Table 1.

Clinically proven immunoceuticals for treating respiratory and/or gastrointestinal tract infections, cancers, and acquired immunodeficiency syndrome (AIDS).

Immunoceuticals	Authors	Study Design	Disease/Pathological Condition Addressed with Immunoceuticals	Dose	Results
Vitamin D3 (Cholecalciferol)	[31]	Multi-center, randomized clinical trial	Severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2) infection	5000 IU or 1000 IU of Vit D3 once daily for two weeks	Vit D supplementation significantly increased serum 25(OH)D levels in the 5000 international units (IU) group 5000 IU of daily Vit D3 supplementation reduced recovery time for cough and gustatory sensory loss in patients with mild to moderate COVID-19
	[32]	Quasi-experimental study	SARS-CoV-2 infection	Oral bolus of 80,000 IU Vit D3 during or just before infection with COVID-19	82.5% of participants in intervention group survived infection with COVID-19 versus 44.4% in comparator group Intervention group had longer survival time than Comparator group (log-rank p = 0.002) Vit D3 supplementation inversely associated with Ordinal Scale for Clinical Improvement score for COVID-19 (β = −3.84 (95% CI:−6.07;−1.62), p = 0.001)
	[33]	Randomized clinical trial	SARS-CoV-2 infection	Oral supplementation of 10,000 IU daily of Vit D3 for 14 days	10,000 IU of Vit D3 daily for 14 days was sufficient to raise Vit D concentrations supplemented group presented fewer symptoms than non-supplemented on day seven and fourteen of follow-up
	[34]	Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial	Influenza A infection	1200 IU of Vit D3 daily	Vit D3 supplementation during winter season may reduce incidence of influenza A-mediated illness Influenza A infections occurred in 18/167 children in the Vit D3 group versus 31/167 children in the placebo group
Polysaccharide K (PSK)	[35]	Randomized double-blind trial	Colorectal cancer	3 g/day starting 10–15 days after surgery until two months after surgery, then 2 g daily until 24 months and 1 g daily thereafter	rate of patients in remission was significantly higher in PSK group versus placebo group Survival rate in PSK group significantly higher (p < 0.05) than control group Polymorphonuclear leukocyte activities in PSK-treated patients significantly enhanced
	[36]	Randomized, controlled trial	Colorectal cancer	3 g of PSK per day for over three years	Disease-free and overall survival of PSK group were longer than those of the control group
Polysaccharide-Peptides (PSP)	[37]	Double-blind placebo-controlled randomized study	Non-small cell lung cancer (NSCLC)	340 mg of purified Yun-zhi PSP capsules three times daily for 28 days	significant improvement in blood leukocyte and neutrophil counts, serum IgG and IgM, and % of body fat in PSP group, but not control (p < 0.05) 5.9% of PSP patients were withdrawn due to disease progression versus 23.5% of control patients PSP treatment associated with slower deterioration in advanced NSCLC patients
Probiotics	[38]	Randomized controlled open-label trial	Acute upper respiratory tract infections (acute URTI)	300 mL/day of yogurt supplemented with a probiotic strain, Lactobacillus paracasei N1115 (N1115), 3.6 × 107 CFU/mL for 12 weeks	number of persons diagnosed with acute URTI and number of URTI events significantly decreased in probiotic group versus control Percentage of CD3+ cells in intervention group significantly higher than in control
Prebiotic and probiotic	[39]	Community based double-masked, randomized controlled trial	Diarrhea, respiratory infections and severe illnesses in children aged 1–4 years of age	milk fortified with 2.4 g/day of prebiotic oligosaccharide and 1.9 × 107 CFU of probiotic Bifidobacterium lactis HN019	incidence of dysentery episodes, pneumonia and severe acute lower respiratory infection reduced by 21%, 24%, and 35%, respectively
Quercetin	[40]	Prospective, randomized, controlled, and open-label study	SARS-CoV-2 infection	1000 mg of Quercetin/day for 30 days	statistical improvement of all clinical outcomes (need and length of hospitalization, need of non-invasive oxygen therapy, progression to Intensive care unit, and number of deaths) 1000 mg of Quercetin/day was well tolerated by all subjects
	[41]	Second, pilot, randomized, controlled and open-label clinical trial	SARS-CoV-2 infection	600 mg of Quercetin/day for seven days, followed by 400 mg of Quercetin/day for another seven days	16 of the 21 COVID-19 outpatients in the Quercetin group tested negative for SARS-CoV-2, and 12 patients in the Quercetin group had all their symptoms diminished one-week post-treatment Quercetin significantly improved virus clearance, symptom frequency, lactate dehydrogenase, and ferritin
Beta-Carotene (Carotenoid)	[42]	Pilot study	AIDS	60 mg/day for four weeks	Total lymphocyte counts increased by 66% and CD4+ cells rose slightly Patients with a baseline CD4+ cells greater than 10/ul demonstrated an average increase of 53 ± 10 cells/ul
Omega-3 fatty acids	[43]	Single-blind randomized controlled trial	SARS-CoV-2 infection	2 g of docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) for 2 weeks	significantly decreased fatigue and body pain, and increased appetite in intervention group decreased erythrocyte sedimentation rate and C-reactive protein following two weeks of omega-3 supplementation
	[44]	Double-blind, randomized clinical trial	SARS-CoV-2 infection	One capsule of 1000 mg omega-3 daily containing 400 mg EPAs and 200 mg DHAs for 14 days	significantly higher one-month survival rate and higher arterial pH, HCO3, and base excess (respiratory function parameters) and lower blood urea nitrogen, creatinine, and potassium (renal function parameters) in intervention group versus control group (both composed of critically ill COVID-19 patients)
Melatonin	[45]	Single-center, double-blind, randomized clinical trial	SARS-CoV-2 infection	3 mg of melatonin three times daily for 14 days	Significant improvement in clinical signs and symptoms (cough, dyspnea and fatigue), as well as C-reactive protein concentrations and pulmonary involvement in intervention versus control Significantly shorter mean time of hospital discharge and return to baseline health in intervention versus control

COVID-19 = Novel coronavirus disease identified in 2019; SARS-CoV-2 = severe acute respiratory syndrome-coronavirus-2; I.U. = international units; PSK = polysaccharide K; PSP = polysaccharide-peptides; Vit D3 = vitamin D3/cholecalciferol; CFU = colony forming units; URTI = upper respiratory tract infection; CD = cluster of differentiation; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; NSCLC = non-small cell lung cancer; IgG = immunoglobulin G; IgM = immunoglobulin M; HC0₃ = bicarbonate.