Oral microbiome makeup key link in NO pathway, expert says

By Hank Schultz contact

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Oral microbiome makeup key link in NO pathway, expert says

Related tags: Nitric oxide

Boosting nitric oxide in the body has long been a goal in sports nutrition.  But without an understanding of the importance of the proper oral microbiome makeup, it may be a forlorn hope, an expert said recently.

Nathan Bryan, PhD, spoke on the subject of the implications of dietary nitrate and nitrite and their relation to sports performance at the recent meeting of the International Society of Sports Nutrition in Phoenix.  Bryan is a professor at Baylor University College of Medicine as well as the founder of a dietary supplement company called HumanN.

Important signaling molecule

Nitric oxide is a gas that functions as one of the very rare gaseous signaling molecules in the body. The Nobel Prize for Medicine in 1998 was awarded to three researchers for their discovery of the role of this molecule in the circulatory system and the place it occupies in cardiovascular disease. NO serves among other things to dilate the peripheral blood vessels and support healthy endothelial function. Indeed, Bryan said the modern understanding of CVD is coming around to viewing these conditions as NO deficiency diseases.

“If you don’t get enough nitrate and nitrite in the diet you become NO deficient, which can increase the risk of heart attacks and strokes,” Bryan told his audience. “It wasn’t discovered until the late 1980s that NO was cardioprotective. What does cause heart disease in the end is insufficient nitric oxide production.”

Vasodilation has been shown to equate to muscular performance increases, and this pot of gold in sports nutrition has attracted piles of investment capital. For a number of years now dietary supplement developers have looked for ways to boost NO, but in Bryan’s view, much of this effort rested on an incomplete understanding of the complicated pathway by which NO is created in the body and also the widely varying amounts of nitrate found in foods thought to be naturally high in this substance.

Arginine dead end

Arginine is involved in one of the steps in this NO pathway, so one of the early attempts was to supplement with this ingredient as a way to boost vasodilation. It was a simplistic analysis, Bryan said, perhaps akin to saying that if you increase the supply of mortar, you’ll end up with a higher brick wall without reference to the supply of bricks or masons. Several studies (two can be found here​ and here​) have failed to support the supplementation of arginine to boost NO, but the claim still flits about the marketplace.

Importance of proper oral microbiome makeup

Ingesting nitrate can, under the right conditions, boost the supply of NO in the body, Bryan said. This is the basis for all of the excitement around beets and other foods high in nitrate. Bacteria, as it turns out, play a key role in the supply of NO in the body, in that they convert dietary nitrate, which by itself is inert in the body, into nitrite, which gives rise to NO.  This conversion happens in the mouth, either directly as a part of chewing, or later when nitrates concentrate in the salivary glands to be secreted in the mouth for another pass through the oral microbiome.  So in this way, with enough nitrate intake, the oral microbiome is supplying a steady stream of nitrite, Bryan said.  Except that a certain segment of the population lacks the proper oral bacteria, either because of overly aggressive oral hygiene with antimicrobial products or because of genetic factors.

Nitrate levels in foods vary

Getting enough nitrate in the diet can alter the makeup of the oral microbiome, with nitrate almost acting as a ‘prebiotic’ in this context, Bryan said. But the strictly dietary approach is complicated by the fact that the level of nitrate in foods known to contain this molecule, such as the aforementioned beets and others like spinach, can vary widely depending on growing conditions.  Broccoli tested in New York City, for example, had a mean concentraiton of 279 PPM of nitrate, and on the low end, some samples had almost none, whereas in Raleigh, NC, the mean concentration was 553 PPM and the range between the high and low samples was much narrower.  Other even wider variances were observed in cabbage, celery, lettuce and spinach among the five markets tested (Los Angeles, Chicago and Dallas were the other three). So in Bryan’s view, without standardization of nitrate levels, supplying foods or even supplements based on powdered forms or extracts of these foods as a way of boosting NO can be an iffy proposition.

Direct nitrite supplementation

This is what led Bryan around to the notion that supplying nitrite directly was the best solution. The supplement company he helped found, HumanN, is based on standardized levels of nitrates and a tablet product that aims to supply nitrite directly.  Nitrite, especially when used as a food preservative, got a bad rap a number of years ago because of a suspected link to cancer, but this has been discounted, Bryan said.

We are looking at a single molecule in a very complex food matrix. We created a lozenge that supplies nitrite and generates free nitric oxide gas,​ he said.

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