke in relation to the energy-adjusted intakes of individual amino acids.

Results: During an average follow-up of 23.7 years, 3058 ischemic, 872 hemorrhagic and 5997 total stroke cases were documented. After correction for multiple testing, lower risks of ischemic stroke were observed with higher intakes of glutamine (HR per 1 SD higher: 0.94, 95% CI: 0.90-0.98, p-value=0.004) and proline (0.94, 0.90-0.98, p-value=0.005). The associations remained directionally consistent across sensitivity analyses, but attenuated upon mutual adjustment. All other amino acids, including branched-chain amino acids, were not significantly associated with ischemic stroke. For hemorrhagic stroke, no significant associations were observed for any of the amino acids. For total stroke, inverse associations were also observed for both glutamine (0.94, 0.91-0.97, p-value<0.001) and proline (0.96, 0.93-0.99, p-value=0.004). In terms of dietary sources, glutamine was most strongly correlated with plant protein and whole grains, while proline was most strongly correlated with dairy protein and dairy products.

Conclusions: Higher intakes of glutamine and proline were associated with lower risks of ischemic and total stroke.