Determination of a reference value for N(G), N(G)-dimethyl-L-arginine in 500 subjects

Eur J Clin Invest. 2005 Oct;35(10):622-6. doi: 10.1111/j.1365-2362.2005.01561.x.


Background: Asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of NO-synthase. In the last years ADMA has emerged as a cardiovascular risk factor. The aim of this study was to determine a reference value for ADMA.

Methods: Plasma samples of 500 healthy subjects in the 19-75 year age group were analyzed. Exclusion criteria from this study were smoking, any known significant disease, body-mass-index (BMI) above 30 kg m(-2), elevated plasma lipid levels, impaired renal function, hypertension, and intake of any medication. The ADMA levels were determined by ELISA, (DLD Diagnostics, Hamburg, Germany).

Results: Mean ADMA plasma concentration of the total population was 0.69 micromol L(-1) (SD 0.20) and 95% of the measured values were in the range from 0.36 micromol L(-1) to 1.17 micromol L(-1). Women below 50 years of age had lower ADMA levels than men below 50 years of age [0.62 (0.17) micromol L(-1) vs. 0.69 (0.19) micromol L(-1); P = 0.001] and woman above 50 years of age had higher ADMA levels than men above 50 years of age [0.80 (0.22) micromol L(-1) vs. 0.73 (0.20) micromol L(-1); P = 0.036]. A regression analysis of ADMA levels and age was performed for each sex. The regression factor was r = 0.444 for women in a squared regression model (P < 0.001) and r = 0.212 for men in a linear regression model (P < 0.001).

Conclusion: The study was able to define a reference value for ADMA plasma levels with 0.36-1.17 micromol L(-1) and found sex dependent correlations between ADMA and age. Women showed a significant increase in ADMA plasma levels with onset of menopause.

MeSH terms

  • Adult
  • Aged
  • Aging / physiology
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Biomarkers
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Enzyme Inhibitors / blood*
  • Enzyme-Linked Immunosorbent Assay / standards
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Reference Values
  • Sensitivity and Specificity
  • Sex Characteristics


  • Biomarkers
  • Enzyme Inhibitors
  • N,N-dimethylarginine
  • Arginine
  • Nitric Oxide Synthase