Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men.
BACKGROUND
Dietary flavonoids may improve endothelial function and ultimately lead to beneficial cardiovascular effects.


OBJECTIVE
The objective was to assess whether pure dietary flavonoids can modulate nitric oxide and endothelin-1 production and thereby improve endothelial function.


METHODS
A randomized, placebo-controlled, crossover trial in 12 healthy men was conducted to compare the acute effects of the oral administration of 200 mg quercetin, (-)-epicatechin, or epigallocatechin gallate on nitric oxide, endothelin-1, and oxidative stress after nitric oxide production was assessed via the measurement of plasma S-nitrosothiols and plasma and urinary nitrite and nitrate concentrations. The effects on oxidative stress were assessed by measuring plasma and urinary F(2)-isoprostanes. Plasma and urinary concentrations of quercetin, (-)-epicatechin, and epigallocatechin gallate were measured to establish the absorption of these flavonoids.


RESULTS
Relative to water (control), quercetin and (-)-epicatechin resulted in a significant increase in plasma S-nitrosothiols, plasma nitrite, and urinary nitrate concentrations (P < 0.05), but not in plasma nitrate or urinary nitrite. Epigallocatechin gallate did not alter any of the measures of nitric oxide production. Quercetin and (-)-epicatechin resulted in a significant reduction in plasma endothelin-1 concentration (P < 0.05), but only quercetin significantly decreased the urinary endothelin-1 concentration. None of the 3 treatments significantly changed plasma or urinary F(2)-isoprostane concentrations. Significant increases in the circulating concentrations of the 3 flavonoids were observed (P < 0.05) after the corresponding treatment.


CONCLUSIONS
Dietary flavonoids, such as quercetin and (-)-epicatechin, can augment nitric oxide status and reduce endothelin-1 concentrations and may thereby improve endothelial function.
Loke
Wai Mun
WM
School of Medicine and Pharmacology and the School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Perth, Western Australia.
Hodgson
Jonathan M
JM
Proudfoot
Julie M
JM
McKinley
Allan J
AJ
Puddey
Ian B
IB
Croft
Kevin D
KD
D000328:Adult; D002392:Catechin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D018592:Cross-Over Studies; D004032:Diet; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D028441:F2-Isoprostanes / Q000652:urine; D005419:Flavonoids / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000097:blood / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011794:Quercetin / Q000493:pharmacokinetics / Q000494:pharmacology; D026403:S-Nitrosothiols / Q000097:blood
D019332:Endothelin-1; D028441:F2-Isoprostanes; D005419:Flavonoids; D009566:Nitrates; D009573:Nitrites; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate