Dietary intake and bio-activation of nitrite and nitrate in newborn infants

Abstract

Nitrate and nitrite are commonly thought of as inert end products of nitric oxide (NO) oxidation, possibly carcinogenic food additives, or well-water contaminants. However, recent studies have shown that nitrate and nitrite play an important role in cardiovascular and gastrointestinal homeostasis through conversion back into NO via a physiological system involving enterosalivary recirculation, bacterial nitrate reductases, and enzyme-catalyzed or acidic reduction of nitrite to NO. The diet is a key source of nitrate in adults; however, infants ingest significantly less nitrate due to low concentrations in breast milk. In the mouth, bacteria convert nitrate to nitrite, which has gastro-protective effects. However, these nitrate-reducing bacteria are relatively inactive in infants. Swallowed nitrite is reduced to NO by acid in the stomach, affecting gastric blood flow, mucus production, and the gastric microbiota. These effects are likely attenuated in the less acidic neonatal stomach. Systemically, nitrite acts as a reservoir of NO bioactivity that can protect against ischemic injury, yet plasma nitrite concentrations are markedly lower in infants than in adults. The physiological importance of the diminished nitrate→nitrite→NO axis in infants and its implications in the etiology and treatment of newborn diseases such as necrotizing enterocolitis and hypoxic/ischemic injury are yet to be determined.

Dietary Nitrate and the Epidemiology of Cardiovascular Disease: Report From a National Heart, Lung, and Blood Institute Workshop

“…Notwithstanding the likely cardiovascular benefits of nitrate from dietary vegetables, high levels of dietary nitrate or nitrite can be problematic for very young infants. In the newborn, both serum nitrate and nitrite are at very low concentrations for the first few weeks of their lives . It is well established that excessive gastrointestinal nitrite absorption puts young infants at risk of methemoglobinemia (met‐Hb) because of a neonate's high proportion of fetal hemoglobin and relative lack of metHb‐reducing capacity .…”

“…It is well established that excessive gastrointestinal nitrite absorption puts young infants at risk of methemoglobinemia (met‐Hb) because of a neonate's high proportion of fetal hemoglobin and relative lack of metHb‐reducing capacity . Very young infants, with their undeveloped oral microbiome, do not produce nitrite from salivary nitrate . But preformed nitrite from improperly stored vegetable purees fed to young infants, or nitrite formed in their stomach from overgrowth of nitrate‐reducing bacteria, can cause MetHb.…”

Nitric Oxide Synthase and Nitric Oxide Involvement in Different Toxicities

“…, and NO 2 − reacts with hemoglobin and prevents oxygen transport to the tissues. As a result, "methemoglobinemia" known as "blue baby syndrome" occurs in infants [47].…”

Changes in plasma and urinary nitrite after birth in premature infants at risk for necrotizing enterocolitis

“…We have previously demonstrated that newborn infants have lower blood nitrite concentrations than adults, possibly due to markedly lower levels of nitrate and nitrite ingestion (12). Preterm infants in particular ingest 50% less nitrite than term infants (12), leading us to hypothesize that nitrate and nitrite levels would be decreased in preterm compared to term infants.…”

“…Preterm infants in particular ingest 50% less nitrite than term infants (12), leading us to hypothesize that nitrate and nitrite levels would be decreased in preterm compared to term infants. Furthermore, given animal evidence for the protective effects of nitrite in the gastrointestinal tract, we hypothesized infants diagnosed with NEC would have lower levels of circulating nitrite in the days prior to diagnosis.…”