Nitrates/Nitrites: From Toxic Food Additives to Indispensable Nutrients

BY JACK DINI – Nitrates, found in beets, celery, cabbage and other leafy green vegetables like spinach and some lettuce, are claimed to lower blood pressure, make more efficient muscles, promote brain health in older adults, and lead to more active lives. Sounds almost too good to be true, but these results aren’t from just one group of researchers but numerous studies published in a variety of scientific journals and a recent monograph. (1)

First some background on nitrates/nitrites. In the United States, concern has focused on nitrate and methemoglobinemia in infants. Bacteria in the mouth and gut convert nitrate into nitrite and nitrite reacts with hemoglobin to produce methemoglobin, which is no longer able to carry oxygen. In the early 1950s, methemoglobinemia and cyanosis were seen in infants fed formula made with contaminated well water. The effect was ascribed to the high nitrate content of these wells. The EPA therefore set a Maximum Contaminant Level for nitrate of 44 ml/L or 10 ppm. The nitrate in the offending wells came from fecal contamination. It is now thought that methemoglobinemia was not caused by nitrate but by fecal bacteria that infected the infants and produced nitric oxide in their gut.

Nitric oxide can convert hemoglobin to methemoglobin. The key role of intestinal infection rather than nitrate was confirmed by an experiment in which infants who were fed nitrate did not develop methemoglobinemia. When they were fed bacteria from the contaminated wells, however, methemoglobinemia did develop. This suggests that the nitrate concentrations commonly encountered in foods and water are unlikely to cause methemoglobinemia. (2)

Then in the late 1970s, despite all the fear and paranoia surrounding nitrate exposure, appreciation and understanding of nitrite and nitrate in the biomedical community took a drastic turn. Studies on nitrogen balance in humans and analyses of fecal samples indicated that nitrite and nitrate are formed de novo [over again] in the intestine. As Nathan Bryan and Norman Hord report, “These early findings significantly altered our conceptions of human exposure to exogenous nitrite and nitrate and represented the original observations that would eventually lead to the discovery of the L-arginine: NO [nitric oxide] pathway. However, the paradigm did not spill over to the lay public and still today some 30 years later public perception is that nitrite and nitrate are harmful food additives that should be avoided.” (3)

It turns out that NO is one of the most important molecules produced by the human body. Over 100,000 papers have appeared on the topic of nitric oxide. NO for many years was stigmatized as a toxic air pollutant in automobile exhaust. Nathan Bryan notes, “You can imagine the impact when it was discovered that such a gaseous molecule is produced in the human body.

Even more remarkable is the fact that such a gas is produced in the body to serve as a signal for cell-to-cell communication and the transduction of nerve impulses. NO is a molecule that regulates blood pressure, causes penile erection, and controls the action of almost every cell in our body. The immune system uses nitric oxide in fighting viral bacterial and parasitic infections, as well as tumors. NO transmits messages between nerve cells and is associated with learning, memory, sleeping, feeling pain, and depression. It is a key mediator in inflammation.” (4)  NO is so important to the body that it was named “Molecule of the Year” by Science magazine in 1992. (5)

Recent publications have highlighted beetroot juice as a good source of nitrites, but as mentioned earlier other leafy vegetables also work. Here are some of the recent claims.

Blood Pressure

Researchers at The London School of Medicine have reported that drinking just 500 ml of beetroot juice a day can significantly reduce blood pressure. The research reveals that it is the ingestion of dietary nitrate contained within the beetroot juice and similarly in green, leafy vegetables which results ultimately in decreased blood pressure. Previously the protective effects of vegetable-rich diets had been attributed to their antioxidant vitamin content.

The researchers found that in healthy volunteers blood pressure was reduced within just 1 hour of ingesting beetroot juice, with a peak drop occurring 3-4 hours after ingestion. Some degree of reduction continued to be observed until up to 24 hours after ingestion. The decrease in blood pressure was due to the chemical formation of nitrite from the dietary nitrate in the juice. The nitrate in the juice is converted in saliva, by bacteria on the tongue, into nitrite. The nitrite-containing saliva is swallowed, and in the acidic environment of the stomach is either converted into nitric oxide or re-enters circulation as nitrite. The peak time of reduction in blood pressure correlated with the appearance and peak levels of nitrite in circulation. (6)

In another report, a diet rich in leafy vegetables is postulated to minimize the tissue damage caused by heart attacks. The findings suggest that the chemical nitrite found in many vegetables could be the secret ingredient in the heart-healthy Mediterranean diet. Researchers now have good evidence that hearts undergoing heart attacks have a ‘backup’ pathway for making nitric oxide. Triggered by falling oxygen levels, enzymes in the heart muscles convert nitrite stored there into nitric acid that can then help minimize tissue damage. (7)

More Efficient Muscles

When consumed, beetroot juice has two marked physiological effects. Firstly, it widens blood vessels, reducing blood pressure and allowing more blood flow. Secondly, it affects muscles during activity. The combined effects have a significant impact on performing physical tasks, whether it involves low-intensity or high-intensity effort. Beetroot juice has been one of the biggest stories in sports science over the past year after researchers at the University of Exeter found it enables people to exercise for up to 16% longer. The startling results have led to a host of athletes—from premiership footballers to professional cyclists—looking into its potential uses. In the latest study, researchers looked at low intensity exercise and found that test subjects used less oxygen while walking; effectively reducing the effort it took to walk by 12%. (8)

After taking a small dose of inorganic nitrate for three days, healthy people consume less oxygen while riding an exercise bike. A study in the February issue of Cell Metabolism traces this improved performance to increased efficiency of the mitochondria that power our cells. (9)

Improved Brain Health and More Active Lives For Older Adults

Research has found that nitrites can help open up the blood vessels in the body, increasing blood flow and oxygen specifically to places that are lacking oxygen. MRIs showed that after eating a high-nitrate diet, older adults had increased blood flow to the white matter of the frontal lobes—the area of the brain commonly associated with degeneration that leads to dementia and other cognitive conditions. (10)

Discussion

“We’re talking about an amount of nitrate equivalent to what is found in two or three red beets or a plate of spinach,” said Eddie Weitzberg of the Karolinska Institute in Sweden. He adds, “We know that diets rich in fruits and vegetables can help prevent cardiovascular disease and diabetes but the active nutrients haven’t been clear. This shows inorganic nitrate as a candidate to help explain these benefits.” (11)

Michigan State University researcher Norman Hord reports, “We and others have shown that components of vegetables and fruits that originate in the soil may function as nutrients by contributing to cardiovascular health. Since these components of plant foods have important health implications, the regulatory limits on the consumption of plant foods that contain nitrates and nitrites need to be seriously reconsidered.

We wanted to show the toxicity risk cited as the basis for federal regulatory levels for nitrate and nitrite are irrational because plant foods contain high concentrations of these food components.” Hord adds, “People consuming a variety of fruits and vegetables may be ingesting much more nitrate and nitrite than recommended—more than 1,000 milligrams—with no adverse effects. (The World Health Organization established a standard of 222 milligrams per day as an acceptable daily nitrate intake.) We’re calling for a systematic reevaluation of the literature to highlight the potential beneficial contributions that nitrates and nitrites from vegetables and fruits make to cardiovascular health.” (12)

References

1. Food, Nutrition and the Nitric Oxide Pathway, Nathan S. Bryan, Editor, (Lancaster, PA, DEStech Publications, 2010), 201
2. Martijn B. Katan, “Nitrate in foods: harmful or healthy? Am. J. Clin. Nutr., 90, 11, July 1., 2009
3. Food, Nutrition and the Nitric Oxide Pathway, Nathan S. Bryan, Editor, 153
4. Food, Nutrition and the Nitric Oxide Pathway, Nathan S. Bryan, Editor, ix
5. D. E. Koshland, Jr., “The Molecule of the Year,” Science, 258, 1861, December 18, 1962
6. Andrew J. Webb, et al., “Acute blood pressure lowering vasoprotective and antiplatelet properties of dietary nitrate via bioconversion to nitrite,” Hypertension, 51, 784, 2008
7. “Eating Your Greens Could Prove Life-Saving If A Heart Attack Strikes,” sciencedaily.com, November 14, 2007
8. K. E. Lansley, et al., “Dietary nitrate supplementation reduces the O₂ costs of walking and running: a placebo-controlled study,” Journal of Applied Physiology, 2010; DOI: 10.1152/japplphysiol.01070.2010
9. Filip J. Larsen, et al., “Dietary Inorganic Nitrate Improves Mitochondrial Efficiency in Humans,” Cell Metabolism, 13, 149, 2011
10. Tennile D. Presley, et al., “Acute effect of a high nitrate diet on brain perfusion in older adults,” Nitric Oxide, 2010; DOI: 10.1016/j.niox.2010.10.002
11. “Want More Efficient Muscles? Eat Your Spinach,” sciencedaily.com, February 4, 2011
12. Norman G. Hord, et al., “Food sources of nitrates and nitrites: the physiologic context for potential health benefits,” Am. J. Clin. Nutr., 90, 1, July 1., 2009

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