Reference intervals for plasma L-arginine and the L-arginine: Asymmetric dimethylarginine ratio in the framingham offspring cohort

Nicole Lüneburg, Vanessa Xanthakis, Edzard Schwedhelm, Lisa M. Sullivan, Renke Maas, Maike Anderssohn, Ulrich Riederer, Nicole L. Glazer, Ramachandran S. Vasan, Rainer H. Böger

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

L-Arginine, as a precursor of NO synthesis, has attracted much scientific attention in recent years. Experimental mouse models suggest that L-arginine supplementation can retard, halt, or even reverse atherogenesis. In human studies, supplementation with L-arginine improved endothelium-dependent vasodilation. However, L-arginine levels are best interpreted in the context of levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of NO synthase. Thus, reference limits for circulating L-arginine and the L-arginine:ADMA ratio may help to determine the nutritional state of individuals at high cardiovascular risk in light of increased ADMA levels. We defined reference limits for plasma L-arginine in 1141 people and for the L-arginine:ADMA ratio in 1138 relatively healthy individuals from the Framingham Offspring Cohort. Plasma L-arginine and ADMA concentrations were determined by using a stable isotope-based LC-MS/MS method. The reference limits (2.5th and 97.5th percentiles) for plasma L-arginine were 41.0 mmol/L (95% CI = 39.5-42.5 mmol/L) and 114 mmol/L (95% CI = 112-115 mmol/L), whereas corresponding reference limits (2.5th and 97.5th percentiles) for the L-arginine:ADMA ratio were 74.3 mmol/L (95% CI = 71.1-77.3 mmol/L) and 225 mmol/L (95% CI = 222-228 mmol/L). Plasma L-arginine was positively associated with the estimated glomerular filtration rate (eGFR) and blood glucose levels, whereas the L-arginine:ADMA ratio was positively associated with eGFR and diastolic blood pressure but inversely associated with homocysteine and (log)C-reactive protein. We report reference levels for plasma L-arginine and for the L-arginine:ADMA ratio that may be helpful for evaluation of the effects of L-arginine supplementation in participants with an impaired L-arginine/NO pathway.

Original languageEnglish (US)
Pages (from-to)2186-2190
Number of pages5
JournalJournal of Nutrition
Volume141
Issue number12
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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