The Pharmacokinetics of Saliva and Plasma N-Oxides Following a Single Administration of a Plant-Based Bioequivalent Inorganic Nitrate Oral Supplement in an Open-Label, Phase 1, Single-Arm Study

Background/Objective: Hypertension and other modifiable risk factors for cardiovascular disease are characterized by a dysfunctional vascular endothelium and decreased nitric oxide (NO) bioavailability. The oral supplementation of inorganic nitrate (NO3−) has been shown to increase the salivary and plasma nitrite (NO2−), a precursor to NO, though there may be significant variation in the pharmacokinetics of this process between different supplements. The purpose of this open-label, phase 1, single-arm study was to investigate the pharmacokinetic profile of the plasma and salivary NO3− and NO2− concentrations following the administration of a single serving of a plant-based bioequivalent inorganic nitrate oral supplement (“Berkeley Life Nitric Oxide Foundation Capsules”, Chicago, IL, USA). Methods: Nine males and three females (age: 33 ± 15 years; BP: 129 ± 6 mmHg; BMI: 27.58 ± 4.27 kg/m2) participated in the protocol. Following the baseline collection of saliva and plasma samples, the participants consumed 314 mg (two capsules) of the supplement. Saliva and plasma samples were collected at 2 h, 4 h, 8 h, and 24 h post consumption. Results: The peak salivary NO3− (13,326.12 ± 4926.60 µM), salivary NO2− (1375.27 ± 679.28 µM), plasma NO3− (498.37 ± 168.89 µM), and plasma NO2− (231.66 ± 97.26 nM) were observed at 2 h post-supplementation (p < 0.01 vs. the baseline). The concentrations of the salivary and plasma NO2− remained elevated at 8 h after administration (220% and 50% above the baseline, respectively), and the concentrations of the salivary and plasma NO3− remained elevated at 24 h after administration (22% and 50% above the baseline, respectively). Conclusions: These data suggest that a single serving of “Berkeley Life Nitric Oxide Foundation Capsules” taken once to twice per day is a viable strategy to provide sustained salivary and plasma NO3− and NO2− availability over 24 h and therefore may provide a viable approach for long-term blood pressure maintenance.