Nitrate toxicosis in humans occurs through enterohepatic metabolism of nitrate to ammonia, with nitrite being an intermediate[3]. Nitrites oxidize the iron atoms in hemoglobin from ferrous iron (2+) to ferric iron (3+), rendering it unable to carry oxygen[4]. This process can lead to generalized lack of oxygen in organ tissue and a dangerous condition called methemoglobinemia. Methemoglobinemia can be treated with methylene blue, which reduces ferric iron (3+) in affected blood cells back to ferrous iron (2+).
Infants in particular are especially vulnerable to methemoglobinemia due to nitrate metabolizing triglycerides present at higher concentrations than at other stages of development. Methemoglobinemia in infants is known as blue baby syndrome. There are now significant scientific doubts as to whether there is a causal link between nitrates in drinking water and 'blue baby syndrome'.[5][6] Blue baby syndrome is now thought to be the product of a number of factors, which can include any factor which causes gastric upset, such as diarrhoeal infection, protein intolerance, heavy metal toxicity etc., with nitrates playing a minor role. Nitrates, if a factor in a specific case, would most often be ingested by infants in high nitrate drinking water. However, nitrate exposure may also occur if eating, for instance, vegetables containing high levels of nitrate. Lettuce may contain elevated nitrate under growth conditions such as reduced sunlight, undersupply of the essential micronutrients molybdenum (Mo) and iron (Fe), or high concentrations of nitrate due to reduced assimilation of nitrate in the plant. High levels of nitrate fertilization also contribute to elevated levels of nitrate in the harvested plant .[7]
Some adults can be more susceptible to the effects of nitrate than others. The methemoglobin reductase enzyme may be under-produced or absent in certain people that have an inherited mutation[8]. Such individuals cannot break down methemoglobin as rapidly as those that do have the enzyme, leading to increased circulating levels of methemoglobin (the implication being that their blood is not as oxygen-rich). Those with insufficient stomach acid[9] (including some vegetarians and vegans) may also be at risk. It is the increased consumption of green, leafy vegetables that typically accompany these types of diets may lead to increased nitrate intake. A wide variety of medical conditions, including food allergies, asthma[10], hepatitis, and gallstones may be linked with low stomach acid; these individuals may also be highly sensitive to the effects of nitrate.
