Background and Purpose--Hyperhomocysteinemia is a vascular risk factor that infers with the nitric oxide signaling pathway of endothelial vasoregulation. Most investigations in young healthy humans on the peripheral vasculature using a standardized methionine challenge demonstrated altered vascular reactivity. In contrast, the cerebral autoregulation mechanism was shown to be unaffected by the same methionine load. To obtain additional insight into the compensatory range of the cerebral vasculature during a methionine challenge, we tested the neurovascular coupling mechanism that adjusts cerebral blood flow in accordance with cortical activity.

Methods--Fifteen healthy young adults (age, 24.7±2.3 years; 7 men) were tested with a functional transcranial Doppler test before and 3, 8, and 24 hours after administration of placebo, 20 mg folic acid, 20 mg folic acid and 0.1 g/kg body weight L-methionine, or L-methionine alone. Evoked blood flow response was evaluated according to a control system approach. Plasma concentrations of homocysteine, resting blood flow velocities, and control system parameters of flow velocity change were compared for each time point using a multiple analysis of variance test.

Results--Homocysteine levels increased significantly compared with baseline (before, 7.6±1.9 µmol/L; 3 hours, 22.2±6.0 µmol/L [P<0.0001]; 8 hours, 27.9±8.6 µmol/L [P<0.0001]; 24 hours, 12.6±7.8 µmol/L [P=NS]). Resting flow velocities and control system parameters remained statistically nonsignificant.

Conclusions--Compared with the peripheral vasculature, the regulatory mechanisms controlling adequate cerebral blood flow appear to have a wider compensatory range. This is concluded from statistically nonsignificant results comparing the vascular reactivity in young adults undergoing a standardized methionine challenge. Our data confirm indirectly the reports of high concentrations of homocysteine needed to affect the cerebral vasculature in animal experiments.