The Effects of Nitrate-Based Nutritional Formula on Oxygen Saturation and Patient-Reported Outcomes in COVID-19 Patients: A Randomized Controlled Trial

The main objective of this randomized controlled trial was to analyze the acute effects of a nitrate-based nutritional formula on peripheral oxygen saturation (Sp[O.sub.2]), patient-reported outcomes, and safety indices in patients with acute COVID-19 infection. The participants completing the protocol for the trial (n = 71) were allocated in a double-blind design to receive either a multicomponent nutritional formula (containing 1200 mg of potassium nitrate, 200 mg of magnesium, 50 mg of zinc, and 1000 mg of citric acid), or a placebo (2.5 g of inulin) during a 72-h monitoring period. All participants were requested to take an intervention (four capsules; weight of each capsule was ~2.5 g) every 4 h during the intervention period. A two-way mixed model ANOVA with repeated measures revealed a significant difference in Sp[O.sub.2] between interventions (P = 0.007). As many as 30 out of 38 patients (78.9%) receiving nitrate-based nutritional formula, who all started the treatment with Sp[O.sub.2] < 95%, finished the intervention with Sp[O.sub.2] of at least 95% at 72-h follow-up, whereas in the placebo group, 13 patients out of 33 (39.4%) finished the trial with Sp[O.sub.2] of at least 95% (P < 0.05). The hospital admission rate after the 72-h follow-up was 21.1 % in patients receiving nitrate-based formula compared to 33.3% in the placebo group (P = 0.25). The nitrate-based formula might be recognized as a potent strategy to tackle hypoxemia and concomitant features of the COVID-19 pandemic. In conclusion, it appears that the novel nitrated-based nutritional formulation described here was able to improve oxygen saturation and clinical outcomes in COVID-19 patients. Although the exact mechanism of action remains unknown, the nitrate-based formula might be recognized as a potent, safe, and convenient strategy to tackle hypoxemia and concomitant features of the COVID-19 pandemic. Keywords: COVID-19, Nitrate, Nitric oxide, Oxygen saturation, Randomized controlled trial Abbreviations Used: Analysis of variance, ANOVA; Nitric oxide, NO; Standard deviation, SD; Oxygen saturation, Sp[O.sub.2] Corresponding Author: Professor Sergej M. Ostojic, MD, PhD, Department of Nutrition and Public Health, University of Agder, Universitetsveien 25, 4604 Kristiansand, Norway; Email: sergei.ostoiic@chess.edu.rs; sergei.ostoiic@uio.no