Table 1.
Summary of Randomized controlled trials (RCTs) on the impact of dietary supplements on inflammatory markers and in response to SARS-CoV-2.
| Authors/Year/Country | Duration | Participants | Study Design | TNF-α | IL-1β | IL-4 | IL-6 | IL-10 | CRP | IFN-γ | Other Outcomes |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Rastogi et al., 2020 [50] India |
7-d | 40 SARS-CoV-2 RNA positive individuals | RCT: 1.Daily oral cholecalciferol (60,000 IU) with therapeutic target 25(OH)D > 50 ng/mL 2. Control |
- | - | - | - | - | Ø | - | ↓ † Fibrinogen ↑ † Negative conversion of SARS-CoV-2 RNA (62.5% vs. 20.8%) |
| Murai et al., 2021 [53] Brazil |
- | 237 patients hospitalized for moderate to severe COVID-19 |
RCT: 1.A single oral dose of 200,000 IU of vit. D3 2. Placebo |
- | - | - | - | - | Ø | - | Ø Same LOS (median of 7.0 vs. 7.0 days) |
| Lakkireddy et al., 2021 [49] India |
8–10-d | 87 Patients hospitalized for COVID-19 Vit. D < 30 ng/m |
RCT: 1. 60,000 IU/day of oral vitamin D +standard treatment 2. Only standard treatment |
- | - | - | 1. ↓ † 2. Ø |
1. ↓ *† 2. ↓ * |
- | ↓ *† LDH, ferritin, N/L ratio | |
| Beigmohammadi et al., 2021 [41] Iran | 7-d | 60 ICU-admitted COVID-19 patients | RCT: 1. Oral Vit. A (25,000 IU) daily, vit.D (600,000 IU; one dose), vit. E (300 IU twice daily), vit. C (500 mg four times daily), and one amp daily of B complex 2. Placebo |
1. ↓ *† 2. ↓ * |
- | - | 1. ↓ *† 2. ↓ * |
- | 1. ↓ *† 2. ↓ * |
1. ↓ * 2. ↓ * |
↓ † Hospitalization rate and ESR in treatment group |
| Sabico et al., 2021 [48] Saudi Arabia |
14-d | 69 patients COVID-19 and sub-optimal vit. D status | RCT: 1.Oral vit. D3 (5000 IU) 2.Oral vit. D3 (1000 IU) |
- | - | - | 1. ↓ * 2. ↓ * |
- |
1. Ø 2. Ø |
- | ↓ † Time to recovery in resolving cough with D3 (5000 IU) vs. D3 (1000 IU) |
| Abd-Elsalam et al., 2021 [57] Egypt |
4 weeks | 191 patients with COVID-19 | RCT: 1.CQ/HCQ + 220 mg of zinc sulfate twice daily 2. HCQ only |
- | - | - | - | - | Ø | - | Ø Clinical efficacy of HCQ |
| Di Pierro et al., 2021 [58] Italy |
2 weeks | 42 COVID-19 outpatients | RCT: 1. Quercetin (500 mg/day (first week) and of 1000 mg/day (second week) 2. Standard of care |
- | - | - | - | - | Ø | - | ↓ † LOS, virus clearance, symptoms frequency, LDH, ferritin |
| Doae et al., 2021 [59] Iran |
2 weeks | 128 critically ill COVID-19 patients | RCT: 1. 1000 mg omega-3 daily (400 mg EPAs and 200 mg DHAs) 2. Control |
- | - | - | - | - | - | - | ↑ † 1-month survival rate, pH, HCO3, and Be ↓ † Levels of BUN, Cr, and K in the treatment group |
| Darban et al., 2021 [42] Iran |
10-d | 20 patients with severe COVID-19 | Pilot RCT: 1. Standard care + oral zinc sulfate (220 mg containing 50 mg zinc) , oral melatonin (6 mg, q6hr), and intravenous vit. C (2 g) 2. Standard care alone |
- | - | - | - | - | 1. ↓ * 2. ↓ * |
- | Ø LOS |
| Sedighian et al., 2021 [60] Iran |
2 weeks | 30 patients with COVID-19 | Single blind RCT: 1. Hydroxychloroquine + 2 g DHAs and EPAs 2. Hydroxychloroquine |
- | - | - | - | - | 1. ↓ † | - | † Body pain and fatigue in the treatment group Ø Olfactory |
| Cannata-Andía et al., 2022 [52] Spain | - | 543 patients with moderate to severe COVID-19 | RCT: 1. A single-oral bolus of 100,000 IU of cholecalciferol 2. Control |
- | - | - | Ø | - | Ø | - | Ø Hospitalization rate and death |
| Shohan et al., 2022 [61] Iran |
7-d | 60 patients with severe COVID-19 | RCT: 1. Quercetin (1000 mg daily) + antiviral drugs 2. Antiviral drugs |
↓ * | ↓ * | - | ↓ † | - | ↓ † | - | ↓ † ALP, LDH Ø Mortality, duration of ICU-admission |
| Pimentel et al., 2022 [62] Brazil |
7-d | 43 adult patients with COVID-19 | RCT: 1. Two 200 mL units of high-protein nutritional supplement (arginine, omega-3 fatty acids and nucleotides) over 24 h 2. Two 200 mL units of high-protein nutritional supplement alone |
- | - | - | - | - | 1. ↓ † 2. Ø |
- |
↑ Lymphocytes in the treatment group ↓ Lymphocytes in the control group |
| Fernandes et al., 2022 [51] Brazil |
- | 200 patients with moderate to severe COVID-19 | RCT: 1. Single oral dose of vit. D3 (200 000 IU) 2. Placebo |
Ø | Ø | Ø | Ø | Ø | - | Ø | - |
| Gutiérrez-Castrellón et al., 2022 [63] Spain |
30-d | 293 COVID-19 outpatients | RCT: 1. Probiotic (Lactiplantibacillus plantarum stains KABP022, KABP023 and KABP033 = Pediococcus acidilactici strain KABP021) 2. Placebo |
- | - | - | - | - | 1. ↓ † hs-CRP Only on day 15 |
- | ↓ † Complete remission (53.1% in probiotic group vs. 28.1% in placebo; p < 0.001) |
-: Not measured. Ø: Non-significant difference between groups. * p < 0.05, Significantly different from baseline (within group effect). † p < 0.05, Significantly different from the control or. comparison group. TNF-α: tumor necrosis factor -α; IL-1β: Interleukin-1β; IL-4: Interleukin-4; IL-6:Interleukin-6; IL-10: Interleukin-10; IFN-γ: Interferon gamma; CQ/HCQ:Chloroquine/hydroxychloroquine; HCQ: Hydroxychloroquine; ALP: Alkaline phosphatase; Lactate dehydrogenase; Be: Base excess; BUN: Blood urea nitrogen; Cr: creatinine; LOS: Length of hospital stay; LDH: Lactate dehydrogenase; N/L ratio: Neutrophil/Lymphocyte ratio; ESR: Erythrocyte sedimentation rate; DHA: Docosahexaenoic acid; EPA: eicosapentaenoic acid.