Antiseptic mouthwash use and effect on resting metabolic rate and blood pressure among healthy females: a randomized, double-blind, crossover study

Abstract

BACKGROUND Inorganic nitrate, from dietary or endogenous sources can be metabolized in vivo to generate bio‐active nitrogen oxides including nitric oxide (NO) with robust NO‐like cardiovascular and metabolic effects. The bio‐activation of nitrate involves its active accumulation in saliva followed by a sequential reduction to nitrite, nitric oxide, and other reactive nitrogen species. Commensal oral bacteria have a key role in nitrate bio‐activation since they reduce salivary nitrate to the more reactive nitrite anion. A recent study demonstrates that resting metabolic rate (RMR) decreases significantly after dietary supplementation with nitrate. This effect is likely caused by bio‐active nitrogen oxides directly interacting with mitochondria to affect proton leak and other parameters. It is unclear however if endogenous nitrate, derived mainly from the oxidation of NO in blood and tissues, also has this effect. We recently showed that blocking oral bacterial conversion of nitrate to nitrite with an antiseptic mouthwash, leads to a reduction in salivary and plasma nitrite levels together with a concomitant increase in blood pressure. Such effect indicates that endogenous nitrate is sufficient to have physiological effects after reduction to nitrite and then NO. OBJECTIVE Here we studied the effects of an antiseptic mouthwash on nitrate and nitrite kinetics and RMR in humans. DESIGN In a randomized, double‐blind, crossover study, we measured the RMR using indirect calorimetry in 17 healthy young females after a 3‐d intervention with a chlorhexidine‐containing antiseptic mouthwash. The subjects were instructed to use antiseptic mouthwash or placebo 3 times a day after meals. We measured 24h ambulatory blood pressure (ABP) and collected saliva‐ and blood samples in the end of the intervention period. RESULTS Saliva nitrate levels were significantly increased after mouthwash compared to placebo (mouthwash: 1443 ± 262 μmol/L; placebo: 652 ± 199 μmol/L, p = 0.002), but nitrate and nitrite levels in plasma showed no significant changes. There was no significant increase in RMR after mouthwash compared to placebo (p = 0.982) and saliva nitrate did not correlate with RMR. The 3‐d use of antiseptic mouthwash did not significantly change ABP. CONCLUSIONS Differently from a recent study, the use of an antiseptic mouthwash did not affect circulating nitrite levels in this group of healthy young females, despite markedly reducing salivary conversion of nitrate to nitrite. Similarly, RMR was not affected by this intervention. Further studies are needed to clarify the role of endogenous nitrate, derived from NOS activity, in regulation of NO homeostasis in blood and tissues.