Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19—Results From a Pilot Open-Label, Randomized Controlled Trial

DOI record: { "DOI": "10.3389/fphar.2022.898062", "ISSN": [ "1663-9812" ], "URL": "http://dx.doi.org/10.3389/fphar.2022.898062", "abstract": "<jats:p><jats:bold>Background:</jats:bold> Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant activities.</jats:p><jats:p><jats:bold>Objective:</jats:bold> The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical University, Lahore, Pakistan.</jats:p><jats:p><jats:bold>Methods:</jats:bold> Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic COVID-19 outpatients were randomized to receive either the standard of care (SOC) (<jats:italic>n</jats:italic> = 25) (control arm) or a daily oral co-supplementation of 168 mg curcumin, 260 mg quercetin, and 9 µg (360 IU) of cholecalciferol, as two oral soft capsules b.i.d. as an add-on to the SOC (<jats:italic>n</jats:italic> = 25) (CQC arm) for 14 days. The SOC includes paracetamol with or without antibiotic (azithromycin). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, and complete blood count were evaluated at baseline and follow-up day seven.</jats:p><jats:p><jats:bold>Results:</jats:bold> Patients who received the CQC adjuvant therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. five (20.0%) of the control arm, <jats:italic>p</jats:italic> = 0.009. COVID-19- associated acute symptoms were rapidly resolved in the CQC arm, i.e., 15 (60.0%) vs. 10 (40.0%) of the control arm, <jats:italic>p</jats:italic> = 0.154. Patients in the CQC arm experienced a greater fall in serum CRP levels, i.e., from (median (IQR) 34.0 (21.0, 45.0) to 11.0 (5.0, 16.0) mg/dl as compared to the control arm, i.e., from 36.0 (28.0, 47.0) to 22.0 (15.0, 25.0) mg/dl, <jats:italic>p</jats:italic> = 0.006. The adjuvant therapy of co-supplementation of CQC was safe and well-tolerated by all 25 patients and no treatment-emergent effects, complications, side effects, or serious adverse events were reported.</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> The co-supplementation of CQC may possibly have a therapeutic role in the early stage of COVID-19 infection including speedy negativization of the SARS-CoV-2 RT-PCR test, resolution of acute symptoms, and modulation of the hyperinflammatory response. In combination with routine care, the adjuvant co-supplementation of CQC may possibly help in the speedy recovery from early-stage mild to moderate symptoms of COVID-19. Further research is warranted.</jats:p><jats:p><jats:bold>Clinical Trial Registration:</jats:bold><jats:ext-link>Clinicaltrials.gov</jats:ext-link>, identifier NCT05130671</jats:p>", "alternative-id": [ "10.3389/fphar.2022.898062" ], "author": [ { "affiliation": [], "family": "Khan", "given": "Amjad", "sequence": "first" }, { "affiliation": [], "family": "Iqtadar", "given": "Somia", "sequence": "additional" }, { "affiliation": [], "family": "Mumtaz", "given": "Sami Ullah", "sequence": "additional" }, { "affiliation": [], "family": "Heinrich", "given": "Michael", "sequence": "additional" }, { "affiliation": [], "family": "Pascual-Figal", "given": "Domingo A.", "sequence": "additional" }, { "affiliation": [], "family": "Livingstone", "given": "Shona", "sequence": "additional" }, { "affiliation": [], "family": "Abaidullah", "given": "Sajid", "sequence": "additional" } ], "container-title": "Frontiers in Pharmacology", "container-title-short": "Front. Pharmacol.", "content-domain": { "crossmark-restriction": true, "domain": [ "frontiersin.org" ] }, "created": { "date-parts": [ [ 2022, 6, 7 ] ], "date-time": "2022-06-07T15:05:34Z", "timestamp": 1654614334000 }, "deposited": { "date-parts": [ [ 2022, 6, 7 ] ], "date-time": "2022-06-07T15:05:41Z", "timestamp": 1654614341000 }, "indexed": { "date-parts": [ [ 2022, 6, 7 ] ], "date-time": "2022-06-07T15:42:45Z", "timestamp": 1654616565317 }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2022, 6, 7 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 6, 7 ] ], "date-time": "2022-06-07T00:00:00Z", "timestamp": 1654560000000 } } ], "link": [ { "URL": "https://www.frontiersin.org/articles/10.3389/fphar.2022.898062/full", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1965", "original-title": [], "prefix": "10.3389", "published": { "date-parts": [ [ 2022, 6, 7 ] ] }, "published-online": { "date-parts": [ [ 2022, 6, 7 ] ] }, "publisher": "Frontiers Media SA", "reference": [ { "DOI": "10.1016/j.ijbiomac.2020.07.235", "article-title": "Structural Stability of SARS-CoV-2 3CLpro and Identification of Quercetin as an Inhibitor by Experimental Screening", "author": "Abian", "doi-asserted-by": "publisher", "first-page": "1693", "journal-title": "Int. 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