Physiological regulation of oral saliva ion composition and flow rate are not coupled in healthy humans—Partial revision of our current knowledge required

Appropriate composition of oral saliva is essential for a healthy milieu that protects mucosa and teeth. Only few studies, with small sample numbers, investigated physiological saliva ion composition in humans. We determined saliva ion composition in a sufficiently large cohort of healthy adults and analyzed the effect of physiological stimulation. We collected saliva from 102 adults under non-stimulated and physiologically stimulated conditions (chewing). Individual flow rates, pH, osmolality, Na⁺, K⁺, Cl⁻, and HCO₃⁻ concentrations under both conditions as well as the individual changes due to stimulation (Δvalues) were determined. Non-stimulated saliva was hypoosmolal and acidic. Na⁺, Cl⁻, and HCO₃⁻ concentrations remained well below physiological plasma values, whereas K⁺ concentrations exceeded plasma values more than twofold. Stimulation resulted in a doubling of flow rates and substantial increases in pH, HCO₃⁻, and Na⁺ concentrations. Overall, stimulation did not considerably affect osmolality nor K⁺ or Cl⁻ concentrations of saliva. An in-depth analysis of stimulation effects, using individual Δvalues, showed no correlation of Δflow rate with Δion concentrations, indicating independent regulation of acinar volume and ductal ion transport. Stimulation-induced Δ[Na⁺] correlated with Δ[HCO₃⁻] and Δ[Cl⁻] but not with Δ[K⁺], indicating common regulation of ductal Na⁺, Cl⁻, and HCO₃⁻ transport. We present a robust data set of human oral saliva ion composition in healthy adults and functional insights into physiological stimulation. Our data show (i) that flow-dependence exists for Na⁺ and HCO₃⁻ but not for K⁺ and Cl⁻ concentrations, (ii) osmolality is flow-independent, (iii) regulation of Na⁺, Cl⁻, and HCO₃⁻ transport is coupled, (iv) regulation of flow rate and ion concentrations are independent and (v) spatially separated between acini and ducts, respectively.