Oral Microbiome, Nitric Oxide Metabolism, and Cardiometabolic Health
About Nitric Oxide:
The potential oral benefits of mouthwash and the effectiveness of mouthwash in reducing oral microbes and gingivitis are well established. Hence, antiseptic mouthwash is widely prescribed or recommended with the goal of reducing oral bacteria and gingivitis. Mouthwashes, most of which have some bactericidal properties, are used weekly by two thirds and daily by a third of the US population. Regular over-the-counter mouthwash use is also common in low income and minority populations. Recent literature suggests a possible detrimental impact of mouthwash on blood pressure, mediated by destruction of oral bacteria that play a beneficial role in nitric oxide synthesis. NO is an oxidative stress marker, and plays a major role in vascular function. The role of Nitric oxide as a vasodilator is well established and reduced NO bioavailability might mediate vascular changes through damage to endothelial and vascular smooth muscle cells, as well as by stimulation of inflammatory and other mechanisms. Many of the signaling functions of NO, like vasodilation are transmitted by the activation of soluble guanylyl cyclase that leads to increased cGMP, an important second messenger. Nitric oxide is also related to insulin resistance and hyperglycemia. Studies to date are mostly small clinical trials showing short-term effects of Chlorhexidine (a prescription mouthwash) on reducing conversion of nitrate to nitrite, and increasing blood pressure. These studies have shown that disruption of the oral microflora by antiseptic mouthwash use abolishes the effects of exogenous nitrate and also reduces endogenous nitrate, reduces salivary NO levels and increases blood pressure, among hypertensive as well as among normotensive individuals. The long-term impact of regular use of over-the-counter mouthwash under normal conditions has not been evaluated. The San Juan Overweight Adults Longitudinal Study (SOALS), where information on mouthwash use, saliva and blood specimens and clinical outcome measures and pertinent covariates are already collected, provides a unique opportunity to evaluate the impact of mouthwash use on cardiometabolic outcomes in a time and cost-efficient manner. The study recruited over 1,300 overweight/obese adults at baseline, with 3 year follow-up data on over 75% of the participants. Preliminary analysis from this cohort shows an inverse association between mouthwash use at baseline and incidence of pre-diabetes/diabetes and hypertension over the follow-up period. An additional follow-up will be conducted for this project. The overall goal is to evaluate whether regular mouthwash use is associated with incidence of hypertension and pre-diabetes/diabetes and the extent to which this is mediated by reduced bioavailability of nitric oxide. Given the high rates of regular mouthwash use and the high occurrence of diabetes and hypertension in the general population, evaluating the potential detrimental systemic impact of mouthwash use on these outcomes is critical with a large potential public health impact.