Effectiveness of a sustained-release ammonium chloride formulation in reducing the viral load of patients with COVID-19 or influenza: A prospective, randomized, double-blind, placebo-controlled study

Background We estimated the effectiveness of a novel sustained-release dietary supplement formulation containing 500 mg ammonium chloride and 2,000 IU vitamin D (ACF;) in reducing the viral load of patients with COVID-19 or influenza. Methods In this prospective, randomized, double-blind, placebo-controlled, study. Eligible patients with COVID-19 or influenza were randomized to receive ACF twice daily or placebo (2,000 IU vitamin D/twice daily; VDF) for 10 days. Nasopharyngeal swab samples were collected at Day 1, Day 3–5 and Day 10–11 and tested for SARS-CoV-2 and influenza via RT-PCR. Cycle threshold (Ct) values were measured. The study has been retrospectively registered in ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT07254052) and the ISRCTN registry (ISRCTN study registration number: ISRCTN48259966). Results Thirty two patients were studied, 28 with COVID-19 and 4 with influenza. No patient developed severe disease, was hospitalized, or died. Sixteen patients received ACF and 16 VDF (mean age: 58.1 and 60.7 years, respectively; 68.8% and 25% with comorbidities, respectively). On Day 1, the mean Cts were 22.49 in ACF group and 21.01 in VDF group, on Day 3–5, the mean Cts were 33.20 and 30.82, respectively, and on Day 10–11, the mean Cts were 43.66 and 40.21, respectively. On Day 10–11 the adjusted mean difference was + 3.12 cycles (95% confidence interval: 0.22–6.02; p-value = 0.036). The Kaplan Meier analysis indicated faster clearance in the ACF group compared to the VDF group (p-value = 0.016). Conclusions Our data indicate that ACF-receiving patients had a statistically significant reduction in viral load compared to placebo-receiving patients. This is attributed to the pharmacodynamic action of ammonium chloride and the pharmacokinetic properties of ACF. Larger studies are needed to further investigate the role of ACF in various RNA-viral infections. Trial registration: This study was retrospectively registered in ClinicalTrials.gov (identifier: NCT07254052; registered on 22 October 2025) and in the ISRCTN registry (registration number: ISRCTN48259966; registered on 27 November 2025).