Asymmetric dimethylarginine and total homocysteine in plasma after oral methionine loading

P Wanby, L Brattstrom, L Brudin, Björn Hultberg, T Teerlink

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Background: Elevation of homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) in plasma are believed to be involved in the pathogenesis of cardiovascular disease (CVD). In humans, oral methionine loading results in acute elevation of plasma Hcy. This is associated with impaired NO-dependent vasodilatation, a mechanism that may explain the relationship between elevated Hcy and risk of CVD. ADMA, an endogenous competitive inhibitor of NO-synthase, may be elevated in plasma of patients with CVD. It was proposed that ADMA is synthesized in a methionine-dependent reaction which also forms Hcy. In this study plasma total homocysteine (tHcy) and ADMA concentrations were measured before and after oral methionine loading of human subjects. Methods: Plasma tHcy and ADMA levels were measured in 12 healthy males (age 32-58 years) before and after oral loading with L-methionine (100 mg/kg body weight in orange juice). Results: At noon, 4 h after methionine loading, tHcy and ADMA levels (35.4 +/- 10.9 and 0.80 +/- 0.13 mumol/L, mean +/-SD) were significantly higher than the corresponding values obtained at noon the day before (15.6 +/- 7.4 and 0.63 +/- 0.10 mumol/L, both p < 0.001). Noon values 4 h after methionine loading were also significantly higher than values obtained immediately before the methionine load (13.7 &PLUSMN; 5.9 and 0.66 &PLUSMN; 0.10 μmol/L, both p < 0.001). Reinvestigation of 8 of 12 subjects showed that at 4 and 8 h after compared with levels immediately before methionine loading there was a significant increase in tHcy (28.4 +/- 10.2 and 33.45 +/- 11.1 vs. 10.8 +/- 3.3 mumol/L, both p < 0.001). However, the corresponding ADMA levels did not increase (0.73 &PLUSMN; 0.17 and 0.76 &PLUSMN; 0.22 vs. 0.70 &PLUSMN; 0.10 μmol/L, both not significant). Conclusions: No clear evidence was found to support the supposition that methionine-induced hyperhomocysteinaemia may be accompanied by elevated levels of ADMA, an endogenous competitive NO-synthase inhibitor that may represent an alternative pathogenic mechanism for homocysteine-associated impairment of endothelial NO-dependent functions.
Original languageEnglish
Pages (from-to)347-353
JournalScandinavian Journal of Clinical & Laboratory Investigation
Issue number5
Publication statusPublished - 2003

Subject classification (UKÄ)

  • Medicinal Chemistry
  • Pharmacology and Toxicology


  • renal function
  • nitric oxide
  • endothelium
  • atherosclerosis
  • cardiovascular diseases
  • risk factors


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