Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects

Area of Science:

• Cardiovascular Science
• Nutritional Biochemistry
• Vascular Physiology

Background:

• Elevated plasma homocysteine levels are linked to endothelial dysfunction and atherosclerosis.
• The impact of physiological increments in homocysteine, induced by dietary factors, on vascular function requires further elucidation.

Purpose of the Study:

• To investigate if physiological increases in plasma homocysteine, following oral methionine or dietary animal protein, induce vascular endothelial dysfunction.
• To determine if there is a graded, inverse relationship between homocysteine concentration and endothelial function.

Main Methods:

• Eighteen healthy volunteers underwent measurements of brachial artery flow-mediated and glyceryltrinitrate-induced dilatation.
• Vascular function was assessed after oral L-methionine (10, 25, 100 mg/kg), dietary animal protein, or a methionine-free amino acid mix.
• Plasma homocysteine levels and endothelial function markers were measured at baseline and at 4 hours post-intervention.

Main Results:

• Oral methionine induced a dose-related increase in plasma homocysteine and a significant reduction in flow-mediated dilatation.
• Dietary animal protein consumption also elevated plasma homocysteine and impaired flow-mediated dilatation compared to a usual meal.
• No changes in vascular function were observed after the methionine-free amino acid mix, and glyceryltrinitrate-induced dilatation remained unchanged.

Conclusions:

• Small, physiological increases in plasma homocysteine, resulting from methionine and animal protein intake, induce vascular endothelial dysfunction.
• Dietary protein intake may have detrimental effects on vascular function through homocysteine elevation.
• These findings suggest a potential role for protein-induced homocysteine increments in the development and progression of atherosclerosis.