Medium-term methionine supplementation increases plasma homocysteine but not ADMA and improves blood pressure control in rats fed a diet rich in protein and adequate in folate and choline

Eur J Nutr. 2006 Oct;45(7):383-90. doi: 10.1007/s00394-006-0611-1. Epub 2006 Sep 1.


Background: Hyperhomocysteinemia (HHcy) is associated with cardiovascular risk, possibly because it increases asymmetric dimethyl-arginine (ADMA), but the general association remains unclear and may vary with nutritional and physiological conditions.

Aim of the study: We aimed to monitor the effect of methionine supplementation, and subsequent HHcy, on plasma ADMA and hemodynamics in the context of a diet rich in protein and adequate in folic acid and choline.

Methods: For 6 weeks, rats were fed a 29% protein diet supplemented (M) or not (C) with 8 g/kg L: -methionine. Blood pressure and plasma amino acids, including homocysteine and ADMA, were measured throughout the experiment and additional parameters, including in vivo hemodynamic response to acetylcholine, were measured at week 5-6.

Results: As compared to the C diet, the M diet induced a marked HHcy during the first 3 weeks, which lessened at week 5. In contrast, plasma ADMA stayed similar in the C and M diet. Paradoxically, M rats had lower mean and diastolic blood pressure values over the experiment, together with a lower left ventricular mass at week 6, when compared with C rats. No difference was observed between groups regarding vascular reactivity and plasma NOx at week 6.

Conclusions: In a context of a diet rich in protein and adequate in methyl donors, rats exhibit a complex adaptation to the medium-term methionine supplementation, with improvement in blood pressure control despite marked HHcy. The lack of increase in plasma ADMA may account for the absence of detrimental effects of HHcy on hemodynamics.

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Area Under Curve
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Blood Pressure / drug effects*
  • Choline / administration & dosage
  • Dietary Proteins / administration & dosage
  • Dietary Supplements
  • Folic Acid / administration & dosage
  • Homocysteine / blood*
  • Male
  • Methionine / administration & dosage
  • Methionine / pharmacology*
  • Methylation
  • Nitric Oxide / blood
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Time Factors


  • Dietary Proteins
  • Homocysteine
  • Nitric Oxide
  • N,N-dimethylarginine
  • Folic Acid
  • Arginine
  • Methionine
  • Choline