Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 15 No. 2 • March-April 2012

Reversal of Several Features of the Metabolic Syndrome in Mice with Dietary Inorganic Nitrate

We discussed some of the health benefits of dietary nitrate (as found in green leafy vegetables, such as spinach) in the Jan.-Feb. 2012 issue of this newsletter. As we reported there, a recent paper1 in which researchers studied the effects of spinach consumption by healthy human volunteers found a substantial acute augmentation of nitric oxide status and a small, but significant increase in flow-mediated dilation (expansion of the brachial artery in response to nitric oxide). As the paper’s authors had explained, “[t]his is consistent with previous studies which demonstrated that high-dose nitrate increased plasma nitrite levels, improved endothelial function, and lowered blood pressure when given in a dietary (beetroot juice) or pure (KNO3 capsules) form.” The dietary (not high dose) amount of nitrate provided by the 200 g serving of spinach in the spinach study was 182 mg.

Studies of the effects of dietary nitrate has become something of a hot research area, as the nitric oxide supplied by nitrate (after conversion to nitrite by the salivary glands and swallowed) has been identified as an important alternative source of nitric oxide besides the nitric oxide produced by nitric oxide synthase from the amino acid arginine. In a recent study,2 researchers looked at the effects of supplementing eNOS deficient mice (e.g., mice that cannot make nitric oxide in endothelial cells in blood vessels because they do not have the necessary form of nitric oxide synthase) with supplemental inorganic nitrate. The dose used was comparable to the amount a human would get from a diet with a rich intake of vegetables as the nitrate source.

The results2 support the results of earlier work which established a nitrate-nitrite-nitric oxide pathway and showed that the operation of this pathway (via the ingestion of dietary nitrate) can partly compensate for disturbances in endogenous nitric oxide production in animals deficient in eNOS. The eNOS-deficient mice that received 10 weeks of nitrate supplementation had an almost normalized blood glucose concentration curve as compared to the untreated eNOS-deficient mice, which had a disturbed blood glucose concentration curve. The glycosylated hemoglobin levels, a measure of long-term blood glucose control, were lower in the nitrate fed eNOS-deficient mice. Moreover, the nitrate treated eNOS-deficient mice had reduced amounts of visceral fat and lower levels of circulating triglycerides as compared with untreated animals.

NOTE OF CAUTION: Nitrate consumption can increase the risk of stomach cancer because nitrates can become converted to carcinogenic nitrosamines. This risk can be minimized by being sure to take plenty of vitamins C and E along with your meal (or supplement) containing nitrate.


  1. Bondonno et al. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women. a randomized controlled trial. Free Radic Biol Med 52:95-102 (2012).
  2. Carlstrom et al. Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase- deficient mice. Proc Natl Acad Sci USA 107(41):17716-20 (2010).

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