Table 3.

Kinetic processes in the handling of dietary nitrate and inorganic nitrite derived from nitrate. XOR (xanthine oxidoreductase), AO (aldehyde oxidase), ALDH2 (aldehyde dehydrogenase type 2)

Kinetics	Dietary nitrate	Nitrite (derived from nitrate)
Absorption	Readily absorbed across upper gastrointestinal tract [b110]. Do not undergo first pass metabolism [b112]. Only a small fraction reaches the large bowel: <1% ingested nitrate excreted in faeces [b113]; <2% is present in ileostomy fluid in patients with a total colectomy [b113,b114], with negligible nitrite concentrations.
	Bioavailability of nitrate from cooked spinach, raw lettuce and cooked beetroot ∼100% [b111]. Plasma tmax of 1.5–1.8 h [111].	Bioavailability of nitrite ∼95–98% [b112]. Plasma tmax ∼3 h, when derived from oral nitrate [b82], and 15–45 min following oral nitrite administration [b112].
Distribution	Volume of distribution moderate ∼0.3 l kg−1 [b111], compared with that of water (∼0.6 l kg−1). Plasma half‐life of 5–8 h [77,79,111,141,142]. Concentrated in the salivary glands: 20–28% of a nitrate load is secreted in saliva [107,113,115,116]. Entero‐salivary circulation [1].	Volume of distribution of nitrite at steady‐state is similar to that of nitrate, ∼0.35 l kg−1 [b86]. Rapid uptake into most tissues [b108]. Half‐life of 1–5 min ex vivo [b77,b142] to ∼20–45 min in vivo [b86,b112].
Metabolism	Symbiotic bacteria on the posterior third of the tongue which contain nitrate reductases, predominantly Veillonella species, as well as Actinomyces, Rothia and Staphylococcus epidermidis convert nitrate into nitrite which is then swallowed [b117,b118]. May be inhibited by mouthwash [b80]. Minimal or no conversion of nitrate to nitrite in the circulation in humans (though demonstrated in germ‐free mice).	In the stomach, nitrite reacts with the acidic gastric environment producing nitrous acid which decomposes to form nitric oxide as well as other reactive nitrogen oxides [b95]. Vitamin C and polyphenols have been shown to reduce nitrite to NO [b188].
		In the circulation and tissues, nitrite is metabolized to nitric oxide by: deoxyhaemoglobin [6] [b119–b121], deoxymyoglobin [b122], cytoglobin and neuroglobin [b123,b124], XOR [b7,b125], aldehyde oxidase [b126], ALDH2 [b127], carbonic anhydrase [b137], eNOS [125,128,129,130], cytochrome P450 [b131–b134]. Additional pathways: formation of nitro‐fatty acids [b139], nitrosothiols [b138].
Excretion	∼65–75% of absorbed nitrate is renally excreted [b110].	Renally excreted, with renal carbonic anhydrases involved in nitrite reabsorption [b140].