Until recently, nitrite has been considered a stable and inert metabolite of nitric oxide ( • NO) metabolism. This view is now changing as it has been shown that nitrite can be reduced back to • NO and thus one may consider a reversible interaction regarding ˙NO:nitrite couple. Not only physiological regulatory actions have been assigned to nitrite but also may represent, in addition to nitrate, the largest ˙NO reservoir in the body. This notion has obvious importance when considering that ˙NO is a ubiquitous regulator of cell functions, ranging from neuromodulation to the regulation of vascular tone. Particularly in the stomach, following ingestion of nitrate and food or beverages-containing polyphenols, a rich chemistry occurs in which ˙NO, ˙NO-derived species and nitroso or nitrated derivatives may be formed. Most of these molecules may play an important role in vivo. For instance, it has been shown that polyphenol-catalyzed nitrite reduction to ˙NO may induce local vasodilation and that ethanol (from wine) reacts with ˙NO-derived species yielding nitroso derivatives endowed with ˙NO-donating properties. Thus, this review reveals new pathways for the biological effects of dietary nitrite encompassing its interaction with dietary components (polyphenols, red wine, lipids), yielding products with impact on human physiology and pathology, namely cardiovascular, urinary and gastrointestinal systems. Novel therapeutic strategies are therefore expected to follow the elucidation of the mechanisms of nitrite biology.

To identify dietary phenolic compounds capable of improving vitamin E status, male Sprague-Dawley rats were fed for 4 weeks either a basal diet (control) with 2 g/kg cholesterol and an adequate content of vitamin E or the basal diet fortified with quercetin (Q), (−)-epicatechin (EC), or (+)-catechin (C) at concentrations of 2 g/kg. All three catechol derivatives substantially increased concentrations of α-tocopherol (α-T) in blood plasma and liver. To study potential mechanisms underlying the observed increase of α-T, the capacities of the flavonoids to i) protect α-T from oxidation in LDL exposed to peroxyl radicals, ii) reduce α-tocopheroxyl radicals (α-T ^· ) in SDS micelles, and iii) inhibit the metabolism of tocopherols in HepG2 cells were determined. All flavonoids protected α-T from oxidation in human LDL ex vivo and dose-dependently reduced the concentrations of α-T ^· . None of the test compounds affected vitamin E metabolism in the hepatocyte cultures. In conclusion, fortification of the diet of Sprague-Dawley rats with Q, EC, or C considerably improved their vitamin E status. The underlying mechanism does not appear to involve vitamin E metabolism but may involve direct quenching of free radicals or reduction of the α-T ^· by the flavonoids.