Folic acid does not limit endothelial dysfunction induced by ischemia and reperfusion: A human study

Saverio Dragoni, Tommaso Gori, Giuseppe Di Stolfo, Silvia Sicuro, Sandra Forconi, John D. Parker

Research output: Contribution to journalArticlepeer-review


Nitric oxide synthase (NOS) uncoupling is a condition of increased production of superoxide anion associated with a decreased production of nitric oxide (NO) by this enzyme. Folic acid can prevent and/or reverse NOS uncoupling in the setting of diabetes, smoking, hypercholesterolemia, and nitrate tolerance. Whereas animal studies showed a protective effect of folic acid in ischemia and reperfusion (IR) injury, no study tested whether folic acid administration limits IR-induced endothelial dysfunction in humans. In a double-blind, parallel study, 20 healthy young male volunteers were randomized to receive folic acid, 10 mg/d for 7 days, or matching placebo. At the end of the treatment period, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR injury (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference at baseline between groups in any variable. In the placebo group, IR significantly blunted FMD (before IR, 6.7 ± 1.0%; after IR, 1.5 ± 1.3%, P <0.01). A similar effect was observed in the folic acid group (before IR, 6.3 ± 1.1%; after IR, 2.1 ± 1.0%, P = ns compared with placebo). As opposed to animal studies, high-dose folic acid does not protect the vascular endothelium from IR injury in humans.

Original languageEnglish
Pages (from-to)494-497
Number of pages4
JournalJournal of Cardiovascular Pharmacology
Issue number4
Publication statusPublished - Oct 2005


  • Folic acid
  • Ischemia-reperfusion injury
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine


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