Oral L-arginine improves endothelial function in healthy individuals older than 70 years

Vasc Med. 2003 May;8(2):77-81. doi: 10.1191/1358863x03vm474oa.


Ageing is associated with progressive endothelial dysfunction in normal humans. Flow-mediated dilation (FMD) of the brachial artery is impaired in elderly individuals with cardiovascular disease and vascular nitric oxide (NO) bioavailability is reduced. We investigated whether oral L-arginine, the substrate for NO synthesis, can improve impaired FMD in healthy very old people. In a prospective, double-blind, randomized crossover trial, 12 healthy old subjects (age 73.8 +/- 2.7 years) took L-arginine (8 g p.o. two times daily) or placebo for 14 days each, separated by a wash-out period of 14 days. FMD was determined by high-resolution ultrasound in the brachial artery during reactive hyperaemia. Baseline artery diameter was 3.88 +/- 0.18 mm. L-Arginine significantly improved FMD (to 5.7 +/- 1.2%, p < 0.0001), whereas placebo had no effect (-0.25 +/- 0.7%; n.s.). After L-arginine, plasma levels of L-arginine increased significantly (114.9 +/- 11.6 versus 57.4 +/- 5.0 micromol/l), but placebo had no effect. As NO synthesis can be antagonized by its endogenous inhibitor asymmetric dimethyl L-arginine (ADMA), we determined ADMA plasma concentrations, which were elevated at baseline in comparison to healthy middle-aged individuals (3.9 +/- 0.2 versus 1.0 +/- 0.1 micromol/l; p < 0.0001). ADMA remained unchanged during treatment, but L-arginine supplementation normalized the L-arginine/ADMA ratio (p < 0.05). We conclude that in healthy very old age endothelial function is impaired and may be improved by oral L-arginine supplementation, probably due to normalization of the L-arginine/ADMA ratio.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Aging / physiology*
  • Analysis of Variance
  • Arginine / administration & dosage*
  • Blood Flow Velocity
  • Brachial Artery / physiopathology
  • Cross-Over Studies
  • Double-Blind Method
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Linear Models
  • Male
  • Prospective Studies
  • Vasodilation / drug effects
  • Vasodilation / physiology


  • Arginine