Table 4.

Antioxidants and COVID-19.

Supplement	Mechanism of action and potential benefits	Potential harms or adverse reactions	Association with COVID-19 infection	Ongoing registered clinical trials related to COVID-19
Glutathione	Antioxidant involved in metabolic regulation and promoting cellular homeostasis	Gastric cramping, nausea, abdominal bloating, and allergic reactions have been reported. Chronic supplementation linked to low serum zinc concentrations. Inhaled glutathione reported to trigger asthma attacks. FDA has warned that glutathione powders used to prepare injectable forms may contain endotoxins that can cause myalgia, arthralgia, nausea, vomiting, and hypotension.	May help to mitigate ARDS response to COVID-19 infection	There are 5 registered clinical trials related to glutathione supplementation and COVID19 on clinicaltrials.gov
N-acetylcysteine	Antioxidant in the extracellular environment to increase intracellular penetration of glutathione Increases pulmonary defense mechanisms through its natural antioxidant properties and its indirect role in glutathione synthesis Has been shown to thin mucus buildup in the lungs of elderly individuals with influenza Has been shown to reduce levels of toxic hydrogen peroxide concentration in exhaled air condensate,	As noted above for glutathione	May help to mitigate ARDS response to COVID-19 infection	There are 14 registered clinical trials related to glutathione supplementation and COVID19 on clinicaltrials.gov
Quercetin	Anti-carcinogenic, anti-inflammatory, antiviral, antioxidant, and psychostimulant activities Ability to inhibit lipid peroxidation, platelet aggregation and capillary permeability, and to stimulate mitochondrial biogenesis	Prior studies demonstrated that quercetin unexpectedly depleted intracellular glutathione, causing pro-oxidant effects. Potentially harmful interactions with statins, cyclosporine, and fexofenadine have been reported	May alter the expression of human genes encoding protein targets of SARS-CoV-2	There are 4 registered clinical trials related to quercetin supplementation and COVID19 on clinicaltrials.gov
Curcumin	Anti-inflammatory, antioxidant Potentially binds to both the ACE2 receptor and receptor-binding domain of the SARS-CoV-2 spike protein (blocking viral entry)	Cardiotoxicity from binding hERG channels	May inhibit COVID-19 binding of spike protein, thereby reducing viral infectivity	There is 1 registered clinical trial related to curcumin and COVID19 on clinicaltrials.gov
Melatonin	Anti-inflammatory, antioxidant Inhibition of the NLRP3 inflammasome May reduce vessel permeability, alleviate anxiety, and improve sleep quality	Alters sleep cycles, which may contribute to poor sleeping patterns and insomnia May cause headache, confusion, dizziness, somnolence, and nausea	COVID-19 may attack the melatonin synthetic pathway Melatonin may reduce vessel permeability, alleviate anxiety, and improve sleep quality in COVID19 patients	There are 8 registered clinical trials related to melatonin and COVID19 on clinicaltrials.gov
Cannabidiol (CBD)	Interferes with ACE2-mediated viral entry into cells Anti-inflammatory	Risk of anxiety, psychosis, and euphoria in products containing THC Lung damage and inflammation from smoking or vaping marijuana products	Downregulation of inflammatory cytokines including TNFa and IL-6, major contributors to progression to ARDS in COVID-19	There are 8 registered clinical trials related to cannabinoids and COVID19 on clinicaltrials.gov