Nitrate

Nitrate compounds (eg sodium nitrate) are found naturally on earth as large deposits. Nitrate (NO3−) naturally results from the breakdown of animal (or human) waste, but nitrate in groundwater mainly comes from fertilizers (eg ammonium nitrate) used in agriculture. Nitrate is much less toxic than ammonia. Nitrate is naturally consumed by growing plants, including fruit trees. Particularly vegetables may contain high levels of nitrate due to (besides nitrate fertilization) reduced sunlight exposure, undersupply of molybdenum and iron, and/or reduced assimilation of nitrate in the plant.

Methemoglobinemia

Methemoglobinemia is characterized by elevated levels of oxidized hemoglobin (= methemoglobin = metHb) Normally, metHb levels are below 1% (of total Hb). Only when oxidative stress cannot sufficiently be prevented, the normal Fe2+ in hemoglobin (Hb) is oxidized to Fe3+ (in metHb). This results in a decreased capacity to release oxygen to tissues. The higher the level of metHb, the less oxygen released.

Normally, spontaneously formed metHb is reduced to Hb by mainly NADH metHb reductase, but also the vitamin C and glutathione enzyme systems. Exposure to nitrates may accelerate the rate of formation of methemoglobin up to one-thousandfold, overwhelming the protective enzyme systems and acutely increasing methemoglobin levels.

Infants are particularly vulnerable to methemoglobinemia due to nitrate metabolizing triglycerides present at higher concentrations than at other stages of development.

Other causes/contributing factors of methemoglobinaemia include dehydration caused by diarrhea, sepsis, the use of antibiotics (trimethoprim, sulfonamides and dapsone Zosel A et al, local anesthetics (especially articaine and prilocaine Adams V et al, and others such as aniline dyes, metoclopramide, chlorates and bromates.