The relationship between plasma and salivary NOx

Abstract

Several studies have shown that fasting plasma nitrite (NO2−) is an indicator of endothelial nitric oxide synthase (NOS) activity while plasma nitrate (NO3−) or the sum of NO2− and NO3− (NOx) do not reflect NOS function. Plasma NO2− can also be elevated through dietary NO3− where the NO3− is partially reduced to NO2− by oral bacteria and enters the plasma through the digestive system. NO3− is taken up from plasma by salivary glands and the cycle repeats itself. Thus, one may propose that salivary NO2− is an indicator of plasma NO2− and consequently of NO production. Many brands of nitric oxide (NO) saliva test strips have been developed that suggest that their product is indicative of circulatory NO availability. However, data supporting a relationship between salivary and plasma NO2− or NO bioavailability is lacking. Here we have measured basal salivary and plasma NO2− and NO3− to determine if any correlation exists between these in 13 adult volunteers. We found no significant correlation between basal salivary and plasma NO2−. Also no correlation exists between salivary NO3− and plasma NO2−. However, we did see a correlation between salivary NO3− and plasma NO3−, and between salivary NO2− and plasma NO3−. In a separate study, we compared the efficiency of salivary NO3− reduction with the efficacy of increasing plasma NO3− and NO2− after drinking beet juice, a high NO3−-containing beverage, in 10 adult volunteers. No significant correlation was observed between the ex vivo salivary reduction of NO3− to NO2− and plasma increases in NO3− or NO2−. These results suggest that measures of salivary NO3−, NO2− or NOx are not good indicators of endothelial function. In addition, the efficiency of saliva to reduce NO3− to NO2− ex-vivo does not demonstrate one’s ability to increase plasma NO2− following consumption of dietary NO3−.

Validation of two point-of-care tests against standard lab measures of NO in saliva and in serum

“…Therefore, the saliva NO test strips are unlikely to be of use for assessment of circulating NO-bioavailability. This is consistent with a recent report showing no correlation between saliva and plasma nitrite (20) and likely reflects the fact that circulating nitrite levels can be modulated by multiple reactions and processes including endogenous formation via NO-oxidation, swallowing of salivary nitrite and stomach metabolism and transport into the circulation, versus nitrite oxidation or reduction (by metalloproteins) and nitrite excretion in sweat and urine (46). …”

“…Among the obese and overweight individuals, the overall production and levels of NO are increased along with high nitrite excretion (47). Consistent with previous studies (20), there were significant correlations between the levels of nitrate and nitrite in the saliva, and between salivary nitrite and serum nitrate levels. In contrast to the previous report there was no significant correlation between the salivary and serum concentrations of nitrate, but we did observe a significant correlation between salivary nitrate and serum nitrite levels.…”

“…The range of concentrations of nitrate and nitrite in our study were similar to those reported in a previous study (20); however, the range of serum nitrite levels in our study was higher compared to the previous report (0.37 to 7.49 uM compared to 0.06 to 0.184 uM). This could be due to the fact that our population consisted of overweight to obese people.…”

“…In contrast to the previous report there was no significant correlation between the salivary and serum concentrations of nitrate, but we did observe a significant correlation between salivary nitrate and serum nitrite levels. A possible explanation for the difference with the previous study (20) is that we used serum instead of plasma samples. Serum is considered the gold standard for many clinical assays (21,22), and demonstrates a higher sensitivity and reliability in biomarker detection compared to plasma (24).…”

“…These simple to use and inexpensive POC tests for measuring nitrite are attractive as a cheap and easy way to estimate NO-bioavailability and may also have potential use in research as a low burden low cost test but it is important to validate these POC tests against standard lab-based methods. To our knowledge, saliva strips have been validated in only one study (20) where plasma from healthy donors was used as the standard. Compared to plasma, serum is considered the gold standard for many clinical assays (21,22), and demonstrates a higher sensitivity in biomarker detection (23).…”