The effects of nitrates in the diet have been discussed a bit on these forums, and I think @Amazoniac and @haidut will find the study interesting.
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2012.04420.x/full
[...interesting stuff but the post would be too long...]
[...]The dilatory effect of nitrite has been shown to be greatly enhanced during hypoxia in humans in both arteries and veins [75] and in tissues, oxygen is a potent regulator of the rate and products of tissue nitrite metabolism. At low oxygen concentrations nitrite reduction to NO predominates, whereas at normal to high oxygen levels oxidation of nitrite to nitrate predominates [76].[...]
[...]
Importantly, the beetroot juice did not contain any detectable nitrite, and whilst plasma nitrate levels were already increasing by 30 min, the BP did not start to fall until the plasma nitrite concentration started to rise, with maximum changes in both occurring at ∼2.5–3 h, reflecting the time to produce nitrite from nitrate and for it to accumulate via the enterosalivary circulation (described below). Indeed, interruption of this process by asking volunteers to spit out all their saliva for 3 h immediately following beetroot juice ingestion completely blocked the rise in plasma nitrite and the reduction BP. This increase in plasma nitrite is also inhibited by the use of an antibacterial mouthwash just prior to nitrate ingestion in humans [80] and also blocks the 5 mmHg blood pressure reduction consequent to nitrate supplemented drinking water in Sprague-Dawley rats [81], in addition to attenuating the gastric mucus thickness with loss of gastroprotective effects against ulcerogenic insults.
These studies therefore provided evidence for a ‘nitrate-nitrite-NO’ pathway. In order to provide further evidence that this effect was due to nitrite, Kapil et al., used potassium nitrate capsules, and demonstrated a dose dependent reduction in BP (with 4, 12 and 24 mmol nitrate) equivalent to beetroot juice [nitrate] with no effect seen with potassium chloride as control [82], suggesting a BP lowering effect of nitrate rich vegetables independent of any potential effect due to their potassium content [83, 84]. This study also demonstrated that the peak increase in plasma nitrite at ∼3 h was associated with a significant increase in cGMP, the most sensitive indicator of NO bioactivity [85], thus providing evidence of bioactive NO generation from nitrite.
The Kapil et al. study also provided a clue to the heterogeneity of blood pressure responses to dietary nitrate. Post hoc analysis revealed that nitrate reduced blood pressure in males – from a higher baseline (associated with a lower baseline plasma nitrite concentration) compared with BP in females, who had no response to nitrate (possibly a result of their higher baseline plasma nitrite concentrations). Whether there is a sex difference per se, or whether the BP response to dietary nitrate is dependent on baseline plasma nitrite/BP remains to be determined.
[...]
The enterosalivary circulation also provides an inherent limiting mechanism to prevent excessive conversion of nitrate to nitrite, avoiding the risk of nitrite toxicity.[...]
An important potential advantage of inorganic nitrate/nitrite is the apparent lack of tolerance induction [86], which commonly limits the therapeutic use of organic nitrates [87].
For those who are intereted (@Travis) they also go into the chemistry of it.
A little more after a well deserved break:
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2012.04420.x/full
[...interesting stuff but the post would be too long...]
[...]The dilatory effect of nitrite has been shown to be greatly enhanced during hypoxia in humans in both arteries and veins [75] and in tissues, oxygen is a potent regulator of the rate and products of tissue nitrite metabolism. At low oxygen concentrations nitrite reduction to NO predominates, whereas at normal to high oxygen levels oxidation of nitrite to nitrate predominates [76].[...]
[...]
Importantly, the beetroot juice did not contain any detectable nitrite, and whilst plasma nitrate levels were already increasing by 30 min, the BP did not start to fall until the plasma nitrite concentration started to rise, with maximum changes in both occurring at ∼2.5–3 h, reflecting the time to produce nitrite from nitrate and for it to accumulate via the enterosalivary circulation (described below). Indeed, interruption of this process by asking volunteers to spit out all their saliva for 3 h immediately following beetroot juice ingestion completely blocked the rise in plasma nitrite and the reduction BP. This increase in plasma nitrite is also inhibited by the use of an antibacterial mouthwash just prior to nitrate ingestion in humans [80] and also blocks the 5 mmHg blood pressure reduction consequent to nitrate supplemented drinking water in Sprague-Dawley rats [81], in addition to attenuating the gastric mucus thickness with loss of gastroprotective effects against ulcerogenic insults.
These studies therefore provided evidence for a ‘nitrate-nitrite-NO’ pathway. In order to provide further evidence that this effect was due to nitrite, Kapil et al., used potassium nitrate capsules, and demonstrated a dose dependent reduction in BP (with 4, 12 and 24 mmol nitrate) equivalent to beetroot juice [nitrate] with no effect seen with potassium chloride as control [82], suggesting a BP lowering effect of nitrate rich vegetables independent of any potential effect due to their potassium content [83, 84]. This study also demonstrated that the peak increase in plasma nitrite at ∼3 h was associated with a significant increase in cGMP, the most sensitive indicator of NO bioactivity [85], thus providing evidence of bioactive NO generation from nitrite.
The Kapil et al. study also provided a clue to the heterogeneity of blood pressure responses to dietary nitrate. Post hoc analysis revealed that nitrate reduced blood pressure in males – from a higher baseline (associated with a lower baseline plasma nitrite concentration) compared with BP in females, who had no response to nitrate (possibly a result of their higher baseline plasma nitrite concentrations). Whether there is a sex difference per se, or whether the BP response to dietary nitrate is dependent on baseline plasma nitrite/BP remains to be determined.
[...]
The enterosalivary circulation also provides an inherent limiting mechanism to prevent excessive conversion of nitrate to nitrite, avoiding the risk of nitrite toxicity.[...]
An important potential advantage of inorganic nitrate/nitrite is the apparent lack of tolerance induction [86], which commonly limits the therapeutic use of organic nitrates [87].
A little more after a well deserved break:
Interaction of nitrate-nitrite with other nutrients
The effects of dietary nitrate may be considerably enhanced or altered through interactions with other nutrients. For example, in addition to polyphenols in fruit and vegetables, Gago et al. found that red wine polyphenols [anthocyanin fraction and catechol (caffeic acid)] are very effective at converting nitrite to NO in vitro and in the human stomach [188]. Indeed, nitrite reductase activity has been associated with a broad range of dietary phenols (greatest to least activity): epicatechin-3-O-gallate, quercetin, procyanidin B8 dimer, oleuropein, procyanidin B2 dimer, chlorogenic acid, epicatechin, catechin, procyanidin B5 dimer [189]. Hawthorn berry extract has been found to have extremely potent nitrite reductase activity, in addition to containing polyphenols (∼5%) and Zand et al. recently performed a placebo-controlled study of 30 days twice daily supplementation with a formulation containing sodium nitrite, hawthorn berry extract, vitamin C, beetroot powder, vitamin B12 and L-citrulline in patients with three or more cardiovascular risk factors and found that it reduced triglycerides in patients with elevated triglycerides (>150 mg dl–1) at baseline. No significant reduction in blood pressure was seen however [190]. In addition, in wine, ethanol is nitrosated resulting in the formation of ethylnitrite, an organic nitrite, which has been shown to be a potent vasodilator [191]. Indeed, Moya et al. have previously demonstrated that inhaled ethyl nitrite results in sustained improvements in arterial oxygenation and haemodynamics in persistent pulmonary hypertension of the newborn [192].
Unsaturated fatty acids in the diet, such as linoleic and oleic acid are nitrated by nitrous acid, derived from nitrite in the acid environment of the stomach, forming nitro-fatty acids (NO2-FAs) [193]. NO2-FAs have several anti-inflammatory actions, inhibiting neutrophils, platelets and macrophages. Signalling pathways are mediated through S-alkylation of, for example, nuclear factor κ B (resulting in inhibition of macrophage cytokine and iNOS expression) [194] and peroxisome proliferator-activated receptor-γ (PPAR-γ) [195]. Rudolph et al. demonstrated that subcutaneous injection of nitro-oleic acid markedly reduced atherosclerotic lesion formation in apoliproprotein E-deficient mice associated with a variety of anti-inflammatory effects including reduction in foam cell formation through attenuation of oxidized LDL-induced phosphorylation of signal transducer and activator of transcription-1 (STAT-1) [139]. The oral administration of nitro-oleic acid has also been shown to be effective in suppressing inflammation in experimental inflammatory bowel disease [196]. Also, Kelley et al., have found that nitro-oleic acid inhibits XOR, and is surprisingly more potent than allopurinol in terms of inhibition of superoxide production [197] and may be part of the mechanism by which nitro-oleic acid confers protection in a mouse model of renal ischaemia-reperfusion [198].
The study by Bondonno et al. examined the interaction of apple skin rich in flavonoids, quercetin and (−)-epicatechin and spinach as a source of dietary nitrate. Whilst apple and spinach reduced SBP (by ∼−3.3 mmHg and ∼−2.7 mmHg after 2 h respectively) compared with control, the combination of apple and spinach had no effect and resulted in an intermediate plasma nitrite concentration suggesting possible extravascular (e.g. stomach) reduction of nitrite by the apple flavonoids and ascorbic acid, as intravascular reduction might be expected to enhance BP reduction [89].
[...]
The effects of dietary nitrate may be considerably enhanced or altered through interactions with other nutrients. For example, in addition to polyphenols in fruit and vegetables, Gago et al. found that red wine polyphenols [anthocyanin fraction and catechol (caffeic acid)] are very effective at converting nitrite to NO in vitro and in the human stomach [188]. Indeed, nitrite reductase activity has been associated with a broad range of dietary phenols (greatest to least activity): epicatechin-3-O-gallate, quercetin, procyanidin B8 dimer, oleuropein, procyanidin B2 dimer, chlorogenic acid, epicatechin, catechin, procyanidin B5 dimer [189]. Hawthorn berry extract has been found to have extremely potent nitrite reductase activity, in addition to containing polyphenols (∼5%) and Zand et al. recently performed a placebo-controlled study of 30 days twice daily supplementation with a formulation containing sodium nitrite, hawthorn berry extract, vitamin C, beetroot powder, vitamin B12 and L-citrulline in patients with three or more cardiovascular risk factors and found that it reduced triglycerides in patients with elevated triglycerides (>150 mg dl–1) at baseline. No significant reduction in blood pressure was seen however [190]. In addition, in wine, ethanol is nitrosated resulting in the formation of ethylnitrite, an organic nitrite, which has been shown to be a potent vasodilator [191]. Indeed, Moya et al. have previously demonstrated that inhaled ethyl nitrite results in sustained improvements in arterial oxygenation and haemodynamics in persistent pulmonary hypertension of the newborn [192].
Unsaturated fatty acids in the diet, such as linoleic and oleic acid are nitrated by nitrous acid, derived from nitrite in the acid environment of the stomach, forming nitro-fatty acids (NO2-FAs) [193]. NO2-FAs have several anti-inflammatory actions, inhibiting neutrophils, platelets and macrophages. Signalling pathways are mediated through S-alkylation of, for example, nuclear factor κ B (resulting in inhibition of macrophage cytokine and iNOS expression) [194] and peroxisome proliferator-activated receptor-γ (PPAR-γ) [195]. Rudolph et al. demonstrated that subcutaneous injection of nitro-oleic acid markedly reduced atherosclerotic lesion formation in apoliproprotein E-deficient mice associated with a variety of anti-inflammatory effects including reduction in foam cell formation through attenuation of oxidized LDL-induced phosphorylation of signal transducer and activator of transcription-1 (STAT-1) [139]. The oral administration of nitro-oleic acid has also been shown to be effective in suppressing inflammation in experimental inflammatory bowel disease [196]. Also, Kelley et al., have found that nitro-oleic acid inhibits XOR, and is surprisingly more potent than allopurinol in terms of inhibition of superoxide production [197] and may be part of the mechanism by which nitro-oleic acid confers protection in a mouse model of renal ischaemia-reperfusion [198].
The study by Bondonno et al. examined the interaction of apple skin rich in flavonoids, quercetin and (−)-epicatechin and spinach as a source of dietary nitrate. Whilst apple and spinach reduced SBP (by ∼−3.3 mmHg and ∼−2.7 mmHg after 2 h respectively) compared with control, the combination of apple and spinach had no effect and resulted in an intermediate plasma nitrite concentration suggesting possible extravascular (e.g. stomach) reduction of nitrite by the apple flavonoids and ascorbic acid, as intravascular reduction might be expected to enhance BP reduction [89].
[...]
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