Liver disease and COVID-19: The link with oxidative stress, antioxidants and nutrition

Table 1 Ongoing clinical trials of antioxidant supplementation in coronavirus disease 2019 patients

Antioxidants and nutrients	Plant and/or animal sources	Potential target pathways	Recommended dietary intake; Effective dose for respiratory infection)	Registered clinical trials of COVID-19, rial number	Intervention dose	Primary outcome
Vitamin A	Carrots (raw); Cantaloupe; Mango; Salmon; Eggs	Role in immune competence; Immunomodulatory action	900/700 μg M/F	IRCT20200319046819N1[49]	25000 IU vitamin A and 600000 IU vitamin D per day, 300 IU vitamin E twice a week, 2000 mg vitamin C 4 times in a day, amp vitamin B; Soluvit in a day, for 1 wk	Weight, height, BMI; Severity of pulmonary involvement (CT scan); Respiratory support (invasive or non-invasive); WBC, CRP, IL6, TNF-α, IFN-γ, ESR; Body temperature; Organ involvement; Hospital duration; Mortality
Vitamin D	Portabella mushrooms; Dairy products; Eggs; Fish	Maintenance of cell physical barrier integrity; Increased antimicrobial protein production; Anti-inflammatory state; ACE2 and other members of the RAS expression	5- 15 μg; 20-50 μg[60]	NCT04334005[61]	25000 IU vitamin D	Mortality, all-cause mortality within 14 d
				NCT04344041[62]	400000 IU/or 50000 IU	Serum 25(OH)D3 changes during treatment
				NCT04636086[63]	50000 IU vitamin D ; 25000 IU vitamin D ; Days 1-4, 8,15, 22, 29 and 36	Vitamin D serum concentration, clinical improvement, biological markers
				NCT04621058[64]	D deficiency (< 30 ng/mL) 0.532 mg vitamin D (< 40 ng/mL): 0.266 mg vitamin D	Mortality reduction, lent of hospital reduction
				NCT04483635[65]	100000 IU vitamin D tab. baseline + 10000 IU/wk; 16 wk	Change in incidence laboratory-confirmed COVID-19 infection
				NCT04386850[66]	25 µg 25(OH)D3; 2 mo	Hospitalization, disease duration, death, mortality, ventilation
Vitamin C	Oranges; Lemon; Green and red peppers; Tomato; Broccoli; Brussel sprouts; Cabbage; Cauliflower; Spinach; Sweet potato; Winter squash	Antioxidant capacity; Immunomodulatory effects on interferon production; Cytokine production down-regulation	40-80 mg; 6–8 g[77]	NCT04323514[74]	10 g vitamin C infusion	Hospital mortality
				NCT04530539[75]	1000 mg vitamin C	Severity of symptoms
				NCT04682574[76]	30 g/d 2 d with standard treatment	Partial pressure of oxygen in arterial blood to fraction of inspired oxygen
Vitamin E	Sunflower seeds; Nuts; Almonds; Blueberries; Kivi; Broccoli	Antioxidant action; Immunomodulatory effects	7–10 mg; 30–200 mg[82]
Zinc	Pumpkin and squash seeds nuts; Soybean; Beef; Mollusks; Lamb	Reduces ROS in viral infections; Replication inhibition; Immunomodulatory effects; Antibody production; NK cell activity; Cytokine production by mononuclear cells; Chemotaxis response reduction; Neutrophil respiratory burst reduction	8–14 mg; 30–50 mg[43]	NCT04335084[90]	Zinc, vitamin D, vitamin C 12 wk and hydroxychloroquine for 1 d	Prevention of COVID-19 symptoms recorded in a daily diary
Selenium	Sunflower seeds; Coconut meat; Mollusks; Salmon; Turkey; Ham	Antioxidant balanceROS balance in inflammatory processes	60–70 mg
Copper	Cashew nuts; Tofu; Mushrooms; Beef; Oyster; Cereals; Roots, tubers: Sweet potato; Quinoa	Role in immunity antimicrobial action due to copper toxicity; Enhance macrophage activity in lung infection	900 μg
Curcumin	Rhizome of turmeric (Curcuma longa)	Antioxidant capacity; Virus-ACE2 interaction reduction; ACE2 level increase; Antiviral activities SARS-CoV-2 protease, spike glycoprotein-RBD and PD-ACE2 binding		IRCT20200611047735N1[114]	160 mg curcumin; 2 wk	Immune responses (IFN-γ, IL-17, IL-4 and TGF-β)
				IRCT20121216011763N46[115]	1000 mg curcumin + 10 mg piperine twice/day, 2 wk	Clinical symptoms, duration, severity, inflammatory mediators
Silymarin	Milk thistle (Silybum marianum)	Antioxidant capacity; Anti-inflammatory; p38 MAPK pathway antiviral		NCT04394208[116]	420 mg/d; 3 divided doses	Clinical outcome duration of mechanical ventilation hospitalization

ACE2: Angiotensin converting enzyme 2; COVID-19: Coronavirus disease 2019; CRP: C-reactive protein; CT: Computed tomography; ESR: Erythrocyte sedimentation rate; IFN-γ: Interferon-gamma; IL: Interleukin; NK: Natural killer; PD: Protease domain; RAS: Renin-angiotensin system; RBD: Receptor binding domain; ROS: Reactive oxygen species; SARS-CoV-2: Severe acute respiratory syndrome-coronavirus-2; tab.: Tablet; TGF-β: Transforming growth factor-beta; TNF-α: Tumor necrosis factor-alpha; WBC: White blood cell.